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PathologyGeneral PathologyAbscess and PusPusComposed of two phasesSolid: live/dead polymorphs, macrophages Bacteria/causative agent (eg irritant chemicals) Dead human cells Fluid: contains exudate Immunoglobulins (for opsonisation - 1IgG, 2IgM) Complement - chemotaxis, anaphylaxis, opsonisation Clotting factors Inflammatory mediators AbscessLocalised collection of pus If loculated = pus, if free = empyema Wall composed of granulation tissue "pyogenic membrane" Natural history is to dischage through line of least resistance enzymes released from polymorphs/macrophagtes break down long chain molecules increases osmotic pressure (as more molecules) Swells pus collection Discharges Agenesis Aplasia AtrophyAgenesisComplete failure of organ to develop (at all)Di George syndrome - failure of developement of third and fourth pharyngeal pouches (leads to no thymus and parathyroid glands) ?AplasiaFailure to attain size or function - recognizable tissue that has failed to fully developBiliary atresia - failure to develop a lumen within the biliary tree! ?AtrophyReduction in normal cell size or number. (Cf hypertrophy - increase in size, hyperplasia - increase in number) Physiological Childhood: thymus, umbilical vessels Adulthood: Menopausal uterus/vagina Pathological Starvation, ischaemia, disuse (immobilizationAmyloidosisAmyloidFamily of extracellular proteins composed of B-pleated sheets Mammalian systems have no enzyme to degrade these compounds (similar to silk ligatures) Have apple-green birefringnce on polarised light after staining with Congo redClassificationALAmyloid Lymphocyte origin: Primary amyloidSoluble precursor Ig light chains (esp from myeloma)Heart: restrictive cardiomyopathy Nerves: neuropathy Skin: may result in carpal tunnel syndrome AASecondary/Reactive amyloidFrom chronic conditions - macrophages secrete ILs that stimulate hepatocytes to secrete serum amyloid precursor protein (SAA)Kidney: walls renal arteries, GM, BM Liver: in sinusoidal space of Diss Spleen: forms"sago spleenChronic infection: TB, syphillis, leprosy Chronic inflammatory diseases: RhA, Crohns, UC Neoplasms: Hodgkin's, renal cell carcionoma AH/ABOccurs with Alzheimer's disease with APP as precursor AnaemiaRed cell precursorsMyeloblasts Myelocytes Early normoblasts Late normoblasts Reticulocytes? ?AnaemiaMicrocyticNormocytic Macrocytic Iron deficiency anaemia Haemolytic Anaemia of chronic disease B12 (3 year stores in liver - functions as co-enzyme) / Folate (3 months stores - used to produce methionine from homocysteine) Alcoholism (leading to B12, folate), liver damage Thyroid disease Renal failure ????Megaloblastic AnaemiaMegaloblast = abnormal nucleated cell not usually?found in the body, present in BM and occasionally?found in peripheral bloodB12Functions as co-enzyme to produce methionine from tetrahydrofolate?3 years storeDeficiency in (1) Pernicious anaemia GPC antibodies (2) partial/total gastrectomy (3) failure to absorp from terminal ileumFolateTetrahydrofolate used to form methionine from homocysteine3 months store in liverDeficiency (1) inadequate intake?or excess demand in pregnancy (2) vegans (3) drugs which have an anti-folate action???Haemolytic anaemiaCongenital Membrane abnormalities: spherocytosis (spectrin), elliptocytosis, abetalipoproteinaemia Abnormal Haemoglobinopathies: SCC, HbC, HbD, thalassaemia Enzyme deficiency: G6PD, pyurvate kinase, glutathione synthetase deficiency Acquired Immune Mechanical - artificial heart valves, microangiopathic haemolytic anaemia Diagnosis: low Hb, normochromic normocytic - macrocytic (raised Red cell distribution width) Raised reticulocyte count Excess unconjugated bilirubin ?Haematocrit Proportion of total blood volume that consists of red cellsExpressed as percentage / fractionNormally = 0.4 - 0.45Determines oxygen-carrying capacity of bloodDetermines blood viscosity ?DeterminantsRed cell volume Blood loss Plasma volume Loss of water Plasma expansion - pregnancy AsbestosOccupations associated with asbestos exposureshipworkers Builders Clinically significant asbestosWhite asbestos (Chrysotile) 90% asbestos used in industy Long woolly fibres: associated with fibrosis Blue asbestos (Crocidolite) Straight short fibres: associated with malignancy, fibrosis (penetrate more deeply into lungs and are associated with greater pathology) Brown asbestos (Amosite) Straight long fibres: associated with fibrosis Asbestos-related diseasesCa Bronchus (esp blue/crocidolite) Malignant mesothelioma Asbesosis - fibrotic lung disease Chronic bronchitis? ?AscitiesAscitiesAbnormal free fluid within the peritoneal cavity?Transudate: Hydrostatic: cirrhosis, right heart failure, Budd-chiari (hepatic vein obstruction) Oncotic: loss of protein (starvation, liver failure, nephritic/nephrotic syndrome) Exudate:?Inflammatory: peritonitis, pancreatitis, malignancy Atheroma / atherosclerosisAtheromaAccumulation of lipid within the intima of large and medium sized arteriesAeitological factors:hypertension, smoking, hyperlipidaemia, DM, hereditary factors?ComplicationsIschaemia Infarction (from progressive occlusion, rupture of plaque leading to thrombosis, haemorrhage into plaque) Embolus Aneurysm? Blood cellsPolymorphonuclear leucocytes are classed as neutrophils, basophils and oesinophils.NeutrophilsPolysegmented nuclei (hypersegmented in B12/folate deficiency) Clear cytoplasm with fine granules (contain elastase, protease, A1AT, lysosyme, lactoferrin) Close relation with acute inflammation BasophilsUnlobulated or bilobate nuclei Granules contain histamine, eosinophil chemotactic factor, slow-releasing substance of anaphylaxis Close relation with allergic reactions/anaphylaxis EosinophilsBilobed nuclei Bright eosinophilic granules contai: major basic protein, eosinophil cationic protein Close relation with parasitic infections PlateletsAdhese to vessel wall in presence of Von Willebrand factor leading to shape change and degranulation Aggregates with contraction to form solid mass in vessel Releases PGs, serotonin, TXs ?Giant CellsNormal Osteoclasts Syncytiotrophoblasts Megakaryocytes Skeletal muscle cells Oocytes Abnormal Macrophage and related giant cell Virus induced Tumour giant cells (Reed-sternberg cells in Hodgkin's = modified B lymphocytes)CalcificationCalcificationOrthotopic Bone / teeth Otoliths Heterotopic Metastatic: occurs as a result of hypercalcaemia, in regions that secrete acid (lung CO2, Kidney, stomach) Dystrophic: occurs in dead or damaged tissues in the presence of a normal circulating calcium concentration - atheroma, scars, aortic valve CalculiCalculiAbnormal mass of precipitated solid material in a duct Prostatic (commonest: most TURP and prostatectomy specimens have calculi) Biliary Urinary Pancreatic Salivary Principles of formationFlow Stasis Wall Constituents Nidus (desqumated cells, secretion, infection) Increased colloid / reduced solvent Change in pH Complications of Calculi(Depends on site and size) ObstructionHaemorrhageInfectionStricturePerforationMetaplasia/Malignant changeCellulitis / Erysipelas / Nec fascititisClinical differentiation?ConditionPathology OrganismsManagementCellulitisInfection of the skin and underlying subcutaneous tissuesStaph aureus / epidermidis Streptoocci HistorySwabIV antibiotics - benpen/fluclox or clindamycin/erythromycin (if penicillin allergic) ErysipelasA form of cellulitisOccurs in immunocompromised, young, old Lancefield A B-haemolytic streptococci ?Necrotising fascititsNecrotising process of the deep fasciaFormsFournier's gangrene (of the scrotum)? Lancefield A B-haemolytic streptococci ResuscitationBlood cultures / wound swabAntibioticsRadical tissue debridement?Complement CascadeThe Complement systemImportant mechanism to control infection Promotes phagocytosis Involved in bactericidal mechanisms Promotes lymphocyte function Mediates inflammation through mast cell degranulation and chemotaxis ?Classical pathwayAlternate pathway ?IgG or 2 IgM fix to cell membrane C1q binds to long chains and then to C1r and C1s Whole activates C4 and C2. C2,4 cleaves C3 into components C3a is chemotactic and anaphylactic. C3b is an opsonin and also acts with C2,4 to cleave C5 C5a is chemotactic and anaphylactic. C5b binds with C6, C, C8 and C9 to form membrane attack complex ?C3 activated directly by endotoxins, viruses, bacteria, fungi Does not need immunoglobulin activation CoronerDeaths that must be reported to the coronerSuspicious or Unnatural Death unknown Violent / unnatural Suicide Due to abortion In detention / custody Ill treatment, starvation or neglect Medical Death within 24 hours of hospital admission Due to medical intervention (of any sort) During operation or before recovery Not been seen by certifying doctor after death or within 14 days before death Industrial Industrial disease or related to deceased employment Service disability pensioners CystCystAbnormal fluid-fillled space (lined with epithelial cells) - cf pseudocyst (filled with granulation tisse - pancreatic)?Pathological process involvedCongenital Thyroglossal Branchial Biliary Polycystic kidney disease Inflammation Infection - ameoba, cysticercosis, hydatid Obstruction - spermatocoele, meiboniam cyst, epipdydimal Degeneration Bone - osteoarthritis Cerebral cysts post infarction Implantation Epidermal / dermal Hyperplasia Breast cysts Neoplastic Ovarian cysts Cystic neoplasms of the pancreas DiverticulaDiverticulumAbnormal outpouching of a hollow visucs into surrounding tissues ClassificationTrue and False True: all components of the viscus (tend