DENTAL ANATOMY AND OCCLUSION - 1 File Download
MICROBIOLOGY AND PATHOLOGY
Green is pre 2002
Yellow is post 2002
USC messed up the following questions:
1981Q61 – wrong – should be ‘(c) fibroblasts & endothelial cells’
1981Q68 – wrong – should be ‘basophils & mast cells’, not ‘eosinophils & mast cells’
Questions to Find
Which of the following affects the widest organ range?
Herpes, rubella, varicella, Moluscam m.
CELLS/ORGANELLES
Cell parts:
Mitochondrion – double MB structure responsible for cellular metabolism – powerhouse of the cell
Nucleus – controls synthetic activities and stores genetic information
Ribosome – site of mRNA attachment and amino acid assembly, protein synthesis
Endoplasmic reticulum – functions in intracellular transportation
Gogli apparatus/complex – composed of membranous sacs – involved in production of large CHO molecules & lysosomes
Lysosome – organelle contains hydrolytic enzymes necessary for intracellular digestion
Membrane bag containing digestive enzymes
Cellular food digestion – lysosome MB fuses w/ MB of food vacuole & squirts the enzymes inside
Digested food diffuses through the vacuole MB to enter the cell to be used for energy or growth
Lysosome MB keeps the cell iself from being digested
Involved mostly in cells that like to phagocytose
Involved in autolytic and digestive processes
Formed when the Golgi complex packages up an especially large vesicle of digestive enzyme proteins
Phagosome – vesicle that forms around a particle (bacterial or other) w/in the phagocyte that engulfed it
Then separates from the cell MB & fuses w/ lysozome to receive contents
This coupling forms phagolysosomes in which digestion of the engulfed particle occurs
Microbodies:
Contain catalase
Bounded by a single MB
Compartments specialized for specific metabolic pathways
Similar in function to lysosomes, but are smaller & isolate metabolic reactions involving H2O2
Two general families:
Peroxisomes: transfer H2 to O2, producing H2O2 – generally not found in plants
Glyoxysomes: common in fat-storing tissues of the germinating seeds of plants
Contain enzymes that convert fats to sugar to make the energy stored in the oils of the seed available
Inclusions – transitory, non-living metabolic byproducts found in the cytoplasm of the cell
May appear as fat droplets, CHO accumulations, or engulfed foreign matter.
The cell cycle
1) Labile cells (GI tract, blood cells)
Described as parenchymal cells that are normally found in the G0 phase that can be stimulated to enter the G1
Undergo continuous replication, and the interval between two consecutive mitoses is designated as the cell cycle
After division, the cells enter a gap phase (G1), in which they pursue their own specialized activities
If they continue in the cycle, after passing the restriction point (R), they are committed to a new round of division
The G1 phase is followed by a period of nuclear DNA synthesis (S) in which all chromosomes are replicated
The S phase is followed by a short gap phase (G2) and then by mitosis
After each cycle, one daughter cell will become committed to differentiation, and the other will continue cycling
2) Stable cells (Hepatocytes, Kidney)
After mitosis, the cells take up their specialized functions (G0).
They do not re-enter the cycle unless stimulated by the loss of other cells
3) Permanent cells (neurons)
Become terminally differentiated after mitosis and cannot re-enter the cell cycle
Which cells do not have the ability to differentiate? ⋄ Cardiac myocytes
Enzymes:
Serum lysozyme:
Provides innate & nonspecific immunity
Lysozyme is a hydrolytic enzyme capable of digesting bacterial cell walls containing peptidoglycan
In the process of cell death, lysosomal NZs fxn mainly to aulolyse necrotic cells (NOT “mediate cell degradation”)
Attacks bacterial cells by breaking the bond between NAG and NAM.
Peptidoglycan – the rigid component of cell walls in most bacteria – not found in archaebacteria or eukaryotic cells
Lysozyme is found in serum, tears, saliva, egg whites & phagocytic cells protecting the host nonspecifically from microorganisms
Superoxide dismutase: catalyzes the destruction of O2 free radicals protecting O2-metabolizing cells against harmful effects
Catalase:
catalyzes the decomposition of H2O2 into H2O & O2
Aerobic bacteria and facultative anaerobic w/ catalase are able to resist the effects of H2O2
Anaerobic bacteria w/o catalase are sensitive to H2O2 (Peroxide), like Strep
Anaerobic bacteria (obligate anaerobes) lack superoxide dismutase &/or catalase
Staph makes catalase, where Strep does not have enough staff to make it!!
Coagulase
NOT an NZ, its an adhesin
Converts Fibronogen to fibrin
Coagulase test is the prime criterion for classifying a bug as Staph aureus – from other Staph species
Coagulase is important to the pathogenicity of S. aureus because it helps to establish the typical abscess lesion
Coagulase also coats the surface w/ fibrin upon contact w/ blood, making it harder to phagocytize
NOTE: this is NOT a polysaccharide capsule that forms
Cell Functions:
Autolysis:
degradative reactions in cells caused by indigenous intracellular enzymes – usually occurs after cell death
Irreversible (along with Coagulative necrosis or infarcts) – reversible: fatty degeneration, & hydropic degeneration
Autolysin:
Ab causing cellular lysis in the presence of complement
Autolytic enzymes produced by the organism degrade the cell’s own cell wall structures
In the presence of cephalosporins & penicillins, growing bacterial cells lyse
W/o functional cell wall structures, the bacterial cell bursts
Heterolysis: cellular degradation by enzymes derived from sources extrinsic to the cell (e.g., bacteria)
Necrosis: sum of intracellular degradative reactions occurring after individual cell death w/in a living organism
Lymph nodes
If a foreign antigen enters through the skin, it will first hit the lymphoid system in the lymph nodes
NOT the MALT, liver, spleen, or thymus
Lymphocytes
Motile
Immunoglobulin production
Produce MIF (Macrophage inhibiting factor)
If a T-lymphocyte from a pt with chronic periodontitis were cultered in vitro with dental plaque antigen, production of MIF would occur
DO NOT PHAGOCYTIZE
When T cells from people with chronic PD are reacted with certain plaque bacterial antigens, they produce:
MIF, OAF, & lymphotoxin (NOT Ab, collagenase, or C3)
B-lymphocytes:
Are WBCs that complete maturation in bone marrow then migrate to lymphoid organs
Search out, identify, & bind w/ specific Ag/s
Recognize specific antigens by virtue of membrane-bound immunoglobulin
Committed to differentiate into Ab-producing plasma cells involved in Ab-mediated immunity
When an immature B cell is exposed to a specific Ag (they recognize Ag by MB-bound Ig), the cell is activated
It then travels to spleen or lymph nodes, differentiates, and rapidly produces plasma & memory cells
Mature B cells have surface IgM & IgD that bind Ag & cause release of immunoglobulins
B-cell immunodeficiency can be treated with injections of gamma-globulin
Plasma cells:
The predominant cell in synthesis of Abs
More common in chronic inflammation than acute inflammation
Cells of Chronic inflammation are Lymphocytes, Plasma cells, and Macrophages
T-lymphocytes:
Affected by IL-4???
WBC that complete maturation in thymus & become thymocytes
Responsible for initially recognition of antigen
In pts with chronic PD, when the T cells react with certain plaque bacterial antigens, they produce:
IL-2, TNF-alpha, IFN-gamma
NOT Immunoglobulin – That would be B-cells.
Responses to viral infections:
Production of lymphokines
Direct cell-mediated cytotoxicity
Helper activity to B cells to make Abs
Major classes include helper T-cells, suppressor T-cells, & cytotoxic (killer) T-cells
T helper cells:
CD4+
NOT antigen-specific
(Antigen-specific cells are):
B cells, Macrophages, Dendritic, and Langerhans (So, reticuloendothelial cells + B-cells).
Two classes of helper T cells→Th1 & Th2 cells
Distinguished by the types of cytokines they secrete
Th1: release IL-2 & IFN-gamma
Stimulate proliferation & cytotoxic responses
Th2: release Il-4, IL-5, IL-6, Il-10
Stimulate B cell maturation, differentiation & class-switching
Cytotoxic T-cells
CD8+
First activated w/ IL-2, which is secreted by active helper T-cells
Act by recognizing foreign Ag & MHC I molecules w/ their TCR
Natural Killer (NK) cells
Also activated w/ IL-2
Recognize foreign Ag w/o need for Ag presentation on MHC molecules
NON specific immunity
Activated by cytokines, such as IFN-gamma
Deficiency in T-cells can predispose a person to candidiasis (NOT a deficiency in basophils/eosinophils/plasma cells/MФs)
Eosinophils
Release histaminase & aryl sulfatase to help control allergic reactions
Basophils
Have receptors for the Fc portion of IgE
IgE binding promotes degranulation = release of histamine, etc, which lead to symptoms seen in atopic allergies
Mast Cells
IgE has an affinity for the Fc portion of Mast cells
Type I Hypersensitivity
Secrete
Histamine
Heparin
ECF-A (Eosinophil Chemotactic Factor of Anaphylaxis)
SRS-A (Slow-Reacting Substances of anaphylaxis (SRS-As)
Leukotrienes
|Lymphocytes |Function |
|T helper cells (Th) |Help or assist other T cells and B cells to express their immune function |
|Cytotoxic T cells (Tc) |Kill target cells expressing foreign Ag/s (cells containing obligate intracellular parasistes & tumor cells) |
|T suppressor cells (Ts) |Suppress or inhibit the immune function of other lymphocytes |
|T memory cells |Long-lived cells that recognize previously encountered T dependent antigens |
|B lymphocytes |Differentiate into antibody-producing plasma cells and B memory cells in response to an antigen |
|B memory cells |Long lived cells that recognize a previously encounter antigen |
|Natural killer cells (NK) |Kill and lyse target cells that express foreign antigens |
|Plasma cells |Actively secrete antibody |
Cells that maintain latent capacity for mitotic division:
Blood (RBCs live for 120 days, WBCs only 2-5 hours), bone marrow, liver, and salivary glands
Liver undergoes regeneration: occurs as adaptive mechanism for restoring a tissue or organ
After removal of 70% of liver, numerous mitoses of hepatocytes occur reaching a peak at 33 hours
By day 12 the mass of liver is totally restored
Liver is the least common site for infarcts (than brain, heart, kidney, adrenals)
NOTE: Bone cartilage & intestinal mucosa are also able to regenerate
Cells that do not have ability to undergo mitosis:
Nerve cells (least ability to regenerate) in the CNS, skeletal, cardiac, & smooth muscle cells, lungs
Striated muscle is harder to regenerate than smooth muscle
Heart, brain, & lungs are very vulnerable to hypoxia & anoxia
They die & are unable to regenerate
The heart can undergo hypertrophy in response to injury
BACTERIA
A quick note on organisms in general:
Commensalism:
Interaction between two populations of different species living together in which one population benefits from the association, while the other is not affected
Symbiosis:
An obligatory interactive association between members of two populations
Produces a stable condition in which the two organisms live together in close physical proximity
It may, but does not necessarily, benefit each member
Mutualism:
Form of symbiosis – both members live together w/ mutual benefit
Cell types:
Eukaryote
Has a true nucleus – surrounded by a nuclear MB & uses a mitotic apparatus in allocating chromosomes
Contains organelles & larger (80S) ribosomes
Mitotic replication
EXs: plants, animals, protozoa, fungi
Prokaryote
No nucleus, organelles, or cytoskeleton
Nuclear material NOT contained w/in a nucleus
Naked, single circular molecule of losely organized dsDNA
Single chromosome
Located in nucleoid (membraneless structure/region containing DNA – little resemblance to eukaryotic nucleus)
Contains no MB-bound organelles & smaller (70S) ribosomes
Has a rigid external cell wall containing peptidoglycan (mycoplasmas lack a cell wall) - that’s why they don’t stain.
EXs: BACTERIA, mycoplasmas, rickettsia, chlamydia
Gram-staining
Based on interaction w/ cell wall
Limitations:
Treponema (too thin to be visualized) ⋄ Use Darkfield for Syphilis
Rickettsia (intracellular parasite)
Mycobacteria (high-lipid content cell wall) ⋄ Use acid-fast
Mycoplasma (NO cell wall) – M. pneumoniae (walking pneumonia)
Legionella Pneumophila (Primarily Intracellular) ⋄ Use Silver stain
Chlamydia (intracellular parasite)
Acid-fast organisms appear red against blue background (due to lipids/waxes [mycolic acids] in the cell wall)
Staining in tubercle bacilli is due to lipid/waxes mycolic acid
Mycobacteria & Nocardia are acid-fast
True bacteria multiply by binary fission
NOTE: viruses are not cells – they are “obligate intracellular parasites”
Either RNA or DNA; no organelles; protein capsid & lipoprotein envelope
Classification:
Neutrophiles (pH = 7.0)
P. aeruginosa
Clostridium sporogenes
Proteus species
Acidophiles (pH < 7.0)
Thiobacillus thiooxidans
Sulfollobus acidocaldaarius
Bacillus acidocaldarius
Alkaliphiles (pH > 7.0)
Nitrobacter species
Streptococcus pneumoniae
Bacterial growth
1) Lag phase (Think lagging behind)
Metabolically active, non-dividing
2) Log phase = logarithmic phase (Log Growth)
Exponential growth
Most of the cidal Abx work best in this phase
i.e. Ampicillin
Best phase for staining bacterial cultures
For uniform staining rxn, morphology, and biochemical activity
3) Stationary phase
# of cells are dying = # of cells being produced
4) Death phase/phase of decline
More death than new cell production
Logarithmic decrease in cell #
Glucose metabolism (respiration)
Oxidative phosphorylation involves the Cell MB in bacterial cells
BUT, ETC in Eukaryotes happens on the inner mitochondrial MB
Aerobic respiration
Results in greatest release of energy
The primary result of bacterial carbohydrate metabolism is production of energy (NOT heat, alcohol, or acetone)
Involves a cell MB respiratory chain (electron transport chain = ETC)
O2 is the terminal hydrogen acceptor, with final end products of H2O and CO2
Fermentation
Substrate phosphorylation
Formation of ATP not coupled to electron transfer
Occurs when final electron acceptor is an organic compound
An intermediate glucose product (i.e., pyruvate) is the final hydrogen acceptor
Takes place in cytoplasm
How Anaerobic bugs get their energy
Aerobic metabolism (obligate aerobes & facultative anaerobes) – They have the Faculty to be Aerobes too
Toxic byproducts: H2O2 & free superoxide radicals
Final endproducts are H2O and CO2
Cells possess a defense system to destroy these endproducts:
Enzymes include superoxide dismutase & catalase
1) Superoxide dismutase catalyzes the decomposition of free superoxide radicals into H2O2 & H2O
2) Catalase then catalyzes H2O2 → H2O + O2
Cytochromes:
Respiratory enzymes capable of undergoing alternate reduction & oxidation
Contain central iron atom which can be cycled between oxidized ferric state (Fe3+) & reduced ferrous state (Fe2+)
Chemically related to hemoglobin
Aerobic organotropic (heterotrophic) bacteria which oxidize a substance to CO2 and H2O in the final electron transport, use NZs containing cytochromes
EXs:
Cytochrome oxidase – terminal enzyme in chain of events constituting cellular O2 consumption – found in mitochondria
Cytochrome P450 – important in metabolism of many drugs – found in liver microsomes (small particles typically consisting of fragmented endoplasmic reticulum to which ribosomes are attached)
Cytochrome b – cytochrome of respiratory chain
Cytochrome b5 – cytochrome of endoplasmic reticulum
Transcription
Synthesis of mRNA from DNA by DNA-dependent RNA polymerase
Occurs in cytoplasm of prokaryotes (nucleus of eukaryotes)
Two strands of DNA are temporarily pulled apart to allow RNA polymerase to access DNA as a template
Translation
Process wherein nitrogenous bases are used to determine the aa sequence of a protein
Reverse transcription
Formation of DNA from RNA template
Retroviruses (HIV, RNA tumor viruses) use this process
RNA genome is used as a template for RNA-dependent DNA polymerase
The virion-associated reverse transcriptase makes DNA copies from RNA
This DNA is then integrated into the host genome
**Retrovirus is an oncogenic RNA virus (papillomavirus is NOT – because it is a DNA virus – don’t get clowned)
3 types of RNA:
1) rRNA – combines w/ proteins to form ribosomes
2) mRNA – dictates sequence of aa assembly
3) tRNA – transports aa’s to ribosomes for protein assembly
Genetic Transfer in Bacteria – 3 processes:
1) DNA Transformation
Process in which DNA is released by lysis of one bacterium & taken up by a second, leading to a change in phenotype
Another Q: Transformation is best described as acquisition of an inheritable trait by bacteria mediated by DNA
Transfer of inheritable characteristics among bacteria is dependent upon DNA
Rough pneumoncocci grown in the presence of DNA from smooth pneumococci developed capsules
The most primitive mechanism for gene transfer among bacteria
Used in lab to create recombinant DNA & to map gene locations
No cell-to-cell contact required
Involves the uptake of naked DNA molecules (the other processe of genetic transfer do NOT involve…)
The DNA picked up by the recipient cell must be dsDNA
Intracellular DNAase (endonuclease) degrades one strand, providing energy for uptake of the other ssDNA
Uptake depends on presence of protein called competence factor
The ssDNA inserts into homologous regions of recipient chromosome
2) Transduction
Transfer of genetic material from one bacterial cell to another by viral infection
No cell-to-cell contact required
Least susceptible to DNAase
Transfer of DNA via a bacteriorphage = phage-mediated
3) Conjugation (THINK Conjugal Visit)
A form of sexual reproduction in which ssDNA is transferred from one live bacterium to another through direct contact
Pili establish the physical contact
Does NOT require flagella for pair formation
NOTE about pili: The most important function of bacterial pili in causing human infectious disease is by allowing bacteria to adhere to human cells, and NOT in the transfer of DNA between bacteria – although pili do both
This process transfers the greatest amount of genetic information (compared to transformation & transduction)
Ability to grow in the presence of ABX is passed in vivo from one bacterium to another
The pattern of resistance is transferred to other bacteria via conjugation
F factors
Plasmids transferred from a donor cell (F+ cell) to a recipient cell (F– cell) during conjugation
Integration of the F factor plasmid into the chromosome is essential in order for the F factor to be transferred during conjugation
An Hfr (high freq of recombination) is a cell w/ an F plasmid incorporated into the chromosome
During conjugation, portions of the Hfr chromosome are transferred from the Hfr bacterium to the F– bacterium
NOTE: all 3 processes contribute to increase in genetic variation w/in a population
Cell Parts (inside→out):
Nuclear material
Single, double stranded DNA molecule not confined within a nuclear membrane
Plasmid
Contains a variety of genes for ABX resistance, enzymes, and toxins
DNAs
Ribosome
Protein Synthesis
RNA and protein in 50S and 30S subunits
Cell MB = Cytoplasmic Membrane = Plasma MB
Dynamic, selectively permeable MB involved in energy transformations (i.e., oxidative phosphorylation)
Regulates movement of substances, including water, into/out of the cell
Most active cellular structure of bacteria that controls the intake of solutions
Encloses the cytoplasm
Bordered externally by the cell wall
In gram + bacteria, the teichoic acid induces TNF and IL-1 (acute phase)
Periplasm
Space between the cytoplasmic membrane and outer membrane in gram – bacteria
Contains many hydrolytic NZs, including Beta-lactamases
Cell Wall – see notes below on G+ & G- cell wall contents
The basic difference between G+ & G- bacteria is the cell wall structure
Surrounds plamsa MB
Protects cell from changes in osmotic pressure
Anchors flagella
Maintains cell shape
Controls transport of molecules into/out of the cell
N-acetylmuramic acid (NAM) is intermediate (also NAG) in cell wall biosynthesis
In gram - bacteria, the Lipid A induces TNF and IL-1 (acute phase)
Capsule
Gelatinous (polysaccharide) coat often used 1) as an indicator of virulence (Enables them to stick to other cells) & 2) to determine bacterial pathogenicity
**All are polysaccharide, except for Bacillus anthracis, which is D-glutamate
Surrounds cell wall of certain bacteria
Protective against phagocytosis by eukaryotic cells
Loss of capsule promotes phagocytosis
Prevents opsonization by complement
1) The capsule is slimy, making it hard for phagocytes to hold onto the bacterial surface
2) Complement receptors are masked by the capsule, making it difficult/impossible for complement to bind
Capsule must be first coated w/ specific anticapsular antibodies & complement
EXs of bacteria w/ capsules:
Streptococcus pneumoniae
Hemophilius influenzae
Klebsiella pneumoniae
Cryptococcus neoformans (except this is a yeast)
Pilus/Fimbria
Mediates adherence of bacteria to cell surface
Sex pilus forms attachment beween 2 bacteria during conjugation
Glycoprotein
Flagellum
Motility
Protein
Spore
Provides resistance to dehydratin, heat, and chemicals
Keratin-like coat
Dipicolinic acid
Glycocalix
Mediates adherence to surfaces, especially foreign surfaces (i.e. catheters)
Polysaccharide
Extracellular
NOTE: Protoplasts –
A bacterial cell that is free of a cell wall and a capsule
Spherical body produced under appropriate conditions from certain bacilli by the axn of lysozyme or PCN
Cells that have their cell walls & capsules removed by enzymatic (lysozyme) or Abx (penicillin) Tx
G+ cell envelope (inside→out):
Inner Cell Membrane
Cell Wall – components:
Thick murein (peptidoglycan) layer
The backbone biochemical of the bacterial cell wall (makes up ~90% of the cell wall)
Peptidoglycan (murein):
The rigid component of the cell wall in most bacteria – not found in archaebacteria or any eukaryotic cell
Two parts of molecule:
Peptide portion: short, attached, cross-linked peptide chains containing unusual amino acids
Glycan portion: alternating units of amino sugars N-acetylglucosamine and N-acetylmuramic acid
The NAG-NAM backbone is attacked by the enzyme lysozyme
Lipoteichoic acids
Teichoic acids
Unique to G+ bacteria
Polysaccharides that serve as attachment sites for bacteriophages
No outer membrance
Capsule (sometimes)
G- cell envelope (inside→out):
Inner Cell Membrane
Outer Membrane
Cell Wall – components:
More complex than G+ cell wall
Thin murein layer (~10% of cell wall)
Lipoproteins are an integral part of cell wall
Lipopolysaccharide (LPS) layers (= endotoxin)
Located in the outer MB of G- bacteria
Basic chemical structure consists of:
Somatic O Polysaccharide, Core Polysaccharide, and Lipid A (and Keto-deoxy-octanoate!!!)
NOT Teichoic acid (That is only in G+ cell wall !!!)
Lipid A is the most responsible for the endotoxin’s toxic activity
Induces TNF alpha and IL-1
Endotoxin is made of Lipid A
NOT Protein A, O antigen, or core polysaccharide
Only released (toxic) after cell dies & outer MB is broken down (i.e., not “secreted”)
Pathogenic effects occur via activation of complement cascade
Has a chemotactic effect on neutrophilic granulocytes – induces phagocytosis
Host response includes: chills, fever, weakness, aches, shock, death
Accumulates in the gingival crevice in the absence of gingival hygiene
Don’t get clowned by “bacterial metabolites including enzymes” accumulating in the crevice
Shwartzman reaction
In this reaction, endotoxin elicits the response
Rabbit is injected intradermally with a small quantity of lipopolysaccharide (endotoxin) followed by a second intravenous injection 24 hours later and will develop a hemorrhagic and necrotic lesion at the site of the first injection
Phospholipids
Proteins
Other Cell Contents:
Granules (inclusion bodies) – storage areas for nutrients
Volutin – reserve of high energy stored in the form of polymerized metaphosphate that can be used in synthesis of ATP
Commonly associated w/ Pseudomonas aeruginosa & Cornybacterium diphtheriae
Sulfur granules
PHB (polyhydroxybutyric acid)
Metachromatic granules ⋄ Diphtheria
Plasmids –
Extrachromosomal, circular, dsDNA molecules capable of replicating independently of the chromosome
Molecules of DNA that are separate from the bacterial chromosome
Confer conjugal fertility – shooting blanks
Carry genetic information between bacteria
Example: R (resistance) factor
Replicate while attached to the bacterial cell membrane
Do NOT exist as circular RNA molecues
Multiple drug resistance is related most closely to plasmids (NOT viruses, transformation, or cell chromosomes)
ABX Resistance
Most antibiotic resistance in bacteria is caused by genes that are carried on plasmids
Plasma-mediated antibiotic resistance has been observed with all of the following EXCEPT one:
S. aureus, B. pertussis, and H. influenzae, N. gonorrhea, S. pyogenes???
(Google says they all do!!!)
PCN resistance in N. gonorrhea is explained by its production of a plasmid encoded beta-lactamase
Strep pyogenes is resistant to erythromycin (plasma-mediated??), but is sensitive to bacitracin & penicillin
Determine traits not essential for the viability of the organism but that change the organism’s ability to adapt
Transposons –
Consists of two insertion sequences flanking an ABX resistance gene
Pieces of DNA that move readily from one site to another, either w/in or between the DNAs of bacteria, plasmids, or bacteriophages
Genes that often encode proteins necessary for ABX resistance and that can change positions on a chromosome or “jump” from a plasmid to a chromosome
Frequently associated w/ formation of multiple-drug resistance plasmids
Encapuslated Bacteria
Polysaccharide capsule is antiphagocytic virulence factor
IgG2 necessary for immune response`
Capsule serves as antigen in vaccines (Pneumovax, H. influenzae b., Meningococcal vaccines)
Quellung Rxn = Caspsular “Swellung” rxn ⋄ capsule swells when specific anticapsular antisera are added
Streptococcus Pnuemoniae
Haemophilus influenzae
Neisseria meningitides -BIodome
Klebsiella pneumoniae
Cryptococcus Neoformans – Inside the Crypt - yeast
Exotoxin Vs. Endotoxin
|Property |Exotoxin |Endotoxin |
|Source |Some Gram + and Gram - |Cell wall of most Gram – ONLY |
|Secreted |Yes (Diffuse out) |No (Just a breakdown product) |
|Chemistry |Polypeptide |Lipopolysaccharide |
| | |Most bacterial endotoxins are composed of |
| | |lipoprotein-polysaccharide complexes |
|Location of genes |Plasmid or bacteriophage |Bacterial chromosome |
|Toxicity/Potency |High (fatal if dose on the order of 1microg) |Low (fatal dose on the order of hundreds of |
| | |micrograms) |
|Clinical effects |Various |Fever, shock |
|Mode of action |Various |Includes TNF and IL-1 |
|Antigencity |Induces high titer antibodies called antitoxins |Poorly antigenic – that’s why no vaccine to this. |
|Vaccines |Toxoids are used |No toxoids formed and no vaccine avail. |
|Heat Stability |Destroyed rapidly at 60 degrees C (except Staph |Stable at 100 degrees C for 1 hour |
| |enterotoxin) (Heat Labile) | |
|Typical Diseases |Tetanus, botulism, diphtheria, anthrax |Meningococcemia, sepsis by Gram- rods |
|Specificity |High | |
|Miscellaneous |Detoxified by formalin |Different from exotoxins in that they activate |
| |Highly immunogenic |complement via the alternate pathway |
| | |Play a role in PD because the role endotoxins play in |
| | |inciting an inflammatory response |
Effects of Endotoxin
1. Activates Macrophages
⋄Produce IL-1 (acts on T + B cells)⋄ Fever
⋄Produce TNF ⋄ Fever, Hemorrhagic tissue necrosis
⋄Produce Nitric Oxide ⋄ Hypotension (shock)
2. Activates Complement (Alternative Pathway)
⋄Produce C3a ⋄ Hypotension, Edema
⋄Produce C5a ⋄ Neutrophil Chemotaxis
3. Activates Hageman Factor (Clotting Factor)
⋄Coagulation Cascade ⋄ DIC (Disseminated Intravascular Coagulation)
|Some Protein Toxins (Exotoxins) Produced by Microorganisms That Cause Disease in Humans |
|Organism |Exotoxins |Disease |Action |
|Gram + | | | |
|Clostridium botulinum |Several neurotoxins (A,B,E) |Botulism |Paralysis, blocks neural transmission |
|(Gram +) | | |Blocks release of Ach – just like Lambert Eaton’s |
| | | |Spores found in Canned Food, Honey |
|Clostridium perfringes |a-toxin (a lecinthinase) |Gas gangrene |Destroys integrity of cell MBs |
|(Gram +) |K-toxin (a collagenase) | |Breaks down fibrous tissue |
| | | |Get double zone of hemolysis on blood agar |
|Clostridium tetany |Neurotoxin (tetanospasmin) |Tetanus |Spastic paralysis interferes w/ motor neurons |
|(Gram +) | | |Blocks release of inhibitor glycine |
| | | |Causes Lockjaw |
|Corynebacterium |Diphtheria toxin |Diphtheria |Blocks protein synthesis at level of translation |
|(Gram +) |*a lysogenic phage encodes it | |Inactivated E2-F by ADP ribosylation (similar to |
| | | |Exotoxin A of Psuedomonas) |
| | | |Causes Pharyngitits/Psuedomembrane |
|Streptococcus Pyogenes (Group A Strep) |Various hemolysis | |Lysis of RBCs |
|(Gram +) |Streptolysin O |Rheuamtic fever |Causes symptoms of rheumatic fever |
| |Streptolysin S | |Causes rash of scarlet fever |
| |Erythrogenic |Scarlet fever | |
|Staphylococcus aureus |Enterotoxin –Very fast food poisoning |Food poisoning |Intestinal inflammation |
|(Gram +) | |Toxic Shock Syndrome |Toxin is a superantigen that binds to MHC II and T |
| | | |cell receptor, inducing IL-1 and IL-2 synthesis in |
| | | |toxic shock syndrome |
|Bacillus anthracis | |Anthrax |One toxin in the Tripartite toxin complex is an |
|(Gram +) | | |adenylate cyclase |
|Gram - | | | |
|Shigella dynsenteriae |Neurotoxin |Bacterial (bacillary) |Hemorrhage, paralysis |
| | |dysentery | |
|Escherichia coli | |Diarrrhea |Heat labile toxin stimulates adenylate cyclase by |
| | | |ADP ribosylation of G protein |
|Vibrio Cholerae | |Rice-water diarrhea |Stimulates adenylate cyclase by ADP ribosylation of |
| | | |G protein, increasing pumping of Cl- and H20 into |
| | | |the gut |
|Bordetella pertussis | |Whooping Cough |Stimulates adenylate cyclase by ADP ribosylation |
| | | |Inhibits chemokine receptor, causing lymphocytosis |
Two other examples:
Pyrogenic exotoxin A – similar to the staphylococcal toxic shock syndrome toxin
Exotoxin B – a protease that rapidly destroys tissue
NOTE: one Q reads, “tetanus & diphtheria are similar in nature w/ respect to production of exotoxins”
Botulism:
Uncommon, life-threatening poisoning (not infection)
An intoxication, not an infection – THINK BOTU TOXU
Caused by the toxins produced by the G+ anaerobic bacillus Clostridium botulinum
Heat-labile neurotoxin usually from improperly canned food
These exotoxins (neurotoxins) are the most potent poisons known to humans
Can severely damage nerves & muscle
Bind to presynaptic nerve & block release of ACh from CNS nerve cells
Causes flaccid paralysis of skeletal muscle
Cause loss of motor function, including respiratory failure = death
Occurs w/ botulism food poisoning, wound botulism, & infant botulism
Infant botulism = floppy baby syndrome – leads to failure to thrive
Foods most commonly contaminated – home-canned vegetables, cured pork/ham, smoked/raw fish, & honey or corn syrup
Cannot grow in human body – only the toxin causes disease
So another Q reads: It does NOT require the presence of a live organism
Mortality from botulism is ~25% – death usually caused by respiratory failure during the 1st week of illness
Symptoms appear 8-48 hours after ingestion of toxin:
Initial CN paralysis w/ diplopia (double vision), dysathria (difficulty speaking), & pupil dilation
Followed by limb & trunk muscle weakness or paralysis
Antitoxin is given, along w/ respiratory support – Don’t give Abx bc you’ll kill bact and rls more exotoxin.
Cannot undo damage, but may slow/stop further physical & mental deterioration – body can heal itself over months
Diphtheria
ABCDEFG
ADP ribosylation
Beta-prophage (exotoxin is encoded by)
Club Shaped (Coryne means club shaped)
Diphtheria
Elongation Factor 2 (Exotoxin inhibitrs protein synthesis via ADP ribosylation of EF-2)
Granules (Metachromatic Granules)
Causes pseudomembranous pharyngitis
Grows on tellurite agar
Bacteria Groupings
The following diseases are transmitted by droplets or droplet spray:
Whooping cough
Meningitis
Diphtheria
Pneumonia
VSV
NOT Condylatum acuminatum
Gram + (purple/blue)
Rods
Clostridium (tetany, botulism, difficile – psuedomemb. Colitis, Gas gangrene - perfringes) – SPORE FORMING
Corynebacterium (Diphtheria)
Listeria (Fetal Death, cholera, dysentery, meningitis)
Bacillus (Anthrax) – SPORE FORMING
Cocci
⋄ Catalase +
Staphylococcus
⋄ Coagulase +
S. aureus
⋄ Coagulase –
S. epidermidis (Nosocomial with valves/joint replacement)
S. saphrophyticus (UTIs in sexually active women)
⋄ Catalase –
Streptococcus
Hemolysis
Alpha
Capsule (optochin sensitive)
S. Peumoniae (Pneumonia)
NO Capsule (optochin resistant)
Viridans Streptococci (i.e. S. mutans) (Endocarditis, caries, Brain abscess)
Beta
Group A (Bacitracin Sensitive) -- according to carb found in cell wall
S. Pyogenes
Group B (Bacitracin Resistant)
S. agalactiae (Neonatal meningitis, pneumonia, sepsis)
Gamma
Enterococcus (E. Faecalis and Peptostreptococcus)
**Can be either gamma or alpha
Gram - (Pink)
Cocci
Neisseria
Maltose Fermenter
N. meningitidis (Meningitis and Septicemia)
Non-Maltose Fermenter
N. gonorrhoeae
“Coccoid” (rods)
Haemophilus influenzae
Pasteurella (Cat and dog bites ⋄ Cellulitis)
Brucella (Brucellosis fever)
Bordetella pertussis (whooping cough)
Rods
Lactose Fermenter (pink on MacConkey’s)
Fast Fermenter
Klebsiella (Bronchopneumonia and Nosocomial UTIs)
Escherichia coli (UTIs, Diarrhea)
Enterobacter (Diarrhea)
Slow Fermenter
Citrobacter
Serratia (Makes make red pigment)
Others
NON-Lactose Fermenters
Oxidase -
Shigella (Bloody Diarrhea, Paralysis)
Salmonella (Enteric Fever, Typhoid Fever, Bloody Diarrhea, Osteomyelitis in Sickle Cell pts)
Proteus (UTIs)
Oxidase +
Pseudomonas (Pneumonia, Burn wound infection, Osteomyelitis, UTI, Contact lens infection)
MORE on G- aerobic rods and cocci:
Pseudomonas family (really just P. aeruginosa):
G-, straight or curved rods, most are obligate AERobes (PETS -- AIR)
Think PSEUdomonas – Pneumonia (in CF pts), Sepsis (black skin lesion), External Otitis (swimmer’s ear), UTI
Motile by means of polar flagella
Produce characteristic fluorescent pigments (P. aeruginosa), but others do not
Has ability to adapt and thrive in many ecological niches, from water to soil to plants & animals, including humans
Exotoxin A
Inhibits protein synthesis (not DNA synthesis)
Inactivates E2-F
Important nosocomial infection in immunocompromised & chronically ill patients
People w/ cystic fibrosis, burn victims, individuals w/ cancer & pts requiring extensive care in hospitals
Nosocomial infections often caused by:
Staph, Strep, E. coli, & P. aeruginosa are common bugs in hospital-acquired infections
Once established, produces a number of toxic proteins which cause not only extensive tissue damage, but also interfere w/ the human immune defense mechanisms
An infection followed a serious skin burn that is characterized by greenish pus and is resistant to ABX is probably caused by P. aeruginosa (think P. aeru-green-osa)
Pyocyanin pigment
Gentamicin is a broad spectrum aminoglycoside antibiotic effective in treating bacteremias caused by P. aeruginosa
Volutin (aka “metachromatic granule”) is a reserve of high energy stored in the form of polymerized metaphosphate that can be used in synthesis of ATP
Metachromatic granules are commonly associated w/ Pseudomonas aeruginosa & Corynebacterium diphtheriae (Remember ABCDEFG)
Burn victims
Which of the following will not affect burn victims?
P. aeruginosa, Mycobacterium ulcernus, C. tetany, Staph aureus --- VERIFY
Bordetella
Neisseria
Brucella
Legionella
Gram – rod
Stains poorly, use Silver stain
Grown on charcoal yeast extract culture with iron and cysteine
Aerosol transmission from water source habitat
Legionella pneumophilia is transmitted via aerosolized organisms in air conditioning cooling towers
French Legionnaire with his Silver Helmet, sitting around a campfire (charcoal) with his iron because he’ no Cissy (cysteine) and his atypical Pontiac Car parked out front with the A/C on
Young Healthy person exposed to Legionella Pneumophilia, what happens ⋄
Initial symptoms are flu-like, including fever, chills, and dry cough. Advanced stages of the disease cause problems with the gastrointestinal tract and the nervous system and lead to diarrhea and nausea
Causes Pontiac fever and Legionnaires’ disease and Atypical Pneumonia
Treat w/ erythromycin
Haemophilus Influenzae – The Haemophilus influenza POEM – here it is.
haEMOPhilus causes Pneumonia, Otitis, Epiglottitis, Meningitis,
Large Capsule
Small gram – coccobacillary “coccoid” rod
Aerosol transmission
Most invasive disease is caused by capsular type b
Vaccine contains type b capsular polysaccharide conjugated to diphtheria toxoid or other protein
Tx with Cephalosporin
Think use CEPH because its your brain (MENINGITIS)
Produces IgA protease
Culture on chocolate agar requires Factor V (NAD) and X (hematin) – Go to the FIVE (V) and DIME (X) store to buy chocolate
Does NOT cause the Flu – that is a VIRUS
Helicobacter pylori
Gram – rod
Causes gastritis and 90% of duodenal ulcers
Risk factor for peptic ulcer and gastric carcinoma – Now officially considered a carcinogen.
Urease positive (cleaves urea to ammonia) – along with Proteus
Bacteria in the mouth use all for nutrients except????
Bicarb or Urea
Tx with Triple Tx
Bismuth ⋄ Pepto-bismal (think Stomach)
Metronidazole
Tetracyclin or Amoxicillin
G- anaerobic rods:
Bacteroides
Fusobacterium
Prevotella
Facultative anaerobic, G- rods
Highly invasive & can readily become resistant to Abx
Enterobacteria
All have endotoxin
All are found in GI tract (except Y. pestis)
All are motile (except Klebsiella & Shigella) – Kevin Schaffer never liked to go proselyting.
All ferment glucose and are oxidase negative
Think COFFEe
Capsular ⋄ Related to the virulence
O-antigen, and Oxidase Negative ⋄ All have Somatic O-antigen (Polysaccharide of Endotoxin)
Flagellar antigen ⋄ The Flagellar H antigen is found in motile species
Ferment glucose
Enterobacteriaceae
Escherichia
Short, G-, facultative anaerobic rods
Motile via a peritrichous flagella
Normally present in intestines
Contaminates water supply
DON’T Giardia is NOT in our water supply
Capable of causing mild to severe forms of enterocolitis
The most common cause of UTIs (cystitis)
The most common causative organism in G- sepsis
Etiologic agent of traveler’s diarrhea
Use ELISA assay to detect an enterotoxin produced by E. coli
ELISA can also detect:
An enterotoxin produced by Vibrio cholerae (a curved, G- bacillus)
An enterotoxin produced by S. aureus, which toxin causes acute-onset food poisoning
Viral gastroenteritis
Shigella vs. Salmonella (not usually found in human GI???)
Both cause bloody diarrhea
Both non-lactose fermenters
Both invade intestinal mucosa
salMonella is Motile and can invade heMatogenously
Symptoms of Salmonella can be prolonged if tx with ABX
Salmon (animal reservoir)
Oh, Shiii, Shigella is more virulent
Shigella is transmitted via food, fingers, feces, and flies
Klebsiella
Causes severe lobar pneumonia in people w/ underlying conditions like alcoholism, diabetes, COPD
Yersinia
Enterobacter
Vibrionaceae – Vibrio cholerae
Pasteurellas – Haemophilus, Gardnerella, Pasteurella
Gram - and PCN
ALL gram - are resistant to PEN-G, but may be susceptible to PCN derivatives, like ampiciliin
The gram – outer membrane layer inhibits entry of PEN-G and Vancomycin
Spirochetes – Treponema & Borrelia
Treponema pallidum
Found elsewhere in the file – syphilis
Darkfield exam
Dx
FTA-ABS
Specific for Treponema, and turns positive earliest in disease
Find The Antibody- ABSolutely
VDRL
Many false positives
Viruses, Drugs, Rheumatic fever, Lupus/Leprosy
Borrelia Burgdorferi – Lyme Disease:
B for Big
Only Borrelia can ve seen using aniline dyes (Wright or Giemsa stain) in light microscopy
Named after Lyme, Connecticut
Most commmon vector-borne disease in the northern hemisphere (from arthropods)
Signs/symptoms: skin rashes, arthritis, & neurological symptoms
Hallmark: erythema chronicum migrans – red macule w/ central clearing – “bullseye” at site of bite
Organism found in tick vectors that have fed on infected deer or mice reservoirs
After hiking through the woods, pts presents with polyarthritis, paresthesias, and a skin rash
Rickettsiae & Chlamydiae – Rickettsia, Coxiella, Chlamydia
Both rickettsia & chlamydia:
Can cause human disease
Posess both DNA & RNA – Bacteria have Both.
Growth can be inhibited by antimicrobial drugs
Are inactivated by heat, drying, and chemical agents
NOT “multiply in bacterial cells”
CHLAMYDIA:
C. trachomatis
Lots of info found elsewhere in file
C. psittaci
Transmitted by inhalation of organisms from infected birds & their droppings
Birds + pneumonia = think C. psittaci
Rickettsia:
Small G- aerobic coccobacillary bacteria that are obligate intracellular parasites
Rickettsia and viruses have in Common they are both intracellular parasites
The only bacteria that are IPs are Rickettsia and Chlamydia (they stay inside when it’s Really Cold)
This means they only survive by establishing residence inside animal cells and utilizing the host’s ATP
Both Rickettsia and Chlamydia have this ATP/ADP translocator to assist them in “stealing” ATP
Rickettsia still can oxidize certain molecules and create ATP, whereas Chlamydia does not have a cytochrome system and can not produce ATP
Rickettsia needs CoA and NAD
Results from insect bites – arthropod transmission
Requires an insect vector in the transmission to humans – think Rickettsia = Insectsia
Triad:
Headache, Fever, Vasculitis
Most rickettsial diseases produce severe illness in humans because rickettsiae are destructive for endothelial cells
NOT because they produce potent exotoxins, cause extensive CNS damage, or are destructive to epithelial cells
For Dx and culturing
You can inoculate into living tissues (chicken embryo yolk sac or cell culture)
Target cell: endothelial cell of capillaries and other small blood vessels
Produce severe illness in humans because they attack the endothelial cells
Present as systemic symptoms of headache, myalgias, and fever, followed by rash
Maculopapular rash appears on palms of hands & soles of feet
Rash spreads to the trunk
Can be dx with certain strains of Proteus vulgaris because they both have certain antigens in common
Rickettsia and Viruses have the following in common:
Growth environment – both require living cells for growth
Small Size
Being obligate intracellular parasites
NOT in common with virus (in other words…what they have in common with fellow bacteria):
Have BOTH DNA and RNA (viruses only have one or the other)
Synthesize their own proteins (viruses do not)
Are sensitive to ABX (obviously viruses are not)
Reproduce by a complex cycle w/ Binary Fission (Bacteria = Binary Fission; Viruses = synthesis & assembly)
Possess an energy yielding, autonomous enzyme metabolism (Rickettsia only)
Divided into two groups:
Spotted-Fever Group – Rash is inward (from palms inward)
Rocky mountain spotted fever tick
R. rickettsii (which accounts for 95% of rickettsial diseases in U.S.)
Endemic in East Coast, that is why it’s a fever only in the Rockies
Queensland tick fever tick
Boutonneuse fever, Kenya tick fever tick
Siberian tick fever tick
Rickettsial pox mite
Is the rickettsia disease that may have oral manifestations (NOT Brill’s disease, or epidemic typhus)
Rash that spreads to lips and Buccal mucosa.
Typhus Group – Rash is outward spread
Louse-borne typhus (epidemic typhus) louse
R. prowazekii
Murine typhus (endemic typhus) flea
R. typhi
Scrub typhus mite
R. tsutsu-gamushi
Q fever (Queer – has no rash) inhalation
Coxiella burnetii
Does NOT cause a skin rash
Does NOT require an arthropod vector
**The Only rickettsia that is xmitted via aerosol (dust)
Tx: tetracycline & chloramphenicol
Mycoplasmas – Mycoplasma, Ureaplasma
Lack a cell wall – resistant to beta-lactam ABX
Has ergosterol in cell membrane
Require sterols for growth
M. pneumoniae
Transmitted by respiratory droplets
Frequent in military recruits and prisons
Cause atypical pneumonia “walking pneumonia”= #1 cause of pneumonia in young adults
Cold agglutinins used in presumptive dx (IgM)
PCN resistant so tx with Ery or Tetra
G+ cocci – Staphylococcus, Streptococcus, Enterococcus, Peptostreptococcus
Endospore forming rods & cocci – Bacillus, Clostridium
Regular non-spore forming G+ rods – Lactobacillus
Irregular non-spore forming G+ rods – Corynebacterium, Actinomyces
Actinomycetes – Streptomyces, Nocardia, Rhodococcus
Staphylococcus
G+ coccus that grows in grape-like, usually occur in irregular clusters in culture (NOT in pairs, chains, etc)
Kaplan says they CAN occur in pairs & short chains
Facultative
Posess both superoxide dismutase & catalase
Bacteria most commonly found on the skin
Most common manifestation of staph infections in humans is cutaneous abscesses
One answer option, Scalded skin syndrome, is staph-related, but not the most common manifestation of staph
Resistance to PCN
Most frequently develops resistance to PCN
Gains resistance to PCN by an having an NZ that attacks PCN
Staph infections are suppurative infections usually caused by S. aureus
Abscess formation is characteristic
EXs: abscesses, endocarditis, impetigo, osteomyelitis, pneumonia, septicemia, cavernous sinus thrombosis
S. aureus
Not part of normal flora
Can cause acute-onset food poisoning via enterotoxins
Most common cause of suppurative infections involving the skin, joints, & bones
Osteomyelitis is most commonly caused by S. aureus
Causes Acute Bacterial Endocarditis
Most commonly causes skin infections (pyoderma)
Most often associated with fatalities following influenzal infection
Coagulase(+) [other Staphylococci are coagulase(-)]
Coagulase test is the prime criterion for classifying a bug as Staph aureus – from other Staph species
Coagulase is important to the pathogenicity of S. aureus because it helps to establish the typical abscess lesion – see 2000 Q56 to discuss w/ Jake
Coagulase also coats the surface w/ fibrin upon contact w/ blood, making it harder to phagocytize
NOTE: this is NOT a polysaccharide capsule that forms
Resistant to PCN
Tx: methicillin, nafcillin, oxacillin [or for MRSA – vancomycin]
Protein A – Know this.
Binds the Fc receptor of IgG, thereby blocking complement activation by the classical pathway and inhibiting phagocytosis
(cell wall component) may be responsible for virulence
Antiphagocytic
Elicits Hypersensitivity
Causes Platelet injury
Staphylokinase cleaves plasminogen to plasmin (Streptokinase & Urokinase do, too) – Kind of anti-coagulase
Staphylococcal food poisoning:
Food contaminated w/ toxins of certain types of Staph; generally results in diarrhea & vomiting
Gastroenteritis is principal feature
Incubation period of 2-4 hours (quick) (NOT the case for cholera, botulism, salmonellosis)
Streptococcus
General Info
Facultative anaerobic G+ cocci that grow in pairs or chains in culture
Does have some aerobics, so:
If you pull human saliva out and let it grow on agar in air for 24 hours, strep will have the most out of the other Facultative Anaerobics (Lactobacillus, Staph, Fusobacterium, and Actinomycetes)
When growing glucose in an unbuffered medium, will cause pH to drop
Most numerous group in the oral cavity
Most predominant bug in dental plaque
Streptococcal pharyngitis infections are preferentially treated w/ Abx affecting cell wall synthesis
Lack catalase – although they can live in conditions where O2 is present
1) α-hemolytic Streptococcus – Know this.
Produce a zone of incomplete hemolysis around the colony & adjacent green discoloration
Most common organism producting subacute bacterial endocardititis (S. sanguis, under Viridans Streptococci, below)
Most often associated w/ infective endocarditis
Most oral Streptococci are alpha-hemolytic streptococcus
S. pneumoniae (aka Pneumococcus ) (Optochin sensitive)
Think breathing in through the nose, because its AFRAID of the CHIN)
Most common cause of community acquired bacterial pneumonia in the U.S.
Very well known for its large polysaccharide capsule (so is Cryptococcus neoformans – a yeast.)
Strains of Strep pneumonia are distinquished by their polysaccharide capsules
Host response are chiefly mediated by opsonins
Antigens
Capsular
Virulence of pneumococcus is associated with its capsular polysaccharide
C-polysaccharide
F-antigen
M-protein
NOT erythrogenic toxin (that’s strep pyogenes – Scarlet fever/Rheumatic Fever)
Treatment/Prevention:
Vancomycin or erythromycin
PCN resistance on the rise – due to transformation
Vaccine: 23-valent vaccine available
Viridans Streptococcus (optochin resistant)
NOT afraid of the CHIN
Normal flora of the oropharynx and cause dental caries and bacterial endocarditis
S. sanguis – the major cause of subacute endocarditis in those w/ abnormal heart valves
Lots of Blood in heart
S. mutans – causes dental caries
Treat w/ PCN
2) β-hemolytic Streptococcus
Produce a clear zone of hemolysis around the colony = complete hemolysis
How do you classify Strep? ⋄ By Hemolysis, BUT if it says How do you classify Beta hemolytic Strep? ⋄ Lancefield
Group A, B, C, etc., based on CHO found in the cell wall (C Carbohydrate) (Lancefield groups)
1) Group A β-hemolytic Streptococcus
Most likely Pathogenic for humans (among Strep bacteria, or what?)
M-protein: -- JUST like S. PneuMoniae
Is closely associated w/ the virulence of the bacteria
Specific antigenic subtypes based on the cell wall M-protein
Affects the host by inhibiting phagocytosis
Antibody to M-protein enhances host defenses against S. pyogenes
Consists only of S. pyogenes
Streptococcus pyogenes
G+ coccus that occurs in pairs or chains
Frequently part of the endogenous microflora that colonizes the skin & oropharynx
But NOT usually found in plaque
Cause of several acute pyogenic infections in man (Scarlet fever, erysipelas, sore throat [strep throat])
Pyogenic pathogens are associated with acute suppurative inflammation type
Toxins:
Erythrogenic exotoxin (aka pyrogenic exotoxin) –
Causes the rash of Scarlet fever
A Strep virulence factor that acts like a superantigen, mediating a variety of cytokine-induced effects that can result in life threatening disease
Streptokinase –
Cleaves plasminogen to plasmin
Hence has the ability to dissolve a preformed blood clot (same with Stapylokinase and Urokinase)
Streptolysin O –
A hemolysin that is inactivated by oxidation (oxygen-labile); antigenic
Streptolysin S –
a hemolysin that is not inactivated by oxygen (oxygen-stable); not antigenic
Hyaluronidase
The spreading factor produced by certain streptococci
NOT involved in Arthus reaction, Shwartzman phenomenon, or localization of staph infections
Streptokinase, Streptodornase, deoxyribonuclease
Diseases of S. pyogenes:
Toxigenic
Scarlet Fever
Toxic Shock Syndrome
Suppurative
Strep throat
Erysipelas – acute contagious disease marked by a circumscribed red eruption on the skin + chills/fever
Impetigo – localized, intraepidermal skin infection seen in preschool-aged children
Cellulitis –
Results from traumatic inoculation
Diffuse inflammation of soft tissue – painful swelling from purulent exudates that spread along the facial planes and separate the muscle bundles
Not circumscribed
Not confined to one area
Non-Suppurative (Immunologic)
Rheumatic fever (search ‘rheumatic fever’ – more info elsewhere in the file)
PECCS
Polyarthritis, Eythema marginatum, Chorea, Carditis, Subcutaneous nodules
Begins w/ sore throat, then progresses to rapid temperature rise, prostration, joint inflammation
The heart is often affected
Can be a sequela of Scarlet Fever
Can result in pathologic changes in the heart valves
Acute poststreptococcal glomerulonephritis
Symptoms: fluid retention, dark tea-colored urine, BP elevation
Occurs primarily in children
Allergic reaction of glomerular and vascular tissue to beta-hemolytic streptococcal products
The two most important post-streptococcal diseases are:
1) Rheumatic fever
2) Glomerulonephritis
Different Q: Which of the following are related to streptococcal cross-antigenicty…
Rheumatic fever & acute glomerulonephritis
Remember they are from Hemolytic sequelae
2) Group B β-hemolytic Streptococcus
Consists of S. agalactiae
Leading cause of neonatal pneumonia, meningitis, & sepsis
***Although not Streptococci, BOTH Staph aureus and Listeria are ALSO Beta hemolytic
3) γ-hemolytic Streptococcus
Produce no hemolysis
Enterococci
Pen G resistant
Major concern with enterococci in the hospital
Cause UTI and Subacute endocarditis
Part of normal fecal flora
Lactic Acid bacteria
General
Use lactic acid fermentation pathway (pyruvate → lactic acid)
Aciduric – can tolerate acid environment
Acidogenic – acid-forming
NOTE: lactic acid is the main cause of enamel decalcification
Lactobacillus
Labeled as cariogenic because of ability to produce acid
Significant secondary invader of dental caries
In coronal caries, causes progression of existing caries
Found in deep dental caries and increases in the saliva during periods of caries activity
Regular, non-sporing, G+ bacteria
Most likely to tolerate the lowest pH (lower than even Streptococci)
Found in vagina, GI tract, mouth
L. acidophilus – added to milk products to aid in digestion of milk products
Bacterial enzymes convert milk sugars to digestible products
Streptococcus
Streptococci are the predominant bacteria found in saliva
S. mutans – Know this.
Smooth surface caries
First stable organism to colonize oral cavity and remains in significant numbers??? LOOK-UP – 2002 Q05
In the presence of sucrose, produces deposits of a gummy polysaccharide called glucan
Produces Glycosyltransferase from Sucrose
End product of glucose metabolism is lactate
Lactic acid forms in large quantities during the degradation of glucose
Capsule has importance virulence factor that enhances oral accumulation
Can be distinguished from other Streptococci by:
Production of adherent Extracellular polysaccharide
Fermentation of mannitol or sorbitol
(The previous two are the two most important factors for initiation of caries)
Production of intracellular polysaccharide
Colonial morphology on mitis-salivarius agar
NOT gram stain (they’re all G+)
Actinomyces – root surface caries
Mycobacteria
M. tuberculosis – Often resistant to multiple drugs
M. kansasii – Pulmonary like TB symptoms
M. scrofulaceum – Cervical lymphadenitis in kids
M. avium-intracellulare – Causes disseminated disease in AIDS
M. leprae – leprosy (M. leprae = Hansen’s bacillus)
Form mycolic acids, which are unusual acids associated w/ the cell wall
Mycolic acids:
Localized in the inner leaflet of the mycobacterial cell wall
Involved in maintaining rigid cell shape
Contribute to resistance to chemical injury
Protect against hydrophobic Abx (isoniazid – inhibits mycolic acid biosynthesis)
NOTE: also present in cell walls of actinomycetes
G+, nonmotile, rod-shaped bacteria
Produces neither exotoxins nor endotoxins
Acid-fast staining
Important in the early diagnosis of active mycobacterial infections
Smear is stained w/ carbol-fuschin stain, decolorized w/ acid alcohol, counterstained w/ methylene blue
Acid-fast organisms appear red against blue background (due to lipids/waxes [including mycolic acids] in the cell wall)
Has highest lipid count in cell wall
Remember Gram + is normally BLUE, but here it is RED
Classic skin test (PPD skin test)
May indicate an infection, but not whether the infection is active
A PPD (purified protein derivative) from M. tuberculosis is injected subcutaneously
Observation of a delayed (Type IV) hypersensitivity reaction indicates a hypersensitivity to tuberculoproteins
M. tuberculosis – TB –
Obligate aerobe
Cord Factor ⋄ Glycolipid found in the cell wall of M. Tb and allows them to grow in serpentine cords
Slow-growing – 20-60 days before growth can be visualized
NO exotoxins or endotoxins
Tubercle (Ghon focus) –
A small, rounded nodule produced by infection w/ M. tuberculosis
Primary lung lesion in the periphery
Usually in lower lobes
Primary lung lesion of pulmonary TB
Primary TB
Nonimmune host (usually child)
⋄ Ghon Focus ⋄ Ghon complex (from there it can go to below options)
Heal by fibrosis ⋄ Immunity and Hypersensitivy ⋄ Tuberculin positive
Progressive lung disease (HIV) ⋄ Death (rare)
Severe bacteremia ⋄ Miliary TB ⋄ Death
Preallergic lymphatic or hematogenous dissemination ⋄ Dormant tubercle bacilli in several organs ⋄ Reactivation in adulthood ⋄ Extrapulmonary TB (See below)
Secondary TB
Partially immune hypersensitized host (usually adult)
From either Reinfection or Reactivation tuberculosis in the lungs
Causes fibrocasseous cavitary lesion in upper lobes
Goes to Extrapulmonary TB
CNS (parenchymal TB or meningitis
Vertebral body
Lymphadenitis
Renal
GI
Hypersensitivity (IV) to M. tuberculosis is manifested by necrosis
Tuberculosis is produced by an agent that does NOT produce exotoxin NOR endotoxin. Know this
M. tuberculosis has the highest lipid content in the cell wall (compared to E. coli, L. casei, S. aureus)
Granulomas w/ multinucleate giant cells and caseation necrosis characterize lymph node involvement w/ M. tuberculosis in the lateral neck
M. leprae – leprosy (M. leprae = Hansen’s bacillus)
Also induces delayed-type hypersensitivity in patients
Cannot grow in vitro on ay culture medium (same for syphilis)
Likes cool temperatures
Reservoir in US – Armadillos
LEthal
Spore-forming bacteria
Spores are specialized resistant cells produced by many microorganisms to enhance the survival potential of the organism
Spores are primitive, usually unicellular cells by which bacteria, fungi, green plants reproduce
Spores grow into new organisms via asexual reproduction (w/o uniting w/ another reproductive cell)
Active spores are thin-walled; dormant spores are thick-walled
Spores contain large amounts of Calcium Dipicolinate = calcium + dipicolinic acid
Calcium dipicolinate is thought to be responsible for the heat resistance of the spore
Spores are a problem in sterilizing instruments & equipment because they are resistant to physical & chemical agents
EX: bacterial endospore – heat-resistant spore
More difficult to destroy than HIV, HBV, TB virus
Requires autoclaving at 121°C for 20 min at 15 psi
Most important endospore producers: Bacillus & Clostridium genera (perfingens and tetany)
Difference between Clostridium and Bacillus is that Bacillus is aerobic (Nice Pets Must BBBBreath)
Clostridium
C. Botulism
Botulism is caused by C. botulinum
From Bad Bottles of food or honey from Bees
Floppy Baby
C. Perfringens
Gas gangrene is caused by C. perfringens
Gas gangrene is produced by a G+, spore-forming anaerobic bacillus
Perforates a gangrenous leg
C. Difficile
Produces a cytotoxin, an exotoxin that kills enterocytes, causing pseudomembranous colitis
Often secondary to ABX use, especially clindamycin or ampicillin
Causes Diarrhea
Tx with Metronidazole
C. tetani
Tetanus is caused by C. tetani
Exotoxin blocks glycine release, which normally is a neurotransmitter inhibitor, so paralysis ensues
Lockjaw
Bacillus ⋄ Think B for Breathing!!
