9/5



9/5

Cardio

-respiration = exchange of gases

-respiratory failure – not exchanging gas (still breathing)

-ventilatory failure – not breathing

-VQ-balance (V=ventilation; Q=blood) ( V/Q=life

-air+blood=life

-ultimately all deaths are caused from an imbalance b/n air and blood

- CPR (heart-lung respiration = air+blood)

-if can keep air/blood going, patient will live

-gun shot wound – loss of blood causes death

-5 abnormalities of cardiac function (95% of all cardiac problems):

1-rate

2-rhythm

3-axis

4-conduction

5-perfusion

-normal heart rate = 60-100 bpm

-above 100 = tachycardia

-below 60 = bradycardia

-SA node determines heart rate

-SA node is a cluster of myocytes (not a cluster of nerves)

-pacemaker = paces the rate of the heart

-depolarizes about 80 times per minute on its own

-symp and parasymp both have affects on SA node – changing the permeability to Na

-symp: NE ( depolarize faster (tissue function is enhanced)

-parasymp:

-AV node is also not a nerve, but muscle cells

-difference b/n SA node cells and cells around them: SA node cells depolarize faster

-Na travels in and K out (outside of cell becomes less positive and inside less negative)

-node from latin nidus (meaning “nest”)

-sinus tachycardia – SA node is firing too fast

(“sinus” always refers to SA node)

-sinus bradycardia – slow heart rate due to SA node not firing fast enough

-incr symp = sinus tachycardia

-incr parasymp = sinus bradycardia

-ventricular tachycardia – issue is in the ventricle muscle cells

-a cluster of muscle cells is depolarizing faster than SA node

-any area in the cardiac muscle has the potential of depolarizing faster than SA node

-if patient has parasymp-otonia (vagus inhibiting SA node), it is possible that another cluster of muscle cells could take over

-ectopic = away from normal site

-ventricular tachycardia is much more dangerous than sinus tachycardia (SA node no longer in control)

-NSR = normal sinus rhythm

-atropine = vagal inhibitor drug

-by inhibiting the vagus, the SA node is released from excessive parasymp stimulation

-upper cervicals communicates with nodose ganglion, which is vagal

-if excite upper cervs, then excite nodose ganglion, and excite vagal nerve = decr Heart Rate ↓

-the elderly commonly experience vagotonia

-after eating or going to the bathroom causes the parasymp (vagus) kick in

-people often have heart attacks either after a big meal or while going to the bathroom

9/11/07

EKG/ECG (ekg is german)

Lead – a view

-ie a 12-lead ECG provides 12 views of the heart (12 different angles)

-10 electrodes that provide 12 views

-by changing polarities, you can change the view

-Einthoven’s triangle – 4 electrodes (one is grounded)

-polarities can be changed around and have 6 different views

II, III, and aVF are (inferior-leads), and look at right coronary artery

-if IMI (inferior MI) – viewed from these 3 leads

-if ischemia in inferior portion of heart, the right coronary artery is the problem

Left main coronary artery – divides in circumflex and left anterior descending (LAD)

-aVL and lead I (lateral views) – important for circumflex artery territory

-if lesion of left main, then both LAD and circumflex affected

-left ventricle is fed from LAD (anterior views: V4, V5, V6)

-precordial (chest) leads – (V1-V6), provide anterior view

-unipolar leads (all positive)

-AMI (ant MI) – left ventricle is damaged

-Decr cardiac output (CO), if left ventricle begins to fail

-normally, CO>55% otherwise serious trouble

-pulmonary edema (fluid backed up into lungs, which then leaks out into pulmonary capillaries)

-a good indicator that the heart is in cardiac failure

-AMI is most dangerous, and IMI is often most common

-when leads are close together, they often look alike

-aVF looks like II and III

-aVR is the ONLY view from the right side of the body

-lead II is the normal PQRST graph, but in physio, we’re not taught other views

-PQRST is upside-down for aVR – heart signal travels away from it

-all hearts depolarize from rt to left side

-signal is upward when headed towards the lead

-when the signal heads away from the lead, it goes in a negative/downward deflection

-aVL – biphasic – both positive and negative – sometimes depolarization heads towards and other times away from it

1) atrial depolarization

2) ventricular depolarization – signal goes to right side

3) “ “ - signal is parallel with lead II

4) “ “ - signal is slightly to the left side

-Rhythm strip – lead II

-for diagnostic ECG, must have 12 leads

9/11[2]

-rt ventricle is 1/3 energy/strength of left ventricle b/c lung pressure is 1/3 systemic pressure

-when take a deep breath, resistance against capillaries drops dramatically and HR incr,

back pressure against ventricles is reduced

-as breath out, pressure is restored in lungs, against rt side of heart and rate will go down

-respiratory rhythm – incr and decr heart rate correlates with breathing (desirable)

-smoking, age, and disease decr respiratory rhythm

-if systemic hypertension, then left side of heart pushes harder against that and causes hypertrophy

-smoking – damaged capillaries, decr surface area, rt ventricle hypertrophy, decr CO from rt ventricle,

and leads to ankle edema

-patient taking diuretics: reduces patient’s potassium levels

-SA and AV bundle – muscle fibers – **NOT NERVES**

-depolarization cannot get through septal wall of the heart

-P wave: atrial depolarization – walls have depolarized

-atrial depolarization travels toward lead II, therefore it is positive

-P wave does not mean the SA node fired, but rather that the atrial walls have depolarized

-Bachmann’s bundle carries the single (from rt atrium) through septal wall into left atrium

-if extra long P-wave (atrial depolarization is prolonged), could be from enlarged atrial wall

-if two humps in P-wave, rt atrium is normal, and signal is delayed in left atrium

- left atrial wall might be enlarged (if Mitral stenosis or if Mitral regurgitation)

-P-mitrale: P-wave resembles letter “M” – due to left atrial enlargement

-if P-wave negative: SA node not firing, AV node is possibly behaving as pacemaker

-normal axis: 0-90 degrees

-SVT- supraventricular tachycardia

-tachycardia is the result of a supraventricular spot (on atrial wall)

-a renegade spot of tissue on atrial wall that is firing

-if tachycardia is from SA node – sinus tachycardia

9/12/07

-the more in line with a lead the depolarization is, the taller it is

-lead II has tallest “R”wave, b/c vector is headed directly toward lead II

-for the standard – all three (I, II, and III) must be positive, and II must be tallest