to be congenital) False: Only part of wall represented (tend to be acquired) - eg. sigmoid colon diverticulum, pharyngeal diverticulum through Killian's dehiscence between thryopharyngeus and cricopharyngeus msucles (components of the inferior pharyngeal constrictor) Congenital or acquired Eg. Meckel's diverticulum - 2inches long, 2ft from ileocaecal valve, 2% population# Duodenal diverticula Pulsation and traction ComplicationsGeneral Inflammation Haemorrhage Perforation Function Ectopic secretion of peptic acid, as in Meckel's diverticulum "Blind loop" syndrome - causing vitamin deficiencies secondary to bacterial overgrowth Cellular Metaplasia, as a bladder diverticulum Malignant change as in bladder diverticula Erosion UlcerErosionPartial loss of epithelial or mucosal surface that heals by resolution (ie. replacement by fully functional tissue) Ulcer Full thickness loss of epithelial or mucosal surface which heals by repair (replacement with fibrous tissue) with or without resolution Factors affecting rate of healing of ulcer Local Persisting cause (acid secretion, continuing infection, continuing sepsis) Persisting inability to detect damage (hypoasthesia, anaesthesia) Poor blood supply - ischaemia Neoplastic process (ulcerated carcinoma) Systemic Malnutrition Immune deficienc: diabetes, AIDS GoutPurines (adenine, guanine) are metabolised to hypoxanthine changed by xanthine oxidase to xanthine Further metabolised to uric acid Pyrimidines (thymine, cytosine) are metabolised to ammonium salts + urea. Nucleoside = Base + ribose: Eg. RNANucleotide = Base + ribose + phosphate radical?Classification of hyperuricaemiaPrimary: absolute/relative abnormality of xanthine-hypoxanthine handling Deficiency of PPRT (Lesch-Nyhan syndrome) leads to inability of xanthine/hypoxanthine to be recycled into purines Secondary: increased purine breakdown with increased formation of uric acid Ingestion - caviar, roe Increased cell turnover: psoriasis, sickle cell, leukaemia, malignancy Decreased excretion: CRF, diuretics Complications of goutJoints: destructive osteoarthropathy Renal tract? - stones, renal failure from a big stone FistulaFistulaAbnormal connection between two epithelial surfaces ?ClassificationSimple / Complex (associated with abscess cavity) Anatomy Respiratory: Bronchopulmonary fistula, tracheo-oesophageal GI tract: tracheo-oesophageal, enterocutaneous, perianal Urinary tract: entero-vesical fistula, urethrocutaneous (in circumcision) Reproductive tract: Entero-vaginal fistula Circulation system: arterio-venous fistula, AAAs Salivary gland fistula (following parotidectomy) High output (>500mls/day) or Low output Associated electrolyte disturbance / fluid disturbance Associated malnutrition & sepsis Aetiology Trauma/iatrogenic (AV fistula, post surgery, tracheostomy, earings) Inflammatory (IBD) Sepsis (from anastamotic leaks, abscesses) Malignancy Radiotherapy ExamplesEarings Perianal fistula Enteric fistula (Crohn's disease) Factors controlling healingLocal Persisting cause / material Persisting sepsis Persisting flow through fistula Width of fistula Ischaemia Epidermidisation of track Malignant change Systemic Nutrition, vitamin deficiency Immunosuppression - DM, AID ?Principles in ManagementHope Hospital protocol - SNAP - Sepsis / Nutrition / Anatomy / Proceed Sepsis Remove cause Drain abscess cavities Avoid antibiotics Skin protection Nutrition to promote healing Restrict / control fluid intake (determines output of fistula) Total Parenteral nutrition / distal enteral nutrition Anatomy Fistulography Bowel enema CT / MRI: define abscess cavities Procedure (1) excision - karydakis procedure (2) laying open (3) seton to cut through tract Haemoglobinopathies????HaemoglobinopathyPathology Blood picture Complications Sickle cell diseaseSingle amino acid substitution on B-chain at position 6 of valine for glutamic acidAutosomal co-dominant: homozygotes have 90-100% HbS, heterozygotes have 20-40%? Normochromic Microcytic anaemia Sickled cells Reticulocytosis Features of splenic atrophy (target cells, acanthocytes, Howell-Jolly bodies) Haemolytic anaemia results in cardiac failure Pigment gallstones Thrombosis and infarction - abdomen, chest, splene, bone Infection - salmonella osteomyelitis, pneumococcal sepsis ThalassaemiaDefective globin chain synthesis - causes abnormal haemoglobin production Alpha Thalassaemia - China, Asia, Africa Beta Thalassaemia - Mediterranean, Middle East Hypochromic microcytic anaemia Reticulocytosis Target cells Nucleated red cells Increased haemoglobin F Marrow hyperplasia Iron overload (cirrhosis, endocrine disturbance, pancreatitis) Hypersplenism - decreased red cell survival time, leucopaenia, thrombocytopenia HamartomaHamartomaTumour-like malformation composed of haphazard arrangement of different amounts of tissues normally found at that site ("error") No tendency for lesion to grow other than normal growth controls of the body ?ExamplesHaemangiomas Peutz-Jegher's polyp of bowel Bronchial hamartoma Melanocytic naevi Neurofibromatosis Tuberous Sclerosis? Morbidity from HamartomaObstruction Pressure Infection Infarction Haemorrhage Fracture? HerniaHerniaProtusion of a viscus or tissue from the body compartment in which it normally resides into another body compartment ClassificationCongenital / acquired Complete / partial Complete: inguinal, femoral Partial: Richters, sliding gastric Predisposing featuresIncreased donor compartment pressure Abdomen: inguinal, femoral, obturator, diaphragmatic, hiatus Brain: ICP - brain herniation? Weakness of tissues with normal pressure in donor compartment Incisional hernia: poor technique, nutrition ComplicationsObstruction Ischaemia / infarction Pressure effects rupture? Hyperplasia & hypertrophy?HyperplasiaHypertrophy?DefinitionIncrease in number, number, number, number, number of cells?Increase in?SIZE?of cells?PhysiologicalBreast in pregnancyThyroid in pregnancyPituitary in pregnancy (cf Sheehan's syndrome)?Uterus in pregnancySkeletal muscle with exercise?PathologicalOverstimulationGraves diseaseAdrenals in CushinsEndometrium in oestrogen excessOverstimulationGraves diseaseCardiomyopathiesCongenital muscular dystrophies??Inflammatory MarkersClassification of inflammatory mediatorsSubstances stored irrespective of need and released when requiredHistamineSerotoninSubstances synthesized in cells as required when inflammatory events dictateLeucotrinesProstaglandinsCytokinesCascades that are activated as part of the inflammatory responseClotting cascadeComplement cascade - opsonins, chemoattractants, anaphylactic agentsKinin cascade?Prime plasma-derived mediators in acute inflammationFibrin-related peptides and plasminKallikrein and bradykininC3a C5a?CRPC-reactive proteinHalf-life ~6hoursMarker of acute inflammationProtein derived produced in liverFunctionally similar to IgG (but not specific) Ischaemia & InfarctionIschaemiaAbnormal reduction in blood supply to or drainage from an organ or tissueInfarction is the result of cessation of the blood supply to or drainage from an organ or tissue?Classification of causesLocalArterial obstruction: thrombus, embolus, artheroma, pressure, spasmVenous: thrombus, pressure, stasisCapillary obstruction: vasculitis (meningococcal septicaemia, drugs), obstruction (sickle cell)External pressureGeneralHypoxaemiaAnaemiaV/Q defect?Factor determining the extent of ischaemic damage in arterial obstructionTissue involved - brain low reserveSpeed of onsetDegree of obstructionPresence of collateralsLevel of oxygenationPresence of concomitant heart failureState of microcirculationMetaplasiaMetaplasiaChange from one fully differentiated cell type to anotherCan become dysplastic if the agent that caused the metaplasia persists Can be misdiagnosed clinically? ?ClassificationEpithelial Squamous - endocervix, bronchi, bladder, prostate Glandular or columnar cell: intestinal with h.pylori; gastric with barrett's oesophagus Connective tissue Osseous metaplasia (formation of metaplastic bone) in bladder, bronchus Chondroid metaplasia (formation of metaplastic cartilage) in scars Myeloid metaplasia (formation of metaplastic bone marrow) - liver, spleen, lymph nodes ? MetastasisMetastatisMigration of cells from a malignant tumour to a site distant from the primary ?Routes of MetastasisLymphatic Haematogneous Transcoelomic - stomach, ovary, colon, pancreas Perineural - adenoid cystic carcinoma of salivary glands CSF - medulloblastoma Iatrogenic - implantation during surgery NecrosisNecrosisAbnormal tissue death during life Energy independent Occurs as a result of factors outside the cell Associated with inflammatory changes ?ClassificationCoagulative Tissue architecture preserved - kidney, heart, spleen Proteins coagulate rapidly from heat Colliquative Tissues rich in lipid, lysosomal enzymes denature fats and cause liquifaction - brain Caseous Unstructured Impossible to identify tissue affected by necrosis as architecture is destroyed - classical of TB ?Fat Necrosis?GangreneDry: mummification of tissue without infection Wet: Necrosis with putrefaction caused by infection (anaerobic streptococci, bacteroides) ?AutolysisDegradation of a cell by activation of enzymes presnet in the affected cell (self-digestion) May occur in necrosis or apoptosis HeterolysisDegradation of a cell by activation of enzymes present in cells other than the affected cell ? Organisation resolution and repairOrganisationTransformation of inanimate material (clot, thrombus, pus) into living tissue responsive to growth control factors of the body Achieved by replacement with