Anthrax is caused by B. anthracis
The antiphagocytic capsule is composed of D-glutamate, not polysaccharide
Contact via malignant pustule (painless ulcer), but can progress to death
Black skin lesions ⋄ vesicular papules covered by black eschar
Inhalation can cause life-threatening pneumonia
Septicemia = sepsis
Happens when there are too many bacteria in the bloodstream (or their toxins) to be removed easily
Symptoms include: fever, weakness, nausea, vomiting, diarrhea, chills
Can lead to septic shock
Associated w/: S. aureus, E. coli, Klebsiella
The most common causative organism in G- sepsis is E. coli
Bacteremia
Refers to the presence of viable bacteria in circulating blood
Clinical signs/symptoms usually not present
EX: From dental prophy, bugs around teeth enter the blood stream→bacteremia
Viremia
A viral infection of the bloodstream
Major feature of disseminated infections
The infecting virus is most susceptible to circulating antibodies
Some enzymes:
Streptodornase (DNAase) – depolymerizes DNA in exudates or necrotic tissue
Hyaluronidase – degrades HA, which is the ground substance of subcutaneous tissue
Produced by Streptococcus, Staphylococcus, Clostridium (Think Perfringens)
The purposes of Hyaluronidase are
Avoid the immune system
Cause disease in host
Disseminate
NOT for Nutrition
The spreading factor produced by some Strep
|Some Extracellular Enzymes Involved in Microbial Virulence |
|Enzyme |Action |Example of Bacteria producing enzymes |
|Hyaluronidase |Breaks down hyaluronic acid |Strep, Staph, and Clostridium |
|Coagulase |Converts fibrinogen to fibrin |Staph. Aureus |
| |*coagulase is actually an adhesin, not an enzyme. It | |
| |results in a clot formation so the bug can establish | |
| |residence | |
|Lecithinase |Destroys RBC and other tissue cells |Clostridium |
|Collagenase |Breaks down collagen (CT fiber) |Clostridium, Bacteroides, Actinobacillus, AA, and |
| | |Bacillus (Think PD bugs) |
|Phospholipase |Lyses RBC |Staph. Aureus |
|Fibrinolysin, staphlokinase, streptokinase |Dissolve blood clots (Plasminogen ⋄ Plasmin) |Staph and Strep |
|Body site |Normal Microbiota |
|Oral cavity (saliva, tongue, plaque) |Streptococcuus, Veillonella, Bacteriodes, Fusobacterium, Peptostreptococcus, and |
| |Actinomyces |
|Gastrointestinal tract |Lactobacillus, Streptococcus, Clostridium, Veillonella, Bacteroides, Fusobacterium,|
| |Escherichia, Proteus vulgaris (natural to intestinal flora), Klebsiella, and |
| |Enterobacter |
|Upper respiratory tract (nasal cavity and nasopharynx |Streptococcus, Staphylococcus, Moraxella, Neisseria, Haemophilus, Bacteroides, and |
| |Fusobacterium |
|Lower respiratory tract |None |
|Upper urinary tract (kidney and bladder) |None |
|Genitourinary tract (urethra and vaginal tracks) |Streptococcus, Lactobacillus, Bacteroides, and Clostridium |
Predominant subgingival bacteria associated w/ gingival health:
Streptococcus mitis & S. sanguis
Actinomyces viscosus & A. naeslundii
Rothia dentocariosus
Staphylococcus epidermidis
Small spirochetes
Periodontal disease:
IgG is found in the highest concentration in serum samples from pts w/ PD disease
Prevotella melaninogenica and Prevotella intermedia (NEW NAMES)
[Bacteroides melaninogenicus = OLD NAME]
Anaerobic bug from gingival scrapings
Forms a black pigmented colonies on hemin-containinng culture media
Found in higher concentrations in the gingival crevice than on the tongue or in plaque
Collagen degradation is observed in chronic periodontal disease, which occurs by collagenase NZs from….Porphyromonas species
Juvenile periodontitis:
1) Generalized
P. intermedia & E. corrodens predominate
12-25 y.o.
Prevotella Intermedia ⋄ (Intermediate, think Juvenile)
First detectable in the oral cavity in adolescence
is a collagenase producing bug associated with PD disease
Rapid, severe perio destruction around most teeth
Associated w/ DM type 1, Down syndrome, neutropenias, Papillon-Lefevre syndrome, leukemias
2) Localized
A. actinomycetemcomitans & Capnocytophaga ochraceus predominate
12-19 y.o.
Severe perio destruction around Mx/Mn 1st molars or Mx/Mn Anteriors
Relative absence of local factors (plaque) to explain it
A.actinomycetemcomitans & C. ochraceus are also associated w/ periodontitis in juvenile diabetes
Adult periodontitis:
Porphyromonas gingivalis
High levels of antibodies are seen in adult periodontitis against P. gingivalis (these antibodies are IgG)
Known for its collagenase NZs in breaking down collagen in chronic PD
G-, so causes inflammation by endotoxin (lipopolysaccharide)
Prevotella intermedia
Bacteroides forsythus
Campylobacter rectus
Fusobacterium nucleatum
Spirochetes
**When T cells from people with chronic periodontitis react with certain plaque bacterial antigens they produce:
MIF & Lymphotoxin
Lymphotoxin is synonymous with TNF-beta
MIF = (macrophage) migration inhibitory factor
Here’s the story:
T cells produce lymphokines as a result of interaction w/ bacterial antigens
In PD disease, these lymphokines include IL-1, TNF, MAF, MIF & CTX
Refractory periodontitis: (SAME AS ADULT) – Know this.
Porphyromonas gingivalis
Bacteroides forsythus
Campylobacter rectus
Prevotella intermedia
Rapidly progressive periodontitis:
Features:
Most commonly seen in young adults (20-35 y.o.)
Marked inflammation, rapid bone loss, periods of spontaneous remission
Most of these pts have depressed neutrophil chemotaxis
Predominant bugs:
Porphyromonas gingivalis
Eubacterium
Prevotella intermedia
Fusobacterium nucleatum
Campylobacter rectus
Eikenella corrodens
ANUG = acute necrotizing ulcerative gingivitis
Principal bacteria: 1) Prevotella intermedia & 2) Spirochetes
An anaerobic infection of gingival margins causing ulcerations & ultimately destruction of gingiva & underlying bone
IP areas affected first
Spirochetes invade the epithelium & CT
SOME BACTERIAL STDs
Chlamydia:
Any of several common, often asymptomatic, STDs
Most common cause of STD in the U.S.
Caused by C. trachomatis:
An obligate intracellular parasite (NOT a virus)
Along with Rickettsia – Only bacteria to be
Cannot survive on the host extracellularly
Also causes ocular trachoma & inclusion conjunctivitis (described elsewhere in file)
Serotypes
A,B,C
Africa, Blindness, Chronic infection
D-K
Everything else
L1, L2, L3
Lymphogranuloma venerum
2 Forms
Elementary Body (small, dense) – Kids get tons of infections in Elementary school
Infectious agent of chlamydia
Enters cell via Endocytosis
Initial or Reticulate Body
Replicates in cell by fission
Young women w/ chlamydia may also acquire salpingitis (inflammation of the fallopian tubes)
Most common chlamydial disease in the U.S. is nongonococcal urethritis
There is a large number of asymptomatic carriers.
Frequent co-infection w/ gonorrhea
Most infections of Chlamydia are located on the eyes, genitals, and inside human cells
Tx newborns with Ery eye drops as soon as their born
Cell wall lacks muramic acid (NAM) – beta-lactam resistant
What is not caused by Chlamydia trachomatis? Look up.
Inclusion conjunctivitis
Ocular trachoma
LGV
Lymphadenopathy ??
Pruritus ??
Chlamydia trachomatis. Which is false?
Most women are Sx-atic, More men are Sx-atic than women, causes keratoconjunctivitis
Gonorrhea: (“the clap”) – BIODOME with Rock Climbers get arthritis
STD caused by bacterium Neisseria gonorrhea
Species of Neisseria are differentiated by sugar fermentation
MeninGococci ferment Maltose and Glucose
Gonococci ferment Glucose
Most common cause of septic arthritis in adults is caused by Neisseria gonnorrhea
Neisseria gonorrhea has affinity for mucous membrane (NOT skin)
Portal entry of the nasopharynx (in one question, could be other membrane-like questions)
One of the most common infectious bacterial diseases
2nd only to chlamydial infections in # of cases
~50% of women w/ gonorrhea have no symptoms
Symptoms appear 2–10 days after infection
Treated w/ a single injection of ceftriaxone or spectinomycin
REMEMBER POEM (hemophilus) was also tx with CEPH
No longer susceptible to PCN:
Plasmid-mediated beta-lactamase
Chromosomally mediated decrease in affinity of PCN-binding proteins
What makes gonorrhea pathogenic? ⋄ PCN resistance via Beta-lactamase??
Often occurs together w/ chlamydia and syphilis
Ophthalmia neonatorum
A very serious complication of an infant delivered of mother with gonorrhea
Pt who has minimal resistance to a gonococcal infection most probably has:
Deficiency in cell-mediated immunity
Women
1st symptoms:
Bleeding associated w/ vaginal intercourse
Painful or burning urination
Yellow or bloody vaginal discharge
More advanced symptoms (may indicate PID):
Cramps and pain
Bleeding between menstrual periods
Vomiting or fever
Men
Have symptoms more often than women
Pus from the penis
Painful, burning urination (may be severe)
Syphilis:
STD caused by infection w/ Treponema pallidum (a spirochete)
Produces neither endotoxins nor exotoxins (unlike cholera, gonorrhea, brucellosis, and gas gangrene)
SAME WITH M. TB
Congenital infections in neonates & infants can occur
Late manifestations include Hutchinson’s triad – abnormal teeth, interstitial keratitis, 8th nerve deafness
Cannot be grown on artificial media (neither can M. leprae) -- armadillos
Also disrupts the vasa vasorum of aorta with consequent dilation of aorta and valve ring, often affects the aortic root and ascending aorta, Associated with tree bark appearance of the aorta, Responsible also for some Aortic anuerysms
3 stages of Syphillis:
Primary:
Non-painful chancre – reddish lesion w/ raised border (appears in 3-6 wks at the site of local contact)
Lips are most common site for chancres to appear in 1° oral syphilis
Secondary:
Characterized by:
Cutaneous lesions
Positive VDRL test
Mucous membrane lesions
Presence of Spirochetes in the lesions
NOT Development of a gumma (tertiary)
Highly infectious stage – 6 wks after non-treatment of 1° syphilis
Maculopapular rash
Rash appears on palms of hands & soles of feet – just like in Rocky Mountain spotted fever
Condyloma latum/lata
Flat-topped papules (mucous patches) appearing on moist skin/mucosal surfaces
LATENT:
Develops in 30-40% of infected individuals
Mucocutaneous relapses are most common
Tertiary:
Occurs in 30% of infected persons many years after non-treatment of 2° syphilis
The gumma (focal nodular mass) typifies this stage. Most commonly occurs on the palate and tongue
Neurologic symptoms are also evident at this stage
Gumma:
Infectious granuloma characteristic of tertiary syphilis
Characterized by a firm, irregular central portion, sometimes partially hyalinized, & consisting of coagulative necrosis in which “ghosts” of structures may be recognized; a poorly defined middle zone of epithelioid cells, w/ occasional multinucleated giant cells; and a peripheral zone of fibroblasts and numerous capillaries, w/ infiltrated lymphocytes and plasma cells
Causes irreversible heart failure, dementia, and disability (CNS & cardiac involvement)
Good prognosis for early Dx/Tx
Parenteral Penicillin G is the drug of choice for treating all stages
Dx: Darkfield microscope – useful in examining blood for T. pallidum
USMLE RANDOM ADD-ONS
Pigment-producing Bacteria
Staph aureus ⋄ Yellow (Gold – Au)
Pseudomonas Aeruginosa ⋄ Blue-green
Serratia marcescens ⋄ Red (Maraschino cherries are red)
IgA Protease Bacteria
IgA normally prevents attachment
Streptococcus pneumoniae
Neisseria meningitidis
Neisseria gonorrhoeae
Haemophilus influenzae
Culture Requirements
H. influenzae ⋄ Chocolate agar with Factors V (NAD) and X (hematin)
N. gonorrhoeae ⋄ Thayer-Martin (VCN) media
B. pertussis ⋄ Bordet-Gengou (potato) agar
C. diphtheriae ⋄ Tellurite agar
M. tuberculosis ⋄ Lowenstein-Jensen agar
Lactose fermenting ⋄ MacConkey’s agar (PINK)
Legionella pneumophila ⋄ Charcoal yeast extract agar buffered with increased iron and cysteine
Fungi ⋄ Sabouraud’s agar
Stains
Congo Red ⋄ Amyloid; apple-green birefringence in polarized light
Giemsa’s ⋄ Borrelia, trypanosomes, Chlamydia
PAS (Periodic Acid Schiff) ⋄ Stains glycogen, mucopolysaccharides, Dx Whipple’s disease
Ziehl-Neelson ⋄ Acid-fast bacteria (military TB) – or Kinyoun’s acid-fast stain – Think German Military
India ink ⋄ Cryptococcus neoformans
Obligate Aerobes
Use O2 dependent system to generate ATP
Nice Pets Must Breathe
Nocardia
Psuedomonas aeruginosa ⋄ Seen in burn wounds, nosocomial pneumonia, and Cystic Fibrosis pneumonia
Mycobacterium tuberculosis
Bacillus – The spore forming bug that DOES breath
BOTH Nocardia an Psuedomanas Aeruginosa are both surrounded by mycolic acid
Brucella
Bordetella
Obligate Anaerobes
Lack catalase and/or superoxide dismutase, and are thus susceptible to oxidative damage
Generally the foul smelling, difficult to culture, and produce gas in tissue (CO2 and H2)
Normal flora in GI tract, pathogenic elsewhere
They DON’T know the ABCs of Breathing
Actinomyces -- Sulcus Dwellers
Bacteroides
Clostridium – Spore forming that doesn’t breath
Food Posioning Bugs
Staph aureus ⋄ (Meats, mayonnaise, and custard) THE FASTEST!!
Vibrio parahaemolyticus and Vibrio vulnificus⋄ (Seafood)
Bacillus cereus ⋄ (Reheated Rice)
Clostridium perfringens⋄ (Reheated Meat dishes)
Clostridium botulism⋄ (Canned foods)
E. coli⋄ (Undercooked meat)
Salmonella⋄ (Poultry, meat, eggs)
Diarrhea Bugs
E. coli ⋄ Ferments lactose No Fever Watery/Bloody
Vibrio cholerae⋄ Comma-shaped organism No Fever Watery
Salmonella⋄ No lactose fermentation, mobile Fever Bloody
Shigella⋄ No lactose ferm, nonmobile, Fever Bloody
Campylobacter jejuni⋄ Comma or S shaped organism Fever Bloody
Vibrio parahaemolyticus⋄ Transmitted by Seafood Fever
Yersinia enterocolitica⋄ From Pet feces (puppies) Fever Bloody
Cholera vs. Pertussis
Vibrio cholera
Toxin permanently activates Gs, causing rice water diarrhea
Turns the “on” on
Pertussis
Toxin permanently inactivates Gi, causing whooping cough
Turns the “off” off
Lactose-fermenting enteric bacteria
Think pink colonies growing on MacConkey’s agar
Think MacKonKEEs
Klebsiella
E. coli
Enterobacter
Zoonotic Bacteria
Think Bugs From Your Pets
Borrelia burgdorferi Lyme Disease Tick bites (living on deer and mice)
Brucella Brucellosis Fever Dairy products, contact with animals
Francisella tularensis Tularemia Tick bites; rabbits, deer
Yersinia pestis Plaques Flea bite; rodents; especially prairie dogs
Pasteurella multocida Cellulitis Cat, Dog bites
Normal Flora
Skin S. epidermidis
Nose S. aureus
Oropharynx viridans Streptococcoi (S. mutans)
Dental Plaque S. mutans
Colon B. fragilis, and S. young
Vagina Lactobacillus, colonized by E. coli, group B strep, J. Cragun
VIRUSES
Virion: the complete infectious viral particle
A viral nucleic acid (genome) is composed of DNA or RNA (NOT both) encased in a protein coat called a capsid
Capsid or Protein coat
Composed of polypeptide units called capsomers
Makes protective vaccines a possibility
The capsid surrounds viral DNA – NOT a nucleocapsid
Cellular tropism of viruses is dependent upon cell surface receptors
NOTe: the nucleocapsid = the protein shell + the nucleic acid
Naked or enveloped (an envelope is a lipid bilayer surrounding the capsid)
Only naked DNA viruses are Papovaviruses, Adenoviruses, and Parvoviruses (cause gotta be naked for PAP smear).
Almost all are haploid – contain a single copy of their geneome (exception: retrovirus family – diploid)
Replicate only in living cells – obligate intracellular parasites
The only bacteria are Rickettsia and Chlamydia (they stay inside when it’s Really Cold)
Not sensitive to antibiotics – but are sensitive to interferon, which inhibits their replication
Depend on host cells for energy production
Cannot be observed w/ a light microscope – they are smaller than cells (duh!)
Pass through filters that retain bacteria
Peplomers:
Protein spikes (glycoproteinaceous projections) found in the envelope of some viruses
The spikes contain hemagglutinin, neuraminidase, OR a fusion protein that causes cell fusion & sometimes hemolysis
EXs: orthomyxoviruses & paramyxoviruses
Viriods:
Consist solely of a single molecule of circular RNA w/out a protein coat or envelope
Cause several plant diseases but are not implicated in any human disease
Prions:
Infectious protein particles composed solely of protein (No RNA or DNA)
Cause certain “slow” diseases such as Creutzfeldt-Jakob disease in humans & scrapie in sheep
Mad Cow Disease
Associated with spongiform encephalopathy
Harder than spores to get rid of
Host cell: cell w/in which a virus replicates
Once inside the host cell, the viral genome achieves control of the cell’s metabolic activities
The virus then uses the metabolic capacity of the host cell to reproduce new viruses
Host cell provides the metabolic NZs, and the virus provides the genetic information
Often the replication of these new viruses causes death of the host cell
Viruses must first adsorb to the cell surface of the host cell
This involves a specific interaction between a viral surface component and a specifice cell receptor on the cell membrane
Adsorption does NOT involve insertion of virally specified glycoproteins into the host cell membrane
Cellular tropism by viruses is dependent upon cell surface receptors (they interact with the spikes on the viruses)
For a retrovirus, what precedes integration into the host?
Synthesis of complement DNA from RNA
NOT synthesis of viral protein, capsid from nuclear membrane, or budding
Identifying viruses:
Whether or not antisera neutralize the virus
The most generally accepted laboratory method for dx of most common viral infections
Morphology of protein coat
Nature of viral nucleic acid (RNA or DNA)
The ability of ether or chloroform inactivate the virus
NOT the ability of virus to grow on complex media – Just Like M. leprae and Treponema (syphilis)
Viruses cause disease by any of the following:
Lysing many cells of the host
Transforming cells to malignant cells
Making vital target cells nonfunctional
Disrupting the normal defense mechanisms of the host
Viral antigens
Viral antigen recognition by CD4+ T-Helper cell from an APC LOOK UP!!! – 2002 Q6
Each of the following is necessary:
Cleavage of viral proteins into small peptides
Internalization of the virus or viral protein by an antigen presenting cell
Transport of viral peptides to a cell surface by MHC II molecule
Binding of the TCR to a MHC II bound viral peptide
Viral replication in host – NOT necessary by T-Helper cell
Most viral Ag/s of diagnostic value are proteins
Bacteriophage (aka “phage”)
Virus that can only replicate w/in specific host bacterial cells
Very delicate bacterial virus which may attach to & destroy bacterial cells under certain conditions
Contains a nucleic acid core (DNA or RNA) & a protein coat
Some have tail-like structures for injecting the nucleic acid into host cell
Phage Conversion
Responsible for conversion of erythrogenic toxin by Strep pyogenes!!!!!
Responsible for production of a pyrogenic toxin
Serological & phage typing of pathogenic bacterial species are used to identify bacterial strains in disease outbreaks
The best evidence for causal relationship between a nasal carrier of staph and a staph infection in a hospital is the demonstration that both bugs are of the same phage type – only genetically similar bacteria within a species will be lysed by the same phage.
Bacteriophage follows one of two courses:
1) Lysis: virus multiplies w/in the host cell & destroys it
The virus is said to be a lytic or virulent phage (lyses & kills host)
2) Lysogeny: virus does not replicate but rather (prophase) integrates into the bacterial chromosome
The virus is said to be a temperate or lysogenic phage (replicates to incorporate phage genome into host genome)
Temperate phage persists through many cell divisions w/o killing host
Can spontaneously become lytic
Presence of the integrated virus (called a prophage) renders the cell resistant to infection by similar phages
Lysogenic bacterium
Harbors a temperate bacteriophage
Example is Corynebacterium diphtheriae
Lysogenic conversion
Alteration of a bacterium to a virulent strain by the transfer of a DNA temperate bacteriophage
Presence of temperate phage renders C. diphtheriae pathogenic (harmless w/o the phage)
The following may be transmitted by respiratory droplets:
Rubeola, Adenoviruses, Influenza virus, Varicella-zoster virus, Diphtheria, Bordetella Pertussis
Arthropods:
Transmission by arthropod vectors occurs in:
Malaria
Typhus fever – NOT Q fever
Dengue
Rocky mountain spotted fever (Tick)
NOT Diphteria
Viral Replication
For RNA viruses:
Transcription occurs in the cytoplasm except for retroviruses and influenza viruses – nucleus
Transcription involves an RNA-dependent RNA polymerase except for retrovirus, which has a reverse transcriptase enzyme (RNA-dependent DNA polymerase)
All RNA viruses have Continuous single stranded RNA, except for 4 (BOAR) – which are Segmented
Bunyaviruses, Orthomyxoviruses (Flu virus), Arenaviruses, Reoviruses
The influenza virus (Orthomyxo) has 8 segments that can reassort a lot, and is the reason for worldwide epidemics of the flu
Antigenic shift of influenza is caused by Genetic reassortment (then you get new surface receptors)
Polarity:
Positive polarity = RNA w/ same base sequence as the mRNA
Use RNA genome directly as mRNA
Negative polarity = complimentary sequence to mRNA
Must transcribe its own mRNA using the negative strand as template
The virus must carry its own RNA-dependent RNA polymerase
EXs – orthomyxoviruses & paramyxoviruses
Only HIV does not function as a positive or negative sense molecule
It acts as a template for the production of viral DNA
For DNA viruses:
Transcription occurs in the nucleus except for poxviruses – in a box
Transcription involves a host-cell DNA dependent polymerase (to synthesize mRNA)
All DNA viruses consist of dsDNA except for the parvoviruses, which have a ssDNA
(Sean has only made a SINGLE PARhole is whole life)
All DNA viruses consist of Linear dsDNA except for Papovavirus and Hepadnavirus, which have circular
Viral Genetics
Recombination
Exhchange of genes between 2 chromosomes by crossing over within regions of significant base sequence homology
Reassortment
When viruses with segmented genomes (influenza virus) exchange segments
High frequency recombination
Cause of worldwide pandemics
Complementation
When 1 of 2 viruses that infect the cell has a mutation that results in a nonfunctional protein
The nonmutaed virus “complements” the mutated one by making a functional protein that serves both viruses
Phenotypic Mixing
Genome of virus A can be coated with the surface proteins of virus B
Type B protein coat determines the infectivity of the phenotypically mixed virus
However, the progeny from this infection has a type A coat and is encoded by its type A genetic material
“Late” proteins synthesized in viral replication:
Include viral structural proteins
One-step growth curve:
Lysis of bacterial cell release a large number of phages simultaneously
Consequently, the lytic reproduction cycle exhibits a one-step growth curve
Growth curve begins w/ an eclipse period:
Period in which there are no complete infective phage particles
Characterized by absence of demonstrable virus particle
Eclipse period is the time between the injection of the viral DNA & formation of the first complete virus w/in host
Eclipse period is the 1st portion of the latent period, which ends when the 1st assembled virus from the infected cell appears extracellularly
Cytopathic effect (CPE): (old term was cytopathogenic effect, I think)
Is characteristic of each virus and can be used for detection of that virus, it is a hallmark of viral infection
This change starts w/ alterations of cell morphlogy accompanied by marked derangement of cell function
Culminates in cell lysis
The cytopathic reactions include: necrosis, hypertrophy, giant cell formation, hypoplasia, and metaplasia
These changes provide useful evidence for the Dx of the viruses that induce the CPEs seen
Not all viruses cause CPE
Slow Growth Viruses
In most slow viruses, tissue damage occurs in the brain
Dermatotropic viral diseases:
Measles, Smallpox, and Chickenpox
Latency:
State of dormancy – may be latent for extended period of time & become active under certain conditions
Interval of time between an exposure to a carcinogen and emergence of a neoplasm
Existing as a potential, as in TB or HSV infection
HOW TO REMEMBER DNA vs. RNA…
Remember the DNA viruses – the rest are RNA
Think HHAPPP: (* = exception)
Herpes
HepaDNA⋄ (* Circular but incomplete DNA)
Adeno
Papova⋄ (* Linear DNA)
Parvo ⋄ (* ssDNA)
Pox ⋄ (* Circular but supercoiled DNA)
(*NOT Icosahedral)
(*Replicates in Cyto [Own DNA-dep RNA polymerase])
CAREFUL ⋄(picorna & paramyxo are RNA, but start w/ P, clown)
PAP = Naked DNA viruses ⋄ Girls are naked when they get a PAP smear
HPH = Enveloped DNA (Think Pox in a Box)
Hepatitis viruses
Include DNA & RNA viruses
Detailed info is found in the section on the Liver
RNA Viruses
RNA enveloped viruses
Orthomyxovirus
ssRNA Segmented
Influenza A, B, C
Causes influenza, duh!
Composed of unique segmented ssRNA genome, a helical nucleocapsid, and an outer lipoprotein envelope
Envelope is covered w/ two different types of spikes that contain either hemagglutinin or neuraminidase
Causes a fever, runny nose, cough, headache, malaise, muscle ache
Fever distinguishes flu from common cold
Classified as type A, B, or C depending on the nucleocapsid Ag
Passed on via respiratory droplets
Microorganism characteristic of requiring a specific receptor site to infect a host
(incorrect options included anthrax, syphilis, dysentery, gas gangrene)
Influenza A:
Most common flu; causes the most severe disease
Ability to cause epidemics depends on antigenic changes in the hemagglutinin & neuraminidase
Two types of changes:
Antigenic shifts
which are major changes based on reassortment of genome pieces
This leads to new surface molecules (change in envelope)
Antigenic drifts
which are minor changes based on random mutations
Amantadine/Rimantadine
Inhibits replication of influenza A virus by interfering w/ viral attachment & uncoating
Effective in prophylaxis & Tx of influenza A
Main mode of prevention is vaccine – consists of killed influenza A & B viruses
Staph aureus is associated with fatalities post influenzal infection
One serious complication associated w/ outbreaks of influenza is the development of Reye’s syndrome, which is an acute pathological condition affecting the CNS
Seems to be associated w/ outbreak of influenza B virus for unknown reasons
This syndrome is principally associated w/ children who have take aspirin to treat the trivial infection
No cause-and-effect relationship between ASA use & Reye’s syndrome
Reye’s syndrome is characterized by vomiting for one week after infection and either recover in 2 days or go into coma w/ intracranial pressure
Paramyxovirus ⋄ “Para of Ms”
ssRNA
Cause respiratory infections in children
Differ from orthomyxoviruses in that the genomes are not segmented, have a larger diameter & different surface spikes
Cytopathic effect for paramyxoviruses is syncitia formation (they induce cells to form multinucleated giant cells)
Multinucleated giant cells of the foreign-body type originate from fusion or division of mononuclear cells
Parainfluenza viruses
Cause croup (acute laryngotracheobronchitis) & pneumonia in children
Characteristic barking cough
Surface spikes include hemagglutinin, neuraminidase, or fusion proteins
Disease resembles common cold in adults
Transmitted by respiratory droplets & direct contact
Has 4 serotypes
Neither an antiviral therapy nor a vaccine is available
RSV
Disease primarily in infants
Most common cause of pneumonia & bronchiolitis in infants
Only one of the paramyxovirus lacking the glycoproteins hemagglutinin & neuraminidase (surface spikes)
RSV surface spikes are fusion proteins
Fusion proteins cause cells to fuse, forming multinucleated giant cells (syncitial, as in RSV)
Multinucleated giant cells of the foreign-body type originate from fusion/division of mononuclear cells
Aerosolized ribavirin is used to treat severely ill, hospitalized infants
Mumps
Transmitted via respiratory droplets
Occurs worldwide – peak incidence in the winter
Most noticeable symptom – painful swelling of the parotid glands PAROTITIS (unilateral or bilateral)
Typically benign & resolves w/in a week
10 yr old child had case of mumps when she was 5 yrs old Look up
Her specific memory cells are B cells, CD4+ T cells, and CD8+ T cells – maybe only CD8+ T cells, maybe only CD4+ only
Complications:
Orchitis – (Lumps in my Man Bumps from Mumps)
Chief complication in males
Painful swelling of the testicles in postpubertal males, which can result in sterility
Deafness – in children
Measles (sarampion)
Caused by Rubeola virus (RNA paramyxovirus)
Rubeola is characterized by skin rash w/ Koplik’s spots in the oral cavity (BAD cops in Mexico)
Koplik’s spots – small, bluish-white lesions surrounded by a red ring; occur opposite the molars
So, Koplik spot = measles = paramyxovirus
Pt can have:
A cold and red & runny eyes
Blotchy reddish rash behind ears and on the face
3 Cs ⋄ Cough, Coryza, Conjunctivitis
Transmitted by respiratory droplets
what are features of measles except:
koplik
negri body – this is the answer – seen in Rabies
synctial formation – happens in all Paramyxos
Rash
measles can affect lots of organs because:
lots of cells are tropic for its receptor
Arbovirus
Colorado tick fever virus
Transmitted by arthropods (mosquitoes, tics) ⋄ (Also Flavivirus, Bunyavirus, and Togavirus)
Dengue fever
Yellow Fever
Togavirus
Alphaviruses – (Think Alpha Males wearing Red Togas in Germany)
Eastern equine encephalitis
Weatern equine encephalitis
Rubivirus = rubella
Aka “German measles” - Think kiLLa virus, germans are killers
Caused by rubella virus (RNA virus)
Enveloped virus composed of an icosahedral nucleocapsid and a positive, ssRNA genome
Transmitted by respiratory droplets
The only togavirus not transmitted by an arthropod vector
Initial replication occurs in the nasopharynx & local lymph nodes
From there it spread via the blood to the internal organs & skin
Incubation period of 2-3 wks followed by prodromal period of fever & malaise
This is followed by a characteristic maculopapular rash (appears first on face, then extremities), lasts 2-3 days
Prevention involves immunization w/ live, attenuated vaccine
Posterior auricular lymphadenopathy is characteristic
Milder, shorter disease than measles
A teratogen – causes malformation of an embryo or a fetus (TORCH)
NOT Koplik’s spots ⋄ That’s Regular measles (Rubeola not Rubella)
Congenital rubella syndrome:
When a nonimmune women is infected during the 1st trimester, especially the 1st month, significant congenital malformations can occur in the fetus
The malformations are widespread & involve primarily:
The heart (e.g., patent dutus arteriosus)
The eyes (e.g., cataracts)
The brain (e.g., deafness & mental retardation)
Flavivirus (Flavi = Yellow)
Yellow fever – a mosquito-borne flavivirus infection
Has a monkey or human reservoir
Symptoms: fever, black vomit, jaundice (yellow)
Councilman bodies (acidophilic inclusions) may be seen in liver
Dengue fever – also a mosquito-borne illness – characterized by fever, rash, arthralgia, lymphadenopathy
Hepatitis C
Transmitted via blood and resembles Hep B in course and severity
Common cause of IV drug use hepatitis in US
C = Chronic, Cirrhosis, Carcinoma, Carriers
Bunyavirus
California encephalitis virus
Hantavirus
Rhabdovirus
Rabies virus
Has the longest incubation period (up to 3 weeks to months)
HBV, HIV????
Use of vaccines for preventing clinical symptoms after introduction of the virus is most likely to be effective against rabies virus (NOT influenza, poliomyelitis, or herpes zoster)
You can administer vaccine even after inoculation!
Administer Human rabies immunoglobulin (HHIG) immediately in probable cases of rabies
Affects warm-blooded animals ⋄ reason for human/dog infections
More commonly from bat, raccoon, and skunk bites in areas of vaccinated dogs, otherwise worldwide dogs are most common
Bullet-shaped virus transmitted by the bite of a rabid animal
Virulence shown is due to?? ⋄ Envelope (presence of arginine or lysine residue at position 333 in glycoprotein residue)
Negri bodies
Characteristic cytoplamic inclusions in neurons infected by rabies
are pathogenic for the infection
Negri bodies = Rabies = rhabdovirus (Blacks shoot bullets)
Retrovirus
Enveloped, linear, positive-polarity ssRNA virus
Their genome surrounded by an inner protein envelope & an outer envelope that contains lipid & glycoprotein spikes
The spikes serve to attach the virus to host cells
“Retro” refers to the enzyme reverse transcriptase (an RNA-dependent DNA polymerase)
RT is packaged w/ the viral RNA genome
RT transcribes RNA to DNA during the process of viral nucleic acid syntheseis
The viral DNA integrates into the host cell genome
Reverse Transcriptase is unique to RNA tumor viruses
The viral genome encodes 3 groups of proteins:
Pol, Env, Gag
Three groups:
1) Oncovirus group (HTLV): produces leukemias, lymphomas, breast carcinomas, & sarcomas
HTLV III (HIV) is least likely virus to be spread in dental office
HTLV III is an obsolete term for HIV
2) Lentivirus group: causes AIDS
HIV occurs primarily by sexual contact and by transfer of infected blood
Virus infects/kills helper (CD4) T cells, resulting in the depression of both humoral & cell-mediated immunity
It travels throughout the body, particularly in macrophages
Induces a dinstinctive CPE (cytopathic effect) called giant cell (syncytial) formation
3) Spumavirus group: there are no known pathogens
HIV
Only virus with Diploid
Gp41 = Envelope protein
gp120 glycoprotein spike protrudes from the envelope
This is the ligand for CD4 molecules
p24 = rectangular nucleocapsid protein (surrounds RNA)
Black balls = Reverse Transcriptase
Directly affects:
Neurons, Macrophages, CD4 (helper) lymphocytes
NOT CD8 (suppressor) lymphocytes
Transmitted by:
Semen, Serum, Amniotic fluid, Breast milk
NOT Saliva
Initial manifestation of Early, acute HIV infection
Mononucleosis-like syndrome
HIV is responsible for resurgence of Mycobacterium Tuberculosis
Opportunistic Infections
Bacterial
Tuberculosis, M. avium-intracellulare complex
Viral
Herpes simplex, Varicella zoster, CMV, Progressive mulitfocal leukoencephalopathy (PML), Hairy Leukoplakia
NOT Adenovirus (conjunctivitis)
Fungal
Candidiasis, Cryptococcus (meningitis), Histoplasmosis, Pneumocystic carinii pneumonia (PCP)
Most common cause of pneumonia in HIV pts is from PCP
Protozoan
Toxoplasmosis, Cryptosporidium Enterocolitis
NOT Adenovirus conjunctivitis
Strains
New strains of HIV are the result of errors in transcription (remember, reverse transcriptase!)
In other words, by frequent errors induced by viral reverse transcriptase
NOT the result of genomic recombination or errors in translation
Dx
Made with ELISA ⋄ High false positive rate, simply a Rule Out test
Positive ELISA are then confirmed with Western blot assay, Rule In test
HIV is NOT oncogenic
AIDS
Info available elsewhere in file
RNA non-enveloped viruses
NAKED ⋄ CPR (Calicivirus, Picornavirus, Reovirus)
PicoRNAvirus = picornavirus
Very small, non-enveloped; composed of positive stranded, ssRNA genome
NOT capable of causing cell transformation (naked DNA)
Retrovirus, Herpes, Hepatitis B, and Human Papilloma are capable of causing cell transformation
Subdivision: Enteroviruses
Poliovirus
Causes poliomyelitis
RNA is the Only nucleic acid present…duh
Transmitted by the fecal-oral route via consumption of water w/ fecal contaminants
Replicates in the mucosa of the oropharynx and GI tract before entering the blood – Think swimming in stomach POOL
Travels to the spinal cord & infects the anterior horn cells (motor cells) leading to Lower Motor Neuron destruction
Uncommon in the U.S. due to successful vaccination program initiated in the 1950s
Initial symptoms: headache, vomiting, constipation, and sore throat
Does NOT form a latent infection
Paralysis may follow and is asymmetric & flaccid
Findings include CSF w/ lymphocytic pleocytosis w/ slight elevation of protein
Virus recovered from stool or throat
Two vaccines used currently:
Inactivated polio vaccine -- salk (IPV) vaccine & trivalent oral live virus vaccine (OPV)
Polio vaccine uses acquired artificial immunity (and Active)
Effective Polio Vaccine forms what kind of antibodies?? ⋄ Membrane bound IgG??? – I think
This is why SABIN (OPV or live) is better because it ALSO induces sIgA synthesis
Vaccine for Polio would be most affective if directed at Intestinal Mucosa
These immunize against polio in more than 90% of recipients
Coxsackie A & B virus
Most commonly isolated virus in the feces
Incorrect options: Hep C, influenza, rubella, herpes simplex
NOTE: you can get avian influenza from bird feces…just “food” for thought; Coxsackie is right fo sho
Group A:
Causes herpangina and hand-foot-and-mouth disease
Summer illness that produces nodular lesions of the uvula, anterior pillars, and posterior pharynx
Location of the oral lesions distinguishes these two diseases:
1) Herpangina –
Throat, palate, or tongue, the oral lesions
A viral disease with oral manifestations
3-yr-old w/ fever, vesicles / ulcers on soft palate, pharynx → herpangina
Herpangina & Coxsackie virus – you can make the connection, right…
2) Hand-foot-and-mouth disease – buccal mucosa and gingiva
Group B:
Causes focal necrosis of skeletal muscle & degeneration in brain & other tissues
Pleurodynia (pain in chest), myocardidits, and juvenile diabetes
Cause mild infections in human
Replicates in mucosa of the pharynx & GI tract before entering the blood
Echovirus
Echoviruses cause aseptic (viral) meningitis, upper respiratory infections, and severe diarrhea in newborns
Subdivision: Rhinoviruses
Rhinovirus
Main cause of the common cold
There are >100 different serotypes – hence, development of a vaccine is very difficult
The common cold also caused by coronaviruses in adults
NOT a persistant virus
Hepatitis A
RNA virus
Causes infectious hepatitis
Transmitted via Fecal-oral route – Just Like Hep E
Short incubation (3 weeks)
A for Asymptomatic usually
Reovirus
Have a double-shelled icosahedral capsid containing 10 or 11 segments of dsRNA
Replicate in cytoplasm
Produce minor respiratory tract infections & GI disease
Rotavirus
Segmented (BOAR)
ROTA ⋄ Right Out of The Anus
Causes infantile diarrhea
Most common cause of viral gastroenteritis in children (2 & under)
A self-limiting disease (aka, “24-hour flu” or “intestinal flu” – not caused by influenza virus)
Sudden onset of GI pain, vomiting, diarrhea
Dehydration is a major concern, especially in infants (can be fatal)
DNA Viruses (HHAPPPy)
DNA enveloped viruses
Herpesvirus
Herpes simplex virus
General
All are large (120–200 nm diameter) – 2nd only to poxvirus in size
Are medium-sized enveloped viruses w/ an icosahedral nucleocapsid containing linear, dsDNA
Replicate in the nucleus of the host cell and are the only viruses to obtain their envelopes by budding from the nuclear membrane
Cause acute (primary) infections
Produces a latent virus (ECHO, measles, smallpox, coxsackie all do NOT)
Latency in the ganglion
Most common site of latent infection to 1° oral infection by HSV I is in the sensory trigeminal ganglion
Characterized by latency and then clinical symptoms that can follow trauma, fever, and nerve damage
For the majority of individuals, the initial infection results in a subclinical disease
HSV 1&2 and varicella-zoster cause vesicular rash
Often associated with recurrent attacks of dermatitis herpetiformis
NOT aphthous stomatitis or erythema multiforme
HSV Type 1 = primary herpetic gingivostomatitis = recurrent herpes labialis
May involve primary infection (gingivostomatitis) or a recurrent infection (cold sores)
First clinical manifestation is usually gingivostomatitis
Affects children under 10 y.o. & 15-25 y.o.
Transmitted by direct contact
Nearly all infections are subclinical (but they range from subclinical to severe systemic infection)
Many children have asymptomatic primary infections
Associated with oral and ocular lesions
Pt may have acute symptoms
Affects the lips, face, skin, & oral mucosa (above the waist)
Recurrent herpes most likely found on the labial mucosa
Fever; irritability; cervical lymphadenopathy; fiery red gingival tissues; small, yellowish vesicles
Most serious potential problem is dehydration due to child not wanting to eat/drink
Often reappears later as the familiar “cold sore”, usually at the mucocutaneous junction of the lips
Disease is referred to as recurrent herpes labialis
Emotional stress, trauma, and excessive exposure to sunlight have been implicated as factors for the appearance of the recurrent herpetic lesions on the lip
May be diagnosed by a Tzanck smear for rapid identification when skin lesions are involved
Enveloped that was acquired by budding through the nuclear membrane – WOW!!!!!
Supportive tx – relieve acute symptoms
Acyclovir 5% ointment (Zovirax) has been successful in reducing the duration and severity of these sores
Acyclovir preferentially inhibits viral DNA polymerase when phosphorylated by viral thymidine kinase (which is far more effective in phosphorylation than cellular thymidine kinase)
Clinical use: HSV, VZV, EBV, mucocutaneous & genital herpes lesions
Healing takes 2-3 weeks; non-scarring
Recurrent infection in otherwise healthy people
Occurs in people who have been infected with the herpes virus AND do have Abs against the virus
Recurrent infections include: keratoconjunctivitis & encephalitis
Herpes conjunctivitis
Specific chemotherapy is used in tx (NOT used to tx measles, hepatitis, herpangina, or infectious mono)
Recurrent Herpes
Similar to recurrent apthae in that symptoms are similar, but don’t include apthous stomatitis
HSV Type 2 = Genital herpes
Spread by sexual contact
Affects the mucosa of the genital and anal regions (below the waist)
HSV-2 becomes latent in the lumbar and sacral ganglion
May have serious consequences in pregnant women
The virus may be transmitted to the infant during vaginal delivery
Can cause damage to the infant’s CNS &/or eyes
What causes cervicitis?
HSV 2, syphilis, HPV, chlamydia
Has been shown to have relationship to carcinoma of the cervix
Candidate virus for the induction of cervical cancer (carcinoma)
Varicella-zoster virus
Member of the herpes virus group
Causes 2 distinct diseases in different age groups
Very contagious and may be spread by direct contact or respiratory droplets
90% of cases of chickenpox occur in children under 9 years of age
Chickenpox (varicella)
Local lesions (vesicles) occur in the skin after dissemination of the virus through the body
Lesions become encrusted & fall off in ~1 week
Shingles (herpes zoster)
Unilateral
Pain along a dermatome (usually 1-3)
Only occurs in an individual having a latent VZV infection
More common in individuals that are Immunocompromised
DOES NOT occur repeatedly in Immunocompromised pts – Look up
Reactiviation of latent varicella-zoster that may have remained w/in the body from previous chickenpox
Reaches the sensory ganglia of the spinal or cranial nerves (most frequently the trigeminal nerve) producing an inflammatory response
Latent In the sensory ganglia
Characterized by painful vesicles on the skin or mucosal surfaces along the distribution of a sensory nerve
Characterized by individual, blister-like lesions affecting specific dermatomes, usually causing burning pain
Tzanck Test
Smear of an opened skin vesicle to detect multinucleated giant cells
Used for HSV-1, HSV-2, and VZV
Epstein-Barr virus
Causes infectious mononucleosis
Infects B lymphocytes & some epithelial cells
Latent EBV is called SBV
Hodkin’s Lymphoma
Associated w/ development of Burkitt’s lymphoma & nasopharyngeal carcinoma
Assocated w/ hairy leukoplakia – a whitish, nonmalignant lesion on the tongue (seen especially in AIDS pts)
Has splenomegaly and elevated heterophile titer
Heterophile agglutination test greater than 1:128
You get a sploner (splenomegaly) when you acquired the kissing disease (IM) from a girl (heterophile)
Associated w/ production of atypical lymphocytes & IgM heterophile antibodies ID’d by the hereophile test
(aka: “mononucleosis spot test” or “monospot test”)
Ab eventually appears in serum of > 80% of pts w/ IM, hence it is highly diagnostic
Infectious Mononucleosis (IM):
Viral infection causing high temperature, sore throat, & swollen lymph glands, especially in the neck, necrotizing pharyngititis, and splenomegaly
Typically caused by EBV – can also be cause by CMV
EBV-caused IM is responsible for approximately 85% of IM cases
Often transmitted by saliva
Occurs most often in 15-17 y.o. (may occur in any age) – most often diagnosed between ages 10-35
Hematologically – a relative lymphocytic leukocytosis w/ atypical lymphocytes & a positive heterophile test (increased)
Heterophile agglutination test greater than 1:128
EBV commonly produces a positive heterophile Ab test
After 1 week, many pts develop heterophile Ab/s, which peak at 2-5 wks – may persist for several months to 1 yr
Ab eventually appears in 80% of pts – highly diagnostic
Serum of the pt will agglutinate sheep red cells
Spontaneous recovery usually occurs in 2-3 weeks
No antiviral therapy necessary for uncomplicated IM; there is no EBV vaccine
NOTE: EBV is associated w/ Burkitt’s lymphoma, nasopharyngeal carcinoma, & hairy leukoplakia
Cytomegalovirus
Congenital abnormalities
CMV is the major viral cause of birth defects in infants in developed countries
C in TORCH
HHV-6
6th disease = roseola infection
|Virus |Usual site of latency |Recurrent infection |Route of transmission |
|HSV-1 |Cranial sensory ganglion (CN V) |Herpes labialis, encephalitis, keratitis |Via respiratory secretions and saliva |
|HSV-2 |Lumbar or sacral sensory |Herpes genitalis |Sexual contact, perinatal infection |
|Varicella zoster |Cranial/thoracic sensory ganglia |Zoster |Via respiratory secretions |
|Epstein-Barr |B lymphocytes |None |Via respiratory secretions and saliva |
|CMV |Uncertain |None |Intrauterine infection, transfusions, sexual |
| | | |contact, via secretions (eg saliva and urine) |
HepaDNAvirus
Hepatitis B
Blood borne virus
Parenteral, sexual, maternal-fetal
Long incubation period (3 months)
Reverse transcription occurs?????
Poxviruses
DNA viruses – the largest & most complex animal viruses
Brick shaped particles containing enveloped linear dsDNA genome
Multiply in the cytoplasm of host cell & are usually associated w/ skin rashes
Smallpox
Caused by variola virus
An acute, highly infectious, often fatal disease
Characterized by high fever, prostration, & a vesicular, pustular rash
Man is the only reservoir for the virus
Smallpox has been eradicated by global use of the vaccine which contains live, attenuated vaccinia virus
Protection against smallpox afforded by prior injection with cowpox
This represents antigenic cross reactivity
Vaccinia virus
A related poxvirus used to eradicate smallpox
Molluscum contagiosum
Causes umbilicated wart-like skin lesions
DNA non-enveloped viruses
Papovavirus
Pa = Papilloma virus
Po = Polyoma virus
Va = Vacuolating virus
HPV (Human Papilloma Virus)
Most common cause of VIRAL STD
Cause papillomas (warts) on skin & mucus MBs
A DNA oncogenic virus (NOT RNA oncogenic, that’s retrovirus)
Associated with the induction of cervical carcinoma (16,18)
Condyloma Acuminatum
NOT passed on via respiratory droplets
Adenovirus
Naked, medium sized, icosahedral nucleocapsid & linear dsDNA genome
Have hemagglutinin spikes
Frequently cause subclinical infections
Cause upper & lower respiratory infections – “cold”
Transmitted via aerosol droplets, fecal-oral route, or direct inoculation
Can be transmitted via ocular secretions
Diseases associated w/ adenoviruses:
Acute respiratory infections
Acute contagious conjunctivitis (pink eye)
NOT associated with HIV opportunistic infection
Pharyngoconjunctival fever characterized by fever, pharyngitis, & conjunctivitis
Parvovirus (PAR – V – Fifth’s disease)
Erythema infectiosum (slapped-cheeks syndrome, 5th disease)
Transient aplastic anemia crisis
Fetal infections
|Virus |Disease |Vaccine available |Treatment |
|RNA viruses | | | |
|Influenza A |Influenza |Yes |Amantadine/Rimantadine |
|Parainfluenza |Croup |No |None |
|Respiratory synctial |Bronchiolitis and pneumonia in infants |No |Ribaviron |
|Rubella |Rubella |Yes |None |
|Measles |Measles |Yes |None |
|Mumps |Parotitis, meningitis |Yes |None |
|Rhinovirus |Common cold |No |None |
|Coronavirus |Common cold |No |None |
|Coxsackie |Herpangina, hand foot and mouth |No |None |
|DNA viruses | | | |
|Herpes simplex type1 |Gingivostomatitis |No |Acyclovir in immunodeficient pt |
|Epstein barr |Infection mononucleuosis |No |None |
|Varicella |Chickenpox, shingles |No |None |
|Adenovirus |Pharyngitis, pneumonia |No |None |
|Portal of Entry |Virus |Disease |
|Respiratory tract |Adenovirus |Pneumonia |
| |Cytomegalovirus |Mononucleosis syndrome – most common pneumonia in bone |
| | |marrow transplant pt |
| |Epstein barr |Infection mononucleosis |
| |HSV type 1 |Herpes labialis |
| |Influenza |Influenza |
| |Measles |Measles |
| |Mumps |Mumps |
| |Respiratory synctial |Bronchiolitis and pneumonia in infants |
| |Rhinovirus |Common cold |
| |Rubella virus |Rubella |
| |Varicella zoster |Chickenpox |
|Gastrointestinal |Hep A |Hep A |
| |Polio |Poliomyelitis |
| |Rota |Diarrhea |
|Skin |Rabies |Rabies |
| |HPV |Papillomas (warts) |
|Genital |HPV |Papillomas (warts) |
| |Hep B |Hep B |
| |HIV |AIDS |
| |HSV type II |Herpes genitalis and neonatal herpes |
|Blood |Hep B |Hep B |
| |Hep C |Hep C |
| |HIV |AIDS |
| |Cytomegalovirus |Mononucleosis syndrome or pneumonia |
USMLE ADD-ONS
Naked/Enveloped Viruses
Naked
Most dsDNA (Not Pox) and (+) strand ssRNA viruses are infectious – positively infectious
Naked nucleic acids of (-) strand ssRNA and dsRNA are not infectious
Enveloped
Usually acquire their envelope from plasma membrane when they exit from the cell
Except Herpes, which gets it from the nuclear membrane
Virus Ploidy
All are Haploid! (one copy of DNA or RNA)
Except for Retroviruses, which have 2 identical ssRNA molecules (diploid)
Nosocomial Infections
Newborn Nursery CMV, RSV
Urinary Catheter **E. Coli, Proteus
Respiratory Equipment P. aeruginosa
Work in renal dialysis HBV
Hyperalimentation Candida
Water aerosols Legionella
Wound Infection **S. aureus
**2 most common nosocomials
If all else Fails
Pus, emphysema, abscess S. aureus
Pediatric infection H. influenzae
Pneumonia in CF, burn infection P. aeruginosa
Branching rods in oral infection Actinomyces israelii
Traumatic open wound C. perfringens
Surgical wound S. aureus
Dog or cat bite Pasteurella multocida
Sepsis/meningitis in newborn Group B strep
FUNGI
Fungi:
Eukaryotic, all are G+; contain both DNA & RNA
Grow in Sabouraud’s agar medium
Cell walls contain chitin, glucans, & protein
Cell MB contain sterols (ergosterol)
Two types:
Yeasts – grow as single cell that reproduces by asexually budding
Molds – grow as long filaments (hyphae) and form a mat or mass which is referred to as mycelium
Hyphae can be septate or nonseptate
All fungi (except for zygomycetes) are septate
Dimorphism is characteristic of some fungi
Dimorphism = the fungus forms different structures at different temperatures
Can exist as either filamentous (mold) or yeast (spore) forms
Cold = Mold/Mycelial (soil) Heat = Yeast (tissues)
Characterized by the capability to produce both a yeast & a mycelial phase
Exist as molds in the saprophytic, free-living state at ambient temperatures
Exist as yeasts in host tissue at body temperature
These fungi include the major pathogens – Blastomyces, Histoplasma, Coccidioides, and Candida
Reproduction
Asexual:
Most fungal spores are asexual
Asexual spores (conidia) form through mitosis
Differentiating conidia help to ID various fungi
Sexual:
They mate & form sexual spores
Mechanism for disease is through type IV hypersensitivity reaction
Fungal spores:
Morphological characteristics (e.g., shape, color, & arrangement) of conidia help to ID fungi
Conidium is an asexually formed fungal spore
Fungal spores cause allergies in some people
Most fungal spores are completely killed when heated at 80° for 30 min (unlike bacterial spores)
Examples of asexual spores (conidia)
Arthrospores: formed by fragementation of the ends of hyphae; are the mode of transmission of Coccidioides immitis
Chlamydospores: thick walled & quite resistant; characteristic of C. albicans
Blastospores: formed by budding, as in yeasts; multiple buds are called pseudohyphae (also characteristic of C. albicans)
Sporangiospores: formed w/in a sac on a stalk by molds such as Rhizopus and Mucor
Example of sexual spores:
Zygospores: single large spores w/ thick walls
Ascospores: formed in sacs which are called an ascus
Basidiospores: formed externally on the tip of a pedestal called a basidium
Many fungi respond to infection by forming granulomas (as seen in coccidioidomycosis, histoplasmosis, blastomycosis)
Nosocomial infections:
Infections acquired during hospitalization, unrelated to the pt’s primary condition
Often caused by: C. albicans, Apsergillus, E. coli, Hepatitis viruses, Herpes zoster virus, P. aeruginosa, Strep, & Staph
Ability to become resistant to ABX is most important characteristic of enterobacteria in hospitals
CUTANEOUS MYCOSES
Dermatophytes:
EXs: Trichophyton, Epidermophyton, and Microsporum
Cause superficial skin infections (Trichophyton) – think Tinea…from Dr. Christensen’s Path course
Infect only the skin, nails, and hairs
Athlete’s Foot caused by Trichophyton
Trichophyton also is involved in ALL types of Tineas
Tx ⋄ Griseofulvin (You have to be greasy to have these diseases)
Responsible for causing dermatophytosis
Common among people who live in communities w/ low standard of sanitation
Source – from soil & dust
Characterized microscopically by intracytoplasmic microorganisms of Reticuloendothelial system
|Epidemiology of Dermatomycoses |
|Disease |Causative agent |Examples of sources |
|Tinea capitis (ringworm of scalp) |Microsporum, Trichophyton |Lesions, combs, toilet articles, headrests |
|Tinea corporis (ringworm of body) |Epidermophyton, Microsporum, Trichophyton |Lesions, floors, shower stals, clothing |
|Tinea pedis (ringworm of feet (athletes foot) |Epidermophyton, Trichophyton |Lesions, floors, shoes & socks, shower stalls |
|Tinea unguium (ringworm of nails) |Trichophyton |Lesions |
|Tinea cruris (ringworm of groin [jock itch]) |Trichophyton, Epidermophyton |Lesions, athletic supports |
9 yr old boy has tinea capitis
For tx, he should be given an anti-mycotic agent
SUBCUTANEOUS MYCOSES
Sporotrichosis:
Caused by Sporothrix schenckii
Classically associated w/ rose thorns
Cigar-shaped budding yeast visible in pus
Mycetoma:
Lesions usually occur on feet or hands
Caused by infection w/ several fungi
SYSTEMIC MYCOSES – Can mimic TB granuloma formation – ALL 3 can come from Soil
Histoplasmosis:
Caused by Histoplasma capsulatum – a dimorphic fungus
Found in bird & bat droppings
Exists 1) as a mold in soil & 2) as a yeast in tissue
Endemic in Central and Eastern U.S., especially in the Ohio & Mississippi River valleys
Principal source of endemic form is from soil and dust
Infection results from inhaling contaminated air
Infection is usually asymptomatic, but may produce a benign, mild pulmonary illness (primary form of disease)
Infection with Histoplasma capsulatum in normal, healthy individuals results in a self-limiting, benign disease
“systemic disease, most commonly of the lungs, characterized by production of tuberculate chlamydospores in culture”
Frequently causes pulmonary nodules
An oral lesion that may appear as an ulcer, nodule, or vegetative process, and is often mistaken for SCC (squamous cell carcinoma)
Uncommon disseminated form of the infection is quite serious
Intracellular Parasite of Macrophages --- Have in common with Viruses
In infected tissues, yeast cells of Histoplasma capsulatum are found w/in macrophages
Characterized microscopically by intracytoplasmic microorganisms in the RE (reticulo-endothelial or macrophage) system (incorrect options were: intranuclear inclusion bodies, flask-shaped ulcers of the ileum, focal liver abscesses)
Often mistaken for TB in the lungs because it can cause calcifications in the lungs also
Resembles TB, causing a granulomatous, tuberculosis-like infection both clinically and pathologically
Produces tuberculate chlamydospores in culture
Histoplasmosis and blastomycosis are rarely acquired from another individual (along with Sporotrichosis)
Coccidioidomycosis:
Caused by the inhalation of dust aerosols containing Coccidioides immitis arthrospores (highly infectious)
Fungus that grows as a saprophyte (MOLD) in the soil
Endemic in hot, dry regions of the Southwest U.S. & northern Mexico
Referred to as “Valley Fever” or “San Joaquin fever”
Primary infection or lesion is in the lung
It is by and large an inapparent and self limiting infection in endemic areas
Amphotericin B is the drug of choice in treatment of fungal infection
Fluconazole & itraconazole are also used to treat various fungal infections
Blastomycosis: (aka “Gilchrist’s disease” or “North American blastomycosis”)
Caused by Blastomyces dermatidis – a dimorphic fungus that exists 1) as a mold in soil & 2) as a yeast in tissue
Causes necrotic skin and bone lesions – Blasted through my Skin to my Bone
Think B for Big, Broad-Based Budding
Fungus is endemic in North & Central America
Grows in moist soil rich in organic material (poop), forming hyphae w/ small, pear shaped conidia
Inhalation of the conidia cause human infection
Rarely, if ever acquire from another individual (Along with Histoplamosis, and Sporotrichosis)
OPPORTUNISTIC MYCOSES
Candida:
C. albicans most important species of Candida
Characterized by white patches on buccal mucosa, consisting of pseudomycelia & minimal erosion of MBs
Psuedo cause not in mold
Causes thrush, vaginitis, and other diseases
An oval yeast w/ a single bud – Not dimorphic
NOT an airborne fungus that causes opportunistic infections in debilitated individuals
Rhizopus, Aspergillus, and Cryptococcus ARE
Overgrowth of C. albicans in those w/ impaired host defenses produces candidiasis
Chlamydospores – thick walled & quite resistant; characteristic of C. albicans
Genus of fungi most frequently recovered from healthy mucous membranes
Prolonged ABX (antibacterials) tx can predispose to infection from indigenous oral microorganism – Candida albicans
Pts exposed to chemotherapy for leukemia are particularly prone to widespread oral infection caused by c. albicans
Pts with deficiency in T lymphocytes are predisposed
Pt exposed to long-term corticosteroids are predisposed to candidiasis
Candidiasis:
An infection of the oral cavity or vagina, usually by C. albicans
Common in patients 1) w/ a T-cell deficiency, 2) receiving chemotherapy & 3) who are immunosuppressed
C. albicans causes an inflammatory, pruritic infection characterized by a thick, white discharge
This yeast-like fungi is a normal inhabitant of the oral cavity & vaginal tract
Normally held in check by indigenous bacteria
Chemotherapy for leukemia predisposes for oral infections by C. albicans
Oral Candidiasis:
Acute
Pseudomembraneous (“thrush”) – creamy, loose patches of desquamative epithelium containing numerous matted mycelia over an erythematous mucosa that is easily removed; common in patients with more severe predisposing factors
Pseudomembrane (false MB) = desquamative and necrotic epithelial cells and matted and tangled mycelia
Tx = Ketoconazole or Fluconazole (not Nystatin)
Atrophic (“erythematous”) – the mucosa is thinned, smooth, and bright red with symptoms of burning and increased sensitivity commonly found on the palate under a denture but also on the tongue and other mucosal surfaces
Areas of superficial erosion and petechiae ⋄ necrosis
Tongue: beefy red appearance due to loss of filiform & fungiform papillae, generalized thinning of the epithelium and excessive inflammation of the CT
Chronic mucocutaneous candidiasis
Chronic Hyperplastic (“candidal leukoplakia”) – white plaques or papules against an erythematous background containing hyphae in the parakeratin layer of the thickened epithelium.
Firmly adherent white plaque to the oral cavity
Differential diagnosis is required: termed “candidal leukoplakia” ⋄ resembles speckeled leukoplakia or speckled erythroplasia conditions which are epithelial dysplasia ∴ MUST BIOPSY!
Usually unilateral, don’t rub off like pseudomembranous candidiasis
Oral Lesions
Angular Cheilitis (perleche) –
Symptomatic bilateral fissures of the corners of the mouth that are common in patients with C. albicans infection
Intensified with mouth overclosure
Tx = antifungal medication (nystatin ointment)
Median Rhomboid Glossitis –
An asymptomatic, elongated, erythematous patch of atrophic mucosa of the middorsal surface of the tongue due to a chronic C. albicans infection
Gradually enlarges
May have on the midline of palate opposite the tongue lesion
Chronic Mucocutaneous Candidiasis –
Persistent and refractory candidiasis occuring on mucous MBs, skin & nails of the affected patients
Watch out for w/ diabetic pts
Tx = topical clotrimazole troches
Cryptococcus:
Cryptococcus neoformans causes Cryptococcosis
Latex agglutination test detects polysaccharide capsular antigen
Antiphagocytic polysaccharide capsules (along with strep pneumoniae – think opsonins)
An oval, budding yeast – not dimorphic
Narrow-based, unequal budding
Found in soil, pigeon droppings
More common than other fungal infections
Severe only in people w/ underlying immune system disorders such as AIDS
May spread to the meninges, where the resulting disease is cryptococcal meningitis
***Think Cryptococcus for immunocompromised pts and meningeal signs
Culture ⋄ Sabouraud’s agar, Stain with India ink – enCrypted message with India ink
Aspergillus:
Species exist only as molds and are not dimorphic
Septate hyphae that branch at V-shaped 45 degree angle
Aspergillus fumigatus causes an aspergilloma (fungus ball) in the lungs & Aspergillosis
Aspergilliosis is most commonly caused by A. fumigatus, A. niger, or A. flavus
Aspergilliosis takes one of three forms:
Mycetoma (grows in the lung cavities)
Fungus Ball
Invasive aspergillosis (begins in lungs, spreads to other organs)
Allergic bronchopulmonary aspergillosis (allergy to spores that produces asthmatic attacks)
One clinical manifestation is eosinophila
Cause pulmonary infections in AIDS pts or have undergone organ transplantation
Aflatoxin: (A. Flavus)
Coumarin derivatives produced by Aspergillus flavus
Causes liver damage & tumors in animals
Ingestion of food contaminated with Aspergillus is associated with carcinoma of the liver
Think “As” for LIVER problems
Toxin binds to DNA & prevents transcription of genetic information
Ingested w/ spoiled grains and peanuts and are metabolized by the liver to epoxide (a potent carcinogen)
Zygomycosis (MUCORMYCOSIS): (aka “phycomycosis”)
Relatively rare fungal infection caused by saprophytic mold (e.g. Mucor, Rhisopuz, and Absidia)
These fungi are not dimorphic – Mold
Are morphologically characterized by the lack of septa in their hypha – the only non-septate fungus
Characterized by Hyphae growing in and around vessels
Pts w/ diabetic ketoacidosis, burns, or leukemias are particularly susceptible to this fungal infection
Pts w/ uncontrolled DM presents with nasal obstruction, proptosis, & perforation of the palate
Results in:
Fungi proliferate in the walls of blood vessels and cause infarction of distal tissue
Hemorrhagic infarction and necrosis following fungal infection
Massive necrotizing lesions of palate w/ poorly controlled DM
Black, dead tissue in the nasal cavity and blocks the blood supply to the brain
Leads to neurologic symptoms such as headaches and blindness
NOTE: other infections associated w/ AIDS pts: candidiasis, hairy leukoplakia, and cryptosporidium enterocolitis
Pneumocystis Carinii
Causes Pneumonia (PCP)
Originally classified as protozoan, but it’s a yeast
Inhaled
Most infections are asymptomatic, but due to AIDS, etc.