-left ventricle is the only one that produces the QRS

-normally, there are two left bundle branches, and one right

-AV delay allows ventricles fill to maximum

-when AV delay is not there, we have Wolff-Parkinson-White (WPW) syndrome

-go right from atrial depolarization to ventricle

-ventricles not as full as they should be

-heart pumps faster to compensate

-heart requires more oxygen when pumping faster

-decr oxygen to cardiac mm ( leads to angina

(1) P wave – atrial depolarization

(2) Q is septal depolarization

(3) R is early ventricular depolarization

(4) S – late ventricular depolarization

(5) T – ventricular repolarization

-Q is always negative and indicates ventricular depolarization from view II only

(there should not be Q-wave in lead aVR)

-R is always positive

-S is always negative

-if no Q, heart could be tilted a little differently, or electrodes could have just not picked it up

9/13/07

-QS pattern is indicative of pathology

-infarction (dead tissue) – nothing depolarizing toward lead II

-tissue is not depolarizing

-possible patterns: QRS, RS, QR, QS, QRSR’, RSR’

-when R and R’, ventricles are not beating/contracting synchronously

-bundle branch block – delays the ventricular depolarization

-could have bundle branch block appearance (as common as being left-handed)

-CT does not conduct current

-on EKG, vertical lines = 1/5 sec

-300 vertical lines per minute

-if PR segment lengthens – AV delay is increased

-AV node is innervated by vagus

-parasympatheticotonia could contribute to AV delay

-1st degree block if AV node holds onto the signal too long

-slowing down the heart after an MI is not good – AV blocks are feared

-PR interval should never be larger than one box (1/5 second)

-interval between end of P-wave and start of QRS should be less than 0.2 seconds

-atropine: blocks the vagus

-if atropine removes the AV block, then lesion is vagal nerve

-but if atropine has no effect on AV block, then pblm is with the AV node itself

-ischemia to right coronary artery

-vagus will incr its firing if AV node doesn’t respond

-if ventricles are ischemic and don’t respond to sympathetics, then symp incr amt of NE released

-Sinus –

-sinus rhythm – rhythm of the heart is all due to the SA node

-sinus arrest – SA node has arrested

-atrial –

-premature atrial contraction – renegade spot on atrial wall that caused the heart to beat

-atrial beat (not a sinus beat) – ectopic beat coming from anywhere in the atrial wall (not at SA node)

-ectopic – if event didn’t come from normal site (SA node)

- event did not originate from SA node

-nodal & junctional– both always in reference to AV node

-junctional rhythm – AV node is pacing the heart (sinus arrest)

-junctional beats – ectopic

-supraventricular – above the ventricle

-supraventricular tachycardia - heart is beating too fast from atrial wall from site other than atrial node

-ventricular – ventricular wall

-ventricular contraction – signal from ventricular wall (very bad)

9/18/07[1]

-infranodal – below AV node

-in reference to the common bundle of His

-infranodal pacing – bundle of His is pacemaker

-1 beat every box = 300 beats/min

-1 beat every 6 boxes = 50beats/min

-sinus tachycardia –

-if can see Pwave, it is sinus, as opposed to supraventricular tachycardia

-sharp, narrow, tall Pwave = P-pulmonale

-height of Pwave is due to incr in size of atrium

-patient likely has pulmonary hypertension or pulmonary (or tricuspid) valve stenosis

(diet pills are linked to pulmonary hypertension)

-sinus bradycardia – incr length of time b/n Twave and Pwave

-inverted Twave - repolarization in opposite direction – ischemia (heart does not have sufficient blood)

-angina

-if heart is beating slowly, it might not be feeding itself, and patient feels chest pain

-atropine blocks vagus, and incr heart rate

-supraventricular tachycardia

-multifocal atrial tachycardia – many sites in atrial wall causing tachycardia

-fat QRS – taking longer for ventricles to contract

-bundle branch block

-a sneeze slows down the heart rate

-dyspnea – shortness of breath

-large Twave could be electrolyte imbalance

-often COPD patients are on dialysis

-poor skin contact leads to staticky appearance

-Vtach = ventricular tachycardia – no PQRST (signal follows no pathway)

-signal coming from ventricular wall

9/18/07[2]

-Wandering pacemaker

-PAC - premature atrial contraction

-one Pwave has different morphology than other Pwaves

-group of cells close to SA node are excited and fire slightly before SA node fires

-PACs occur in young people, but not in older people

-heart reacts to catecholamines in the blood and could fire a group of cells prematurely

-irregular heart beat could be:

-PAC (following a PAC, there is always a pause)

-sinus arrhythmia (premature sinus contraction – Pwave looks like the others)

-2nd degree block – two Pwaves

-SA contracted, but signal did not travel to ventricles

-block was probably at the common bundle

-fear of ventricular arrest (asystole), during exercise

-Atrial flutter - extreme arrhythmia, no definable Pwave – bombardment to AV node so strong

-atrial flutter: 250-350 beats/min

-atrial fibrillation: >350 beats/min

9/19/07

Sinus arrest –no Pwave – atrium not depolarizing

Sinus arrhythmia – irregular heart beat, originating from SA node

-common in young people ( < age 30)

Vtach - no visible morphology; no PQRST; every beat is ventricular

– looks like a full-wave rectified graph

– carotid massage would not help

– can rapidly deteriorate to ventricular fibrillation, which is fatal

-carotid massage is only effective for sinus tachycardia

-common lesion above ventricle: atrial wall can become involved in fibrillation ( > 350 beats/min)

-atrial fibrillation: numerous sites on atrial wall firing simultaneously (usually idiopathic)

-not all atrial contractions make it to the ventricle

-rate is elevated and rhythm irregular

-doctors treat atrial fibrillation as sympatheticotonia

-pulmonary or systemic embolism is greatest fear (if blood coagulates in the atrium)

-Pwave and Twave are often both missing

-atrial flutter: picket-fence appearance

-whenever there is fibrillation, doctors always look for ischemia

-multifocal PVC (premature ventricular contraction) – absolute emergency situation

-at lease two renegade spots on ventricular wall

-morphology of 2 spots looks different on EKG

-IMI = inferior myocardial infarction (leads II, III, aVF)

-TPA drug (tissue plasminogen activator): powerful clot buster – can cause a stroke

9/20

PVC = premature ventricular contraction (signal started in the ventricle)

-catecholamine (NE) build up in walls immediately following MI due to VA-VE reflex

-beta-blockers try to reduce influence of this VA-VE reflex

“The Somatic Component of MI” – British Medical Journal?

