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UT Southwestern School of Medicine physiology block 2, 2010

Quiz yourself by thinking what should be in each of the black spaces below before clicking on it to display the answer.
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Question
Answer
Normal alveolar ventilation   4.5-5 L/min  
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Normal pulmonary blood flow   5 L/min  
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alveolar dead space   ventilation but no perfusion (e.g. pulmonary embolism). blood diverted to other alveoli -> abnormal V/Q (<0.8)  
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normal alveolar V/Q   0.8 = 4/5  
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effects of alveolar dead space (physiological compensations)   1) low [CO2] in dead space -> alkalosis in surrounding insterstitium -> bronchoconstriction. 2) decreased surfactant production in dead space -> decreased compliance -> decreased ventilation.  
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effects of airway obstruction (physiological)   V/Q = 0 for all lung. arteriolar O2 & CO2 reach levels similar to venous. . When airways only partially obstructed, anoxic alveoli = "PHYSIOLOGICAL SHUNT" of deoxy blood that mixes with normoxic blood in "VENOUS ADMIXTURE"  
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What mechanism compensates for venous admixtures?   average PaO2 is low b/c HbO2 equilibrium curve has sigmoidal shape. cannot compensate w/high V/Q elsewhere. NOTE: PaCO2 not much affected (linear Hb curve). hypoxemia with or without hypercapnia.  
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R-L pulmonary shunt   blood bypasses lungs, and so does not participate in gas exchange -> venous admixture.  
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normal pulmonary shunt   NORMAL 5% of blood = L-R shunt (bronchial circulation + thebesian vein in heart). Explains 1/3 of normal A-aDO2.  
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Pathological R-L shunt   1) Tetrology of Fallot = 75% blood shunted past lungs. 2) Pulmonary Edema w/abnormal vasoregulation, 3) Chronic L-R shunt (e.g. patent ductus arteriosus)-> pulmonary hypertension -> increased pressure of pulmonary vessels -> R->L intracardiac shunt.  
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Alveolar Ventilation Equation   alveolar V = rate of CO2 production/alveolar PCO2 x K. K = 0.863. (NOTE: PACO2 = PaCO2) *USED TO COMPUTE WASTED VENTILATION TO OBTAIN INDEX OF EFFICIENCY OF VENTILATION. *HYPOVENTILATION ALWAYS -> HYPERCAPNIA.  
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normal MINUTE VENTILATION   7500 ml/min @ rest  
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causes of hypoventilation   1) damage to respiratory centers (barbiturates, heroin, stroke), 2) chest wall damage or respiratory muscle paralysis (e.g. ALS, SC injury, muscular dystrophy), 3) Airway obstruction (e.g. choking, COPD), 4) high altitude/burning building low PiO2  
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Diffusion Impairment causes   1) any change in components of Fick's Law of Diffusion, OR 2) large increase in rate of blood flow that decreases alveolar contact time. Not usually a cause of respiratory failure, but contributes to emphysema & ARDS.  
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Poiseuille's Law of flow   Q=(pi*r^4*deltaP)/8*viscosity*length (P=QR, do substitutions to find R equation)  
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systemic vascular bed (SVR) calculation   SVR = (P.aorta -P.right.atrium)/CO  
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blood & poiseuille's law   YES: incompressible fluid, v @ surface = 0, flow is (mostly) laminar. NO: tube is straight & rigid, viscosity is constant, flow is steady (not pulsatile)  
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Reynold's number   N=density*diameter*velocity/viscosity. above 2000 = not great. Above 4000 = turbulence.  
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viscosity of whole blood   decreases with increasing shear rate (not Newtonian). @ low shear rates (low velocities) viscosity increases due to RBC interaction w/fibrinogen. also higher viscosity @ higher % hematocrit.  
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mechanism for converting pulsatile bloodflow from heart into steady flow by arteries   arterial elasticity (pressure wave)  
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MAP equation & normal MAP   MAP= Pd+ 1/3(Ps-Pd) = CO x SVR . normal MAP = 93 mmHg  
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Korotkoff sounds   1. tapping, 2. murmurs, 3. thumping, 4. muffling, 5. silence  
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BP for prehypertensive, stage I, & stage II hypertension   prehypertensive 120-139/80-89. stage I 140-159/90-99. stage II >160/>100. 5% = 2ndary hypertension due to disease process (e.g. renal artery stenosis or adrenal tumor)  
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fxn of blood vessels in closed circulatory system   PRIMARY: maintain pressure head. also: maintain selectively permeable barrier, distribute flow selectively, metabolize circulating materials, modulate hemostasis & inflammation, permit growth  
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site of the greatest pressure drop in circulation   systemic arterioles  
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pericytes   live on arterioles, capillaries, venules, create stability & secrete matrix proteins around microcirculation vessels  
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rate of material movement across a membrane   Rate of material movement = surface area * permeability * [ ] difference of material. add more capillaries = increase surface area.  
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Starling Equation   F =K*(Pc-Pi + Πi- +Πc). measures flow across a capillary wall.  
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endothelial permeability of different tissues   intestinal mucosa 15x > heart 8x > skin 25x > brain  
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substances that open EC junctions   histamine, bradykinin, lymphokines  
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leukocyte recruitment   1. inflammatory signals = ECs display P-selectin & secrete PAF. 2. leukocytes bind P-selectin (rolling). 3. PAF binds R on leukocyte -> activates integrin on leukocyte. 4. Integrin adheres tightly to EC ICAM. 5. leukocyte extravasates  
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fxns of the lymphatics   1. deliver fluid & protein from interstitium to circulation, 2. transport fat from si to circulation, 3. immunological defense via lymphocytes  
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lymph flow   2-4 L/day. 100-200 g protein/day  
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structure of lymphatics   1. no basement membrane (takes in large particles), 2. 1-way valves in vessels + smooth muscle, 3. filtration via lymph nodes before going to blood  
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causes of edema   1. low plasma oncotic P, 2. elevated venous P, 3. increased capillary permeability, 4. lymphatic blockage, 5. LV failure/mitral stenosis  
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% blood in different blood vessels   systemic veins 60-68%. lungs 10-12%. heart 8-10%. arteries 10-12%. capillaries 4-5%.  
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factors increasing venous return   1. cardiac suction, 2. respiratory pump, 3. muscle pump, 4. venomotor tone  
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% blood in different organs   liver 25% (incl. portal), kidney/intestine/skeletal muscle 20%, brain 15%, skin/other 8%, heart 4%  
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changes in blood flow x organ during exercise   brain 15 -> 4%. skeletal muscle 25 -> 75%. liver 25 ->4%. intestines/kidney 20 -> 3%. heart same.  
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intrinsic control of circulation   (serves organ needs) 1. autoregulation, 2. local metabolic regulation, 3. paracrine regulation  
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extrinsic control of circulation   (preserves MAP) 1. autonomic NS, 2. humoral factors  
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autoregulation of circulation   (intrinsic mech) 1. myogenic = response to stretch, impt't in kidneys , 2. metabolic = vasodilators wash out w/high flow e.g. H+ impt't in brain, 3. tissue pressure = high pressure from organ capsule constricts capillaries, kidney.  
