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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<0 ( depolarizing in wrong direction -confirmed by looking at the “axis” chart on the ECG -axis deviation -sinus rhythm – every beat is under control of SA node -chest leads do no participate in the axis -axis from aVF, aVL, aVR? -normally QRS is ventricles contracting, and left predominates over right -if QRR’ – see one ventricle trailing behind the other just a little -if atrial fib, then P-axis is indeterminate (Ind) -II, III, and aVF – diaphragmatic/inferior view of heart -profused by right coronary artery -V4, V5, V6 – anterior view (looking at left ventricle) -profused by left anterior descending coronary artery -ischemia can cause a bundle branch block and create RR’ pattern -because of slowing of conduction through ventricles, one ventricle beats just before other one -change in the vector of the QRS wave 9/25/07[2] -lateral view: lead I and aVL -an occasional PAC does not change the P-axis, but if wandering pacemaker, than dramatic change in P-axis -during pregnancy, heart takes on a more horizontal orientation (incr left axis deviation) -beer gut also causes dramatic left axis deviation -heart can hang perpendicular in chest (rt axis deviation) in tall, slender young men (above 6’3”) -chamber hypertrophy can also change deviation -if rt chamber becomes enlarged, vectors directed more toward rt side -(leads I, II, and III should always be positive) -if left ventricular hypertrophy, lead I has tallest R, lead III is negative, & lead II is biphasic or neg. -biphasic: equal positive and negative signals -systemic hypertension or aortic stenosis (aortic valve is tight) -if rt ventricular enlargement, lead III has tallest R, and lead I is negative -pulmonary hypertension -conduction blocking (primarily bundle branch block): major cause for skewed vectors -if lead I has RR’, then probably rt bundle branch block -scarring on cardiac wall can lead to changes in vectors -scars do not conduct current -tall P-wave=enlarged rt atrium (P-pulmonale) -due to enlarged rt ventricle – from emphysema (COPD) 9/26/07 -bigeminy (two-headed) – one atrial, one ventricular contraction -trigeminy – 2 atrial, one ventricular -quadrigeminy – 3 atrial followed by one ventricular Conduction Blocks – interrupt flow (1) SA block = sinus arrest -if SA node suddenly decides not to fire, heart may miss a few beats -sick sinus syndrome (common event in elderly) -an elderly person could faint (syncope) -vagotonia is most common cause -responds well medically to atropine, which is a vagal inhibitor -“demand pacemaker” would be more ideal, since atropine should not be used long-term -escape beats (junctional or nodal escape beats): from AV node taking over -heart would otherwise cease to function -ventricular escape beat (not a PVC) -if 3 or more in a row, heart is in ventricular rhythm -ventricular rhythm notoriously deteriorates to Vtach which leads to Vfib -possibly upper cervical adjustment could reduce a stimulated vagus nerve (2) AV block (1°, 2°, 3°) -QRS should start within 0.2 sec after P-wave starts -vagotonia is the cause -1st degree: too long of a delay between P-wave and QRS (atrial and ventricular contraction) -longer than 0.2 sec delay -2nd degree block is very serious -signal from SA node does not get past the AV node -P-wave is nonconducted: Pwave seen, but no QRST (ie two consecutive P-waves) -type 1 and type 2, second degree blocks -type 1: (Wenckebach) -type 2: non-conducted P-wave – patient MUST be referred out -athletic kids that drop dead are from this problem -EKG could pick it up, but not necessarily -heart could enter asystole (aka ventricular standstill) -an infranodal lesion is more serious than a lesion in the AV node b/c an escape beat likely would come from the common bundle 9/27/07 -SA node block, causing a missed beat -symptoms: dizziness -junctional rhythm (AV-node is pacemaker) -no P-wave -P-mitrale: two humps in P-wave (from rt and left atrial walls) – indication of left atrial enlargement -PRSS’T -SS’: can see both ventricles contracting -bundle branch block – when you can see both ventricles contracting (ie RR’ or SS’) -if V1 is positive, then right bundle branch block (V1 should always be negative) -if there is left axis deviation, then appearance is more of a left bundle branch block -if positive V1 with left axis deviation, then both left