-evidence of this VA-VE reflex before MI with spastic muscles & fixation around T1-T4

-hypokinesis – decreased movement

-ejection volume (EV) – how much blood is rejected with every beat

-If EV below 55%, problem

-coated stints promote inflammation and can promote clotting (but their purpose was to reduce clotting)

-if heart attack victim, give two small baby aspirin, wait 2 minutes, then give 2 more (provides fasted absorption)

-PAC (premature atrial contraction)

-inverted Pwave – comes from ectopic spot on atrial wall

-wandering pacemaker

-rhythm: 3 or more consecutive beats

9/25/07

Ventricular ectopic rhythms

-ventricular wall renegade spots

-multifocal PVCs – at least two or more sites on wall of ventricle are irritated and renegade

-almost always the rhythm is too fast if a ventricular ectopic spot

-leads to Vtach and Vfib

-clinically significant if more than 6 per minute

-can be caused by ephedrine

-if unifocal, not as significant as multifocal

QRS= 80% then restrictive

-in healthy people, the lungs are slightly more ventilated than perfused (V>Q)

-normal V/Q balance is 1.0, but this never happens

-the accepted norm is 0.8

-every ventilatory disease creates a low V/Q (less ventilation than blood)

-two conditions reduce ventilation: obstructive and restrictive

-if poorly ventilated, reduced alveolar O2 (PAO2)

-most RBC’s have between 95-100% saturation, but will drop quickly if hold breath for a few seconds

-when SaO2 decr, PaO2 will decr

-if tissue is getting low in O2, then body responds by producing more RBC’s (polycythemia)

10/24

-high V/Q = more air than blood

-if person is hemorrhaging, if pulmonary embolism, if anemia

-low V/Q

-pulmonary fibrosis

-V/Q imbalance leads to: decr PaO2, incr PaCO2 (decr pH) – leading to respiratory acidosis

-will NOT have O2 deprivation

-silent unit = neither perfused nor ventilated (no blood and no air)

-hypoventilated ( absolute shunt

-absolute shunt: no air at all (giving oxygen does no good)

-reduced oxygen due to: hypoventilation, diffusion impairment, V/Q imbalance, shunts

-atelectasis (example of an absolute shunt)

-collapsed alveolus (no ventilation)

-pneumonia is characterized by atelectases (plural)

-consolidation – the area has been completely solidified by fibrous tissues

-as V decr, PAO2 decr, and PACO2 incr, then SaO2 decr, and PaO2 decr (hypoxemia), incr PaCO2 (hypercapnia)

-to correct this problem:

1) increase ventilation

2) increase # of RBC’s, which in turn increases Hematocrit, which increases viscosity of blood

-leads to even less saturation (SaO2 decreases more)

3) increase 2-3 DPG, which reduces the affinity of the RBC for oxygen

-RBC’s are more capable of dumping O2 in the needed tissues, but can’t pick up as much O2 in the lung

-if give patient O2, ventilation will reduce even more, which will increase the CO2

-patients can go into respiratory acidosis in 20 minutes

-don’t ever advise a patient to turn up the oxygen a little bit, because it will reduce ventilation

-nitric oxide is produced by endothelial cells, but they require oxygen

-muscles constrict if reduced oxygen, which reduces the amount of blood flow to that area

-a decreased V will lead to a decreased Q – leads to a silent unit

-pulmonary hypertension (will destroy the right side of the heart)

-for emphysema patient, solution is to get rid of the fluid (ie with diuretics)

-by pushing blood through a poorly ventilated unit (ie with nitric oxide), you run the risk of respiratory acidosis

10/25/07

-any person with a ventilatory disorder (measured by vital capacity) has a low V/Q

-only healthy people can hyperventilate

-shunt unit: unit in which the ventilation is going down

-absolute shunt =absolutely no ventilation

-venous admixture: 5% of blood that enters the lung is no longer oxygenated by the time it enters the heart

1) bronchial circulation

2) pleural circulation

3) thebesian circulation (feeds the heart)

-if venous admixture increases to 6%, it becomes noticeable as cyanosis (bluish appearance)

-increase venous admixture by adding poorly oxygenated blood to it

-if hypoxic areas of the lung, the blood will be reduced in oxygen saturation

-acid environment = shift to the right of the oxygen dissociation curve

-lungs should be a shift toward the left

Pulmonary hypertension

-viscosity of blood can increase the pressure

-reduction in surface area (emphysema)

-vasoconstriction of capillaries through poorly ventilated units (trying to divert the blood to other areas)

-when a deficit of O2, endothelial cells reduce production of nitric oxide

-when poor ventilation and low O2, we run the risk of respiratory acidosis if give O2 supplementation

-but they could go into cardiac failure if they don’t give ambient oxygen

-nitric oxide should not be given to patients with emphysema (will cause respiratory acidosis)

10/30/07[1]

Example: 22 y.o. with asthma, PO2 = 60, PCO2 = 35, pH = 7.35, SaO2 = 90%

-person is hypoxemic, even though 90% saturated

-28% O2 is administered and 1 hour later, PO2 was 90, PCO2 = 38, pH = 7.37, and SaO2 = 96%

Was this patient’s hypoxemia caused by hypoventilation, shunt, or V/Q mismatch?