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active hyperemia   (intrinsic mech: blood flow to organ =proportional to its metabolic ACTIVe-ity) 1. high CO2/lactate/H+ -> K channel opens -> vasodilation (+ Na/K ATPase), 2. low O2 lowers ATP -> adenosine released -> Gs R-> vasodilation  
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passive/reactive hyperemia   (intrinsic mech) vasodilators accumulate when no blood flow -> sudden increase in flow. longer ischemias -> larger response.  
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AVP function   antidiuretic. released from post. pit. due to high osmolarity of blood (salt or dehydration) or low pressure receptors. aquaporins inserted in proximal collecting duct, increases plasma volume. vasoconstriction ONLY with hemorrhage.  
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AngII fx   increases plasma volume. vasoconstriction ONLY w/ intense decline in BP, or w/salt-free diet  
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ANP   diuretic, increases glomerular flow -> reduces plasma volume). vasodilation via membrane-bound guanylyl cyclase receptor.  
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VEGF   vascular endothelial growth factor. causes EC's to digest basement membrane, move & mitose. EC vacuoles combine to form a lumen -> new blood vessel. mechanism can be used by tumors.  
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carotid sinus receptor   50-200 mmHg, sinus nerve -> glossopharyngeal -> medullary cardiovascular center.  
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aortic arch baroreceptor   100-200+ mmHg, depressor/aortic nerve -> vagus nerve -> nucleus ambiguus & dorsal nucleus of vagus. requires hypothal.  
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baroreceptor firing rate   starts out signal-locked to systolic increase in arterial pressure, but @ ~200 mmHg, firing becomes tonic (saturation)  
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baroreceptor denervation   decreases specificity of MAP (broader and shorter curve)  
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hemostasis   >10% blood loss -> hypovolumic shock. >30% blood loss fatal (shock). 1 low BP & CO. 2 baroreceptor reflex -> sympathetics (tachycardia, vasoconstriction). 3 low kidney flow -> renin-ang-aldo. 4 atrial volume receptors decrease firing -> AVP release.  
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signs of hypovolumic shock   low BP, high pulse, cold skin, reduced urine  
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low pressure mechanoreceptors   venous side (atrial wall, RV, pulmonary arteries, liver). = volume receptors.  
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atrial mechanoreceptor reflexes   (promote diuresis & reduced blood vol.) 1. Bainbridge (increased HR via SA node), 2. inhibited sympathetics to kidney arterioles (increases flow), 3. inhibited AVP  
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V-P relationship in arteries & aging   given volume -> greater pressure w/age  
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relationship b/tw CO & circulating volume   directly related (volume control = essential for controlling MAP)  
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Aldosterone   renin ->Ang ->Aldo System (RAAS). renin released due to decreased MAP & increased sympathetics. inserts Na/K ch's in collecting duct (sodium resorption)  
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abdominal visceral receptors   stomach, small/large intestine, gallbladder, pancreas. mechano (distension) & chemoreceptors (capsaicin/bradykinin). reflex -> high HR & BP.  
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skeletal muscle receptors   isometric contraction of skeletal muscle -> high systemic BP (exercise pressor reflex). -> sympathetically induced increased peripheral resistance & CO. afferents via DRG's to SC & brain.  
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arterial chemoreceptors   carotid & aortic bodies. run w/ baroreceptor nerves. mainly low PO2 (also low pH, high CO2, & large change in BP). -> increased ventilation + sympathetic vasoconstriction-> increased arterial BP. not impt't in humans as much as in diving mammals.  
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treatment for hypertension   decrease blood volume  
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cardiovascular control from higher brain centers   increased HR & BP by strong emotions, anticipation of exercise. first hypothalamus, then medullary centers. hypothal regulates blood vessels in skin for body temp.  
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diving reflex   HR increases w/ventilation, but decreases when ventilation not possible (i.e. underwater)  
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CO equation   CO = HR x SV  
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% plasma that is protein   7-9%  
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hemostasis mechanisms   1 vascular spasm (myogenic, local nerves, 5HT, TXA2), 2 platelet plug (primary), 3 coagulation (2ndary, hematoma), 4 fibrous tissue deposition, 5 1st aid (pressure applied)  
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modulation of blood response to injury   1 nonvascular cells-> TF-> extrinsic coagulation, 2 release fWF-> platelet adhesion, 3 release NO & PGI2-> inhibits platelet aggregation, 4 bind antithrombin III-> inactivates thrombin/Xa/IXa, 5 bind thrombin-> activates Protein C-> inactivates Va & VIIIa  
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platelet morphology   open cannaliculae, dense granules (ADP, serotonin), alpha granules (vWF, fibrinogen), Mt  
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# per mm^3 of blood of diff. elements   platelets 300k,  
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vWF   high affinity linking of platelet glycoprotein 1b (GPIb) to subendothelial collagen  
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substances promoting platelet activation   collagen, thrombin, ADP, TXA2, contact w/foreign surfaces. NOTE: TxA2 also released from platelets -> feed forward.  
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platelet intracellular activation pathway   binding -> increased PLA2 -> Arachidonic acid cleaved from P'lipids -> PGG2 -> PGH2 -> TXA2(thromboxane sythetase)-> Ca++ -> ADP+TxA2 (platelet aggregation) & 5HT (vasoconstriction) released  
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FX of aspirin on clotting   irreversibly blocks AA conversion to PGG2 (Cox)  
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platelet aggregation   platelets cross-link GPIIb & IIIa via fibrinogen & vWF. =clumping/agglutination.  
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procoagulation activity   plasma membrane PF3 (phosphatidylserine) moves to outer leaflet = docking site for Xa, Va, thrombin  
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platelet retraction   shrinkage of a clot by actomyosin  
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final common coagulation pathway   factor Xa-> converts prothrombin to thrombin -> converts fibrinogen to fibrin  
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activation of fibrin   thrombin cleaves fibrinogen alpha & beta chain n-terminals -> polymerization sites  
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Where are coagulation factors synthesized?   LIVER, except VIII is synthesized in ECs & megakaryocytes  
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Vitamin K is necessary for synthesis of which factors?   needed for Ca++ binding domain. Factors 2, 7, 9, 10  
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Tissue Factor (TF)   integral membrane protein on non-vascular cells. increase fx of Factor7 1000x -> activates Factor10  
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prothrombinase complex   = Factor10a, Factor5, Ca, PF3. increases thrombin activation 300K times over Factor10a alone.  
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interaction of extrinsic & intrinsic coagulation pathways   Factor3 + Ca + Factor7a can activate Factor9  
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thrombin feed-forward effects   thrombin can activate factor5 to increase its production. can also activate Factor13a -> stabilizes fibrin polymers.  
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prevention of blood clotting   1 antithrombin III (via heparin)-> inactivates thrombin + Xa + IXa. 2 thrombin binds thrombomodulin on EC -> Protein C activated -> inactivates Va & VIIIa. 3 NO & PGI2 released from EC -> inhibit platelet aggregation, 4 ECs physically block interstium  
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tissue factor pathway inhibitor   plasma protein. activated by Xa & Va. binds Factor7a & inhibits. Feedback inhibition.  