granulation tissue ResolutionReplacement of damaged tissue by fully functional tissue normally found at that site (no scar tissue) Found in liver, bone marrow, mucosal defects, minor injury to epidermis Repair Replacement of damaged tissue by fibrosis or gliosis filling defect but has no intrinsic specialised function relevant to organ Occurs in most instances PneumoniaDefinitionInflammatory condition of the lung??ClassificationPrimary vs secondary Organism Viral Bacterial Fungal Anatomy Lobar pneumonia: exudate forms directly in bronchioles/aveoli spills into adjacent segments via pores of Kohn Confined to a lobe Usually staph Phases: (1) Congestion - inflammatory exudate (2) Red hepatisation - Neutrophils and extravasated erythrocytes (3) Grey hepatisation - Fibrin meshwork and degenerating erythrocytes (4) Resolution - Macrophage release fibrinolytic enzymes Bronchopneumonia: starts at bronchioles, extends to alveoli.? Common in extremes of age Interstitial pneumonia: chronic alveolar inflammation Aetiology Hospital acquired: loss of barriers, instrumentation, impaired cough reflex, aspiration Early: - OP organisms - staph aureus, strep pneumoniae Late: Gram negative - pseudomonas, enterobacter, acinetobacter, morganella Community acquired Severity score : CURB?Normal respiratory defencesCough reflex Mucociliary function Aleolar macrophages Secretory IgA ?Complications of PneumoniaPleuritis - pleural effusion Empyema Lung abscess Generalised sepsis? ?Prevention of pneumoniaProtection / isolation Intermittent feeding Controlled use of antibiotics Regular suctioning / chest physio SinusPathological sinusBlind-ending tract that communicates with an epithelial surface Result of inflammatory process, usually lined with granulation tissue Anatomical sinusCoronary sinus Intracranial venous sinus (cavernous sinus) Air sinuses? SkinLayers of the skinFunction of skinPhysical barrier Filtration of light / ionising radiation Secretion: sweat, contains Igs and is acidic due to lactic acid Commensals - protects against pathogens Immunological - Langerhan's cells UV light generates vitamin D ?Skin CancerSquamous cells Malignant melanoma Basal cell carcinoma Merkel cell tumour Risk factors for skin cancerCongenital Familial syndromes - BK mole syndrome xeroderma pigmentosum Acquired UV light - skin grading (1) chalk white burns easily (2) fair tans difficulty (3) fair tans easily (4) olive (5) brown (6) black Ionising radiation Chemical carcinogens (tars, dyes, rubber products) Viruses - HPV Immunosuppression ??Subtypes Grading TreatmentBCC (above lips)Nodular Cystic Pigmented Superficial spreading ?Local excision with 3-7mm margin SCC (below lips)??Local excision with 5-10mm margin +/- block dissection of draining lymph nodes MMSuperficial spreading (64%) Nodular (12-25%) Lentigo maligna (7-15%) with best prognosis Acral lentiginous (10-13%) Amelanotic Breslow Thickness<1mm1 - 2mm2 - 4mm>4mmClarke LevelsI: epidermisII: papillary dermisIII: papillary/reticular junctionIV: reticular dermisV: subcutanous fatLocal excision with 10mm margin if 1mm depth Local excision with 20mm margin if 2mm depth Local excision with 30mm margin if 3mm depth ? Spread of infectionSources of infectionAnimals Humans - TB, MM, influenza, neisseria, MRSA Animals - zoonoses, vets, mos Plants Soil Environment Soil Air Routes of infection - the "I"s Inhalation / droplet spread Ingestion Intercourse Innoculation - catherisation, injection, insects In-utero: trans Endemic: Exists continously in a population, usually of low prevalenceEpidemic: Sporadic disease in a population, usually involves large numbers of peoplePandemic: Epidemic that affects many parts of the world Syndromes LipomaLipomaCommonest benign tumour of mature fat cells (adipocytes) Occur anywhere in body Commonest in subcutaneous layer of skin (neck and trunk) Malignant change is thought to not occur Multiple painful lipomas are known as adiposis dolorosa or Dercum's disease (associated with peripheral neuropathy) Variants Liposarcomas arise de novo (and not via lipomas) Classification Well-differentiated: ring or long markers, chromosomes derived from long arm of Chromosome 12 Myxoid and round cell (poorly differentiated) liposarcoma Pleomorphic liposarcoma: characterised by complex karyotypes Angiolipomas have prominent vascular component Hibernomas: tumours of brown fat cells - seen in hibernating animals Cowden's disease: association of lipoma, palmoplantar keratoses, multiple fascial papules, oral papillomatotis, vitiligo with involvement of the thyroid and disgestive tract Bannayan-Zonana syndrome: rare AD hamartomatous disoder: multiple lipomas, macrocephaly, haemangiomas Treatment Non-surgical: watch and wait Surgical: (indications are pain / cosmesis) - options: (1) suction lipolysis via small remote incision (2) excision under LA InspectionDiscoid / hemispherical swelling May appear lobulated Look for scars (recurrent lipoma / Dercum's disease) PalpationLobulated Soft / firm depending on nature of fat in lipoma If soft and large may be fluctuant Slip sign: manner in which lipoma tends to slip away from examining finger on gentle pressure Skin freely mobile over the lipoma (compared to sebaceous cysts) Determine if lipoma is in skin or intramuscular (disappears on contraction of muscle) CompletionLife impact: cosmesis Similar lumps elsewhere (Dercum's disease) Thrombosis / ClottingThrombusSolid material formed from constiuents in flowing blood (A blood clot inside a blood vessel when the patient is alive) Function of platelets + clotting cascade Factors contributing to thrombosis (Virchow's triad)Wall Flow Constituents? Clot Solid material formed from constituents of stationary blood Primarily function of clotting cascade Urinary tract calculiTypePrevalence CompositionCalcium oxalate75%Spiky / mulberry shapedCaused by hypercalciuria (moans, stones, psychic groans)Rare enzyme deficiencyIncreased oxalate absorption: coeliac, diverticulae of bowel, chronic pancreatitis Ammonium phosphate15%Associated with proteus infection"Staghorn calculi" (from urease) Urate5%Primary gout: HGPRT deficiency (Leesh-Nyhan)Secondary gout: increased purine breakdown - tumours, RT, chemo, psoriasis...Cysteine3%Results from primary cysteinuria, inborn error of metabolismManagementHistory: precipitants, family history, personal history Examination Investigations Urine dipstick - blood, nitrates (UTI cause) U/Es, serum electrolytes, WCC, CRP KUB - 90% renal tract stones are radio-opaque (calcium, ammonium , cysteine) - urate/xanthine stones radiolucent IVU: determines degree / level of obstruction (hydronephrosis) - sites for blockage: (1) renal pelvis (2) pelvic brim (3) insertion into bladder - contrast contraindicated in pregnancy, allergy, anaphylaxis, raised serum creatinine USS: - no contrast, detects stones >5mm, determines hydronephrosis and obstruction CT Abdo: identifies radio-opaque and lucent stones, secondary signs of obstructionAnalgesia - morphine, pethidine, NSAIDs Hydration Definitive treatment<4mm4-6mm?>5mmWatch and wait 90% pass spontaneously60% pass spontaneouslyExtra-corporeal shockwave lithotripsy: stones < 2cm in upper or lower 1/3 (middle difficult to visualise apparently) - contraindicated in pregnancy, aneurysms, pacemakers Ureteroscopy +lithotripsy: stones in lower 1/3 collected using stone basket or fragmented and pieces collected Percutaneous nephrolithotomy: stones > 2cm in renal pelvis - tract made percutaneously into renal collecting system and stone extracted (large stones can be broken up first) If obstructed - percutaneous decompression + JJ stenting Open surgery (less than 1% patients) - for stones that just are bad to the bone ?Urinary tract infectionsUrinary tract infectionInfection of bladder, ureter, kidney (via renal pelvis) NB. Urethral infection is considered a STD ??PredispositionAnatomy Female anatomy: proximity of urethra to anus Congenital abnormalities affecting flow: ectopic vesicae, ureteric duplication, urethral valves, congenital stricture, VUJ reflux Urine stasis Mechanical obstruction: hydronephrosis, stricture, stone, neurogenic bladder, prostatic hypertrophy Prostatic enlargement Instrumentation Indwelling catheters Systemic disease Diabetes Immune deficiencies OrganismsEnterococci: E.coli, proteus, pseudomonas, klebsiella, staph aureus ??DiagnosisUrine dipstick: RBCS, WCC, nitrates Microscopy Culture? GI pathologyAlcohol-related diseasesMetabolism of alcoholMicrosomal ethanol oxidising system (MEOS) Alcohol dehydrogenase Catalase? ?Biochemistry/HaematologyRaised GGT Macrocytosis? ?Laryngeal disease associations?Laryngeal inflammation SCC larynx SCC pharynx / oesophagus Hepatic effects of chronic alcoholFatty liver Alcoholic hepatitis Cirrhosis: End stage of all chronic liver insults (1) nodules (2) fibrosis (3) distorted architecture Hepatocellular carcinoma GI associationsGastritis/erosions Pancreatitis Carcinoma of pancreas CNS effectsDis-inhibition, violence, trauma, chronic malnutrition Cerebellar degeneration Korsakov's psychosis Wernicke's: antegrade amnesia (?related to thiamine deficiency) Colorectal pathology?Layers of the bowel wallMucosaMuscularis mucosaeSubmucosaMuscularis propriaSubserosaSerosa?Dukes staging A:B: Penetrating wall (including touching wall)C1: Local nodes/peri-rectal nodes C2: Apical nodesD: Distant spread?Dukes staging system does not take into account the lesion that extends laterally (rather than through wall). Therefore one can have a massive superficial tumour. Diverticular diseaseDiverticulum [pathology]Outpouching of colonic wall which