-not hypoventilation b/c can’t possible blow off CO2 if hypoventilating

-not shunt (absolute shunt – no ventilation), b/c oxygen helped

-must be V/Q mismatch

-pneumonia completely shuts down areas of the lung (shunts) and cannot oxygenate those areas

-pneumonia will cause atelectasis

-you cannot oxygenate a complete shunt

-carotid and aortic bodies are the chemoreceptors for ventilation (when become low in O2)

PO2 of 80 is mild hypoxemia

60 is moderate

40 is severe

-all ventilatory disorders create a low V/Q (obstructive/resitrictive)

-deadspace units (high V/Q)

-plenty of air, but no blood

-circulatory problems, anemias, cardiac problems, pulmonary embolism, etc

-both low or high V/Q will:

Reduce PaO2, Incr PaCO2, reduce SaO2, reduce pH

-acidosis = pH < 7.2

-silent unit = no air and no blood

-the body creates a silent unit if no air or no blood

-blood pressure increases

-collapsed lung (makes no sound)

-upper lobes are more ventilated than perfused

-lower lobes are more perfused than ventilated (b/c of gravity)

-a ventilatory disorder affecting the lower lobes is better off than affecting upper lobes

-polio (paralyze respiratory muscles) – low V/Q

-asthma – low V/Q

-pulmonary fibrosis – low V/Q

-pulmonary embolism – high V/Q

-ventricular fibrillation – high V/Q

-cor pulmonale (enlarged rt side of heart) – high V/Q

-sick sinus syndrome – high V/Q

-pneumonia – low V/Q

-primary pulmonary hypertension – high V/Q

-decreased FVC – low V/Q

-pulmonary edema (edema in lungs reduces ventilation) – low V/Q

Deadspace = good air (ventilated air)

-wasted air (located where it cannot be used)

-high V/Q

-anatomical deadspace (normal)

-in upper respiratory, conducting zone (trachea and bronchi) – 150ml of air

-vital capacity includes deadspace

-alveolar deadspace (the bad stuff)

-no blood (high V/Q)

-physiological deadspace = anatomical deadspace + alveolar deadspace

-if healthy, physiological deadspace = anatomical deadspace

-no alveolar deadspace, if healthy

-a heart attack, pulmonary embolism, etc. would incr physiologic deadspace

-people that are barrel-chested are not due to dead space

-barrel-chest is because he is not ventilating (residual volume – nonventilated tissue)

-a person with emphysema does NOT have incr deadspace

-Raw = airway resistance

-Raw incr in airway diseases: asthma, emphysema, and bronchitis

-if you can blow 80% of air out in first second, then you don’t have airway resistance

10/31/07

-retrograde activation of sensory nerves by a local axon reflex, resulting in the release of peptides, may contribute to inflammation of the airways.

-neurogenic inflammation is probably not relevant to mild asthma (adult onset), however, but it may be more important is severe disease such as brittle asthma.

-Neurogenic switching is proposed as a hypothesis for a mechanism by which a stimulus at one site can lead to inflammation at a distant site. (ie one could have inflammation in the hand and end up with inflammation in the viscera)

-Neurogenic switching is proposed to result when a sensory impulse from a site of activation is rerouted via the CNS to a distant location to produce neurogenic inflammation at the second location.

-if have shoulder problems for years and don’t get it taken care of, likely will result in severe arthritis of c/s facets

-substance P (pro-inflammatory) released via axon reflex

-Asthma is possibly a neurogenic disorder and therefore we cannot rule out any source of afferentation

-Although, nowadays, asthma is recognized as an inflammatory disorder of the airways, neural mechanisms remain very important; axon reflexes, in particular have received greater attention in recent years. Therefore, it has been suggested that modulation of axon reflexes could be of potential benefit in axon treatment.

-peripheral & central chemoreceptors (keep us breathing)

-peripheral chemoreceptors

-aortic & carotid bodies

-innervated by vagus (VA fibers)

-measure oxygen and pH

-when oxygen is below 60 (moderate hypoxemia), these fibers fire

-increases the rate and depth of breathing

-“the hypoxic drive”

-when oxygen is below 30, these fibers quit firing and patient quits breathing

-central chemoreceptors

-sensitive to levels of CO2

-these receptors are protected by the blood-brain barrier

-nervous system is the first system to be damaged by an acidic condition

-CNS is very sensitive to pH

-active transport of HCO3 through BBB into CSF to buffer CO2

-COPD wipes out the central chemoreceptor

-if central chemoreceptor is wiped out, and then give O2 to patient, the peripheral chemoreceptor no longer fires

-no ventilatory drive

11/1/07

-the neurogenic switching hypothesis was introduced by Meggs which meant to explain the etiopathogenesis of allergic disease, migraine, arthritis and other inflammatory diseases. It is proposed that a local inflammation was able to initiate another inflammation in other parts of the body….

-the propagation of oral fecal infection to system could be conducted by several mechanisms, via the blood stream or the neurogenic switching mechanism. The interplay b/n immunogenic and neurogenic inflammation was called the neurogenic switching mechanism.

-atopy = allergy

Meggs postulates that neurogenic switching explains inflammatory response, including how an inflammatory stimulus applied to one tissue can result in inflammation in a different tissue

-neurogenic switching is proposed to result when a sensory impulse from a site of activation is rerouted via the CNS to a distant location to produce neurogenic inflammation at the second location.

-peripheral chemoreceptors = hypoxic drive (sensitive to decreased oxygen)

-central chemoreceptors – sensitive to hypercapnia (either drowning or quit breathing)

-CO2 is so readily gotten rid of, the ultimately CO2 doesn’t build up (except in extreme cases)

-increase rate and depth of breathing to get rid of CO2

-except in COPD, where ventilation is not successful in blowing off CO2

-in this case, HCO3 is used as a buffer to control pH in CSF

-central chemoreceptors become desensitized (no longer sensitive to CO2)

-mechanoreceptors in respiratory muscles sends signal to cortex, which then sends signal to respiratory control center

-dyspnea sensation comes from mechanoreceptors (not from blood gases)

-shortness of breath is a mechanical problem and not a chemical problem

-high CO2 & low oxygen would put you to sleep

-know recoil is decreased by the FEV1/FVC

-unable to blow air out (recoil is the function that blows air out)

-obstructive airway disease

-residual volume is not the same as dead space

-a patient with a heart attack would experience lots of dead space (ventilation but no blood)

-both dead space or shunts will put you into acidosis

11/6/07

-normal immune response:

-IgA (secreted by plasma cells) lodges onto toxin and serves as a way for the macrophage to identify invading agent

-allergic reactions in the airway

-plasma cells produce IgE, which lands on the surface of mast cells (sensitizing the mast cells)

-the next time the allergen enters the airway, it attaches to the surface of the mast cell causing it to release histamine

-certain steroids prevent the lysis of the mast cell, reducing the inflammation in the airways

-IgE is normally found in the intestines and is there to protect us from parasites

-Extrinsic asthmatics

-people react to things outside of themselves

-seasonal asthmatics

-Intrinsic asthmatics (aka neurogenic aka adult onset)

-people not shown to be allergic to certain allergens

-perennial, not seasonal

-chemical sensitivity to inhalants refers to an abnormal sensitivity to a class of inhalants that is different from allergy to protein aeroallergens (ie mold, pollen, etc)

-ie a chemical sensitivity to formaldehyde is not an “allergy” to formaldehyde

-in general, allergic reaction are only in response to certain proteins (and not to chemicals)

-It is natural to consider neurogenic inflammation as a possible mechanism of chemical sensitivity. For many decades it has been known that sensory neurons are involved in an inflammatory process, and that this neurogenic inflammation is triggered by chemicals that stimulate these sensory neurons.