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antithrombin activity   80-90% adheres to fibrin mesh -> prevents spread. antithrombinIII binds & inactivates thrombin (helped by Heparin)  
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thrombomodulin activity   thrombomodulin on EC binds thrombin -> Protein C activated (APC) -> binds protein X -> inactivates Factor5 & Factor8  
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lysis of blood clots   1 fibrin clot binds plasminogen (circulation). 2 tissue plasminogen activator (tPA) slowly released by EC's cleaves(activates) plasmin. 3 plasmin cleaves fibrin into soluble fragments.  
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inhibition of tPA   plasminogen activator inhibitor (PAI-1 & 2) from EC's (also inhibit plasmin formation) is released to prevent activation of tPA in general circulation.  
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disorders of excessive bleeding   1. vitamin K deficiency (Factors 9,7,10), 2. hemophilia (B = Factor9; A = Factor8), 3. thrombocytopenia (PF-3 in intrinsic & common pathway)  
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thrombus   =abnormal clot in blood vessel  
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Virchow Triad   3 influences of thrombus formation: 1 endothelial injury (arteriosclerosis/infection/trauma). 2 stasis/turbulent blood (immobility). 3 blood hypercoagulability (insufficient anticoagulant factors)  
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thrombin-activatable fibrinolysis inhibitor (TAFI)   activated by thrombin, inhibits fibrinolysis.  
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heparin   anticoagulant, accelerates antithrombinIII inactivation of Xa & thrombin.  
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coumarin   e.g. warfarin, coumadin, dicumarol. interferes w/vitamin K-dpdt synthesis of procoagulants in liver.  
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TPA   dissolves clots via LOCAL administration  
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Ca chelators   removes Ca from blood to prevent clotting IN VITRO ONLY  
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normal venous O2 content   15 ml/dl  
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hypoxemia definition & causes   =low PaO2 caused by: 1) hypoventilation, 2) impaired diffusion, 3) R->L shunt, 4) low V/Q, 5) low inhaled O2  
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hypoxemia definition & cause   =inadequate tissue O2 caused by: 1) low PaO2, 2) inadequate tissue perfusion, 3) low O2 capacity of blood, 4) inability to use O2 effectively (e.g. histotoxic)  
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extreme causes of abnormal V/Q   pulmonary embolism. airway obstruction.  
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what are the compensatory reflexes for V/Q inequality?   1) bronchoconstriction due to low PaCO2. 2) decreased surfactant production. 3) hyperventilation.  
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in what situation does pure O2 not increase PaO2 to high PAO2 values?   "absolute" shunt (very large intrapulmonary shunting in patients w/hypoxemia & elevated A-aDO2  
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Alveolar Gas Equation   alveolarPO2 = (inhaled_PO2) -(arterial_PCO2/R). R = respiratory exchange ratio. (NOTE: PACO2 = PaCO2). used clinically to calculate PAO2 which is used to calculate AaDO2.  
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Normal alveolar ventilation   4.5-5 L/min  
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Respiratory Exchange Ratio definition & normal value.   rate of generation of CO2/rate of O2 consumption. normal = 0.8.  
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FIO2   fractional concentration of O2 in atmospheric air being inhaled. = 0.21 everywhere, when air is normal.  
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reduction of alveolar PO2   1) low O2 in inspired air (e.g. brning building), 2) decreased barometric pressure @ high altitude  
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PH2O value   ALWAYS 47 mm Hg  
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barometric pressure @ sea level vs. Mount Rainier   760 mmHg sea level. 430 mm Hg Mount Rainier.  
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PIO2   partial pressure of O2 that has been moistened in the trachea. PIO2 = (barometric pressure - PH2O)*FIO2  
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physiological causes of hypercapnia   1) hypoventilation, 2) severe V/Q mismatch (high physiologic dead space)  
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causes of hypoventilation   pump problem (respiratory muscle damage) or control problem (SC injury, stroke, drug overdose)  
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FVC   max. volume air exhaled rapidly after maximal inspiration. forced vital capacity.  
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FEV1   volume of air expired in 1 second of forced expiration. < 25% predicted value associated w/increased PaCO2. "forced expiratory volume 1 sec".  
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FEV1/FVC definition & normal value   normal = 80%. airway obstruction =47%. severe airway obstruction (e.g. asthma) =20%.  
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spirometry & OBSTRUCTIVE disease   1) volume of exhalation reduced (airway narrowing, loss of elasticity) -> low FVC. 2) slower exhalation (dynamic airway compression) ->VERY low FEV1. overall, FEV1/FVC = VERY LOW. decreased ERV, increased FRC, RV & TLC.  
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spirometry & RESTRICTIVE disease   1) noncompliance of lungs -> low expiratory volume. 2) normal to high elastic recoil = FEV1 not very reduced. 3) FEV1/FVC = normal to HIGH. Decreased FRC, TLC.  
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Asthma   spastic bronchoconstriction caused by allergens/irritants. 1) mast cells activated -> histamine & cytokines -> local edema + mucus + spasm -> HIGH R. 2) dynamic airway compression. 3) LOW FEV1, FVC, FEV1/FVC.  
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COPD pathology   1) chronic bronchitis: irritants -> cilia paralysis, HIGH mucus, inhibited macrophages, infection, edema -> stretched alveoli -> alveolar death (50-80%). 2) emphysema = enlarged lung airspace + alveolar wall destruction.  
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COPD causes   environment: smoking, pollution, dust, chemicals. genetics: alpha1-antitrypsin deficiency (1% cases).  
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COPD physiology   1) LOW FEV1/FVC. 2) HIGH TLC & RV. 3) V/Q mismatch (shunts or dead space). 4) decreased diffusion (loss of alveolar walls). 5) fewer capillaries -> pulmonary hypertension -> right sided heart failure. 6) increased CO2 -> acidosis & mortality.  
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inspiratory ramp   2 sec ramp-up (dorsal respiratory neurons) = inhalation + cutoff for 3 sec (pneumotaxic center) = exhalation  
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increasing ventilation to maintain tissue needs   HYPERPNEA  
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rapid but normal breathing   TACHYPNEA. Total ventilation HIGH. Alveolar ventilation depends on Vt & Vd/Vt  
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Vt definition & normal value   Tidal Volume = air entering body during single breath. ~400-500 ml @ rest.  
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FRC definition & normal value   Functional Residual Capacity = air in lung @ end of normal expiration (e.g. @ rest). ~2600-3400 ml. determined by compliance & elasticity.  
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VC definition & normal value   Vital Capacity = max. volume air exhaled after max. inhalation. ~3400-4500 ml. most common test.  
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RV definition & normal value   Residual Volume = air remaining in lung after max. expiration. ~1500-1900 ml. CANNOT BE MEASURED BY SPIROMETRY!  
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TLC definition & normal value   Total Lung Capacity = air in lung @ max. inspiration. ~6000 ml. determined by elasticity, stiffness of lung, inspiratory muscle strength.  
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awareness of difficulty in breathing (feels shot of breath)   DYSPNEA.  