results from herniation of mucosa through muscular wallOccur at sites where mesenteric vessles penetrate bowel wall Lage of dietary fibre in western diets results in low stool bulk which stimulates increased segmentation of colonic musculature, resulting in hypertophy Increased intraluminal pressure results in herniation Complications of diverticular diseaseHaemorrhage Inflammation - diverticulitis Obstruction from diverticular stricture Fistulation to bladder, vagina or skin Pneumaturia Faecaluria Chronic urinary tract infections Perforation Pericolic or pelvic abscess Hydatid diseaseD: The result of infection with adult tapeworm (Echinoccocus granulosus)G: Common in mediterranean P: Large parasitic cyst grows slowly and asymptomaticallyCan have pressure effects on organs Can Rupture (can also release daughter cysts within them) Cysts can become infected with bacteria Life CycleIngestion of canine tapeworm eggs (dogs are asymptomatic) Eggs hatch in duodenum + embryos cross mucosal membrane Travel via portal blood supply to liver Primary site of infection is the liver (can affect any organ in body) S: Can present as acute abdomen from minor trauma from ruptureRupture: pain Into biliary tract: Obstructive jaundice, cholangitis S: I: Diagnosis is by serology and scans Serology/ELISA assay - Enzyme Linked ImmunoSorbent Assay for antibodies to hydatid antigen USS: Multiloculated cysts CT: "floating membrane" T: Albendazole chemotherapy. Surgical enucleation is required occasionally.Chemotherapy: Albendazole/Mebendazole Percutaneous hypertonic saline and alcohol Surgery: (1) complete resection (2) local excision of cysts (3) de-roofing of cyst with evacuation of contents. Contamination of peritoneal cavity at time to surgery should be avoided by continuing drug therapy. Inflammatory bowel diseaseCauses of ColitisInfection Inflammation - Crohn's, UC Ischaemia Radiation Drugs (antibiotic induced pseudomembranous) ?Crohn'sUlcerative Colitis DefinitionDisease of inappropriate activation of gut mucosal immune system Driven by normal bowel flora ?Defective barrier mechanism Incidence40/100,00080/100,000Age?20 - 35 yearsSex??Geography??AetiologyGenetics Smoking Diet: low fibre Immune mechanisms Genetics Smoking protective PathologyTransmural inflammation Serositis common Mucosal inflammation (with crypt abscesses Serosa normal MacroscopicAnywhere along GIT (but esp terminal ileum) Patchy "skip lesions" "Cobblestone" appearance with fissuring Strictures common Fistulae common Starts at rectum and progresses proximally (ileum 10%) Continous lesions No fissuring Strictures uncommon Fistulae uncommon MicroscopicNon-caseating granuloma (aggregation of macrophages) Inflammation - neutrophils, macrophages PrognosisPossible malignant change Malignant change well recognised Symptoms?Severe acute colitis Frequent stools >6/day Fever, tachcardia Systemically "unwell" Rectal bleeding Low albumin Intermittent relapsing colitis Chronic persistant colitis Asymptomatic SignsSkin: Erythema nodosum, pyoderma gangrenosum Eyes: iritis Joints: Endoscopic grading Investigations??Treatment Depends onSite of disease Type of disease Disease severity Medical treatment5-ASA (blocks prostaglandins and leukotrienes) Steroids Immunosuppressants - Azathioprine (mercaptopurine derivative), infliximab (anti TNF antibody), methotrexate (antimetabolite) ?Indications for sugeryLimited Resections Strictureplasty Bypass procedures Elective Chronic symptoms despite medical therapy Malignancy Fistulating disease Chronic obstruction Emergency Clinical: Severe colitis, haemorrhage Biochemical: WCC, CRP Radiographical: Perforation ?Depends onSite of disease Type of disease Disease severity Medical treatment5-ASA (blocks prostaglandins and leukotrienes) Steroids Immunosuppressants - Azathioprine (mercaptopurine derivative), infliximab (anti TNF antibody), methotrexate (antimetabolite) ?Indications for sugeryTotal colectomy + ileostomy + mucous fistula Proctocolectomy + ileoanal pouch (depends on adequate anal musculature) Types of pouch: S-pouch, J-pouch, Four-loop W-pouch Elective Chronic symptoms despite medical therapy Malignancy Emergency Clinical: Severe colitis, haemorrhage Biochemical: WCC, CRP Radiographical: Perforation, toxic megacolon Peptic ulcer diseaseCommon aetiological factorsH.pylori - 90% duodenal ulcers, 70% gastric ulcers NSAIDS - systemically suppress (protective) prostaglanding production Systemic illness - leading to stress ulcers: Curling's in burns / Cushing's in trauma Cigarette smoking Chronic disease Complications of peptic ulcerationPerforation (anterior wall ulcers - cause peritonitis): needs oversewing Haemorrahge (posterior wall ulcers - erode gastoduodenal artery): needs under-running Gastric outlet obstruction (duodenal ulcers - stricture of first part of duodenum) Recurrent ulceration ?Confirmation of perforated peptic ulcerHistory - risk factors (smoking, medications) Examination - rigid abdomen, peritonitis, absent bowel sounds (may be no clinical signs in elderly) CXR - free air under diaphragm (85% of cases) Serum amylase to exclude pancreatitis ECG to exclude MI? PolypPolypTumour protruding?from the epithelium of an organ?Classification of PolypsCongenital acquired Shape Aeitiology Metaplastic or hyperplastic Inflammatory - UC Hamartomatous - Peutz-Jegher's, juvenile retention polyps Neoplastic ?Complicationsulceration haemorrhage infection intesussception Function effects: protein loss, potassium loss Malignant change ??Bowel Polyp syndromesPeutz-Jehger's Familial adenomatous polyposis Pyloric stenosisClinical featuresFamilial tendency, 20% affected parents Especially male children? ?Pathophysiology of Alkalosis in Pyloric stenosisStomach: Loss of gastric acid secretions (rich in protons and chloride) Pancreas: Reduced pancreatic juice secretion (reduced load in duodenum) - Pancreatic juice rich in bicarbonate which is retained Volume depletion maintains alkalosis by leading to bicarbonate absorption over chloride Kidneys: Increased uptake of bicarbonate at renal tubules (due to loss of chloride) to maintain electrochemical neutrality VolvulusVolvulusMalrotation of a segment of intestine about its own mesenteric axisResults inPartial / complete obstruction of lumen + proximal dilation Compromise of blood flow leading to ischaemia Infarction from venous congestion ?Pre-disposing factorsAnatomy - long narrow-based sigmoid mesentry prone to twisting High residue diet Chronic constipation? Areas affectedSmall bowel Caecum Sigmoid colon (75%) ManagementHistory Examination Investigations AXR - dilated loops of bowel extending diagonally ABG - acidosis, lactate Treatment Conservative: if no features of ischaemia (80% will resolve) Sigmoidoscopy - diagnostic and therapeutic Flatus tube insertion (can be left for 2-3 days) Laparotomy for decompression (untwisting) with excision of redundant sigmoid colon (sigmoid colectomy + primary anastamosis) HaematologyDisseminated intravascular coagulopathy (DIC)Cytokine-mediated disease CausesTissue injury - burns, trauma, fat embolus Infections Vascular/perfusion disorders: vasculitis, PAN, ARDS Haematological disorders Neoplasms Systemic: pancreatitis, burns, embolism, hypothermia Recognition intraoperatively / clinicallyUnderstand risk factors Bleeding / oozing which is difficult to control Hypotension Tachycardia Low oxygen saturations Bleeding from ususual areas - venepuncture, cannulation sites, epistaxis, haematuria from uncomplicated bladder catheterisation Diagnosis Low platelets Low plasma fibrinogen (used up in coagulating) Increased PT and APTT (clotting factors used up) Increased FDPs / D-dimers (more degradation products) Haemolysed fragmented red cells LymphomaLymphomaMalignant tumour of lymphoid tissue PresentationPrimary Tumour Painless progressive lymph node enlargement SVC obstruction Systemic effects Malaise Weight loss Splenomegaly / Hepatomegaly Metastatic features Bone pain Paraneoplastic syndromes Classification?Hodgkin's LymphomaNon-Hodgkin's Lymphoma CellularDorothy Reed-Sternberg cells Polymorphic B-cell tumour Monomorphic Clinical featuresBimodal age distribution Step-by-step spread 80% curable Peak 50 years (older) Random spread Poor prognosis Classification (grading)Rye ClassificationLymphocyte predominant Nodular sclerosing Mixed cellularity Lymphocyte deplete? ?Staging?Ann Arbor SystemA - Absence of systemic symptoms (wt loss, fever) B - Presence ?Stage I: one node Stage II: many nodes (same side) Stage III: Both sides of diaphragm Stage IV: Metastatic spread? DiagnosisHistory Examination Imaging CXR IVU - retroperitoneal nodes compress renal calyces CT scan Tissue diagnosis Node excision biospy [Splenectomy previously] TreatmentRadiotherapy + Chemotherapy?PlateletsPlateletsDerived from megakaryocytesFunctions - adhesion, activation, secretion, aggregationRelease: serotonin, adrenalin, ADP, prostaglandins, thromboxanes?Classification of platelet abnormalitiesDisorders of numberThrombocytopenia: bleeding - petechiae, ecchymosis, epistaxisThrombocythaemia: splenomegaly, haemorrhages, thrombotic episodesDisorders of functionThrombastheniaPolycythaemiaClassificationPrimary Polycythaemia rubra vera: myeloproliferative disease Secondary Appropriate EPO excess: hypoxia (emphysema, lung diseases), CCF, high altitude Inappropriate EPO excess: renal neoplasms Relative Apparent polycythaemia because of a reduction in plasma volume AIDSHuman Immunodeficiency VirusRNA retrovirus requires reverse transcriptase Core protein RNA surrounded by glycoprotein envelope Infects cells via CD4 receptors (T-helper)? ???Neoplastic associationsLymphoma B-cell NHL / T-cell NHL Aggressive form HL Kaposi's sarcoma Skin cancer SCP SCC: anus, vulva Laryngeal neoplasm SCC larynx Surgical RelevanceBacterial enteritis Haemorrhage from KS of GIT CMV infection leading to megacolon GIT lymphoma Hypersensitivity reactions?Type IImmediate / AnaphylacticIgE linkage by an antigen leads to release of mast cell contents (histamine, 5HT, heparin, PAF, chemokines) Minutes Eg. eczema, asthma, allergic rhinitis Type IICytotoxicAntibody in serum reacts against tissue components resulting in cell death from (1) complement action (2) destruction by killer T-cells (3) phagocytosis by macrophages Minutes-hours Eg. transfusion reactions Type IIIImmune complexImmune complex formed that activates complement/platelets - cause damage by formation of membrane attack complex (MAC) and enzyme release from inflammatory cells Hours Eg. Type IVDelayedMediated by sensitised T-lymphocytes Days TB, organ transplants ImmunodeficiencyBody's defencesInnate Skin Complement Interactive Cellular Antibody? ImmunisationActive or Passive Active: pre-formed antibodies (HBsAG, immunocompromised patients with shingles, botulism, rabies) Passive: transplacental transfer of IgG protects for first 6 months of life Natural?or artificial? Natural: following infection Following vaccination Different types of vaccinationsLive attenuated: - BCG, sabine for polio, MMR Long lasting immunity Potentially dangerous in immunocompromised patients Killed organisms: typhoid, cholera, pertussis Smaller immune response: usually boosters are required Toxoid Not the infection but the effects of toxin that result from infection (eg. Tetanus toxoid) Other bacterial constiuents? Surface polysaccharides and proteins ImmunoglobulinAntigen binding sites (light and heavy chain regions) Complement activation parts Immune adherence Heavy chains determine the class of immunoglobulin -?GAMDE Light chains are kappa- or lambda- irrespective of the immunoglobulin class IgG: most important Monomeric: activates complement, binds to killer t-cells IgA: present in secretions of BIT, respiratory tract; Dimer with J-chain IgM: Largest - Pentamer IgE: Monomer bound to mast cells Immunodeficiency Acquired Drugs Infections Congenital Bruton's X-linked gammopathy T-cells: Thymic atrophy in Di-George anomaly SCID Lymphoma ??Infections in Compromised patientsCongenital Bruton type hypogammaglobulinaemia Di George type Combined Deficiency of neutrophil function in chronic granulomatous disease? Acquired Infections: AIDS Drugs: steroids, cytotoxics Diabetes (also because glucose as a culture medium in urine and on skin) Instrumentation - lines, catheters, ventilation Prosthesis: hips, knees, heart valves ?Sources of infectionEndogenous Colonic bacteria GIT Skin Exogenous Foamites Other people Transplanted tissues "Opportunist" Metabolic / EndocrineAdrenal pathologyLayers of the adrenal glandGlomerulosa: Salt: aldosteroneFasiculata: Sugar: glucocorticoidsReticularis: Sex hormones - dehydroepiandrosterone / oestradiolMedulla - catecholamines?Mechanism of action of Steroid hormonesIntracellular receptor binding Results in gene stimulation Hormone release (RAS)Glucocorticoids ACTH Aldosterone Renin (stimulated by low BP, sympathetics); Low Na; Hyperkalaemia Renin - activates Angiotensinogen Angiotensinogen activates angiotensin I Angiotensin I to Angiotensi II by ACE (in the lungs) Stimulates aldosterone release ?Cushing's syndrome / DiseaseHypercortisolaemia (Cf disease - hypercortisolaemia secondary to pituitary adenoma secreting ACTH) Causes: ACTH - pituitary tumours, ectopic ACTH from oat cell, carcinoid, pancreas Steroid secreting adenoma iatrogenic steroids ?Cushingoid features (1) Head and neck - moon face from fat and oedema, acne from testosterone effects, male pattern baldness, hisutism in ladies (2) Chest and trunk - buffalo hump from fat distribution, central obesity, striae, ecchymoses from capillary fragility (4) Limbs - muscle wasting from cortisol effect Endocrine effects Fat / salt handling Diabetes Secondary osteoporosis Amenorrhoea from suppression ?HyperaldosteronismPrimary: Conn's syndrome - autonomic secretion from adenoma Salt/water retention leads to hypertension Hypernatraemia / hypokalaemia / metabolic alkalosis (in association with hypokalaemia) Rx: Spironalactone (Aldosterone antagonist) Secondary: RAS activation following dehydration ?Adrenocortical insufficiency / Addison's diseaseBilateral destruction of the layers of the adrenal gland Infection - TB, fungi, Friederichsen-Waterhouse (meningococcal emboli) Deposition - haemochromatosis, amyloid, malignancy Auto-immune Drugs - adrenolytic drugs (ketoconazole), steroid withdrawal Iatrogenic- Adrenalectomy Clinical features General: Weight loss, malaise Skin: - Hyperpigmentation due to POMC (pro-opio melano cortin) from anterior pituitary with increase in MSH and ACTH Biochemical: Hyponatraemia, hyperkalaemia, increased ACTH, decreased aldosterone and cortisol ?Adrenal Medulla ?Hormones producedCatecholamines: produced from tyrosine (tyrosine hydroxylase)> DOPA (Dopa decarboxylase)> Norad (Dopamine B-hydroxylase)> Dopamine (Phenylethanolamine-N-methyl-transferase)> Adrenaline From chromaffin cells: Dopamine, somatostatin, substance P, enkephalins Innervation: Ach from pre-ganglionic sympathetic fibres?Effects of hormones:Cardiovascular effects Hypertension, tachycardia Respiratory GI: Metabolic Carbohydrate - cause hyperglycaemia (1) stimulates gluconeogenesis (2) glycolysis (3) inhibit release or insulin - mediated via alpha-receptors Lipids - stimulates lipolysis DiabetesDiabetes MellitusDue to absolute / relative insulin resistance?[Pancreas]DiagnosisHistory: polyuria, polydipsia, unexplained weight loss Plus: RPG: >11.1 FPG: > 7.0 GTT: >11.1 2 hours after 75g oral glucose ComplicationsArterial disease Renal disease Skin disease Anaesthetic complications Eye disease: cataracts, retinopathy, infections Bone/Joint disease - septic arthritis, osteomyelitis ?Systemic: immune deficiency Clinical FeaturesSkin Necrobiosis lipodica diabeticorum Leg ulcers Fat atrophy Skin infection Eyes Diabetic retinopathy Cataracts Peripheral vascular Amputations Gangrene Neurological Charcot's joint Diabetic neuropathy - dorsal column disease Renal disease Skin pigmentation Hypertension AV fistulae? HyperparathyroidismClassification?Causes/sourcesSerum biochemisty?ComplicationsPrimary - tumour? 85% parathyroid adenoma 15% parathyroid hyperplasia 1% carcinoma High calciumLow phoshate?Bone disease: pathological fractures Psychic effects Abdominal pains Renal effects: calculi, nephrocalcinosis Secondary - to hypocalcaemia? Renal - decreased metabolism of vitamin D Dietary deficiency Decreased sunlight Pregancy - increased demands Low calcium High phosphate??Tertiary - autonomous adenoma?High calciumLow phosphate?Multiple Endocrine NeoplasiaType I: pituitary, pancreas, parathyroid (PPP)?Type IIa: parathyroid, thyroid, phaeochromocytoma (PTP)?Type IIb: phaeochromocytoma, thyroid, neuroma (PTN) Paget's disease of boneOsteitis Deformans D: Second most common metabolic bone disease (first is osteoporosis) characterised by excessive / disorganised bone formation and resorption I/A: Increasing incidence with age - 3-4% over 40 years, 10% 85+ S: More common in men than women G: More common in the west, less common in east asian countries A: Unknown but though to be persistent infection in bone from a virus (Measles, mumps, RSV) P: Alternating phases of rapid bone resorption/formation M: Long bones have thicked shafts/deformities, cysts and stress fractures seen. May be areas of localised softening - "osteoporosis circumscripta". M: (1) Osteolytic phase - clasts produce excavations which are filled with vascular fibrous tissue (2) Mixed lytic-sclerotic phase - blasts lay down woven bone which is subsequently resorbed by osteoclasts (3) Quiescent osteosclerotic stage - clasts less active, eroded areas filled with brittle woven bone P Clinical features Usually asymptomatic Bone: 15% monostotic, 85% polyostotic Long bones - become bowed/deformed Cranium - compression of cranial nerves as pass through foramina (8th - leading to deafness), compression of nerve roots (causing pain) Pathological fractures Osteosarcoma (1%) Cardiac High output cardiac failure - most common in polyostotic disease (increased bone blood flow) InvestigationsRadiology Increased ALP (reflects osteoblastic activity) Plasma calcium normal/raised TreatmentControl pain Suppress bone turnover - bisphosphonates, serum ALP for measuring disease progression Surgery - pathological fractures, joint replacement, nerve/cord decompression PancreatitisAcute PancreatitisInflammation of the pancreas?