Most common cause of pneumonia in HIV pts is PCP
Tx when CD4 drop below 200 cells/mL in HIV pts
PARASITES/PROTOZOA
Protozoa
Diverse group of eukaryotic, typically unicellular, nonphotosynthetic microorganisms generally lacking a rigid cell wall
Infestation = presence of parasites on the body (e.g., ticks, mites, lice) or in the organs (e.g., nematodes or worms)
Balantidium coli: non-pathogenic, nonflagellated protozoan
Selective Cytotoxicity
A drug action which affects the parasite more strongly than host cell
INTESTINAL/MUCOCUTANEOUS PROTOZOA
Cyst = environmental form of a protozoa
Once inside the intestine, the organisms excyst & colonize
Trophozoite = motile, feeding, colonizing form found w/in intestine
Giardiasis:
Infection of the small intestine caused by a flagellated protozoan Giardia lamblia
One of the most common parasite infections of the small intestine
More common in male homosexuals & people who have traveled to developing countries
See in campers & hikers who present w/ diarrhea, bloating, flatulence, etc.
Amebiasis:
Infection of the large intestine caused by a flagellated protozoan Entamoeba histolytica
Acute intestinal amebiasis presents w/ dysentery (bloody, mucous-containing diarrhea)
Can also produce liver abscess
Trichomoniasis:
STD of the vagina or urethra (men) caused by flagellated protozoan Trichomonas vaginalis
Transmitted sexually
Causes vaginitis in women; can lead to urethritis or prostatitis in men
Symptoms are more common in women
One of the most common infections worldwide
Exists only as a trophozoite
Entamoeba and Trichomonas species are found in the oral cavity (appear to be nonpathogenic in the “O.C.”)
NOT found in O.C.: giordio, plasmodium, leishmania, balantidium
Cryptosporidosis:
Caused by Cryptosporidium parvum
Main symptom is watery diarrhea accompanied sometimes by abnormal cramps, nausea, & vomiting
Most severe in immunocompromised pts – may be fatal in these pts
BLOOD/TISSUE PROTOZOA
Malaria:
An infection of RBC by parasite Plasmodium vivax, ovale, falciparum & malariae
Drugs taken for prevention are not 100% effective
Symptoms can begin a month after the infecting female mosquito bite, Anopheles
Early symptoms are nonspecific & often mistaken for influenza
Rapid Dx & early Tx are important, particularly for falciparum malaria, which is fatal in up to 20% of infected people
P. vivax & P. falciparum are more common causes of malaria than P. ovale & P. malariae
Often first symptoms are a milde fever, headache, muscle aches, and chills (flu-like symptoms)
Enlarged spleen – characteristic of malaria due to congestin of sinusoids w/ RBCs
Total WBC count is usually normal – but, hyperplasia of the lymphocytes & macrophages
Antimalarial drugs – chloroquine, mefloquine, & pirmaquien
babesiosis:
Caused by Babesia microti
Common in the Northeast U.S.
Leishmania:
Transmitted by the sandfly
Trypanosomiasis:
Cause by the trypanosoma species
1) African sleeping sickness = African trypanosomiasis
2) Chagas’ disease = American trypanosomiasis
Toxoplasmosis:
Caused by Toxoplasma gondii
Teratogenic (Remember ToRCHeS)
Toxoplasma
Rubella
CMV
HSV, HIV
Syphilis
Sexual reproduction by this parasite occurs only in the cells lining the intestine of cats
Eggs are shed in the cat’s stool
People become infected by eating raw/undercooked meat containing the dormant form (cysts) of the parasite
May resemble a mild cold or infectious mononucleosis in adults
Treated w/ Sulfadiazine (an ABX)
Nematodes:
Roundworms w/ a cylindrical body & a complete digestive tract
Two categories based on primary location of body:
Intestinal nematodes: enterobius (pinworm), trichuris (whipworm), ascaris (giant roundworm) and Necator and Ancylostoma (the two hookworms)
Tissue nematodes: Wuchereria, Onchocerca, and Lao are called “filarial worms”
Bx of tongue mass – small, coiled, encysted larvae of nematode worms: Trichinae
Infections caused by certain nematodes cause marked eosinophilia (abnormally large numbers of eosiopnils in the blood)
Eosinophils do not ingest the parasites – they attach to the surface of parasites via IgE & secrete cytotoxic enzymes contained w/in their eosinophilic granules
Cestodes
Tapeworms
Trematodes
Flukes
ANTIMICROBIAL AGENTS
ANTIBIOTICS:
Broad-spectrum antibiotics: Tetracycline, Chlormycetin, & Cephalosporins
(NOT isoniazid, PCN, Dihydrostreptomy, or streptomycin)
Prolonged use of streptomycin can result in damage to auditory nerve
Steptomycin is an ABX which inhibits the process of transcription in prokaryotes
The indiscriminate use of broad-spectrum ABX is contraindicated because…
They interfere with indigenous bacteria (NOT produce dependency rxns – Susan Kinder Haake would be pissed)
Possible toxic effects of the antibiotics
Allergic reactions induced in patients
Development of drug resistance by an infectious agent
Secondary effects experienced due to creation of an imbalance in the normal body flora
Alteration of the immune response
Mechanisms of Action:
Cell wall inhibitors:
***Inhibit terminal step in peptidoglycan formation – NOT cell membrane
***The first 4 in this list are beta-lactams
Penicillins
Cephalosporins
Carbapenems
Monobactams
Vancomycin
Bacitracin
Cycloserine
Protein synthesis inhibitors:
TAs are usually 30 yrs old
30S – Tetracyclines
30S – Aminoglycosides
30s – Streptomycin
CLEC
50S – Chloramphenicol – Protein synthesis inhibition by inhibiting translocation by binding to 50S subunit
50S – Lincomycin
50S – Erythromycin – ABX of choice for a dental pt w/ a heart valve abnormality AND a PCN allergy
If you have a bact sensitive to penicillin but pt is allergic what would u use instead
Cephalosporin – NO: cross-allergenic
Amoxicillin – NO, duh!
erythromycin
clindamycin would have been a better choice??? – except for pseudomembranous colitis – only use when have to.
tetracycline
50S – Clindamycin
Antimetabolites:
Sulfonamides (sulfa drugs)
Trimethoprim
Cell MB inhibitors:
In G- bacteria: Polymyxin & Colistin
In fungi: Amphotericin B, Nystatin, Fluconazole, Clotrimazole, Ketoconazole
Nucleic acid synthesis inhibitors:
Fluoroquinolone (e.g., ciprofloxacin)
Represents a DNA gyrase inhibitor with a broad spectrum of activity
Affects Replication, NOT a metabolic pathway
Quinolones
Blocks DNA topisomerase (which normally helps in the breakage and linkages of phosphodiester linkages) -- Bacteriocidal
Rifampin
Binds to DNA-dependent RNA polymerase and inhibits RNA synthesis
PenicillinS
The ABX of choice for prophylactic dental work
Cephalosporins are related both structurally & by mode of action
Penicillin will work only on growing cells that contain peptidoglycan in their cell wall
It inhibits the terminal step in the peptidoglycan synthesis (cell wall synthesis)
Usually non-toxic to humans because humans lack peptidoglycans
Greatest bacteriocidal activity against growing G+ bacteria (thick peptiodoglycan layer)
Don’t use with Erythromycin – Because Ery stops growth and PCN only works if bacteria is growing
Penicillinase is produced by certain bacteria (e.g., some strains of Staphlococcus) that degrade the β-lactam ring structure
Certain penicillins have a structural modification that provides resistance to penicillinase
This may also narrow the spectrum of action, limiting the primary use of such Abx to tx of Staph infections
Penicillinase-resistant penicillins:
Used during Log Phase
Methicillin, cloxacillin, dicloxacillin, nafcillin, oxacillin, amoxicillin/clavulonate potassium (Augmentin), ampicillin/sulbactim (Unasyn), piperacillin/tazobactam (zosyn), ticarcillin/clavulonate potassium (Timentin)
Penicillin G:
Used for growing Gram + bacteria
Penicillin V:
Methicillin:
Prescribed primarily in the treatment of severe penicillinase-producing staphylococcal infections
Given IV
Not frequently used due to:
Incidence of interstitial nephritis
Availabitily of equally efficacious alternatives (nafcillin & oxacillin)
Methicillin-resistant Staph aureus (MRSA)
Group of resistant Staph bacteria that can be life threatening
Resistant to all penicillinase-resistant penicillins & cephalosporins
Usually resistant to aminoglycosides, tetracyclines, erythromycins, & clindamycin
In past vancomycin has been used against MRSA but there are some organisms resistant to it (VRE)
Broad-spectrum penicillins:
Ampicillin:
Amoxicillin
Amoxicillin Rxn:
Pt becomes hypotensive, itchy, and having difficult breathing
Amox reacts with IgE and activates cytotoxic T cells that release lymphokines
BOTH TYPE I and IV activate cytoxic cells????
CephalosporinS
Cefactor (Ceclor) is a broad-spectrum antibiotic
Bactericidal antibiotics
Act like penicillins – affect the bacterial cell wall during cell division, preventing closure
Bacteria eventually lyse & die
Act against a wide range of G+ & G-
There are four generations of cephalosporins
Progression from the first through the fourth is associated w/ a broadening of action against more G- bacteria and a decreased activity against G+
1st – cephalexin, cephradine, cefadroxil, cefazolin
2nd – cefaclor, cefuroxime, cefoxitin
3rd – cefixime, cefoperazone
4th – cefepime
Approx. 10% of individuals w/ a penicillin allergy have cross allergenicity to cephalosporins
MONOBACTAMS:
CARBAPENEMS:
VANCOMYCIN:
Clindamycin:
Binds to 50S ribosomal subunit, blocking bacterial protein synthesis
Restricted use due to severe diarrhea, GI upset, & pseudomembranous colitis
Pseudomembranous colitis is a major adverse effect of prolonged therapy with clindamycin
Side effects are caused by overgrowth of Clostridium difficile (95% of Pseudo… cases caused by C. difficile)
Bacteriostatic & active against most G+ & many anaerobic organisms, including Bacteroides fragilis (anaerobic G-)
Is alternate antibiotic used in dentistry when:
Amoxicillin cannot be used for bacterial endocarditis prophylaxis
Tx of common oral-facial infections caused by aerobic G+ cocci & susceptible anaerobes
For prophylaxis for dental patients w/ total joint replacement
Can be given to patients allergic to penicillins since there is no cross allergencitiy
AMINOGLYCOSIDES:
TETRACYCLINES:
Tetracycline
No tetracycline for pregnant women or children under 9 years of age
Causes pigmentation of developing teeth
Doxycycline & Minocycline
MACROLIDES & LINCOSAMIDES: CLEC
***These three bind to 50S ribosomal subunit
Erythromycin
Clindamycin
Chloramphenicol
Prophylaxis – Dental Treatment
All are given orally, 1 hour prior to the appointment
If no amoxicillin allergy:
Amoxicillin
Adults: 2g
Children: 50 mg/kg
Amoxicillin allergy:
Clindamycin
Adults: 600 mg
Children: 20 mg/kg
Cephalexin
Adults: 2g
Children:: 50 mg/kg
Azithromycin
Adults: 500 mg
Children: 15 mg/kg
Most likely mechanism for the increased occurrence of drug-resistant bugs is R factor transfer of resistance
Don’t get clowned by “increased mutation rate”
ANTIMYCOBACTERIAL AGENTS
RIPE: ⋄ For TB
Rifampin
Isoniazid
Pyrazinamide
Ethambutol
ANTIVIRALS
For herpesviruses:
Acyclovir
Vidarabine
Ganciclovir
Foscarnet
For respiratory viral infections:
Amantadine & Rimantadine – Influenza viruses.
Ribavirin
For HIV:
Zidovudine (AZT)
ddC & ddI
3TC
Protease inhibitors
ANTIFUNGALS
Antifungal drugs affect cell MB permeability
Cause leakage of cellular constituents, leading to death of affected cells
Amphotericin B:
Given orally or by IV for tx of severe systemic fungal infections caused by fungi such as Candida species, Histo, Crypto, and Coccoidio (NOT Nocardiosis)
Bacitracin, polymyxin-B & neomycin are not anti-fungal agents – they are antibiotics
Amphotericin B & Nystatin are polyene Abx which impair ergosterol synthesis
Ergosterol is the major sterol of fungal MBs
Systemic administration is associated w/ a high incidence of kidney toxicity
Nystatin & clotrimazole:
Two antifungals that are used as “swish & swallow” to treat oral candida infections
Nystatin (Mycostatin) is taken as an oral suspension
NOT For psuedomembranous (Use Diflucan)
Clotrimazole (Mycelex) is taken as a troche (lozenge)
They work by binding to sterols in the fungal cell MB
Increase permeability & permit leakage of intracellular contents – leads to cell death
IMIDAZOLES:
Aspergillus is very resistant to imidazoles
Treat aspergillus w/ amphotericin B
|Summary of Some Antifungal Agents |
|Topical agent |Use |Mechanism on fungal cell |Form |
|Clotrimazole |Oropharyngeal candidiasis |Alters cell membrane |Troche |
|Nystatin |Oral cavity candidiasis |Alters cell membrane |Oral suspension |
|Topical agents (cream) | | | |
|Amphotericin B |Cutaneous & mucocutaneous Cand |Alters cell membrane |Cream |
|Ketoconazole |Cutaneous and muco Cand |Alters cell membrane |Cream |
|Nystatin |Cutaneous and muco Cand |Alters cell membrane |Ointment |
|Systemic agents | | | |
|Fluconazole |Oral, esophageal, oropharyngeal Cand |Alters cell membrane |Tablets |
|Ketoconazole |Oral, esophageal, oropharyngeal Cand |Alters cell membrane |Tablets |
|Amphotericin |Systemic candidiasis |Alters cell membrane |IV injection |
VACCINES
Toxoids
Are antigenic and Non-toxic
Are most often prepared by treating toxins with formaldehyde
Weakened bacterial toxins that are no longer toxic but do induce Ab production
Bacterial vaccines: (3 general classes – Toxoids, Killed Organisms, and Attenuated)
Given routinely to children
Diphtheria, pertussis, vaccine (Don’t get clowned by the VIRAL pediatric vaccines – MMR)
Capsular polysaccharide vaccines:
Streptococcus pneumonia vaccine – pneumonia
Neisseria meningitidis vaccine – meningitis
Haemophilus influenzae vaccine – meningitis
Most common cause of acute purulent meningitis in kids 3 months to 2 years Think EMOP
Antigenic component of Haemophilus influenzae vaccine is from a capsular antigen (polysaccharide capsule)
Inactivated protein exotoxins (toxoids)
Corynebacterium diphteriae – diphtheria
Exhibits pathogenicty through toxemia (NOT via bacteremia or septicemia)
Clostridium tetani – tetany
Killed bacteria vaccines:
Bordetella pertussis vaccine – whooping cough
Salmonella typhi vaccine – fever
Typhoid Fever
Asymptomatic carriers are a major hazard – “Typhoid Mary”
Vibrio cholerae vaccine – cholera
Live attenuated bacterial vaccines:
Mycobacterium bovis vaccine – Tb
Francisella tularensis vaccine – tularemia
Coxiella burnetii vaccine – Q fever
Active immunity – induced by vaccines prepared from bacteria or their products
Passive immunity – provided by the administration of preformed ab in preparations called immune globulins (toxoids)
Provides immediate protection & a vaccine to provide long-term protection
Rabies and Clostridium tetani vaccines:
Result in artificially acquired active immunity
Can use vaccine after introduction of the virus to stop clinical symptoms
Longest incubation period
Used to elicit an immune response before the onset of disease symptoms
Effectiveness of this type of vaccine depends on:
Slow development of the infecting pathogen prior to the onset of symptoms
Ability of the vaccine to initiate Ab production before the active toxins are produced/released
Viral Vaccines
Live attenuated
Induce humoral immunity AND cell mediated immunity but have reverted to virulence on rare occasions
MMR, Sabin Polio, VZV, Yellow fever (flavaflav)
Killed
Only induce humoral immunity, but are stable
Rabies, Influenza, Hepatitis A, SalK (K for Killed) Polio
Recombinant
HBV (antigen = recombinant HBsAg)
|SOME CURRENT VIRAL VACCINES |
|Disease |Type of Vaccine |
|Smallpox |Attenuated live virus |
|Yellow fever (viral hepatitis) |Attenuated live virus |
|Hepatitis B |Purified HBsAg: recombinants HBsAG |
|Measles |Attenuated live virus |
|Mumps |Attenuated live virus |
|Rubella |Attenuated live virus |
|Polio |Attenuated live virus (Sabin)—oral |
|Polio |Inactivated virus (Salk vaccine)—injection |
|Influenza |Inactivated virus |
|Rabies |Inactivated virus |
|Varicella (chickenpox) |Attenuated live virus |
|Hepatitis A |Inactivated virus |
Adjuvants:
Non-specific, mildly irritating substances
Purpose: to enhance Ab response
Enhance Ag uptake by APCs
Added to vaccines to slow down absorption & increase effectiveness
Freund’s Adjuvant:
Common experimental adjuvant – consists of killed M. tuberculosis suspended in lanolin & mineral oil
Used to elicit stronger T- & B-cell mediated responses when Ag/s alone fail to evoke sufficient response
Human vaccines contain aluminum hydroxide or lipid adjuvants
Alum-precipitated Ag/s:
Formed from protein Ag/s mixed w/ aluminum compounds
Serves as a local inflammatory stimulus
A precipitate is formed that is more useful for establishing immunity than are the proteins alone
Released more slowly in the body, enhancing stimulation of the immune response
Adjuvants eliminate the need for repeated booster doses of Ag & permits use of smaller Ag doses in the vaccine
Toxoid (aka immune globulins):
Inactivated protein exotoxin (bacterial toxin)
Induce formation of specific antitoxin Ab/s that serve as the basis for the specific protection from the toxin
Used for diphtheria, tetanus, and other diseases
Prepared by treating toxins w/ formaldehyde
Not all toxins can be converted to toxoids by treatment w/ formaldehyde
But is strong enough to induce formation of antibodies & immunity to the specific disease
Antigenic, non-toxic
Antitoxin:
An Ab formed in response to a specific toxin
Antitoxins in serum – Tx or prevention of certain bacterial diseases
Can neutralize unbound toxin to prevent the disease from progressing
Tetanus antitoxin – Tx or prevention of tetanus
Botulinum antitoxin – Tx of botulism
An intoxication rather than an infection
Diphtheria antitoxin – Tx of diphtheria
Routine Vaccines
Infants are routinely immunized against:
DPT shot - Bordetella pertussis, Corynebacterium diphtheriae, and Clostridum tetani (NOT Brucella abortus or H. Influenzae)
DPT vaccine (diphtheria-pertussis-tetanis):
BCG vaccine – avirulent bacteria (TB vaccine), not recom’d in us ‘cuz of low chance of infectivity, ruins PPD test
Unlike DPT, BCG vaccine consist of avirulent bacteria
DPT – pertussis is killed whole bact, ∴ in US now suggest DTaP (pertussis Ag/s, not killed bact); diph / tetanus
Rubeola (measles), pertussis, smallpox, poliomyelitis, mumps & tetanus are all prevented by active immunization
INFECTION CONTROL
The most effective means of preventing disease transmission in a dental office is based on the concept of Universal Precautions
Don’t get clowned by “sterilization”, “asepsis”, or “barrier techniques” – Universal precautions encapsulates all of these
FIND OUT ⋄ OSHA’s blood borne pathogen protocol is used to protect whom?????
To protect the employees!!!
OSHA’s Bloodborne Pathogens Standard 29 CFR 1910.1030 recommends the use of a tuberculocidal disinfectant for surfaces/objects that may be contaminated with blood and/or body fluids. (this represents an intermediate level disinfectant)
FIND OUT ⋄ Dental personnel are most at risk for transmission of TB?? ⋄ Dental Instruments Or Aerosolization
FIND OUT ⋄ What does OSHA stand for? ⋄ Occupational Safety and Health Administration
Some general notes/definitions:
Concentration & contact time: critical factors that determine effectiveness of an antimicrobial agent
Any/all of the 3 major portions of microbial cells can be affected: cell MB, cytoplasmic contents (particularly enzymes) & nuclear material
It is not possible, nor necessary to sterilize all environmental surfaces which become contaminated during patient care. In many instances, because of the relatively low risk of microbial transmission, thorough cleaning of the surfaces is sufficient to break the cycles of cross-contamination and cross-infection
Bactericidal:
Antibacterial solution w/ directly kills bacteria
“Cidal” agents & processes are designed to ensure microbial inactivation
EXs: Glutaraldehyde, betabropiolactone, ethylene oxide, formaldehyde are all bacteriocidal
Bacteristatic:
Inhibit their metabolism and replication
Affected organisms can remain viable but inactive for extended intervals
Not directly kill or inactive microbes
Organism resistance: high→low
Prions→Bacterial spores→Mycobacteria→Parasitic bacteria→Small, non-enveloped viruses→Trophozoites→Non-sporulating G- bacteria→Fungi→Large non-enveloped viruses→Non-sporulating G+ bacteria→Enveloped viruses
Sterilization:
The use of physical or chemical procedure to destroy all microbial life, including bacterial endospores
Limiting requirement is removal of spores
Filtration:
Liquids are generally sterilized by filtration
The most commonly used filter is composed of nitrocellulose and has a pores size of 0.22 μm
This size will retain all bacteria and spores
Filters work by physically trapping particles larger than the spore size
Used for liquids that will be destroyed at temps over 90°C
Pre-cleaning:
The most important step in instrument sterilization
Debris acts as barrier to the sterilant and sterilization process
Ultrasonic instrument cleaning is the safest and most efficacious method of precleaning
2 purposes of cleaning:
Reduction in concentration/number of pathogens
Removal blood, tissue, bioburden, & other debris which can interfere w/ disinfection
Heat sterilization is recognized as the most efficient, reliable, biologically monitorable method of sterilization
All reusable items that come in contact w/ pt must be sterilized
Disinfection:
Less lethal than sterilization
Use of chemical agents to destroy virtually all pathogenic microorganisms on inanimate surfaces (headrests, light handles,etc.)
Does not include destruction of all pathogen or resistant spores
Submerging dental instruments for 15 minutes in a cold disinfectant is unacceptable as a sterilizing method because spores are not killed during that time
Immersion of instruments for 30 minutes in cold disinfectant is expected to destroy strep and staph, NOT spores or Hep B
Glutaraldehyde is approved as an immersion sterilant, but takes a long time
Not considered safe for use on living tissue
Disinfectant:
Antimicrobial agents that kill (germicide) or prevent growth (microbiostatic) of pathogenic microorganisms
Not safe for living tissues (antiseptics are safe) – applied only to inanimate objects
Chlorine: a powerful oxidizing agent that inactivates bacteria and most viruses by oxidizing free sulfhydryl groups
Active component of hypochlorite (bleach), which is used as a disinfectant
Phenol: original disinfectant used in hospitals, but is rarely used as a disinfectant today because it is too caustic
DNP ⋄ 2,4-dinitrophenol
P:O = Phosphorylation : Oxygen ratio = amount of ATP produced from ADP + Pi / per nanogram of O2 consumed
DNP disrupts coupling in mitochondria
DNP decreases the P:O ratio in mitochondria, so NOT allowing it to make energy w/ O2
We want the bugs P:O ratio to do down
Formaldehyde: (37% solution in water = formalin) denatures protein and nucleic acids
A “high level” sterilant (disinfectant) is characterized by what?
Capable of killing all microorganisms and low concentrations of bacterial spores. Used mainly as a sterilant for critical medical devices; monitored by the FDA
Examples: glutaraldehyde, formaldehyde, peracetic acid, hydrogen peroxide
Intermedial levels agents:
Phenols, iodophors, hypochlorite, certain preparations containing alcohols & others
These are able to penetrate the wax and lipid outer layers surrounding mycobacteria
M. tuberculosis – recognized as a benchmark criterion for disinfectant effectiveness
Morphology/structure of tubercle bacilli make them relatively resistant to penetration by a # of low-level disinfectants
Examples: chlorine compounds, alcohol, phenol compounds, iodophors, quaternary ammonium compound
Low level agents
Effective against most bacteria, some viruses and fungi, but NOT TB or Spores
These disinfectants contain a lower concentration of active ingredients
Antisepsis:
Antiseptics:
Chemical agents similar to disinfectants but may be applied to living tissue (i.e., handwashing)
Can be applied to external body surfaces or mucous MBs to decrease microbial #s – not to be taken internally
Temporarily lowers the concentration of normal, resident flora
Alcohol
is the most widely used antiseptic
Used to reduce the # of microorganisms on the skin surface in wound area
Denatures proteins, extracts MB lipids & dehydrates
Dissolves lipids
Inactivates some viruses (only lipophilic viruses)
Disadvantages:
Evaproates too quickly
Has diminished activity against viruses in dried blood, saliva & other secretions
So, not regarded as effective surface cleansing agent
Isopropyl alcohol (90-95%) – major form used in hospitals
Isopropyl alcohol 70%
Disinfectants against herpes simplex but NOT rhinovirus
Ethanol (70%) – widely used to clean skin prior to immunization/venipuncture
Iodine – most effective skin antiseptic used in medical practice (oxidizing agent & combines irreversibly w/ proteins)
Handwashing
Primary disease prevention measure in healthcare
Significantly reduces the # of transient & normal microorganisms that colonize host tissue
Soap is only good for removal of bugs from the skin
Handwash agents include: chlorhexidine gluconate & triclosan
Both have been shown to exhibit an antimicrobial effect when used as handwash agents in health care settings
They also show substantivity = a residual action on washed tissues for extended periods
Hand hygiene (not “handwashing”)
Isopropyl alcohol – for hand hygiene procedures – products containing 60-80% alcohol DO NOT use water
Sanitation:
Tx of water supplies to reduce microbial levels to safe public health levels
Pasteurization:
Tx of dairy foods for short intervals w/ heat, to kill certain disease-causing microorganisms
Target of pasteurization is the destruction of M. tuberculosis
Spaulding Classification
Rule of thumb is anything that can be sterilized should be, but for plastics and other, see below
BONE/BLOOD ⋄ Mucous ⋄ Skin ⋄ No contact
|Spaulding Inanimate Objects Classification |
|Category |Level |Risk |Objects |
|Critical |Heat Sterilization |Very high |Touch bone or penetrate tissue; blood present |
| | | |(scalpels, forceps, scalers, probes, implants) |
|Semi-Critical |Sterilization, High-level |Moderate |Touch mucous membrane but not penetrate; no blood, |
| |disinfection | |(mirrors, burnishers, amalgam carriers, etc.) |
|Non-Critical |Intermediate Level |Low |Unbroken skin contact; no blood; (masks, clothing. |
| | | |b.p. cuffs) |
|Environmental surfaces: Equipment |Low Level disinfection; |Minimal |No direct patient contact, no blood units, knobs, |
|housekeeping |sanitation | |light floors, walls, counters |
Saturated steam sterilization (autoclave):
Most practical & economical & most currently effective sporicide
Most efficient method for destruction of viral & fungal microorganisms
Moist heat destroys bacteria by denaturation of the high protein-containing bacteria via heat under pressure
121°C (250°F) at 15 psi for 20 min
Used for wrapped instruments
To positively destroy all living organisms, the minimum required temperature is 121°C
So, a case with solder that melts at 175°C is OK
134°C (270°F) at 30 psi for at least 3 minutes (flash cycle)
Indicated for unwrapped instruments
Usually only 10 min required to destroy all bacteria
Additional time is allowed for penetration when the instruments are wrapped
Spore forming pathogens provide the ultimate test for efficacy of sterilization
Resist boiling at 100°C at sea level – they must be exposed to higher temperatures
Cannot be achieved unless the pressure is increased
Kills even the highly heat resistant spores of Clostridium botulinum
Clostridium and Bacillus anthracis spores used to check effectiveness of autclaving
Weekly spore testing of autoclave units is recommended
Using calibrated biological indicators remains the main guarantee of sterilization
Spores from Bacillus stearothermophilus should be used to verify heat in autoclave
These preparations contain bacterial spores – more heat resistant than vegatiative bacteria, viruses & other microbes
Best method of avoid cross-contamination of Hepatitis B is by autoclaving or using dry heat on all instruments used in Tx
Dry heat sterilization:
320°F (160°C) for 2hrs at 15 psi
340°F (171°C) for 1hr – also effective
According to Spaulding Classification
Semi-critical items should be reprocessed by heat stabilization if the material is heat stable
Items which are usually sterilized by dry heat can be autoclaved
Remove immediately after cycle to diminish possibility of corrosion & dulling sharp points/edges (carbon steel instruments)
Dry heat destroys microorganisms by causing coagulation of proteins
Advantages:
Effective & safe for sterilization of metal instruments
Does not dull or corrode instruments
Disadvantages:
Long cycle
Poor penetration
Ruins heat-sensitive material
Rapid Dry Heat Sterilization
Can NOT be WET
12 minutes at 350 °F/177°C for Wrapped
6 minutes at 350 °F/177°C for Unwrapped
Internal Air control
Provides a very fast cycle time, no dulling of cutting edges, & dry instruments after cycle
Forced air, dry heat convection ovens used for sterilization of heat-stable instruments
Higher temperature is used; shorter duration
Ethylene Oxide: (Unsaturated chemical vapor)
Used extensively in hospitals for sterilization of heat-sensitve (heat-labile) materials such as surgical instruments & plastics
Kills by alkylating both proteins & nucleic acids – irreversibly inactivates them
Primarily inactivates cellular DNA!!!!!
Most reliable gaseous sterilizing agent available for dental instruments
Limited use because:
Fairly toxic to humans and is also flammable – unsafe
Slow process (10-16 hours) depending on the material to be sterilized – Kaplan says 8-12 hours
The method of sterilization that takes the Longest
Advantages:
Highly penetrative
Does not damage heat sensitive materials (rubber, cotton, plastic)
Evaporates w/out leaving a residue
Works well for materials that cannot be exposed to moisture
NOTE: instruments must be dry before both ethylene oxide & dry heat sterilization – water interferes w/ sterilization process
Glutaraldehyde 2%:
Can be used as a disinfectant or sterilant
An alkalizing agent highly lethal to essentially all microorganism
Chemical with broadest antimicrobial spectrum of activity
Recommendend for disinfecting dental units & handpieces
Requires sufficient contact time (12-15 hours)
Requires absence of extraneous organic material
Advantages:
Most potent category of chemical germicide
Can kill spores (after 10 hours)
EPA registered as chemical sterilant
Approved as an immersion sterilant
Can be used on heat sensitive materials
Disadvantages:
Long period required for sterilization
Allergenic
Not an environmental disinfectant
Extremely toxic to tissues
In hospitals, glutaraldehydes are used to sterilize respiratory therapy equipment
Other Disinfectants:
Alcohols, chlorhexidine, & quaternary ammonium compounds
Immersion of dental instruments in cold disinfectants will not destroy spores or the hepatitis viruses (they are resistant to physical and chemical agents)
Quaternary ammonium compounds (e.g., benzalkonium chloride):
Cationic detergents and have the narrowest range of effectiveness
Quaternary ammmonium compounds have the narrowest antimicrobial spectrum
Used as disinfectants & antiseptics
G+ bacteria are most susceptible to destruction
These compounds are not sporicidal, tuberculocidal, or viricidal
Inactivated by anionic detergents (soaps & iron in hard water)
Mechanism of action is against the cytoplasmic membrane
UV Sterilization
UV light at germicidal wavelengths (185 -254 nm) causes thymine molecules in the DNA to dimerize and become inactive
Bacteria is rendered useless, though it may not die
Only used as supplementary sterilization in conjunction with other methods
Irritation dermatitis:
Most common form of adverse epithelial reaction noted for health-care professionals
20–30% of HC workers suffer from occasional or chronic dermatitis on their hands
Most common manifestation of the condition is irritation dermatitis, a non-specific immune reaction caused by contact w/ a substance that physically or chemically damages the skin
Aggravated by frequent hand washing, residual glove powder left on hands, & harshness or repeated use of some antiseptic handwash agents
More common in cold climates during winter months
Face masks should be changed between patients and more often if heavy spatter (becomes moist w/in or w/out) is generated
Personal protective equipment clinical jackets should be long sleeve, high neck and are required to minimize the potential for exposed skin to contact, and therefore become contaminated w/ a pt’s blood, saliva, or other potentially infectious material
Antigens most responsible for an immediate Type I reaction to natural latex are: Proteins
Only a few of over 250 proteins found in sap from rubber tree Hevea brasiliensis are responsible for Type I immediate IgE mediated reactions to natural rubber latex
These are water-soluble macromolecules that can leach out of latex gloves when a person perspires, or be detected on the surface of other products containing natural rubber latex
Vinyl or nitrile gloves are worn to treat individuals who develop Type I immediate allergic reaction to latex
Hypoallergenic latex gloves are still latex w/ a chemical coating
Not an appropriate latex alternative, as allergic manifestation can still develop
Latex allergy risks factors include: person w/ multiple surgeries, atopy (type I), rubber industry workers, persons w/ an allergy to bananas but NOT a person w/ a pollen allergy
Hepatitis and Sterilization
HBV is the most infectious target of Standard Blood Precautions
HBV is the most infectious bloodborne pathogen known = greatest occupation health care risk of bloodborne disease
Infection control precautions aimed at preventing this viral transmission have also been shown to be effective in preventing HBV & HCV cross-infection
Responsible for infection in 10–30% of exposed, susceptible HC workers
Concentration of HBV in chronic carrier ranges between 106 & 109 virions per ml, it is significantly lower for AIDS
Viral concentration of HCV infected individuals is between HIV & HBV
Transmission of Hep B – parenteral, dirty instruments, microabrasions, and blood, feces, saliva
Hepatitis C – transmitted by accidental needle sticks, blood transfusions, drug addicts sharing contaminated syringes
Anionic surface acting substances (soaps/detergents):
These substances alter the nature of interfaces to lower surface tension & increase cleaning
Their primary value appears to be their ability to remove microorganisms mechanically from the skin surface
Include synthetic anionic detergents & soaps
Detergents:
Are “surface-active” agents composed of long-chain, lipid-soluble, hydrophobic portion & a polar hydrophilic group which can be a cation, an anion, or a nonionic group
These surfactants interact w/ cell membrane lipids through their hydrophobic chain and w/ the surrounding water through their polar group and thus disrupt the cell MB
Nonionic chemicals do not possess any antimicrobial properties
IMMUNOLOGY
Immune system
Main function = to prevent or limit infection by microorganisms such as bacteria, viruses, fungi, and parasites
Protection is provided primarily by the cell-mediated & Ab-mediated arms of the immune system
The other two major components of the immune system: 1) complement and 2) phagocytes
Opsonization
***Opsonin helps prepare bacteria for phagocytosis (NOT intracellular microorganisms or viruses)
Phagocyte locates microorganism via chemotaxis
Adherence sometimes facilitated by opsonization:
Opsonization is the coating of the microbial cell w/ plasma proteins
This speeds up phagocytosis!!!
Opsonins = C3 & the Fc portion of the Ab - These both mark bacteria for phagocytosis.
The Fc receptors on macrophages react w/ the Fc region of IgG & hold the microbe close to the phagocytic cell MB, thus facilitating the engulfment process
Pseudopods then encircle/engulf the microbe
The phagocytized microbe, enclosed in a vacuole (phagosome), is killed by lysosomal enzymes & oxidizing agents
Remember, the capsule protects bacteria from phagocytosis
Neutralization
Ab prevents bacterial adherence
Example is sIgA in the mouth
Complement Activation (more below)
Ab activates complement enhancing opsonization and lysis
Phagocytosis
Involves ingestion/digestion of: microorganisms, insoluble particles (like tattoo ink!), damaged/dead host cells, cell debris, activated clotting factors
Mediated by macrophages & PMNs
Both will phagocytize bacteria coated w/ Ab & complement
The C3b fragment of complement binds to bacteria opsonized by Ab
Then the C3b binds to receptors on phagocytic cells & signals them to phagocytize the organism
Stages:
Chemotaxis – movement of cells up a gradient of chemotactic factors
Adherence – works well for whole bacteria/viruses; less so for proteins or encapsulated bacteria
Pseudopodium formation – protrusion of MBs to flow around the “prey”
Phagosome formation – fusion of the psuedopodium w/ a MB enclosing the prey
Phagolysosome formation – phagosome-lysosome fusion
Lysosome contains H2O2, free radicals, peroxidase, lysosyme, hydrolytic enzymes
Elimination – via exocytosis
Phagocytes:
Includes PMNs, Macrophages, Dendrititic cells and Langerhans, and apparently Eosinophils
Bacteria are ingested by Neutrophilic Lymphocytes
Fixed – do not circulate (fixed macrophages & cells of the reticuloendothelial system)
Free – circulate in bloodstream (PMNs & macrophages)
One Q said: PMNs and Eosinophils (remember granulocytes are not part of RE system)
Eosinophils CAN phagocytose antigen/antibody complexes
Macrophages
Macrophages are activated by lymphokines (mostly IFN-gamma)
Chemotactically, C5a and various cytokines are chemoattractants for activated macrophages
Macrophages have MHC II molecules that present antigenic peptides to T cells
Macrophages present Ag to antigen-specific T cells (CD4 T helper cells)
See discussion below on MHC
Hemosiderin:
Insoluble, iron-containing protein derived from ferritin
Normally occurs in small amounts w/in macrophages of bone marrow, liver, & spleen
Can accumulate in tissues in excess amounts, causing:
Hemosiderosis:
Occurs when hemosiderin builds up in tissue macrophages
Usually does not cause tissue or organ damage
Often associated w/ thalassemia major (beta) –
Think H for Hb H and tHalassemia for Hemosiderin and Histoplasmosis
Hemochromatosis (aka bronzed disease):
More extensive accumulation of hemosiderin throughout the body
Tissue & organ damage
Increased ferritin and increased transferritin saturation
Most often is hereditary disorder – develops in men >40 y.o.
Classic triad – micronodular cirrhosis, pancreatic fibrosis, & skin pigmentation “bronze diabetes”
Results in CHF & increase risk of hepatocellular carcinoma
Disease may be primary (auto recessive) or secondary to chronic transfusion therapy
Immunologic Tolerance
Self vs. Non-self --- How the body knows…why individuals do NOT have an immune response to self proteins
Clonal deletion:
Immature lymphocytes that make self reactive receptors, are deleted before they are released to do their thing
In the medulla of the thymus
1 of 3 current theories to explain why we don’t attack ourselves – and Kaplan describes it…
Lack of co-stimulatory signals:
Foreign & self peptides are the same, so both are able to bind to MHC molecules (so, not the answer)
In order for an immune response to occur, the APC presents the Ag to the TCR
It must ALSO have a secondary signal, or costimulator…this is all part of Congitive Recognition, which is the reason Frogs don’t snap at every black particle, it must act like a fly…which is the same thing as why our body’s cells must have dual signals to know when to attack
Humoral vs. Cellular Immunity (i.e. Differentiation of B/T cells)
Microorganism activates either:
Cell Mediated Immunity
⋄ Macrophage ⋄ via IL-12 ⋄ Activates Naïve Helper T-cell (Th-0) ⋄ via IL-12 ⋄ Activates Th-1 cells ⋄
Then Activated Th-1 either
⋄ via Gamma Interferon ⋄ Activates Macrophage
⋄ via IL-2 ⋄ Activates Cytotoxic T cell (CD8)
Humoral Immunity
⋄ (No name cell) ⋄ via IL-4 ⋄ Activates Naïve Helper T-cell (Th-0) ⋄ via IL-4 ⋄ Activates Th-2 cells
Then Activated Th-2 cell ⋄ via IL-4 or Il-5 ⋄ Activates B cell ⋄ Plasma cell ⋄ Produces antibodies
Summary
Th1 (cell mediated)
Produce IL-2 and gamma interferon, activate macrophages and Tc cells
Th2 (humoral)
Produce IL-4 or IL-5, IL-6, IL-10 and help B cells make Ab
Cellular immunity:
Cellular responses involve T-cells, and result in production of helper T cells & cytotoxic T cells
Mediated by T-cells either through 1) release of lymphokines or 2) exertion of direct cytotoxicity
Immunologic resistance to MOST intracellular pathogens is manifested with Cellular immunity
NOT humoral immunity, wheal & flare reactions, or non-specific serum protection
Host defense against M. tuberculosis, viruses, and fungi, Allergy (only poison oak –contact), Graft and tumor rejection, and regulation of antibody response (Help/Suppression)
It comprises delayed-type (type IV) hypersensitivity reactions
Specific acquired immunity involving T-cells
Acts to resist most intracellular pathogens (bacteria & viruses)
Humoral (Ab-mediated) immunity:
Humoral responses are generated against most antigens and require the secretion of Ab by plasma cells (activated B-cells)
The primary response is always IgM
IgM is initially produced (after a 3-5 day lag phase – Ig/s undetectable), followed by class switching & a decline in IgM
Later, IgG & sIgA become detectable
The secondary response is the result of isotype or class switching, resulting in synthesis of IgG, IgA, &/or IgE
An anamnestic response to previously encountered Ag
Memory B & T cells are responsible for this phase
IgG levels rise more rapidly than in 1° phase (requires less Ag to elicit response)
This response explains the efficacy of booster injections of vaccines
May produce high levels of IgE
B-cells (like T-cells) have surface receptors which enable them to recognize the appropriate Ag
Do not themselves interact to neutralize or destroy the Ag
After Ag recognition, B-cells reside in the 2° lymphoid tissue & proliferate to form daughter lymphocytes
These B-cells then develop into short-lived plasma cells
The plasma cells produce Ab/s & release them into blood at the lymph nodes
Some activated B-cells become memory cells instead of plasma cells
They continue to produce small amounts of Ab long after beating the infection
The key to humoral immunity = ability to react specifically w/ Ag/s
Accomplishes neutralization and inactivation of bacterial toxins
Provides protection against encapsulated bacteria
Opsonization may occur as a component of the humoral immune system in response to virulent Strep pneumoniae (Because you have to opsonize the S. pneumoniae’s antiphagocytic capsule before you can kill it)
If B cells were eliminated, how would you achieve humoral immunity???
Injections of gamma (G) globulin (Ig)???
Natural (innate) immunity:
Present at birth
Occurs naturally as a result of a person’s genetic constitution or physiology
Does not arise from a previous infection or vaccination
Comprised of skin, mucous MBs, secretions such as saliva & tears, phagocytic cells & NK cells
Nonspecific
An example of innate immunity is the alternative pathway of complement, which is demonstrated by phagocytosis of microbes by neutrophils and macrophages
See 2000 Q1 & 2001 Q309
Response does not improve after exposure to the organism
Processes have no memory
EX: HCl in stomach, fever, phagocytosis by PMN (NOT sIgA in mother’s milk)
Acquired immunity:
Develops in response to Ag exposure
Comprised of Ab/s (IgG, IgA, etc) and sensitized lymphocytes (T cells & B cells)
Specific
Improves upon repeated exposure to the organism
Long-term memory
May have an anamnestic response – subsequent response is faster & bigger
Due to memory T cells & B cells
Active or passive
Active immunity
Host actively produces an immune response consisting of Ab/s & activates helper and cytotoxic T-cells
Main advantage – resistance is long-term (years)
Major disadvantage – slow onset
Rubeola, pertussis, poliomyelitis, and mumps
Toxoid still give active
Passive immunity
Ab/s are preformed in another host
Main advantage – immediate availability of Ab/s
Rapid onset
Major disadvantage – short duration of active immunity (That’s why you need the tetanus shot every 10 years)
Think To Be Healed Rapidly
Tetanus toxin, Botulism toxin, Hbv, Rabies (After exposure, pts are given preformed antibodies)
Antitoxin is Passive
Occurs naturally or artificially
Natural Active –
REGULAR
Person is exposed to an Ag & body produces Ab/s
EX: Recovery from mumps infection confers lifelong immunity
Natural Passive –
EX: Ab/s (IgG) passed across placenta from mother to fetus
EX: IgA passes from mother to newborn during breast-feeding
Resistance of new-born to whooping cough
Artificial Active – vaccination w/ killed, inactivated or attenuated bacteria or toxoid
Administration of tetanus toxoid – which is a watered-down toxin
Injection of a killed viral vaccine
Artificial Passive – injection of immune serum or γ-globulin
If person were given tetanus antitoxin ⋄ NOTE Toxin = ANTItoxin
NOTE: Hypersensitivity – an exaggerated immunological response upon re-exposure to a specific antigen
EX – positive skin test after having a disease
See below for more info on the four types of hypersensitivity reactions
Immunogens & Antigens:
Antigen = any substance that can be specifically bound by Ab or a TCR
Immunogen = an antigen that induces an immune response
Include all proteins (they are the most antigenic), most polysaccharides, nucleoproteins, and lipoproteins
Epitope –
ON the AntiGEN
the Ab binding site of the Ag for a specific Ab
Antibodies: (See below)
Able to bind to epitopes on a wide variety of molecules
T-cell receptors (TCR):
CD3 molecules link noncovalently to the TCR
This causes internal signaling, triggering the T-cell
Only able to recognize peptides bound to MHC proteins
Cannot recognize Ag alone – only in the context of MHC molecules
Haptens:
Small molecules that act as an Ab epitope, but will not induce immune responses since they are not recognized as T-cell Ag/s
Have antigenic determinants, but are too small to elicit the formation of Ab/s by themselves
Can do so when covalently bound to a carrier protein
Many allergens (e.g., penicillin) are haptens
The catechol in the plant oil that causes poison oak is a hapten
Usually responsible for contact sensitivity
Not immunogenic because they cannot activate helper T cells
Ab production involves activation of 1) B lymphocytes by the hapten & 2) helper T cells by the carrier
MHC (major histocompatibility complex):
Glycoprotein
A collection of polymorphic genes encoding for proteins that regulate immune responses
In humans, the MHC genes are termed HLA (human leukocyte antigens)
MHC is an antigen located where? ⋄ 6th Human chromosome (I don’t know if this is what they really asked)
Fxns ⋄ Present exogenous antigens to T cells and determine tissue type
*Antigen processing = mechanism for internalization & re-expression of Ag on APC MBs by MHC I & II
MHC I: (Think whistle blower, broadcasting that the factory is making something they are not supposed to)
Found on the surface of all nucleated cells & platelets
HLA-1 is found on all nucleated cells
Bind peptides processed from protein synthesized in the cell cytosol
Endogenous Ag/s are presented by MHC I molecules to CD8 T cells
HLA Class I = HLA-A, HLA-B, HLA-C
T-lymphocytes (not B) recognize Ag on the surface of APCs in the context of HLA-B
Cytotoxic T cells (CD8) recognize MHC I on infected cells (Product is 8)
MHC I Ag loading occurs in rER (viral antigens)
MHC II: (Think Public Health Inspector—Ate something that made them sick, so the APCs, via MHC II to CD4s to B cells to post their Poor Health Grade (Ab) everywhere)
Found on some cells, including APCs, B cells, and thymic epithelial cells invovled in T cell maturation
Bind peptide epitopes from endocytosed molecules
Exogenous Ag/s are processed & presented by MHC II molecules to CD4 T cells
Are necessary for Ag recognition by helper T cells
HLA Class II = HLA-DR, HLA-DQ, HLA-DP
CD4 cells recognize viral, bacterial, parasite, or injected proteins in association w/ class II (Product is 8)
Are the main determinant of organ rejection
MHC II Ag loading occurs in acidified endosome
Short Story for Clarification -- REVIEW
1st – Virus or bug infects the cell
2nd – APC (macrophage, B cell, or Dendritic cell) eats part of the produced virus or protein from the infected cell and grabs a viral epitope and then displays it on its MHC II in hopes that a Helper CD4 cell will come to the rescue
3rd—CD4 T cell recognizes the viral epitope on the APC with its own TCR and receives costimulation via IL-1 from the APC to verify the distress signal
The Costimulatory signal is given from APC (B7) to the Helper T-cell (CD 28)
4th—With the newly confirmed distress signal, the CD4 cell either:
Activates Cellular immunity (Tags a CD8 cell with IL-2 to go find a cell with such and such epitope and kill it)
Activates Humoral immunity (Tags a B cell with IL-2,IL-4, IL-5 to start making antibodies against such and such epitope in the lymph node
Interleukins (largest group of cytokines):
Fundamental function appears to be communications between (“inter-”) various populations of WBCs
Group of well-characterized cytokines produced by leukocytes & other cell types
Have broad spectrum of functional activities that regulate the activities & capabilities of a wide variety of cell types
Particularly important as members of cytokine networks that regulate inflammatory & immune responses
Act as messengers between leukocytes involved in the immunologic or inflammatory response
Think mmmm, T-Bone stEAk
IL-1: A macrophage-derived factor
Stimulates activites of T-cells, B-cells, & macrophages (mmmmm for Macrophage)
Stimulates IL-2 secretion
Pyrogenic (HOT)
IL-2: Produced by activated T cells (T- in T-bone)
Stimulates antigen-activated T helper & NK cells (as well as cytotoxic T cells)
Also stimulates B cells
IL-3: T-cell product that stimulates the growth & differentiation of various blood cells in bone marrow
(B in T-Bone)
Secreted by activated T cells
IL-4: Secreted by activated helper T cells & mast cells
Stimulates B-cells
Increases IgG & IgE (E in stEAk)
IL-5: Secreted by activated helper T cells
Promotes B cell maturation
IL-5 is a B-cell growth & differentiation factor
Increases IgA & synthesis of Eosinophils (A in stEAk)
Acute Phase cytokines ⋄ IL-1, IL-6, and TNF alpha (secreted by macrophage to do a bunch of stuff, like suppress viral replication)
IL-6, 7, 8, 10, 12: see Kaplan, p. 101 for thie summaries
Immunoglobulins = Antibodies:
Glycoproteins found in blood serum
Synthesized by plasma cells in the spleen & lymph nodes in response to detection of a foreign Ag
Two functions:
Bind epitopes on Ag/s – direct attack
Stimulate other biologic phenomena such as activating complement & binding Fc receptors on other lymphoid cells
Mediate anaphylaxis, atopic allergies, serum sickness, and arthus reactions
Structure:
Consist of two heavy chains & two light chains
Heavy chain contributes to both Fc and Fab fragments
Light chain only contributes to Fab
Fab (Antibody)
Contains Antigen binding site
Area from the Hinge region and up
Hypervariable Region
Ag binding to the Fab is noncovalent
Fc (Cell)
The Stem of the “Y”
Binds to the Phagocytes, Mast cells, Basophils, Eosinophils, etc.
Think C ⋄ Constant, Carboxy, Complement binding, and Carbohydrate side chains
The variable part
VH and VL (amino terminal side) recognizes the antigens
Constant regions
In IgG and IgM, it fixes complement
Carboxyl terminal side
Disulfide Bonds
Between 2 Heavy Chains
Between Heavy and Light Chains
Ig Epitopes
Allotype (polymorphism)
Ig epitope that differs among members of same species
Can be on light or heavy chain
Isotype (IgG, IgA,etc.)
Ig epitope common to a single class of Ig (five classes, determined by heavy chain)
An immune cell posseses IgM and IgD on its cell surface…which of the following differs between them? ⋄
Heavy Chain Variable - VH
Idiotype (specific for an antigen)
Ig epitope determined by antigen-binding site
Think “Idio” are unique
Immunoglobulin functions (condensed):
IgG: Opsonization, Placental passage, Complement activation, 2ndary Response
IgA: Mucosal (secretory) immunity, prevents attachment, Gets secretory portion from epi cells first
IgM: Complement activation, 1ary Response, does NOT cross placenta, Ag receptor on B cells
IgE: Basophil & mast cell sensitization, Type I hypersensitivity, Immunity to worms
IgD: Antigen triggering of B cells
Ig Isotypes (detailed):
IgG:
Most abundant
Only Ig that crosses the placenta
Activates complement
Predominant serum Ig found during a memory response
Main defense against various pathogenic organisms
As the severity of Periodontal Disease increases, there is an increase in plasma cells that produce IgG
Secondary or amanestic response to protein antigen
Characterized by production of IgG Ab/s with High Titer
T1/2 = 1 month
Where is it activated????
IgA:
2nd most abundant
Remember that IgA produces more than all of the others combined, but SHORT half life, that is why IgG is most abundant
Polymeric IgA
Present in body secretions, such as (saliva, tears, breast milk, especially colostrums)
Protects surface tissues
Synthesized by plasma cells in mucous MBs of the GI, respiratory & urinary tracts
Important in these areas – plays a major role in protecting surface tissue against invasion by pathogenic microorganisms
Provides 1° defense at mucosal surfaces – bronchioles, nasal mucosa, vagina, prostate, & intestine
sIgA
Found in tears, colostrum, saliva, & milk
Producd by plasma cells in lamina propria of Gi & respiratory tracts
A week old baby has sIgA antibodies already, where does the B cell first get exposed to the Antigen?
In spleen of baby
In spleen of mom
In intestine of baby
Intestine of the mom – If it says for the B cell that made the plasma cell that made the IgA
In breast of mom –only if they ask us where the sIgA comes from
Primary fxn:
To bond w/ surface Ag/s of microorganisms, preventing the adherence and ingress of Ag through the mucosa
Aggregates microorganisms, and prevents colonization
Acts against bacteria in the oral cavity
Resistant to hydrolysis by microbial proteolytic NZs (IgA, IgE, IgG are NOT)
J chain is for Dimeric IgA
J chain is for pentamic IgM
Polymeric ⋄ 2 IgAs joined by a J chain (Think J for Joining)
This happens just below the ductal epithelium (lamina propia)
J chain is added by the Plasma cell (step 10)
J chain also connects up the IgM Pentamer
Then the dimer diffuses to the intraepithelial space and binds to Pig R (polymeric Ig Receptor)
Then that complex is endocytosed, then the Pig R becomes the Secretory Component (SC)
Secretory portion added by the epi cell
Enterosalivary Pathway (SEE PIC)
We absorbed antigen in the gut (via M cell of Peyer’s patch)
Stimulates B cells via CD4+ T-cell Switch cell
B cells then migrate back to salivary glands
Gut has inducer site
Salivary gland has effector site
IgD:
Makes up < 1% of Ig/s
Present in high levels in MBs of many circulating, mature B-cells
Functions in Ag recognition by B cells (but function is not fully understood)
IgM:
Largest Ig
First Ab produced in response to infection or after primary immunization (M for priMary iMmunization)
3 days ago, a pt received her 3rd immunization w/ tetanus toxoid, you would expect to see Low IgM and High IgG
If type A blood is transfused into a type B recipient, the immediate hemolytic reaction would be the result of IgM against the A antigen (NOT IgA or IgG)
Efficient activator of complement
IgE:
Present only in trace amounts in serum
Has reagenic acivity
Protects external mucosal surfaces
Tightly bound to its receptors on mast cells and basophils
Responsible for Type I hypersensitivity reactions (allergic & anaphylactic)
IgE is responsible for atopic allergy
Complement:
Collective term for a system of ~20 plasma proteins, which are the primary mediators of Ag-Ab reactions
Present in normal human serum
Plays a role in humoral immuntiy & inflammation
Participates in lysis of foreign cells, inflammation, & phagocytosis
Acts in a cascade w/ one protein activating another
Synthesized mainly by the liver – some are made in macrophages – C1 is made in GI epithelium
Chemotactic component of complement attracts PMNs
Is not an Ig
Is heat labile
Complement system:
Functions to destroy forgein substances
Either directly or in conjunction w/ other components of the immune system
Components of complement bind to IgG, NOT IgA, IgM, Endotoxins, mast cells– 1999 Q78 Are you sure? Maybe not IgA
What does complement NOT bind to??? (If it says Alternate pathway ⋄ then Immune complexes is the answer!!)
Consists of ~20 plasma proteins that function as enzymes or binding proteins
Activated by C1 (classical) or C3 (alternative)
Includes multiple distinct cell surface receptors – specific for physiological fragments of complement proteins
These receptors occur on inflammatory cells & cells of the immune system
Two pathways:
Alternate pathway:
Activated by:
C3 – Think 311 is an alternate band
LPS (endotoxin)
Aggregated IgA, IgG, IgE, IgM
Cobra venom factor
Example of innate immunity – because you don’t need Ab to work like Classical does
This pathway protects the body in the absence of antibody
Seems to be of major importance in host defense against bacterial infection
Activated by invading microorganisms
Ab independent
Classical pathway:
Activated by IgG and IgM (Think GM makes classic cars)
Activated by Ab-Ag complexes (immune complexes)
Activated by C1 – binds to a specific part of the Ab
C1 – composed of three proteins (C1q, C1r, & C1s); Ca2+ is required for activation
Ab dependent
NOTE: both pathways lead to cell lysis by terminal components (C8 & C9); initiation differs
NOTE: C1 esterase deficiency leads to angioedema (overactive complement)
Membrane attack complex (MAC)
End product of the activation
Contains C5b, C6, C7, C8, & C9
Makes holes in the MBs of G- bacteria & RBCs, resulting in cytolysis
Biologically important C proteins:
C2a, C4a = weak anaphylatoxins
C3a, C5a = strong anaphlatoxins (bigger numbers, bigger response)
C5a = potent chemotaxin
C3b = potent opsonin (think C3b-O, like C3PO, O for opsonin)
Complement fixation:
Binding of complement as a result of its interaction w/:
1) Immune complexes (classic pathway) OR
2) Particular surface (alternative pathway)
Used in detecting Ag or Ab (e.g., Wassermann test [for syphilis])
Only IgM and IgG fix complement – meaning activate
Antigen Detection Techniques
Immunofluorescence (fluorescent antibody)
Most frequently used diagnostic lab technique for microscopic detection of Ag/s in tissue secretions & cell suspensions
Fluorescent dyes (fluorescein & rhodamine) are covalently attached to Ab molecules
Made visible by ultraviolet light in the fluorescence microscope
Labeled antibody can be used to identify bacterial surface Ag/s
Radioimmunoassy (RIA)
Used for the quantification of Ag/s or haptens that can be radioactively labeled
Enzyme-linked-immunosorbent assay (ELISA):
Used for the quantification of either Ag/s or Ab/s in pt specimens
Precipitation (precipitin):
Ag is a solution in this test
The Ab cross-links Ag molecules in variable proportions & precipitates form
Agglutination:
The antibody that attacks in agglutination is IgM
Ag is a particulate in this test (e.g., bacteria & RBCs)
Remember agglutination in a mis-matched transfusion would happen on the donor’s RBCs in the pt
The most common side effect of a blood transfusion is ALLERGIC Rxn, NOT agglutination
Because Ab (agglutinin) is divalent or multivalent, it cross-links the multivalent Ag particles & forms a latticework
Clumping (agglutination) can be seen
Hemagglutination – when clumping results from addition of Ab to RBCs (Ag/s must be present on surface of RBCs)
Is the basis for blood typing & distinguishing the presence of A type Ag or B type Ag on the surface of RBCs
If blood mixed with A antiserum, and Rh Positive antiserum and NO agglutination occurs, then they are TYPE B and Rh Negative
If blood mixed with A antiserum, B antiserum, and Rh Positive antiserum and NO agglutination occurs, then they are TYPE O and Rh Negative
If blood mixed with anti-A serum, anti-B serum, and anti-Rh serum, and agglutination DOES occur, this pt has Rh(+) type AB
Prozone
Immune systems with high titers of agglutination often fail to agglutinate homologous bacteria in low dilution
How things leave blood vessels:
Cellular adherence to vascular endothelium
Upregulation of endothelial adhesion molecules (ICAM-1 and VCAM-1) is in part response to cytokine stimulation
ICAM-1 & LFA-1 are specific receptors that make endothelial adherence of leukocytes possible
T cells use LFA-1 to bind to ICAM-1 of the endothelial cell
Margination
Lining up of the leukocytes along the wall of a dilated vessel
Transendothelial migration
Active passage of the leukocytes through the capillary wall happens by means of endothelial pores
Things that happen inside the blood & things that happen outside the blood:
Extravascular events:
Chemotaxis (totally extravascular)
Movement of cells towards chemicals (positive) or away from chemicals (negative)
Intravascular events:
Stasis (Stagnation of the blood or other fluids)
Hyperemia (Presence of increased amount of blood in a part or organ
Margination (Lining up of the leukocytes along the vessel walls in inflammation)
Pavementing – flattening of a cell against the interior wall of the venule
Anaphylatoxins:
Family of peptides C3a, C4a, & C5a produced in the serum during complement activation
Probably mediated indirectly via histamine release from mast cells & basophils
C5a – most powerful
100x more effective than C3a…1000x more effective than C4a
Most important chemotactic factor from the complement pathway
Chemotactic accumulation of inflammatory cells where immune complexes are deposited is most probably due to the presence of C5a
Produce smooth muscle contraction, mast cell histamine release, affect platelet aggregation, & act as mediators of the local inflammatory process
Anaphylaxis caused by complement components is less common that caused by Type 1 (IgE mediated) hypersensitivity
Sensitization
All of the following require prior sensitization:
Anaphylaxis (TYPE I), Arthus rxn (TYPE III), Erythroblastosis fetalis, and Contact Dermatitis (TYPE IV)
Anaphylactoid reactions do not require prior sensitization
Uticaria = Hives
Skin reaction characterized by wheals (small, smooth, slightly elevated areas that are redder or paler than surrounding skin)
Can be allergic reaction to food, medicine, or other substance
1st symptom is usually itching – quickly followed by wheals
Angioedema:
Related to & sometimes coexistant w/ uticaria
The swelling covers large areas & extends deep beneath skin
Involve part or all of the hands, feet, eyelids, lips, genitals, or even oral mucosa, throat, & airways (makes breathing difficult)
Uticaria & angioedema are anaphylactic-type reactions limited to skin & underlying tissues
Uticaria & angioedema are of rapid onset & can either be just annoying or life-threatening
Therapy – use of epinephrine, antihistamines or steroids
Deficiency of C1 esterase inhibition
Angioneurotic edema (Absence of the inhibitor of the C1 component of complement – same as above)
Hereditary angioedema:
Absence of C1 esterase inhibitor
In other words, absense of the inhibitor of C1 component of complement may result in angioneurotic edema
Hypersensitivity reactions:
Think ACID ⋄ 1, Anaphylaxis/Atopic 2, Cytotoxic 3, Immune complex 4, Delayed
Type I: (Anaphylaxis and Atopic)
Think First and Fast
Antigens (allergens) combine w/ specific IgE Ab/s bound to MB receptors on tissue mast cells & blood basophils
Requires previous exposure that sensitizes mast cells & basophils
The Ag-Ab reaction causes rapid release of potent vasoactive & inflammatory mediators
Mediators are preformed (histamine, tryptase) OR newly generated from MB lipids (leukotrienes & prostaglandins)
Leukotrienes & prostaglandins
Anaphlatoxins – C3a & C5a are generated via tryptase action
Bradykinin – generated from kininogen by the action of kallikrein, activated Hageman factor (XIIa) or trypsin
Common allergens – foods, pollen, drugs, insect venom, animal dander, house dust
Severe anaphylaxis (anaphylactic shock):
Physiological shock from anaphylactic hypersensitivity reaction
Occurs suddenly (seconds or minutes) in an allergic individual after Ag exposure
EXs: bee bites or penicillin reaction
PCN rxn is Type I
Anaphylaxis is inducible in a normal host, unlike atopy
Anaphylactic reaction involves degranulation of mast cells
Release of histamine, heparin, platelet-activating factors, SRS-As & serotonin into bloodstream
Histamine is responsible for the principle symptoms of anaphylaxis
1st symptoms – anxiety, weakness, sweating, SOB, & generalized urticaria
Associated with immediate rxn, passive transfer by serum, participation of Abs, smooth muscle spasm and capillary damage
NOT associated with delayed rxn
Constriction of the bronchioli and ↓ BP are the usual causes of death
EX: after an injection of penicillin into a penicillin-sensitized person may lead to death by the above means
Immediate treatment:
Maintain airway
Inject epinephrine
Drug of choice for shock
Opens airways & raises BP by constricting BVs
Conscious pt – IM or subcutaneous
Unconscious pt – IV
Which of the following causes vasoconstriction and vasodilation when administered IV? ⋄ Epinephrine
Antihistamines (e.g., diphenhydramine) & corticosteroids (e.g., prednisone)
May be given to further reduce symptoms
Atopic allergies:
Predisposition of an individual to sensitization is characteristic of atopy
Result from a localized expression of Type I hypersensitivity reactions
Interaction of Ag/s (allergens) w/ cell-bound IgE on the mucosal MBs of the upper respiratory tract & conjunctival tissues initiates a localized type I hypersensitivity reaction
Most allergy sufferers are atopic
Possible to become allergic w/out being atopic
Heredity plays an important role
Allergies can jump a generation
Atopy can only occur in genetically predisposed individuals, unlike anaphylaxis
Atopic individuals are genetically programmed to produce an abundance of IgE Ab/s
IgE strongly reacts against allergens in the environment (pollen, moulds, household dust, etc)
Risk for becoming allergic
One parent w/ allergies = 30% risk
Both parents w/ allergies = 60% risk
Three principal kinds of atopic allergies: (Triad)
Atopic dermatitis (eczema):
Chronic skin disorder categorized by scaly & itching rashes
Most common in infants – at least ½ of the cases clear by 3 y.o.