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paused breathing   APNEA  
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dorsal respoiratory group, MEDULLA   responsible for INSPIRATION & general breathing rhythm. sensory afferents from vagus (lung chemo & stretch R's) & glossopharyngeal nerve (peripheral chemoR inputs). efferents -> phrenic nerve to diaphragm.  
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ventral respiratory group, MEDULLA   INACTIVE during passive breathing. ACTIVE during active respiration (e.g. exercise).  
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pneumotaxic center, UPPER PONS   cuts off inhalation ramp (regulates volume & rate).  
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apneustic center, LOWER PONS   prolongs inhalation, increases volume of inhalation. normally inhibited by pneumotaxic center of upper pons & vagus afferents.  
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Apneusis   deep & prolonged inspiration with periodic expiration  
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central chemoreceptors (ventilation)   sense H+ in CNS (only CO2 crosses BBB though). located near ventral resp. group (medulla). 75% of CO2-induced increase in ventilation.  
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peripheral chemoreceptors (ventilation)   sense PO2<60mmHg, high CO2, low pH. located in carotid/aortic bodies. detect hypoxemia & account for 25% of CO2 increase in ventilation.  
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adaptation to high PaCO2   after 1-2 days of high CO2, kidneys reabsorb bicarbonate to equivocate blood pH.  
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hypercapnia ventilation response   BOTH peripheral & central chemoreceptors activated  
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hypoxic ventilation response   only begins when PaO2<60 mmHg (Hb saturation curve = steep). normally, low O2 enhances normal ventilatory response to CO2.  
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Acute FX of high altitude   decreased PAO2 -> hyperventilation (low O2) -> low CO2 -> central respiratory centers restore normal respiration. high pulmonary vascular resistance (vasoconstriction due to hypoxia). Hb saturation curve = right shift.  
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Chronic FX of high altitude (acclimatization)   chronic low O2 -> brain respiratory centers lose 80% sensitivity to H+ -> hypoxia @ peripheral R's is much more influential.  
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lung stretch R's   airway smooth muscles. respond to large inspiration. activate pneumotaxic center. protect lungs from overinflation. (Vt > 1500 ml)  
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Herring-Bruer response   lung stretch receptors signal pneumotaxic center to terminate inspiration  
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lung irritant R's   large airways. respond to gas, smoke, dust. initiate cough, bronchoconstriction, sneezing. protects alveoli.  
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J receptors   =juxtapulmonary capillary R's. in lung parenchyma, vessels, airways. respond to edema or too high blood flow. cause dyspnea, rapid shallow panting.  
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chest wall receptors   detect force by respiratory muscles. contribute to dyspnea.  
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PaO2 during moderate exercise   O2 usage can be 20x higher. CO2 increases as well. BUT ventilation adapts = arterial levels do not change dramatically.  
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anaerobic threshold   = threshold for metabolic acidosis in heavy exercise: pH decreases w/lactic acid generation.  
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damage to respiratory centers of brain caused by:   1) brain edema. 2) drugs (anesthesia & narcotics)  
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Cheyne-Stokes breathing   deep breathing alternates w/ low/no breathing. depression of brain activity due to: slow blood delivery (congestive heart failure)/abnormal response by respiratory control centers (sleep @ high alt. or brain damage)  
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SIDS   likely due to CO2 ventilation response. infant on back = less risk of re-inhaling exhaled CO2  
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sleep breathing   NonREM = eupneic, decreased CO2 sensitivity. REM = = irregular breathing, V. low CO2 response. barbiturates can stop ventilation in REM.  
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central sleep apnea   decreased central drive to breath  
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obstructive sleep apnea   def: >15 apneic incidents @ >10 sec each per hour sleep. decreased airway tone (collapse). decreased chemoreceptor/central drive, exacerbated by alcohol/depressants.  
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low rate of breathing or shallow breaths   HYPOPNEA  
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contributing factors to sleep apnea   supine position, nasal obstruction, large tonsils, age, obesity (e.g. fat deposits in pharynx & compression due to neck fat), pregnancy  
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pathophysiology of sleep apnea   1) metabolic alkalosis when awake (CO2 builds up in apnea -> kidneys reabsorb HCO3-). 2) hypoxic pulmonary. 3) erythropoiesis -> polycthemia -> high ventricular load & afterload -> RV hypertrophy.  
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cor pulmonale   failure of the right side of the heart brought on by long-term high blood pressure in the pulmonary arteries and RV  
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normal AaDO2   5 mm Hg  
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normal Hb saturation of arterial blood   97% (saturated @ 95 mmHg PaO2) (75% saturated in mixed venous blood)  
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CaO2 normal value   =oxygen content of arterial blood (CaO2 = HbO2 + O2 dissolved). ~  
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O2 capacity of blood definition & normal value   = amt. O2 can be bound to Hb in 100 ml blood. ~20.1 mlO2/100ml blood.  
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%O2 saturation of Hb equation   %SO2 = [HbO2]/O2 capacity x 100  
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normal amt. Hb in blood   normal ~ 15 g/100 ml blood  
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O2 bound to Hb (equation)   [Hb] g/dl x 1.34 ml O2/g Hb x % SHbO2  
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normal oxygen consumption @ rest   ~250 ml O2/minute  
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AV shunts   increase blood flow to capillaries when contracted (thermoregulation & BP control). when open, connect arterioles directly to venules.  
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endothelin 1   endothelial cell vasoconstrictor -- target of "red wine effect"?  
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prostacyclins & blood clotting   relased by tunica intima EC's -> anti-adhesion  
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VEGF   activates stem cells for endothelium for blood vessel growth & differentiation  
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Avastin   anti-VEGF = anti-angiogenic. treatment for metastatic colon cancer.  
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pericytes   contract to control blood flow @ capillaries & postcapillary venules. same stem cells as endothelium. die in diabetic retinopathy -> microaneurysms. serve as progenitors for fibroblasts in wound repair.  
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PDGF   induces stem cells to form into pericytes instead of endothelial cells  
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extrinsic innervation of GI tract   PARASYMP: (preganglionic fibers synapse on enteric interneurons) vagus nerve, pelvic nerve. celiac/sup. SYMP: postganglionic fibers synapse on smooth muscle/vessels/secretory cells) (mesenteric/inf. mesenteric & hypogastric plexi  
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vago-vagal reflex   local GI conditions -> afferents to vagus ->efferents to local circuit  
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GASTRIN   increases H+ secretion from parietal cells. released by G-cells in mucosa of stomach antrum (pyloric gland area), binds ECL cells in xyntic gland area -> histamine production -> parietal cell HCl release. MAY bind parietal cell directly.  
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CCK   released by I cells in duodenum/jejunm + neurons in ileum & colon. increases enzyme & fluid secretion by acinar cells, -> smooth muscle contraction in Ductal cells of pancreas/gallbladder. Decreases gastric emptying  
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SECRETIN   released by S cells of small intestine. -> Gs/PKA -> CFTR Ch. P'ated & opens in Ductule cells of pancreas to increase HCO3- & water secretion.  
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GIP (GASTRIC INHIBITORY PEPTIDE)   released by K cells of duodenum/jejunum. causes decreased fluid absorption, slows gastric emptying, inhibits acid production.  