-many VA fibers in airway (many vagal, and some spinal C-fibers)

-stimulation of these fibers lead to an inflammatory response

-In a controlled study of patients with chemical sensitivity, Doty et al. found significant increases in airway resistance in the chemically sensitive group.

-In asthma, chemical associations have been verified for perfume and tobacco smoke.

-if allergic rhinitis

-trigger: protein aeroallergens

-target cell: mast cell

-mediator released: histamine

-recruited cell: Eosinophil

-sensation: Itching

-symptoms: Rhinorrhea, sneezing

-if chemical irritant rhinitis

-trigger: chemical inhalants

-target cell: sensory nerve cell

-mediator released: substance P

-recruited cell: lymphocyte

-sensation: Burning

-symptoms: Congestion, headache

-if allergic to dust mites, you’re really allergic to their poop

-if allergic to cat hair, you’re really allergic to their saliva

In experimental models of anaphylaxis, ablation of neuronal pathways eliminates the anaphylactic response without blocking histamine release or antibody production. This switching of the site of inflammation in allergy and chemical sensitivity may be due to the same mechanism: there are neuronal pathways from the site of stimulation through the CNS to other peripheral locations. This mechanism of site switching has been termed neurogenic switching.

Sensitized nerves release Substance P which causes mast cell degranulation and histamine release.

-these sensitized nerves excite the cord which then stimulate antidromic conduction along sensory pathways of nerves originating in a similar area of the CNS (antidromic conduction also causes the release of Substance P)

11/6/07[2]

Neurogenic inflammation

1 -sympaticotonia: releasing NE in the tissues, enhancing their function

-continuous sympathetic stimulation to a tissue will ultimately damage that tissue

2 -chemical sensitivity is another way that the nervous system can produce inflammation

3 -a combination of the above two

-allodynia – person perceives pain from a non-painful stimulus

-glutamate and substance P released on sensitized WDR (wide dynamic range neurons) – causing pain

-result of chronic afferentation of C-fibers

Neurogenic switching

11/7/07

FRC = TV + ERV + RV

-bronchodilators, opening up airways will help to reduce RV and incr IRV, which increases VC

-useful in reversible conditions, like asthma

-however, if restrictive disease (cannot inflate lungs), every single lung volume will decrease

-if ventilatory disorder, people have alveolar hypoxia

-they have difficulty ventilating

-stagnant hypoxia = blood is not circulating (Q is decreased, causing high V/Q)

-dead space (wasted air) = well ventilated, but no blood

-shunts (decreased V) – wasted blood

-shunt = less ventilated than perfused

-to tell obstructive vs restrictive, must calculate ratio FEV1/FVC

-obstructive, if ratio is decreased (below 80%)

-RV = unventilated lung tissue

-asthmatics have higher RV, because chronic bronchoconstriction and mucous production

11/8/07

-Tidal Volume rarely changes, even in severe diseases

-ephedrine is a horrible offender in creating suboccipital headaches

-in asthmatic, ERV likely reduces, RV increases, but FRC stays the same

11/14/07

TEST 3 material

3 types of Bronchitis:

1) Acute Bronchitis

-nearly everyone has had this

-lasts 10-14 days, and is self-resolving

-most common cause: exposure to allergens

-chemical sensitivities probably result from epithelial shedding (mast cell degranulation?)

2) Simple chronic Bronchitis

-cellular changes: airway changes that are reversible

-cough for 3 consecutive months for over 2 years (conditions are reversible within 5 year time frame)

3) Chronic obstructive Bronchitis (aka Respiratory bronchiolitis aka Centrilobular(acinar) emphysema)

-not reversible

-cigarette smoking is the most important risk factor

-90% have a smoking history, although only 15% of all smokers are ultimately diagnosed with obstructive airway dx

-syndrome defined by presence of cough on most days for three months (per year) over 2 consecutive years

-accumulation of neutrophils and macrophages in airway lumen

-cough and sputum production

-persons remain colonized with bacteria

Definition of Bronchitis: mucus secretion and coughing

-lots of people get a dry cough following an upper respiratory viral condition

-irritant/cough receptors in airway remain sensitized following viral infections

Mucus:

Top layer: gel

Lower layer: sol

-cilia on columnar epithelial cells (about 200 on each cell)

-propels toxins to mouth where it is swallowed

-cilia must beat in a watery environment

-smoking increases the number of mucus glands and reduces the number of serous glands (it makes the mucus thicker)

-smoking inhibits muco-ciliary escalator by changing the nature of the mucus and reducing the # of cilia by 90%

-if a person quits smoking, it takes 5 years for all this to return to normal (assuming they haven’t developed emphysema)

-hyperplasia and hypertrophy of mucus glands is a reflex generated through the nervous system

-vagus, sympathetics, and C-fibers

-increasing vagal tone promotes mucous production and smooth muscle contraction

11/15/07

-macrophage: last defense

-goblet cells vs serous glands is really not clear

-goblet cells can transform into mucous glands

-thin watery fluid from serous glands

-thick gel layer from mucous glands

-mucous glands increase in size and number in simple chronic bronchitis

-Reid index: measure of the amount of space the mucous glands takes up

-incr Reid index = increase in size of mucous glands

-Reid index is reversible

-Alfred P. Fishman

-mucous hypersecretion, probably by a nervous reflex produces submucosal mucous gland hypertrophy in larger airways

-mucus present in the airways predisposes to colonization by bacteria and offers a nidus in which bacteria can multiply

-a patient’s deterioration is usually gradual and not related to the intermittent bouts of infection. Instead, it seems likely

that hypersecretion of mucus and the presence of secretion within the airway lumen – whether or not it is colonized

by bacteria – are in some way link to the deterioration in airway functions.