[Functions of the pancreas]?CausesGallstones 45% Ethanol 35% Trauma Steroids Mumps, coxsackie Autoimmune Scorpion venom Hypercalcaemia (activates enzymes), hyperlipidaemia ERCP Drugs (steroids, thiazides) PathophysiologyActivation of proteolytic pro-enzymes contained within pancreas Triggers autodigestion Results in severe inflammatory reaction Inflammed acinar cells and invading leucocytes produce cytokines (IL-1) and TNFalpha Cytokines mediate systemic inflammatory response syndrome (SIRS) Persistant inflammation leads to "pancreatic pseudocyst" Collection of fluid rich in pancreatic secretions enclosed within a cyst lined with granulation tissue (as opposed to epithelium) If < 5cm will resolve spontaneously; if > 5cm may beed surgical intervention and drainage Conservative therapy needed for 4-6 weeks to allow cyst wall to mature Surgical treatment: - Radiology-guided percutaneous drainage; endoscopic drainage; internal drainage ??Clinical presentationHistory severe epigastric pain radiating to back and eased by leaning forwards Accompanied by nausea and persistent vomiting Examination tenderness with rigid abdomen and absent bowel sounds Abdominal distension due to ileus bleeding in fascial planes: Grey-Turner's sign (flanks); Cullen's sign (peri-umbilical) Investigations Shock- tachycardia Low pO2 High BM etc... High serum amylase (>500U) or serum lipase AXR: "sentinel loop", CXR - exclude perforation ?Ranson CriteriaAPACHE III score (acute physiology and chronic health evaluation)?Glasgow (Imrie) scoring systemPaO2 < 8kPa Age > 55years Neutrophils > 15 x108/l Calcium <2.0 mmol/l - saponification Raised Urea >16mmol/l Enzymes: AST/ALT >600; LDH >600 Albumin <32g/litre Sugar > 11mmol/l Severe if score 3 or moreShould be managed in HDU setting?ComplicationsPancreatic abscessPancreatic pseudocystSevere destructive pancreatic haemorrhageDuodenal obstructionChylous ascites?Chronic PancreatitisChronic inflammatory disease of pancreas Irreversible glandular destruction Early: may appear "normal" Late: fibrosis and calcification Cysts form within pancreas with duct dilation May occur as result of recurrent acute pancreatitis CausesAlcohol Smoking Hereditary Hypercalcaemia Duct obstruction Strictures Gallstones Cystic fibrosis Clinical featuresAmylase usually normal Interferes with life and leads to opiate abuse Loss of exocrine function - malabsorption, steatorrhoea Loss of endocrine function - diabetes Imaging (CT/MRI-pancreas protocol): demonstrates calcification ManagementDietary modification - low fat, alcohol abstention Avoid opiates Pancreatic enzyme supplements: - Correct endocrine disturbance Pituitary hormone disordersThe pituitary hormone disorders??HormoneExcess??Deficiency?Growth HormoneAcromegalyCausesGH secreting pituitary adenoma Ectopic GH from pancreas/lung/intestine carcinoma ?Surgical Associations Osteoporosis Orthodontic procedures Large bowel polyps/carcinoma Gallstones/GB disease Increased incidence of hernias Diabetes mellitus? Sjogren's syndromePathologyAutoimmune disorder - 90% occur in women, average age 50 years Intermittent or constatn swelling of one or all of hte salivary glands Diagnosis (at least 2/3)Keratoconjunctivitis sicca (dry eyes) xerostomia (dry mouth) associated connective tissue disorders If no associated connective tissue disorders are present, this is known as primary Sjogren's disease Pathology: lymphocyte-mediated destruction of the exocrine glands secondary to B-cell hyper reactivity and associated loss of suppressor T-cell activity x40 increased risk of developing lymphoma, usually B-cell non-Hodgkin's type Antibodies: anti-salivary Ab, rheumatoid factor, anti-SSA-Ro and anti-SSB-La Investigations Schirmer's tests for xerophthalmia (strip of filter paper inserted into each fornix and hyposecretion confirmed by wetting of less than 5mm in 5 minutes - normal is 15 mm) Slit-lamp examination of the cornea Lip biopsy for histological examination of the minor salivary glands Testicular cancerClassificationPrimary 95% Germ cell (seminoma, teratoma) Non-germ cell Secondary 5% Lymphoma Metastatic (lymphoma, leukaemia, melanoma) Risk factorsTesticular maldescent (1/20 have malignancy) Mumps orchitis Trauma Maternal oestrogen exposure Genetics: 12p chromosomal abnormalities ?Royal Marsden Hospital Staging systemI: Confined to testis II: Confined to testis but with persistently raised tumour markers III: Infradiaphragmatic node involvement IV: both sides of diaphragm V: Extralymphatic metastases? ??ManagementHistory Risk factors - trauma, mumps, maledescent, maternal oestrogen Genetics Examination Regional nodes - drain to para-aortic Investigations Blood tests: Tumour marker assay, aFP, LDH, HhcG CXR: Pulmonary metastases USS scrotum Chest / abdominal CT - detection of metastases in retroperitoneum and mediastinum Treatment Scrotal exploration: if diagnosis is uncertain; scrotum can be explored and possible tumour biopsy Orchidectomy: if there is any doubt Radiotherapy (seminomas highly radiosensitive) Chemotherapy for advanced stage disease Thyroid / GoitreFunctional unit of the thyroidFollicleEpithelial cells surround central colloid Follicular cells lie adjacent to a vein / capillary Produces 80% T4 and 20% T3 (rest of T3 is converted in the peripheries) T3 is the active form Parafollicular cellsSecrete calcitonin ?T3/T4 PhysiologyIodine transported across cell membrane, transfered to colloid, then linked to tyrosine Tyrosine iodinated to mono-iodotyrosine + di-iodotyrosine (bound to thyroglobulin) Coupling results in T3 and T4 T3/T4 + thyroglobulin transported into cell as colloid droplets; then separated from TG T3/T4 released into circulation (bound to albumin, thyroxine binding globulin [different from thyroglobulin]) GoitreAny enlargement of the thyroid gland Seen as midline swelling that moves with swallowing SingleMultinodular Diffuse Adenoma Carcinoma Adenoma Carcinoma Painful De Quervain's thyroiditis Painless Iodine deficiency Goitrogens - in foodstuffs Thyroiditis Infiltration - sarcoid Dyshormogenesis HyperthyroidismImmune Graves Hashimoto's "Physiological" Pregnancy Drugs Thyroxine replacement (in block and replace) Amiodarone Carcinoma hyperactive nodule Follicular carcinoma Papillary carcinoma Struma ovarii - thyroid tissue in dermoid cyst Basophil adenoma of pituitary Thyroid disease workupRadioactive scanning (not a very useful test really is it?!) Hot nodule: 95% benign Cold nodule: 80% benign MicrobiologyAmoebiasisDiseases caused by amoebaeGIT: Amoebic dysentry, inflammatory polyps, liver abscess Skin: anal/vulval ulceration CNS: abcesses, meningoencephalitis (Naegleria fowleri)? AntimicrobialsTazocin: contains piperacillin + B-lactamase inhibitor tazobactamFor pseudomonas coverSimilar spectrum as imipenem/meropenem?Tigecyclin BacteriaClassificationShape Cocci Bacilli Vibrios - comma shaped organisms Spirilla - spiral rods that don't bend Spirochetes - spiral rods that bend in the middle Actinomycetes - complex branching dos Gram Stain Positive Negative Ziehl-Neelsen stain: for mycobacterium (which possess a waxy coat and don't stain) ?Pathological EffectsProliferate in tissues Resist phagocytosis in somce cases Secrete exotoxins and release endotoxins Attach to cell membranes and damage them Anaerobic organismsClassificationObligate anaerobes: grow only in absence of oxygen Facultative anaerobe: grows in presence or absence of oxygen ?Gram positiveGram Negative??CocciClostridium???Bacilli?BacteroidesFusobacteriumActinomycosisActinomyces organsismsActinomyces israelii - Gram positive filamentous bacetrium Commensal of alimentary tract - tonsils, mouth, upper intestine Pathogenic when Immunocompromised - Drugs, diabetes, steroids, AIDS, neoplasia Mucosal damage - appendicits, perforation, radiotherapy DiseasesInfection of neck, thorax, abdomen May mimic malignancy ?DiagnosisIndex of suspicion Microscopy - "sulphur granules" / tissue histology ClostridiaCharacteristics of Clostridia :Positive - Spore - Endotoxic - Anaerobic - Saphrophtyic Gram positive Spore forming Subterminal Drumstick Exotoxin producing Botulinum - causes spastic paralysis with release of botulinum toxin (inhibits acetylcholine release) opisthotonus + involvement of respiratory muscles Perfringens (welchii) - proteolytic enzyme lecithinase causes gas production - gas gangrene (with characteristic smell) Tetani - produces tetanospasmin (inhibits inhibitory processes of motor neurones) causing muscular spasm and paralysis; prevented by tetanus toxoid immunisation / human anti-tetanus immunoglobulin Difficile - exotoxin produces cell membrane damage to epithelial cells leading to pseudomembranous colitis Anaerobic Oxygen forms free radicals Cells have little/no defence Saphrophytes - requires soil to protect them from dehydration Helicobacter pyloriClassificationCurved/spiral gram negative bacterium Present in gastric mucus in crypts and on the surface of gastric acid and duodenal biopsies More prevalent in the antrum than in the body of the stomach Microaerophilic, flourishing best in low oxygen and high CO2 / H2 atmospheres Disease associationsGastric erosion and gastric ulcer Duodenal erosion and ulceration Chronic gastritis Gastric lymphoma of mucosa-associated lymphoid tissue Gastric adenocarcinoma Diagnostic testsGastric biopsy Culture Histology with modified Giemsa statin for helicobacter-like organisms Urease test on a biopsy specimen in agar gel with indicator system Urease test on biopsy specimen using detector strip that incorporates the indicator system Urease breath test Radio-labelled 13C or 14C given by mouth and measuring the amount of radioactivity in the breath as a consequence of splitting of Urea Serum test For H.pylori antibodies MycobacteriaClassificationAlcohol acid-fast bacilli Would be gram positive if Gram stain could penetrate walls ?Typical mycobacteria Mycobacterium Tuberculosis Mycobacterium leprae Atypical mycobacteria Resistant to standard antituberculosis drugs, different culture characteristics from MTB (eg pigment production, different growth rate in culture) Mycobacterium avium intracellulare: - infection in AIDS Mycobacterium marinum: - swimming pool granuloma Mycobacterium ulcerans: - causes Buruli ulcer Mycobacterium kansasii: - chronic pulmonary infection Mycobacterium TuberculosisClinical classificationPrimary TB: usually symptomless Lung - primary focus is "Ghon focus" with involvement of lymphatics and