In adults – chronic or recurring condition
A hypersensitivity reaction occurs in the skin, causing chronic inflammation
Result: skin becomes itchy & scaly
Rhinitis (hay fever & year-around symptoms):
When the allergen interacts w/ sensitized cell of the upper respiratory tract
Symptoms – coughing, sneezing, congestion, tearing eyes, & respiratory difficulties
Histamine is the 1° mediator – released from sensitized mast cells & basophils
Allergic asthma:
Allergic reaction primarily affecting the lower respiratory tract
Common in children
Characterized by SOB & wheezing
Specific IgE Ab/s & nonspecific inhaled irritants provoke mast cell degranulation
Release of histamine & leukotrienes (SRS-As) cause bronchospasm & bronchial mucus secretions
Allergic desensitization is produced by competitive inhibition ⋄ Basis for allergy shots
FIND OUT ⋄ What kind of hypersensitivity is it if you take multiple doses of Pen G for syphilis, and then the ABX seeps into the RBCs?????? – I think Type I
Type II: (Cytotoxic) – “C” in “ACID”.
Think Cy-2-toxic
IgG, IgM
Cytotoxic reactions resulting when Ab reacts w/ antigenic cell components or tissue elements or w/ antigen or hapten coupled to a cell or tissue.
Ab reacts w/ cell-surface epitopes
Complement-mediated lysis or phagocytosis
The Ag-Ab reaction may activate certain cytotoxic cells (killer T cells or macrophages) to produce Ab-dependent cell-mediated cytotoxicity, usually involving complement activation
Examples:
Certain drug allergies
Blood transfusion reactions (red cell lysis)
Hemolytic disease of the newborn
Autoimmune hemolytic anemia
Goodpasture’s syndrome
Type III: (Immune complex, Serum Sickess, Lupus, and Arthus Rxn)
Immune complex (IC) reactions – result from deposition of excessive soluble circulating Ag-Ab ICs in BVs or tissue
Think 3 Things stuck together in a complex (Ag –Ab-complement)
Most commonly deposited in kidneys, joints, skin & BVs
Glomerular lesions in the immune complex disease result from IgG
The ICs activate complement & thus initiate sequence of events resulting in PMN cell migration & release of lysosomal proteolytic enzymes & permeability factors in tissues, thereby producing acute inflammation
Active mechanism for damage to BVs in an immune complex disorder is phagocytosis of immune complexes by the RE system (macrophages)
The chemotactic accumulation at the site of the immune complex deposition is a result of complement
Reticuloendothelial system typically clears ICs
NOTE: Histamine does not play a major role in these Type III hypersensitivity reactions
Clinical features:
Urticaria, lymphadenopathy, edema, fever
Serum sickness
The hallmark of Type III hypersensitivity
Results from IC deposition in small vessels
Appears some days after injection of a foreign serum or serum protein
Local & systemic reactions – uticaria, fever, general lymphadenopathy, edema & arthritis
Type of systemic arthus rxn
Arthus rxn:
Is the cutaneous reaction of type III responses
Highly localized, appears w/in 1 hour, resolves w/in 12 hours
Type III hypersentivity – local subacute type III rxn, intradermal injx of ag induces Abs→Ag-Abs complex in skin
Immediate type of reaction where Histamine does NOT play a major role
EX: When horse serum is injected into a rabbit and again into the skin 2 to 3 weeks later, the necrotizing rxn that results at site of injection is an Arthus reaction
Serum Sickness is a type of an systemic Arthus rxn, so says an old Q, but Kaplan doesn’t mention it
Type IV: (Delayed, cell-mediated)
Think 4th and Last (Delayed)
Cellular, cell-mediated, delayed, or tuberculin-type reactions caused by sensitive T-cells after contact w/ a specific Ag
Circulating Ab/s are neither involved in nor necessary for development of tissue injury
Delayed type of hypersensitivity demonstrated by a positive tuberculin skin test
Hypersensitivity to M. Tuberculosis is manifested by necrosis
Delayed type of hypersensitivity can be transferred by sensitized lymphocytes ⋄ encounter Ag and release lymphokines – hence the term “cell-mediated”
Cellular infiltrate in a fully-developed delayed hypersensitivity reaction consists mainly of macrophages & lymphocytes
Th1 cells and macrophages
Contact dermatitis
Usually Latex is Type I (think allergic or atopic contact URTICARIA), but if the questions says it’s a TYPE IV rxn, which would mean Allergic contact DERMATITIS, then go with the following!!!
Type IV reaction due to latex gloves, consists of Macrophages, Lymphokines, and T lymphocytes
Allograft rejection
When a 1st rejected allograft is followed by a 2nd allograft from the same donor…the 2nd rejection occurs more rapidly than the 1st
Hence, a reminder that you need presensitization
Primary tissue transplant, such as allogenic skin, kidney or heart, are most commonly rejected due to
Cell-mediated immune responses to cell-surface autoantigens
Similarities between Type I and IV???
Complement OR Response after 24 hours???
Thymectomized and nude mice:
Have reduced numbers of T-lymphocytes
Can’t reject allografts
Have reduced Ab production to most antigens – no helper Ts
Have decreased or absent delayed type IV hypersensitivity
|Classification of Hypersensitivity Reactions |
|Type |Immunologic Mechanism |Example |
|Type I (anaphylactic type): Immediate |IgE antibody mediated – mast cell activation & degranulation |Hay fever, asthma, anaphylaxis, atopic dermatitis, |
|hypersensitivity | |eczema |
|Type II (cytotoxic type): Cytotoxic |Cytotoxic (IgG, IgM) antibodies formed against cell surface |Autoimmune hemolytic anemias, antibody-dependent |
|antibodies |antigens. Complement is usually involved |cellular cytotoxicity (ADCC), Goodpasture’s syndrome |
|Type III (immune complex type): Immune |Antibodies (IgG, IgM, IgA) formed against exogenous or |SLE, rheumatoid arthritis, most types of |
|complex disease |endogenous antigens. Complement and leukocytes (neutrophils, |glomerulonephritis, arthus rxn, serum sickness |
| |macrophages) are often involved | |
|Type IV (cell mediated type): Delayed type |Mononuclear cell (T lymphocytes, macrophage) w/ interleukin and |Granulomatous disease (Tuberculosis, Sarcoidosis, |
|hypersensitivity |lymphokine production |Crohn’s, Fungus), contact dermatitis, graft rejection |
| |*Q answer: sensitized lymphocytes | |
|Blood Group |Ag/s (agglutinogens) on erythrocytes |Antibodies (agglutinins) in plasma |
|O (universal donor) |*none* |Anti A & Anti B |
|A |A |Anti B |
|B |B |Anti A |
|AB (universal recipient) |A & B (alloantigens – both A & B) |*none* |
Autoantibodies
Anti-nuclear antibodies (ANA) Systemic Lupus
Anti-dsDNA, anti-Smith Specific for Systemic Lupus
Anti-histone Drug-induced Lupus
Anti-IgG Rheumatoid arthritis
Anti-neutrophil Vasculitis
Anti-centromere Scleroderma (CREST)
Anti-Scl-70 Sclerderma (diffuse)
Anti-mitochondria 1ary biliary cirrhosis
Anti-gliadin Celiac disease
Anti-basement membrane Goodpasture’s syndrome
Anti-epithelial cell Pemphigus vulgaris
Anti-microsomal Hashimoto’s thryoiditis
INFLAMMATION & NECROSIS
Inflammation overview:
Exudative component:
Involves the movement of fluid, usually containing important proteins like fibrin and immunoglobulins
BVs are dilated upstream of an infection (causing redness and heat) and constricted downstream
Capillary permeability to the affected tissue is increased, resulting in a net loss of blood plasma into the tissue
This gives rise to edema or swelling
The swelling distends the tissues, compresses nerve endings, and thus causes pain
Cellular component:
Involves the movement of WBCs from blood vessels into the inflamed tissue
The WBCs (leukocytes) take on an important role in inflammation
They extravasate (filter out) from the capillaries into tissue & act as phagocytes
They may also aid by walling off an infection and preventing its spread
If inflammation persists:
Released cytokines IL-1 & TNF will activate endothelial cells to upregulate receptors VCAM-1, ICAM-1, E-selectin, and L-selectin for various immune cells
Receptor upregulation increases extravasation of PMNs, monocytes, activated T-helper and T-cytotoxic cells, as well as memory T and B cells to the infected site
Inflammation can lead to anemia, because shift to making more inflammatory cells rather than RBCs
Cytokines:
Soluble mediators that play an important role in immunity
Small molecular weight peptides of glycopeptides
Many produced by multiple cell types such as lymphocytes, monocytes/macrophages, masts cells, eosinophils, even endothelial cells lining BVs
Each individual cytokine can have multiple functions
Depends upon the cell that produces it & the target cells upon which it acts (pleotropism)
Several different cytokines can have the same biologic function (redundancy)
Exert their effect:
1) on distant targets through the bloodstream (endocrine)
2) on target cells adjacent to those that produce them (paracrine)
3) on the same cell that produces them (autocrine)
Most important effect of most cytokines is paracrine & autocrine functions
Major functions appear to involve host defense or maintenance and repair of blood elements
Four major categories of cytokines:
Interferons:
A family of inducible glycoproteins produced by eukaryotic cells in response to viral infections
The fact that eukaryotic cells produce interferon can be used to distinguish viral infections from other microbial assaults!!!!!
Interfere w/ virus replication
Act to prevent the replication of a range of viruses by inducing resistance
Elaborated by infected host cells that protect non-infected cells from viral infections
Induce viral resistance in adjacent, non-infected cells
Do not block the entry of the virus into a cell, but rather prevent the replication of viral pathogens w/in protected cells
Are not antiviral antibodies
Have no direct effect on viruses
Antiviral action is mediated by cells in which they induce an antiviral state
Considered a non-specific innate resistance factor (as are lysozyme, complement, etc.)
Interferon proteins do not exhibit specificity toward a particular pathogen
Means interferon produced in response to one virus is also effective in preventing replication of other viruses
Alpha and Beta ⋄ Inhibit viral protein synthesis
Gamma ⋄ Increase MHC I expression and Antigen presentation in all cells
Tumor Necrosis Factors (TNF):
Injecting them into animals causes a hemorrhagic necrosis of their tumors
Secreted by activated macrophages – Easier to eat dead stuff
Interleukins (largest group of cytokines):
Fundamental function appears to be communications between (“inter-”) various populations of WBCs
Group of well-characterized cytokines produced by leukocytes & other cell types
Have broad spectrum of functional activities that regulate the activities & capabilities of a wide variety of cell types
Particularly important as members of cytokine networks that regulate inflammatory & immune responses
Act as messengers between leukocytes involved in the immunologic or inflammatory response
Think mmmm, Hot T-Bone stEAk
IL-1: A macrophage-derived factor (mmmm)
Stimulates activites of T-cells, B-cells, & macrophages
Stimulates IL-2 secretion
Pyrogenic (HOT)
IL-2: Produced by activated T cells (T- in T-bone)
Stimulates antigen-activated T helper & NK cells (as well as cytotoxic T cells)
Also stimulates B cells
IL-3: T-cell product that stimulates the growth & differentiation of various blood cells in bone marrow
(B in T-Bone)
Secreted by activated T cells
IL-4: Secreted by activated helper T cells & mast cells
Stimulates B-cells
Increases IgG & IgE (E in stEAk)
IL-5: Secreted by activated helper T cells
Promotes B cell maturation
IL-5 is a B-cell growth & differentiation factor
Increases IgA & synthesis of Eosinophils (A in stEAk)
Acute Phase cytokines ⋄ IL-1, IL-6, and TNF alpha (secreted by macrophage to do a bunch of stuff)
IL-6, 7, 8, 10, 12: see Kaplan, p. 101 for thie summaries
Colony Stimulating factors (CSF):
They support the growth and differentiation of various elements of the bone marrow
Neutrophils: (aka polymorphonuclear leukocytes or PMNs)
Most numerous WBC (50–75%)
Increase dramatically in response to infection/inflammation
Fxns:
Phagocytosis of bacteria
Elaboration of proteolytic NZs
1st cells to infiltrate the inflammation site
PMNs kill by 1) toxic O2 metabolites & 2) digestive enzymes from lysosomal granules
Oxygen-dependent killing of bacteria by PMNs involves:
Superoxide, Myeloperoxidase, Hydrogen Peroxide, NADP Dehydrogenase
NOT collagenase
Remember in Gingivitis you have lots of PMNs,
In order get to PD, you need Collagenase, which comes from Lymphocytes!!!!
Enzymes include myeloperoxidase (azurophilic granules) & lactoferrin (specific granules)
Primary constituent of pus
Highly mobile cells – attracted to areas of inflammation by chemotaxis
They reach the tissues by diapedisis
Identify, attach to & begin engulfing the invading organisms in attempt to contain the infection
If infection continues, monocytes arrive (better engulfing ability)
NZs responsible for suppuration in an abscess are derived from PMNs
Inflammatory substances:
Process of attraction and recruiting cells in which a cell moves toward a higher concentration of a chemical substance
The Vasodilators:
Histamine
Bradykinin
C3 and C5 (via mast cells/Histamine)
Prostaglandins
Histamine:
Formed from histidine by decarboxylation
Released from the coarse cytoplasmic granules of tissue mast cells & basophils
In early stages of acute inflammation, histamine mediates the contraction of endothelial cells
Histamine is liberated by degranulation triggered by the following stimuli:
Binding of specific Ag to basophil & mast cell MB-bound IgE
TEST wording: Histamine release requires antibodies (IgE) attached to mast cells and reacting with antigen
Binding of anaphylatoxins (C3a & C5a) to specific cell-surface receptors on basophils & mast cells
Release causes: increased capillary permeability, bronchial constriction, increased gastric secretion, and a drop in BP
Responsible for the principal symptoms of anaphylaxis
Serotinin has similar actions
Serotonin:
Also called 5-hydroxytryptamine
Synthesized from the aa tryptophan by enteroendocrine cells in the gut & bronchi
Plays a role in temperature regulation, in sensory perception, and in the onset of sleep
Powerful vasoconstrictor Downstream??? And vasodilator
Stimulates platelet aggregation (blood clotting) – rls by platelets.
Largest amount is found in cells of the intestinal mucosa
Smaller amounts in platelets & in CNS
In CNS:
Acts as a neurotransmitter in the brain
Inhibitor of pain pathways in spinal cord
Lysergic acid diethylamide – interferes w/ action of serotonin in the brain
Secreted in tremendous quantities by carcinoid tumors (tumors composed of chromaffin tissue)
Kaplan says, 5-HIAA is secreted, which is a metabolite of serotonin
Bradykinin:
Vasoactive kinin – potent vasodilator
Mediates vascular permability, arteriolar dilation, & pain
Pain in inflamed tissue is associated with the Bradykinin mediator
Produced by the action of kallikrein (generated by activated Hageman factor, factor XIIa) on an alpha-2 globulin (kininogen)
Chemical mediator of acute inflammation that is generated through the activation of an enzyme precursor (Kallikerin) that requires activated Hageman factor
Hageman factor helps to create Bradykinin
May be involved in BP regulation
Arachidonic acid:
An unsaturated fatty acid generated by inflammatory cells and injured tissue
Major compound from which prostaglandins, prostacyclin thromboxanes, & leukotrienes are derived
Part of phospholipids in plasma MBs
When a neurotransmitter or hormone stimulates a cell, activating phosholipase A (a plasma MB enzyme)
PLA splits arachidonic acid from the phospholipids
Different metabolic pathways utilize different enzymes that convert arachidonic acid into the different messengers:
1) Cyclooxygenase: prostaglandins, prostacyclins, & thromboxanes (NOT leukotrienes)
Prostaglandins – chemical messengers present in every body tissue
Act primarily as local messengers that exert their effect in the tissues that synthesize them
*PGG2 is converted to PGH2, which is ultimately converted to TxA2
2) Lipooxygenase: leukotrienes, HETEs, diHETEs
Leukotrienes:
A group of compounds derived from unsaturated FAs (arachidonic acid & other polyunsaturated FAs)
Extremely potent mediators of immediate hypersensitivity reactions & inflammation
Leukotrienes C4, D4, & E4
Collectively known as slow-reacting substances of anaphylaxis (SRS-As)
Responsible for development of many symptoms associated w/ allergic-type reactions
100-1000x as potent as histamine or prostaglandins in constricting bronchi
In asthma, the allergic reaction occurs in the bronchioles of lungs
The most important products released by mast cells are SRS-As (the 1° mediators of asthma)
SRS-As causes bronchiolar smooth muscle spasms
Anaphylatoxins C3a & C5a – induce physiological response that results in BV dilation, hypotension, ↑ vascular permeability
Acute Inflammation:
The initial response of tissue to injury, particularly bacterial infections, involving vascular and cellular responses
What is involved in the early phase of wound repair?
Inflammatory ⋄ bacteria and debris are phagocytosed and removed, factors are released that cause the migration and division of cells involved in proliferative stage
Proliferative and Maturation are more in chronic
Three major phenomena:
1) Increased vascular permeability – tissue exudate forms
Mean capillary pressure decrease and osmotic pressure decreases in acute inflammation
2) Leukocytic cellular infiltration – mainly PMNs via C5a & C3a
3) Repair – regeneration or replacement
Chemotactic accumulation of mononuclear cells which occurs at the sites where immune complexes were deposited is probably the result of C3 (only if C5a is not an answer)
Local signs:
Redness = rubor, Heat = calor, Swelling = tumor, Pain = dolor, organ dysfunction
Systemic effects:
Fever, Tachycardia, Leukocytsosis (esp. PMNs)
Vascular phase:
Vasoconstriction (temporary) – seen as blanching of skin
What happens before Vasodilation in inflammation??? ⋄ Vasoconstriction
Only transient
Vasodilation – increased blood flow to infected area
Happens immediately after vasoconstriction
Done by Histamine, Bradykinin, and Serotonin
The 1st vascular reaction (following transient vasoconstriction) to injury in the sequence of events in inflammation
Increased permeability – allows diffusible components to enter the site
Congestion in the early stages of inflammation is caused by active hyperemia (NOT ischemia, venous dilitation, venous constriction, lymphatic obstruction)
Cells
Basophils, Mast cells, Platelets – present in vascular phase – all release histamine
Vasodilation and increased permeability lasting for several days in an area of inflammation indicate
Endothelial cell damage and dysfunction
Cellular phase:
Leukocytes (mainly PMNs) are the 1st defense cell to migrate to the injured tissue – chemotaxis
Leukocytes engulf particulate matter by phagocytosis
Engulfed matter becomes a phagosome – combines w/ lysosomal granules to form a phagolysome for digestion
Cells
PMNs – predominate
Macrophages – appear late & mark transition between acute & chronic inflammation
NOTE: Eosinophils – predominate in allergic reactions & parasitic infections
Chronic Inflammation:
Develops at a site of injury that persists longer than several days
Cells: Lymphocytes, Macrophages, and Plasma Cells – not PMNs or Mast Cells
Necrosis commonly occurs & recurs
EXs: chronic hepatitis, pyelonephritis, and autoimmune diseases
Granulomatous inflammation:
A subtype of chronic inflammation characterized morphologically by granulomas
Proliferative processes dominate (NOT exudation, transudation, and congestion)
Characterized by a circumscribed collections of lymphocytes, macrophages, epitheliod cells with a background of fibroblasts, capillaries, and delicate collagen fibers
EXs: TB, sarcoidosis, & silicosis
Vasodilation & ↑vasopermeability lasting several days in inflamed area indicate formation of granulation tissue
Initial vasodilation of inflammation is due to serotonin, histamine, bradykinin
SIDENOTE
Chronic Granulomatous Disease
Hereditary disease where neutrophil granulocytes are unable to destroy ingested pathogens
Neutrophils normally require a set of enzymes to a reactive oxygen species to destroy bacteria after their phagocytosis
These NZs are called phagocyte NADPH oxidase complex, which is responsible for initiating the respiratory burst
SO in CGD, PMNs ingest baceria but then cannot kill them
MOST infections are caused by Staph Aureus, or CATALSE + bugs
Hence bugs that destroy the respiratory burst are left behind to cause chronic GD
Inflammatory Infiltrate
Fluids, PMNs, and Macrophages
Exudates:
Principally water – also contains nutrients, oxygen, Ab/s & WBCs
Characterized by being protein-rich, cell-rich, glucose-poor & has a high specific gravity (> 1.020)
First role – flush away any foreign material from site of injury
If fluid is cloudy/discolored – strong indication of infection
Acts as a carrier to bring fibrin, etc., to the site of injury
Acts as a carrier for leukocytes – provides oxygen/nutrients for ingestion of bacteria & debris
Nutrients are used by the new tissue to help in the generation of granulation tissue
Act as a lubricant, speeding up epithelial cell migration across wound surface to complete initial repair
Types of imflammatory exudates:
Suppurative
Purulent
Fibrinous
Pseudomembranous
Serous
NOT Fibrous
Acute inflammatory exudates
Includes Plasma fluid, plasma proteins and WBCs
NOT Plasma cells
Transudates:
Result from ↑ intravascular hydrostatic pressure or from altered osmotic pressure
Thin & watery – characterized by few blood cells, low protein content, & low specific gravity (< 1.020)
Differs from Exudate by having a lower protein concentration
Present in non-inflammatory conditions, such as cardiac failure
Most common acute inflammatory reactions
Contain large # of PMNs
Termed suppurative (produce purulent matter)
Suppuration is the result of tissue necrosis, proteolytic enzymes, WBCs, & fluid buildup
NZs responsible for suppuration are found in the PMNs
NOT the result of the presence of lymphocytes
Abscess:
Confined collection of pus, which consists of dead WBCs & necrotic tissue
Surrounded by a wall of proliferation fibroblasts (produce collagen) – body’s attempt to limit spread of infection
Cyst:
Abnormal sac w/in the body containing air or fluid
Lined w/ epithelium
Granulation Tissue:
Newly formed, highly vascularized CT associated with inflammation
Composed of:
Lymphocytes
Fibroblasts
Macrophages
Endothelial cells
Newly Formed Collagen
Capillary Buds
NOT Giant cells, Nerve cells, or Epithelioid cells, or Plasma cells – these are Granulomatous
Granuloma:
Differentiate!!!!
Central necrosis surrounded by macrophages, lymphocytes, plasma cells, and occasional giant cells
Nodular collections of epithelioid cells – specialized macrophages
Epithelioid cells are characteristic of granulomas (NOT granulation tissue)
Rim of lymphocytes, plasma cells, & fibroblasts surround the nodule of epithelioid cells
Produced by multinucleated giant cells (aka Langerhans giant cells & foreign body giant cells)
Multinucleated giant cells of the foreign-body type originate from fusion/division of mononuclear cells (macrophages)
Characteristically associated w/ areas of caseous necrosis – produced by infectious agents, particularly M. tuberculosis
Granulomatous inflammation is a subtype of chronic inflammation
Etiologic agents associated w/ granulomatous inflammation:
Infectious agents:
Mycobacterial diseases – TB & leprosy
Girl with ulcerated lesion on tongue has Langerhans cells and granulomatosis, what is the disease???
Tuberculosis Granuloma???
Fungal infections – blastomycosis, histoplasmosis, & coccidiomycosis
Spirochetes: T. pallidum, which causes syphilis
Cat scratch disease – caused by Bartonella henselae
Foreign material – suture or talc
Sarcoidosis – unknown etiology, NON-caseating, NON necrotizing (whereas tuberculosis is caseation necrosis)!!!!!
Crohn’s disease – NON-caseating, NON-necrosis, granulomatous inflammation of the gut wall
Healing:
The restoration to integrity to an injured tissue
After the inflammatory phase, wound healing is accomplished by three mechanisms; contraction, repair, and regeneration.
In most instances, all three mechanisms occur simultaneously
Healing by 1st intention:
Healing by fibrous adhesion, w/out suppuration or granulation tissue formation
Occurs when wound margins are nicely apposed, such as in surgical repair of a surface wound
With well-approximated wounds, there is little granulation tissue & the final scar is minimal
Healing by 2nd intention:
Large wound defects
CT repair occurs when the wound is large & exudative – large amount of necrotic tissue & suppuration formed
Site fills in w/ a highly vascular, pinkish tissue known as granulation tissue
This produces large, irregular scars
Uncomplicated healing of a wound by secondary intention, observed microscopically after 3 days is most likely to show...
Ulceration of the epithelial surface
NOT granulomatous inflammation, lack of acute inflammation, or keloid formation
Healing by 3rd intention:
Slow filling of a wound cavity or ulcer by granulations, w/ subsequent cicatrisation (the process of scar formation)
Which hormone establishes the greatest effect on granulation tissue in healing wounds?
Cortisone
Glucocorticoids have been shown to have the greatest effect on granulation tissue
Tensile strength of healing wound depends upon the formation of collagen fibers
Whether a wound heals by 1° or 2° intention is determined by the nature of the wound, rather than by the healing process
Keloids (cheloids):
A nodular, firm, movable, nonencapsulated, often linear mass of hyperplastic scar tissue, tender and frequently painful
Consist of wide, irregularly distributed bands of collagen fibers
Occur in the dermis & adjacent subcutaneous tissue, usually after trauma, surgery, a burn, or severe cutaneous disease such as cystic acne, and is more common in blacks
Tumor:
Growth of tissue that forms an abnormal mass
Caused by abnormal regulation of cell division
Generally provide no useful function & grow at the expense of healthy tissue
Necrosis:
Set of morphologic changes that accompany cell death w/in a living body
Differs from autolysis – a process of cell death outside a living body
May manifest in different ways, depending on the tissue or organs involved
Coagulative necrosis is the most basic and most common type of necrosis
When larger areas of tissues are dead, the tissue is called gangrene
|Types |Causes |Most likely sites involved |
|Coagulation necrosis |Ischemia (loss of blood supply) |Heart & kidney (renal & cardiac infarcts) |
|Liquefaction necrosis (infarct to brain) |Suppuration, abscesses & ischemic CNS injury |Brain or spinal cord |
|Caseous necrosis (Caseation) |Granulomatous inflammation (typical of TB) |Granulomatous inflammatory sites |
| |Calcification and “Soapy” – Think Cheesy TB Lesion | |
|Gangrenous necrosis |Putrefactive bacteria acting on necrotic bowel or extremity |Lower extremities or bowel |
|Fibrinoid necrosis |Immune-mediated vascular damage |Arterial walls (RA, Scleroderma, RF) |
|Fat necrosis |Injured pancreas, trauma to adipose tissue |Adipose tissue, pancreas |
Basic Types of Necrosis
Two types of necrosis are recognised and are based on the degree of preservation of the architecture of the cells and tissues. These are as follows:
Coagulative necrosis
Coagulative necrosis is characterised by the preservation of cellular and tissue architecture.
Microscopically, the nucleus, cytoplasm, and cellular outlines including the arrangements of cells in the necrotic tissue are still intact.
This type of necrosis is often difficult to detect grossly, except probably when the affected area is large where subtle changes in tissue colour may be recognized. It usually results from acute disease conditions such as acute toxicity (chemical toxicants or biological toxins) and sudden deprivations in blood supply.
Heart and renal Infarct (MI)
Characteristic nuclear changes:
Pyk- = condense
Kary- = nucleus
Karyolysis – destruction of dissolution of the cell nucleus w/ fading of chromatin
Karyolyis of myocardial cell (& probably any other cell type) is irreversible
Karyopyknosis = pyknosis – shrinkage of the cell nuclei & condensation of the chromatin
Another Q reads: condensation & shrinking of the cell nucleus w/ chromatin clumping
Karyorrhexis – fragmentation of the cell nucleus & chromatin
Karyorrhexis follows karyopyknosis during the process of apoptosis
NOTE: the key point is that these nuclear changes are morphologic hallmarks of irreversible cell injury and necrosis
Liquefactive or Lytic necrosis
Rapid enzymatic dissolution of the cell that results in complete destruction is called liquefactive or lytic necrosis (or colliquative necrosis).
It is seen in bacterial infections that lead to pus formation in which proteolytic enzymes are released from leucocytes
Pus is the evidence of liquefactive necrosis – Think suppurative, abscesses, and brain injury
In a pt who had an infarct in the middle cerebral artery…anticipated type of tissue alteration would be liquefaction necrosis
Brain or spinal cord
Suppuration
Acute pyogenic infections are associated with suppuration
Strep Pyogenes ⋄ Causes liquefactive necrosis
Special Forms of Necrosis
1) Fat Necrosis - occur in two forms:
Traumatic Fat Necrosis result from rupture of fat cells because of trauma
Enzymic Fat Necrosis occurs following the enzymic splitting of fat into fatty acid and glycerol by action of lipases (seen in chronic pancreatitis)
2) Zenker Necrosis (Zenker degeneration) - loss of striations in muscles following necrosis (a type of coagulative necrosis in striated muscles)
3) Caseation Necrosis - the presence of friable, cheesy or pasty, amorphous material in necrotic area, usually reserved but not limited to those seen in tuberculous lesions
4) Fibrinoid Necrosis - a special form of necrosis associated with the accumulation of fibrinoid (see protein overload) in connective tissues and blood vessel walls
5) Gangrenous Necrosis (See Below) - necrosis of tissue following deprivation of blood supply, and putrefaction following invasion by saprophytic bacteria. If it is moist, it is called Wet Gangrene. If moisture is not present, it is called Dry Gangrene
6) Infarct - a form of coagulative necrosis resulting from a sudden deprivation of blood supply (process: infarction, see under haemodynamic changes)
Other Terms Used in Association with Necrosis
1) Malacia - an area of liquefactive necrosis of the nervous tissues. Literally mean "softening"
2) Slough - a piece of necrotic tissue separating from viable tissue. Applied to necrosis of surface epithelia.
3) Ulcer - shallow area of necrosis, applied to epithelial surfaces.
4) Sequestrum - an isolated area of necrosis warded off from viable tissue. Applied to isolated necrosis of bones.
Gas Gangrene:
Results from local infection w/ the anaerobic, spore-forming, G+ rod Clostridium perfringens
C. perfringens produces toxins that kill nearby cells
Rare infection generally occurs at site of trauma or a recent surgical wound (devitalized tissues)
Results from compromised arterial circulation
Onset is sudden & dramatic
Inflammation begins at infection site – a pale to brownish-red & extremely painful tissue swelling
Gas may feel as a crackly sensation when the swollen area is pressed on
Margins of infected area expand rapidly – changes are visible over a few minutes
Involved tissue is completely destroyed
Gangrene is the death of tissue – usually associated w/ loss of blood supply to the affected area.
A form of necrosis combined w/ putrefaction (decomposition, rotting)
Systemic symptoms – sweating, fever & anxiety
If untreated, pt develops a shock-like syndrome w/ ↓ BP, renal failure, coma, & death
Prevented by proper wound care
Clostridium bacteria:
Produce many different toxins (alpha, beta, epsilon, iota)
Most important toxin is alpha toxin (lecithinase) – damages cell MBs, including erythrocyte MBs (hemolysis)
GASTROINTESTINAL TRACT
ORAL CAVITY
Normal healthy mouth:
Consists of mainly obligate & facultative anaerobes, aerobes, and acidogenic bacteria
1979 reads: anaerobic, facultative, & acidogenic (NOT “anaerobic, aerobic & facultative”)
1989 reads: the single most numerous group of microorganisms in the oral cavity is facultative streptococci
Most oral streptococci are alpha-hemolytic
Least likely bacteria in the mouth is Mycobacterium
(other options were: Fusobacterium, Prevotella, Actinobacillus, Porphyromonas)
Bacteria with limited range of habitats in the oral cavity are:
Treponema and Bacteroides (Streptococcus & Actinomyces do not have a limited range in the O.C.)
After two teeth were extracted, a foul smelling, purulent material drains, which bugs are responsible:
Bacteroides and Peptostreptococcal (NOT salmonella, clostridium – these should not normally be in the mouth)
Essentially the same bacteria found healthy gingival sulcus become opportunistic & influence the course of PD disease
Obligate anaerobes are found in the oral cavity as part of the normal flora; they are opportunistic
ABX, Anticancer therapy, & corticosteroids all would affect the oral microflora
Progression from a healthy gingival sulcus to gingivitis is associated with a shift towards more G- anaerobic rods (not cocci)
Most dramatic change to the Oral Flora occurs ⋄ when primary teeth erupt
Gingival sulcus (Periodontal Pocket):
Principal oral site for growth of Spirochetes, Fusobacteria, & other G- anaerobes
Endotoxin (LPS) accumulates in the gingival crevice in the absence of gingival hygiene
Inhabitants
Normally G- anaerobic Rods and Fusobacteria
Treponema, Bacteroides, Actinobacillus, and Fusobacterium
NOT Mycobacteria
Actinomyces naeslundii
Branching, filamentous microorganism that is a normal inhabitant of the gingival crevice and tonsilar crypts
Crevicular Fluid
Contains:
IgA, IgG, Lymphocytes, PMNs
NOT IgE
Most numerous Leukocyte is the Gingival Crevicular Fluid is the Neutrophil
Area of stagnation & bacterial proliferation; due to:
1) increase in crevicular gingival fluid
2) desquamation of epithelial cells
3) bacterial acid products
Microbial population of the perio pocket is of a low order of intrinsic pathogenicity – means they are opportunistic
The fact that oral microorganisms can enter the body by way of gingival sulci and perio pockets is evidenced by….
The transient bacteremias following dental procedures
Aerosolizatoin
Dental instrument causing aerosolization of large numbers of bugs is the….ultrasonic scaler
The aerosolization produced during dental procedures usually contains gram POSitive bugs
Most of the the bugs in the dental operatory come from the pts mouth
Xerostomia
Most pronounced effect on reduced salivary flow is a shift toward more acidogenic microflora
Caries:
Strep bacteria (G+, facultative anaerobes):
Most numerous group of bacteria in oral cavity
S. mutans – major cariogenic property is ability to produce dextrans & GTF (glucosyltransferase)
First stable colonizer of the OC
S. sanguis – the most frequently isolated Strep in the oral cavity; produces H2O2; usually 1st to colonize plaque
S. salivarius – found consistently in saliva & oral soft tissue (including under tongue)
Found commonly on the dorsum of the tongue (NOT S. mutans, L. acidophilus, P. melanginogenica)
S. mitis – produces H2O2
Properties necessary for caries formation:
Adhere to tooth surface (colonize)
Produce lactic acid (from degradation of glucose)
Produce a polymeric substance (from CHO metabolism) – causes acid to remain in contact w/ tooth
Produce dextran sucrase (GTF)
Caries process:
GTF catalyzes the formation of extracellular glucans from dietary sucrose
Glucan production contributes to the formation of the dental plaque
Dental plaque holds lactic acid (produced by Strep bacteria) against the tooth
The acid eats through enamel – creating caries
Acidogenic microorganisms are the most important causative agents of dental caries (Lactobacillus and Streptococcus families)
The ability of certain oral bugs to produce caries appears to be correlated with their capacity to produce an extracellular polysaccharide dextran-like substance involved in the formation of dental plaque
Prerequisites for caries development:
Cariogenic bacteria
Susceptible host
Supply of substrate for lactic acid production
Bacteria that may be etiologically related to dental caries:
S. mutans, salivarius, sanguis (not S. mitis, although it is found in dental plaque)
A. viscosus, naeslundii, israelii
A. viscosus & A. naeslundii cause root-surface caries
NOT israeli
L. casei – aciodogenic
Bacteria that initiate caries must have ability to produce extracellular insoluble glucans
Dextrans & mutans – polymers of glucose (Extracellular polysaccharides)
Produced by S. mutans, sanguis, salivarius, & Lactobacillus species
Levans (fructans) – polymers of fructose
Produced by S. mutans, sanguis, salivarius & L. casei, acidophilus
Dextrans, mutans & levans are synthesized from dietary sucrose by cariogenic & plaque bacteria
S. mutans acts on sucrose to produce levans and dextrans
In S. mutans, the end-product of glucose metabolism is lactate
Plaque
Features:
Key etiologic agent in initiation of gingivitis & PD disease
For a bacterium to be seriously considered in the etiology of dental caries, it must exist regularly in the dental plaque
Accumulation of a mixed bacterial community in a dextran matrix
Forms on a cleaned tooth w/in minutes
Composed of 80% solids (95% bacteria) & 20% water
Two categories: supragingival & subgingival
Proportions of varying plaque bacteria (cocci, rods, & filaments) change w/ time, diet & location
Direct association between amount of bacterial plaque and amount of gingival inflammation
Stages of plaque formation:
Formation of the pellicle (acquired pellicle):
Surface coating of salivary origin – primarily protein in nature w/ some CHO complexes
Essentially structureless & bacteria free
Forms w/in minutes on a clean tooth surface due to its salivary origin
Also forms on crowns, dentures, & porcelain
Bacterial colonization:
Bacteria attach to pellicle in a somewhat orderly fashion
Cocci (Streptococci) first colonize – in tremendsouly large #s
After a tooth erupts, what increases most rapidly?? ⋄ aerobic gram +
Facultative Gram + (choose this if listed as an option)
Rods (Bacteroides & Fusobacterium) then colonize tooth surfaces
As plaque matures, shift in morphology to include filamentous types (Actinomyces)
Maturation stage:
Saliva continues to provide agglutinating substances & other proteins to the intercellular matrix
Bacterial intercellular adhesion results
The crystalline structure increases & eventually calcifies
Average time for whole process is 12 days – for calculus
Supragingival plaque
Attached or tooth associated
Consists primarily of G+ facultative anaerobic cocci
Fewer anaerobes than subgingival plaque
S. sanguis, A. viscosus & A. naeslundii predominate?????
With time, Vibrio species, Spirochetes, & G- bacteria predominate
Subgingival plaque:
Attached or loosely adherent (epithelium associated)
Dominated by G- rods as pockets form
More anaerobes than supragingival plaque
Actinomyces species, F. nucleatum, Treponema species (spirochetes), and Veillonella (sulcus)
Young plaque: -- REVIEW
G+ cocci (40-50%) – Streptococcus
G+ rods (10-40%) – Lactobacillus
G- rods (10-15%) – Fusobacterium, Actinobacillus (not many until plaque matures)
Filaments (≤ 4%) – Actinomyces & Veillonella
As plaque age:
50% G+ ⋄ 30% G+
# of cocci ↓ ⋄ # of rods then filaments ↑
# of aerobic bacteria ↓ ⋄ # of anaerobic bacteria ↑
Calculus:
Calcified/mineralized bacterial plaque
Forms by bathing plaque in saliva – high [Ca] & [P]
Surface is very rough & is covered by a layer or bacterial plaque
Inorganic components –
70-90% of the composition
Ca & PO4 w/ small amounts of Mg & CO3 (derived almost entirely from saliva); also hydroxyapatite & F–
Organic components & water –
Remainder of composition
Includes an abundance of Microorganisms (same as plaque), desquamated epithelial cells, leukocytes, & mucin
Main role in PD disease – serves as a collection site for more bacteria
Subgingival calculus is dark due to pigments from blood breakdown
Root Canals
Preferred Bacteriologic media for culturing root canals:
Thioglycollate broth
Periodontal Disease
Gingivitis
Oral bacteria play a role in gingivitis is proven by….a reduction of inflammatory states with ABX OR by reduction in inflammation after removal of the bacteria
Periodontitis
The normal oral microflora causes PD
Most likely source of bacteria playing a role in PD is from the Subgingival plaque
Bacterial endotoxins play a role in PD due to their role in inciting an inflammatory response
As the severity of PD increases, there is an increase in plasma cells that produce IgG
In pts with chronic PD, when the T cells react with certain plaque bacterial antigens, they produce:
IL-2, TNF-alpha, IFN-gamma (looks like here, they want you to know what cytokines are)
NOT Immunoglobulin
Actinobacillus:
G- coccobacillary rods
A. actinomycetemcomitans
Part of normal flora in upper respiratory tract
Rare opportunistic pathogen – causes endocarditis on damaged heart valves & causes sepsis
Most commonly implicated w/ the etiology of:
Localized juvenile periodontitis (LJP)
17 yr old with sparse plaque and periodontitis (A. actinomycetemcomitans)
Periodontitis in juvenile diabetes
Acute necrotizing ulcerative gingivitis (ANUG): “Vincent’s infection” or “trench mouth”
Condition which presents rather pathognomonic (indicative of disease) clinical signs/symptoms
Pathognomonic = “Characteristic of a single disease”
Two most important clinical sings:
1) Interproximal necrosis & pseudomembrane formation on marginal tissues
This is why we know its P. intermedia – think Interproximals
2) History of soreness & bleeding gums caused by eating & brushing
Other signs/symptoms – fetor oris (offensive odor), low grade fever, lymphadenopathy, & malaise
PMN predominates in inflammatory infiltrate of ANUG
Because it’s a gingivitis
Occurs most often in adults between 18-30 y.o.
Predisposing factors – Hx of gingivitis, tobacco smoking, gross neglect, fatigue, & stress
Associated bacteria:
Prevotella intermedia
Fusobacterium species
Intermediate-sized Spirochetes
Selenomonas species
Topical Antimicrobials:
Chlorhexidine:
Most effective antimicrobial agent for long-term reduction of plaque & gingivitis
Leaves greatest residual concentration in mouth after use
Rapidly absorbed onto teeth & pellicle – slowly released
Characterized by a cumulative antimicrobial effect – substantivity!!!
ADA: approved as antimicrobial & antigingivitis agent
Peridex & PerioGard
Stannous fluoride:
Antimicrobial action related to the tin ion rather F–
Available in gel form (e.g., Stop, Gel-Kam)
ADA: approved as anticaries but not antiplaque/antigingivitis
SIDE NOTE: Fluoride is most effective and safest as a prophylactic measure when its added to the water supply
Phenolic compounds:
ADA: approved as antimicrobial & antigingivitis agent
Listerine
Quaternary ammonium coumpounds:
Not as effective as others in reducing plaque or gingivitis
Best at eliminating halitosis
Scope & Cepacol
Mechanism of action is against the cytoplasmic membrane
Mandible Infection
Soft tissue infection spreading along the mandible and into the floor of the mouth would likely involve:
Eikenella corrodens, Staph aureus, Strep pyogenes, Peptostreptococcus anerobius, and Bacteroides!!!!!
Ludwig’s angina:
Aka “submandibular space infection” or “sublingual space infection”
Not often seen
An extension of infection from the Mn molar teeth into the floor of mouth
Characteristics:
First – brawny induration that doesn’t pit on pressure. No fluctuance is present
Secondly – three facial spaces are involved bilaterally: submandibular, submental, and sublingual spaces
Thirdly – the patient has a typical open-mouthed appearance
It has a rapid onset
Dysphagia, dyspnea, and fever are present
May swell to block airway = emergency
Goal of emergency Tx is to maintain open airway (intubation or tracheostomy, if needed)
Abx (usually penicillin-like drugs) are given via IV to treat until symptoms diminish – then given orally
Most cases appear to be mixed infection – Streptococci almost always present
Cervicofacial actinomycosis (Aka “lumpy jaw”):
Chronic infection w/ Actinomyces, usually A. israelii
BOTH Actinomyces and Nocardia are gram + rods forming long branching filaments, LIKE FUNGI
SNAP
Sulfa for Nocardia, Actinomyces use PCN
Branching, G+, microaerophilic, filamentous
NOT dimorphic
Causes very hard, deep infections with broad swelling and draining fistulas
Slow growing, deep, lumpy pyogenic cutaneous abscesses that extrude a thin, purulent exudate through multiple sinuses
A. Israeli causes ⋄ abscesses
Develops chiefly in the jaws and neck, less frequently in the lungs and alimentary tract
Occurs following tissue damage that is contaminated w/ endogenous organism (also found in healthy oral cavities)
Can be treated w/ long-term PCN therapy SNAP
Actinomyces are G+ filamentous bacteria that are normal inhabitants of the oral cavity and GI tract
Lesion have characteristic “sulfur granules” – Actually misnomer
These are actually colonies of infecting actinomycotic organism
Osteomyelitis is a common occurrence
Infection after pulled tooth ⋄ from Actinomyces “lumpy jaw”
Behcet’s syndrome:
Chronic, relapsing inflammatory disease that can produce recurring, painful mouth sores, skin blisters, genital & ocular sores, & swollen joints
Invovles oral, ocular, and genital lesions (incorrect: herpetiform & recurrent aphthous)
Formation of a pus-like fluid in the anterior chamber of the eye
Pyodermas (pus-producing disease of the skin) are common
Often there is CNS involvement in a variety of forms
Aphthous-related condition w/ associated genital lesions and a genetic predisposition
A multisystem disease of uncertain pathogenesis, consisting of multiple oral, anogenital and ocular apthouslike lesions
Uveitis – inflammation of the uveal tract of the eye, including the iris, ciliary body & choroid
Frequently w/ arthralgia (1° ankles and knees), thrombophlebitis, macular and pustular skin lesions and associated CNS involvement
Hypersensitivity to minor scratches or other irritations
Pharyngitis
Inflammation of the pharynx
Main symptom is a sore throat
Other symptoms ⋄ Inflammation, exudates, fever, leukocytosis, lymphadenopathy
Caused by a variety of viruses (adenoviruses & coxsackie viruses)
ESOPHAGUS
Acid reflux:
Backflow of stomach contents upward into the esophagus; most obvious symptom is heartburn
Gastroesophageal reflux:
Clinical symptoms related to reflux of the stomach or duodenal contents into esophagus
Cause: Inappropriate relaxation of lower esophageal sphincter
Crural diaphragm important anti-reflux function, especially w/ increased pressure.
Hiatal hernia interferes w/ crural diaphragm
Crural may be damaged by bile and pancreatic secreations
Associated w/ smoking, some foods and juices
A person with chronic bleeding ulcer in the stomach will most likely present with what?? ⋄ Esophageal reflux???
Maybe Hematemesis
Heatburn most common sign, also accompanied by dysphagia, regurgitation and bleeding if excessive erosion is present
Dx: w/ barium swallow, ambulatory 24 pH monitor, endoscoopy
Complications include esophageal ulcers, aspiration, and barrett esophagus ⋄ that is lined w/ columnar epithelium increasing incidence of adenocarcinoma. Chronic GERD is associated w/ esophageal carcinoma
Tx: lose weight, use antacids, H2 blockers, and surgery
Barrett’s esophagus: BARRett’s = Becomes Adenocarcinoma, Results from Reflux
Glandular (columnar epithelila) metaplasia: replacement of nonkeratinized squamous epithelium w/ gastric (columnar) epithelium in the distal esophagus
Achalasia (A-chalasia = absence of relaxation):
Nerve related disorder of unknown cause that can interfere w/ two processes:
1) Rhythmic waves of peristalsis
2) Opening of lower esophageal sphincter [due to the loss of myenteric (Auerbach’s) plexus]
Main symptom: difficulty swallowing both solids & liquids (progressive dyshpagia)
Barium swallow shows dilated esophagus w/ an area of distal stenosis
Associated w/ increase risk of esophageal carcinoma
Hiatal hernia:
Protrusion of a portion of the stomach through the diaphragm
Cause is unknown; most people have minor symptoms
Plummer-Vinson syndrome
Atrophic glossitis, esophageal webs, dysphagia
Associated w/ iron deficiency anemia
Mallory-Weiss syndrome:
Mild to massive, usually painless bleeding due to a tear in the mucous MB at junction of esophagus & stomach
Also characterized by hematemesis (vomiting of blood)
Most common in men > 40, especially alcoholics
Tears are usually caused by severe retching & vomiting
Most common after excessive intake of alcohol DRUNK DUCKS (Mallory (mallard))
Treatment varies w/ severity of bleeding
GI bleeding usually stops spontaneously
Tear usually heals in ~10 days w/o special Tx – surgery rarely required
Esophageal varices:
Found elsewhere in file
Esophageal cancer:
Risk factors include ABCDEF: achalasia, Barretts esophagus, Corrosive esophagitis/Cigarettes, Diverticuli (eg., Zenker’s diverticulum), Esophageal web/EtOH, Familial
Most common malignant neoplasm of the esophagus is a squamous cell carcinoma – not adenocarcinoma from Barrett’s
STOMACH
Pyloric stenosis:
Associated w/ polyhydramnios, hypertrophy of the pylorus causes obstruction
Palpable mass in epigastric region and projectile vomiting at 2 weeks of age. Tx = surgery
Acute Gastritis
Alcoholics??
NOT associated with Smoking????
Chronic gastritis:
Type A (fundal): (most superior part)
Think 4 A’s ⋄ Autoimmune disease, Autoantibodies to parietal cells, pernicious Anemia, Achlorhydria
Type B (antral): (End part of the stomach)
Think B for Bug
Caused by H. pylori infections
Both increase risk of gastric carcinoma
Not caused by Cigarette Smoke – (why should it be affected by cigarette smoke…very little smoke gets into stomach.)
Peptic ulcers: (Duodenal)
Circumscribed lesions in the mucosal MB from gastric acid & pepsin
80% occur in the duodenum – can also develop in lower esophagus, stomach, pylorus, or jejunum
Most commonly occur in men between ages 20-50
Most commonly located in the first part of the duodenum
Most common symptom = pain
Temporarily relieved by eating
Diet changes don’t help
If erosion is sufficiently severe, stomach wall BVs are damaged, & bleeding occurs into stomach itself
Complications:
Duodenal peptic ulcer causes bleeding, stricture, perforation, NOT cancer
This is my good ulcer, pain relieved with eating and NO cancer
Hemorrhage
Most common complication of chronic peptic ulcers
Most likely with duodenal peptic ulcers
Perforation
Most common complication destructive for endothelial cells of peptic ulcers that RESULTS IN DEATH
Perforation with peritonitis
In extreme cases a peptic ulcer can lead to perforation (a hole entirely through the wall of the GI tract
Causes acute peritonitis – can lead to death
Stenosis
LEAST common complication is malignant degeneration
Esophageal ulcers:
Caused by repeated regurgitation of stomach acid (HCl) into lower esophagus
Gastric ulcer:
Affect stomach mucosa
Most common in middle-aged & elderly men
Most are benign but carcinoma must be ruled out
Think G ⋄ Pain Greater w/ meals, which leads to weight loss
Caused by H. pylori infection in 70%; NSAIDs is also implicated
Due to decrease in mucosal protection against HCL
Duodenal ulcer: (Peptic from above)
DO NOT become malignant.
Erosion in the duodenum lining
Type of peptic disease caused by an imbalance between acid & pepsin secretion and the defenses of the mucosal lining
Inflammation may be precipitated by aspirin & NSAIDs
Commonly associated w/ presence of H. pylori in the stomach
Risk factors – aspirin, NSAID use, cigarette smoking, older age
Due to increase in gastric acid secretion or decrease in mucosal protection. (gastric ulcers tend to have less acid secretion than normal).
Think D ⋄ Pain Decreases w/ meals, leading to weight gain
Hypertrophy of Brunner’s glands
Tend to have clean “punched out” margins unlike the raised/irregular margins of carcinoma
Not associated w/ corticosteroids and alcohol
20% aren’t related to H. pylori (other source says that almost 100% are caused by H. pylori), NSAIDs or elevated gastrin & are idiopathic
Tx of H. pylori w/ triple therapy:
metronidazole, bismuth salicylate, & amoxicillin or tetracycline
Zollinger-Ellison syndrome (uncommon):
Gastrin-producing tumor leading to increased HCl & multiple persistant ulcers
Usually located in the pancreas
May be associated with MEN Type I
50% are malignant
A decubital ulcer is an example of tissue destruction caused by ischemia – (Same thing as bed sores??)
A chronic ulcer that appears in pressure areas of skin overlying a bony prominence in debilitated patients confined to bed or otherwise immobilized, due to a circulatory defect, hence the ischemia.
Stomach cancer:
Almost always adenocarcinoma
Esophagus is SCC - esoph has no glands so ⋄ SCC. (Except w/Barrets where epithel has changed to columnar just like stomach, so now, just like stomach ⋄ Adenocarcinoma)
LUNG is Adenocarcinoma
Early aggressive local spread and node/liver metastasis
It is associated w/ dietary nitrosamines, achlorhydra, chronic gastritis
Is NOT etiologically associated w/ smoking – smoke doesn’t get into stomach.
BUT…Smoking about doubles the risk of stomach cancer for smokers – American Cancer Society
Termed linitis plastica when diffusely infiltrative (thickened, rigid appearance)
Associated:
Virchow’s node: involvement of supraclavicular node by metastasis from stomach
Krukenberg’s tumor: bilateral metastasis to ovaries. Abundant mucus, signet-ring cells
SMALL INTESTINE
Meckel’s diverticulum
A true diverticulum due to persistence of the omphalomesenteric vitelline duct
True meaning it has the muscularias propria layer
Most are acquired, and False
Atresia – congenital absence of a region of bowel. Atresia = absence
Stenosis – narrowing, which may lead to obstruction
Diarrhea:
Types:
Osmotic: secondary to poorly absorbable solutes, (laxatives), slows w/ fasting
Secretory: caused by toxins like enterotoxigenic E. Coli or cholera,⋄large amounts of water, doesn’t slow w/ fasting
Drinking water is usually checked for E. Coli
You treat Cholera by replacing fluids (Vibrio cholera)
Exudative: secondary to invasive bacteria like shigella, includes inflammatory bowel diseases. Mainly involves colon.
White cells in stool
Motility disorder: irritable bowel syndrome, surgical bypass
Tx: treat underlying cause, opiates to slow peristalsis (except in acute infx), replace lost fluids
Bismuth subsalicylate—inhibit colonization of enterotoxins
Antibacterial and anitprotozoal
Malabsorption:
Impaired intestinal absorption of dietary constituents
Can cause deficiencies of nutrients, proteins, fats, vitamins, or minerals
Symptoms vary depending on the deficiency
Clinical features: diarrhea, steatorrhea, weakness, weight loss
Steatorrhea – results in deficiency of A, D, E, K, and calcium
Vitamin B12 malabsorption occurs in pernicious anemia (due to the absence of intrinsic factor) & in Crohn’s disease
|Summary of Fat-Soluble Vitamins |
|Vitamin |Physiologic function |Result of deficiency |
|A |Helps maintain normal body growth & health of specialized tissues (esp. |Night blindness, skin lesions, xerophthalmia |
| |retina); production of rhodopsin (photopigment) |(keratinization & dryness of eye tissues) |
| |Promotes differentiation of epithelial cells | |
|D |Essential in bone formation |Rickets in children; osteomalacia in adults |
|E |Antioxidant |Possible neurologic dysfunction |
|K |Involved blood clotting |Tendency to hemorrhage |
| |*Helps Produce Prothrombin | |
|Vitamin |Deficiency Leads To |Characteristic of Deficiency |Symptoms |
|Vitamin B1 |Wet beriberi, dry beriberi |High cardiac output; peripheral neuropathy |Pins and needles sensation, especially in feet |
|(thiamine) | | | |
|Vitamin B2 |Cheilosis; glossitis |Skin fissures at angle of mouth; |Sore tongue and cracks at edge of mouth |
|(riboflavin) | |inflammation of tongue | |
|Vitamin B3 |Pellagra |Dementia, dermatitis, & diarrhea | |
|(niacin) | | | |
|Vitamin B6 |Cheilosis; glossitis, anemia |Skin fissures at angles of mouth; | |
|(pyridoxine) | |inflammation of tongue; # of RBCs is below | |
| | |normal | |
|Vitamin B12 |Megaloblastic anemia (i.e., pernicious anemia)|Anemia in which there is a predominant # of |Anemia, pins and needles sensation |
|(cobalamin) |Neurologic dysfunction |megaloblasts & few normoblasts | |
|Folic acid |Megaloblastic anemia |Anemia w/ a predominant # of megaloblasts |Anemia |
| |Neuroligic dysfunction is not a feature |(abnormally large nucleated RBCs) | |
|Vitamin C |Scurvy, defective formation of mesenchymal |Swollen, bleeding gums, muscle, joint, & |Weakness, bleeding gums |
|(ascorbic acid) |tissue & osteoid matrix; defective wound |bone pain, abnormal bleeding | |
|Essential in bone |healing | | |
|formation |Impaired collagen formation | | |
Other nutrient deficiencies
Iron – anemia
Calcium – bone thinning
Vitamin D – Bone thinning (Rickets, Osteomalacia, Rachitic Rosary
Vitamin K – Tendency to bruise & bleed
Protein – Tissue swelling, usually in legs
Malabsorption syndromes:
Develop when nutirents are not absorbed properly into blood
Main characteristic finding = steatorrhea – light-colored, soft, bulky, & foul-smelling stool
Celiac sprue = celiac disease:
Autoantibodies to gluten (gliadin) in grains leading to steatorrhea
Associated with people of North European decent
Villus flattening (blunting of villi) and lymphocytic infiltrate, and abnormal D-xylose test
Think you flattened out the Spruce trees
Tends to affect the jejunem, associated w/ dermatitis hepretiformis
10-15% lead to malignancy, often T-cell lymphoma, can be fatal in adults due to development of lymphoma in intestine
Some people develop symptoms as children & others as adults
The longer a person was breastfed, the later the symptoms appear
Other factors – the age at which one began eating gluten-containing foods & how much gluten was eaten
Tropical sprue:
Cause is unknown – may be related to an infectious organism (E. coli) since it responds to Ab/s
Affects residents of or visitors to the tropics
Typical symptoms – steatorrhea, diarrhea, weight loss, & a sore tongue from Vit B deficiency
Disaccharidase deficiency:
Most common is lactase deficiency
Whipple’s disease:
Rare, causes malabsorption due to intestinal infection
Caused by infection w/ Tropheryma whippelii
Contains PAS positive macrophages
Primarily affects middle-aged white men
Slow onset of symptoms – skin darkening, inflamed & painful joints, & diarrhea
May be fatal w/o Tx
Intestinal lymphangiectasia:
Disorder of children & young adults in which lymph vessels supplying the lining of small intestines enlarges
Main symptom = massive fluid retention
LARGE INTESTINE
Hirschsprung’s disease:
Think you bowels Have SPRUNG out of control (Parasympathetic)
Congenital megacolon characterized by lack of enteric nervous plexus in segment (Auerbach’s and Meissner’s plexuses) on intestinal biopsy
Due to failure of neural crest cell migration
Presents as chronic constipation early in life.