-The prophylactic use of appropriate antibiotics has failed to arrest the long-term decline in the FEV1 and merely tends

to shorten the duration of exacerbations in those thus treated. Yet the absence of evidence concerning the benefit of

antibacterial chemotherapy does not deter physicians from thus treating patients with all but the most trivial of exacerbations and then claiming benefit.

-Addition mechanism, such as neurogenic inflammation, may develop, and the symptomatic flare-up of chronic bronchitis

may continue by means of sustained inflammatory mediators.

-Goblet cell metaplasia is a routine feature of airway alteration in both asthma and chronic bronchitis.

-In a model of neurogenic inflammation, airway inflammation is initiated with epithelial cell injury caused by various

stimuli. Various products may then activate mucosal sensory nerve fibers, resulting in the antidromic release of

nonadrenergic, noncholinergic neuropeptides, such as substance P, neurokinin A, and calcitonin gene-related peptide.

-Injury ( inflammation ( leukocytes ( group IV fibers (C-fibers) excitation ( substance P exciting leukocytes along with cord excitation and pain ( sympathetics excited ( NE and prostaglandins ( excite group IV fibers

-Viscerogenic secondary lesions are segmentally related to distant pathophysiology…By way of illustration, consider a case in which bronchitis is the initial visceral disorder… In our hypothetical case there is a secondary group lesion in the articulations between T2-T5, involving the corresponding costovertebral articulations, associated muscles, and other periarticular soft tissues… the structures become irritated or reactive to the point that after the bronchitis is resolved and the viscerogenic afference ceases, the secondary osteopathic lesion continues – but now it is a primary lesion on its own, continuing to cause vasomotor disturbances in the bronchi, or perhaps bronchospasms and hypersecretion.

Extrinsic asthma

-mainly atopy, antigen-related, IgE mediated, eczema/(hay fever) common, environmental control is useful, relief between …, effective results from treatment, typical attack is acute & mild, often positive hypersensitivity skin tests

-primarily children, seasonal

Intrinsic asthma

-non-antigen related, not IgE mediated, eczema uncommon, environmental control is not useful, variable results from treatment, typical attack is often severe, usually negative hypersensitivity skin tests, desensitization is not helpful

-adult onset, not seasonal

11/20/07

ASTHMA

-respiratory zone (vs bronchitis, which is in the conductive zone – upper respiratory area)

-emphysema = bronchitis in lower respiratory zone (chronic obstructive bronchitis)

-dyspnea is the most common symptom associated with asthma

-wheezing also exists with asthma (but not with bronchitis)

-anything that causes a tonic bronchoconstrictive state = asthma

-xanthines – class of drugs for treating asthma

-theophelan was the most popular drug in the xanthine class

-block the phosphodiesterase enzyme – forces the muscle to quit constricting

-these xanthines led to hypertension, sympathetic stimulation, cardiac arrhythmias, and stroke

-epinephrine – attaches to the beta receptor

-aimed at relaxing smooth muscle

-mucolytic drugs used to reduce mucus in airways

-then emphasis is on the anti-inflammatory drugs

-ie prednisone (but numerous systemic side-effects)

-then inhaled steroids became popular

-reduce output of inflammatory cytokines

-singulaire (sp?) drug, and albuterol

-if bronchospasms are not stopped in early childhood, the nervous system habituates them and leads to asthma

-the highest incidence cases of asthma are in low-income unsanitary areas

-extrinsic and intrinsic asthma

-chemical sensitivity vs allergies

-chemical sensitivity has nothing to do with IgE levels

-smooth muscle constricts and blocks airways

-SRS-A (slow reactive substance – anaphylaxis) – released by the Mast cell

-most powerful naturally produced bronchoconstrictor

-this is what kills people

-vagus nerve also causes the smooth muscle to constrict (also innervates mucus glands)

-vagovagal reflex = bronchoconstriction

-only one built-in mechanism to cause bronchorelaxation

-Beta2 receptor (beta-adrenergic receptor) causes bronchorelaxation

-phosphodiesterase is an intracellular enzyme that interferes with bronchorelaxation

-if Beta2 is stimulated too much then phosphodiesterase production increases to block the Beta2 reaction

-if overuse albuterol inhaler, its effectiveness reduces dramatically

-status asthmaticus (a tragic end to severe asthma)

-bronchorestriction that is refractory to bronchotherapy (doesn’t respond to bronchotherapy)

-theophelan (a xanthine) is a phosphodiesterase inhibitor

-C-fiber in airways

-nodose ganglion is the site in the neck with the cell bodies of the vagal afferent fibers

-irritant receptor cell bodies**

-it is joined by the spinal accessory nerve, the hypoglossal nerve, and the loop b/n 1st two cervical nerves

-nobody knows what exactly is occurring in this ganglion

-it is known that it communicates with the upper two cervical nerves

-50% of chiropractors who treat asthma, do so with upper cervical adjustments

-antigen stimulates immunoblasts to produce IgE, which lands on Mast cell surface

-ideally, IgA would be produced, not IgE

-decreased IgA production in high catecholamine (NE) environment

-making a person less resistant to invasion

-IgA inhibits pathogen attachment to endothelium

-IgA also helps macrophages to recognize and phagocytize the antigens

-antigens latch on to IgE (on mast cell surface), which causes them to release inflammatory products (histamine, etc)

-NE also lands on the surface of the mast cell causing it to release histamine, SRS-A, etc

-NE causes mast cells to release pro-inflammatory products THE SAME WAY that an allergy does

-neurogenic inflammation

-NE is not synaptically related to tissue in lungs

Summary: nodose stimulates vagus, and upper thoracics stimulate sympathetics (and NE)

11-21-07

-Joel Pickar

-a subluxation should not affect a visceral disorder, if pain referral did not exist (?)

-paraspinal muscles can evoke a somatovisceral reflex

-neurogenic inflammation (Barnes)

-inflammation occurs (do to mast cell degranulation) when NE is released into tissues

-strategies to reduce inflammation:

-inhibit neuropeptides release from sensory nerves (inhibiting input)

-both SA or VA (aka C) fibers

-when GABA attaches to receptor sites, the no longer release substance P and glutamate (inhibiting the input)

-airway sensitivity to histamine is increased by stress (of which substance P contributes to)

11/27/07

J receptors (juxta-alveolar or juxtacapillary receptors)

-sensory fibers in lung parenchyma

-spinal afferents (some textbooks say they’re vagal, but most say they’re spinal)

-more mechanical than chemosensitive

-give aberrant firing pattern in the midst of inflammation (?)