and right bundle branch blocks -1st degree AV block -consistently long PR interval (longer than 0.2 seconds) -2nd degree AV block -type I (Mobitz I or Wenckebach) -lesion in AV node (AV block) -PR interval increases in length after a few contractions, and then Pwave is followed by nothing (cycle repeats) -progressive P-R intervals before nonconductive Pwave -can’t diagnosis without the EKG -probably nodal and usually benign -type II (Mobitz II or non-Wenckebach) -certainly infranodal (lesion is below the AV node, probably common bundle) and definitely malignant -definitely requires the insertion of a pacemaker -if can’t differentiate b/n type I and II, then assume type II until proven not -3rd degree block (aka AV dissociation) -no communication between atrium and ventricle -atrial and ventricular depolarizations occur independent of each other -complete heart block with ventricular escape 10/2/07 -atrial flutter: from increased sympathetic tone -mural thrombosis (blood clot usually along left atrial wall) -shock the heart (cardio conversion) -asystole: heart quits beating (not a sinus block, but a 2nd degree block) -leads I, II, and III should always be positive -biphasic Pwave (both pos and neg Pwave) – indicate atrial hypertrophy 10/2/07[2] -any block is always exacerbated by vagal tone and vice versa -sneezing increases vagal tone -no electrical activity over an area of infarct -inferior leads: II, III, aVF: inferior artery -anterior leads: V2-V6: left anterior descending coronary artery -lateral leads: I, aVL: lateral a. (circumflex) -good chance of complete recovery (from?) if one can make it to the hospital in time 3 zones: zone of ischemia, zone of injury, zone of necrosis (infarction) -always happen in this order: ischemia, injury, infarction (necrosis) 1) Ischemia -inverted Twave (pathognomonic) -repolarization delay from ischemia (insufficient oxygen to help repolarization) 2) Injury -injured area within ischemic area -during time of injury (6-hour window), changes in QRS -depolarization delay (prolonged depolarization) – elevated ST (fireman’s hat appearance) -acute phase (ongoing event) – will last a few weeks to months -will one day go away – will either go back to stage 1 or degenerate to infarction appearance 3) Infarct A) Transmural infarction -entire wall is involved in event -elevated ST B) Epicardial -just on superior surface -elevated ST C) Subendocardial infarction -on surface of interior wall -ST depression D) Intramural (non-Qwave MI) -buried deep within the wall -does not create anything discernable -EKG does not reveal infarct -indicators of potential MI include: crushing, sudden chest pain, pain down arm/jaw, (change in the pain pattern), nausea, etc -best indicator comes from blood (cardiac) enzymes (but might take 3 hours to elevate enzymes) -Master’s test (aka Stress test) -walk on treadmill with 12-leads attached to skin and incr heart rate to max for 6 minutes -heart is entering injury if depression or elevation of ST segment, and test is stopped immediately -nitroglycerin (and NOS) is a vasodilator (dilates coronary arteries) -but can give horrible migraine headaches as a side effect -Qwave is significant if it is at least ½ the size of the Rwave (1/3 of total height of QR segment) -generally wide (along with deep) -this Qwave morphology is permanent -if elevated ST at same time as deep Qwave – recent/current acute MI 10/3/07 -acute infarction: heart has trouble depolarizing -V leads looking at left ventricle (anterior portion of heart) -R progression: (start with more negativity than positive) R progressively increases -V1 is most QRS negativity -V3 is the transitional segment: much more positive than negative -V4-V6: much more positive than negative -R progression is an indicator of health of the heart -tall, peaked Pwave: P-pulmonale -cause is atrial hypertrophy from pulmonary hypertension (due to COPD) -PVC’s lead to Vtach, which lead to Vfib 10/4/07 -Rt coronary artery supplies the SA node and a portion of the AV node -rt coronary artery notoriously cause bradycardia (from damage to SA node) PVC – wall is irritated (sympatheticotonia) -MI’s change the R-progression: presence of Qwaves -sympathetics innervate ventricles and parasympathetics dominate in the atria -nervous system tends to (paradoxically) put more demands on tissue than the tissue is capable of handling -when tissue is damaged, nerve activity increases -left main coronary artery feeds: LAD and left lateral circumflex aa -III and aVL are reciprocal leads (usually give a mirror-image of each other, esp when infarct occurs) -to determine positive nature of a lead, must subtract any negativity Review Tachycardia (above 100) vs bradycardia (below 60) Sinus tachycardia vs ventricular tachycardia -sinus best treated by carotid massage -axis(vector): reference to depolarization and repolarization of the heart -if QRS axis is “-20”, it is depolarizing to the left shoulder -systemic hypertension (causing left ventricular hypertrophy) -atrial fib -atrial ectopic foci (will cause PAC) -What is a PAC? Premature atrial contraction due to ectopic focus -sinus arrhythmia vs respiratory rhythm (when patient takes breath IN, the rate Increases) -sinus arrhythmia: shows no pattern -SA block (sinus arrest, sick sinus syndrome) -escape beats (from atrium, node, or ventricle) -wandering pacemaker: renegade spots on atrial wall take over roll of SA node -innervations of SA and AV node -right vagus innervates: SA node -left vagus innervates: AV node -sympathetics have very small amt of innervation to AV node and practically no signal to atrium) -AV delay: allows chambers to fill -Wolf Parkinson White (WPW) syndrome – accessory pathways bypassing AV node -no AV delay (PR interval decreased) -heart beats faster to compensate for lack of AV delay -3 types of AV blocks (and where are lesions): 1) Wenckebach (type I) 2) nonWenckebach 3) AV dissociation (complete heart block) -every heart beat is ventricular (nothing from SA node is getting down) -P-pulmonale (tall peaked Pwave – rt ventricular hypertrophy) -P-mitrale – long, prolonged Pwave – left atrial enlargement -Cause of axis deviations -bundle branch block -keeps ventricles from depolarizing in normal manner (takes longer for ventricles to contract) -ischemia causes problem with repolarization -Injury causes pblm with depolarization -Infarction causes loss of conduction -what does an elevated vs depressed ST segment mean? -elevated ST: infarction is Epicardial (or Transmural) -depressed ST: infarction is subendocardial -What is happening during the P, QRS, and T segments -what artery and what leads? -Inferior view: leads II, III, and aVF ( right coronary artery -Anterior: leads V4, V5, and V6 ( left anterior descending artery -Lateral: leads I, and aVL ( circumflex artery -What is a PVC? Unifocal vs multifocal PVC’s? -Sympatheticotonia following cardiac damage (significant) -What is bigeminy? Trigeminy? Quadrigeminy? -R-progression 10/11/07 TEST 2 material -respiration does NOT mean breathing, but rather “an exchange of gas” (O2 and CO2) -ventilation = breathing (mechanical act of pushing air in and taking air out) -must do both (air in & air out) to be ventilating -two types of ventilatory disorders: obstruction & restriction -no such thing as “respirator”, but rather they are “ventilators” -air and blood must be at the same place at the same time -pulmonary embolism: deficient in blood, but not in air -V = ventilation -Q = perfusion -V/Q imbalance puts person into respiratory failure -ABG (arterial blood gases) (to tell if patient is in respiratory distress) -carbon dioxide is the key gas -PaCO2 (a=arteriole): normal is 40-45 mm Hg -the slightest elevation of CO2 leads to acidosis -PaO2: 95-100 mm Hg -8 times easier to blow off CO2 than to bring in O2 -if heart can’t pump sufficient blood into lungs, then blood is not well oxygenated -CO2 builds up because of poor perfusion -upper part of the lung is well ventilated and lower lung is well perfused -always more blood in lower lobes, due to gravity -CPR attempts to both ventilate and perfuse -2 types of lung diseases: obstructive and restrictive -2 zones: conductive and respiratory zone -gas exchange occurs in respiratory zone (not in the conducting zone) -conducting zone starts with the trachea and ends at the beginning of the terminal bronchioles -primarily supported by cartilage -a disease of this area is an obstructive disease (ie bronchitis is most common) -bronchitis is inflammation of conducting zone, and will not interfere with gas exchange -vagus innervates this area -vagus supplies nerve irritant receptor endings (cough receptor) -vagal afferent fibers -coughing is number one protection for keeping stuff out of lungs -mucus glands are also innervated by the vagus -asthma: bronchoconstrictive state + mucus production -coughing spells throw them into bronchospasms -people with asthma who get bronchitis: is a serious concern (vagovagal reflex) -status asthmaticus: will be placed on a ventilator -respiratory zone: from respiratory bronchioles to alveoli -respiratory bronchioles, alveolar duct, and alveolar sac -asthma is disease of respiratory bronchioles -emphysema is disease in alveolar ducts/sacs -obstructive: diseases of the airways (a ventilatory disorder) – problem blowing air out -asthma, bronchitis, emphysema -a person can have problems with ventilation and still have good respiration -restrictive: diseases of the lung interstitium or interstitial tissue) – problem sucking air in -pneumonia, pulmonary edema, pulmonary fibrosis, most lung cancers -subluxations in thoracic spine irritate sympathetics and cause NE (alpha-adrenergic) to be released in lung (but lung tissue has beta receptors) 10/16/07[1] -ABG=arterial blood gases -oxygen levels: 95-100 mm Hg -CO2 levels: 40-45 mm Hg -cause of CO2 rising in blood: ventilation/perfusion (V/Q) mismatch -we can survive long with low O2, but can’t survive long with CO2 levels increasing -respiratory failure and respiratory acidosis – high CO2 levels -V/Q balance = life support -nervous system is first system to go – awareness of situation disappears -hyperventilation: blowing off too much CO2 -leads to respiratory alkalosis -breath into paper sack to increase CO2 levels -only healthy people can hyperventilate -can only blow off CO2 if air and blood meet -patient in cardiac failure cannot hyperventilate (because can’t pump enough blood into lungs) -light-headed and dizzy if either too much or too little CO2 -mucus glands begin to appear in respiratory bronchiole (due to nervous reflex) -asthma = mucus production and bronchoconstriction -bronchoconstriction demonstrated by spirometry -emphysema: complete and irreversible loss of alveolar sacs (and sometimes the ducts) -acinus = respiratory bronchiole + alveoli -emphysema that is panacinar: everything destroyed -emphysema that is centroacinar: alveolar sacs are preserved -vagus (cholinergic): innervates the smooth muscle -releases muscarinic Acetylcholine (causes smooth muscle to constrict) -vagus always attached directly to something -vagus has direct attachment to smooth muscle and mucus glands -smooth muscles only have one myoneural junction (and it is with the vagus) -sympathetics dilate -the symp nerves (from upper thoracics) are everywhere – they innervate the interstitial tissue and secret NE -NE is alpha (alpha-adrenergic) – will land on alpha receptors -but the receptors on the smooth muscle are not alpha, but they are beta -therefore, the NE has little to no effect on bronchoconstriction -epinephrine is both alpha and beta (ie Primatene mist) -inhaling NE will actually create more bronchoconstriction rather than less -true mechanism for bronchodilation from sympathetics: hypothalamus signal to cord to adrenal gland which will secrete epinephrine into the blood & relax smooth muscle -it takes 6-8 seconds for all this to happen -splanchnic (long preganglionic myelinated fibers, and short postganglionic) -NE enhances the innate function of tissue -it behaves like a catalyst -mast cells degranulate and release histamine (and other proinflammatory cytokines) -mast cells have alpha receptors -mast cells also release SRSA (slow reactive substance A) -SRSA causes bronchoconstriction -a constant and overproduction of NE into this area can contribute to asthma -neurogenic inflammation -status asthmaticus (stays in an asthmatic state): epinephrine is not successful in relaxing the smooth muscle -patient can die -must override the plus’s (in a severe asthmatic attack) -vagus has direct attachment to smooth muscle and mucus glands -atropine is a vagal blocker – routinely given for asthma (in Canada) -atropine extracted from 1) Deadly Nightshade - Atropa belladonna 2) Jimsonweed – Datura stramonium 3) Black Nightshade – Solanum nigrum -must measure blood gases in asthmatic patient 10/16/07[2] -3rd nerve that innervates alveoli -juxtaalveolar receptors (J-receptors): mechanoreceptors 1) they are mechanical (but can be stimulated chemically, ie by histamine) 2) sensitive to ventilation (they fire on expansion) -when we inhale/exhale, J-receptors send oscillating signal back to cord, which eventually reaches the cortex -if signal flattens out, brain interprets it as dyspnea (shortness