Dilated portion of the colon proximal to the ganglionic segment, resulting in “transition zone”
Diverticular disease:
Diverticulum:
Blind pouch leading off the alimentary tract, lined by mucosa, muscularis, and serosa, that communicates w/ the lumen of the gut
Most diverticula (esophagus, stomach, duodenum, colon) are acquired and are termed false in that they lack or have an attenuated muscularis propria
Meckel’s is TRUE
Diverticulosis:
The prevalence of diverticulosis (many diverticula) in pt older than 60 approaches 50%
Caused by increase intraluminal pressure and focal weakness in the colonic wall
Most frequently involve the sigmoid colon
Associated w/ low-fiber diets
Most often asymptomatic or associated w/ vague discomfort
Diverticulitis:
Inflammation of diverticula classically causing lower left quadrant pain (Sigmoid area)
May be complicated by perforation, peritonitis, abscess formation, or bowel stenosis
Inflammatory bowel diseases
Crohn’s disease & Ulcerative colitis
| |Crohn’s Disease |Ulcerative colitis |
|Possible etiology |Infectious |Autoimmune |
|Location |May involve any portion of the GI tract, usually the terminal ileum, |Colitis = colon inflammation. Continuous lesion w/ |
| |small intestines, and colon. Skip lesions, rectal sparing |rectal involvement |
|Gross morphology |Transmural inflammation. Cobblestone mucosa, creeping fat, bowel |Mucosal inflammation. Friable mucosal pseudopolyps w/|
| |wall thickening (“string sign” on x ray) linear ulcers, fissures |freely hanging mesentery |
|Microscopic morphology |Noncaseating granulomas |Crypt abscesses and ulcers |
|Complications |Strictures, fistulas, perianal disease, malabsorption—nutritional |Severe stenosis, toxic megacolon, colorectal carcinoma|
| |depletion | |
|Extraintestinal manifestation |Migratory polyarthritis, erythema nodosum |Pyoderma gangrenosum, sclerosing cholangitis |
Crohn’s disease = Granulomatous enteritis
Chronic granulomatous inflammation involving any part of the GI tract – ileocolitis most common – usually skip-lesions
Characterized by non-necrotizing granulomatous inflammation w/ ulcers, strictures, fistulas
Transmural (not limited to mucosa/submucosa)
Etiology unknown; no cure
Think Fat old Crone skipping down a cobblestone road looking at mural – scratching his anal fissures.
Symptoms:
Cobblestone fissuring of buccal mucosa
Presence of anal fissures
Abdominal pain – often right lower quadrant; diarrhea, weight loss, bleeding is uncommon, rectal abscess and fistula
Complications -intestinal obstruction, fistulas, malabsorption, extra intestinal similar to U.C.
Treatment – antibiotics, immunosuppression, anti-TNF antibody, surgical -only w/ complications, since disease may recur, hyperalimentation if significant absorptive problems are present
Ulcerative colitis:
Chronic disease in which the large intestine becomes inflammed & ulcerated
Not transmural
Leads to episodes of bloody mucous diarrhea, abdominal cramps, & fever
Increased familial incidence, decreased incidence in Blacks and increased in Jews
Onset often occurs after smoking stopped, etiology is unknown
Increased incidence of colon cancer w/ pancolitis and duration of more than 10 years
Complications include massive hemorrhage, colonic stricture, polyp, greater risk of adenocarcinoma than Crohn’s, toxic dilation and perforation; extra intestinal pyroderma gangrenosum, and erythema nodusm, arthritis, and kidney stones
Pseudomembranous colitis
Clindamycin use allows for proliferation of C. difficile
Tx: vancomycin or metronidazole
Hemorrhoids
External or internal hemorrhoids
Familial polyposis
Familial adenomatous polyposis = familial polyposis coli
Colon becomes covered w/ adenomatous polyps after puberty
Progresses to colon cancer unless resected, associated w/ Gardner’s syndrome
Deletion on chromosome 5; 5 letters in polyp
Polyps appear in 20s, become symptomatic by 30s, and become adenocarcinoma by age 40 (100% of the time)
Gardner’s syndrome:
Type of hereditary polyposis
Autosomal Dominant
Various types of noncancerous tumors occur in intestines & elsewhere in the body
Characterized by polyposis of the colon
Carries a high risk of colon cancer
Peutz-Jehgers syndrome: (Polyps – Jejunum Syndrome)
Condition in which many small lumps (juvenile polyps) appear in a variety of sites in the GI tract
Most common site = small intestine (esp. jejunum)
Hereditary condition affecting males/females equally
Characterized by melanin pigmentation of oral mucosa, especially of lips & gums
Polyps are hamartomas – not true neoplasms
They do not increase risk of cancer in intestinal tract
Pts are at increased risk for cancer of pancreas, breast, lung, ovary, & uterus (Wow, that’s tricky!! Intestinal related dsz that d.n. increase intestinal CA risk, but does increase it for all these other things).
Turcots syndrome:
Characterized by polyps along w/ tumors of the CNS
Gastrointestinal Cancer:
Most commonly associated with villous adenoma (NOT diverticulosis, Meckel’s diverticulum, or duodenal peptic ulcer)
Colon Cancer:
Adenocarcinoma is the most common type of colon cancer
Presents w/ rectal bleeding, changed bowel habits, weight loss
Tumors of the L side are more likely to cause symptoms
More common in industrialized nations
Sigmoidoscopic exam can disclose a majority of tumors
Symptoms generally only in late disease
Transverse is NOT most common (Sigmoid)
Another Q says: Adenocarcinomas are most common in Rectosigmoid section – hence, then Roto-rooter job
NOT etiologically associated with cigarette smoke (Along with STOMACH). Again, smoke d.n. get to these areas.
(Lung, Esophageal, Oral, Laryngeal and Urinary bladder ARE)
BUT…Recent studies have shown that smokers are 30-40% more likely to die of colorectal cancer than nonsmokers – American Cancer Society
Intussusception: telescoping of one bowel segment into distal segment; can compromise blood supply (Like a telescope)
Volvulus: twisting of portion of bowel around its mesentery; can lead to obstruction
APPENDIX
Appendicitis:
Possible sequelae of acute appendicitis: general peritonitis, periappendiceal abscess formation, pylephlebitis, hepatic abscess
Sudden inflammation of the appendix
One of the most common causes of emergency abdominal surgery in children
More common in males – peak in the teens & early 20s
Leukocytosis is a “Sign” of appendicitis
Generally follows obstruction of the appendix by feces, a foreign body, or a tumor (rare)
1st symptom is typically crampy or “colicky” pain around the navel.
Usually a marked reduction in or total absence of appetite
Often assocatied w/ nausea and occasionally vomiting & low grade fever
As inflammation in increase, pain moves down & to the right – localizes directly above the appendix
Appendix is found at “McBurnery’s point” – 2/3 of the way from the navel to the right superior iliac crest
Momentary increase in pain when abdomen is pressed, held momentarily, & then rapidly released
“Rebound tenderness” suggests inflammation has spread to the peritoneum
If rupture, pain may disappear briefly & pt may feel suddenly better
However, once peritonitis sets in, pain returns & pt becomes progressively more ill
Abdomen may become rigid & extremely tender
Appendectomy performed ASAP after Dx
Differntial Dx for acute appendicitis:
Crohn’s (Left)
Meckel’s diverticulitis (Duodenum)
Pelvic Inflammatory Disease
Gastroenteritis with mesenteric adenitis
NOT Duodenal Peptic Ulcer (heart burn) – relieved pain with eating
Carcinoid tumor
The most common neoplasm of the appendix – rarely metastasizes
Tumors secrete high levels of 5HT that does not get metabolized by the liver due to the liver metastases
Results in recurrent diarrhea, cutaneous flushing, asthmatic wheezing, and right-sided valvular disease
PANCREAS (non-endocrine)
Pancreatitis:
Inflammation or infection of the pancreas
Often caused by digestion of parts of pancreas by pancreatic enzymes normally carried to small intestine w/ pancreatic ducts
Acute hemorrhagic pancreatitis:
Caused by obstruction of normal pathway of secretion of pancreatic juice into intestine
Causes
GET SMASHeD
Gallstones, Ethanol, Trauma, Steriods, Mumps, Autoimmune disease, Scorpion sting, Hyperlipidemia, Drugs
Zymogens of proteolytic enzymes are converted into catalytically active form prematurely inside pancreatic cells
Causes painful & serious destruction of the organ – can be fatal
Associated w/ alcoholism & biliary disease
Manifestations/consequences –
Enzymatic hemorrhagic fat necrosis w/ calcium soap formation & resultant hypocalcemia
Hemmorrhage
Inlammation
Fat necrosis
Parenchymal necrosis
NOT Fibrosis
Outstanding symptom – severe, knife-like, upper abdominal pain
Dx – made by noting the type of pain & by detecting elevated serum lipase (mostly) & amylase enzymes in pt’s serum & urine
Chronic pancreatitis:
Strongly associated with alcoholism
Presents w/ steatorrhea, diabetes, and abdominal mass (pseudocyst)
Dx – elevated amylase and alkaline phosphatase
BRAIN / NERVOUS SYSTEM
Counterparts
Thyroid CAUSE:
Hyper (Thyrotoxicosis) Graves’/Plummer’s
Hypo (Myxedema/Cretinism) Hashimoto’s
Adrenal
Hyper Cushing’s
Hypo Addison’s
HEAD / BRAIN PROBLEMS
One out-of-place congenital problem:
Neural tube defects:
associated w/ high levels of alpha fetoprotein in the amniotic fluid and maternal serum. Their incidenc is decreased w/ maternal folate ingesting during pregnancy
Spina bifida occulta:
failure of bony spinal canal to close, but no structural herniation. Usually seen in lower vertebral levels in association w/ tuft of hair (associated with increased levels of AFP)
Meningocele:
meninges herniate through spinal defect
Meningomyelocele:
meninges and spinal cord herniate through spinal canal defect
Anencephaly: no development
Concussion:
Transient paralysis of cerebral function immediately after head trauma
Manifested by dizziness, cold perspiration, visual disturbance & loss of consciousness
Most people recover completely w/in a few hours or days
Contusion:
Bruise of the brain parenchyma typically involving the subunit of the gyrus
Brain Tumors
Adult
70% above Tentorium (i.e. cerebral hemispheres)
Incidence: Metastases > Astrocytoma (including glioblastoma) > Meningioma
Child
70% below Tentorium (i.e. cerebellum)
Incidence: Astrocytoma > Medulloblastoma > Ependymoma
Subdural head injury:
Traumatic subdural hematomas are among the most lethal of all head injuries, common during abuse cases
See in 15% of head traumas
Tiny “bridging veins” running between brain surface & its outer covering stretch & tear, allowing blood to collect
These veins rupture due to sudden change in velocity of head during trauma
Signs/symptoms – confusion, headaches, disorientation, fluctuating levels of consciousness or coma
Develop gradually over time, occurring several hours or even days after initial injury
Intracranial hemorrhage:
Epidural hematoma
Rupture of middle meningeal artery, often secondary to fracture of temporal bone
Lucid interval; CT shows biconcave disk not crossing suture lines
Subdural hematoma
Rupture of bridging veins.
Venous bleeding (less pressure) w/ delayed onset of symptoms.
Seen in elderly individuals, alcoholics, and blunt trauma.
Crescent shaped hemorrhage that crosses suture lines
Pt lapses into a coma and fluctuating levels consiousness hours after blunt trauma→dx: subdural hematoma
Subarachnoid hemorrhage
Rupture of an aneurysm (usually Berry aneurysm) or AV malformation
Patient complains of “worst headache of my life”
Bloody or xanthochromic spinal tap
Berry aneurysms:
Aka “saccular aneurysms”
Most common cause of nontraumatic subarachnoid hemorrhage
90% are in the anterior part of the circle of Willis
MOST common site is the anterior communicating artery (Or branch of the middle cerebral)
In the past, middle meningeal
Rupture, is the most common complication, causes severe headache, and leads to hemorrhagic stroke
Associated with adult polycystic kidney disease, Ehlers-Danlos syndrome, and Marfan’s syndrome
May result in cerebrovascular accident
Parenchymal Hematoma
Caused by HTN, amyloid angiopathy, DM, and Tumor
Meningioma:
Intracranial tumor arising from arachnoid, usually occurring in adults >30 y.o.
Cerebral infarction (stroke):
Infarction of cerebrum due to arterial occlusion by a thrombus or embolus from the heart or carotid artery
Common signs/symptoms – sudden paralysis & numbness on one side of body
Encephalitis:
An uncommon inflammation of the brain
Most commonly caused by viral infection –Like HSV
Exposure to viruses via:
Insect bites, food/drink contamination, inhalation of respiratory droplets, skin contact
In rural settings – arboviruses carried by mosquitos or ticks or that are accidentally ingested
In urban settings – enteroviruses are most common (Coxsackie virus, poliovirus, & echovirus)
Other causes:
HSV, varicella, measles, mumps, rubella, adenovirus, rabies, West Nile virus
Once virus is in blood it can localize in brain tissue causing inflammation
WBCs invade to try to fight off infection – brain swells – can cause destruction of nerve cells, bleeding & brain damage
Symptoms – fever, headache, vomiting, photophobia, stiff neck/back, confusion (disorientation, drowsiness, clumsiness)
Meningitis:
Brain & spinal cord meninges become inflamed
May be bacterial OR may be caused by a number of viruses (Echovirus, Coxsackie, Mumps, etc.)
Bacteria are the most common cause of Meningitis – think Neisseria meningitides is BActeria
Don’t get clowned, because Encephalitis is from VIRAL
Viral meningitis rarely results in permanent neural damage
CSF Findings in Meningitis
Type Pressure Cell Type Protein Sugar
Bacterial Up PMNs Up Up Down
Fungal/TB Up Lymphos Up Up Down
Viral Normal/Up Lymphos Up Normal Normal
May be transferred by respiratory droplets
Most common in adults – Neisseria meningitidis & S. pneumoniae (elderly)
N. meningitidis:
Transmission via respiratory droplets
Key virulence factor in N. meningitidis is its antiphagocytic capsule, same as S. Pneumoniae
IgA protease also in an important virulence factor
Treat it w/ PEN G
Most common in children < 2 y.o. – H. influenzae
Most common in adults – Neisseria meningitidis & S. pneumoniae
Most common in the elderly – S. pneumoniae
NOTE all 3 of the most common have Capules
Common Causes of Meningitis
Newborn (0-6 m) ⋄ Group B Strep, E. coli, Listeria
Listeria Monocytogenes might cause Fetal Death or meningitis (Think the baby goes LISTless)
Don’t confuse with Floppy baby (Botulism)
Also causes Dysentery, Cholera, and Gastroenteritis
Children (6 m – 6y)⋄ S. pneumoniae, N. meningitidis, H. influenza B, Enteroviruses
Adults (6y – 60y) ⋄ N. meningitides, Enteroviruses, S. pneumoniae, HSV
Adults (60+) ⋄ S. pneumoniae (#1 in eldely), Gram – rods, Listeria
Infecting organism enters body through nose & throat
Signs & symptoms – high fever, severe headache, & neck stiffness
Arnold-chiari Malformation
Brain coming through Foramen Magnum
Syringomyelia
Softening and cavitation around central canal of spinal cord
Crossing fibers of spinothalamic tract are damaged
Bilateral loss of pain and temperature sensation in upper extremities with preservation of touch sensation
Most common C8-T1
Common in Arnold Chiari malformation
Tabes Dorsalis
Degeneration of dorsal columns and dorsal roots due to tertiary syphilis, resulting in impaired proprioception and locomotor ataxia
Associated with Charcot joints, shooting lightening pain, Argyll-Robertson pupils, and absence of deep tendon reflexes
One out-of-place disorder:
Fetal alcohol syndrome:
Newborns of moms who consumed significant amounts of alcohol (teratogen) during pregnancy (highest risk at 3-8 wks)
Have increased incidence of congenital abnormalities, including pre- & postnatal developmental retardation, microcephaly, facial abnormalities, limb dislocation, and heart and lung fistulas
Mechanism may include inhibition of cell migration
The #1 cause of congenital malformations in the U.S.
NERVOUS SYSTEM
Degenerative disease:
Cerebral cortex:
Alzheimer’s disease:
Most common cause of dementia in the elderly
Multi-infarct dementia is the 2nd most common cause
Associated w/ senile plaques (beta amyloid core) & neurofibrillary tangles (abnormally phospharylated tau protein)
Gross cortical atrophy
Familial form (10%) associated w/ specific genes
Pick’s disease:
Associated w/ Pick bodies (intracytoplasmic inclusion bodies) & is specific for the frontal & temporal lobes
Basal ganglia and brain stem:
Huntington’s disease:
Autosomal dominant inheritance, choréa, dementia
Atrophy of caudate nucleus (loss of GABA neurons)
Parkinson’s disease:
Think TRAP for being trapped in your body ⋄ Tremor (at rest), Rigidity, Akinesia, Postural Instability
Associated w/ Lewy bodies and depigmentation of the substantia nigra
Due to loss of dopaminergic neurons in the caudate & putamen
Rare cases have been linked to exposure to MPTP, a contaminant in illicit street drugs
Signs/symptoms:
Bradykinesia, rigidity, resting tremor, masked faces, dementia
Motor Neuron
Amyotropic Lateral Sclerosis (ALS) (AKA Lou Gehrig’s Disease)
Associated with BOTH lower and upper motor neurons (Think ALLS the motor neurons)
Werdnig-Hoffmann Disease
Present at birth as a “floppy baby” --- Botulism
Tongue fasciculations
Polio
Lower motor neuron signs
Think Can’t play water polio because no lower motor neurons to tread water
Demyelinating Diseases
Multiple Sclerosis:
Demyelinating disease
Disorder of brain & spinal cord (CNS) caused by progressive damage to myelin
Cause is unknown
Results in ↓ nerve functioning – leads to a variety of symptoms
Spontaneous exacerbations & remissions
90% of pts develop pyramidal tract dysfunction (hyperreflexia, weakness, spasticity)
Disease involves repeated episodes of inflammation of nervous tissue in any area of CNS
Episodes occur when body’s own immune cells attack nervous system
Inflammation destroys myelin sheath in that area, leaving multiple areas of scar tissue (sclerosis) along the myelin
Results in slower transmission of nerve impulse, leading to symptoms of MS
Affects approximately 1/1000 – women more commonly affected
Commonly begins between 20-40 y.o.
Characterized by paresthesia, unsteadiness of gait, incontinence, paralysis, and plaques of demyelination
Plaques are evident in the white matter
Large amounts of protein are found in CSF
Injectable interferon reduces frequency of MS relapses
Periventricular plaques, preservation of axons, loss of oligodendrocytes, reactive astrocytic gliosis
Patients present w/ sudden loss of vision
Classic triad is: Think SIN ⋄ Scanning speech, Intention tremor, and Nystagmus
Increase incident w/ increased distance from equator
Progressive multifocal leukoencephalopathy:
Associated w/ JC virus and seen in 2-4% of AIDS patients (reactivation of latent viral infection)
Postinfectious Encephalomyelitis
Metachromatic Leukodystrophy
Guillain Barre syndrome: (Guillen can’t lift the Barre)
Inflammation and demyelination of peripheral nerves & motor fibers of ventral roots (sensory effect less severe than motor)
Causing symmetric ascending muscle weakness beginning in distal lower extremities
Facial diplegia in 50% of cases
Autonomic function may be severly affected (eg., cardiac irregularities, hypertension)
Findings include: elevated CSF protein w/ normal cell count (“albumino-cytologic dissociation) and elevated protein⋄papilledema
Associated with C. jejuni or herpesvirus, but non definite link to pathology
Seizures:
Causes
Children ⋄ Genetic, infection, trauma, congenital, metabolic
Adults ⋄ Tumors, trauma, stroke, infection
Elderly ⋄ Stroke, tumor, trauma, metabolic, infection
Partial seizures: 1 area of the brain
They can secondarily generalize
Simple partial (awareness intact): motor, sensory, autonomic, psychic
Complex partial (impaired awareness)
Generalized seizures:
Absence: blank stare (petit mal)
Myoclonic: quick, repetitive jerks
Tonic clonic: alternating stiffening and movements (grand mal)
Tonic: stiffening
Atonic: “drop” siezures
Aphasia:
Broca’s (expressive): nonfluent aphasia w/ intact comprehension: Broca’s area—inferior frontal gyrus
Think Broca for Broken speech
Wernicke’s (receptive): fluent aphasia w/ impaired comprehension. Wernicke’s area—superior temporal gyrus
Wernicke’s encephalopathy is characterized by confusion, ocular disturbance & ataxia of gait
Results from vitamin B1 deficiency
Think W for Wordy, but makes no sense
Beriberi peripheral neuropathy:
Results from vitamin B1 deficiency
An axonal degeneration w/ 2° demyelination
Mechanism unknown
Myasthenia Gravis:
Neuromuscular disorder characterized by variable weakness of voluntary muscles
Often improves w/ rest & worsens w/ activity
Condition is caused by an abnormal immune response
Immune system produces Ab/s that attack ACh receptors that lie on the muscle side of the neuromuscular junction
This decreases responsiveness of muscle fibers to ACh released from motor neuron endings
Characterized by:
Muscle atrophy
Thymic hyperplasia or neoplasm (THYMOMA)
Antibody to acetylcholine receptors
NOT CNS degeneration
Pts have higher risk of having other autoimmune disorders (e.g., thyrotoxicosis, RA, & SLE)
Affects ~3/10,000 people – most common in young women & older men
~10% of the pts develop a life-threatening weakness of muscles needed for breathing (called myasthenic crisis)
Eaton-Lambert syndrome:
Similar to myasthenia gravis in that it’s also an autoimmune disease that causes weakness
Caused by inadequate release of ACh rather than by abnormal Ab/s to ACh receptors
(Think they were “Eaton” up all the Ach!!!)
Similar to Clostridium Botulism (FLOPPY BABY) – Inhibits Ach Release
CNS infections with AIDS
Toxoplasma ⋄ Diffuse (intracerebral calcifications)
Cryptococcus ⋄ Periventricular calcifications
LIVER / BILIARY / GALLBLADDER
LIVER
Chronic Passive Liver Congestion
“nutmeg” liver, from Right sided failure leads to liver congestion, and widening of sinusoids and central veins
Portal hypertension:
High BP in the portal vein
Portal vein receives blood drained from entire intestines, spleen, pancreas, & gallbladder
After entering the liver, the blood divides into tiny channels
Blood drains back into the general circulation via central vein ⋄ hepatic vein
Indicators/Complications of portal HTN:
Esophageal varices (first sign) – diluted tortuous veins in the submucosa of the lower esophagus
Common complications of cirrhosis (varices are NOT a complication of other liver disorders/diseases)
Esophageal varices is the sequelae of fatty nutritional cirrhosis that is the most likely to result in death AND exsanguination
Obstruction of portal circulation
Most common cause of esophageal varices is Portal HTN
Most common cause of massive hematemesis in alcoholics
Hemorrhoids
Testicular atrophy
Enlarged veins on the anterior abdominal wall (caput Medusae)
Ascities (fluid w/in abdominal cavity)
Splenomegaly – single most important sign of portal HTN
Factors increasing BP:
Increased blood volume flowing through vessels
Increased resistance to blood flow through liver – most common cause of portal HTN
Jaundice (aka “icterus”):
Yellow discoloring of skin, mucous MBs & eyes, caused by excessive amount of bilirubin dissolving in subcutaneous fat
Bilirubin – waste product resulting from breakdown of heme moiety of hemoglobin molecules (from worn out RBCs)
Ordinarily excreted from body as chief component of bile
Conjugated bilirubin – formed by the conjugation of bilirubin w/ glucuronic acid
Unconjugated (free) bilirubin – toxic (unlike that bound to albumin or conjugated)
High bilirubin levels in blood – can cause kernicterus (deposition of pigments in gray matter - permanent damage to certain areas of the brain of newborns)
This can cause a characteristic form of crippling – athetoid cerebral palsy
Normally, liver cells conjugate bilirubin and excrete it into bile, where it is converted by bacteria to urobilinogen (some of which is reabsorbed)
Some urobilinogen is also formed directly from heme metabolism
Termed unconjugated (indirect) bilirubin before conjugation and conjugated (direct) after.
Conjugated can enter urine and is soluble
Defects in bile excretion produce elevated levels of conjugated or unconjugated bilirubin
BUT Acute biliary obstruction causes a rise in conjugated bilirubin in the serum
Common in newborns in 1st week of life
All types (except physiologic jaundice in newborns) indicate:
Overload or damage to the liver
Inability to move bilirubin from the liver through the biliary tract to the gut
Very common; leading manifestation of liver disease
Common causes:
Increased destruction of RBCs w/ rapid release of bilirubin into the blood (unconjugated)
Obstruction of bile ducts or damage to liver cells causing inability of bilirubin to be excreted into GI tract (conjugated)
Pathogenesis of jaundice in patients with infectious hepatitis is the result from damage to liver cells
Gallstones, hemolytic anemia, infection hepatitis, carcinoma of common bile duct, carcinoma of head of the pancreas
Hemolysis of any cause usually results in unconjugated bilirubin predomination
NOT Causes:
Aplastic anemia –Don’t have the cells
Fibrosis of the liver
Vitamin K Deficiency
Obstructive jaundice:
Often caused by gallstones blocking the common bile duct
Hepatomegaly:
Most common cause of hepatomegaly w/o other signs and symptoms is fatty change (NOT ascites, hepatitis, etc)
Hepatic Failure:
These things can be Attributed to hepatic failure:
Tremor (Encephalitis), Gynecomastia, Hypoalbuminemia, Asterixis, and Spider Telangiectasia
NOT Mallory Bodies
Mallory bodies are large, poorly defined accumulations of eosinophilic material in the cytoplasm of damaged hepatic cells in certain forms of cirrhosis and marked fatty change especially due to alcoholism
DRUNK DUCKS
Budd-Chiari syndrome:
Occlusion of IVC or hepatic veins w/ centrilobular congestion and necrosis, leading to congestive liver disease (heptomegaly, ascites, abdominal pian, and eventual liver failure)
Associated w/ polycythemia vera, pregnancy, hepatocelluar carcinoma
Ascites:
Accumulation of free serous fluid in the peritoneal cavity
Almost pure plasma containing tremendous quantities of protein
Typically results from liver disease
Disorders that may be associated w/ ascites
Cirrhosis, hepatitis, portal vein thrombosis, portal HTN, constrictive pericarditis, CHF, liver cancer, nephritic syndrome, pancreatitis, Decreased protein production by the liver (no albumin to maintain capillary osmotic pressure)
Does NOT develop as a result of esophageal varices
Cirrhosis:
Chronic liver disease characterized by generalized disorganization of hepatic architecture w/ scarring & nodule formation
Normal hepatic architecture is destroyed & replaced by bands of fibrous scar tissue
Characterized by diffuse destruction & fibrotic regeneration of hepatic cells
Most common chronic liver disease
2x more common in men
Among people 45-65 y.o., cirrhosis is 3rd most common cause of death (after heart disease & cancer)
Signs/Symptoms/Complications:
Ascites
Bleeding disorders (coagulopathy, i.e. hemophilia)
NOTE: PT (not PTT) is used to assess coaguopathy due to liver disease
Portal hypertension
Complication of Cirrhosis is obstruction of portal circulation
Confusion or change in level of consciousness (hepatic encephalopathy) – TREMORS – asterixis (hand tremor)
Splenomegaly
Indicates portal HTN, which in turn causes esophageal varices
Esophageal varices are most common source of massive hematemesis in alcoholics
Hematemesis ⋄ Vomiting blood
Hemoptysis (coughing up blood) ⋄ Lung
Esophageal varices is the sequelae of fatty nutritional cirrhosis that is the most likely to result in death and exsanguination
Spider angiomas are common in alcoholics
Sudden onset of upper GI bleeding w/ massive hematemesis (vomiting of blood)
Jaundice
Causes:
Alcohol abuse (most common – 75%), use of certain drugs, and the exposure to certain chemicals
Infections (includig Hep B & C)
Biliary obstruction
Hemochromatosis (iron overload)
Congestive heart failure
Wilson’s disease
(A hereditary accumulation of copper in the liver, kidney, brain, and cornea)
Other inborn metabolism errors: galactosemia, glycogen storage disease, or alpha1-antitrypsin deficiency
alpha1-antitrypsin deficiency affects BOTH the Lung and the Liver
Associated w/ an increased incidence of hepatocellular carcinoma
Is especially prevalent among malnourished persons >50 y.o. w/ chronic alcoholism
Mortality is high; many patients die w/in 5 years of onset
Nodular Regeneration
Types:
Micronodular: nodules < 3mm, uniform size, due to metabolic insult (e.g., alcohol)
Macronodular: nodules > 3mm, varied sized. Usually due to significant liver injury leading to hepatic necrosis (eg., postinfectious or drug induced hepatitis). Has increase risk of developing hepatocellular carcinoma
Tx: portacaval shunt between splenic vein and left renal vein may relieve portal hypertension
Fatty Liver
Fat is deposited in the hepatocytes (Intracellularly)
Hepatocellular carcinoma: (hepatoma)
Most common primary malignancy in liver of adult
Risk factors include: Hep B and C, Wilsons disease, hemochromatosis, alpha-1 antitrypsin deficiency, alcoholic cirrhosis, and carcinogens (aflatoxin B1)
Commonly spread through hematogenous dissemination yielding alpha fetoprotein (AFP)
Reye’s syndrome:
Involves brain damage (encephalopathy) & fatty liver changes
Most often seen in children 4-12 y.o. (peak = age 6)
Associated w/ use of ASA in children to Tx chickenpox or influenza
Typically follows an upper respiratory infection or chickenpox by ~1 week
Rapid onset & varying symptoms
Changes in mental status occur including delirium, combative behavior, & coma
Frequently begins w/ vomiting – persistent over many hours
Vomiting is rapidly followed by irritable & combative behaivior
As condition progresses, child may become semi-conscious or stuporous
Ultimatley, seizures & coma develop – can quickly lead to death
Is associated w/ the use of aspirin in children to treat chickenpox or influenza
Wilson’s disease:
Think Wilson in Castaway ⋄ He was so hungry he ate copper
Aka hepatolenticular degeneration
Inherited disorder of copper metabolism
Results in excessive deposits of copper in liver cells
Copper fails to enter circulation in form of ceruloplasmin
Characterized by
Think ABCsD ⋄ Asterixis, Basal ganglia degeneration, Ceruloplasmin decrease, Cirrhosis, Corneal Deposits, Copper Accumulation, Carcinoma, Choreiform movements, Dementia
cirrhosis, degeneration of basal ganglia, & deposition of green pigment in the periphery of the cornea
Hepatitis A:
A picoRNAvirus
A FOR ASYMPTOMATIC
Aka viral, infectious, or short-incubation hepatitis (15-40 days)
Least serious, most mild among Hep A, B & C
High morbidity, low mortality
Highly contagious infectious disease involving liver
Usually transmitted by the fecal-oral route
Also transmitted parenterally or sexually
May also be transmitted via blood products
Usually from ingestion of contaminated food, milk, or water
Outbreaks often traced to ingestion of seafood from polluted water
Also caused by an RNA enterovirus
Occurs most often in young Adults
Does not lead to chronic liver disease, only 0.5% suffer from fatal liver necrosis
Symptoms – fever, malaise, abdominal pain, anorexia, jaundice
Appear after incubation period of 3-6 wks
Jaundice
Pathogenesis by Hepatitis A characterized by damage to the liver cells
Damage to liver cells results in increased serum levels of enzymes (e.g., transaminases) in liver cells
Detection of increases enzyme levels used to diagnose Hep A
Most cases are self-limiting and recovery occurs w/in 4 months
Surface Ag (A or B) in pt’s serum indicates the pt is potentially infectious for Hep (carrier state)
Hepatitis viruses are very heat resistant (more so than AIDS virus)
Proper autoclaving kills Hep
IgM-anti-HAV diagnostic of acute active or recent infection
IgG-anti-HAV indicates immunity to Hep A
Vaccine is available and should be taken when traveling to endemic areas
A = Asymptomatic (usually), young Adults, Arrives Quickly
Hepatitis B:
Transmitted by a DNA virus
Aka “Serum Hepatitis” – Hep B for Blood
HB5 antigen in the plasma is associated with Serum Hepatitis
Infectious disease producing liver inflammation & necrosis
Commonly transmitted by blood-derived products (more so than CMV, Hep A, herpes simplex keratitis)
Including perinatal, parenteral of sexual exposure, or mucous or skin openend and exposed to blood, saliva, or feces
Not by fecal-oral route
Severity varies from an asymptomatic carrier state to fulminate hepatitis
Chronic Hep is common, as are hepatomas
Less easily transmitted than Hep A
Can be transmitted through blood or by contact w/ human secretions & feces
Common among injection drug users who share needles, as well as between sexual partners
Signs/symptoms similar to Hep A (fever, abdominal pain, nausea etc.)
Longer incubation period of 6-8 weeks (one Q says: 1-6 months)
Symptoms are slower in developing, but longer in duration
Clinical manifestations:
Elevated transaminases, hyperbilirubinemia, elevated alkaline phosphatase
Most patients recover fully
Some develop chronic persistent hepatitis or chronic active hepatitis
Markers:
A patient recovering from Hep B:
Detection of the Hep B antigen in serum is indicative of the carrier state
EX: Pt’s lab results show both the HBs and anti-HBs…means pt is a carrier
HBsAg – surface antigen
Indicates active infection with HBV
Earliest marker of virus in serum
Continued presence indicates carrier state (Both HBsAg and anti-HBsAg)
It usually disappears with antibody IgG for the sAg
If IgG comes and takes out HBs-Ag
Confers immunity (IgG anti-HBsAg) and affords protection
If no antibody (IgG) develops:
sAg remains high and the person is a carrier and potentially infectious
Persisting for more than six months indicates chronic hepatitis B
HBsAb
Indicates successful immunization
HBcAg (core antigen)
Is found in the capsid
HBeAg (e-antigen)
Indicates active HBV replication making patient highly infective
IgM-anti-HBc
Indicates acute Hepatitis B
IgG-anti HBc
Indicates previous exposure to hepatitis B (may confer immunity)
How does Hep B cause disease in the liver???
Type III-- Ag/Ab complexes lead to extrahepatic problems like rash, urticaria, arthritis, vasculitis and glomerulonephritis
Vaccines available and all health care professionals should be vaccinated and children
Hepatitis B immune globulin (HBIG) conferes passive immunity
B = Blood borne
Non-A and Non-B Hepatitis [HEY: this is actually Hepatitis C]
Type of infection most commonly transmitted via transfusion of properly screened blood
Hepatitis C:
Serum hepatitis that is caused by a virus antigenically different from Hep A or B
Most likely results in chronic hepatitis
Most often transmitted through blood-transfusions (or via needle stick in a dental office)
Death from advanced liver disease caused by hepatitis C infection is primarily due to inhibition of urea synthesis
Accounts for 85% of post-transfusion hepatitis but w/ screnning for anti HCV it is reduced
Much milder than A or B but is otherwise clinically indistinguishable from them
Higher incidence of chronic disease (85%), cirrhosis (20%)
Increased risk of Hepatocellular Carcinoma
Most common reason for liver transplantation in the U.S.
Extrahepatic manifestations: rash, arthritis, glomerulonephris, all mediated by cryoglobulins
Anti-HCV and RT-PCR available for dx and genotyping
Interferon plus ribavirin used in therapy
C = Chronic, Cirrhosis, Carcinoma, Carriers
Hepatitis D:
Found in pts w/ acute or chronic episodes of Hepatitis B
Makes Hep B infection more severe
Drug addicts are at relatively high risk
Depends on host having been previoiusly infected with Hep B
Prevention of Hep B also prevents Hep D
D = Defective, Dependent on HBV
Hepatitis E:
RNA Calcivirus (NAKED CPR)
Transmitted enterically much like Hepatitis A
Causes occasional epidemics similar to those of Hepatitis A
Hep E epidemics have only occurred in underdeveloped countries
Responsible for most waterborne outbreaks
Self limited illness but can be fulminant (worse) in pregnant women
E = Enteric, Expectant, Epidemics
A and E by Fecal-Oral Routes
“The vowels hit your bowels”
Alcoholic hepatitis:
Swollen and necrotic hepatocytes, neutrophil infiltration
Mallory bodies (hyaline), fatty change, and sclerosis around central vein
DRUNK DUCKS – Eosinophils in the liver of drunkies
AST is elevated. AST ratio to ALT is > 1.5
Think A Scotch and Tonic
BILIARY
Cholelithiasis (Gallstones):
Stone or calculi in gallbladder result from changes in the bile component
Virtually all gallstones are formed w/in the gallbladder
Bile:
Composed of water, bile salts, lecithin, cholesterol & some other small solutes
Primary component is Cholesterol
Changes in relative concentrations may cause precipitation & formation of a nidus, or nest, around which gallstones form
Risk Factors:
Think 4 Fs ⋄ Female, Fat, Fertile, Forty
Signs:
Pt with conjugated hyperbilirubinemia and an absence of urobilinogen
Urobilinogen is low because the bile can’t get down into the intestine where it is made
(pt does NOT have aplastic anemia, hemolytic anemia, acute hepatitis, or alcoholic cirrhosis)
Types:
Cholesterol stones (radiolucent w/ 10-20% opaque due to calicifications):
Associated w/ obesity, Crohn’s disease, cystic fibrosis, advanced age & Native American origin
Mixed stones (radiolucent):
Have both cholesterol and pigmented components
Most common type
Pigement stones (radiopaque):
Seen in patients w/ chronic RBC hemolysis, alcoholic cirrhosis, advanced age, & biliary infection
Choledocholithiasis – term for gallstones are in bile duct
Size – from grain of sand to > 1 inch
Color – from yellow to other pigment, depending on what it is made of
GALLBLADDER
Cholesterolosis (strawberry gallbladder):
Characterized by small, yellow, cholesterol-containing flecks highlighted against a red background in the gallbladder lining
Polyps may form inside gallbladder & require its removal
Diverticulosis of the gallbladder:
Small, finger-like out-pouchings of the gallbladder lining – may develop as a person ages
May cause inflammation & require gallbladder removal
KIDNEY DISEASE
Renin:
Renal hormone associated with HTN (don’t get clowned by angiotensin)
Does not directly invoke vasodilation
Proteolytic enzyme formed in kidney & released into bloodstream where it has an important role in activating angiotensin
Produced by & stored in the juxtaglomerular apparatus that surrounds each arteriole as it enters a glomerulus
Release is controlled by activity of sympathetic nerves to kidney & renal arterial BP (if ↓ pressure, renin secretion ↑)
Acts on angiotensinogen (manufactured by the liver & present in the blood)
Converts angiotensinogen to angiotensin I
In turn AT I is converted to AT II by ACE – associated w/ capillary walls, particularly in the lungs
AT II stimulates aldosterone release from the zona glomerulosa of the adrenal cortex
Aldosterone causes Na+ retention by enhancing Na+ reabsorption by distal convoluted tubules & collecting ducts
Nephrolithiasis (Kidney Stones)
Presence of renal calculi (kidney stones) w/in renal pelvis or calyces
Calcium stones are the most commonly occurring form of nephrolithiasis
Most likely the result from Hyperparathyroidism
Many stones are asymptomatic until they pass into the ureter – causes renal colic (characterized by severe pain)
Complications:
Obstruction of the ureter
Acute or chronic pyelonephritis
Hydronephrosis
Stone formation w/in urinary tract represents a potential complication of many different diseases
4 types of stones:
Composed of Calcium salts, Uric acid, Cystine , and Ammonium Magnesium Phosphage (struvite)
Each has its own group of causes & specific management
All are caused by excessive supersaturation of the urine w/ a poorly soluble material
Stones grow upon the surfaces of the papillae, which detach & accompany the urine through the collecting system
Many stones are too large to negotiate the narrow circuit – they obstruct flow of urine & can cause severe pain
More common in men; rare in children
Exact cause is unknown
Predisposing factors: dehydration, infection, changes in urine pH, obstruction of urine flow, immobilization causing bone reabsorption, metabolic factors (such as hyperparathyroidism [leads to hypercalcemia]), renal acidosis, eleveated uric acid, & defective oxalate metabolism
Painless hematuria as a common early clinical sign in acute diffuse glomerulonephritis, carcinoma of the bladder, focal glomerulonephritis, and renal cell carcinoma – so, if you see urinary disease, think hematuria.
BUT NOT Nephrolithiasis (because that mofo just plain hurts)
Hydronephrosis:
Abnormal dilation of the renal pelvis & calyces
Caused by an obstruction of urine flow in the genitourinary tract
Not a separate disease entity
Rather, a physical manifestation of the disease process that causes impairment of urine drainage
“Nephrosis” describes kidney disease usually of the tubules, NOT the glomeruli
Urolithiasis:
Urinary calculus, formed in any part of the urinary tract
Associated with obstruction of urine flow
Composed of calcium oxalate &/or calcium phosphate
Calcium stones account for 80-90% of urinary stones
Associated with:
Gout, Hypercalcemia, Renal Infection, and Hyperparathyroidism
NOT systemic HTN
Pyelonephritis:
Bacterial infection (usually E. coli) of the renal pelvis & ureters
Fever, chills, flank pain, CVA tenderness
Acute – active infection of the renal pelvis – the pelvis may become inflamed & filled w/ pus
One feature is costovertebral angle tenderness
Chronic – extensive scar tissue forms in the kidney – renal failure becomes a possibility
Most often result from UTIs (from urinary refux), particularly in the presence of occasional or persistent backflow or urine from the bladder into the ureters or kidney pelvis (vesicoureteric reflux); abscesses often develop
Cystitis:
UTI
Dysuria, Frequency, suprapubic pain
Most common causing bugs are E. Coli and Proteus
Staph saprophyticus is 2nd common cause in young ambulatory women
Think SSEEK PP ⋄ Serratia marcescens, Staph saprophyticus, E. coli, Enterobacter, Klebsiella, Proteus, Pseudomonas Aer.
Women have it 10x as much as men (short urethra)
NOT associated with blocked urinary flow (Hydronephrosis and Pyelonephritis are!!)
Kidney infections are usually caused by microorganisms ascending from the lower urinary tract
Nephrosis generally implies renal disease associated w/ the tubules
Tubulointerstitial disease: tubular defects
From a variety of conditions and may be acute or chronic
Causes include drugs, obstruction, infections, toxins and vascular problems
Urine contains RBC, WBC, and WBC casts but proteinuria is less common w/ low molecular weight proteins
Can lead to renal tubular acidosis, aminoaciduria, salt, potassium magnesium wasting, and concentrating defect
Glomerulopathies:
Kidney disorders in which inflammation affects mainly the glomeruli
Nephrosis is only Tubules
Causes vary – glomerulopathies are similar since glomeruli respond similarly to several types of injury
Four major types of glomerulopathies:
1) NephrOTIC syndrome:
Subtypes:
Membranous glomerulonephritis
Minimal change disease (lipoid nephrosis)
Focal segmental glomerular sclerosis
Diabetic nephropathy
SLE ⋄ Wire loop appearance
Collection of symptoms caused by many diseases that affect the kidneys
Condition characterized by marked prOteinuria, generalized edema, hypOalbuminemia
Signs/symptoms: result from increased permeability of glomerular capillareis
PrOteinuria
Severe loss of protein into the urine (>3.5 grams/day)
Hypoalbuminemia & decreased levels of other blood proteins
Generalized edema
Hyperlipidemia
Hypercholesterolemia
Retention of excess salt & water
NOT anemia, hematuria, hypertension, or red cell casts in the urine
Not a disease itself – results from a specific glomerular defect & indicates renal damage
Caused by:
Amyloidosis, cancer, diabetes, HIV, glomerulopathies, leukemia, lymphomas, multimple myeloma and SLE
75% of cases result from primary glomerulonephritis
Can occur at any age
In children it is most common between ages 18 months & 4 years
Affects more boys than girls
In older people the sexes are more eqully affected
Early symptoms:
Loss of appetite, malaise, puffy eyelids, abdominal pain, muscle wasting, tissue swelling (excess salt & water retention), & frothy urine
2) Acute nephrITIS syndrome
Subtypes:
Acute poststreptococcal glomerulonephririts ⋄ Glomeruli large and bumpy with hypercellular neutrophils
Rapidly progressive ⋄ Glomerulonephritis, crescent, moon-shaped
Goodpasture’s syndrome ⋄ Type II Hypersensitivity, Linear pattern, anti GBM antibodies
Membranoproliferative glomerlonephritis ⋄ Subendothelial humps, tram track
IgA Nephropathy (Berger’s disease) ⋄ Mesangial deposits of IgA
Glomerluar inflammation resulting in sudden appearance of hematuria w/ clumps of RBCs (casts) & variable proteinuria
Most common in 3-7 y.o. boys
Starts suddenly and usually resolves quickly
Associated with destruction of basement membranes via PMNs (NOT lymphokines, eosinophils, or IgE Ab/s)
Elevated antistreptolysin O (ASLO) titers
Low serum complement
3) Chronic nephrotic syndrome
Aka chronic glomerulonephritis
Slowly progressive disease characterized by glomerular inflammation resulting in sclerosis, scarring & renal failure
Conditions that can lead to chronic GN – SLE, Goodpastures’ syndrome, & acute GN
4) Rapidly progressive glomerulonephritis (RPGN)
Aka ‘rapidly progressive nephritic syndrome’ or ‘crescentic GN’
May be idiopathic or associated w/ a proliferative glomerular disease such as acute GN
Uncommon disorder in which most of the glomeruli are partly destroyed, resulting in kidney failure
Starts suddenly & worsens rapidly
Occurs most commonly in 50-60 y.o. people
Glomerular diseases:
Damage to glomeruli caused by antibodies directed against glomerular basement membrane or antibody-antigen complex deposition in which complement helps or hurts condition
Hematuria, proteinuria, and renal insufficiency are hallmarks and renal biopsy is needed to establish diagnosis
Renal Insufficiency
May produce Parathyroid Hyperplasia
I think it has to do with lacking the Vitamin D formation, so PTH has to work harder to increase serum Ca
May have a hemorrhagic tendency
RENAL FAILURE
Failure to make urine and excrete nitrogenous waste
Consequences ⋄ Anemia (no erythropoietin), Renal osteodystrophy (No active Vit D), Hyperkalemia (Leads to cardiac arrhthymias, Metabolic acidosis (due to decreased acid secretion and decreased generation of bicarb), Uremia (increased BUN and creatinine), Sodium and H20 excess, Chronic pyelonephritis, HTN
Acute renal failure:
Often due to hypoxia
acute reduction in renal excretory capacity causing nitrogenous waste retention
Various causes classified according to location:
Prerenal: intravascular and extracellular volume loss (dehydration, bleeds, burns); decreased intravascular volume but increased extracellular volume (congestive heart failure, cirrhosis); in all cases renal perfusion is diminished
Renal: diseases of the renal parenchyma (glomerulonephritis, interstitial disease, drug toxicities, vasculities, acute tubular necrosis or renal artery)
Post renal: might occur in tubules (uric acid nephropathy, or stones or enlarged prostate)
Characteristics and dx:
use of blood urea nitrogen (BUN—normal levels 8 – 20 mg/dL) and creatine (normal levels 0.7 – 1.5 mg/dL) to estimate change in GFR
RBC, WBC, protein, casts, Na, urea, or urine
Structural evaluation using ultrasound, radionuclides scanning
Chronic renal failure:
Often due to HTN and DM
GFR decreased by 25% and leads to uremia. It is most likely casued by diabetes mellitus and hypertension and a decrease in protein intake will slow progression.
Uremia: clinical condition from renal failure w/ no underlying chemical basis.
Causes many problems including: fluid and electrolyte imbalance (acidosis, hyperkalemia) metabolic (osteomalacia, hyperuricemia), neuromuscular neuropathys and myopathies, cardiovascular pericarditis and hypertension, pruritis and anemia
Treat w/ hemodialysis and peritoneal dialysis or renal transplant
Hematuria:
Blood in urine (more than 5 erythrocytes per high power field)
Many causes including infections, stones, malignancies, connective tissue ds, renal disease that originate anywhere in genitourinal tract
Polycystic kidney (PKD):
Inherited kidney disorder in which multiple cysts form on the kidneys
Exact mechanism triggering cyst formation is unknown
Early stages of disease
Cysts enlarge the kidney & interfere w/ function
Results in chronic high BP, anemia, & kidney infections
Cysts may cause kidneys to increase production of erythropoietin
Results in increased # of RBCs – rather than the expected anemia
Bleeding into a cyst can cause flank pain
Increases incidence of kidney stones
HTN caused by polycystic kidneys may be difficult to control
Slowly progressive – eventually results in end-stage kidney failure
Also associated w/ liver disease, including infection of liver cysts
An autosomal recessive form of PKD exists & appears in infancy or childhood
Tends to be very serious & progresses rapidly
Results in end-stage kidney failure & death in infancy or childhood
Medullary cystic disease:
Disorder in which kidney failure develops along w/ cysts deep w/in kidneys (in medulla).
Uncommon & affects older children
Medullary sponge kidney:
Congenital disorder in which urine-containing tubules are dilated, causing the kidney tissue to appear spongy
Malignant HTN:
A medical emergency condition where there is a severe rise in BP
Cause is unknown – often a prior Hx of HTN, especially HTN resulting from kidney disorders (2° HTN)
More common in younger adults, especially African American men
Also occurs in women w/ toxemia of pregnancy & people w/ renal or collagen vascular disorders
Can cause severe, permanent, life-threatening consequences from pressure damage to brain, eyes, BVs, heart, & kidneys
If left untreated usually leads to death in 3-6 months
Characterized by:
Marked elevation levels of plasma renin
Generally younger pts than benign HTN
Corresponding renal lesion is known as Malignant nephrosclerosis
May arise as de novo, or appear suddenly in a pt w/ previous mild HTN
NOT that pts will live a normal lifespan if untreated
Benign Essential HTN:
Constriction of arterioles is most likely the cause
Hyaline arteriosclerosis (see below: ‘nephrosclerosis’) is the renal lesion most commonly associated w/ benign essential HTN
Chronic HTN:
Leads to reactive changes in the smaller arteries & arterioles throughout the body
These changes are collectively referred to as arteriosclerosis
The vascular changes are particularly evident in the kidney
They result in a loss of renal parenchyma, refered to as benign nephrosclerosis
Nephrosclerosis: (aka: arteriolonephrosclerosis = hyaline arteriosclerosis)
Renal impairment secondary to arteriosclerosis or HTN
Disease most commonly related to benign HTN (incorrect: renal atresia, acute pyelonephritis & chronic pyelonephritis)
Benign Nephroscerosis is the most common autopsy find of essential HTN
Three types:
1) Arterial – atrophy & scarring of the kidney due to arteriosclerotic thickenings of walls of large branches of renal artery
2) Arteriolar – renal changes associated w/ HTN in which the arterioles thicken & the areas they supply undergo ischemic atrophy & interstitial fibrosis
3) Malignant – rapid deterioration of renal function caused by inflammation of renal arterioles
This type accompanies malignant HTN
Von Gierke’s disease: Think VON GlyKe’s
Massive accumulation of glycogen in the liver and the kidney
The most common of the glycogen storage diseases
Genetic disease resulting from deficiency of glucose-6-phosphatase, which helps to make glucose from glycogen
Deficient in the last NZ of Glyogneolysis
Renal Cell Carcinoma
Most common renal malignancy
Most common in men 50-70
Increased incidence in smokers
Associated with von Hippel-Lindau and gene deletion in chromosome 3
Originates in renal tubule cell ⋄ polygonal clear cells
Signs ⋄ Hematuria, palpable mass, 2ndary Polycythemia, Flank Pain, and Fever
Invades IVC and spreads hematogenously – normally carcinomas spread lymphatically
Associated with paraneoplastic syndromes
LUNG DISORDERS
Pulmonary edema:
Accumulation of fluid in the extravascular spaces of the lungs
Increased pressure in lung veins due to backup from failing left ventricle (CHF)
Increased intravascular hydrostatic pressure
Fluid is pushed into the air spaces (alveoli)
Fluid becomes a barrier to normal O2 exchange resulting in SOB
Physiologically, caused by increase in intracapillary hydrostatic pressure or increase in capillary permeability
Early symptoms – dyspnea, orthopnea, and coughing
Clinical signs – tachycardia, tachypnea, dependent crackles, & neck vein distension
Causes – arteriosclerosis, HTN, cardiomyopathies, valvular heart disease, & left-sided heart failure
Treatment – reduce extravascular fluid & improve gas exchange & heart function (oxygen, diuretics, vasopressors, positive inotropic agents, & antiarrhythmics)
Chronic passive congestion of the lungs
Characterized by thickening of the alveolar walls and hemisiderosis
Another Q said….by edema of the alveolar walls and “heart failure” cells
Is secondary to atherosclerotic heart disease
Productive cough present in:
Chronic lung abscess
TB
Lobar pneumonia
Bronchogenic carcinomas
Pulmonary embolism
Brochiectasis
Sputum contains mucus, cellular debris, bacteria, & may contain blood or pus
Infarcts (Red vs. Pale)
Red RED LILly (Lung, Intestine, Liver)
Occur in loose tissues with collaterals, such as lungs, intestine, or following reperfusion (REd for REperfusion)
Hemorrhagic (red) infarcts most commonly found in the LUNG (NOT brain, spleen, or kidney)
Even if there’s a stoppage, think red is still all around
Pale
Occur in solid tissues with single blood supply, such as the brain, heart, kidney, and spleen
Bronchiectasis
Irreversible, abnormal dilatation of bronchi/bronchioles caused by destruction of supporting structures by a chronic necrotizing infection
Common in children w/ cystic fibrosis
Most common symptom – chronic, productive cough w/ a foul-smelling, purulent sputum
Chronic dilation as result of inflammatory disease/chronic obstruction – obstruction, hydothorax, pneumothorax
Atelectasis:
Shrunken & airless state of the lung, or portion thereof
Due to a failure of expansion or resorption of air from the alveoli
Common in premature infants due to a lack of surfactant
Collapse of alveoli
May be secondary to:
Blockage of bronchus to aspirated foreign body
Blockage fo bronchus by mucous
Hydrothorax
Pneumothorax
Pneumonia
General info:
Very common lung infection involving the alveoli & the tissues around them
Most common fatal infection acquired in hospitals
Characterized by chills & fever, productive cough, blood-tinged sputum, & hypoxia w/ SOB
Interstitial pulmonary inflammation is most charactistic of viral pneumonia – Think Viruses are IN (interstilial/intracellular)
Clinical signs: crackles are heard when listening to the chest w/ a stethoscope (auscultation)
Caused by various organisms: bacteria, viruses, & fungi
Bacterial pneumonia:
Tend to be the most serious cause of pneumonia
Streptococcus pneumonia (aka Pneumococcus) most common cause in adults
Most common cause of community acquired bacterial pneumonia in the U.S.
Well known for its large polysaccharide capsule (so is Cryptococcus neoformans)
Strains of Strep pneumonia are distinquished by their polysaccharide capsules
Antibodies formed against encapsulated bacteria, like strep pneum., initially fxn as Opsonins
Viral pneumonia:
Aka “atypical pneumonia” or “interstitial pneumonia”
Legionella
Most common causes of pneumonia in young children (peak between ages 2-3)
Viral pneumonia is most characteristic of interstitial pulmonary inflammation (IN is IN)
Diffuse and patchy (>1 lobe)
No alveolar exudate
Dry hacking cough
Elevated cold agglutinins
Bronchopneumonia:
Affects infants & elderly
Inflammation of the walls of the smaller bronchial tubes
Also spread of inflammation into alveoli & alveolar ducts
Patchy distribution of lobular inflammation; not just the bronchus itself
B for Bacteria
S. aureus, H. flu, Klebsiella, S. Pyogenes
Lobar pneumonia:
Diffuse distribution of inflammation
Pneumococcus most frequent (Strep pneumoniae)
Affects middle-aged people
Marked by fever, chest pains, cough & blood-stained sputum
Rusty sputum
Inflammation & consolidation of one or more lobes of the lunugs
Chest pain associated w/ lobar pneumonia attributable to coexistent pleurisy (inflammation of pleura)
Diplococcus pneumoniae
The essential antigen which determines both its virulence & its specific type is the distinct capsular polysaccharide
Common Causes of Pneumonia
Children (6 wk – 18 y)⋄ Viruses (RSV), Mycoplasma, Chlamydia pneumoniae, S. pneumoniae
Adults (18 y – 40 y) ⋄ Mycoplasma #1 in Young Adults (THEY WALK a LOT), Chalymdia pneumoniae, S. pneumoniae
Adults (41 y – 65 y) ⋄ S. pneumoniae, H. influenzae, Anaerobes, Viruses, Mycoplasma
Elderly (65+) ⋄ S. pnuemoniae, Viruses, Anaerobes, H. influenzae, Gram – rods
Special Types of Pneumonia
Nosocomial Staph, Gram – rods
Immunocompromised Staph, Gram – rods, Fungi, Viruses, PCP
Aspiration Anaerobes
Alcoholic/IV drug user S. pneumoniae, Klebsiella, Staph
Postviral Staph, H. influenzae
Neonate Group B Strep, E. coli
Atypical Mycoplasma, Legionella, Chlamydia
Pneumocystis carinii pneumonia:
Originally thought to be a protozoa
But is a YEAST
Caused by Pneumocystis carinii in immunocompromised pts (commonly seen in AIDS pts)
Causes interstitial pneumonia – often fatal
|Type |Organism |Characteristics |
|Lobar |S. pneumoniae (Pneumococcus) |Intra-alveolar exudate⋄ consolidation, may involve entire lung |
| |It’s got a big capsule, to go everywhere | |
|Bronchopneumonia |S. aureus, H. influenza, Klebsiella, S. Pyogenes |Acute inflammatory infiltrates from bronchioles into adjacent alveoli; |
| | |patchy distribution involving > 1 lobes |
|Interstitial (atypical) pneumonia |Viruses (RSV, adenoviruses), M. pneumoniae, |Diffuse patchy inflammation localized to interstitial areas at alveolar|
| |Legionella, Chlamydia psittaci (Birds) |walls; distribution involving primary lobes |
Inflammatory exudates in pneumonia
Definitely present in lobar pneumonia, lobular pneumonia & bronchopneumonia
Least likely to occur in primary atypical pneumonia (walking pneumonia) – 1999 Q100
Pulmonary Tuberculosis:
Contagious bacterial infection caused by M. tuberculosis
NOT from endotoxin or exotoxin (Histoplasmosis is another answer)
Lungs are involved, but the infection can spread to other organs
Histo:
Granulomas with giant multinucleated cells and caseation necrosis
Can develop after inhaling droplets from a cough or sneeze by infected person
Symptoms – minor cough, mild fever, fatigue, weight loss, hemoptysis, night sweats & a cough w/ phlegm
Primary TB:
Immediately follows invasion by tubercle bacilli
Characterized by the Ghon focus – 2002 Q8
Lesion at the pulmonary site of primary TB infection
Usually in middle or lower lung (Micro made simple, Dr. Cragun, and UCSF)
Other sources say subpleural parenchyma (U. of Utah, U. of Delhi)
Kaplan says, “The primary lung infection is usually found subadjacent to the pleura in the lower part of an upper lobe or in the upper part a lower lobe in one lung” – due to high air flow to these areas
Then the immune system ramps up in 2-4 weeks & now forms a similar caseation granuloma in hilar lymph nodes
When this happens, it is now called the Ghon Complex
Calcifications in pulmonary parenchyma from earlier TB not to be confused w/ Ranke Complex
Ranke Complex is a lung lesion w/ calcified lymph nodes
Secondary TB:
Disease that develops long after the 1° infection – due to reactiviation of the 1° infection
Characterized by tubercle formation (caseous granulomas)—[unlike sarcoidosis] & subsequent cavity lesions
Lungs are the most common site for secondary TB
Miliary TB :
Results from spread of tubercle bacilli by way of hematogenous spread
Results in the seeding of several organs w/ multiple, small, millet, seed-like lesions
Disseminated TB
Treatment of TB:
Generally prolonged & involves daily oral doses of multiple drugs
May include combinations of rifampin, isoniazid, pyrayzinamide, ethambutol = “RIPE”
Possible serious adverse reactions of these drugs
Ototoxicity, nephrotoxicity, muscle weakness, & allergic reaction
Chronic obstructive pulmonary disease
General info:
Group of lung diseases characterized by increased airflow resistance
Chronic airway obstruction resulting from emphysema, chronic bronchitis, asthma, or a combo of any of these diseases
In most cases, bronchitis & emphysema occur together
Secondary pulmonary HTN is most often caused by COPD
|Chronic Obstructive Pulmonary Disease |
|Disorder |Characteristics |
|Bronchial asthma |Dyspnea and wheezing expiration |
|Chronic bronchitis |Productive cough characterized by hypersecretion of mucus |
|Emphysema (pulmonary emphysema) |Often coexists w/ chronic bronchitis, labored breathing, and an increased susceptibility to |
| |infection |
|Bronchiecstasis |Copious purulent sputum, hemoptysis, and recurrent pulmonary infection |
Bronchial asthma:
1st definition: disease in which inflammation of the airways causes restriction of airflow
2nd definition: chronic reactive airway disorder that causes episodic airway obstruction
Results from bronchospasms, ↑ mucus secretion, airway edema, & ↑ airway resistance
NOT decreased surfactant
NOT enlarged air spaces (that’s emphysema)
NOT associated with purulent sputum-producing cough (only chronic bronchitis & chronic lung abscess)
Caused by the interaction of Ag & IgE on the surface of mast cells with the release of histamine
Here’s what happens:
Prostaglandin D elicits bronchoconstriction & vasodilation
Chemotactic factors recruit & activate eosinophils & neutrophils
Platelet-activating factor (PAF) aggregates platelets & induces histamine release
Leukotrienes C4, D4, & E4 cause prolonged bronchoconstriction & mucin secretion
Found in 3-5% of adults & 7-10% of children
½ of cases develop before age 10; most before age 30
Reversible; symptoms can decrease w/ time
Recurring bronchial asthma attacks may predispose pt for future emphysema
Two types: 1) allergic asthma (most common) & 2) idiosyncratic asthma
Common condition – can strike at any age – ½ of all cases first occur < 10 y.o. (2x as often in boys)
Findings – cough, characteristic wheezing expiration, dyspnea, tachypnea, hypoxia, & decreased I/E ratio, pulsus paradoxus
Symptoms may be triggered by:
Inhaled allergens – pet dander, dust mites, molds, pollens
Respiratory infections, exercise, cold air, tobacco smoke, stress, food or drug allergies
Aspirin/NSAIDs in some pts
Tx of an acute asthmatic attack – inhalation of a selective β2-agonist (terbutaline, albuterol)
Status asthmaticus
Particularly severe episode of asthma
Usually requires hospitalization
Does not respond adequately to ordinary therapeutic measures
Emphysema: (pink puffer)
Form of COPD that involves damage to the air sacs (alveoli)
Air sacs are unable to completely deflate (hyperinflation) – unable to fill w/ fresh air to ensure adequate O2 supply to body
Characterized by normal or increased lung capacity
Lack of elastic recoil in the lungs
Generally bilateral
More common in males
May lead to cardiac failure
Is a significant public health problem
Does NOT show hemoptysis
A tissue change, rather than mucous production (seen in asthma & chronic bronchitis)
Cigarette smoker with gradual onset of progressive, labored breathing, with prolonged expiratory effort
Labored breathing
Show Pursed Lips
Dyspnea, decrease in breathing sounds, tachycardia and decreased I/E ration
Increased susceptibility to infection
May be fatal, results from degenerative atrophy; and may be secondary to bronchial inflammatory disease
Two problems:
1) Lungs are fixed in inspiration
2) Respiratory surfaces of lungs have deteriorated so much that they no longer adequately exchange gases
Complete blood count likely shows polycythemia
Recurring attacks of bronchial asthma may predispose to emphysema
Most commonly caused by cigarette smoking
Tobacco smoke & other pollutants are thought to cause lungs to release chemicals that damage the walls of alveoli
Damage worsens over time, affecting O2 & CO2 exchange in the lungs
A naturally occurring substance in the lungs called alpha-1 antitrypsin may protect against this damage
People w/ alpha-1 antitrypsin deficiency are at increased risk
Alpha-1 antitrypsin deficiency affects both the Lung and Liver
Two important types:
Centrilobar – upper lobes of lungs most affected – cigarette smoking is major cause
Panlobular – lower lobes of lungs most affected – familiar antiproteinase (caused by alpha-1 antitrypsin deficiency)
Chronic bronchitis: (blue bloater)
Common, debilitating respiratory disease, characterized by ↑ mucous production by the glands of trachea & bronchi
Characterized by:
Productive cough, often w/ wheezing (universal factor in all cases)
Produces purulent sputum for 3+ months in at least 2 consecutive years w/o any other disease that could account for symptom
Dyspnea on exertion
Ventilation-perfusion imbalance
NOT decreased airway resistance
Strong association w/ smoking
Common results of chronic bronchitis:
Cor pulmonale (enlargement of the right ventricle) – from working too hard to push blood through pulmonary system
Airway narrowing
Obstruction of the bronchial tree along w/ squamous metaplasia
Squamous metaplasia is most commonly encountered in the bronchial mucosa (NOT stomach, oral mucosa, etc.)