-when fail to ventilate (air in/out), J receptors send dyspneic signal to the cortex

Exercise ( incr cardiac output ( incr capillary pressure ( incr interstitial pressure ( Jreceptors ( signal to cortex ( decr

limb muscle activity (decr blood flow to limb muscles) ( makes us want to stop exercise

-this is a VA-VE reflex

exercise-induced asthma

-highly sensitized J-receptors (quickly reducing blood flow to skeletal muscles)

“Dietary Salt, Airway Inflammation, and Diffusion Capacity in Exercise-Induced Asthma” (Mickleborough, Lindley, & Ray)

-dietary salt loading enhances airway inflammation in asthmatics

Emphysema

-blue bloater vs pink puffer

Blue Bloater (aka respiratory bronchiolitis aka Centrilobular emphysema aka chronic obstructive bronchitis)

-blood gases are compromised (blood is poorly oxygenated – respiratory distress)

-bloating is the result of fluid retention which is caused by heart failure

-patient will die from CHF before he dies from the emphysema itself

-terrible pulmonary hypertension, and swollen ankles

-95% of patients have history of chronic obstructive bronchitis

-commonly have a history of smoking

-these people have less dyspnea than the pink puffers

Blue bloater continued

-majority of damage occurs in upper lung lobes (which are more ventilated than the lower lobes)

-respiratory bronchiole (centrilobular zone) is damaged, while the alveolar sacs are preserved

-takes 20-30 years of smoking before this kind of damage occurs

-Jreceptors exist around the alveoli

-relatively fewer inflammatory events which preserves the Jreceptors

-less dyspnea b/c Jreceptors are not stimulated as much as with the pink puffer

-when a unit is less and less ventilated, air becomes trapped in the unit which reduces proper gas exchange

-recoil is missing

-vasoconstriction (with NO) of vessels in the area, and sending blood inferiorly

-then there is too much blood in an area that cannot sufficiently accommodate it

-blood pressure increases in lung (b/c of low V/Q) putting stress on the heart and leading to CHF

-even if the patient quits smoking, this has become a self-perpetuating inflammatory event

-Tcells are not seen in asthma or bronchitis, but they are seen in emphysema

-an immune response takes place in the lungs (similar to autoimmune disease)

-COPD is being reclassified as an autoimmune disease

-an immune response is triggered that causes Tcells to enter area

-Tcell activation causes apoptosis in the lung tissue

-once this process starts, it is unstoppable

Pink Puffer (aka panlobular emphysema)

-commonly these people have never smoked

-leads to cachexia

-musculature and skin is wasting away (skin tears easily)

-“pink” because blood gases are relatively good (they exchange gas well)

-“puffer” because of terrible dyspnea

-wasting is the result of medical treatment (high doses of prednisone)

-prednisone has an anti-inflammatory effect that helps to reduce the sensation of shortness of breath

-these patients also utilize albuterol excessively

-osteoporosis from the steroids that they people are on

-also leads to diabetes, and causes gluconeogenesis

-terrible high blood pressure

-these people tend to survive longer than the blue bloaters

-also develop Tcells, but likely is a blood born situation rather than an inhaled situation

-whenever a macrophage dies, it releases trypsin (a protease that eats protein)

-alpha1 antitrypsin (produced in the liver) protects us from the effects of the macrophage lysis and trypsin release

-pink puffers have little to none alpha-1 antitrypsin

-the destruction of alveolar walls is due to an imbalance in the normal protease-antiprotease mechanism in favor of

increased protease activity

-Tcell mediated immunity is the main problem, and once it starts, it is difficult to stop

-macrophages are where the blood is, and the blood is predominantly in the lower lobes

-therefore the degranulation and tissue destruction is greater in the lower lobes cause a Tcell mediated response

-since lower tissue is destroyed the body sends blood to upper lobes, which improves the V/Q balance

-these patients maintain a normal blood gas balance, and have far less pulmonary hypertension

-panacinar (aka panlobular) destruction – destruction of entire alveolar unit

-Jreceptors found around alveoli are stimulated, and therefore patient is dyspneic

-dyspnea is not related to blood gases

-nicotine is chemotactic for neutrophils (it is proinflammatory)

-smoking also increases the amount of elastase released by macrophages or neutrophils

-smoking increases protease activity and reduces antiprotease activity

-However, it is unlikely that smoking/nicotine is the sole explanation for emphysema

-even in healthy smokers, there is probably still an imbalance in protease/antiprotease activity, but they don’t develop emphysema – the difference is that these “healthy” smokers don’t have Tcells in their lungs

It is increasingly recognized that the immune and nervous systems are closely integrated to optimize defense systems with the lung. On release, neuropeptides (such as substance P, calcitonin gene-related peptide, vasoactive intestinal peptide and somatostatin) can exert both direct stimulatory and inhibitory effects on Tcell activation. ... Substance P has a number of important immunological functions, among which are direct effects on Tcell activation.

Retrograde activation of sensory nerves by a local axon reflex, resulting in the release of peptides, may contribute to inflammation of the airways.

The tachykinins are a family of peptide NT’s and include substance P. … They are found in the airways and are chemotactic for leukocytes. … They are prime candidates to be mediators for neurogenic inflammation.

Sensory nerve activation (C fibers in airways) send signal to dorsal horn

-tachykinins (via antidromic conduction) are released on mucus glands on vessels, and on smooth muscle

-antidromic conduction could possibly be mediated at the dorsal horn

Spinal mechanisms appear to regulate immune cell recruitment to a peripheral site and seem to interfere with antinociception.

Substance P & NE cause mast cell degranulation and macrophage activity that releases histamine and TNF

11/28/07

Substance P is a known mediator of inflammation.

CGRP is a vasodilator and neutrophil activator (released from the same C-fiber as substance P).

SP and CGRP are involved in the development of airway inflammation, and likely contributes to the pathogenesis of airway hyper-responsiveness and other lung inflammatory diseases (ie emphysema). ( neurogenic inflammation

Pulmonary edema results from both obstructive and restrictive diseases

-it is a consequence of many different diseases, and not a disease on its own

Interstitial space is a potential space that could be filled with exudates.