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GUANYLIN   released x ileum & colon. targets small & large intestine to increase fluid absorption.  
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MOTILIN   released by endocrin cells in upper GI tract. targets stomach & duodenum to increase smooth muscle contraction.  
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PEPTIDE YY   endocrine cells in ileum & colon (maybe also enteric nerves) -> lowers acid secretion  
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SOMATOSTATIN   released by D CELLS in stomach & duodenum, due to pH < 4.5. Inhibits parietal, ECL, & G cells -> decrease acid secretion.  
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SUBSTANCE P   neurotransmitter between enteric neurons  
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VIP   released by enteric NS, causes smooth muscle cells to increase fluid secretions in small intestine. opens lower esophageal sphincter. inhibits BER.  
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Neurotensin   released by endocrine cells in GI tract. targets smooth muscle to release histamine.  
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BER (basic electrical rhythm)   periodic fluctuations in the V_rest of GI smooth muscles originating @ pacemaker(L-type Ca & Ca-activated K Chs). stretch/ACh -> higher Vrest + APs. NE/NO/VIP -> lower Vrest.  
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physiological ileus   inhibitory intrinsic neurons inhibit most of lumen smooth muscle. EXCEPTIONS: sphincters, parts of proximal stomach under chronic contraction.  
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contents of saliva   (hypotonic vs. plasma). alpha amylase, lingual lipase, lysozyme/RNase/DNase/peroxidase (antibiotic), mucus  
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generation of saliva   GENERATION: basal Na/K/2Cl, apical Cl, Na & H2O -> transcellular. CONCENTRATION: apical K/H, Na/H, anion exchanger, CFTR, ENaC (net K/HCO3 out). Basal K-leak, CFTR (net NaCl absorbed).  
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neural influence on saliva production   sympathetics: transient protein-rich, low vol. paraysmpathetics: long-lasting protein-poor, high vol.  
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alpha amylase   cleaves alpha-1,4 linkages, not alpha-1,6 linkages. mostly faced w/glucose-based amylose (alpha-1,4 only) & amylopectin (both), not as much glycogen (both). doesn't work @ low pH.  
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lingual lipase   cleaves FA's from triglycerides & cholesterol esters. functions well @ low pH but proteolytically degraded.  
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esophageal sphincters   UES (upper esophageal sphincter) = tonically contracted, but reflexively relaxes when food present. LES (lower) = opens when smooth muscle inhibited by VIP from vagus or by NO.  
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swallowing   PRIMARY (voluntary/pharyngeal reflex to food). SECONDARY if food doesn't reach stomach w/1st swallow (mechanoreceptors in esophagus initiate, can be local reflex or reinstation of full motor sequence by medulla)  
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Achalasia   LES doesn't open during swallow  
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normal pulmonary systolic & diastolic pressures & mean pressure   25/8 mmHg (mean = 14 mmHg)  
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pulmonary : systemic vascular resistance   1: 10  
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equation for vascular resistance   R = (systolic P - diastolic P)/CO (P=QR). NOTE: pulmonary R drops as CO increases!  
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lung zones x pressure gradients   1) A > a > v. 2) a > A > v. 3) a > v > A  
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controls of pulmonary blood flow   low PAO2 -> vasoconstriction.  
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Hypoxic Pulmonary Vasoconstriction   low PAO2 or blood pH -> decreased K+ current in smooth muscle of small arteries -> depolarization & Ca entry in L-type Ch's -> vasoconstriction  
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blood flow to the coronary arteries   Left coronary = blood flow only during diastole. Right coronary = blood flow during both systole & diastole.  
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is the LV or RV more susceptible to ischemia?   ?  
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tissue pressure in LV during systole   pressure is greater in subendocardium than subepicardium in the LV during systole (thus subendocardium has greater risk of ischemia during partial coronary artery occlusion)  
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cerebral blood flow   750 ml/min. DOESN'T CHANGE.  
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neural pathway for swallowing   medulla to: 1) trigeminal/facial/hypoglossal nerves. 2) nucleus ambiguus -> esophageal striated muscle. 3) dorsal motor nucleus of the vagus -> enteric NS -> esophageal smooth muscle  
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gastric juice origin & composition   secreted from oxyntic glands of the gastric mucosa. HCl pepsinogen, mucus, Intrinsic Factor.  
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PEPSINOGEN   =protease. ACH -> stomach oxyntic gland CHIEF CELLS, pH <5 activates it-> pepsin. Cephalic & Gastric Phases.  
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acid secretion   PARIETAL CELLS. 1) Na/K ATPase brings K in basal (K leaks out). H+/K ATPase brings H+ out (K leaks in). net = H+ apical!!! 2) w/out H+, more HCO3 made. HCO3/Cl antiporter -> HCO3 out. Cl leaves apical. net = Cl apical & HCO3 basal!! sum = HCl apical, Na  
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regulation of acid secretion   H+/K+ ATPase pumps in vesicles moved to membrane during fed state, retrieved during non-fed state  
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molecular regulation of parietal cell acid secretion   histamine->Gs->cAMP->PKA->>>pumps in membrane OR (Gastrin?)/ACh ->Gq ->PLC->Ca++ & PKC ->>>pumps in membrane. POTENTIATION of diff. signaling pathways  
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histamine in the GI tract   paracrine-release from enterochromaffin-like (ECL) cells. binds H2 receptor on parietal cells  
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Zantac mech. of action   target H2 receptor on parietal cells to block histamine-related acid secretion  
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phases of acid secretion   CEPHALIC~30% response; vagus nerve ->ACh -> GRP (gastrin releasing peptide). GASTRIC~60%; distension-> ACh & GRP + vago-vagal reflex, peptides/aa's-> act on G cells. INTESTINAL~10%, aa's in s.i. -> parietal cell stim. OR enterooxyntin released.  
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GRP (gastrin releasing peptide)   released by intrinsic neurons of stomach, promotes gastrin release by G cells. stimulated by vagus nerve or mechanoreceptors of intrinsic neurons.  
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enterooxyntin   released by distension of duodenum or in response to aa's & peptides. stimulates parietal cell acid secretion (unknown mech)  
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attenuation of acid secretion   gastric pH, somatostatin, prostaglandins, CCK, secretin, VIP, GIP, peptide YY.  
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mucus in the stomach   1) vagal ACh -> mucus neck cells produce SOLUBLE mucus (in response to irritating foods & alcohol). 2)  
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intrinsic factor   vitamin B12 absorption. secreted by parietal cells.  
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receptive relaxation of the tummy   tonically contracted smooth muscle -> relaxes in presence of bolus -> larger tummy space. initiated x mechanoreceptors, modified by vago-vagal reflex.  
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orad of stomach   in fundus toward cardia region. contractions = weak & infrequent.  
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mixing & grinding of tummy   contractions begin @ jxn of orad & caudad & propogate toward pylorus. w/time contractions initiate more and more rostral to "pinch off" portions of bolus in orad for processing.  