Characteristic pathologic change:
Hyperplasia of bronchial submucosal glands & bronchial smooth muscle hypertrophy
Hypertrophy quantified by the Reid index (ratio of glandular layer thickness to bronchial wall thickness) of > 50
Predisposed to bronchogenic carcinoma
Predisposition is based on bronchitis causing squamous metaplasia of bronchial epithelium
Wheezing, crackles, cyanosis
Restrictive lung disease
General info:
Restricted lung expansion causes decrease in volumes (decreased Vc and TLC)
PFTs ⋄ FEV1/FVC Ratio = >80%
In other words, your ratio of blowing volume out at 1 sec vs FVC is greater because the volumes dropped
But in Obstructive, your ratio is less than 80%, because you can’t blow as fast, so less than 80% of the volume is out at 1 second
Types:
Poor breathing mechanics (extrapulmonary): poor musclar effort—polio, myasthnia gravis; poor apparatus—scoliosis
Interstitial lung disease (pulmonary): adult respiratory distress syndrome, neonatal respiratory distress syndrome, pneumoconiosis, Sarcoidosis, Goodpasture’s
Adult respiratory distress syndrome
Pneumoconioses
Lung diseases caused by prolonged inhalation of foreign material
Lead to fibrosis of the lungs
Main symptoms – chronic dry cough & SOB
Coal workers’ pneumoconiosis
Blackened sputum
Progressive massive fibrosis
Coal dust macules = aggregated macrophages…creates intensly pigmented areas
Silicosis:
Aka Stone Mason’s disease (S for Stone for Serious)
Progressive disease characterized by nodular lesions – commonly progress to fibrosis
The most common & most serious pneumoconiosis (NOT siderosis, calcinosis, or anthracosis)
Characterized by massive fibrosis of the lung
Production of fibroblast growth factor (FGF)
Associated w/ increased susceptibility to TB
Asbestosis:
Characterized by diffuse interstial fibrosis caused by inhaled asbestos fibers
Can develop up to 15-20 yrs after regular asbestos exposure – long latency
Results in marked predisposition to bronchogenic carcinoma & malignant mesothelioma of the pleura & peritoneum
Histologically – ferruginous bodies found in lung (asbestos fibers coated w/ hemosiderin) & w/ ivory pleural plaques
Berylliosis:
A systemic granulomatous disorder w/ dominant pulmonary manifestations
Anthracosis:
Aka Coal Worker’s pneumoconiosis, Black Lung disease
NOT known to predispose a pt to cancer
Progressive nodular pulmonary disease caused by deposits of coal dust in lungs
Ocurrs in two forms:
1) Simple – small lung opacities
2) Complicated – aka “progressive massive fibrosis” – masses of fibrous tissue occasionally develop in pt’s lungs
Goodpasture’s syndrome:
Anti-glomerular basement membrane antibodies produce linear staining on immunofluorescence
Findings: pulmonary hemorrhage leading to hemoptysis; renal lesions lead glomerulonephritis w/ hematuria
This is a type II hypersensitivity
Think GP ⋄ Good Pasture, Glomerular and Pulmonary
Most common in men between ages 20-40
Cystic Fibrosis
Autonomic recessive disorder – heterozygotes unaffected
Generalized dysfunction of the exocrine glands affecting multiple organ systems
Inherited disease caused by a defective gene, chromosome 7q
The gene encodes a MB-associated protein called “cystic fibrosis transmembrane regulator (CFTR)”
Is thought to regulate Cl– & Na+ across epithelial MBs
Results in defective Cl- channels, leading to very thick mucous secretions
Has elevation of Na+ and Cl- secretions
Affects mucus & sweat glands & Na+ channels
Causes respiratory & digestive problems
Thick mucus forms in breathing passages of lungs & predisposes pt to chronic lung infections
Effects males & females – life expectancy = 28 yrs
Present usually in 1st year of life w/ steatorrhea
Most common fatal genetic disease in white children
Dx with Sweat Chloride test (elevated Cl- in sweat)
Complications include:
Pulmonary disease, pancreatic insufficiency, & meconium ileus (form of intestinal obstruction in newborns)
Lung abscess:
Pus-filled cavity in the lung surrounded by inflamed tissue & caused by infection
Most common cause is aspiration – often in the settings of altered consciousness
Associated with aspiration of material from caries teeth
Alcoholism is the single most common condition predisposing to lung abscess
Also at risk: persons suffering from drug OD, epileptics, & pts w/ neuroloic dysfunction impairing the gag reflex
Almost all pts w/ a lung abscess present w/ cough & fever:
Characteristic symptoms:
Production of large amounts of foul-smelling sputum
Also dyspnea, chest pain, & cyanosis may be present
Common causes:
Most common – aspiration of anaerobic bacteria (decayed teeth, vomitus, foreign material) from the oral cavity
Staphylococcus (most common bacterial cause) – NOT strep which you would think
Inhaled Endo File, you may get a lung abscess
Also Pseudomonas, Klebsiella, & Proteus
Complications of pneumonia or bronchiestasis
Septic arterial embolus from a heart valve
Aspiration of Food
May cause Pneumonia, Lung abscess, Atelectasis, and Asphyxiation
NOT Pneumothorax
Adult respiratory distress syndrome
Might be caused by each of the following:
Shock
Heroine overdose
Viral pneumonia
Breathing 100% O2 – Too much O2 causes respiratory depression, same result as heroine – person may go into respiratory arrest; because person is not breathing, respiratory acidosis occurs = bad news
NOT cigarette smoking – You’re not going to immediately die due to smoking a cig
Neonatal respiratory distress syndrome:
Surfactant deficiency leading to increase surface tension, resulting in alveolar collapse
Surfactant is made by type II pneumocytes most abundantly after 35 weeks in gestation. The lecithin to sphingomyelin ratio in the amniotic fluid, a measure of the lung maturity, is usually less than 1.5 in neonatal respiratory distress syndrome.
Surfactant = dipalmitoyl phosphatidylcholine
Tx with maternal steroids before birth, artificial surfactant for infant
Kartagener’s syndrome:
Think Can’t move you grocery KART
Immotile cilia due to a dynein arm defect. Results in sterility (sperm also immotile) bronchiectasis, and recurrent sinusitis
Bronchogenic cancers:
Lung cancer usually develops in the wall or epithelium of the bronchial tree – such cancer is called bronchogenic carcinoma
Lung cancer that starts in the bronchoepithelium
Tumors that arise centrally:
Epidermoid (squamous) carcinoma:
Most arise in the central portion of the lung
Appears as a hilar mass & frequently undergoes central cavitation.
Clearly linked to cigarette smoking
SCC is also linked to increase in PTH, and endocrine effect of hyperparathyroidism
Pulmonary neoplasm to which the endocrine effect of hyperparathyroidism is attributed!!!
Small cell (oat cell) carcinoma:
Most arise in the central portion of the lungs
Most aggressive & highly malignant
Most commonly affects men (80%), 90% of whom are cigarette smokers
Clearly linked to cigarette smoking
Oat cell that is observed in these carcinomas is a short, bluntly spindle-shaped, anaplastic cell containing a relatively large hyperchromatic nucleus w/ little or no cytoplasm
Associated w/ ectopic hormone production (ADH, ACTH)
May lead to Lambert Eaton syndrome (muscle weakness due to Ag against motor nerve – can’t rls ACh)
Tumors that arise peripherally:
Adenocarcinoma:
Most common bronchogenic cancer
Tends to arise in the periphery, usually in the upper lobes of the lung
Develops on site of prior pulmonary inflammation or injury (old TB, scars, healed infarcts)
Less clearly linked to cigarette smoking
Large cell (anaplastic) carcinoma:
Tends to arise in the periphery
Very poorly differentiated
Bronchioalveolar Carcinoma
Only about 14% of patients w/ lung cancer survive 5 years after Dx
The Cancer with the best 5 yr prognosis is ⋄ Lungs 15%, Stomach 21%, Colon 60%, Pancreas 4%, Esophagus15%
Metastases is very common to brain, bone, & liver
Pancoast’s tumor:
May result from intrathoracic spread of bronchogenic cancer
Carcinoma that occurs in apex of lung and may affect cervical sympathetic plexus, causing Horner’s syndrome:
Ptosis (slight drooping of eye)
Anhidrosis (absence of sweating) and flushing (rubo of affected side of face)
Miosis (pupil constriction)
3 neuron oclusosympathetic pathway above projects from the hypothalamus to intermediolateral column of the spinal cord, then to the superior cervical (sympathetic ganglion, and finally to the pupil, the smooth muscles of the eyelids, and the sweat glands of the forehead and face
Interruption of these pathways result in Horner’s syndrome
HEART DISORDERS
Congenital heart defects:
Infective endocardititis
The following are predisposers:
Tetraology of Fallot
Congenital aortic stenosis
Patent ductus arteriosus
Ventricular septal defect
Right-to-left shunts – cyanotic congenital heart disease (“Blue Babies”)
Think the 3 T’s ⋄ Tetralogy, Transposition, Truncus
Eisenmenger’s
Tetralogy of Fallot (most common cause of early cyanosis) – PROVe:
1) Pulmonary stenosis
2) Right ventricular hypertrophy
3) Overriding aorta (overrides the ventricular septal defect)
4) Ventricular septal defect – patient suffers from cyanoic spells
Caused by anterosuperior displacement of infundibular septum
Transposition of great vessels:
Aorta leaves the right ventricle and pulmonary trunk leaves the left ventricle which separates the systemic and the pulmonary circulations. Pt will die
Due to failure of aorticopulmonary septum to spiral, common in babies to diabetic mothers
Persistent truncus arteriosus:
Left-to-right shunts – acyanotic congenital heart disease (“Blue Kids”)
Ventricular septal defect (most common congenital cardiac anomaly)
Atrial septal defect: has loud S2; wide, fixed split S2
Patent ductus arteriosus:
there is a minor vessel that connects the blood from the aortic arch to the pulmonary artery
Lung resistance decreases and shunt becomes left to right w/ subsequent right ventricular hypertrophy and failure
Associated w/ continuous “machine-like” murmur. Patency maintained by PGE synthesis and low O2 tension
Indomethacin is used to close patent ductus arteriosus, and PGE is used to keep it open to sustain life in case of transposition of greater vessels
Eisenmenger’s syndrome:
Uncorrected ventricular septal defect, arterial septal defect & patent ductus arteriosus leads to progressively pulmonary HTN
As pulmonary resistance increases, the shunt changes from left to right to right to left, which causes late cyanosis (clubbing and polycythemia)
Coarctation of aorta:
Infantile type (preductal): aortic stenosis proximal to insertion of ductus arteriousus. Male to female 3:1
INfantile: IN close to the heart (associated w/ Turner syndrome)
Adult type (postductal): stenosis distal to ductus arteriosus, associated w/ notching of the ribs, hypertension in upper extremities, weak pulses in lower extremities
aDult: Distal to Ductus
Pericarditis:
Causes ⋄ infection, ischemic heart disease, chronic renal failure, CT diseases
Effusions are usually serious; hemorrhagic effusion are associated with TB and malignancy
Findings ⋄ Pericardial pain, friction rub, EKG changes, Pulsus paradoxus
Can resolve w/o scarring or lead to chronic adhesive or chronic constrictive pericarditis
Acute Pericarditis:
Inflammation of pericardium that begins suddenly & is often painful
Inflammation causes fluid & blood products (e.g., fibrin, RBCs, & WBCs) to pour into the pericardial space
Constrictive Pericarditis:
Post-inflammatory thickening & scarring of the pericardial MB – constricts chambers
Can be caused by TB
Serous Pericarditis:
Caused by SLE, rheumatoid arthritis, infection, uremia, renal failure
Fibrinous Pericarditis:
Caused by uremia, MI, rheumatic fever, renal failure
Hemorrhagic Pericarditis:
Caused by TB or malignancy
Findings – pericardial pain, friction rub, ECG changes (diffuse ST elevations in all leads), distant heart sounds
Can resolve w/out scarring or lead to chronic adhesive or chronic constrictive pericarditis
Cardiac Tamponade:
Heart compression caused by blood or fluid accumulation in the space between myocardium & pericardium – leads to ↓ CO
Blood cannot flow into the right atrium – pt can die suddenly of decreased CO
Most likely to cause sudden arrest of heart fxn (incorrect answers: cardiac cirrhosis, mitral stenosis, constrictive pericarditis)
Can occur after large myocardial infarction
Dead heart musculature of a ventricle can rupture, causing blood loss into the pericardial space
Signs – distended neck veins, hypotension, decreased heart sounds, tachypnea, & weak or absent peripheral pulses
The most serious complication of percarditis
Aneurysms
Berry aneurysm
Atherosclerotic aneurysm
Syphilitic aneurysm
Microaneurysm
Dissecting aneurysm:
Most frequently occur in the aorta
Characteristically results in aortic ruptures, most often into the pericardial sac, causing fatal cardiac tamponade
Ischemic heart disease = Coronary artery disease (CAD):
Leading cause of death in U.S.
Usually caused by atherosclerosis
Condition in which fatty deposits (plaques) accumulate in cells lining coronary artery walls – obstructs blood flow
As coronary artery obstruction worsens, ischemia to heart muscle can develop – damages heart
Primary effect is loss of O2 & nutrients to myocardial tissue due to diminished blood flow
NOTE: right coronary artery supplies blood from aorta to right side of heart
Characteristic features:
Represents an imbalance between myocardial oxygen demand and available blood supply
Has a peak incidence in men over 60 years and women over 70
Contributing factors include chronic HTN and high levels of LDLs
NOT Usually results from complete occlusion of one or more coronary arteries
Doesn’t have to be complete occlusion – that would be a heart attack.
Risk factors – high BP, hyperlipidemia, smoking, being overweight, inactivity
Dx – based on pt Hx, especially Hx w/ characteristic risk factors
Major complications of CAD = 1) angina pectoris & 2) myocardial infarction
1) Angina:
Specific type of chest discomfort caused by inadequate blood flow through BVs of heart
Usually described as burning, squeezing or tight feeling in substernal chest
May radiate to left arm, neck, jaw, or shoulder blade
Most people w/ chronic angina feel pain only during exercise
Occurs when heart load becomes too great relative to coronary blood flow
Relieved by rest or nitrates (myocardial infarction is not)
2) Myocardial Infarction:
Heals by way of organization of collagen
Most frequently characterized by coagulation necrosis (eosinophilic masses w/ nuclei; result protein coagulation)
Most commonly caused by coronary atherosclerosis – interrupts blood supply to heart
The most common autopsy finding in sudden death caused by a M.I. is coronary thrombosis
Very common in males & postmenopausal females
Signs & symptoms – crushing pain in chest area over the heart, pain in left arm and/or jaw, sweating, GI upset, fatigue, shortness of breath
Prognosis is fairly good if pt reaches hospital – most deaths occur outside hospital – due to arrhythmias
Most acute MIs are caused by coronary artery thrombosis
Coronary artery occlusion ⋄ LAD (left anterior descending) > RCA > circumflex
Acute MI is the most common cause of death in industrialized nations
Pain from an MI is NOT relieved by vasodilators such as nitroglycerin – only angina is relieved by this.
Thrombolytic agents such as streptokinase often limit the size of infarction
Myocardial necrosis usually begins 20-30 min after coronary artery occlusion
Dx of a MI
First 6 hours, EKG is the gold standard
ST elevation (transmural ischemia)
Q Waves (transmural infarct)
There is death of heart muscle tissue causes leakage of enzymes into blood
Elevated enzyme levels following a myocardial infarction:
Cardiac troponin – GOLD STANDARD w/in 1st 4 hours up to 7-10 days, more specific than other protein markers
Serum Glutamate-Pyruvate Transaminase (SGPT) = AST, nonspecific and can be found in cardiac, liver, and skeletal muscle cells
Serum Glutamic-Oxaloacetic Transaminase (SGOT)
Serum Lactic Dehydrogenase (LDH) – former test of choice is also elevated from 2-7 days post-MI
Creatine Kinase (CK), or CK-MB test – test of choice in 1st 24 hours post- MI
Evolution of a MI
First Day
Occluded artery ⋄ Infarct ⋄ Pallor
Coagulative necrosis – w/in the first (20-30min) 24 hours leads to release of contents of necrotic cells into bloodstream with the beginning of neutrophil emigration
2 – 4 Days
Pallor ⋄ Hyperemia
Tissue surrounding infarct shows acute inflammation
Dilated vessels (hyperemia)
Neutrophil emigration
Muscle shows extensive coagulative necrosis
5 – 10 Days
Hyperemic border; central yellow-brown softening, maximally yellow and soft by 10 days
Outer zone (in growth of granulation tissue)
Macrophages, and Neutrophils
7 weeks
Now its Grey-white
Contracted scar is complete
Infarcts heal by organization
ECG changes:
ST elevation (transmural infact), ST depression (subendocardial infarct), & Q waves (transmural infarct)
Complications of myocardial infarctions:
Cardiac arrhythmia (90%), highest rise 2 days postinfarct
LV failure and pulmonary edema (60%)
Thromboembolism—mural thrombus (a thrombus produced as a result of damage to the ventricular endocardium)
Death from MI and Bx reveals thromboembolism ⋄ From the Right Ventricle
Cardiogenic shock (large infarct—highest risk of mortality)
Rupture of ventricular free wall, interventricular septum, papillary muscle (4 – 10 days post MI), cardiac tamponade
Fibrinous pericarditis—friction rub (3-5 days post MI)
Dressler syndrome—autoimmune phenomenon resulting in fibrinous pericarditis (several weeks post MI)
3) Sudden cardiac death
Death from cardiac causes within 1 hour of onset of symptoms, most commonly due to lethal arrhythmia
4) Chronic ischemic heart disease
Progressive onset of congestive heart failure over many years due to chronic ischemic myocardial damage
Rheumatic Fever:
Acute inflammatory disease w/ systemic manifestations & particular involvement of heart valves
Follows an upper respiratory infection w/ a Group A, β-hemolytic streptococcus
Secondary infection from Group A strep, due to autoimmune, not from bacteria
Can be a sequelae to Scarlet Fever
Most common in children 5-15 y.o.
Onset is usually sudden
Occurs 1-5 symptom-free wks following recovery from sore throat or scarlet fever
Mild cases may last 3-4 wks, severe cases may last 2-3 months
Treatment – penicillin & rest
Although RF may follow a streptococcal infection, it is not an infection
It is an inflammatory reaction to an infection
Heart is damaged because of a hypersensitivity rxn to group A, Beta Hemolytic streptococci
Clinical Dx – requires 2 major criteria or 1 major + 2 minor (the Jones criteria)
Major – carditis, arthritis, chorea, erythema marginatum & subcutaneous nodules
Minor – fever, arthralgias (joint pain w/o inflammation), Hx of RF, EKG changes & lab tests
Heart inflammation
A pt with rheumatic heart disease would most likely develop congestive heart failure due to valvular insufficiency
Disappears gradually, usually w/in 5 months
May permanently damage heart valves – resulting in rheumatic heart disease
Mitral valve (between left atrium & ventricle) is most commonly damaged
Valve may become leaky (mitral valve regurgitation) abnormally narrow (mitral valve stenosis) or both
Classic lesion of rheumatic fever is the Aschoff body – FEVER Causes ASHES
An area of focal interstitial myocardial inflammation
Characterized by fragmented collagen & fibrinoid material by large unusual cells (Anitschkow cells) & by occasional multinucleated giant cells (Aschoff myocytes)
NOTE: Most common characteristic lesion of rheumatic fever, scleroderma and RA is fibrinoid degeneration
Think FEVERSS ⋄ Fever, Erythema marginatum, Valvular damage, ESR increase, Red-hot joints, Subcutaneous nodules, St. Vitus’ dance (chorea)
Valvular Heart Disease:
Mitral valve prolase
Mitral valve leaflets billow into the left atrium during systole, leading to insufficiency
High pitched murmur, & mid-systolic click are characteristic of MVP
Mitral stenosis
Due to scarring, calcification, or fusion of the mitral valve
Early diastolic opening snap is characteristic of MS
Aortic valve insufficiency
Insufficiency = regurgitation
Backflow thru aortic valve leads to increased LV volume, raising filling pressure, leading to LV failure
Aortic valve stenosis
Congestive heart failure (CHF):
Disorder in which heart loses ability to pump blood efficiently
Almost always a chronic, long-term condition – it can sometimes develop suddenly
May affect the right &/or left side
Left ventricle usually fails first – right-sided failure soon follows
Earliest & most common signs:
Exertional dyspnea
Paroxysmal nocturnal dyspnea (pt wakes up up grasping for air)
Other signs:
Peripheral edema (ankle edema), cyanosis, high venous pressure, passive congestion of the liver, and orthopnea (sitting or standing in order to breath comfortably)
Left-sided failure:
Common causes:
Coronary heart disease
Leading cause of cardiac death in the U.S.
HTN ⋄ causes left ventricular hypertrophy
Aortic & mitral valvular disease
Myocardial disease
Rheumatic heart disease – 1988 Q96
Presence of hemosiderin-laden macrophages (heart failure cells) w/ pulmonary congestion in LV failure
Complications of left-sided failure:
Life-threatening complication = pulmonary edema
Most reliable post mortem indicator is chronic passive congestion of the lungs
Presence of hemosiderin-laden macrophages (“heart failure”) cells
Orthopnea ⋄ pooling of blood in lungs in supine position adds volume to congested pulmonary vascular system
Dyspnea ⋄ Failure of LV output to increase during exercise
Pleural effusion
Bacterial pneumonia
Paroxysmal nocturnal dyspnea
NOT Myocardial hyperplasia (HYPERTROPHY!!)
Right-sided failure:
Most common cause = left-sided failure
Most common cause of pure RS-CHF = cor pulmonale
Cor pulmonale –
Enlargement of the right ventricle
Most commonly direct result of pulmonary HTN due to resistance to blood flow thru lungs
Right sided heart failure w/out involvement of the left side of the heart occurs most often w/ cor pulmonale
Most conspicuous sign is systemic venous congestion & peripheral edema
Clinical hallmarks of right-sided failure:
Jugular venous distension
Hepatomegaly ⋄ Increased venous pressure, leads to increased portal resistance
Splenomegaly
Generalized edema
Affects the kidneys by causing: (All because BP is Down)
Renal hypoxia
Venous congestion
Retention of H2O and NaCl
Decreased GFR
Cells of Heart Failure:
Hemosiderin-laden macrophage in alveoli, aka siderophore
Hemosiderin in the lungs is caused by…Heart Failure!
Infectious endocarditis:
Type of inflammation of heart valves
Vegetations on the valves usually consist of fused platelets, fibrin, and masses of bacteria
Can affect the heart muscle (myocarditis) or lining of the heart (pericarditis)
Mitral valve is most commonly involved, followed by aortic valve
Source of infection:
Transient bacteremia (presence of bacteria in the blood)
Common during dental, upper respiratory, urologic, & lower GI diagnostic & surgical procedures
Most common: Streptococcus viridans – α-hemolytic strep causes ~½ of cases
Most common cause from a dental procedure ⋄ S. viridans
Other common organisms: Staph, Group D Strep
Less common organisms: Pseudomonas, Serratia, Candida
Can cause growths on heart valves, lining of heart or lining of the BVs
Fused platelets, fibrin, bugs are found in vegetation due to bacterial endocarditis
Growths may be dislodged & send clots to brain, lungs, kidneys or spleen
Health care provider may hear changing murmurs & detect enlarged spleen & mild anemia
Murmurs result from changes in valvular blood flow when clumps of bacteria, fibrin & cellular debris collect on valves
Self-infection (esp. by IV drug users) w/ S. aureus causes most severe damage (acute endocarditis)
Endocarditis on right side of the heart suggests IV drug abuse
Symptoms:
Fever is hallmark – may be present daily for months before other symptoms appear
Fatigue, headache, malaise, night sweats
Janeway lesions (small red lesions on palm/sole) – Roth’s spots (round white spots on retina surrounded by hemorrhage)
Nail bed (splinter) hemorrhages – Osler’s nodes (tender raised lesions on finger or toe pads)
Fever – Anemia – Murmur – Emboli
Think JR = NO FAME ⋄ Janeway Lesions, Roth’s spots, Nail-bed hemorrhage, Osler nodes, Fever, Anemia, Murmur, Emboli
TYPES OF ENDOCARDITIS:
Acute bacterial endocarditis: HIGH VIRULENCE
Staphylococcus aureus
Large vegetations on previously normal valves, rapid onset
Subacute bacterial endocarditis: LOW VIRULENCE
Streptococcus viridans
The most common organism producing subacute bacterial endocarditis is alpha-hemolytic streptococcus
(S. sanguis, which is a Viridans Streptococcus)
Smaller vegetations on congenitally abnormal or diseased valves
Sequela of dental procedures
More insidious onset than Acute
Tetralogy of Fallot, Congenital aortic stenosis; Patent ductus arteriosus; & Ventricular septal defect are all at risk of developing secondary endocartitis
Myocarditis = Cardiomyopathy:
Disease of myocardium w/ unknown etiology
Dilated (congestive) cardiomyopathies: heart dilates and looks like a balloon on chest X ray
Systolic dysfunction ensues
most common 90% of casts
Think ABCsDs ⋄ Alcohol, Beriberi, Coxsackie B, Cocaine, Chagas’ disease, Doxorubicin, Diastolic Dysfunction
Hypertrophic cardiomyopathy (formerly IHSS):
Diastolic dysfunction ensues
often asymmetric and involving the intraventricular septum.
50% of cases are familial and are inheritied as an autosomal-dominant trait
Cause of sudden death in young athletes
Walls of LV are thickened and chamber becomes banana shaped on echocardiogram
Restrictive/obliterative cardiomyopathy:
major causes include sacroidosis, amyloidosis, scleroderma, hemochromatoisis, endcardial fibroelastosis, and endomyocaridal fibrosis (Loffler’s)
Cardiac tumors:
Myxomas are the most common primary tumor in adults.
90% occur in the atria (mostly LA)
Myxomas are usually described as a “ball-valve” obstruction in the LA
Rhabdomyomas are the most frequent primary cardiac tumor in children
Metastases most common heart tumor
Cardiac muscle:
Following injury, restores fxnal capacity via hypertrophy
Creatine phosphokinase:
Found in heart, brain & skeletal muscle – NOT found in liver
If total CPK level is substantially elevated, usually indicates injury/stress to one or more of these tissue
Heart Murmurs
Aortic stenosis ⋄ Crescendo-decrescendo systoslic ejection murmur, with LV >> aortic pressure during systole
Aortic Regurgitation ⋄ High-pitched “blowing” diastolic murmur. Wide pulse pressure
Mitral Stenosis ⋄ Rumbling late diastolic murmurs. LA >> LV pressure during diastole. Opening snap
Mitral Regurgitation ⋄ High-pitched “blowing” holosystolic murmur
Mitral Prolapse ⋄ Systolic murmur with midsystolic check. Most frequent valvular lesion, especially in young women
VSD (Ventricular Septal Defect)⋄ Holosystolic murmur
PDA (Patent Ductos Arteriosus)⋄ Continous machine-like murmur
Buerger’s Disease
Known as smoker’s disease and thromboangitis obliterans
Idiopathic, segmental, thrombosing vasculitis of intermediate and small peripheral arteries and veins
Findings ⋄ Intermittent claudication, superficial nodular phlebitis, cold sensitivity, severe pain in affected part, may lead to gangrene
Tx with Cessation of Smoking
Don’t smoke in Burger King
VS. Raynaud’s Disease
Symmetric asphyxia (impaired oxygen exchange); idiopathic paroxysmal bilateral cyanosis of the digits due to arterial and arteriolar contraction
Caused by cold or emotion
Takayasu’s Arteritis
“Pulseless Disease”
Thickening of aortic arch and/or proximal great vessels, causing weak pulse in upper extremeities and ocular disturbances
Associated with elevated ESR
Think FAN My Skin ⋄ Fever, Arthralgia, Night sweats, MYalgia, SKIN nodules
HEMODYNAMIC DYSFUNCTION
Edema
Abnormal accumulation of fluid in the interstitial spaces or body cavities
Edema due to hemodynamic dysfunction may result in the brain, lung, subcutaneous tissue, peritoneal cavity
NOT the pancreas
May result from:
Increased capillary permeability (principal factor)
Elevated capillary pressure
Increased interstitial fluid colloid osmotic pressure
Decreased plasma colloid osmotic pressure
Increased sodium retention
Increased venule blood pressure
Lymphatic obstruction
Types of edema:
Anasarca – Can’t see your Sarcs (Muscles because you’re so swollen)
generalized swelling or massive edema; generalized infiltration of edema fluid into subcutaneous CT
NOT usually associated with CHF
Hydrothorax – excess serous fluid in the pleural cavity
Usually from cardiac failure
Hydropericardium – excess watery fluid in the pericardial cavity
Ascities (hydroperitoneum) – excess serous fluid in the peritoneal cavity
Transudate – noninflammatory edema fluid resulting from altered intravascular hydrostatic or osmotic pressure
Exudate – inflammatory edema fluid from increased vascular permeability
Right sided CHF leads to peripheral edema
Most conspicuous clinical sign of right sided heart failure
Left-sided CHF leads to pulmonary edema
Edema may described as:
1) Pitting edema – press against swollen area for 5 sec, then quickly remove it – indentation left that fills slowly
2) Nonpitting edema – press against swollen area for 5 sec, then quickly remove it – no indentation left in skin
Thrombus:
Solid mass of clotted blood that develops in & is attached to a BV wall
Formation enhanced by endothelial injury, alteration in blood flow (turbulence), & hypercoagulability
Arterial thrombi show alternating red & white laminations (lines of Zahn)
Venous thrombi are more uniformly red w/ distinct lines
Conditions predisposing to venous thrombosis:
Heart failure, extensive tissue damage, bed rest, pregnancy, oral contraceptives, age, obesity, & smoking, Just had surgery, bound to wheelchair, cirrhosis/Increased Portal HTN
Except COPD
A whole thrombus may detach to form a large embolus or fragments may break off to generate small emboli
Different types of Thrombi:
Agonal – forms in heart during the dying process after prolonged heart failure
Mural –
forms as a result of damage to ventricular endocardium (usually left ventricle, following myocardial infarct)
A major complication is a cerebral embolism
It complicates myocardial infarctions, atrial fibrillation, & atherosclerosis of the aorta
White – composed chiefly of blood platelets
Red – rapidly forms by coagulation of stagnating blood – composed of RBCs rather than platelets
Fibrin – formed by repeated deposits of fibrin from circulating blood – usually does not completely occlude the vessels
Ten days after hospitalization for a large, incapacitating myocardial infarct, a 50-year-old man suddenly develops paralysis of the right side of his body. The best explanation for his brain damage is…detachment of a mural thrombus from the left ventricle
Stoke following MI is caused by arterial thrombi (not venous)
Thrombosis:
Formation or presence of a blood clot inside a blood vessel or cavity of the heart
Deep Vein Thrombosis
Predisposed by Virchow’s triad
Stasis, Hypercoagulability, and Endothelial damage
Thrombotic occlusion in a coronary artery may result in:
Infarction
Fibrosis
Conductive changes
Nothing
Thrombolysis:
Breaking up of a blood clot
Embolus:
Blood clot that moves through the bloodstream until it lodges in a narrowed vessel and blocks circulation
Mass of solid, liquid, or gas that moves w/in a BV to lodge at a site distant from its origin
Most emboli are thromboemboli
Can lodge in the vascular beds of vital organs, occluding blood flow & possibly causing infarction
Splenic infarcts most commonly result from emboli originating in the left side of the heart
56-yr-old with atrial fibrillation and hx of MI 2 yrs ago, experiences a right flank pain and hematuria, paralysis of the right side of the body and ischemia to the left foot
DUE to arterial emboli (NOT septicemia, venous thrombi or venous emboli)
A pt w/ cardiovascular disease has chronic atrial fibrillation. She is prescribed warfarin (Coumadin) to prevent stroke
Think FAT BAT ⋄ Fat, Air, Thrombus, Bacteria, Amniotic fluid, Tumor
Fat embolism
Associated w/ long bone fractures
More info found elsewhere in file
Air Pulmonary thromboembolus = pulmonary embolus
Very common occurrence
Occurs during times of venous stasis (prolonged bed rest or sitting, CHF)
Most common source of a pulmonary embolism is thrombophlebitis (a thrombus formed w/in a vein)
95% of pulmonary embolus come from Deep Leg Veins
In this case, a deep leg vein is the common source for the origination of the thrombus
A thrombotic embolus originating in the femoral vein usually becomes arrested in the pulmonary circulation
Saddle Embolus:
A large embolus that may occlude the bifurcation of the main pulmonary artery
Usually results in sudden death
Symptoms:
Sudden shortness of breath, tachycardia, hyperventilation, cardiognenic shock
May result in:
Atelectasias
Cardiogenic shock
Pulmonary hemorrhage
Pulmonary HTN
NOT absence of symptoms
Diagnosis:
Ventilation/perfusion scan
Amniotic Fluid embolus
Can lead to DIC, especially postpartum
Atheroslcerotic Brain Infarction
Most likely warning sign of impending brain infarction is transient ischemic attacks
So, here’s the story on TIAs:
TIAs are caused by a temporary disturbance of blood supply to a restricted portion of the brain
TIAs are called mini strokes, because their neurological symptoms last < 24 hours
TIAs are often called a warning sign for an approaching cerebrovascular accident, or “stroke”
Strokes last > 24 hours
The most common cause of a TIA is an embolus, which most frequently arises from an atherosclerotic plaque OR from a thrombus
Phlebitis:
Inflammation of a vein
Pylephlebitis:
Inflammation of portal vein or any branches
Congestion:
Accumulation of excessive blood w/in BVs
Shock:
Set of hemodynamic changes reducing blood flow below a level providing adequate O2 for metabolic needs of organs/ tissues
Requires immediate medical Tx – can worsen very rapidly
Clinical signs:
Reduced cardiac output is the main factor in all types of shock
Tachycardia, hypotension, pallor, diminished urinary output, & muscular weakness
Anoxia most severly affects brain & heart
The body produces excess acid in the advanced stages of shock, when lactic acid is formed through the metabolism of sugar
Major classes of shock:
Hypovolemic
Produced by a reduction of blood volume
Causes include hemorrhage, dehydration, vomiting, diarrhea, & fluid loss from burns
Cardiogenic
Due to the sudden reduction of cardiac output
Main cause is myocardial infarction
Septic
Due to severe infection
Most frequently caused by endotoxins from G- bacteria!!!!!
Minor classes of shock:
Neurogenic
Results from injury to the CNS
Anaphylactic
Shock that occurs w/ severe allergic reactions
Stages of shock:
1) Non-progressive (early)
Compensatory mechanisms maintain perfusion of vital organs (↑ HR & ↑ peripheral resistance)
2) Progressive
Metabolic acidosis occurs (compensatory mechanisms are no longer adequate)
3) Irreversible
Organ damage – survival not possible
Tx:
Epinephrine is the drug of choice
Amoxicillin Rxn
Pt becomes hypotensive, itchy, and having difficult breathing
This means Amox reacts with IgE and activates cytotoxic T cells that release lymphokines
BLOOD DISORDERS
Purpura spots:
Purplish discolorations in the skin produced by small bleeding BVs near skin surface
Petechiae = small purpura spots, small pinpoint hemorrhages
Ecchymoses = large purpura spots
Both ecchymosis & purpura are manifestations of hemorrhage
May also occur in the mucous MBs (e.g., lining of mouth) & in internal organs
By itself is only a sign of other underlying causes of bleeding
May occur w/ either normal platelet counts or decreased platelet counts
Kinds of Purpura:
Thrombocytopenic Purpura (Werlhof’s disease):
Autoimmune disorder
Bleeding disorder characterized by deficiency in platelet #
Results in multiple bruises, petechiae, & hemorrhage into the tissues
Thrombotic Thrombocytopenic Purpura (TTP):
Severe & frequently fatal form characterized by low blood platelet count
Due to consumption of platelets by thrombosis in terminal arterioles & capillaries of many organs
Melena:
Presence of dark, tarry stools, due to the presence of blood altered by the intestinal juices
Refers to digested blood in the stool – a manifestation of hemorrhage
BLEEDING/CLOTTING DISRODERS:
Laboratory values:
PT = prothrombin time
Measures Factors I, II, V, VII, X
PTT = partial thromboplastin time
Measures Factor XII, prekallikren, kininogen, Factors I, II, V, VII, IX, X, XI
TT = thrombin time
Measures Factor I
Clotting/Clot lysis
Process:
Prothrombin converted to thrombin (in presence of thromboplastin & calcium ions)
Thromboplastin is released by damaged cells, thereby initiating the formation of fibrin
Prothrombin is produced in the liver with help from Vitamin K
Thrombin in turn converts fibrinogen to fibrin
Fibrin threads then entrap blood cells, platelets, & plasma to form a blood clot
Fibrinogen:
Plasma protein that is essential for the coagulation of blood and is converted to fibrin by thrombin & ionized calcium
NOT in serum
Fibrin:
Stringy, insoluble protein responsible for the semisolid character of blood clot
Serves as a template for fibroblasts to repair tissue & walls of the area to infection
The product of the action of thrombin on fibrinogen in the clotting process
Plasminogen:
Inactive precursor to plasmin that is present in tissues, body fluids, circulating blood, & w/in clots
Converted by Steptokinase, Staphylokinase, and Urokinase
Fibrinolysin = Plasmin:
A proteolytic enzyme derived from plasminogen
Essential in blood clot dissolution
Not a component of the body’s nonspecific disease mechanism
Lysozyme, complement, interferon & properdin ARE components of the body’s nonspecific disease mechanism
The most important fibrinolytic protease
Fibrinolysis:
Restores blood flow in the vessels occluded by a thrombus and facilitates healing after inflammation and injury
Aspirin
Marked with normal clotting time and normal platelet count, but prolonged bleeding time
It just inactivates them, meaning they are still there, but don’t work
Factors causing delayed blood clotting:
**Pt taking Heparin (anticoagulant) – acts as an antithrombin by preventing platelet agglutination
Heparin is found in the blood
**Pt w/ leukemia – often has thrombocytopenia (reduced # of platelets)
Spontaneous gingival bleeding with leukemia
**Pts w/ cirrhosis – have hypoprothrombinemia (abnormally small smounts of prothrombin in circulation)
In pts w/ liver disorders, it is difficult to curb hemorrhage due to hypoprothrombinemia
Prothrobmin is formed & stored in parenchymal cells of liver
In cirrhosis, these cells are profusely damaged
Pts w/ severe liver disease may have hemorrhages due to a deficiency in prothrombin
**Scurvy
**Thrombocytopenia:
Condition in which there is a reduced number of platelets
Causes bleeding states wherein blood loss occurs through capillaries & other small vessels
Most common cause of bleeding disorders
Causes spontaneous bleeding
Most common sign is petechiae and purpura
Platelet count must reach a very low value (15,000 – 20,000/mm) before generalized bleeding occurs
Is the cause of prolonged bleeding time in pts w/ leukemia
Bleeding time increases but neither PT or PTT are affected (bc thrombin and thromboplastin and all the factors they measure (1,2,5,7,10…) are unaffected)
They don’t change because they measure FACTORS, not platelets
**Von Willebrand’s disease:
Characterized by spontaneous bleeding from mucous MBs & excessive bleeding following trauma
Deficiency of vWf resulting in impaired platelet adhesion (although there’s nothing wrong w/ the platelets)
Autosomal dominant bleeding disorder – equal frequency in both sexes
Prolonged bleeding time; Normal platelet count & PT; Prolonged PTT
Results in a functional Factor VIII deficiency, because vWf serves as a carrier for factor VIII (hence prolonged PTT)
**Long-term ASA (cyclooxygenase inhibitor) Tx
Rsults in impaired thromboxane production (important platelet aggregants)
**Dicumarol:
An anticoagulant that inhibits formation of prothrombin in liver
Interferes w/ metabolism of Vit K (needed for prothrombin synthesis)
Used to delay blood clotting especially in preventing & treating thromboembolic disease
Has largely been replaced by Warfarin
**Bernard-Soulier disease – hereditary platelet adhesion disorder
**Glanzmann’s thombasthenia – defect of platelet aggregation
Hemophilia:
Hereditary bleeding disorder causing 1) increase in clotting time & 2) abnormal bleeding
Normal PT (Prothrombin time) but Prolonged PTT (Partial Thromboplastin Time)
Hemophilia A & B are inherited as a sex-linked recessive trait
Males are affected & females are carriers
Majority of people have type A & it presents under age 25
Excessive bleeding form minor cuts, epistaxis, hematomas, & hemarthroses
Classifications of hemophilia:
A – classical type – deficiency of coagulation factor VIII (antihemophilic factor)
10 yr old boy dies post tooth extraction. He also had bleeding into his joints, especially his knees, maternal uncle and male cousin had similar experience
B (Christmas disease) – deficiency of factor IX (plasma thromboplastin component)
C (Rosenthal’s syndrome) – not sex-linked, less severe bleeding – deficiency of factor XI (plasma thromboplastin antecedent)
True hemophiliac is characterized by:
Prolonged partial thromboplastin time (PTT) – because it measures Intrinsic Pathway 12-11-9-10
Normal prothrombin time (PT)
Normal bleeding time
HYPERTENSION:
Usually has no symptoms at all (called the silent killer) – millions of people w/ high BP don’t even know they have it
Factors ⋄ age, obesity, DM, smoking, genetics, race (black > white > asian)
Predisposes to Coronary heart disease, CVA, CHF, renal failure, and aortic dissection
Pathology ⋄ Hyaline thickening and atherosclerosis
The following may be evident:
Tiredness, confusion, visual changes, nausea, vomiting, anxiety, perspiration, pale skin, or an angina-like pain
Hypertensive heart disease is usually associated with left ventricular hypertrophy as an anatomic finding
Organs damaged due to prolonged HTN:
Heart – 60% die of complications
Kidneys – 25% die to complications
Brain – 15% die of complications
Essential HTN:
High BP from no identifiable cause
Accounts for 90-95% of HTN cases (related to increased CO or increased TPR)
If left untreated can lead to retinal changes, left ventricular hypertrophy, & cardiac failure
Genetic factors include family Hx of HTN – more common & usually more severe in blacks
Benign Nephrosclerosis is the most common autopsy find of essential HTN
Environmental factors – stress, obesity, cigarette smoking & physical inactivity
Secondary HTN:
Kidney failure = most common cause
Others causes: Obstructive sleep apnea, Aldosteronism, Renal artery bruits (suggests renal artery stenosis)
If renal artery is occluded, you get secondary HTN – kidney thinks blood volume is low, so tries to compensate and you get HTN.
Others causes still: Renal parenchymal disease, Excess catecholamines, Coarctation of the aorta, Cushing’s syndrome
Even more other causes: Drugs, Diet, Excess erythropoietin, Endocrine disorders
|Findings in HTN |
|Findings |Basis of findings |
|Cardiovascular | |
|BP persistently >140/90 |Constricted arterioles – cause abnormal resistance to blood flow |
|Angina pain |Insufficient blood flow to coronary vasculature |
|Dyspnea on exertion |Left-sided heart failure |
|Edema of extremities |Right-sided heart failure |
|Intermittent claudication |Decrease in blood supply from peripheral vessels to legs |
|Neurologic | |
|Severe occipital headaches w/ nausea & vomiting; drowsiness, giddiness;|Vessel damage w/in brain, characteristic of severe HTN |
|anxiety; mental impairment | |
|Renal | |
|Polyuria; nocturin; diminished ability to concentrate urine; protein & |Arteriolar nephrosclerosis (hardening of arterioles w/in kidney) 25% die of |
|RBCs in urine |renal failure |
|Ocular | |
|Retinal hemorrhage & exudates |Damage to arterioles that supply retina |
Preeclampsia (Pregnancy-Induced HTN)
Triad ⋄ HTN, proteinuria, and Edema
When seizures are added, its called Eclampsia
Affects 7% of pregnant women from 20 weeks gestation to 6 weeks postpartum
Increased incidence in pts with preexisting HTN, DM, Chronic renal disease, and autoimmune disorder
Can be associated with HELLP ⋄ Hemolysis, Elevated LFTs, Low Platelets
Clinical features ⋄ Headache, blurred vision, abdominal pain, edema of face and extremities, altered mentation, hyperreflexia,
Tx ⋄ Deliver fetus ASAP
Anemia:
Condition in which # of RBCs is lower than normal
Measured by a decrease in hemoglobin
Body gets less O2 & therefore less energy than it needs
Symptoms – fatigue, weakness, inability to exercise, & lightheadedness
Megaloblastic anemia:
Any anemia usually caused by deficiency of vitamin B12 or folic acid
Deficiency in Folic acid is most common
Characterized by macrocytic erythrocytes (same as below under macrocytic)
Includes pernicious anemia & anemias caused by folic acid deficiency (sprue & megaloblastic anemia of pregnancy)
Pernicious anemia:
Caused by lack of intrinsic factor (needed to absorb Vit B12 from GI tract)
Vit B12 is necessary for formation of RBCs
Vit B12 also needed to help by nerve cells function properly
Best Tx with Vit B12
Causes a wide variety of symptoms – fatigue, SOB (shorthness of breath), tingling sensation, difficulty walking & diarrhea
Characteristics –
Reduction in acid secretion by the stomach
An increased tendency toward gastric carcinoma
Atrophic glossitis
Myelin degeneration in the spinal cord
Easy fatigability
Peripheral neuropathy
NOT Microcytic or hypochromic
A type of megaloblastic anemia
Erythrocytes produced are macrocytic & appear hyperchromic
Atrophic glossitis AND Atrophic gastritis is common
Aplastic anemia:
Result of inadequate erythrocyte production – due to inhibition or destruction of red bone marrow
A stem cell defect, leading to pancytopenia
Results from drug-induced bone marrow suppression
Can be caused by radiation, various toxins, & certain medications
In drug-induced aplastic anemias:
RBCs appear normochromic (normal [hemoglobin]) & normocytic (normal size)
Just Few in #
Pancytopenia characterizd by severe anemia, neutropenia, and thrombocytopenia caused by failure or destruction of multipotent myeloid stem cells, w/ inadequate production of differentiated lines
Tx: withdrawal of offending agent, allogenic bone marrow transplant, RBC & platelet transfusion w/ G-CSF & GM-CSF
Hemolytic anemias:
Anemias due to shortening of RBC life span (↑ RBC destruction)
Problems often result from the subsequent increase in bilirubin levels (breakdown product of hemoglobin)
Elevated levels of urobilinogen (compound formed in intestine by reduction of bilirubin)
Elevated kernicterus – Jaundice of the KERNAL – your head
Elevated levels of unconjugated bilirubin (water-insoluble bilirubin)
Unconjugated bilirubin normally combines w/ serum albumin in the liver to become water-soluble (conjugated)
Conjugated bilirubin is then secreted w/ other bile components into the small intestine
Kernicterus = toxic accumulation of unconjugated bilirubin in the brain & spinal cord
EXs of hemolytic anemia: 1) Erythroblastosis fetalis, 2) Sickle cell anemia, 3) Thalassemias, 4) Hereditary spherocytosis
By the way, these are all red cell disorders
1) Erythroblastosis fetalis:
Not an autoimmune Disease
Fetus is Rh-positive because the father passed along the dominant trait
Mother is Rh-negative & responds to the incompatible blood by producing Ab/s against it
High risk = Dad is Rh-positive and Mom is Rh-negative
In a case of Erythrblastosis fetalis, the mother has very high levels of serum complement and anti-Rh IgE
Antibodies cross placenta into fetus’ circulation, where they attach to & destroy the fetus’ RBC – leads to anemia
Can also result from blood type incompatibilities (i.e., mother may be type O & fetus may be type A or B)
2) Sickle Cell anemia:
Caused by Hemoglobin S – an abnormal type of hemoglobin
Autosomal recessive
Heterozygous get the trait
Homozygous get the disease (You know Homos are bad)
So if pt homozygous, bad
Globin portion of Hb S is abnormal – valine is substituted for glutamic acid in the 6th position of Hb molecule
Valine replacing glutamic acid is a MISSENSE mutation – base substitution leading to different AA
When Hb molecules are exposed to low [O2], they form fibrous precipitates w/ the erythrocytes
This distorts the RBCs into a sickle (crescent) shape
Sickle cells function abnormally & cause microvascular occlusion & hemolysis
The clots give rise to recurrent painful episodes called “sickle cell pain crisis”
Also characteristic – non-healing leg ulcers & recurrent bouts of abnormal chest pain
4 yr old black kid, long bones, enlarged spleen and liver, Lesion of skull ⋄ Hair on end
Homozygotes have sickle cell disease
Occurs primarily in blacks
Heterozygotes have sickle cell trait
Relatively malaria resistant (balanced polymorphism)
Becomes life-threatening when:
1) Damaged RBCs break down (hemolytic crisis)
2) The spleen enlarges & traps the RBCs (splenic sequestration crisis)
3) A certain type of infection causes the marrow to stop producing RBCs (aplastic crisis)
**Repeated crises can cause damage to kidneys, lungs, bones, eyes, & CNS
Blocked BVs & damaged organs can cause acute painful episodes (occur in almost all pts at some point)
Episodes can last hours to days, affecting bones of the back, long bones, & the chest
Complications – aplastic crisis due to B19 parvovirus infection, autosplenectomy, increase risk of encapsulated organism infection, Salmonella osteomyelitis, painful crisis (vaso occlusive) & splenic sequestration crisis
3) Thalassemias:
Group of inherited disorders resulting from imbalance in production of 1 of 4 chains of aa/s making up hemoglobin
Characterized by low levels of erthhyrocytes & abnormal hemoglobin
Common in Mediterranean populations (ThalaSEAmia)
Alpha Thalassemias:
Due to gene deletion
No compensatory increase of any other chain. Some forms result in hydrops fetalis and intrauterine fetal death
Beta Thalassemias:
Due to defect in mRNA processing
Beta chain is underproduced
In beta thalassemia major (homozygous), the beta chain is absent – results in severe anemia requiring blood transfusion. Cardiac failure is due to secondary hemochromatosis
In both cases, fetal hemoglobin production is compensatorily increased but is inadequate
HbS/beta thalassemia heterozygotes has mild to moderate disease
4) Hereditary Spherocytosis
Macrocytic anemia/Megaloblastic:
Any anemia in which average size of circulating RBCs is greater than normal
Frequently caused by deficiency of folic acid & Vit B12 (cyanocobalamin)
These are associated w/ hypersegmented PMNs
Unlike folate deficiency, Vitamin B12 is associated w/ neurologic problems
Folate deficiency can develop w/in months
Vitamin B12 deficiency takes years to develop
Also caused by drugs that block DNA synthesis (sulfa drugs, AZT)
Marked by reticulocytosis
Microcytic anemia:
Any anemia in which average size of circulating RBCs is smaller than normal
Frequently associated w/ chronic blood loss or nutritional anemia as in iron deficiency anemia
Iron deficiency anemia – NO iron, then they’re SMALLER
Most likely caused by chronic blood loss to a long standing peptic ulcer
Total iron binding capacity increases while ferritin and serum iron decreases
Hypochromic, microcytic, MCV < 80
MCV = mean corpuscular volume
Diagnosis commonly made by demonstrating low serum iron, high TIBC, , & low serum ferritin
Normocytic normochromic anemias:
Include: Size is still normal
Myelophthisic
Acute hemorrhage
Enzyme defects (G6PH, PK deficiency)
RBC membrane defects (eg., hereditary spherocytosis)
Bone marrow disorders (aplastic anemia, leukemia, drug-induced bone marrow suppression)
Hemoglobinopathies (eg., sickle cell disease)
Autoimmune hemolytic anemia
Anemia of chronic disease
Disseminated Intravascular Coagulation (DIC):
Activation of coagulation cascade leading to microthrombi & global consumption of platelets, fibrin, & coagulation factors
Splenic embolism most likely stems from DIC
Caused by obstetric complications (most common), G- sepsis, transfusion, trauma, malignancy, acute pancreatitis, nephritic syndrome
Increased PT, PTT, fibrin split products (D dimers), low platelets, low fibrinogen
Characterized by helmet shaped cells on blood smear
Several days after an extraction, pt comes in with malaise and splinter hemorrhages beneath the fingernails ⋄
Caused from DIC or ENDOCARDITIS????? – Endocarditis.
Arteriosclerosis:
“Hardening of the arteries” – arterial walls become thicker & less elastic (harder)
Aorta & coronary arteries most affected
Abdominal aorta is the most common location for an atherosclerotic induced aneurysm
Atherosclerosis:
Is a form of arteriosclerosis
Disease of elastic arteries and large and medium sized muscular arteries
Most important & common form of arteriosclerosis
Fatty material (atherosclerotic plaque) accumulates under inner lining of arterial wall
Eventually the fatty tissue erodes arterial wall, diminishing elasticity (stretchiness) & interfere w/ blood flow
Plaques can also rupture, causing debris to migrate downstream w/in an artery
Signs & symptoms – Angina, claudication, changes in skin color & temperature, headache, dizziness, & memory defects
Consequences of atherosclerosis:
Ischemic heart disease (coronary artery disease) & heart attack (myocardial infarct)
Stroke or aneurysm formation
Described as degenerative changes in the walls of the arteries
Microscopically:
Fibrous cap of smooth muscle cells, collagen, CT matrix, leukocytes
Cellular zone of necrotic cells, lipid-filled foam cells, plasma proteins
Proliferating capillaries in advanced lesions
Location ⋄ Abdominal aorta > Coronary artery > Popliteal artery > Carotid artery
More common in men in all age groups & in post-menopausal women
In very advanced cases, atherosclerotic plaques can become calcified & ulcerated
Risks – smoking, HTN, heredity, nephrosclerosis, diabetes, & hyperlipidemia – NOT alcoholism
Glass of wine a day
Arteriolosclerosis:
Diffuse thickening of the arterioles & small arteries
The kidney is particularly vulnerable to arteriolosclerosis
Carbon monoxide poisoning:
Very dangerous, colorless, odorless gas, generally associated w/ fumes from a car or a home heating system
Attaches to hemoglobin & blocks their ability to carry O2
Severe CO poisoning can cause a coma or irreversible brain damage because of O2 deprivation
Hemoglobin has higher affinity to CO than to O2, even when minute amounts of CO is inhaled (Carboxyhemoglobin)
Hemoglobin-CO bone is strong that very little is ever removed from blood
Patients w/ acute CO poisoning exhibit cherry-red discoloration of the skin, mucosa, & tissues
Think CO from your Cherry-red Porsche!!!