of breath) -a sense that your lungs are not inflating (feel like you just can’t take a deep breath) -if nerves become sensitized (from NE), they send a signal that we are bloated (will not deflate – also dyspnea) -there are alpha receptors on these nerve endings (NE is alpha) -when ribs become fixated, lends to feelings of mild dyspnea -albuterol (inhaler): powerful beta-2 agonist, relaxing smooth muscle -inhaler should not be used more than twice per week -the majority of asthmatics in ER are hyperventilating – blowing off CO2 -V/Q balance is good enough, yet they still feel dyspnea -we have evidence that chiropractic treatment reduces dyspnea (patient can rely less on drugs) -endothelial cells produce nitric oxide -interstitial space: potential space between alveolar epithelium and capillary endothelium -restrictive disease: interstitial disease -ie pneumonia (increase in exudates in interstitial space) -restrictive diseases can interfere with the “A to a” gradient (Alveoli to arteriole) A=alveoli a=arteriole capillaries -if “A to a” gradient is increasing, PAO2 is much higher than PaO2 -ie interstitial space full of: exudate from pneumonia, or blood from pulmonary edema, or collagen in pulmonary fibrosis -hypercapnea = incr CO2 V/Q imbalance is the only cause -mechanisms of defense against invading toxins, microbes or gases: Cough, mucus, bronchoconstriction, alveolar macrophages -people on prednisone are highly susceptible to invading toxins -chlorine gas (from swimming pool) – mast cells release heparin, which incr permeability & leads to pulmonary edema -visceroafferent C-fibers are wrapped around all of these structures -will send afferentation back to the cord, traveling the sympathetics -VA and VE fibers are traveling together -C fibers stimulate the cord and cause central excitation (aka central sensitization) 10/17/07 -Dr. Yunus, MD -the unifying concept of central sensitivity related to IBS -CSS -gas exchange abnormalities do NOT explain the presence of dyspnea -presence of dyspnea often indicates in deficit in ventilation, not in respiration -mechanoreceptor traffic that imports inflation of the lung relieves dyspnea -studies have shown that chiropractic helps to relieve the symptoms of dyspnea Obstructive Diseases -airway is obstructed by something (obstructive disease = airway disease) -2 most prevalent causes: bronchoconstriction and mucus -3rd cause: after years of chronic inflammation, the airway walls begin to weaken and deteriorate -when person tries to breath out, then the external pressures that are exerted lead to early airway collapse -air is trapped in alveoli -airways supported by cartilage, muscle, and CT – lose their integrity after years of chronic integrity -only 3 airway diseases: asthma, bronchitis, emphysema -negative pressure sucks air in, when breathing in, then gas exchange, then exhalation (which is passive) -surface tension allows the alveoli to empty during exhalation -alveoli (with trapped air), expands more and more with each breath, increasing SA and decreasing surface tension -increase in residual volume (air left behind after a maximal exhalation) -LaPlace law: as increase surface area, surface tension decreases -residual volume in average adult male is 1200 ml TLC=IRV+TV+ERV+RV -as residual volume increases (trapped air increases), PAO2 decreases, which decreases arteriole O2 -also PACO2 increases, which increases arteriole CO2 -dropping of blood-oxygen occurs before the CO2 builds up in the blood -venous admixture = blood that enters the left side of the heart -approximately 4% of unoxygenated blood (in healthy individual) -Bohr Effect -muscles and tissues in extremities are acidic, but in lung it is alkaline -Hb gives up oxygen better in acidic environment -if lung CO2 increases, environment becomes acidic, which decr ability RBC to pick up oxygen -ventilator is only known solution to try to pull CO2 out of lungs -saturation of O2 measures saturation of O2 on a RBC -fallible measurement b/c doesn’t consider quantity of RBC’s, and other issues 10/18/07 -inspiration is active process (using muscles) -expiration is passive (elastic recoil) -normal Inspiration:Expiration ratio (I:E) = 1:2 (if takes two seconds to suck air in, it takes 4 seconds to blow air out) -in obstructive disease, I:E = 1:4 (spend significantly more time blowing air out) -an I:E of 1:1 is rapid shallow breathing (restrictive disease) -also