enlargement of hilar lymph nodes. Ghon focus forms at periphery of lung in mid-zone on a chest X-ray Tonsils with cervical lymph node involvement "scrofula" Terminal ileum with mesenteric lymph node involvement "tabes mesenterica" Post-primary TB: cough, fever, weight loss. Spread of infection limited by severe local response with cavitation and fibrosis Haematogenous spread: miliary TB in many organs, TB meningitis, bone/joint TB, renal TB Spread by rupture into air spaces - TB bronchopneumonia Staphyloccoci and streptococciSpecies?Staphylococci?StreptococciMain typeGram positive cocci arranged in clusters (hence "cocci") Form colonies - golden, white colonies Type by bacteriophage (bacterium-specific virus) Gram positive cocci arranged in chains or pairs Transparent colonies Typed by API strips ClassificationBy presence of absence of coagulaseCoagulase positive Staph aureus Coagulase negative Staph epidermidis Staph saprophyticus? By type of haemolysis on culture on blood-agar platePartial haemolysis - alpha: strep pneumoniae Complete haemolysis - Beta: strep pyogenes (causes erysipelas/nec fasc) No haemolysis - Gamma: enterococci By Lancefield group antigensGroup A: Strep pyogenes Group B: none (strep agalactiae) Group C: none (strep equisimilis) Group D: enterococcus faecalis Group F: Viridans group Treponemal diseasesMotile spiral organisms (spirochetes) - flex in middle as they move?ClassificationVeneral T.pallidum pallidum - syphilis Non veneral T.pallidum pertenue - yaws T.pallidum endemicum - bejel T.pallidum carateum - pinta Culture MediaSolid - Isolation of separate colonies (esp when mixed growths) Liquid - grow some sensitive organisms using enrichment broths Exotoxins and Endotoxins?ExotoxinEndotoxin?DefinitionImmunogenic protein secreted from a living organism (that is heat labile and has a specific molecular targetLipopolysaccharide derived from the cell wall of an organism that is not usually immunogenic (is heat stable) ExamplesEnzymes: vibrio Neurotoxins: clostridium Disrupters of membranes: clostridium? CauseCytokine formation Fibrin degredation Activation of clotting cascade Kinin formation Nitric oxide formation Prostaglanding formation Complement activation Platelet activating factor formation Leucotriene formation? DiseasesCholera (vibrio) Dipheri Gas gangrene: cl.perfringens Food poisioning Botulism Shock DIC Hypotension Organ failure Pyrexia? ?FungiFungi are larger than bacteriaHave nuclei with multiple chromosomes and cytoplasm containing mitochondria and ribosomesCan reproduce sexually by meiosisPathological by (1) infection - superficial, subcutaneous, systemic (2) toxin production (3) hypersensitivity reactionsPredisposition - Immunocompromise; premature, AIDS, indwelling lines ?ClassificationYeasts Filamentous fungi Dimorphic fungi ?CandidaCommonest human pathogen is candida albicans sp Affects mucous membranes (vagina, cervix, oropharynx), skin, respiratory tract, urinary tract Risk: Diabetes Immunocompromised Acquired: drugs (steroids, cytotoxics), AIDS, leukaemia Congenital Diagnosis: (1) Microscopy (2) Culture (3) Antigen detection in urine, blood (4) Antibody detection (5) Increased arabinitol - a metabolite of candida in serum? ?Pathogenic fungiCryptococcus neoformans Malassezia furfur Dematophytes Toulosis glabrata Aspergillus fumigatus Microsporum audouinii Pneumocystis carinii VirusesClassificationRNA / DNA RNA: Influenzae, HIV, Rubella DNA: HSV, HPV, HIV Size: parvovirus, picornavirus Shape: rhabdovirus, small round virus Tissue - Adeno (glandular), enterovirus Neoplastic virusesDirectly cause neoplasia EBV: Burkitt's lymphoma (8:14), Nasopharyngeal carcinoma HPV: Cervical carcinoma Predispose to neoplasia Chronic hepatitis: hepatocellular carcinoma AIDS: Lymphoma MusculoskeletalOsteoarthritisDegenerative joint disease??CausesMetabolic joint disease Abnormal lipid handling Inherited hypercholesterolaemia and related disroders Gout Pyrophosphate arthropathies Diabetes mellitus Inflammatory joint disease Infective arthritis - gonococcus, salmonella Non-infective: RA, ank spond, psoriatic Trauma Joint trauma Repetitive strain Congenital Achondroplasia ?Joints affectedHip Knee Shoulder Elbow TMJ OsteomyelitisOsteomyelitisInflammation of bone and bone marrow?CausesInfective Bacteria - staph aureus, ecoli, streptococci, bowel organisms Viruses Fungi Parasites Non-infective Radiotherapy ?Pathological SequlaeSuppuration with pus in marrow cavity Sequestrum: dead bone within periosteum that forms inner part of infected bone marrow Involucrum: reaction of periosteum to form new bone that 'envelops' the infected site and contains it Cloacae "sewer": holes in the involucrum through which pus formed in the medulla discharges Sinus: drainage tract from the cloaca to skin Septicaemia and pyaemia ?Late complicationsAmyloidosis Malignant change in the sinus - Marjolin's ulcer Septicaemia and pyaemia Suppurative arthritis ?Pathological FracturesPathological FractureFracture through previously abnormal bone?CausesOsteoporosis Metabolic bone disease Radiotherapy Primary neoplasia Paget's disease of bone OncologyApoptosisApoptosisProgrammed cell death Energy dependent process, requires specific protein synthesis (p53.Chr17).? Does not stimulate inflammatory response May be physiological or pathological PhysiologicalPathological?Embryology: finger development, development gut lumens Thymus: physiological degeneration Endometrial cycle Menopause Following cellular damage: virus, bacteria, RT, drugs Reaction to normal cell cycle In response to tumours ?Apoptosis GenesPromotorsUn promotors?p53 - Chromosome 17c-myc BrCA1/2bcl-2?CarcinogenesisCarcinogenesisRemote carcinogen Precursor of carcinogenic agent Proximate carcinogen Metabolite of remote carcinogen with potential Needs further modification into ultimate Ultimate carcinogen DNA interaction causes cancer B-naphthylamine - ingested and absorbed from small bowel, metabolised in liver, made soluble, excreted by kidney and causes cancer in bladder (after being gluconurated by bladder epithelium).?Initiator: Alters DNA making it abnormalPromoter: Leads to altered gene expression (eg hormones) Cell cycleCell tissue classification in terms of ability to regenerateLabile cells: - Bone marrow, testis, small, bowel (all contain stem cells) Stable cells: liver, kidney, adrenal, bone Permanent cells: CNS, skeletal muscle G1: Gap phase. Variation by lenght of cell's cycle is determined mostly by the lenght of time it spends in G1Retinoblastoma gene (Rb1) serves as restriction point (for cyclin dependent kinase)p53 gene produces p53 protein which arrests cell cycle by increasing concentration of p31 (cyclin-dependent kinase inhibitor)G0 - resting phase S: Synthesis phaseCell wall, cytoplasm, nuclear proteins made G2: Second gap phase M: Mitosis ?OncogeneAbberant genes which were previously important in the regulation of the cell cycle?Mechanisms of oncogenesisAmplification: increases copies of proto-oncogene result in excessive activity Point mutation: conversion of proto-oncogene into permanently active gene Incorporation of new promoter: viruses can insert promotor sequences into human DNA Incorpation of enhancers Translocation of chromosomal material ?Mechanisms of actionSignal transduction pathway effects Regulation of nuclear activity Growth factors / receptors Inhibition of apoptosis ?PromotorInhibitor CyclinCyclin-dependent KinasesEpidermal growth factor (EGF) / c-erbB-2PDGF / c-sisInsulin-like growth factor-1Transforming growth factor Bp53, p27, p21Rb - restrictionBrCA1, BrCA2APC geneWilm's tumour geneInterferon-alphaProstaglandin E2HeparinChromosomal abnormalitiesNormal chromosomal arrangementNormal cells: 44 autosomes + 2 sex chromosomes 0,23,46, 46(n) - normal number of chromosomes in a cell (eg. RBC has none, striated muscle 46n) 023 46 46n ErythrocytesHaploid cellsGonads - sperm, oocytesNormal cellsTetraploid - before divisionMultinucleated cells - osteoclasts, syncitiotrophoblasts, muscle cells Classification Chromosome abnormalities??AutosomeSex chromosome StructureTranslocations - one part onto another Delections - loss of material NumberMonosomy - loss of one pair of chromosomes Turners XO Trisomy - increase to three of one type of chromosom Downs Chromosome 23 Edwards Patau Polyploidy - extra sets of entire chromosomes Kleinfelter's Location???Autosomal dominantAutosomal recessive?X-linked?Single copy of gene responsible for disease Both copies of abnormal gene must be present Disease due to abnormality on X-chromosome FAP APKD Achondroplasia Marfan's (fibrillin) Spherocytosis (spectrin) Cystic fibrosis (7q CFTR) Alpha-1-Anti-trypsin deficiency Haemophilia A/B G6PD Fragile X Red-green colour blindness Red-green colour blindess (1/10) ?Down's syndromeChromosomal abnormalityThree copies of chromosome 21Non-disjunction (esp mothers > 40 years) Non-disjunction of a gamete: one progeny gets TWO chromosomes (and the other one gets none) which is then fertilised by a normal gamete from the other parent enduing up with THREE copies of chromosomes. Usually maternally derived extra copy Translocation (rare) Parents phenotypically normal but have a balanced translocation Chr 23 +Chr 23 / Ab Cr 22; get's one Chr 23 from mum, one Chr23 from dad and AbCr22+Down's shit Mosaism 1/100 cases Normal ovum Non-disjunction after the blastocysts starts to develop ?AssociationsCongenital heart defects: PDA, VSD, ASD Neoplasia Increased incidence glue ear Kleinfelter's syndromeXXY - Extra X chromosomePhenotypic featuresTall stature Small genitalia Gynaecomastia (same risk of breast