Death is ultimately due to hypoxia
Symptoms of low-level CO poisoning are easily mistaken for a common cold, flu or exhaustion – proper Dx can be delayed
Chronic toxicity results in fatty changes in the heart, liver, kidney
Other environmental & chemical agents & their manifestations if ingested:
Carbon tetrachloride – hepatocellular damage (also CNS, but think Liver and kidneys)
Mercury poisoning
Inactivates enzymes & damages cell MBs
Acute toxicity: severe renal tubular necrosis & GI ulceration
Chronic toxicity: excessive salivation, gingivitis, gastritis, cerebral & cerebellar atrophy
Cyanide poisoning – prevents cellular oxidation, results in odor of bitter almonds
Methyl alcohol – blindness
Lead Poisoning
Basophilic stippling of RBCs
Anemia, poorly localized abdominal pain (Abdominal colic)
Peripheral neuropathy due to myelin degeneration – primarily affects motor neurons
Wrist and Foot drop (makes sense – radial nerve is MOST affected)
Lead lines in bone
Acetaminophen
Acetaminophen toxicity causes severe centrilobular hepatic necrosis
Hepatic failure 2-6 days after ingestion
Polyarteritis nodosa:
Serious BV disease wherein small & medium-sized arteries become inflamed & damaged when certain immune cells attack
Result is reduced blood supply to organs
Typically involves renal and visceral vessels
Symptoms ⋄ Fever, weight loss, malaise, abdominal pain, headache, myalgia, HTN
Findings ⋄ Cotton-wool spots, microaneurysms, pericarditis, myocarditis, palpable purpura, Increased ESR,
Associated with Hep B in 30% of pts
P-ANCA is often present in serum and correlates with disease activity, primarily in small vessel disease
Tx ⋄ Corticosteroids
Temporal arteritis:
Chronic inflammatory disease of large arteries
Usually branches of the carotid artery
Findings ⋄ Unilateral headaches, jaw claudication, impaired vision
Half of pts have systemic involvement and syndrome of polymyalgia rheumatica
Associated with elevated ESR, Responds well to steroids
Raynaud's syndrome:
Symmetric asphyxia (impaired oxygen exchange); idiopathic paroxysmal bilateral cyanosis of the digits due to arterial and arteriolar contraction
Caused by cold or emotion
Differentiate from Buerger’s ⋄ caused from smoking
Phlebitis:
Inflammation of the veins
Most common in the legs
Common causes – local irritation (IV line), infection in or near a vein, & blood clots
Thrombophlebitis:
Vein inflammation related to a blood clot
Most common source of pulmonary embolism
Symptoms:
Tenderness over the vein
Pain in the affected part of the body
Skin redness or inflammation (not always present)
Specific disorders associated w/ thrombophlebitis:
Superficial thrombophlebitis – affects veins near skin surface
Deep venous thrombosis – affects deeper, larger veins
90% of cases occur in the deep veins of the leg
Pelvic vein thrombophlebitis
Congestion (hyperemia):
Localized increase in the volume of blood in the capillaries & small vessels
Active congestion – results from localized arteriolar dilation (e.g., inflammation, blushing)
Passive congestion – results from obstructive venous return or increased back pressure from CHF
Occurs secondary to venous obstruction
1) Acute – occurs in shock or right sided heart failure
2) Chronic –
a) of the lung (mostly caused by left-sided failure)
b) of the liver (mostly caused by right-sided failure) ⋄ Leads to “Nutmeg Liver”
Myeloproliferative disorders:
Conditions in which myeloid stem cells develop & reproduce abnormally
Characteristics – peak incidence in middle-aged persons, ↑ in blood basophils, serum uric acid, & prominent splenomegaly
Polycythemia vera:
Aka primary polycythemia or erythemia
A myeloproliferative syndrome characterized by a marked increase in erythrocyte mass
Rare disorder of blood precursors – results in excess of RBCs (opposite of anemia)
Pts may later develop anemia or acute leukemia due to “bone marrow burn out”
Folate deficiency may also develop for the same reason
Characteristics –
Clubbing and cyanotic digits, erythrocytosis, leukocytsosis, thrombocytosis, & splenomegaly, along w/ ↓ [erythropoietin]
2° polycythemia – an excess of RBCs caused by conditions other than polycythemia vera
EXs: chronic hypoxia associated w/ pulmonary disease, residency at high altitudes (Osker’s disease), & heavy smoking or secretion of erythropoietin associated w/ adult polycystic kidney & tumors
Myelofibrosis:
Disorder in which fibrous tissue may replace precursor cells in marrow
Results in an ↑ # of immature RBCs & WBCs & abnormally shaped RBCs, anemia & splenomegaly
CML – disease in which a bone marrow cell becomes cancerous & produces a large # of abnormal granulocytes
White cell count
Differential
Increase in juvenile immature neutrophils or bands (shift to the left) – suggests bacterial infection
Increase in mononuclear cells (shift to the right) – suggests viral, occasionally fungal infections
Increase in eosinophils – suggests parasitic infections among others
Leukocytosis:
Abnormally large # of leukocytes
Found as a result of a systemic bacterial infection
Most often there is a disproportionate increase in PMN # (called Neutrophilic Leukocytosis)
Scarlet Fever, Appendicitis, Staphylococcal Septicemia, Tularemia & acute abscesses all cause leukocytosis
Present in Acute abscess and Osteomyelitis
Not all bacterial infections show this characteristic
EX: typhoid fever & brucellosis actually result in a depression of PMNs
Many viral infections result in leukopenia, particularly of PMNs
Leukocyte count: a general indicator of bacterial vs. viral infection
Normal range for leukocytes: 5k–10k/mm3 blood
Leukemoid reaction – when circulating levels of leukocytes reach very high levels (up to 100k/mm3)
Sometimes difficult to differentiate from leukemia
Parasitic infections cause an increase in eosinophil # in peripheral blood
Pyemia: septicemia due to pyogenic organisms causing multiple abscesses
BONE & JOINT DISORDERS
BONE
Long bones
May be affected by Rickets, osteopetrosis, chondrodystrophy, fibrous dysplasia, osteogenesis imperfecta
Fracture:
A break in the bone, usually accompanied by injury to surrounding tissues
Occurs when force against bone exceeds bone strength
Described as:
Complete – bone breaks into two pieces
Greenstick – bone cracks on one side only (not all the way through )
Single – bone breaks into 2 pieces
Comminuted – bone breaks into 3+ two pieces (or is crushed)
Bending – bone bends but doesn’t break (only happens in kids)
Open – bone sticks through skin
Three phases of fracture healing:
1) Inflammatory phase – characterized by bloot clot formation
2) Reparative phase: characterized by formation of a callus of cartilage (replaced by a bony callus)
3) Remodeling phase: cortex is revitalized
Reasons for failure of a fracture to heal:
Ischemia – navicular bone of wrist, femoral neck, & lower 1/3 of tibia are all poorly vascularized & therefore subject to coagulation necrosis
Inadequate immobilization after fracture – pseudoarthrosis or a pseudojoint may occur
Presence of a sequestrum
Interposition of soft tissue – between fractured ends
Infection – most likely w/ compound fractures
Fat embolism:
Most often a sequela of fracture
Due to mechanical disruption of bone marrow fat & by alterations in plasma lipids
18 yr old male sustains a fracture to the femur, 24 hours later, after manipulating the fragments to help them heal better, the pt dies suddenly….Fat embolism
Osteomyelitis:
Acute pyogenic bone infection most often caused by Staph. Aureus
Sexually active ⋄ N. gonorrheae
Druggies ⋄ Pseudomonas Aeruginosa
Sickle Cell ⋄ Salmonella
Prosthetic Replacement ⋄ S. aureus and S. epidermidis
Vertebral ⋄ M. tuberculosis
The infection causing osteomyelitis is often in another part of body – spreads to bone via blood
Affected bone may have been predisposed to infection due to recent trauma
In children – long bones usually affected
In adults – vertebrae & pelvis are most commonly affected
Infected bone usually produces pus – may causes an abscess
The Abscess deprives bone of blood supply
Presents w/ pain, redness, swelling; also fever & malaise
Risk factors – recent trauma, diabetes, hemodialysis, IV drug abuse, & people w/ removed spleen
Chronic osteomyelitis
Results when bone tissue dies as a result of lost blood supply
Can persist intermittently for years
Osteoporosis:
Thinning of bone tinssue & loss of bone density over time
Most common type of bone disease
Occurs when 1) body fails to form enough new bone, 2) too much old bone is reabsorbed, or 3) both happen
Calcium & phosphate – two minerals essential for normal bone formation
With age, minerals may be reabsorbed into body from bones, weakening bone tissue
End result in brittle, fragile bones that are subject to pathologic fracture even in absence of trauma
Type I ⋄ Postmenopausal, increased bone resorption due to decreased estrogen levels, Tx with estrogen replacement
Type II ⋄ Senile osteoporosis, affects men and women >70 years
Affects whites > blacks > Asians
Causes:
Leading cause –
Drop in estrogen in women at time of menopause
Drop in testosterone in men
Corticosteroids
Prolonged immobilization
Chronic malnutrition
Advanced age
NOT hypervitaminosis D
Women, especially > 50 get it more often than men
Can result from prolonged corticosteroid administration
Osteomalacia: (in adults)
Softening of bones caused by Vit D deficiency or problems w/ Vit D metabolism
In children = Rickets
Bones become bowed in rickets because of failure of osteoid tissue to calcify (failure of bone matrix calcification)
Conditions leading to osteomalacia:
Inadequate dietary intake of Vit D
Inadequate exposure to sunlight (UV radiation) – normally produces Vit D in body
Malabsorption of vitamin D by intestines
Hereditary or acquired disorders of Vit D metabolism
Kidney failure & acidosis
Phosphate depletion associated w/ low dietary intake of phosphates
Kidney disease or cancer (rare)
Side effects of mediations used to treat seizures
Characterized radiographically by diffuse radiolucency – can mimic osteoporosis
Bone biospsy is often only way to differentiate between osteoporosis & osteomalacia
Symptoms: diffuse bone pain (esp. in hips), muscle weakness, & bone fractures w/ minimal trauma
More common in women
Softening of bones occurs because bones contain osteoid tissue which has failed to calcify due to lack of Vit D
Teeth in child w/ Rickets – delayed eruption, malocclusion, developmental abnormalities of dentin/enamel, & ↑ caries rate
Osteopetrosis = Albers-Schonberg disease = marble bone disease – Think FAT ALBERtS BONE
May be inherited as a dominant OR recessive trait
Marked by ↑ bone density, brittle bones, & in some cases skeletal abnormalities
Often initially asymptomatic, trivial injuries may cause bone fractures due to bone abnormalities
Adult type is milder than the malignant infantile & intermediate types
Main features:
Overgrowth & sclerosis of bone
Thickening of cortex
Narrowing (or obliteration) of medullary cavity
Liver & spleen may become enlarged, blindness & progressive deafness may occur
Achondroplasia:
One of the most common causes of dwarfism
Autosomal dominant disorder characterized by short limbs w/ normal-sized head & trunk
Due to defect of fibroblast growth factor (FGF)
Best known form of dwarfism: Short limbs, large body, frontal bossing, & saddle nose
Osteogenesis imperfecta: Unbreakable
Hereditary disorder (aka “brittle bones”)
Rare but demonstrates the effect of inadequate osteoid production
Defect in synthesis of type I collagen
Chris Kaman
Results in skeletal fragility, thin skin, poor teeth, thin blue sclera, tendency towards macular bleeding, & joint hypermotility
Joint hypermobility = ligamentous laxity
Teeth are poor because of malformation of dentin (dentinogenesis imperfecta)
Patients have Hx of multiple fractures
Fibrous dysplasia:
Characterized by replacement of normal bone w/ fibrous tissue
Three classifications depending on extensiveness of skeletal involvement:
Monostatic = 1 bone involved
Polyostic = 2+ bones involved
Polyostic associated w/ endocrine disturbances (Albright’s syndrome)
NOTE: Albright’s syndrome is a disease where two of the following three are present:
Café-au-lait spots
Fibrous dysplasia
Endocrine hyperfunction (includes precocious puberty)
Pathologic fractures are often presenting complaint
Paget’s Disease (aka Osteitis deformans):
Metabolic bone disease involving bone destruction & regrowth – resulting in deformity
Diffuse, “cotton-wool” opacities
Cause is unknown – early viral infections (possibly w/ mumps) & genetic causes have been theorized
Characterized by excessive breakdown of bone tissue, followed by abnormal bone formation
Reversal lines with mosaic pattern
New bone is structurally enlarged, but weakened & filled w/ new BVs
Predisposition for osteosarcoma
Irregular resorption of bone with a poorly mineralized osteoid matrix
NOT decreased serum Ca & elevated serum P
May localize or be widespread – frequently in pelvis, femur, tibia, vertebrae, clavicle, or humerus
Skull may enlarge the head size & cause hearing loss if cranial nerves are damaged by bone growth
Intraorally the teeth are spread
Lab findings:
Anemia
Markedly increased serum ALP (alkaline phosphatase – NOT acid phosphatase) levels
ALP is an index of osteoblastic activity & bone formation
Elevated 24-hr UHP (urinary hydroxyproline), an index of osteoclastic hyperactivity
Von Recklinghasuen’s disease:
Disease of bone (osteitis fibrosa cystica) caused by hyperparathyroidism
Characterized by ↓ serum phosphorus & ↑ serum calcium & alkaline phosphatase
Condensing Osteitis (Sclerosing osteitis):
Unusual reaction or inflammatory response of dental pulp of the tooth to a low-grade infection
Osteochondroma:
Big mushroom-like neoplasm of bone showing peripheral cartilage cap in metaphyseal area of young person
Most common benign bone tumor
Usually seen in men < 25 y.o.
Commonly originates in the long metaphysic
Malignant transformation to chondorsarcoma is rare
Osteochondroses:
Group of diseases in children & adolescents (years of rapid bone growth)
Localized tissue death (necrosis) occurs, usually followed by full regeneration of healthy bone tissue
Blood supply to growing ends of bones (epiphyses) may become insufficient resulting in necrotic bone, usually near joints
Avascular necrosis is used to described osteochondrosis
Necrotic areas are most often self-repaired over period of weeks or months
Characterized by degeneration & aseptic necrosis followed by regeneration & reossiffication
Affects different parts of body – categorized by one of three locations:
1) Physeal:
Aka Scheuermann’s disease
Occurs in the spine at intervertebral joints (physes), esp. in thoracic region
2) Articular:
Occurs at the joints (articulations)
Legg-Calvé-Perthes disease – occurs at the hip
Kohlers disease – foot
Freiberg’s disease – 2nd toe
The only type of osteochondrosis more common in females – all others affect sexes equally
Panner’s disease: elbow
3) Non-articular:
Occurs at any other skeletal location
EX: Osgood-Schlatter disease of the tibia – relatively common
JOINTS
Suppurative arthritis:
Usually monoarticular
Primarily a hematogenous seeding of joints during bacteremia (mostly Staph, Strep, or Gonococci)
Tender, swollen, erythematous joints – requires rapid intervention to prevent permanent damage
Cloudy synovial fluid & high PMN count
Rheumatoid arthritis:
Chronic inflammatory disease primarily affecting the synovial joints & surrounding tissue – can also affect other organ systems
Cause is unknown – there is a genetic predisposition
Characterized by the classic microscopic lesion called pannus
What is pannus, you ask? – it is a hanging flap of skin…that sounds a lot like another kind of hanging flap of skin
Usually starts in the small joints of hands & feet – usually symmetric involvement
Classic presentation: Morning stiffness (gross – think Pannus) improving with use, symmetric AND systemic symptoms!!
RA involves an attack on body by its own immune cells (may be an autoimmune disease)
80% have positive rheumatoid factor (anti-IgG Ab)
Marked by proliferative inflammation of the synovial MBs leading to deformity, ankylosis, & invalidism
Primarily attacks peripheral joints & surrounding muscles, tendons, ligaments, & BVs
Synovia are the sites of the earliest changes in RA
Begins most often between ages 25-55
More common in older people – women are more affected (2.5x)
Affects ~1-2% of population – course & severity can vary considerably
Still’s disease = type of RA occurring in young people
Gradual onset – fatigue, weakness, morning stiffness (lasting >1hr), diffuse muscular aches, loss of appetite
Joint pain eventually appears w/ warmth, swelling, tenderness, & stiffness of joint after inactivity
NOTE: RA, SLE, polyarteritis nodosa, dermatomyositis & scleroderma are all classified as collagen diseases
All have common inflammatory damage to CTs & BVs w/ deposition of fibrinoid material
NOTE: Most common characteristic lesion of rheumatic fever, scleroderma and RA is Fibrinoid degeneration
Osteoarthritis (OA):
Chronic inflammation that causes:
1) articular cartilage of affected joint to gradually degenerate
2) development of bony spurs, osteophytes
NOTE: Osteophyte (bony spur) formation is a cardinal feature of osteoarthritis not RA
Most common form of arthritis
Inflammation is accompanied by pain, swelling, & stiffness
Most commonly affects joints constantly exposed to wear & tear
Classic presentation: is pain in weight-bearing joints after use, improving with rest, but no systemic symptoms
X-rays show loss of joint space
Higher incidence in women, most often >50 y.o.
Joints most often affected – intervertebral joints, phalangeal joints, knees, & hips
Heberden’s nodes: (Heber City is far away -- distal)
Hard nodules/bony swellings which develop around the distal IP joints in patients w/ osteoarthritis
Produced by osteophytes of articular cartilage at the base of terminal planges in OA
2nd & 3rd fingers are most often affected
More common in females – onset in middle life
Bouchard’s nodes
Same as Heberden’s, but…
Found in the proximal IP joint
Characteristic morphologic changes in OA (in addition to Heberden’s & Bouchard’s nodes):
Eburnation of bone – polished ivory like appearance of bone
Osteophyte formation – bony spur formation
They fracture & float into synovial fluid along w/ fragments of separated cartilage & are called joint mice
Gout
Inherited disorder of purine metabolism occurring predominantly in men
Marked by uric acid deposits in the joints
There is hyperuricemia, too
Can be characterized by acute arthritis of big toe
Asymmetric
Caused by a metabolic defect resulting in either:
1) Overproduction of uric acid (monosodium urate crystals) OR
Uric acid – end-product of purine metabolism, specifically xanthine metabolism
Overproduction due to hyperuricemia (caused by Lesch-Nyhan syndrome, decreased uric acid excretion, or G6P Deficiency)
2) Reduced ability of the kidney to eliminate uric acid
Almost 25% of all people who have gout develop kidney stones
Exact cause of the metabolic defect is unknown
May also develop in people w/ diabetes, obesity, sickle cell anemia, & kidney disease, or it may follow drug therapy (Thiazide Diuretics inhibit the secretion of uric acid)
Crystals are needle shaped and negatively birefringent
Gout has 4 stages:
1) Asymptomatic
2) Acute
Causes painful arthritis – especially in joints of feet & legs
Symptoms develop suddenly & usually involve only one or a few joints (asymmetric)
Pain frequently starts at night – described as throbbing, crushing or excruciating
Joint appears infected – signs of warmth, redness, & tenderness
Attacks may subside in several days, but may recur at irregular intervals
Subsequent attacks usually have a longer duration
Acute attack tends to occur after alchol consumption or large meal
Some pts progress to chronic gouty arthritis – others may have no further attacks
Tophus formation – often on external ear or Achilles tendon
Tophi are pathognomonic of gout
3) Intercritical
4) Chronic
Pseudogout:
Disorder characterized by intermittent attacks of painful arthritis caused by deposits of calcium pyrophosphate crystals
Usually occurs in older people – affects both sexes equally
Forms basophilic, rhomboid crystals (as opposed to the negatively birefringent, needle shaped of gout)
Usually affects large joints
Ankylosing spondylitis:
CT disease characterized by inflammation of spine & large joints, resulting in stiffness & pain, along w/ aortic regurgitation
Associated w/ HLA-B27, gene that codes for HLA-MHC I
Reiter’s syndrome:
Inflammation of joints & tendon attachments at the joints, often accompanied by inflammation of conjunctiva & mucous MBs (mouth, urinary tract, etc.) & by a distinctive rash
Males ⋄ Can’t see (conjunctivitis), can’t pee (urethritis), can’t climb a tree (arthritis)
Common in post GI or Chlamydia infections
NEOPLASMS
Changes in Cell Growth
Atrophy:
Decrease in organ or tissue size resulting from a pathological decrease in mass of preexisting cells
Most often results from disuse, aging, or a disease process
Long standing gradual ischemia of an organ or tissue most likely result in atrophy
General causes of pathologic atrophy are:
Disuse
Pressure
Loss of innervation
Lack of nutrition
NOT chemical stimulation or oversstimulation w/ hormones
Hypertrophy (reversible):
Increase in organ or tissue size due to an increase in cell size
Cardiac muscle
Following injury, restores functional capacity via hypertrophy
Increase in ventricular wall thickness in pt with HTN
Increase in the size of a heart of an athlete
Hyperplasia:
An increase in the size of the organ caused by an increase in the number of cells
Hypoplasia:
Decrease in cell production less extreme than aplasia
Example is the underdevelopment of an organ, NOT an acquired reduction in the size of the organ
Aplasia:
Failure of cell production
During fetal development, aplasia results in agenesis (the absence of an organ)
Abnormal cells lacking differentiation, often equated w/ undifferentiated malignant neoplasms
Tumor giant cells may be formed
NOT a feature of malignancy (Anaplasia is)
Anaplasia:
Absence of cellular differentiation (which is a measure of tumor’s resemblance to normal tissue)
When malignant cells resemble more primitive undifferentiated cells
Metaplasia:
Process whereby one cell type changes to another cell type in response to stress
Change of a more specialized cell type to a less specialized cell type
Generally assists the host to adapt to the stress
Does NOT change the number of cells involved only type of cell
Examples:
The most common type of epithelial metaplasia involves replacement of columnar cells by stratified squamous epithelium (respiratory tract – smokers)
Early bronchial mucosal alteration most likely seen in cigarette smokers
Bone production in scar tissue
Transformation of mucous secreting bronchial epithelium to a squamous epithelium
Dysplasia (reversible):
Type of nonmalignant cellular growth – it may precede malignant changes (preneoplastic)
Epithelial change most predictive of cancer
Associated w/ chronic tissue irritation by:
1) chemical agents (e.g., cigarette smoke) OR
2) chronic inflammatory irritation (e.g., chronic cervitis)
Tissue appears somewhat structureless/disorganized & may consist of atypical cells w/o invasion
Abnormal tissue development
Epithelium exhibitis acanthosis (abnormal thickening of the prickle cell layer)
Changes in epithelial dysplasia: hyperchromatic nuclei, mitosis near the surface, pleomorphism of cells
EX: squamous cells exhibiting acanthosis, disorganization & atypical cells w/o invasion is diagnostic of dysplasia
May be reversed if causative factor is removed
Desmoplasia:
Excessive fibrous tissue formation in tumor stroma
Neoplasia
Clonal proliferation of cells that is uncontrolled and excessive
When cells grow out of control and proliferate
Tumor grade vs. stage:
Grade: (Think missing Histo by 1 point)
Histologic appearance of tumor
Usually graded I – IV based on degree of differentiation & # of mitoses per high power field; character of tumor itself
Stage:
Based on site & size of primary lesion, spread to regional lymph nodes, presence of metastases
Spread of tumor in a specific pattern
Has more prognostic value than grade
TNM staging system: T = size of tumor; N = Node involvement; M = Metastases
What’s more important???? ⋄ STAGE
Neoplasm vs. Inflammatory Overgrowth
Most characteristic feature of neoplasm as opposed to inflammatory overgrowth is that there is still progressive growth after removal of causative stimuli (NOT abnormal mitosis, tendency to grow rapidly, or tendency to recur after removal)
Oncogenes
Proteins that serve in normal control, but can be mutated or come in contact with a retrovirus and then growth occurs uncontrollably
C-myc Burkitt’s lymphoma
Bcl-2 Follicular and undifferentiated lymphomas (inhibits apoptosis) – Think Blood Cell Lesion -2
Erb-B2 Breast, ovarian, and gastric carcinomas
Ras Colon carcinoma – It’s in your Ass
Protooncogene
Gene sequences (in human cells) that are homologous to virus genome sequences known to cause cancer in animals
Tumor Suppressor Genes
Gene Chromosome Tumor
Rb 13q Retinoblastoma, osteosarcoma
BRCA-1 and 2 17q, 13q Breast and ovarian cancer
P53 17q Most human cancers, Li-Fraumeni syndrome
Genetic Hypothesis of Cancer:
Implies that a single progenitor cell is damaged, resulting in a tumor mass of Monoclonal cells
Mutation:
Stable, heritable change in nucleotide sequence of DNA
Results in an alteration in products coded for by the gene
Result from 3 types of molecular change:
1) Base substitutions – one base is inserted in place of another – results in either a missense or nonsense mutation
Missense mutation:
Results in substitution of one aa for another
Example ⋄ Val to glut in Sickle Cell
Nonsense mutation:
When base substitution generates a termination codon that prematurely stops protein synthesis
These mutations almost always destroy protein function
Transverse mutation:
Point mutation involving base substitutions in which the orientation of purine and pyrimidine is reversed
A purine is replaced by a pyrimidine or vice versa
Transition mutation:
Point mutation involving substitution of one base pair for another by replacing one purine by another purine & one pyrimidine by another pyrimidine – no change in the purine-pyrimidine orientation.
Caused by base analogues
2) Frame shift mutation –
occurs when 1+ base pairs are added or deleted
3) Transposons
(insertion sequence) or deletions are integrated into DNA
Caused by:
Chemicals – nitrous oxide & alkylating agents alter the existing base
Ionizing radiation (gamma & x-rays) – produce free radicals that attack DNA bases
UV radiation – has lower energy than x-rays, causes cross-linking of adjacent pyrimidine bases to form dimers
Nucleic acids in bacteria and viruses are most sensitive to UV radiation (versus protein, lipid, CHOs)
Thymine dimers result in inability of the DNA to replicate properly
THINK UV STERILIZATION
Viruses – bacterial virus Mu (mutator bacteriophage) causes either frame-shift mutations or deletions
Bacterial mutation leading to the requirement for a single amino acid is due to absence of a single NZ activity
Radiosensitivity
High radiosensitivity cells: lymphocytes > blood-forming cells >reproductive cells > epithelial cells of GI tract
Low radiosensitivity (radioresistant) – nerve cells, mature bone cells, muscle cells
Most to least radiosensitive: spermatogonium > intestinal mucosa > endothelial > skeletal muscle > osteocytes
Most closely related to mitotic rate
X-radiation
Repeated exposure of low dose x-radiation can cause:
Genetic mutations
Carcinogenesis
Basic effect on living tissues is ionization (NOT denaturation, etc)
Benign tumor:
Localized, has a fibrous capsule, limited potential for growth, a regular shape, & well differentiated cells
Does not invade surrounding tissue or metastasize to distant sites
Grow by expansion
Causes harm only by:
Pressure, hormone overproduction, or hemorrhage following ulcerations of overlying mucosal surface
Usually do not recur after surgical excision
Benign neoplasms:
Adenoma, Fibroma, Hemangioma, Lipoma
Malignant tumors spread by local invasion and metastasis
Malignant neoplasms:
Hepatoma, Lymphoma, Melanoma, Myeloma, Seminoma
Metastasis occurs via bloodstream or lymph system
Lymphatic – tumor 1st spreads to local & regional lymph nodes – then disseminates via blood
Hematogenous – 2° tumor nodules develop in liver, lung, brain, bone marrow, & sometimes spleen & soft tissue
|Benign |Malignant |
|Well-differentiated (neoplastic cells resemble comparable normal |Less well differentiated (anaplastic: loss of structural difference) |
|cells – meaning blasts are still making it to cytes, etc.) |**Can be either (Can either be well or poorly differentiated) |
|Slow growth |Rapid growth |
|Encapsulated; well circumscribed |Invasion |
|Localized |Metastasis – most important distinguishing characteristic |
|Movable |Immovable |
Host response to a malignancy is best reflected by lymphocytic infiltration at the edge of the tumor
Malignancy differentiated from inflammation in that malignancy will grow after removal of the causative agent
Most important characteristic of malignant neoplasms (distinguishing them from benign neoplasms) – ability to invade & metastasize
Seed vs. Soil Metastasis
Soil = Target organ ⋄ liver, lungs, bone, brain, etc.
Seed = Tumor Embolus
Implantation or seeding metastasis
Most often seen in stomach, ovary, colon (NOT in tongue, skin)
These most often send out SEEDS
B and L are always Breast and Lung for Pneumonics
Metastasis to brain:
Lots of Bad Stuff Kills Glia: Lung, Breast, Skin (melanoma), Kidney (renal cell carcinoma), GI
~50% of brain tumors are from metastasis
Metastasis to liver:
Cancer Sometimes Penetrates Benign Liver: Colon>Stomach>Pancreas>Breast>Lung
Liver & lung are the most common sites of metastasis after the regional lymph nodes
Metastasis to liver are much more common than primary liver tumors
Metastasis to bone:
BLT2 w/ Kosher Pickles: Breast, Lung, Thyroid, Testes, Kidney, Prostate
Primary tumor of the tongue is LEAST likely to metastasis to bone
Brain tumors also tend NOT to metastasize to bone
Lung = lytic
Prostate = blastic
Breast = both lytic & blastic
Metastases from breast & prostate are most common
Metastisis to jaw: breast > lung (breast & prostate greatest)
Most likely to metastasize to jaw ⋄ Breast
Metastatic bone tumors are far more common than 1° bone tumors
MOST common organ receiving metastasis ⋄ Adrenal Glands (Rich blood supply)
Usually first in medulla and then rest of gland
MOST common organ sending metastasis ⋄ LUNG>Breast>Stomach
|Paraneoplastic effects of tumors |
|Neoplasm |Effects of tumors |Effect |
|Small cell lung carcinoma (oat cell) |ACTH or ACTH-like peptide |Cushing’s syndrome |
|Small cell lung carcinoma and intracranial neoplasms |ADH or ANP |SIADH |
|Squamous cell lung carcinoma, renal cell carcinoma, |PTH-related peptide, TGF-alpha, TNF-alpha, IL-2 |Hypercalcemia |
|breast carcinoma, multiple myeloma, & bone metastasis | | |
|(lysed bone) | | |
|Renal cell carcinoma |Erythropoietin |Polycythemia |
|Thymoma, bronchogenic carcinoma |Antiboides against presynaptic Ca channels at |Lambert-Eaton syndrome (muscle weakness) |
| |neuromuscular junction | |
|Various neoplasms |Hyperuricemia due to excesss nuclei acid turnover |Gout |
| |(cytotoxic therapy) | |
|Cell type |Benign |Malignant |
|Epithelium |Adenoma, papilloma |Adenocarcinoma, papillary carcinoma |
|Mesenchyme | | |
|Blood cells | |Leukemia, lymphoma |
|Blood vessels |Hemangioma |Angiosarcoma |
|Smooth muscle |Leiomyoma (uterus) |Leiomyosarcoma |
|Skeletal muscle (voluntary m) |Rhabdomyoma |Rhabdomyosarcoma |
|Bone |Osteoma |Osteosarcoma |
|Fat |Lipoma |Liposarcoma |
|>1 cell type |Mature teratoma |Immature teratoma |
Predisposers of cancer:
Abestosis - mesothelioma
Hepatitis C – hepatocellular carcinoma
Gardner’s syndrome – multiple polyps ⋄ 100% malignant change
Ulcerative colitis – colonic adenocarcinoma.
NOT Anthracosis – Coal miners (black lung) – doesn’t ⋄ CA
Histological features of malignancy:
Anaplasia
Absence of differentiation (which is a measure of tumor’s resemblance to normal tissue)
When malignant cells resemble more primitive undifferentiated cells
Invasion
Hyperchromatism
Pleomorphism
Abnormal mitosis
|Diseases associated w/ neoplasms |
|Condition |Neoplasm |
|Down syndrome |Acute lymphoblastic leukemia –ALL We DOWN |
|Xeroderma pigmentosum |Squamous cell and basal cell carcinoma of the skin |
|Chronic atrophic gastritis, pernicious anemia |Gastric adenocarcinoma |
|Tuberous sclerosis (facial angiofibroma, seizures, mental retardation) |Astrocytoma and cardia rhabdomyoma |
|Actinic keratosis |Squamous cell carcinoma of skin |
|Barrett’s esophagus (chronic GI reflux) |Esophageal adenocarcinoma |
|Plummer-Vinson syndrome (atrophic glossitis, esophageal webs, anemia; all due to |Squamous cell carcinoma of esophagus (most common CA of esophagus – more so than |
|iron deficiency) |adenocarcinoma) |
|Cirrhosis (alcoholic, hepatitis B or C) |Hepatocellular carcinoma |
|Ulcerative colitis |Colonic adenocarcinoma |
|Paget’s disease of bone |Secondary osteosarcoma and fibrosarcoma |
|Immunodeficiency states |Malignant lymphomas |
|AIDS |Aggressive malignant lymphomas (non-Hodgkin’s & Kaposi’s) |
|Autoimmune disease (e.g., Hashimoto’s thyroiditis, myasthenia gravis) |Benign and malignant thymomas |
|Acanthosis nigricans (hyperpigmentation and epidermal thickening) |Visceral malignancy (stomach, lung, breast, uterus) |
|Dysplastic nevus |Malignant melanoma |
Tumor markers: should not be used as primary tool for cancer diagnosis. They may be used to confirm diagnosis, to monitor for tumor recurrence, and to monitor response to therapy:
|Marker |Tumor |
|PSA (prostate-specific antigen) |Prostatic carcinoma |
|Carcinoembryoonic antigen (CEA) |Carcinoembryonic antigen. Very nonspecific but produced by 70% of colorectal and|
| |pancreatic cancers; also produced by gastric and breast carcinoma |
|Alpha fetoprotein (AFP) |Normally made by fetus. Hepatocellular carcinomas. Nonseminomatous germ cell |
| |tumors of the testis (yolk sac tumor) |
|Human Chorionic Gonadotropin (Beta hCG) |Think HCG ⋄ Hydatidiform moles, Choriocarcinomas, and Gestational trophoblastic |
| |tumor |
|CA-125 |Ovarian, malignant epithelial tumors |
|S-100 |Melanoma, neural tumors, astrocytomas |
|Alkaline phosphatase (OSTEOBLASTS) |Metastases to bone, obstructive biliary disease, Paget’s disease |
|Acid phosphatase |Prostate tumors extending outside prostate capsule (Stage C or D) |
|Bombesin |Neuroblastoma, lung and gastric cancer |
|TRAP |Tartate-resistant acid phosphatase. Hairy cell leukemia—a B cell neoplasm |
|Oncogenic Virus |Associated Cancer |
|HTLV-1 |Adult T-cell leukemia |
|HBV, HCV |Hepatocellular carcinoma |
|EBV |Burkitt’s lymphoma, nasopharyngeal carcinoma |
|HPV |Cervical carcinoma (16,18) penile/anal carcinoma |
|HHV-8 (Kaposi’s sarcoma associated herpes virus) |Kaposi’s sarcoma, body cavity fluid B cell lymphoma |
|Chemical Carcinogens |Associated Cancer |
|Aflatoxins, vinyl chloride |Liver |
|Nitrosamines |Esophagus, stomach |
|Asbestos |Lung (mesothelioma and bronchogenic carcinoma) |
|Arsenic |Skin (squamous cell) |
|CCl4 |Liver (centrilobular necrosis, fatty change) |
|Naphthalene (aniline dyes) |Bladder (transitional cell carcinoma) |
Carcinoma in situ:
Pleomorphism
Disorderly maturation
Hyperchromatic nuclei
BUT Basement membrane remains intact
Carcinoma:
Malignant tumor of epithelial origin – think squamous cells carcinoma
Usually metastasize via lymphatics
Occurs in the following variations:
Squamous cell carcinoma – originates from stratified squamous epithelium; marked by production of keratin
Transitional cell carcinoma – arises from transitional cell epithelium of urinary tract
Adenocarcinoma – a carcinoma of glandular epithelium
Metastatic Carcinoma
Most common malignancy found in bone (NOT osteosarcoma, giant cell tumor, chondrosarcoma, multiple myeloma) - Most bone CA came from somewhere else.
Sarcoma:
Malignant tumor of mesenchymal origin. Think liposarcoma.
Usually metastasize via blood
EXs: osteosarcoma (bone), leiomyosarcoma (smooth muscle), & liposarcoma (adipose tissue)
Cancer Facts/Figures
Men
Most common = Lung > Colorectal > Prostate
Highest Mortality = Lung > Colorectal > Prostate
Women
Most common = Breast > Lung > Colorectal
Highest Mortality = Lung > Breast > Colorectal
IN general
Cancer is the second leading cause of death in the US (Heart disease is 1st)
Lung cancer:
Most common cause of cancer in men
Most common cause of cancer death in women and Men
Affects males 4x more than females—outdated????
But in the past 30 years, the mortality rate for women has increased
Most common types:
Adenocarcinoma –
Most common primary malignancy of the lung
Epidermoid (SCC)
Most forms arise from lining epithelium of the tracheobronchial tree
SCC of lung associated endocrine effect of hyperparathyroidism; calcitonin
Small cell (oat cell) – 25%
Most commonly associated with Paraneoplastic Syndrome
Large cell (anaplastic) – 15%
Most arise from main bronchus & are therefore termed bronchogenic carcinomas
Primary malignant neoplasm of the lung, originating from transformed epithelium of bronchial tree walls
Main symptom – persistent cough (smoker’s cough)
Other signs & symptoms – hoarseness, wheezing, dyspnea, hemoptysis, & chest pains
½ of the cancers are inoperable by the time pt is first seen in hospital
First signs of lung cancer are often related to metastatic spread, particularly to the brain
Other areas include to endocrine glands, skin, liver, & bones
Metastasis is through lymphatic channels
Metastasis to lungs commonly from breast, colon, prostate, kidney, thyroid, stomach, cervix, rectum, testis, bone, & skin
Etiologic agents in causation of lung cancer: cigarette smoking, industrial & air pollutants, familial susceptibility
Other diseases due to smoking:
Chronic obstructive pulmonary disease, which includes emphysema, chronic bronchitis
Carcinoma of the larynx and oral cavity
Dx for a pt with a hx of smoking, dysphonia, dysphagia, and weight loss
Increased incidence of carcinoma of the esophagus, pancreas, kidney, & bladder
Peptic ulcer disease
Low birth weight infants
NOT – 5 things
STOMACH or COLON CANCER, CHRONIC GASTRITIS (Acute?), or Acute Respiratory Distress Syndrome - smoking has nothing to do with GI tract beyond the esophagus.
Carcinogens
Most potent is Benzopyrene
Benzopyrene is a very potent carcinogen found in cigarette smoke
Binds to existing DNA bases & causes frame-shift mutations
Breast Cancer:
Most common cancer affecting women
# 2 Killer of women ages 35-54 ⋄ Second to Lung
Lifetime risk: 1 out of 11 ¾
Rare before age 25 & increasingly more common w/ age until menopause – incidence then slows down
Almost always an adenocarcinoma
Factors increasing risk: from Wikipedia
Age (40+)
Nulliparity
Family Hx
Strongest association – family Hx, specifically breast cancer in 1st-degree relatives (mother, sister, daughter)
Early menarche
Late menopause
Fibrocystic disease
Previous Hx of breast cancer
Obesity (but NOT Estrogen deficiency or silicone implants)
Younai says silicone implants for sure increased risk!!
Wikipedia begs to differ with Fariba, search ‘silicone implants’ and click on the risks link
Alcohol / Hormones – both are debated
More common in left breast than right & more commonly in the outer upper quadrant –Boys are right handed!!
Widespread metastasis can occur by way of lymphatic system & bloodstream, through right side of heart & lungs, eventually to the other breast, chest wall, liver, bone, & brain
A women with metastastic carcinoma of the jaws most likely came from Breast cancer
Characterized by:
Painless mass is usually the initial sign or symptom
Retraction of skin or nipple
Peau d’orange (swollen pitted skin surface) along w/ …
Enlargement of axillary lymph nodes may also be present
Increased pigmentation of the nipple
NOT spontaneous acute redness, swelling, and tenderness of the breast
Lymph node involvement is most valuable prognostic predictor
With adjuvant therapy, 70-75% w/ negative nodes will survive 10+ years; only 20-25% of women w/ positive nodes
Growth is influenced by hormones (same as Prostatic carcinoma)
Fibrocystic disease:
Most common cause of a clinically palpable breast mass in women (28-44 y.o.)
Signs & symptoms – lumpiness throughout both breasts
Pain is common, especially prior to menstruation
Non-malignant – may lead to increased risk of developing carcinoma
Teratoma:
Tumor composed of multiple tissues (may contain elements of all 3 embryonic germ cell layers)
Includes tissues not normally found in the organ in which they arise
Occurs most frequently in the ovary – here it is usually benign & forms dermoid cysts
Also occurs commonly in testes – here it is usually malignant
Pancreatic Cancer
Tumors MORE common in the HEAD (because obstructive)
Carcinoma of the tail of the pancreas is the LEAST likely to cause acute pain
Pt with this malignancy have the WORST Px of any malignancy
Associated w/ ↑ serum concentration of carcinoembryonic antigen (CEA)
Colon & rectal cancer:
Malignant neoplasm of colonic or rectal mucosa
Almost always an adenocarcinoma
2nd most common cancer-causing death in men; 3rd most common cancer-causing death in women
Disease is entirely treatable if caught early
Greatest 5 yr survival Rate @ 60%
No single cause, but almost all begin as a polyp
Most colorectal carcinomas arise from Adenomatous polyps (NOT hemorrhoids, diverticula, etc)
Associated w/ ↑ serum concentration of carcinoembryonic antigen (CEA) – and Pancreas
Predisposing factors – adenomatous polyps, inherited multiple polyposis syndromes, long-standing ulcerative colitis, genetic factors, & low fiber, high animal fat diet, more common in industrialized nations
Rapidly increasing incidence w/ age, starting at age 40
Symptoms – rectal bleeding w/ diarrhea, abdominal pain, & weight loss
Tumors on the left side are more likely to cause symptoms
Symptoms usually only occur in advanced states
Sigmoid colon – most common site (NOT TRANSVERSE)
Sigmoidoscopy can disclose the majority of the tumors
Tumors of descending colon usually cause constipation & are generally dx’d at an earlier stage than tumors ascending colon
Prostate cancer:
3rd most common cause of death from cancer in men of all ages
Most common cause of death from cancer in men >75 y.o., common in men > 50 y.o., rarely found in men 30 y.o. (during the reproductive years)
Other areas (less frequent) – stomach, esophagus, & small intestine
Prognosis is good
Cause of fibroid tumors of uterus is unknown
Suggested that fibroids may enlarge w/ estrogen therapy (such as oral contraceptives) or w/ pregnancy
Growth depends on regular estrogen stimulation – rare before age 20 & shrinks after menopause
Fibroid will continue to grow as long as women menstruates, but growth is slow
Uterine fibroids – most common pelvic tumor – present in 15-20% of reproductive-age women, 30-40% of women > 30 y.o.
Endometrial Carcinoma/Uterine Cancer
Risk factor is Hyperestrogenism
Cervical Cancer
Predisposed by ⋄ Multiple sex partners, Having Sex with Uncircumcized Males, Smoking, HIV, Chlamydia, Oral Contraceptives, Lots of pregnancies, Early age of Intercourse, HPV
NOT Early Menarche
Early Menarche
Risk factor for,
The ones involved in the Menses Process ⋄ Endometrial (uterine), Ovarian, Uterine Sarcoma, Breast (sensitive during Menses)
Keratoacanthoma:
Relatively common low grade malignancy that originates in the pilosebaceous glands
Pathologically resembles SCC
Characterized by rapid growth over a few wks to months, followed by spontaneous resolution over 4-6 months in most cases
Etiologic factors – sunlight, chemical carcinogens, trauma, HPV, genetic factors, immunocompromised status
Can (rarely) progress to invasive or metastatic carcinoma
Aggressive surgical Tx is advocated
Dermatofibromas:
Benign neoplasms that appear as small, red-to-brown nodules that result from fibroblast accumumlation
Acrochordon (aka skin tag):
Extremmly common lesion – most often found on neck, in armpit, or groin
Actinic keratosis:
Premalignant epidermal lesion caused by excessive chronic sunlight exposure
NOTE: don’t get clowned by verrucus vulgaris (wart) as an option for “What is generally considered precancerous?”
Common in light-skinned elderly people
Seborrheic keratosis (aka seborrheic warts):
Extremely common benign neoplasm of older people
Flesh-colored, brown, gray, or black growths that can appear anywhere on skin
Think “gray, scaly, & greasy” (typical appearance)
Acanthosis nigricans:
Cutaneous disorder marked by hyperkeratosis & pigmentation of axilla, neck, flexures, & anogenital region
More than ½ of these pts have cancer (GI carcinomas, particularly of the stomach)
More skin disorders (while we’re here):
Dermatitis:
Group of inflammatory pruritic skin disorders
Etiology: allergy (usually type IV hypersensitivity), chemic injury, or infection
Psoriasis:
Nonpruritic chronic inflammation of the skin, particularly on the knees and elbows
Associated w/ HLA-B27, HLA-13, etc
Auspitz sign: seen when removal of scale results in pinpoint areas of bleeding
Treat w/ topical steroids & UV irradiation
Bullous pemphigoid:
Autoimmune disorder w/ IgG antibody against epidural basement membrane (linear immunofluorescence). Similar to but less severe than pemphigus vulgaris—affects skin but spares oral mucosa
Pemphigus vulgaris:
Potentially fat autoimmune skin disorder. Intrdermal bullae involving the oral mucosa and skin. Findings: acantholysis (breakdown of epithelial cell-to-cell junctions), IgG antibody against epidermal cell surface.
Impetigo:
Highly infectious skin infection most common in pre-school aged children during warm weather
Results from epidermal invasion by Staph. aureus or Strep. pyogenes
Similar to cellulitis, but more superficial
Begins as an itchy, red sore that blisters, oozes & finally becomes covered w/ a tightly adherent crust
Tends to grow & spread
Impetigo sores heal slowly & seldom scar
Impetigo is contagious – infection is carried in the fluid that oozes from the blister
Rarely, impetigo may form deep skin ulcers
Tx – mild infection typically treated w/ Rx antibacterial cream (Bactroban)
Oral Abx (erythromycin or dicloxacillin) frequently prescribed – rapid clearing of lesions
Cure rate is extremely high but often recurs in young children
Acute glomerulonephritis – one of the more common renal diseases in children – an occasional complication of impetigo
Erythema multiforme (EM):
Type of hypersensitivity (allergic) IgM reaction occurring in response to medication, infections, or illness
Medications – sulfonamides, penicillin, barbiturates, & phenytoin
Infections – HSV & mycoplasma
Exact cause is unknown
Believed to involve damage to BVs of skin w/ subsequent damage to skin tissues
Fairly common, w/ a peak incidence in 2nd & 3rd decades of life
May present w/ classic skin lesions over dorsal aspect of hands/forearms w/ or w/o systemic symptoms
Classic lesion – a central lesion surrounded by concentric rings of pallor & redness (“target”, “bull’s eye” shape)
Stevens-Johnson syndrome:
Severe systemic symptoms & extensive lesions involving multiple body areas (especially mucous MBs)
Toxic epidermal necrolysis (TEN syndrome, or Lyell’s syndrome)
Involves multiple large blisters (bullae) that coalesce, followed by sloughing of all or most of the skin & mucous MBs
Lymphadenitis
Inflammation of a lymph node or nodes
Lymphadenopathy
Any disease process affecting a lymph node or nodes
The Q reads: Enlarged, tender, & inflamed lymph nodes are one form of….Lymphadenitis or Lymphadenopathy??? – 2000 Q86
Hodgkin’s lymphoma = Hodgkin’s disease (Ryan Hodges is nice ⋄ not as malignant)
Malignancy characterized by painless progressive enlargement of lymphoid tissue
1st sign – often an enlarged lymph node that appears w/o a known cause
Can spread to adjacent lymph nodes & later may spread outside lymph nodes - to lungs, liver, bones, or bone marrow
Unknown cause
BIMODAL (Also Think also HOMOzygous Histo)
Affects 2x as many males as females; usually develops between ages 15-35
Splenomegaly is common
Most important – presence of Reed-Sternberg cells (Ryan Hodges looks like a Reed) – the actual neoplastic cells (Reed S. cells are CD30+ & CD15+)
Heterozygous Histology is NOT characteristic of Hodgkin’s
Symptoms – anorexia, weight loss, generalized pruritus, low-grade fever, night sweats, anemia, & leukocytosis
Prognosis – most favorable w/ early Dx & limited involvement & with lymphocytic predominance
Believed to start as an inflammatory/infectious process & then become a neoplasm
Some believe it is an immune disorder
50% of cases are associated with EBV
Non-Hodgkin’s lymphomas = “malignant lymphomas” = “lymphosarcomas”
Heterogenous group of malignant diseases originating in lymphoid tissue
Associated with HIV and immunosuppression
Most involve B cells
Cause is unknown – some suggest a viral source
Occur in all age groups; 2-3x more common in males
More common than Hodgkin’s disease
Present as solid tumors composed of cells that appear primitive or resemble lymphocytes, plasma cells, histiocytes
Small lymphocytic lymphoma: adult B cells, that clinically presents like CLL, low grade.
Follicular lymphoma: (small cleaved cell): Adult B cells with t(14;18) chromosome, bcl-2 expression. It is difficult to cure; indolent course; bcl-2 is involved in apoptosis
Diffuse large cell: usually older adules, but 20% are children w/ 80% B cell and 20% T cells (mature). It is aggressive but 50% are curable
Lymphobalstic lymphoma: children most often affected, T cells are immature. Commonly presents w/ ALL and mediastinal mass; very aggressive T cell lymphoma
Burkitt’s lymphoma:
High-grade B-cell lymphoma (lymph gland tumor) classified as a non-Hodgkin’s type of lymphoma
EBV may be the cause of this lymphoma
The 1st human cancer that has been strongly linked to a virus
Undifferentiated malignant lymphoma that usually begins as:
African form: (ENDEMIC FORM)
95% of cases associated w/ EBV
Affects children of middle African regions
Usually begins as a large mass in the jaw
American form:
Less closely associated w/ EBV
Usually begins as an abdominal mass
Jaw tumors are rare
Both types are caused by defective B-cells
Children affected most, their B cells: t(18;14) c myc gene moves next to heavy chain Ig gene 14.
Starry sky appearance (sheets of lymphocytes w/ interspersed macrophages, associated w/ EBV; jaw lesions in endemic form in Africa, pelvis or abdomen in sporadic form
Mycoisis fungoides:
Rare, persistent, slow-growing type of non-Hodgkin’s lymphoma originating from a mature T-cell
Affects the skin; may progress to lymph nodes & internal organs
1st indication – swollen lymph glands (lymphadenopathy), enlarged tonsils & adenoids; painless, rubbery nodes in cervical supraclavicular areas
Pt develops symptoms specific to involved area & systemic complains – fatigue, malaise, weight loss, fever, & night sweats
Pathophysiologically similar to Hodgkin’s disease, but:
Reed-Sternberg cells are not present
Specific mechanism of lymph node destruction is different
Biopsy differentiates Non-Hodgkin’s from Hodgkin’s
|Hodgkin’s |Non-Hodgkin’s |
|Presence of Reed-Sternberg cells |Non-Hodgkin’s associated w/ HIV and immunosuppression |
|Localized, single group of nodes, extranodal rare; contiguous spread |Multiple, peripheral nodes;extranodal involvement common; noncontinguous spread |
|Constitutional signs/symptoms—low-grade fever, night sweats, weight loss |Majority involve B cells (except lymphoblastic T cell origin) |
|Mediastinal lymphadenopathy |No hypergammaglobulinemia (cf., multiple myeloma, where excess B cells are in |
| |resting stage) |
|50% of cases associated w/ EB; bimodal distribution: young and old; more common in|Fewer constitutional symptoms |
|men except nodular sclerosis type | |
|Good prognosis = increase lymphocytes, low number of Reed Sternberg cells |Peak incidence 20 -40 years old |
Ann Arbor staging of Hodgkin’s: ⋄ HENCE Extranodal a definite possibility
I: single lymph node or single extralymph organ
II: 2 or more sites, on same side of diaphragm
III: 2 or more sites; on both sides of diaphragm
IV: Disseminated
Which type of Hodkin’s is dx at Stage IV??
A: without constitutional symptoms
B: with constitutional symptoms (fever, night sweats, weight loss)
Multiple Myeloma:
A cancer of plasma cells arising in bone marrow (a monoclonal plasma cell w/ “fried-egg” appearance) or older aged adults
Disease associated with proliferation of plasma cells showing “punched out” lesions
Most common bone tumor arising from w/in the bone in adults
Characterized by excessive growth & malfunction of plasma cells in bone marrow
Hyperglobulinemia
Produces large amounts of IgG (55%) or IgA (25%)
Growth of these extra plasma cells interferes w/ the production of RBC, WBC, & platelets
Causes anemia & susceptibility to infection
Clinical features:
Anemia, pathologic bone fractures, increased susceptibility to infection (most common cause of death), increased bleeding tendencies, anemia, hypercalcemia, renal failure, & amyloidosis
Cancer cells produce osteolytic lesions throughout skeleton (flat bones, vertebrae, skull, pelvis, ribs)
Renal failure is frequent complication – caused by excess calcium in blood from bone destruction
This increases the susceptibility of pt to infection & anemia
Accounts for 1% of all cancers – mostly found in men >40 y.o.
Earliest indication – severe, constant back & rib pain increasing w/ exercise – may be worse at night
The pain arises from pressure created by malignant plasma cells on nerves in the periosteum
Radiographs – punched-out appearance & primary amyloidosis
Bence Jones protein in urine & hypercalciuria
Result of light-chain dimers in urine
Absence does not rule out multiple myeloma
Has monoclonal Ig spike (M-protein, also found in Waldenstrom’s macroglobulinemia)
SIDENOTE on Waldenstrom’s:
Neoplasms of lymphocytoid plasma cells that produce monoclonal IgM
Lacks the lytic bone lesions of multiple myeloma
Blood smear shows RBC stacked like poker chips (rouleaux formation)
Skin cancer:
General info:
Most common malignancy in U.S.
Most to least common: Basal cell carcinoma – SCC – Malignant melanoma
Basal cell carcinoma (BCC):
Most common skin malignancy in man
75% of all skin cancers – most common of all cancers in U.S.
Derived from epidermal basal cells
>90% occur on areas of skin regularly exposed to sunglight/UV radiation
Most common site is the upper face
Invasive, ulcerative, often indurated, slow-growing & locally destructive – does NOT metastasize
53-yr-old pt with chronic, indurated lesion near the inner canthus
Prognosis is good – usually cured by excision; radiosensitive (if necessary)
Px is Better than multiple myeloma, osteosarcoma, carcinoma of breast or esophagus
Characterized by clusters of darkly staining cells w/ typical palisade arrangement of cell nuclei at periphery of cell cluster
Also has “pearly papules” in gross pathology
Usually occurs in persons > 40
More prevalent in blond, fair-skinned males on skin exposed to regular sunlight/UV radiant
Similar to SCC in that BOTH are:
Invasive
Exhibit mitotic figures
Cured by early excision
Incorrect: readily metastasize, commonly occur in the oral cavity
Least likely to metastasize (among neuroblastoma, chondrosarcoma, epidermoid carcinoma, or mucinous adenocarcinoma)
Squamous Cell Carcinoma (SCC):
Involves cancerous changes to keratinocytes – middle portion of epidermal skin layer
Usually painless initially – may become painful w/ development of non-healing ulcers
May begin on normal skin; skin of a burn, injury, or scar; or site of chronic inflammation
Commonly found on hands & face
Most often originates from sun-damaged skin areas, such as actinic keratosis
Actinic keratosis is a precursor to SCC
Usually begins > age 50
Usually metastasizes via lymphatics
Malignant & more aggressive than basal cell carcinoma, but still may grow slowly
Also associated w/ chemical carcinogens (e.g., arsenic) & radiation
Most often locally invasive – but SCC can infiltrate underlying tissue or metastasize in lymphatic channels
Oral Cancer (squamous cell) most commonly resembles the most common form of cervical cancer in histology & behavior
Adenocarcinoma is the most common primary malignant neoplasm of the lung
Histopathologically contains squamous / epithelial / keratin pearls and intercellular bridges
Resemble prickle cells & form keratin pearls
Malignant epithelial cells have ↑ # of laminin receptors
Laminin (a glycoprotein) = major component of basement MBs???????
Has as numerous biological activities including promotion of cell adhesion, migration, growth & differentiation
IS in the ECM, where as tubulin is NOT, remember laminins in the lamina lucida!!
Malignant melanoma:
Involves the melanocytes – produce melanin – responsible for skin & hair color
Can spread very rapidly
Most severe & most deadly skin cancer – leading cause of death from skin disease
May appear on normal skin OR may begin at a mole (nevus) or other area that has changed appearance
Relevance to prognosis of pt:
Depth of invasion has the Greatest relevance to Px
Vertical invasion or growth is related to Px of Melanoma
Degree of pigmentation has the LEAST relevance to Px
Multiple biopsies
Sex of the pt
Palpable lymphadenopathy
Some moles that are present at birth may develop into melanomas
Development is related to sun exposure, particularly to sunburns during childhood
Most common among people w/ fair skin, blue or green eyes, & red or blonde hair
Depth of tumor correlates w/ risk of metastasis
Four Types:
Superficial spreading melanoma (most common):
Usually flat & irregular in shape & color, w/ varying shades of black & brown
May occur at any age or site
Most common in Caucasions
Nodular melanoma:
Usually starts as a raised area – dark blackish-blue or bluish-red (although some lack color)
Poorest prognosis
Lentigo maligna melanoma:
Usually occurs in the elderly
Most common in sun-damaged skin on face, neck, & arms
Abnormal skin areas are usually large, flat, & tan w/ intermixed areas of brown
Develops from preexisting lentigo maligna (Hutchinson freckle)
Acral lentiginous melanoma:
Least common form of melanoma.
Usually occurs on palms, soles & under nails
More common in African Americans
Tumor growth patterns w/in skin:
Initial radial growth (do not metastasize) – characteristic of spreading types
Vertical growth (metastasis may occur) – characteristic of nodular melanoma
Tumors of the adrenal medulla:
1) Pheochromocytoma:
Chronic chromaffin-cell tumor of the adrenal medulla that secretes an excess of epinephrine & norepinephrine
Results in severe HTN, increasd metabolism, & hyperglycemia
Endocrine effect of HTN
Common between ages 30-60 – most common tumor of adrenal medulla in adults
If tumor is derived from extra-adrenal chromaffin cells, it is called a paraganglia (metastasis is more common in this tumor)
Episodic hyperadrenergic symptoms: 5 P’s—Pressure (elevated BP); Pain (headache), Perspiration; Palpitations; Pallor/diaphoresis
Rule of 10s ⋄ 10% are malignant, bilateral, extraadrenal, calcify, kids, familial
Tx with alpha antagonists, especially pheoxybenzamine, a nonselective irreversible alpha blocker
May be a part of or associated w/ MEN II and III(multiple endocrine neoplasia), neurofibromatosis (von Recklinghausen’s disease) or von Hipple-Lindau disease (multiple hemangiomas)
2) Neuroblastoma:
Highly malignant tumor of early childhood – most common malignant tumor of childhood & infancy
Think NEUW and BLASTIC
Usually originates in the adrenal medulla, but it can go anywhere on the sympathetic chain
Complications – invasion of abdominal organs by direct spread & metastasis to liver, lung or bones
First symptoms in many children – large abdomen, sensation of fullness, & abdominal pain
These are followed by an abdominal mass
~90% of neuroblastomas produce hormones, such as epinephrine, which can ↑ HR & cause anxiety
I think it has highest incidence in Causcasians
NOT schwannoma, Wilms’ tumor, carcinoid tumor
Multiple endocrine neoplasm: all have auto dom characteristic, II, and II have ret gene association
Think MEN have large Adam’s apple or THYROID
MEN type I (Wermer’s syndrome):
three P organs, pancreas, pituitary, and parathyroid. Presents w/ kidney stones and stomach ulcers.
MEN type II (Sipple’s syndrome): -- Sipping get to your thyroid
medullary carcinoma of the thyroid, pheochromacytoma, parathyroid tumor, or adenoma
MEN type III (Formerly MEN IIb):
medullary carcinoma of the thyroid, pheochromocytoma, and oral and intestinal ganglioneuromatosis
Increased incidence of medullary carcinoma of the thyroid with pts suffereing from MEN type III
Von Hippel-Lindau disease (neurofibromatosis II):
Characterized by hemangiomas of the retina, medulla, & the cerebellum
Associated w/ cysts of liver, kidney (bilateral renal cell carcinomas), adrenal glands, & pancreas
Autosomal dominant associated w/ VHL gene (tumor suppressor on chromosome 3 (3p)
Bone tumors:
Most are secondary (caused by seeding from a primary site) – From Stomach, Ovary, and Colon
Primary tumors are more common in males, usually children & adolescents – some types occur in persons ages 35-60
They may originate in osseous or nonosseous tissue
Osseous bone tumors arise from bony structure itself
Non-osseous tumors arise from hematopoietic, vascular, or neural tissue
Primary malignant bone tumors (aka sarcomas of bone)
Rare, constituting less than 1% of all malignant tumors
Metastatic bone tumors
Have spread to bone from original site elsewhere in the body
Cancers most likely spread to bone – breast, lung, prostate, kidney, & thyroid cancers
In children, the most common types of bone tumors are Osteogenic & Ewings’s sarcomas
Most common malignancy in bone is metastatic carcinoma
Bone tumors of osseous origin:
Osteogenic sarcoma: (aka Osteosarcoma)
Most common
Usually in males ages 10-30
Occurs most often in femur, but also tibia & humerus; occasionally, in fibula, ileum, vertebra, or Mn
Tumor arises from bone-forming osteoblasts and bone-digesting osteoclast
Most often in metaphysis of long bones
Bone lesion w/ radiopaque structures radiating from the periphery
Predisposing factors include: Paget’s disease, bone infarcts, radiation, and familial retinoblastoma – think Rb gene
Periosteal osteogenic sarcoma:
Usually in females ages 30-40
Occurs most often in distal femur, may also be in humerus, tibia, & ulna
Develops on bone surface (instead of interior) & progresses slowly
Chondrosarcoma:
Usually in males ages 30-50
Occurs most often in pelvis, proximal femur, ribs, & shoulder girdle
Develops from cartilage & grows slowly
Usually painless; locally recurrent & invasive
May be from primary origin or from osteochondroma
Malignant giant cell tumor:
Usually in females ages 18-50
Arises from benign giant cell tumor
Found most often in long bones, more so in knee area (epiphysis)
Locally aggressive tumore found around the distal femur, proximal tubial region
Characteristic “double bubble” or soap bubble appearance on x-ray; spindle-shaped cells w/ multinucleated giant cells
Bone pain is the most common indication of 1° malignant bone tumors
Bone pain has greater intensity at night, is associated w/ movement & is dull & usually localized
Bone tumors of nonosseous origin:
Ewing’s Sarcoma:
Malignant tumor that can occur any time during childhood – usually develops during puberty during rapid bone growth
NOTE: osteogenic sarcoma is another malignant tumor in kids – myeloma is not (Mark’s Dad).
Characteristic of kids and Teens??? ⋄ Ewing’s Sarcoma (I watched Patrick Ewing when I was in my teens)
Usually in males ages 10-20
Usually originates in bone marrow & invades diaphyses of long & flat bones
Usually affects lower extremeties, most often in femur, innominate bones, ribs, tibia, humerus, vertebra, & fibula
Often metastasizes to lungs & other bones
Metastasis in ~ 1/3 of children at time of Dx
From anaplastic small blue cell malignant tumor
Extrememly aggressive w/ early metastisis
Few symptoms – most common is pain
Pain is increasingly severe & persistent
Occasionally swelling at tumor site
Fever may also be present
Children may also have a pathologic fracture
Very radiosensitive tumor
Also exhibits characteristic onion skin
Often difficult to distinguish histologically from a neuroblastoma or reticulum cell sarcoma
Fibrosarcoma:
Usually in males ages 30-40
Originates in fibrous tissues of bone
Invades long or flat bones – femur, tibia, & Mn
Also involves periosteum & overlying muscle
Chordoma:
Usually in males ages 50-60
Derived from embryonic remnants of notochord
Progresses slowly
Usually found at end of spinal column & in spheno-occipital, sacrococcygeal, & vertebral areas
Characterized by constipation & visual disturbances
Benign tumors of mesenchymal origin (& where they’re derived from):
Leiomyoma – from smooth muscle – includes the uterine leiomyoma or fibroid tumor – most common neoplasm of women
Rhabdomyom – skeletal muscle
Lipoma – adipose tissue – most common soft tissue tumor
Chondroma – cartilage
Papilloma – surface epithelium (e.g., squamous epithelium of skin or tongue)
Adenoma – glandular epithelium
Myxoma – connective tissue
Angioma – neoplasm of either blood or lymph vessels
Choristoma:
Small, benign mass of normal tissue misplaced w/in another organ, such as liver tissue w/in intestinal wall
Hamartoma:
Benign tumor-like overgrowth of cell types; regularly found w/in affected organ, such as a hemangioma
Glioblastoma Multiforme:
Most common type of astrocytoma
FIND OUT ⋄ Malignant Myoepithelia is associated with ⋄ cigarettes, asbestos, polyaromatic hydrocarbons?????