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ANTRAL SYSTOLE   BER occurs in pairs (bookending bolus). 1st wave -> closes pylorus even more. 2nd wave = bolus arrives @ closed sphincter & "slams" into pylorus = ANTRAL SYSTOLE  
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chyme   mixed-up digestive juice in tummy.  
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mechanisms that decrease gastric emptying   1) duodenal chemoreceptors sense acid/fat/hypertonicity/peptides/aa's-> intrinsic NS. 2) intrinsic NS ->CNS -> increase symp decrease parasymp tone. 3) duodenal cells release SECRETIN, CCK, GIP, GASTRIN  
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renal blood flow   afferent arteriole = 50 mmHg pressure -> 20 mmHg @ efferent arteriole. blood flow = 25% systemic. increased colloid osmotic pressure due to fluid filtration almost stops filtration @ distal kidneys.  
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Cephalic Phase of pancreatic secretion   1) vagus nerve (ACh) stimulates acinar cells. 2) Gastrin (neuro), VIP, GRP (enteric NS) potentiate FX. Gall bladder empties.  
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Intestinal Phase of pancreatic secretion   1)H+-> SECRETIN-> ductule cell CFTR Ch's open-> HCO3 secreted. 2)vago-vagal reflex-> acinar&ductules increase secretion. 3)FA's & small peptides-> CCK-> acinar secretions increased + Gall bladder empties.  
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Gastric Phase of pancreatic secretion   tummy distenstion -> vago-vagal reflex = slight increase in acinar secretions  
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Bile composition   Bile acids/salts 70%, P-lipids 20%, Cholesterol 5%, Bilirubin 1%, "remainder" 4%. Isotonic to plasma (~290 mOsm). bile duct cells add HCO3 & H2O (secretin-stimulated).  
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Bile Acids   carboxylic acids. primary choleic acid -> 2ndary deoxycholic acid. primary chenodeoxycholic acid -> 2ndary lithocholic acid (via s.i. bacteria). 2ndary = VERY insoluble.  
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Conjugated Bile Acids   modified by the liver to increase solubility. covalent addition of glycine/taurine. low pKa, exist as Na+ salts. solubilize bilirubin in mixed micelles. [critical micelle] = dpdt on all components, not just bile acids.  
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Bilirubin export from liver   Bilirubin = from Hb in spleen (V. Hydrophobic, toxic) -> liver via Albumin chaperone in blood. Transporter into liver, conjugated w/Glucuronide to detoxify. APICAL: ATPase transporter.  
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control of bile secretion from liver   1) bile acid-dpdt flow (bile secretion (electrolytes) promotes further secretion). 2) bile acid-indpdt flow (via. secretin -> fluid & HCO3) (3g bile acids secreted 4-12 x per day) amt. excreted == amt. synthesized.  
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Gallstones   excessive precipitation of cholesterol/bilirubin, etc.  
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Gall Bladder secretion of bile   vagal ACh -> gall bladder smooth muscle contraction (cephalic & intestinal phases). CCK increases gall bladder contraction & inhibits Sphincter of Oddi.  
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bile acid reabsorbtion in s.i.   APICAL: Apical sodium-dependent bile acid transporter (ASBT)(Na 2ndary active transport coporter)(recovers>95% bile acids). BASAL: OST (Organic Solute Transporter) transports bile acids into blood stream  
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bile acid recycling in liver & "Bile Acid-Dpdt Component of Bile Secretion"   BASAL: Na-dpdt 2ndary active transport. APICAL: ATPase (primary active transport). Bile Acid movement drives movement of H2O, ions!!!  
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pancreatic amylase   lumenal enzyme: degrades alpha 1-4 linkage of starch -> di/trimers. [NOTE: alpha 1-6 linkages degraded by membrane bound enzymes]. -> glucose/galactose/fructose  
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sugar absorption   monosaccharides only can be absorbed. APICAL: SGLT1 = Na coporter for glucose or galactose. GLUT 5 = fructose passive absorption. BASAL: GLUT2 transports all sugars to bloodsream.  
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protein digestion: lumenal   ENDOPROTEASES: Trypsin, Chymotrypsin, Elastase. EXOPROTEASES: Carboxypeptidases A & B. Trypsinogen activated by trypsin/enterokinase  
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Enterokinase   = PROTEASE that cleaves & activates trypsinogen  
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protein absorption   aa's, di/tripeptides transported. 2ndary active transport (Na-based) or facilitated diffusion. further degraded to aa's in EC cytoplasm, then basal transporters.  
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pancreatic lipid digestive enzymes   1) pancreatic lipase, 2) cholesterolesterase, 3) phospholipase. watersoluble enzymes work @ lipid interface.  
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fat emulsification   1) mixing in stomach. 2) duodenal bile salts retard separation of water & fat. NOTE: emulsions are not truly in solution  
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colipase   binds lipase, displaces molecule of bile salt from fat droplet. prevents displacement of lipase by bile acids.  
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mixed micelles   formed by bile acids + emulsion. contain CONTAIN LIPID BREAKDOWN PRODUCTS. digestion IN EMULSION, absorption IN SOLUTION (mixed micelle).  
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fat absorption   glycerols: water soluble, diffuse in. micelles: pass through unstirred water layer = lipids transported into cell & bind carrier proteins  
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fat processing in absorptive cells   FAs & monoglycerides + binding protein -> DAGs & TAGs -> chylomicrons. Cholesterol adds straight to chylomicron.  
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NPC1L1   transports unesterified cholesterol & plant sterols into absorptive epithelial cells. Ezetemibe Drug blocks this cholesterol carrier!!! (statins block cholesterol synthesis)  
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ABC5/8   trasports plant sterols & cholesterol back to lumen from intestinal absorptive cells (in bilirubin family)  
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fat soluble vitamin absorption   A, D, E, K into mixed micelles or protein-mediated, likely transported into epithelial cells  
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water soluble vitamin absorption: e.g. FOLATE   B, C, Folate, Biotin. protein-mediated absorption. Folate glutamates are cleaved until Pteroyl-Glu(1). antiported against OH- -> converted in cell to biologically active BH2 & BH4  
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iron absorption in s.i.   Heme imported directly (endocytosis) -> Heme Oxygenase extracts iron + bilirubin -> liver w/transferrin. Iron converted to Fe2, coported w/H+ (apical), transported to transferring (basal) in circulation.  
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migrating motor complex (MMC)   begin in duodenum/stomach. point of initiation moves more distal until @ 6 hours reaches ileum. intrinsic enteric NS activity. hormone motilin = initiates. food ingestion ends it.  
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motilin   initiates migrating motor complex.  
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vomiting reflex   vomiting center (4th ventricle chemoreceptor trigger zone)/emotional brain/mechanoreceptors in throat/chemoreceptors in GI tract.  
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retching   proceeds vomiting. reverse peristalsis in s.i. = pyloric sphincter & tummy relax, then sphincter closes again. air inhaled into esophagus. LES opens for gastric contents but UES stays closed. When UES opens = vomiting.  
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modulation of body temperature via skin blood vessels   apical skin: cold = sympathetics -> vasoconstriction = decreased heat loss. nonapical skin: no anastomoses, vasoconstriction when warm. vasodilation with continued warming (sympathetic withdrawal). sweat stimulation = bradykinin causes more vasodilation.  