cancer as women) Female distribution of hair? Turner's syndromeXOAssociationsCoarctation of the aorta Webbing of neck Wide carrying angle Shield chest Short stature Streak ovaries No learning difficulties ?NB - normal X chromosome is inactivated by lyonisation.? Lyonisation is incomplete inactivation of X chromosomes.?DysplasiaDysplasiaA degree of failure of maturation of a tissue associated with a tendency to aneuploidy and pleomorphism but without the capacity to spread An abnormality of development of tissue in which fibrous or other non-specialised tissue is present instead of the expected tissue ?Causes of dysplasiaChemicals Smoking Alcohol (larynx, stomach) Viruses HPV 16,18 Specific chronic inflammation UC Non-specific chronic inflammation Cystitis leading to bladder carcinoma ?Sites of DysplasiaRespiratory tract Bronchus: in relation to smoking Gastrointestinal tract Oesophagus - in relation to candidiasis or other chronic irritation with results in squamous dysplasia Oesophagus: Barrett's oesophagus - glandular dysplasia Stomach: H.pylori infection Large bowel: ulcerative colitis Urogenital tract Cervix: CIN Histological featursMultilayering (of a columnar or cuboidal) epithelium Mitotic figures - increased in number, presence of abnormal mitoses Pleomorphism Hyperchromatism Loss of cell-cell adhesion resulting in shedding No invasion of basement membrane? ?Effects of tumours?Cachexia (IL1, TNFa related)Primary / Local effectsPressure effects Obstruction/compression Haemorrhage Infection leading to septicaemia Infarction (torsion of polyp) Pathological fractures Biochemical/hormonal abnormalities Metastatic effects?Paraneoplastic manifestations Syndrome in which there are symptoms and signs caused by a neoplasm other than by its direct involvement, metastatic spread ClassificationEndocrine Cushing's syndrome ADH secretion PTHrP Carcinoid syndrome Haematological Polycythaemia DIC Thrombocythaemia Dermatological Acanthosis nigricans Dermatomyositis Erythema gyratum repens Erythroderma Clubbing Neuromuscular Polymyositis Myopathies - Myasthenia, GBS Hormones & NeoplasiaRelationships with neoplasiaHormones cause neoplasms Tamoxifen: endometrial adenocarcinoma (partial oestrogen agonist) Oestrogen causes endometrial cancer Methylated steroid hormones cause liver neoplasms Hormones treat neoplasms Tamoxifen + breast Progestogens + endometrial cancer Antiandrogens + prostate cancer Thyroid cancer with thyroxine Neoplasms secrete hormones Eutopic (from tumour tissues that normally secrete hormones) - adrenal, ovarian, thyroid, pituitary, kidney Ectopic (from tissues that do not normally secrete hormoneS) -? carcinoid, neuroendocrine tumours Neoplasms may be hormone dependent Papillary carcinoma of thyroid Breast ca may be dependent on oestrogen NomenclatureCarcinomaMalignant tumour of epithelial cellsSquamous epithelium - SCC, melanoma, hepatocellular carcinoma Glandular epithelium - Adenocarcinoma Transitional epithelium (urinary tract) Undifferentiated (anaplastic) ?Sarcoma Malignant tumour composed of connective tissue cells (mesenchyme)Ligament - chondrosarcoma Fat - liposarcoma Bone - osteosarcoma Fibrous tissue - fibrosarcoma Typed by tissue that forms the greatest volumne of the tumour ?BlastomaCharacteristically childhood tumoursEg. Retinoblastoma, nephroblastom (Wilm's tumour), Neuroblastoma, Medulloblastoma, Hepatoblastoma ?TeratomaNeoplasm composed of cells with potential to form all three germ layers.May benign or malignant99% ovary benign, 99% testicular malignant?GradingWell differentiated Moderately differentiated Poorly differentiated Undifferentiated Examples:Rye classification of lymphoma Bloom & Richardson grading system ??StagingDegree of spreadExamples:Royal Marsden Testicular cancer Ann-Arbor Lymphoma Duke's staging of colorectal cancer Breast Manchester / Columbia systemTesticular cancerClassificationPrimary 95% Germ cell (seminoma, teratoma) Non-germ cell Secondary 5% Lymphoma Metastatic (lymphoma, leukaemia, melanoma) Risk factorsTesticular maldescent (1/20 have malignancy) Mumps orchitis Trauma Maternal oestrogen exposure Genetics: 12p chromosomal abnormalities ?Royal Marsden Hospital Staging systemI: Confined to testis II: Confined to testis but with persistently raised tumour markers III: Infradiaphragmatic node involvement IV: both sides of diaphragm V: Extralymphatic metastases? ??ManagementHistory Risk factors - trauma, mumps, maledescent, maternal oestrogen Genetics Examination Regional nodes - drain to para-aortic Investigations Blood tests: Tumour marker assay, aFP, LDH, HhcG CXR: Pulmonary metastases USS scrotum Chest / abdominal CT - detection of metastases in retroperitoneum and mediastinum Treatment Scrotal exploration: if diagnosis is uncertain; scrotum can be explored and possible tumour biopsy Orchidectomy: if there is any doubt Radiotherapy (seminomas highly radiosensitive) Chemotherapy for advanced stage disease RadiationClassificationElectromagnetic Infra-red Ultraviolet X-ray Gamma-ray cosmic rays Particulate alpha particles (electron) beta particles(hydrogen nucleus) Cellular damage mechanismsDirect DNA damage (TT dimers, base deletions, cross linkages) Indirect damage to proteins, membranes, enzymes (via free radicals - unpaired electron) ?RadEffect 100,00010,0001000100Death in minutes (nuclear bomb)Death within hours from CNS effectsDeath in weeks from pancytopeniaNausea & vomiting?Radiation sensitivity is not commensurate with a tissues capacity to regenerate. Radiosensitive (radidly growing)Intermediate Resistant Bone marrowGonadsGrowing cartilage/boneLens of eye (risk from UV)BowelThyroidPituitaryKidneyHeartLungLiverBrainSkin (risk from UV)Tumour MarkersTumour MarkerSubstance found in circulation (or immunohistochemical marker) Directly related to presence of neoplasm Disappears when neoplasm treated, reappears when neoplasm recurs Not usually stoichiometric - not in direct proportion to tumour bulk?ClassificationHormones: Eutopical / ectopical ACTH hGH (pituitary adenoma) EPO - renal cell carcinoma B-hCG: teratomas, choriocarcinoma Enzymes Prostatic acic phosphatase (not prostatic specific antigen) - Ca prostate Placental alkaline phosphatase - ca bronchus, pancreas, colon Oncofetal antigens a-fetoprotein (foetal albumin): germ cell tumours, hepatocellular carcinoma Carcioembryonic antigen (CEA): colorectal UrologicalRenal cell carcinomaPresenting featuresGeneral / primary Weight loss, cachexia Mass in loin New varicocoele on left (as left gonadal vein is longer and thus more easily compressed) Secondary Paraneoplastic manifestations InvestigationsUrine dipstick FBC, LFTs Imaging: USS / CT CXR: cannonball pulmonary metastases? RhabdomyolysisRhabdomyolysisClinical syndrome caused by release of potentially toxic muscle cell components into circulation?TriggersTrauma Crush injury Burns Hypothermia Reperfusion Drugs Congenital ComplicationsRenal failure - ischaemic tubular injury DIC Compartment syndrome Electrolyte imbalances - hyperkalaemia, hypocalcaemia, hyperphosphataemia, hyperuricaemia Hypovolaemia DiagnosisElevated CK (x5 normal) Elevated creatinine Elevated serum lactate dehydrogenase Dark urine + positive urine dipstick ManagementAdequate hydration Diuretics Alkalinise urine Manage electrolyte disturbances? EpistaxisThe NoseBony and cartilaginous framework Overlied by skin and fibrofatty tissue Bones: external: nasal bone + frontal process maxilla Internal: nasal, frontal (crista galli), ethmoid, maxillary (palatine process), sphenoidal Medial septum: vomer, ethmoid perpendicular plate Divided into left and right nasal cavities by nasal septum (perpendicular plate of ethmoid bone) Epithelium: respiratory (ciliated columnar) Conchae/meatus/turbinates Superior meatus: opening of posterior ethmoidal air cells Middle meatus: frontal, maxillary, anterior and middle ethmoidal Inferior meatus: nasolacrimal duct from eye ?Blood Supply to the nose(All derived from external carotid artery)Anterior ethmoidal Posterior ethmoidal Sphenopalatine Greater palatine External branches of labial EpistaxisManagementResuscitate History Duration of bleeding Preceding injuries: nose picking, nasal trauma, infection, neoplasia Medications - anticoagulants, antiplatelet agents PMHx of bleeding diathesis, family history Perpetuating factors - hypertension Assess bleeding FBC, U/Es, LFTs, Coag Examination (personal protection - gown/apron/gloves/visor) Patient should attempt to clear their nose Spray local anaesthetic (with adrenaline as vasoconstrictor) Identify source of bleeding by anterior rhinoscopy with Thudicum's speculum Look at kisselbach's plexus (anterior part of septum in Little's area) If bleeding not visible, may be posterior bleed Emergency Treatment Digital pressure to entire nose + cold compress/ice pack Silver nitrate cautery / electrocautery coagulation of vessel (only one side of septum should be cauterised at once; small risk of septal perforation) Pack nostril with nasal tampon (Merocel) / ribbon gauze (BIPP) - can pack both to increase tamponade effect; complications - sinusitism, airway obstruction, inhalation of pack, infection (risk of toxic shock syndrome) Foley balloon catheter used for tamponade Surgical treatment Posterior nasal packing (under GA) Submucosal resection which decreases blood flow to mucosa Endoscopic visualisation of sphenopalatine artery and bipolar cautery/ ligation Arterial ligation Angiogram and embolisation Follow up BP check with GP Further nasal examination to exclude neoplasia ................
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