increase the # of breaths per minute (around 35 breaths per minute) -normal breaths per minute = 13 +/-3 -compliance vs recoil (two properties of a healthy lung) -compliance = ability of the lung to expand (lung opens up) -recoil = ability of the lung to collapse (shut down) -there is always an inverse relationship between compliance and recoil -if compliance goes down, then recoil goes up -obstructive disease: increase in compliance and decr in recoil -restrictive disease: decr in compliance and incr in recoil Lung volumes IRV = 3000ml TV = 500 ml ERV = 1100 ml RV = 1200 ml -numbers are based on average healthy adult male -Drop numbers by 10% for the healthy adult female -only a portion of TLC is utilized for respiration (gas exchange) Vital Capacity (VC) = volume utilized for respiration -measures the ventilated portion of the lung VC = IRV + TV + ERV -residual volume refers to non-ventilated lung tissue -if VC was normally 4600 ml, but then they only blew 3500 ml out, they have a decreased Forced Vital Capacity (FVC) -if VC is down, then ventilation is down -both obstruction and restriction will reduce the VC -FEV1 = Forced Expiratory Volume in the first second -FEV1/FVC ratio = % of air blown out in the first second -normal ratio is 80% (80% of FVC should come out in the first second of exhalation) -if ratio decreases, then airway disease (ie COPD) -if RV increases, and VC remains the same (barrel-chested, ie from smoking) -only by allowing the lungs to expand can we maintain Vital Capacity -eventually RV starts to take over the VC -a smoker may be barrel-chested for decades while preserving vital capacity -can’t surgically remove the excess RV (b/c RV is throughout the lung tissue) -RV is NOT trapped air -not every bit of lung tissue is ventilatable -VC goes down in obstructed patient b/c RV increases 10/23/07 -RV cannot participate in gas exchange and therefore is not considered a part of FVC -asthma is also called reversible airway disease -drug therapy can dilate a bronchiole and allow more ventilation to occur -the vast majority of people with asthma in their childhood and teen years will improve with their asthma in their 20’s -neurogenic asthma – adult onset asthma -150ml (in adult male) of air in conducting zone -first 150ml of air that is exhaled never got into respiratory zone, therefore it has no CO2 and has high O2 Fibrosis – “small lung disease” -patient cannot take a deep breath -every volume is reduced (even residual volume is reduced) -volumes of air are used to measure lung function -FVC is reduced in both obstructive and restrictive diseases -in the restricted lung, both FEV1 & FVC are reduced, but the FEV1/FVC ratio is normal -average O2 level for a 60 y.o. is 85 -in COPD, imbalance b/n ventilation and perfusion -ventilated and perfused portions of lung are not in same place at same time -normal HCO3 is 23 -asthma does not change the appearance of the lung (does not cause barrel-chest) -if FEV1/FVC ratio < 80% then obstructive -if FEV1/FVC ratio >= 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: Increased hydrostatic pressure Left ventricular failure People who have a myocardial infarction of left ventricle Treated with diuretics Pulmonary emboli Vasoconstriction Depletion of NO, from low V/Q (ie emphysema) Loss of endothelial integrity Infection Exposure to toxins (gases: sulfur dioxide and chlorine) Can develop severe dyspnea due to pulmonary edema Treat with oxygen, diuretics, and steroids (which stop the inflammation) Decreased plasma oncotic pressure Malnutrition (cachexia) Abdomen, ankle swelling, etc., due to lack of protein in the capillaries Treat with an I-V of albumen Kidney Failure Proteinuria causes loss of proteins from blood Lymphatic blockage (lymph carries away the extra fluid and exudates) Cancer Right congestive heart failure (lymph flows into right side of heart) Increased negative intrapleural pressure People with COPD that can suck air in, but not blow it out; this sucks the fluid out of capillaries into lungs 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 -8²³œ  4 5 u ‚ K S ³ ¸ Ë Ü  0 « ì í (G©±ÌëÆp‚<V•–ž¶ºÚïðU÷ý:AK‰Šª¬¹ºüøüñüíéüéåÞéåéÖéÎéÎéÊéÊÆÊÂÊÆʾƾƾéÂé¹µ±µ±­±¥±¡±­±­• hÉw+5hÉw+hÉw+5hÉw+h@êhm(!hx45h•Tçhx4hÿy- hm]Œ>*h !hm]Œhxíhs" hž:Úhž:Ú>*hž:Úhž:Ú6 jàðhÞQÔhÞQÔhž:ÚhF jàðhÒx;hmzØhÒx;8 ,h½Í > o œ à è ò ú   5 N f …  í ! ïßÒÒÒÒÒÒÒÒÒÒÒÒÒÒÒÒÒÒÒÒÒÒ 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