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apical vs. nonapical skin   apical = nose, lips, ears, hands, feet w/anastomoses/shunts/glomus bodies. nonapical = trunk & limbs.  
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splanchnic circulation   25% of CO. sympathetic control. decreased flow during quiet standing, exercise, hemorrhage.veins = large blood reservoir.  
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ascites cause   cirrhosis of the liver  
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fetal circulation   before birth, 2 left-right shunts. @ birth, umbilical cord tied off -> hypoxia & increased peripheral resistance -> gasp & lungs inflate  
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patent ductus arteriosus treatment   COX inhibitors or surgical closure  
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measuring coronary blood flow   Nitrous Oxide method or radioactive washout technique  
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coronary vein drainage   LEFT: coronary sinus (& ant. cardiac veins). RIGHT: anterior cardiac veins (also direct communication via arteriosinusoidal, arterioluminal & thebesian vessels).  
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neuromodulation of coronary vessels   sympathetics -> increased HR & contractility -> vasodilation (2ndary fx). alpha adrenergic blockers can decrease sympathetic tone. ACh -> vasodilation but also decreased HR -> vasoconstriction  
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myocardial oxygen usage   maximal @ rest. must increase blood flow to increase O2 delivery. cardiac muscle extracts ~70% O2 & skeletal muscle extracts ~15%.  
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hypoxic vasodilators of the coronary circulation   K, prostaglandins, NO, adenosine  
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myocardial O2 consumption   electrical activation = .05% total usage. Myocardial O2 use correlates w/wall tension (not external work). 1) HR, 2) Wall Tension, 3) Contractility.  
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Double Product   Systolic Blood Pressure x HR. used most frequently to measure myocardial O2 usage. heart disease = reduced blood flow + pain + ischemic ECG @ given double product.  
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Triple Product   Systolic Blood Pressure x HR x Ejection Time  
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ischemic threshold   myocardial O2 demand exceeds O2 supply. measured w/double product.  
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Restoring coronary artery supply-demand balance   1) Ca Ch blockers increase blood supply. 2) beta blockers decrease cardiac O2 demand.  
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conducting zone of airways   trachea, bronchi, bronchioles  
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respiratory zone of airways   17th airway branches to alveolar sacs. gas exhange @ terminal respiratory unit (bronchioles, alveolar ducts, alveoli)  
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examples of obstructive lung diseases   asthma, COPD (e.g. emphysema). HIGH resistance, LOW airway diameter -> air trapped in lungs.  
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examples of restrictive lung diseases   Fibrosis, Silicosis, Asbestosis, Scoliosis. Cannot expand lungs.  
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Helium Dilution Method   determines RV (cannot be measured w/spirometry). known amt Helium inhaled & exhaled until equilibrium. [He]0 x volume of tank = [He]final x (volume of tank + lungs). volume of lungs ==FRC  
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Anatomic Dead Space estimation (V_subD)   dead space in ml ~= body weight in lb  
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Alveolar Ventilation   = minute ventilation - minute dead space. same overall minute ventilation w/more breaths/min & lower tidal volume -> lower alveolar ventilation.  
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Alveolar Dead Space   due to alveoli that don't receive adequate blood flow  
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Physiological Dead Space   = Anatomical + Alveolar Dead Space  
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water vapor pressure during inhalation   PO2(inhaled) = (P_barometric -PH2O) x Fractional%O2 in air. Thus, water vapor added in airways decreases the partial pressure of O2. when overall barometric pressure is low (e.g. high altitude), PH2O is the same, & so less O2 is inhaled.  
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Hypoventilation def.   inadequate alveolar ventilation for a given amount of CO2 production.  
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minute ventilation   v(dot)E or v(dot)T. = vol. gas entering or leaving breathing passageways in 1 minute  
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Transpulmonary Pressure   P(sub)TP. = transmural pressure across alveolar wall. measure of elasticity working to collapse lungs @ end inhalation. = alveolarP - pleuralP  
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lung compliance   measure of lung distensibility. inversely related to elasticity. C(sub)L = change in lung volume/transpulmonaryP . = slope of lung volume-pressure curve.  
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collapsing pressure of the alveoli   P = 2*surface tension/radius . surfactant reduces surface tension in small more than in large alveoli. decreased surface tension minimizes transudation (leaking) of plasma from capillaries into alveoli.  
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atelectasis   alveolar collapse due to increased surface tension  
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factors influencing FX of surfactant   1) surface density of surfactant (works better @ higher density). 2) whether alveolus is expanding/contracting  
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hysteresis in lung V-P curve   due to fx of surfactant (size-dpdt variable surface tension & prevention of small alveoli collapse during exhalation)  
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lung surfactant physiology   secreted by Type II alveolar cells. Consists of Dipalmitoyl Phosphatidylcholine (DPPC). Rapidly metabolized, so must be constantly remade. pulmonary embolism stops production (->increased work of breathing + atelectasis).  
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alveolar pressure (P(sub)A)   determined by elasticity of alveolar wall. = force that drives out air during exhalation.  
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turbulent air flow   most likely when diameter of tube is large & velocity is high. w/breathing 80% of resistance to airflow b/tw nose & medium sized airways (diam>2mm). COPD increases airway resistance in smaller airways <2mm.  
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what are symptoms and indications related to turbulent flow in a patient's central airways?   "wheezing" indicative of bronchospasm generating turbulent flow.  
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airway cross-sectional area dpdt on:   1) lung volume (i.e. radial traction opens airways during inspiration). 2) elasticity (airways collapse when decreased elasticity holding them open). 3) Bronchiol smooth muscle contraction (i.e. asthma narrows airways)  
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flow in large vs. small diameter airways   in large cross-sectional area (e.g. peripheral) there is more pressure exerted against the walls of the airway. In small cross-sectional areas (trachea) velocity increass -> decreased pressure against walls -> more likely for airway to collapse  
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factors affecting expiratory flow rate   beginning of exhalation = high lung volumes -> effort-dependent flow. end of exhalation = low lung volumes = effort-independent flow.  
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Equal Pressure Point   where airway pressure = pleural pressure (transpulmonary pressure = 0). -> dynamic airway compression. @ low lung volumes, EPP moves down to airways unprotected by cartilage (transpulmonary pressure of alveoli decreases b/c less elastic recoil)  
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EPP & emphysema   less elastic recoil due to missing lung tissues -> dynamic compression of airways @ higher lung volumes (maybe entire exhalation). 1) exhale slowly through pursed lips (lower velocity = less drop in P). 2)deeper breaths (more radial traction)  
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control of bronchoconstriction   1) ACh, 2) irritants, 3) histamine  
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control of bronchodilation   1) Norepi (weak) & Epi (strong) @ beta2R. 2) beta2 agonists ALBUTEROL  
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factors affecting diffusion constant of a gas   Diffusion Constant varies directly w/Solubility. Indirectly w/sqrt of Molecular Weight  
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factors affecting rate of diffusion of a gas   Directly Variable: 1) Diffusion Constant, 2) surface area, 3) [O2] difference b/tw alveoli & venous blood. Indirectly Variable: distance traveled for diffusion  
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Diffusion Capacity of the Lung (D_sub_L)   = amt O2 diffusing across barrier membrane in 1 minute under a pressure difference of 1 mm Hg. Increased during exercise, decreased in some diseases (fibrosis, edema, emphysema/bronchial obstruction, low compliance in silicosis)  
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O2 capacity   max. amt O2 that can combine with Hb. dpdt on: 1)amt Hb, 2) ability of Hb to bind O2.  