LEUKEMIAS
Leukemia:
Form of cancer that begins in blood-forming cells of bone marrow
Damaged leukocytes remain in immature form:
Become poor infection fighters
Multiply excessively & do not die off
Increased number of circulating leukocytes in the blood
Leukemic cells accumulate & reduce production of RBCs, platelets & normal leukocytes
Prolongation of bleeding time in leukemia is a result of thrombocytopenia (reduced #s of platelets)
If untreated, surplus leukemic cells overwhelm the bone marrow, enter the bloodstream, & invade other parts of the body:
Lymph nodes, spleen, liver & CNS
Behavior is different from other cancers, which usually begin in major organs & ultimately spread to bone marrow
Classified by the dominant cell type & by the duration from onset to death
Incidence evenly split (50:50) between acute & chronic leukemias
Can modify the inflammatory reaction
Chemotherapy for leukemia predisposes for oral infections by C. albicans
[pic]
Risk factors for leukemias:
Familial tendency
Congenital disorders (Down syndrome [higher incidence of acute leukemias]; presence of Philadelphia chromosome [CML])
Leukemic pts have high Ab titer to EBV
Ionizing radiation & exposure to benzene & cytotoxins (such as alkylating agents), some anti-cancer drugs
Acute leukemias:
Rapid onset & progression: (few months)
Sudden high fever, weakness, malaise, severe anemia, generalized lymphadenopathy, bone & joint pain
Common in children
Most often seen in the under 20-yr-old age group
Principal organ involved: bone marrow (along w/ liver & spleen)
Characterized by immature, abnormal cells in bone marrow & peripheral blood
Frequently in the liver, spleen, lymph nodes, & other parenchymatous organs
Fatal, unless treated quickly
Petechiae & ecchymosis on skin & mucous MBs, hemorrhage from various sites; bacterial infections common
Clinical picture is marked by:
Effects of severe anemia (fatigue, malaise) & thrombocytopenia
Absence of functioning granulocytes (prone to infection/inflammation)
Spleen & liver usually moderately enlarged
Enlarged lymph nodes seen mainly in ALL
Lab findings: leukocytosis 30k-100k/mm3; immature forms (myeloblasts & lymphoblasts) predominate
In 75% of cases of ALL, the lymphocytes are neither B- nor T-cells (they are called “null cells”)
Untreated pts die w/in 6 months
Wth intensive therapy (chemo, radiation, & bone marrow transplants), remissions may last up to 5 years
Death usually due to hemorrhage (brain) or a superimposed bacterial infection
Shorter, more devastating clinical course than chronic leukemias
Are characterized by proliferations of lymphoid or hematopeoietic cells that are less mature than those of the chronic leukemias
Chronic leukemias:
Slower onset & progression: w/ weakness and weight loss, disease may be detected during examination for some other condition (e.g., anemia, unexplained hemorrhages, or recurrent intractable infection)
Longer, less devastating clinical course than acute leukemias
Develop in more mature cells – can perform some duties, but not well
More difficult to treat in many cases
Characterized by proliferations of lymphoid or hematopoeitic cells (more mature than those of acute leukemias)
Organ involvement
Massive splenomegaly is characteristic of CML
Lymph node enlargement in CLL
Petechiae & ecchymosis, recurrent hemorrhages, baceterial infections
Lymphocytic anemia may be complicated by autoimmune hemolytic anemia
Lab findings: leukocytosis >100k/mm3; mature forms (granulocytes and lymphocytes) predominate
Philadelphia chromosome & low levels of leukocyte ALP alkaline phosphatase common in CML
Median survival time:
CML – 4 years w/ death due to hemorrhage or infection
CLL – runs a variable course (older pt may survive years even w/o Tx)
|Major Types of Leukemias |
|Type |Progression |WBC affected |% of Leukemias |Age group |
|ALL |Rapid |Lymphocytes |20 | 3-5 y.o. |
|AML |Rapid |Myelocytes |27 |Mostly adults |
|CLL |Slow |Lymphocytes |31 |> 60 y.o. |
|CML |Slow |Myelocytes |22 |Any age |
Quick Notes on Several Leukemias:
ALL:
Children/lymphoblasts
Down’s
AML:
Myeloblasts
Auer rods
CLL:
Elderly
Very similar to SLL (small lymphocytic lymphoma)
CML:
Massive splenomegaly
Philadelphia chromosome (9,22)
Acute Lymphoblastic Leukemia (ALL):
Most common type in children
Peak age – 4 y.o.
Characteristics: found in children, is most responsive to therapy and is associated w/ Down syndrome
biologically distinct
has a t(15;17) that juxtaposes the RARα gene on chromosome 17 w/ the PML gene on chromosome 15
associated w/ frequent DIC
responds to All-trans-retinoic acid
In the monoblastic type of leukemia (FAB M5) leukemic cells often infiltrate:
Skin
Gums, perianal area
CNS
Treatment: Chemotherapy bone marrow transplant
Allogeneic form causes graft vs. host disease
But graft vs. leukemia can be beneficial
Prognosis
depends on:
age of patient
cytogenetic pattern of leukemic cells
previous exposure to radiation, benzene or chemotherapy (worse)
aggressiveness of post remission therapy
Overall about 70% of adults enter complete remission
10 yr old with ALL, has clinical features:
CNS infiltration related to headaches, vomiting, and palsies
Bone pain secondary to leukemia infiltration of the marrow and periosteum
Symptoms related to bone marrow suppression, including anemia and thrombocytopenia
NOT multiple, acutely tender lymph nodes due to the central node ischemic necrosis
Same pt, white cell count reveals no neutrophils, Why?
Bone marrow has been replaced by leukemic cells
Acute Myeloid Leukemia (AML): ⋄ Think AMbuLance labs (It’s the Worst)
Most malignant type
Characteristics include: 9 FAB subtypes along myelocytic, monocytic, erythrocytic and megakaryocytic lines
Among the most aggressive malignancies of humans
If left untx’d can → death w/in 40 to 100 days from time of Dx
Most common acute leukemia in adults
Etiological factors (possible) include: ionizing radiation, chemicals such as benzene and chemotherapeutic agents
Symptoms & Signs: Petechiae, sternal tenderness, sometimes adenopathy, splenomegaly and hepatomegaly may be found, testicular, cutaneous, and meningeal involvement as well
Chronic Lymphoid Leukemia (CLL):
Least malignant type – L for Least and NODES
Older adults (average age = 60 y.o.)
Characterized by abnormal small lymphocytes in lymphoid tissue
Affects men 2-3x more than women
Presents w/ lymphadenopathy, hepatospenomegaly and few symptoms
Takes an indolent course
Increase in smudge cells in peripheral blood smear
Warm Ab autoimmune hemolytic anemia
Very similar to SLL (small lymphocytic lymphoma)
Q reads: On the basis of histo and transitions observed clinically, there appears to be a relationship between lymphocytic lymphoma and….. Lymphocytic Leukemia
Chronic Myeloid Leukemia (CML):
Think M for Massive Spleen, cMl, and Ph chroMMMMosome
Invariably fatal
Most common in young & middle-aged adults (slightly more common in men); rare in children
90% of pt have Philadelphia, or Ph1 chromosome – the long arm of chromosome 22 is translocated, usually to chromosome 9
Induced by radiation, carcinogenic chemicals
Characterized by abnormal overgrowth of granulocytic precursors (myeloblasts & promyelocytes) in bone marrow, peripheral blood & body tissues
Characterized by massive splenomegaly
Low-to-absent leukocyte alkaline phosphatase
Cells resemble nearly normal granulocytes
Two distinct phases of clinical course:
1) Insidious chronic phase – anemia & bleeding disorders
2) Blastic crisis or acute phase – rapid proliferation of myeloblasts, the most primitive granulocyte precursors
ENDOCRINE PATHOLOGY
HYPOTHALAMUS/PITUITARY
Gigantism:
Oversecretion of GH in childhood before fusion of growth plates – leads to bone growth & abnormal height
Acromegaly:
Chronic metabolic disorder caused by excessive amounts growth hormone (GH)
Endocrine etiology
Occurs after closure of the growth plates
Cause of ↑ GH secretion – usually a benign tumor of pituitary gland
“Somatotroph adenoma” of the pituitary gland in 30 yr old pt results in acromegaly
Think GH = somatotropin
Results in gradual enlargement of the body tissues – bones of face, jaw, hands, feet, & skull
Usually begins between ages 35-55
Growth plates have closed, so bone becomes deformed rather than elongated
Common findings:
Gradual marked enlargement of the head, face, hands, feet, & chest
Excessive perspiration & offensive body odor
Prognathism
Enlarged tongue
Deep voice
Dwarfism (pituitary dwarfs):
Characterized by arrested growth
Frequently pts have improperly formed or proportioned limbs & features
Caused by undersecretion of GH
Diabetes insipidus (central):
Rare condition caused by damage to hypothalamus (specifically, the supraoptic nuclei) or pituitary gland (posterior)
Due to lack of ADH (vasopressin) – produced in supraoptic nuclei (produced in the hypothalamus) & secreted by posterior pituitary
Damage may be related to surgery, infection, inflammation, tumor, or head injury
Very rarely caused by a genetic defect
Body fluid volumes remain pretty close to normal so long as the pt drinks enough water to make up for increased clearance
Polyuria, Polydipsia
Large volumes of dilute urine
High serum osmolarity
Hypernatremia – Remeber ADH just allows water to leave and doesn’t mess with Na/K pump so relatively more Na left
Marked by extreme thirst & excessive urine output caused by ADH deficiency normally limit amount of urine made
Responds to exogenous ADH therapy
Nephrogenic diabetes insipidus:
Rare disorder characterized by passage of large volumes of urine due to a defect of kidney tubules
Specific kidney defect usually a partial or complete failure of receptors on kidney tubules that respond to ADH
Excessive amounts of water are excreted w/ the urine, producing a large quantity of very dilute urine
May be present at birth as a result of a sex-linked defect (congenital nephrogenic DI)
Usually affects men (women can pass on the gene)
SIADH (Syndrome of Inappropriate ADH)
Excessive water secretion
Hyponatremia
Serum hypo-osmolarity with urine osmolarity>serum osmolarity
Causes ⋄ Ectopic ADH (small cell lung cancer), CNS disorder/head trauma, Pulmonary disease, Drugs
ADRENAL GLANDS
Addison’s disease:
Adrenal insufficiency
Chronic adrenal disorder characterized by anorexia, hypoglycemia, hypotension, and hypovolemia, and skin hyperpigmentation (increased MSH)
Primary deficiency of aldosterone and cortisol due to adrenal atrophy
Hormone deficiency caused by damage to the adrenal cortex
Aka ‘primary adrenal hypofunction’ or ‘adrenal insufficiency’
Life-threatening condition caused by partial or complete failure of adrenocortical function
May be the result of autimmune processes, infection, neoplasm, or hemorrhage in the gland
> 90% of cortex must be destroyed before obvious symptoms occur, but it does involve all 3 cortical divisions (GFR)
Characterized by
Nausea, vomiting, hypotension, and asthenia – feeling of being weak, but not really
Insidious onset of weakness, fatigue, depression hypotension & bronzing of the entire skin
Oral signs:
Consist of diffuse pigmentation of the gingiva, tongue, hard palate, & buccal mucosa = melanosis
The most common oral manifestation of Addison’s is melanosis
Pigmentation of oral tissues tends to persist – cutaneous pigmentation most likely disappears following therapy
Lab tests – low BP, low cortisol level, low serum Na+ & perhaps high serum K+
What disease is associated with Na+ secretion in the urine? ⋄ Addison’s - bc aldosterone can’t do it’s job.
ACTH test: (aka corticotropin test)
Measures pituitary gland function
*Pituitary releases ACTH which stimulates outer layer of adrenal cortex
*ACTH causes release of hydrocortisone, aldosterone, & androgen. – cortisol is most important
Used to determine if too much cortisol (Cushing’s syndrome) or not enough (Addison’s) is being produced
ACTH levels are high in Addison’s disease
Tx – cortisol administration
Distinguished by secondary insufficiency, which has no skin hyperpigmentation
Waterhouse-Friderichsen syndrome:
Catastrophic adrenal insufficiency & vascular collapse due to hemorrhagic necrosis of the adrenal cortex
Rapidly progressing infection caused by N. meningitidis
Most often found in association w/ meningococcal meningitis
Characterized by coagulopathy, hypotension, adrenal cortical necrosis, and sepsis (usually fatal)
Produces severe diarrhea, vomiting, seizures
Cushing’s disease:
Hyperfunction of the adrenal cortex
Excess ACTH production (Also High IN addison’s, trying to compensate)
From pituitary adenomas, higher CNS stimulation CRH
Or from tumors like small cell carcinoma of lung
Excess due to pituitary gland hyperplasa, adenoma, or carcinoma
Unknown cause, Iatrogenic excess, is most common
From Cushing disease (primary pituitary adenoma); increased ACTH
Primary adrenal hyperplasia/neoplasm; decreased ACTH
Ectopic ACTH production (small cell lung cancer); increase ACTH
Pulmonary neoplasm most likely to produce ACTH
Iatrogenic; decrease ACTH
Signs:
Think IRENE
Typical habitus, moon faces, buffalo hump, truncal obesity, striae, and osteoporosis
Increased body weight, edema, hypertension, osteoporosis and pathologic fractures, fatigabiliy, weakness, hirsutism, amenorrhea, ecchymosis, personality change, hyperglycemia (from insulin resistance), hyopkalemia
Dx: test urinary free Cortisol of suppression test w/ dexamethasone
Tx: aims at source – if from pituitary—surgery, radiation (gamma knife), drugs, iatrogenic—taper carefully
Hyperaldosteronism:
Primary (Conn’s syndrome):
Caused by an aldosterone-secreting tumor, resulting in HTN, hypokalemia, metabolic alkalosis, & low plasma renin
Secondary:
Due to renal artery stenosis, chronic renal failure, CHF, cirrhosis, and nephritic syndrome. Kidney perception of low intravascular volume results in an overactive renin-angiotensin system. Therefore it is associated w/ high plasma renin
THYROID
Thyroid Gland:
Secretion of T3 (triiodothyronin) & T4 (thyroxin) – controlled by pituitary gland & hypothalamus
Thyroid disorders may result from defects in thyroid gland itself, & also from abnormalities of the pituitary or hypothalamus
Hyperthyroidism (thyrotoxicosis): -- Jared Corbridge
Imbalance of metabolism caused by overproduction of thyroid hormone
Characterized by exophthalmos, tachycardia, heat intolerance, and fine tremor, warm moist skin, and fine hair
Caused by excessive production of T4 (thyroxin)
Thyroxin stimulates cellular metabolism, growth, & differentiation of all tissues
Excess leads to high basal metabolism, fatigue, weight loss, excitability, ↑ temperature, & generalized osteoporosis
Premature eruption of teeth & loss of deciduous dentition
Findings ⋄ Increased TSH if primary, increased total T4, increased T4, and increased T3 uptake
Graves’ disease (most common form):
Hyperthyroidism with thyroid-stimulating/TSH receptor antibodies
Autoimmune disease occuring most frequently in women between ages 20-40
Arises following an infection or physical/emotional stress
Symptoms:
Diffuse Goiter
Range from anxiety & restlessness to insomnia & weight loss
Eyeballs may begin to protrude (exophthalmos) causing irritation & tearing
Plummer’s disease (toxic nodular goiter):
Arises from long-standing simple/Nodular goiter & occurs most often in the elderly
Symptoms same as Graves’ disease BUT no protruded eyeballs
Risk factors: female > 60 y.o.
Never seen in children
Hypothyroidism:
Characterized by weight gain, cold intolerance, lowered pitch of voice, mental/physical slowness, constipation, dry skin, coarse hair, edema, positive nitrogen balance???—Hypothyroid pts are bigger so they keep it in, decrease in plasma bound iodine, decrease in iodine uptake by thyroid, and increased blood cholesterol
NOT Increased oxygen consumption
Another Q: Congenital hypothyroidism most likely causes delayed eruption of teeth – BUT Jared’s kid has HYPO
Underactivity of the thyroid gland
May cause a variety of symptoms and may affect all body functions
Normal rate of functioning slows down – causes mental & physical sluggishness
Considerably more common in women
Extreme hypothyroidism in adults = Myxedema
Symptoms – fatigue, slowed speech, cold intolerance, dry skin, coarse, brittle hair, puffy face
Characterized by puffiness of face & eyelids, and swelling of tongue & larynx
Skin becomes dry & rough, and hair becomes sparse
Affected individuals also have poor muscle tone, low strength, & get tired very easily
Findings ⋄ Increased TSH (sensitive test for Primary Hypothyroidism, decresed Total T4, Decreased T4, Decreased T3 uptake
Alleviated by administering thyroid hormones
Risk factors – age >50, female, obesity, thyroid surgery, & exposure of the neck to x-ray or radiation Tx
Hashimoto’s Disease:
Most common cause of hypothyroidism
Caused by an autoimmune reaction against the thyroid gland (Thyroiditis)
Common thyroid gland disorder
Production of Ab/s in response to thyroid Ag/s & the replacement of normal thyroid structures w/ lymphocytes & lymphoid germinal centers
Onset is slow – may take months or years for condition to be detected
Most common in middle-aged women & individuals w/ family Hx of thyroid disease
Estimated to affect 0.1-5% of all adults in Western countries
Less common cause – failure of pituitary gland to secrete TSH (secondary hypothyroidism)
Severe hypothyroidism in children leads to Cretinism:
Endemic cretinism occurs wherever endemic goiter is prevalent (lack of dietary iodine)
(Don’t get confused with the goiters of Grave’s and Plummers)
Sporadic cretinism is caused by defect in T4 foramtion or developmental faiulure in thyroid formation
Retardation of growth & abnormal bone development due to lack of thyroid hormone
Mental retardation is caused by improper development of the CNS
If recognized early, it can be markedly improved by use of thyroid hormones
Findings ⋄ Pot-bellied, puffy faced child with protruding umbilicus and protuberant tongue
Dental findings in child – underdeveloped Mn w/ an overdeveloped Mx, delayed eruption & retained deciduous teeth
Mental retardation, delayed growth, and delayed tooth eruption – NOT caused by lack of GH (don’t get clowned)
PARATHYROID GLANDS
1° Hyperparathyroidism
Common; major cause is an adenoma (benign tumor of glandular epithelium)
Lab findings – hypercalcemia, ↓ serum phosphate (because of diuresis), & ↑ serum ALP & serum PTH
Clinical characteristics – cystic bone lesions (osteitis fibrosa cystica or von Recklinghausen’s bone disease), nephrocalcinosis, kidney stone & peptic duodenal ulcers
43-year-old with radiolucencies (not associated with apices), and radiolucencies in humerus. Lab tests indicate elevated calcium, but serum phosphorus and alkaline phosphatase are normal. She also has giant cells in her bone lesion
Dx: hyperparathyroidism – Paget’s doesn’t have Giant Cell lesions
Signs/Symptoms
Urolithiasis/Nephrolithiasis
Elevated serum Calcium
Central Giant-cell bone lesions
Loss of lamina dura surrounding multiple teeth
NOT tetany
NOTE: Osteoporosis, giant cell granulomas, & metastatic calcification are manifestations of hyperparathyroidism
2° Hyperparathyroidism
Caused by hypocalcemia of chronic renal disease
Excessive urinary Ca2+ loss stimulates PT glands to undergo hyperplasia – due to feedback mechanism
Low calcium, high phosphate
Resulting metabolic effects are identical to those w/ 1° Hyperparathyroidism
REMBER PTH-related Peptide
3° Hyperparathyroidism
Hyperparathyroidism that persists after definitive therapy for secondary
Hypoparathyroidism
Most commonly caused by accidental surgery excision during thyroidectomy
May result in tetany (from low Ca)
Pseudoparathyroidism
Defective end-organ responsiveness to PTH
***SIDENOTE on Tetany:***
Clinical neurological syndrome characterized by muscle twitches, cramps & carpopedal spasm
When severe, larygnospasm & seizures develop
Usually associated w/ Ca2+ deficiency, Vit D deficiency or alkalosis
Associated with Parathyroid Hypofunction
Kills patient before other effects can develop
Normally occurs when blood [Ca2+] reaches approximately 6 mg% (normal is ~10 mg%) – lethal at 4 mg%
Chvostek’s sign: tapped with Chop stick
Tap the facial neve above mandibular angle, adjacent to earloble
Facial muscle spasm causing upper lip to twitch confirms tetany
Trousseau’s sign: swordfighter
Apply a BP cuff to the pt’s arm
A carpopedal spasm causing thumb adduction & phalangeal extension confirms tetany
PANCREAS
Diabetes Mellitus:
Recessive Inheritance
Metabolic disease involving mostly CHOs & lipids
Most common pancreatic endocrine disorder
Caused by absolute insulin deficiency (type 1) or resistance to insulin action in peripheral tissues (type 2)
Causes decrease in liver glycogen, hyperglycemia, glucosuria, and polyuria
Classic traid of symptoms = Polydipsia, Polyuria, & Polyphagia
Usually leads to Dehydration or Acidosis ⋄ Coma, death
Only ½ of pts are ever diagnosed
More common in blacks, especially females; American Indians
Characterized by:
Hyperglycemia, glycosuria, Hyperlipemia, and Ketonuria
Increased susceptibility to infection, increased fatigability, recessive inheritance, and polyuria
Signs & symptoms:
Non-specific—fatigue, weakness, polydipsia, polyuria, skin lesions-including fungal infections of skin & mucous MBs
Chronic Manifestations
Small vessel disease ⋄ thickening of BM, retinopathy, nephropathy
Large vessel atherosclerosis, coronary artery disease, peripheral vascular occlusive disease, gangrene, CV disease
Neuropathy
Cataracts, glaucoma
Susceptibility to infections, neuropathies, impotence, ketoacidosis, lipid metabolism abnormalities including atherosclerosis
Long term complications of poorly controlled type I diabetes:
Hyaline arteriosclerosis, Proliferative retinopathy, Nodular glomerulosclerosis, peripheral symmetry neuropathy
NOT Pancreatic Carcinoma
Hyperglycemia increase intercellular sorbitol, which is in turn associated with depletion of intracellular myoinositol levels
Diabetics are a high-risk group for the following infections:
Klebsiella pneumonia
Sinus mucormycosis
Malignant otitis externa (P. aeruginosa)
Chronic osteomyelitis
Sudden onset of a seizure in a non-compliant type I diabetic would be most likely due to hypoglycemia also from hypocalcemia – NOT from ketoacidosis
Pt takes insulin in the am, goes jogging, then comes into the dental office with symptoms of anxiety and is just not his usual self ⋄ Pt is Hypoglycemic He forgot to eat.
Hb A1c – plays role in long-term glucose control
Dx:
Fasting serum glucose, glucose tolerance, HbA1c
impaired fasting glucose is over 100 after 8 hrs of fasting and oral glucose load is over 200 after 2 hours
Tx: diet, oral hypoglycemics, insulin, weigth loss, transplantation, and vigilance for complications
Type 1 DM:
Usually diagnosed in childhood
Diminished beta-cell mass
Body makes little to no insulin
Daily injections of insulin are required to sustain life
Three etiologic mechanisms:
Viral infection, genetic predisposition, autoimmune response
|Type 1 vs. Type 2 Diabetes Mellitus |
|Characteristic |Type 1 Diabetes |Type 2 Diabetes |
|Level of insulin secretion |None or almost none |May be normal or exceed normal |
|Typical age of onset |Childhood 40 |
|Percentage of diabetics |10–20% |80–90% |
|Basic defect |Destruction of B-cells |Reduced sensitivity of insulin’s target cells |
|Associated w/ obesisty |No |Usually |
|Speed of development of symptoms |Rapid |Slow |
|Development of ketosis |Common if untreated |Rare |
|Treatment |Insulin injections, dietary management |Dietary control & weight reduction; occasionally oral |
| | |hypoglycemic drugs |
|Concordance in identical twins |50% |100% |
|Genetic predisposition |Weak, polygenic |Strong, polygenic |
|Association with HLA system |Yes (HLA DR 3 and 4) |No |
|Beta cell numbers in islets |Reduced |Variable |
|Classic symptoms of 3 Polys |Common |Sometimes |
Diabetic Ketoacidosis
One of the most complications of DM Type I
Usually due to an increase in insulin requirements from an increase in stress (i.e. infection)
Excess fat breakdown and increased ketogenesis from the increase in free FAs, which are then made into ketone bodies
Signs
Kussmaul Respirations (Rapid/deep breathing), hyperthermia, nausea/vomiting, abdominal pain, psychosis/dementia, dehydration, Fuity breath odor
Labs
Hyperglycemia, Increased H+, Decreased HCO3-, Increased blood ketone levels, leukocytosis
Complications
Life-threatening mucormycosis, Rhizopus infection, cerebral edema, cardiac arrhythmias, heart failure
Tx
Fluids, insulin, and potassium, glucose is necessary to prevent hypoglycemia
EYES
Ocular trachoma:
Eye infection caused by Chlamydia trachomatis
Incubation period of 5-12 days – begins slowly as conjunctivitis (pink eye)
If untreated, may become chronic & lead to scarring
If eyelids are severly irritated, eyelashes may turn in & rub against cornea
This can cause eye ulcers, further scarring, visual loss, & even blindness
Occurs worldwide – primarily in rural settings in developing countries (rare in U.S.)
Leading cause of blindness in developing countries
Frequently affects children, although the consequences of scarring may not be evident until later in life
Inclusion conjunctivitis:
Conjunctivitis caused by Chlamydia trachomatis
Often affecting newborns – also contracted by adults in swimming pools or during sexual contact
I wonder what happens if someone has sexual contact in a swimming pool…?
Characterized by enlarged papilla on inner eyelids & a purulent discharge
Chronic inflammation/hypertrophy of conjuctiva – forms grayish, yellowish translucent granules
Pinkeye:
Aka “acute contagious conjunctivitis”
Acute, contagious form of conjunctivitis caused by Hemophilius aegyptius
Characterized by inflammation of eyelids & eyeballs w/ a mucopurulent discharge
Keratoconjunctivitis Sicca:
Long-standing dryness of both eyes, leading to dehydration of conjunctiva & cornea
NOTE: dry eyes may be a symptom RA, SLE or Sjogren’s syndrome
Herpes conjunctivitis
Specific chemotherapy is used to tx it (NOT used to tx measles, smallpox, hepatitis, IM)
IMMUNO DISEASES
Sarcoidosis:
Characterized by immune-mediated, widespread noncaseating, non-necrotizing granulomas where TB is Caseating and elevated serum ACE levels
TB–Caseating, Necrotizing
Crohn’s disease – NON-caseating, NON-necrosis, granulomatous inflammation of the gut wall
Common in black females
GRAIN: gammaglobulinemia, rheumatoid arthritis, ACE increase, Interstitial fibrosis, Noncaseating granuloma
Associated w/ restrictive lung disease, bilateral hilar lymphadenopathy, erythema nodosum, Bell’s palsy, etc
IMMUNODEFICIENCIES (as outlined in Kaplan)
PRIMARY IMMUNODEFICIENCY DISEASES
Selective IgA deficiency:
The most common immunodeficient state
Low levels of IgA
Common variable (B lymphocyte hypogammaglobulinemia:
B cells normal, but fail to differentiate into plasma cells
Low circulating Ab levels
X-linked (Bruton’s) agammaglobulinemia:
Rare, sex-linked, & results in decreased production of Ab/s
Tx involves repeated administration of IgG to maintain adequate Ab levels in blood
IgM, IgG, IgA, IgD, IgE, & circulating B-cells are absent or deficient (T-cells are intact)
Almost exclusively affects males
Causes severe, recurrent bacterial infections during infancy (mostly pyogengic bacteria)
Results from failure of B-cells to mature & differentiate into plasma cells (which produce Ab/s)
Think B for Bruton’s, B-cell deficient, and Bacteria infections
Pre-B cells are normal – B cells are absent
Failure to mature is caused by a mutation in the B-cell protein tyrosine kinase
Tx with Giving Gamma Globulins
Normal cell-mediated immunity
Adequate host defense mechanisms exist for resistance to…virus infections (NOT bacterial or fungal)
Remember viruses are in the cell, so usually T-cell mediated
Viruses enter, start production, then MHC I is made in rER!!!!!!
MHC II, deals more with cells eating Bad bugs of bacteria
***The pt is just missing gamma globulins
DiGeorge Syndrome: T-- George
Think T for Thymic aplasia, T-cell deficiency, Tetany due to hypocalcemia – You need Vitamin D-George!!!!
Thymic hypoplasia or aplasia ⋄ Remember you’re BORN with it
Rare immunodeficiency disorder characterized by various congenital abnormalities arising late in fetal development
The causative defects occur in areas known as the 3rd & 4th pharyngeal pouches
These pouches develop into the thymus & parathyroid glands (which may be missing or underdeveloped)
Development abnormalities may also occur in the 4th branchial arch
Primary problem is the repeated occurrence of various infections due to a diminished immune system
Prone to viral & fungal infections – T cell GUYS!!!
Absence of thymus results in T-cell deficiency
These children have normal B-cells & form antibodies
They have decreased or absent delayed-type hypersensitivity
Absence of parathyroids causes hypocalcemia – leads to development of tetany
Severe Combined Immunodeficiency Disease (SCID):
Most dangerous type of congenital (inherited) immunodefieicency
Defects in lymphoid stem cells (results from failure of stem cells to differentiate properly)
Pts have neither B-cells nor T-cells
Pts are incapable of any immunological response
Children usually die before 2 y.o.
ACQUIRED IMMUNODEFICIENCY DISEASES
AIDS = acquired immunodeficiency syndrome
See HIV in virus section for more info
Caused by HIV (a lentivirus)
The viral MB contains a transMB protein, gp160
gp160 is usually detected by Western blot analysis as 2 fragments – gp41 & gp120
Characterized by a profound loss of CD4+ T cells
The virus can also infect CD4+ cells (macrophages & astrocytes)
Cellular consequences:
T cells: loss of CD4+ T cells AND decrease in response of T cells to Ag AND impaired cytokine production
B cells: steadily lose ability to mount an effective Ab response to new Ag/s
Diagnosis:
ELISA – detects Ab/s to HIV
Western blot – confirmatory tests
Associated with:
Loss of cellular immunity defenses
Alteration of Helper T/Suppressor T ratio
Increased susceptibility to opportunistic infections
Results in Opportunistic infections, i.e.:
Pneumocystis carinii
Most common cause of pneumonia in AIDS pts
Mycobacterium avium intracellulari
Malignant neoplasms:
Kaposi’s sarcoma
Non-Hodgkin’s lymphoma
NOT Bronchogenic or Testicular Carcinomas, Neuroblastoma, Rhabdomyosarcoma, or Mycosis fungoides
PHAGOCYTIC CELL DISORDERS
Neutropenias
Cyclic, Hereditary, or Acquired
Opsonic defects
Chemotactic defects
AUTOIMMUNE DISEASES
Autoimmune disorders
Mechanism or cause of autoimmune diseases is not fully known
Arise by way of:
Release of sequestered antigen
Cross rxn between exogenous and self-antigens
Loss of T-suppressor activity against autoreactive (forbidden) clones
NOT from persistant depression of the immune system
Systemic Lupus Erythematosus (SLE):
Chronic, inflammatory autoimmune disorder that may affect many organ systems (skin, joints, kidneys, heart, blood, & CNS)
Results in episodes of inflammation in joints, tendons, & other CT & organs
Appears most often between ages 10-50
90% of SLE cases are in women in late teens to 30s
May be caused by certain drugs (drug-induced lupus erythematosus) – usually reversible when medication is stopped
Disease course varies from mild episodic illness to a severe fatal disease
Symptoms vary widely in a particular pt over time:
Fever, fatigue, weight loss, arthritis, malar rash, photosensitivity, pleuritis, pericarditis, or non-bacterial endocarditis, Raynaud’s, Wire LUP (loop) lesions in kidney with immune complex deposition
NOT clubbing or cyanotic digits (Polycythemia, congenital heart disease, congestive heart failure, chronic pulmonary disease DO) – Remember Raynaud’s is just from Cold, emotion
SLE causes LSE (Libman-Sacks Endocarditis) ⋄ Valvular vegetations found on both sides of mitral valve, No embolizations
Characterized by periods of remission & exacerbation
At onset, perhaps only one organ system involved
Renal failure commonly occurs & is the usual cause of death
Severe CNS involvement may appear
Acrocyanosis (Raynaud’s phenomenon) – often associated w/ SLE
Immunosuppressive therapy and corticosteroids medication allow prolonged survival
Characteristic auto-antibodies:
Positive ANA
Anti-dsDNA & Anti-Sm Ab/s appear to be specific for SLE
Butterfly rash over cheeks & bridge of nose affects ~ ½ of pts w/ SLE – rash worsenes w/ sunlight
A more difuse rash may appear on other body parts exposed to sunlight
False positives on syphilis tests (RPR/VDRL)
Scleroderma (progressive systemic sclerosis-PSS)
Excessive fibrosis & collagen deposition throughout the body
Damage is done to small BVs
75% female
Commonly sclerosis of skin but also of cardiovascular and GI systems & kidney
NOTE: Most common characteristic lesion of rheumatic fever, scleroderma and RA is Fibrinoid degeneration
2 categories:
Diffuse scleroderma:
Associated with anti-Scl-70 antibody
Widespread skin involvement, rapid progression, early visceral invovlement
CREST: (Remember the Teradactyl)
Calcinosis, Raynaud’s phenomenon, Esophageal dysmotility, Sclerodactyly, and Telangiectasia
Limited skin involvement, confined to fingers and face.
More benign clinical course
Assoicated w/ anticentromere Ab/s – pathognomonic for CREST
Sjogren’s syndrome:
2nd most common autoimmune rheumatic disorder after RA
Occurs mainly in women (90% of patients) – mean age is 50
Characterized by diminished lacrimal & salivary gland secretion (sicca complex)
These glands have chronic inflammation caused by WBC infiltration
Usually progresses to fibrosis & atrophy of these glands
Triad of findings:
1) Associated CT disorders (e.g., rheumatoid arthritis)
Chronic arthritis
2) Xerostomia (dry mouth)
May cause rampant caries reminiscent of radiation caries (due to shift toward more acidogenic microflora)
Parotid enlargement
3) Keratoconjunctivitis Sicca (dry eyes)
All three rarely occur in one patient
Definite Dx made only when at least two symptoms are present
Occasionally the lymphocytic infiltration is massive, causing enlargement of the glands (called Mikulicz’s syndrome)
Increased risk for B-cell lymphoma
Sicca syndrome: dry eyes, dry mouth, nasal and vaginal dryness, chronic bronchitis, reflex esophagus
AMYLOIDOSIS
Amyloidosis:
Rare, chronic condition related to abnormal production of Ig by plasma cells
Characterized by deposition of amyloid protein in the extracellular space of various organs & tissues
Results in accumulation of an abnormal fibrillar scleroprotein (amyloid) which infiltrates body organs and soft tissues
In the tongue
Amyloid deposits are primarily in the stromal CT
Usually affects adults – middle-aged & older
Renal disease is often the 1st manifestation
Displays “apple-green” birefringence under polarized light w/ Congo red stain
Forms:
Primary:
Cause unknown
Associated w/ abnormalities of plasma cells (as is multiple myeloma, which may be associated w/ amyloidosis)
Typical sites of amyloid buildup – heart, lungs, skin, tongue, thyroid gland, intestines, liver, kidney, & BVs
Secondary:
Amyloidosis is secondary to another disease such as TB, RA, or familial Mediterranean fever
Amyloid buildup – spleen, liver, kidneys, adrenal glands, & lymph nodes (heart rarely involved)
Hereditary:
Affects nerves & certain organs; has been noted in people form Portugal, Sweden, & Japan
NOTE: Alzheimer’s disease, Type 2 DM, & Familial Mediterranean fever are amyloid associated conditions
Amyloid deposits characterize all of them (EX – Type 2 DM: amyloid deposits in islet cells)
TRANSPLANTATION & TUMOR IMMUNOLOGY
Graft types –
Autograft:
Surgical transplantation of any tissue from one location to another in the same individual
Type of maxillofacial bone graft with best success
Aka – autogenic graft, autologous graft, autoplastic graft or auto transplant
Isograft:
Composed of tissues taken from an individual of the same species who is genetically identical (e.g., identical twins)
Allograft:
Tissue taken from a genetically unrelated individual of the same species
Aka allogenic graft, homologous graft, or homoplastic graft
Xenograft:
Tissue from another species used as a temporary graft in certain cases, as in treating a severely burned patient
Quickly rejected but provides a cover for the burn for the first few days
In skin graft rejection, the major host response is a cell-mediated immune response (delayed type IV hypersensitivity)
Reaction Types
Hyperacute rejection
Antibody mediated due to the presence of preformed anti-donor antibodies in the transplant recipient
Occurs within minutes after transplantation
Acute rejection
Cell mediated due to cytotoxic T lymphos reacting against foreign MHCs
Occurs week after implantation
Reversible with immunosuppressants such as cyclosporine and OKT3
Primary tissue transplants, such as allogenic skin, kidney or heart, are most commonly rejected due to:
Cell-mediated immune responses to cell-surface autoantigens
Chronic rejection
Antibody-mediated vascular damage (fibrinoid necrosis)
Occurs months to years after transplantation
Irreversible
Graft vs. Host Disease
Grafted immunocompetent T cells proliferate in the irradiated immunocomprmised host and reject cells with “foreign” proteins, resulting in severe organ dysfunction
Major symptoms include a maculopapular rash, jaundice, hepatosplenomegaly, and diarrhea
Most feared consequence of graft therapy in immunodeficient pts is graft vs. host reaction
Usually occurs when graft contains its own viable lymphoid cells
Cyclosporin A has been used to control these adverse transplant events (T cell suppressor)
When a graft is rejected once & a graft from the same donor is tried, it will be rejected more rapidly the 2nd time
CONGENITAL PATHOLOGY / GENETIC DISORDERS
Penetrance:
The frequency, expressed as a fraction or percentage, of individuals who are phenotypically affected, among persons of an appropriate genotype (i.e., homozygous or hemizygous for recessives, heterozygotes or homozygotes for dominants); factors affecting expression may be environmental, or due to purely random variation; contrasted with hypostasis where the condition has a genetic origin and therefore tends to cause correlation in relatives.
Example: Autosomal dominant trait showing 50% penetance, will be phenotypically present in what percent of the offspring?
25%, because if (Aa x aa) gives 50% Aa & 50% aa, then 50% of the offspring have the right allele; but, with 50% penetrance, only 25% of all the offspring will phenotypically express the gene
Codominance
Phenotypic expression of BOTH alleles in a gene pair
Pink flower instead of white and red
Teratogens:
Teratology is the study of developmental anomalies
Chemical, physical, & biological agents that cause developmental anomalies
Susceptibility to teratogens is variable
Susceptibility to teratogens is specific for each development state
Mechanism is specific for each teratogen
Teratogens are dose dependent
Produce growth retardation, malformation, functional impairment, or death
Teratogenic agents:
Misc – Ach inhibitors, cocaine, DES, Iodide, Thalidomide
Physical agents – radiation, hypoxia, excessive CO2, & mechanical trauma
Maternal infection (‘TORCH’): Toxoplasmosis, Other agents, Rubella, CMV, and HSV
Rubella and Toxoplasmosis – Both are teratogenic
Rubella
Greatest incidence of rubella associated w/ cardiac anomalies occurs during 1st trimester
CMV
The major viral cause of birth defects in infants in developing countries
Hormones – sex hormones & corticosteroids
Vitamin deficiencies – riboflavin, niacin, folic acid, and vitamin E
Chemotherapy – used for treating malignancies
Antibiotics – mitomycin, dactinomycin, puromycin (used as chemotherapy agents)
Autosomal-dominant diseases:
Familial hypercholesterolemia:
Genetic defect characterized by abnormalities of LDL receptors
Elevated LDL owing to defective or absent LDL receptors.
Heterozygotes have cholesterol = 300 mg/dL
Homozygotes, very rare, have cholesterol of 700 mg/dL
Severe atherosclerotic disease early in life, and tendon xanthomas (classically in the Achilles tendon), myocardial infarcts may develop before age 20
Marfan’s syndrome:
Fibrillin gene mutation leading to a CT disorder:
Uncommon hereditary CT disorder resulting in abnormalities of the eyes, bones, heart, & BV
Pts are tall & thin w/ abnormally long legs & arms & spider-like fingers
Skeletal abnormalities: tall w/ long extremities, hyperextensive joints, and long tapering fingers and toes
Cardiovascular: cystic medial necrosis or aorta leading to aortic incompetence and dissecting aortic aneyrysms. Floppy mitral valve
NOT Mental Retardation
Ocular: subluxation of lenses
Familial adenomatous polyposis = familial polyposis coli
Think FAP ⋄ Familal Adenomatous Polyposis, chromosome 5, Autosomal dom, Positively will get colon cancer
Adenomatous Polyps predispose for Colon Cancer
Info found in GI tract section
Adult polycystic kidney disease:
Always bilateral, massive enlargement of kidneys due to multiple large cysts
Patients present w/ pain, hematuria, hypertension, progressive renal failure
90% of cases are due to mutation in APKD1
Associated w/ polycystic liver disease, berry aneurysms, mitral valve prolapse
Adult form is Autosomal Dominant (renal adenoma, glomerulonephritis, and 2° amyloidosis are NOT)
Juvenile form is recessive
Huntington’s disease:
Progressive neurologic disorder
Depression, progressive dementia, choreiform movments, caudate atrophy, & decreased levels of GABA & Ach in brain
Symptoms manifest affected individuals between the ages of 30 and 50…death follow 15-20 years later
Gene located on chromosome 4, (Hunting 4 Sexy Triplets), triplet repeat disorder
Wilms’ tumor = nephroblastoma
Embryonal tumor
Most common renal malignancy of childhood
Don’t Get Clowned ⋄ Neuroblastoma is most common PLAIN malignancy in children and infants
Involves one or both kidneys
Often reaches enormous size – palpable abdominal mass
Can be part of WAGR complex ⋄ Wilms’ tumor, Aniridia, Genitourinary malformation, mental-motor Retardation
Retinoblastoma
Associated with Rb gene
Embryonal tumor affecting one or both eyes
Osteosarcoma is associated w/ familial forms
Neurofibromatosis I: (von Recklinghausen’s disease)
Characterized by multiple pigmented macules of the skin
TOO reckless with you Coffee and Punch Holes in the Walls (Bone)
Has café au lait spots, neural tumors, Lisch nodules (pigmented iris hamartomas)
Also marked by skeletal disorders (dg. Scoliosis) and increased tumor susceptibility
On long arm of chromosome 17, 17 letters in von Recklinghausen
Heriditary spherocytosis:
Intrinsic, extravascular hemolysis due to spectrin or ankyrin defect
RBCs are small and round w/ no central pallor→less MB leading to increase MCHC
Osmotic fragility test used to confirm
Associated w/ gallstones, splenomegaly, anemia, and jaundice
Distinguish from warm antibody hemolysis by direct Coombs test. Hereditary spherocytosis is Coombs negative
Spheroid erythrocytes; hemolytic anemia, increased MCHC. Splenectomy is curative
Autosomal recessive diseases:
Cystic fibrosis:
Autosomal recessive defect in CFTR gene on chromosome 7
Defective Cl- channels leads to secretion of abnormally thick mucus that plugs lungs, pancreas, and liver which leads to recurrent pulmonary infections (Pseduomonas species and S. aureus)
Chronic bronchitis, bronchiectasis, pancreatic insufficiency (malabsorption & steatorrhea), meconium ileus in newborns
Increased concentration of Na+ and Cl- ion in sweat test diagnostic
Infertile in males due to absent vas deferens
Fat soluble vitamin deficiencies (ADEK)
Can present as failure to thrive in infancy
Most common lethal genetic disease in Caucasions
Treatment: N-acetylcystein to loosen mucous plugs
Glycogen storage diseases
Type I→Type VI, including von Gierke’s disease (found elsewhere in file)
Lysosomal storage diseases
Mucopolysaccaridoses
NOTE: Hunter’s is not an autosomal recessive disease
Hurler syndrome –Can’t stop GAGGING, so you HURL
Caused by a deficiency of the enzyme alpha L-iduronidase, which results in the accumulation of the mucopolysaccharides, heparin sulfate and dermatan sulfate in the heart, brain, liver, and other organs
It is characterized by dwarfism and mental retardation
Death occurs by age 10
NOTE: mucopolysaccharide is an old term for glycosaminoglycan (GAG)
Hurler syndrome is an example of the mucopolysaccharidoses, a group of inherited metabolic diseases caused by the lack of certain enzymes necessary to break down GAGs
Mucopolysaccharidoses are hereditary disorders characterized by the accumulation of GAGs in various tissues due to deficiency of one of the lysosomal hydrolytic enzymes
Sphingolipidoses = Lipid storage diseases:
***AN APPROPRIATE SIDENOTE (you’ll see)***
Reticuloendothelial system (mononuclear phagocyte system):
Composed of monocytes & macrophages located in reticular conntect tissue (e.g., spleen)
Functional, rather than an anatomical system involved in defense against infection & disposal of breakdown products
Constitutes all phagocytic cells of body (except granulocytes) including the cells present in bone marrow, spleen, & liver
EXs:
Microglia = macrophages of the CNS
Kupffer cells = phagocytic cells found within the sinusoids of the liver
Alvoelar macrophage (dust cells) = macrophages fixed in alveolar lining of lungs (aka: reticulum cells of the lungs)
Histiocytes = fixed macrophages in CT
Disorders of the Reticuloendothelial system: ⋄ ALSO LIPID STORAGE DISEASES
Gaucher’s disease – caused by deficiency of glucocerebrosidase
Niemann Pick disease – caused by a deficiency of sphingomyelinase (die w/in a few years)
Tay-Sachs disease – caused by deficiency of hexosaminidase A (rapidly fatal)
All are considered Lipid Storage Diseases
Liposes
Diseases (lipid storage disease) caused by abnormalities in the enzymes that break down (metabolize fats)
They result in a toxic accumulation of fat-by-products in tissues:
Series of disorders due to inborn errors in lipid metabolism – result in abnormal accumulation of lipids
The 4 diseases discussed here are most common in people of Eastern European Jewish (Ashkenazi) ancestory
Tay-Sachs disease:
Tay SaX lacks heXosamididase A (YOU HAVE SACHs of GANGLIOSIDES)
Deficiency of hexosaminidase A leads to accumulation of gangliosides in brain & nerve tissue
This abnormality of fat metabolism in nerve cells causes CNS degeneration
Is an Autosomal recessive hereditary disorder in which the deficiency of the enzyme hexosaminidase A results in the accumulation of gangliosides especially in neurons
Is associated with an inborn error of metabolism involving a specific enzyme which normally degrades gangliosides in the gray matter
Characterized by progressive mental retardation, blindness, convulsions, & ultimately death by age 4
Niemann-Pick disease:
No MAN PICKs his nose with his SPHINGer
Caused by a genetic defect in sphingomyelinase
Deficiency leads to accumulation of sphingomyelin in brain, spleen, & liver
Also causes mental retardation & early death – by age two
Fabry’s disease:
The only sphingolipidosis that is not autosomal recessive (No, I don’t know which category it fall under)
Very rare, inherited & extremely painful systemic disorder related to deficiency of α-galactosidase
Characterized by glycolipid accumulation in body tissues
Gaucher’s disease:
Rare, inherited, potentially fatal disorder
Deficiency of glucocerebrosidase leading to accumulation of glucosylceramide in lysosomes of certain cells
Others: Albinism, alpha-1-antitrypsin deficiency, phenylketonuria (PKU), thalassemias, sickle cell anemias, infant polycystic kidney disease, hemochromatosis
PKU
Occurs because pt cannot convert Phenylalanine to Tyrosine
(Due to deficiency of Phenylalanine Hydroxylase)
X linked recessive:
Female carriers of X-linked recessive disorders rarely affected due to random inactivation of X chromosomes in each cell
Type of disease inherited through the mom while she is not affected ⋄ X linked recessive
Fragile X syndrome:
X linked defect affecting the methylation and expression of the FMR1
2nd most common cause of genetic mental retardation (most common is Down syndrome)
associated w/ macro-orchidism (enlarged testis), long face w/ a large jaw, large everted ears, and autism
Duchenne’s muscular dystrophy:
Frame shift mutation causes deletion of dystrophin gene and accelerated muscle breakdown
Onset occurs before 5 years of age
Dystrophin protein is absent (Think D for Duchenne’s, Deleted Dystrophin, and muscle Decrease)
Usually presesnt in muscle cell MBs (but it’s coded for on the X chromosome)
Weakness begins in pelvic girdle muscles and progresses superiorly
Pseudohypertophy of calf muscles due to fibrofatty replacement of muscle; cardiac muscle
Use of Gowers’ maneuver, requiring assistance of the upper extremities to stand up, is characteristic (indicates proximal lower limb weakness)
Others: Hemophilia A & B, Fabry’s, G6PD deficiency, Hunter’s, Ocular albinism, Lesch Nyhan (Gout – hyperuricemia), Bruton’s agammaglobulineia, Wiskott-Aldrick syndrome
Disorders of Chromosome Number or Structure:
Down syndrome (Trisomy 21):
Most common chromosomal disorder and cause of congenital mental retardation.
Flat facial profile, simian crease, congential heart disease, prominent epicanthal fold, Duodenal atresia, Alzheimer’s disease for people > than 35, increase risk for acute lymphoid leukemia (we ALL go DOWN)
Think D for Drinking age (21) and Down’s, and Decreased AFP – DOWN’s
Causes:
95% due to meiotic nondisjunction of homologous chromosomes, associated w/ advanced maternal age (from 1:1500 in women < than 20 to 1:25 in women > than 45)
4% due to rebersonina translocation
1% due to down mosaicism (no maternal association)
Edwards’ syndrome: (Trisomy 18)
Mental retardation, rocker bottom feet, low-set ears, micrognathia, congenital heart disease, clenched hands (flexion of fingers), prominent occiput
Death usually occurs w/in 1st year
Think E for Election age (18)
Patau’s syndrome: (Trisomy 13)
Severe mental retardation, microphthalmia, microcephaly, cleft lip/palate, abnormal forebrain structures, polydactyly, congenital heart disease
Death occurs w/in 1 year
Think P for Puberty age (13)
Cri-du-chat syndrome: congenital deletion of short arm of 5 (46, XX or XY, 5p–)
Microcephaly, severe mental retardation, high pitched crying/mewing, cardiac abnormalities
Think Cry of the Chat (high pitched crying)
DiGeorge’s syndrome
More info elsewhere in file
Results from a deletion of chromosome 22q11
|TRISOMY DISORDERS |
|Disorder |Incidence |Abnormality |Description |Prognosis |
|Trisomy 21 |1/700 births |Extra chromosome 21 |Delayed physical & mental development; many |Affected people generally |
|Down syndrome | | |physical abnormatlties. Small head w/ broad & |live until their 30s or 40s |
| | | |flat face, slanting eyes & a short nose. Enlarged| |
| | | |tongue, small & low-set ears. Heart defects are | |
| | | |common | |
|Trisomy 18 |1/3000 births |Extra chromosome 18 |Facial abnormalities combine to give the face a |Survival > a few months is |
|Edward’s syndrome | | |pinched appearance. Small head & malformed, |rare; severe mental |
| | | |low-set ears |retardation |
|Trisomy 13 |1/5000 births |Extra chromosome 13 |Severe brain & eye defects are common |> 20% survive beyond 1 year; |
|Patau’s syndrome | | | |severe mental retardation |
Think Johnny DEP
D – Trisomy 21 (21 Jump Street)
E – Trisomy 18 (Edward Scissorhands)
P – Patau Pan (Finding Neverland) – uh…Trisomy 13…
Disorders of Sex Chromosomes:
Sex-linked Dominance
Male with x-linked dominant condition has daughters with an unaffected partner, what percentage of the daughters will be affected = 100%
Klinefelter’s syndrome (male XXY):
Infant appears normal at birth – the defect usually becomes apparent in puberty when 2° sex characteristic fail to develop
Hypogonadism, eunuchoid body shape, tall, long extremities, gynecomastia, female pubic hair distribution
Common cause of hypogonadism seen in infertility workups
Boys tend to be tall w/ long legs
Disorder is associated w/ advanced maternal & paternal age
Person frequently has mild retardation
Diagnosed by presence of inactivated X chromosome (Barr body)
Normal Females and Klinefelter Males Have 1
Turner syndrome (female XO):
Birth defect caused by the absence or defect of an X chromosome (sex chromosome)
Chromosome just looks like 45,X, and NOT 45.Y
Short stature, webbing of neck skin, absent or retarded development of 2° sex characteristics at puberty, absence of menstruation, coarctation of the aorta, and bone & eye abnormalities
Inhibits sexual development & usually causes infertility
Most common cause of amenorrhea
No Barr body (XO) Think Hugs and Kisses XO from Tina Turner
The embryo develops into a female, because to become a male, a Y chromosome is necessary
A condition of just a Y with no X would be incompatible with life
Diagnosed
Either at birth (due to associated anomalies) or puberty (absent or delayed menses & delayed sexual development)
With Karyotyping
Double Y male (male XYY)
Phenotypical normal, very tall, severe acne, antisocial behavior
Seen in 1-2% of XYY males
Observed in higher frequency among inmates of penal institutions
Pseudohermaphroditism:
disagreement between the phenotypic (external genitalia) and gonaldal (testes vs. ovaries) sex
Female (XX): ovaries present, but external genitalia are virilized or ambiguous
Due to excessive and inappropriate exposure to androgenic steroids during early gestation
Male (XY): testes present, but external genitalia are female or ambiguous
Most common form is testicular feminization which results from maturation in androgen receptor gene, blind end vagina
True hermaphrodite:
46 XX, 47 XXY: both ovary and testicular tissue present; ambiguous genitalia
5-alpha deficiency: unable to convert testosterone to DHT. Ambigous genitalia until puberty, when increased testosterone causes masculinzation of genitalia. Testosterone/estrogen levels are normal; LH is normal or increase
RANDOM STUFF
Infection terminology:
Contagious – highly communicable
Subclinical – unapparent; only detected by demonstrating a rise in Ab titer (rising is the most reliable finding) or isolating the organism
Latent state – absence of symptoms until a reactivation occurs
Chronic carrier – organisms continue to grow w/ or w/out producing symptoms in the host
Pandemic – worldwide distribution
Endemic – constantly present at low levels in a specific population and with low incidence of infection
Epidemic – occurs much more frequently than usual
Swelling
In an autopsy, cellular swelling (a commonly observed tissue change, is of little practical diagnostic imporance
Cloudy swelling:
Early degenerative change characterized by increase cytoplamsic granularity & increased size
Swelling of cells due to injury to MBs affecting ionic transfer; causes an accumulation of intracellular water
Shy-drager syndrome (multiple system atrophy)
Rare degenerative condition w/ symptoms similar to Parkinson’s – pt may move slowly, be tremulous, & have shuffling gait
Wiskott-Aldrich syndrome (aka immunodeficiency w/ eczema & thrombocytopenia):
Affects only boys
Characterized by defective B-cell & T-cell functions, Just like SCID mouse
Clinical features – thrombocytopenia w/ severe bleeding, eczema, recurrent infection, & increased risk of lymphoid cancers
Ataxia-telangiectasia:
Inherited disorder that affects many tissues & body systems
Multiple symptoms – telangiectasis (dilation of capillaries), ataxic (uncoordinated) gait, infection prone, defective humoral & cellular immunity, & increased risk of malignancies
Most obvious symptoms – multiple easily visible telangiectases in the sclera & skin areas such as ear & nose, graying of the hair, & irregular pigmentation of areas exposed to sunlight
Decreased coordination of movement (ataxia) in late childhood
Hyper-IgE syndrome (Job syndrome): -- JOB even got ALLERGIES
Immunodeficiency disorder characterized by very high levels of IgE Ab/s & repeated infections (commonly w/ S. aureus)
Tx – continual administration of Abx
Calcification abnormalities:
Metastatic calcification:
Calcification occurring in nonosseous, viable tissue – stomach, lungs, & kidneys
Cells of these organs secrete acid materials & under certain conditions in instances of hypercalcemia, the alteration in pH seems to cause precipitation of calcium salts at these sites
Occurs particularly in hypercalcemia, hyperparathyroidism & hypervitaminosis D, NOT hypoparathyroidism
Pathologic calcification:
Calcification occurring in excretory or secretory passages as calculi (in tissues other than bone & teeth)
Eggshell calcification:
Thin layer of calcification around an intrathoracic lymph node, usually silicosis, seen on a chest radiograph
Dystrophic calcification:
Deposition of calcium in dying or dead tissues
Occurs in degenerated or necrotic tissue, as in hyalinized scars, degenerated foci in leiomyomas, & caseous nodules
Secondary to disease of affected tissue
NOT associated w/ high blood calcium levels
Unlike Metastatic Calcification
Calcinosis:
Presence of calcification in or under skin – often associated w/ scleroderma & sometimes dermatomyositis
Staghorn stones:
Occupy renal pelvis & calyces – big stones!
Hematuria:
Blood in urine – should never be ignored!!
Usually caused by kidney & urinary tract disease
Exceptions:
Women – blood may appear to be in urine when it is actually from the va-jay-jay
Men – blood mistaken for urinary bleeding is sometimes a bloody ejaculation due to prostate problems
Children – coagulation disorders (e.g., hemophilia) or other hematologic problems (e.g., sickle cell disease, renal vein thrombosis, or thrombocytopenias) can be underlying reasons for newly discovered blood in urine
Kidney disease following strep throat is a classic cause of hematuria
Hematemesis:
Vomiting of bright red blood – indication rapid upper GI bleeding
Commonly associated w/ esophageal varices (common in alcoholics) or peptic ulcers
Hemoptysis:
Coughing up blood from respiratory tract
Blood-streaked sputum often occurs in minor upper respiratory infections or in bronchitis
Can also be seen in pts suffering from tuberculosis, lobar pneumonia (Diffuse, rusty sputum, S. pneumoniae), or bronchogenic carcinoma (NOT emphysema)
Also can be seen in pts w/ a pulmonary embolism
Hemoptysis is the main symptom of idiopathic pulmonary hemosiderosis (iron in the lungs)
Glucosuria:
Presence of glucose in urine – common in diabetes
Ketonuria:
Presence of ketones in urine – produced by starvation, uncontrolled diabetes, usually Type I, & occasionally alcohol intoxication
Proteinuria:
Presence of protein in urine – usually a sign of kidney disease
Accumulation of endogenous pigments:
Bilirubin
Hemosiderin
Iron containing protein derived from ferritin, which is an iron storage protein
Melanin – formed from tyrosine, synthesized in melanocytes
Increased melanin pigmentation – seen in Addison’s disease
Decrease melanin pigmentation – seen in albinism & vitiligo, and PKU
Histiocytosis X (aka Langerhans Cell Histiocytosis & Differntiated Histiocytosis)
FIXED macrophages
Group of disorders in which histiocytes (scavenger cells) proliferate, esp. in bones & lung, often causing scars to form
Characterized by abnormal increase in # of histiocytes – includes monocytes, macrophages, & dendritic cells
Eosinophilic granuloma:
Most benign form
More common in males ~20 y.o.
May be totally asymptomatic – there may be local pain or swelling
In the mouth, Mn is most likely affected – loose teeth on affected side w/ signs of gingivitis
Letterer-Siwe disease:
Affects infants (< 2 y.o.) – fatal
Child develops a skin rash w/ persistent fever & malaise
Anemia, hemorrhage, splenomegaly, lymphadenopathy, & localized tumefaction over bones are usually present
Oral lesions are uncommon
Hand-Schuller-Christian disease:
Occurs early in life, usually before 5 y.o. – more common in boys
Triad of symptoms – 1) exophthalmos, 1) diabetes insipidus, 3) bone destruction (skull & jaws are affected)
Oral signs – bad breath, sore mouth, & loose teeth
Treatment – radiation & chemotherapy (poor prognosis)
Habermann’s disease:
Is not an example of Histiocytosis X
Sudden onset of a polymorphous skin eruption of macules, papules, & occasionally vesicles w/ hemorrhage
Polymyalgia rheumatica:
Condition causing severe pain & stiffness in muscles of neck, shoulders, & hips
Hydatidiform Mole
A pathologic ovum (“empty egg” – ovum with no DNA) resulting in cystic swelling of chorionic villi and proliferation of chorionic epithelium (trophoblasts)
Most common precursor of choriocarcinoma
High beta HCG
“Honeycombed uterus, cluster of grapes appearance
Genotype of a complete mole is 46, XX and is purely paternal in origin (no maternal chromosomes); no associated fetus
Partial mole is commonly triploid or tetraploid.
Uterine Pathology
Endometriosis
Non-neoplastic endometrial glands/stroma in abnormal locations outside the uterus
Characterized by cyclic bleeding from ectopic endometrial tissue resulting in blood-filled, chocolate cysts
Ovary is most common site
Clinically is manifest by severe menstrual related pain
Often results in infertility
Endometrial Hyperplasia
Abnormal endometrial gland proliferation usually caused by excess estrogen stimulation
Increased risk for endometrial carcinoma
Most commonly manifest clinically by vaginal bleeding
Endometrial Carcinoma
Most common gynecologic malignancy
Peak age is 55-65
Clinically presents with vaginal bleeding
Typically preceded by endometrial hyperplasia
Risk factors ⋄ prolonged estrogen use, obesity, DM, and HTN
Polycystic Ovarian syndrome
Increased LH due to peripheral estrogen production leads to anovulation
Manifest clinically by amenorrhea, infertility, obesity, and hirsutism
Tx with weight loss, OCPs, gonadotropin analogs, or surgery
Leiomyoma (See “Neoplasm’ section)
Leiomyosarcoma (See “Neoplasm’ section)
Breast Disease
Fibrocystic Disease
Presents with diffuse breast pain and multiple lesions, often bilateral
Bx shows fibrocystic elements
Usually does not indicate increased risk for CA, although it is a risk factor
Histological types
Cystic – fluid filled
Epithelial Hyperplasia – Increase in number of epithlelial cell layers in terminal duct lobule, Increase risk for CA
Fibrosis – Hyperplasia of breast stroma
Sclerosing – Increased acini and intralobular fibrosis
Benign Tumors
Cystosarcoma phyllodes – large, bulky mass of CT and cysts, breast surface has “leaflike” appearance (“I love Fall”)
Fibroadenoma – most common tumor ................
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