The movement of fluid from the capillaries to the interstitial tissue is absolutely normal, but not to the alveoli.

Fluid consistently in the interstitial space is pulmonary edema.

Fluid in the alveoli is a later stage of pulmonary edema.

Diuretics are used to keep the fluid down.

Causes of Pulmonary edema:

1. Increased hydrostatic pressure

a. Left ventricular failure

i. People who have a myocardial infarction of left ventricle

ii. Treated with diuretics

b. Pulmonary emboli

c. Vasoconstriction

i. Depletion of NO, from low V/Q (ie emphysema)

2. Loss of endothelial integrity

a. Infection

b. Exposure to toxins (gases: sulfur dioxide and chlorine)

i. Can develop severe dyspnea due to pulmonary edema

ii. Treat with oxygen, diuretics, and steroids (which stop the inflammation)

3. Decreased plasma oncotic pressure

a. Malnutrition (cachexia)

i. Abdomen, ankle swelling, etc., due to lack of protein in the capillaries

ii. Treat with an I-V of albumen

b. Kidney Failure

i. Proteinuria causes loss of proteins from blood

4. Lymphatic blockage (lymph carries away the extra fluid and exudates)

a. Cancer

b. Right congestive heart failure (lymph flows into right side of heart)

5. Increased negative intrapleural pressure

a. People with COPD that can suck air in, but not blow it out; this sucks the fluid out of capillaries into lungs

b. Treat by helping patient restore ventilation

11/29

Pleural Effusion

Parietal pleura

-innervated (capable of nociception), but poor vascular supply

Visceral pleura

-insensitive to pain (not well innervated ), but is very vascular (it can bleed)

Mesothelial cells in visceral pleural membrane aiding in adhesion b/n two membranes

Pleural effusion – liquid accumulating in the pleural space (b/n parietal and visceral pleura)

-starts to push the lung up

-blunting of the costophrenic angle is a sign of pleural effusion

-compromises ventilation (lung will not fully expand), stimulating J-receptors

-dyspnea is a chief complaint

-the effusion is either called an exudate or transudate

Exudate: thicker, high-protein (liquid with > 30 mg protein/liter)

Transudate: < 30 mg protein / liter

-clear, and more watery

-hydrothorax is the most common transudate

-CHF is main reason for hydrothorax

-pulmonary edema is a precursor to pleural effusion

-once pleural effusion sets in, diuretics don’t work

-must aspirate the area

-an infection will create a pyothorax (in the case of an exudate)

-hemothorax (blood, from the visceral pleura)

-also, in the case of an exudate

-the prognosis is grim

-cancerous growth that is eroding the capillaries causing subsequent bleeding (hemothorax)

-no pain, b/n not innervated

-first s/s is dyspnea

-mesothelioma: tumor primarily from exposure to asbestos

-after inhaling the asbestos, macrophages gobble it up, and the asbestos kills the macrophage (cycle repeats)

-20 years later, the asbestos ends up in the periphery of the lung

-pneumothorax

-air in this area

-can be caused by external trauma

-but the most common type of pneumothorax occurs from within (tall, thin, young males)

-on the surface of the lung, but beneath the pleura, blisters (blebs) filled with air will form

-alveoli will develop a fistula (opening) out to the surface, creating a bulge of air under the surface

-as long as the air stays below the surface of the pleura, it is fine

-but sometimes, the air will cause the pleura to tear and air becomes entrapped

-as the lung begins to collapse, it seals off the fistula

-the patient will experience a stabbing pain (like a heart attack)

-pain is immediately followed by dyspnea

-sympathetics kick in, and patient breaks out in a sweat

-diagnosed by history, nature of patient (tall, young male)

-if serious enough, surgeons will cauterize blebs and then inject EDTA powder to create inflammation which will

cause adhesions

-xray is definitive, and auscultation is silent (silent units)

Exam 3 review

-primary cells of involvement in asthma/emphysema

-mast cells and macrophages

-importance of mast cell sensitization/degranulation

-allergic response (sensitize when exposed to allergen)

-IgE and not necessarily the allergen, is what causes the sensitization

-mast cells degranulate upon the second exposure to antigen)

-identify irritant receptors – their importance in asthma

-vagal cough receptors (VA-VE reflex)

-afferent fibers that stimulate descending vagal fibers causing bronchospasms and mucus production

-very serous in an asthmatic (serious trouble if asthmatic gets bronchitis)

-inflammatory reactions (ie histamine, substance P, NE) can sensitize irritant receptors)

-what is the nodose ganglion

-the site of the cell bodies of the irritant receptors (vagal afferent fiber cell bodies)

-nodose has anatomical connections with the upper 2 cervicals

-intrinsic vs. extrinsic asthma (role of IgE)

-intrinsic is more neurogenic

-identify the Reid index

-the increase in size and number of mucus glands

-incr Reid index happens in simple chronic bronchitis

-Reid index is reversible

-decline from simple chronic to chronic obstructive bronchitis

-the majority of these people are smokers

-chronic obstructive aka respiratory bronchiolitis aka centrilobular emphysema

-2 major types of emphysema

-centrilobular

-panlobular

-how panlobular emphysema preserves the V/Q balance

-pink puffer

-what is the A-a gradient

-the potential space b/n the alveolus and the arterioles (endothelial and epithelial cell)

-pulmonary edema (gradient is spread apart) – can interfere with blood gases

-mechanisms leading to pulmonary edema

-increasing hydrostatic pressure

-decreasing osmotic pressure in the blood (loss of protein)

-blocking lymph channels

-increasing the negative alveolar pressure and sucking the blood out into the interstitial tissue

-certain gases that can destroy the endothelial cell and destroy the integrity of the capillaries

-earliest symptoms of pulmonary edema

-dyspnea

-transudate vs exudate

Hydrothorax – heart failure

Hemothorax – malignancy

Pyothorax – infection

-causes of pleural effusion

-CHF

-things that lead to pulmonary edema (ie infection, malignancy)

-early symptoms of pleural effusion

-dyspnea

-causes of spontaneous pneumothorax

-blebs, and fistula formation

-neurogenic inflammation

................
................

In order to avoid copyright disputes, this page is only a partial summary.

Google Online Preview   Download