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normal amt. Hb/100 ml blood   15 g  
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normal O2 capacity of blood Hb   20.1 ml O2/100 ml blood  
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O2 content   = total amt. O2 in blood (in Hb & in solution). O2 content = (O2 binding capacity x % Hb saturation) + dissolved O2  
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O2 saturation (SO2)   =% total O2 binding sites in Hb not bound to O2. NOT dpdt on amount of Hb. %SO2 = O2 content - O2 dissolved in blood/O2 capacity x 100  
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normal PO2 & SO2 of blood leaving lungs   95 mm Hg, SO2 = 97%  
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normal PO2 & SO2 of venous blood entering lungs   40 mm Hg, SO2 = 75%  
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PO2 for near complete saturation of Hb   PO2 < 70 mmHg  
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Normal amt. O2 dissolved in blood   0.3 ml  
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P50   PO2 @ which 50% Hb saturated. high P50 = low O2 binding affinity  
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normal P50 of human blood   26.5 mm Hg  
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right shift of Hb saturation curve   low pH, high 2-3-DPG & Temp  
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left shift of Hb saturation curve   high pH, low 2-3-DPG & Temp  
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CO2 % in different forms in blood   7% dissolved, 70% bicarbonate, 23% carbaminohemoglobin  
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CO2 content: pressure curve   pretty much linear  
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Haldane Effect   venous blood can transport more CO2 than arterial @ any PCO2  
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Bohr Shift   CO2 binds to Hb decreases Hb's affinity for O2  
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fraction of pulmonary capillaries open @ rest   1/3  
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increase in blood flow through lungs during exercise   4-7x higher  
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passive control of pulmonary vascular resistance   distension & recruitment of capillaries. 1) minimizes load on right heart. 2) prevents edema (lower vascular resistance). 3) ensure adequate O2 exchange (increased perfusion & capillary surface area)  
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hypoxic pulmonary vasoconstriction (HPV)   pulmonary capillaries constrict @ low PO2. pathological systemic HPV during COPD & @ high altitude  
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hypoxemia definition   Arteriolar PO2 < 85 mm Hg. extreme cases = arteriolar CO2 > 45 mm Hg.  
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ARDS   adult respiratory distress syndrome. caused by decreased surfactant production -> pulmonary edema  
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effects of gravity on lung physiology   pleural pressure is less negative @ base than apex -> alveoli more distended @ apex than base of lung. (think suspended slinky).  
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V/Q ratio @ top vs. bottom of lungs   3.6 @ top. 0.6 @ bottom.  
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Normal A-aDO2   10-15 mmHg  
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changes in pulmonary physiology w/age   1) less gas exchange (fewer working alveoli, more physiologic deadspace). 2) less alveolar ventilation (lower compliance, decreased muscle strength). 3) increased V/Q mismatch. 4) increased residual volume & residual capacity (less elastic recoil)  
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gross structure of the large intestines   longitudinal layer is v. thin w/3 thicker teniae coli. haustra = pouch-like structures in series. external anal sphincter = voluntary skeletal muscle. vagus innervates ascending & transverse colon, pelvic sacral nerves innervate descending colon & anus.  
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colon motility   1) localized movement of muscularis mucosa rubs chyme on absorptive cells. 2) Haustral movement for mixing/segmentation. 3) mass movement 3x/day (peristalsis)  
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defecation   1) stretch reflex relaxes internal & contracts external anal sphincter (dpdt on intact SC) -> feeling of need to poo. 2) conscious relaxation of external sphincter. 3) reflex = peristalsis in rectum, relaxation of puborectalis (normally kinks anal canal).  
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valsalva maneuver   contract abdominal muscles to aid in pooing  
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BP during defecation   high abdominal pressures -> pressure on large thoracic veins -> LOW venous return & LOW arterial pressure (decreased CO). can -> stroke.  
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digestion in the large intestine   bacteria break down remaining nutrients into small fatty acids that are absorbed ty epithelium. can contribute significantly to nutrition  
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ileogastric reflex   distended ileum inhibits gastric motility  
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gastroileal reflex   gastric motility increases ileal motility  
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colonocolonic reflex   distension of one part of colon decreases tension & motility in other parts of the colon  
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gastrocolic reflex   distension & motility in the tummy increases motility in the colon, promotes defecation  
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water secretion & absorption in GI tract   10 L/day enter GI tract (2 from intake, 8 from secretion). Crypt Cells in small intestine secrete water & NaCl. 8.5L absorbed by s.i. & 1/2 L absorbed by colon. 100 ml excreted.  
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water secretion by crypt cells   Na/K/2Cl pump basolateral, Cl Ch. apical (opened by phosphorylation by PKA or PKC). Na & H2O follow intercellularly. cholera toxin activates Gs -> PKA -> CFTR opens (treat w/H2O+NaCl+glucose.  
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signaling involved in water secretion by crypt cells   enteric NS: ACh, VIP, 5-HT. Vagus: ACh increases secretion. Hormones: CCK, Gastrin, NO. Motility & GI smooth muscle contraction -> more water secretion (via neurons that stimulate smooth muscle)  
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Immodium   anti-diarrheal medication. decreases GI smooth muscle contractions, therefore lower water secretion & increased absorption  
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Na absorption in GI tract   1) Na/sugar or Na/aa coporter (s.i.). 2) Na/H exchanger (duodenum/jejunum). 3) Na/H exchanger + Cl/HCO3 exchanger (ileum & colon). 4) ENaC channel (colon). all apical  
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Cl absorption in GI tract   1. passive (electrical gradient in whole GI tract; transcellular & paracellular), 2. Cl/HCO3 exchanger (ileum/colon/rectum), 3. Na/H + Cl/HCO3 exchangers (ileum/colon/rectum)  
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K absorption & secretion in GI tract   1. passive paracellular (absorption in tummy & ileum; secretion in colon & rectum), 2. active secretion K Ch (colon), 3. active absorption K/H pump (rectum)  
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GALT   1) Peyer's Patches: mucosa/submucosa in ileum, B-lymphocytes. 2) lamina propria lymphocytes (B-cells) -> IgA. 3) Intraepithelial lymphocytes(basolateral lumenal epithelium)  
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Microfold Cells   = M Cells. endocytose proteins & antigens, give them to dendritic cells & macrophages -> present them to T cells in GALT to produce IgA  
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Pulse Pressure   = systolic-diastolic pressure. normal ~40 mmHg  
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Fick's Law of Diffusion   Flux = -D*A*deltaC/deltaX . in lung, V(dot)O2 = rate of O2 transfer = D*A*(alveolar-venousPO2)/deltaX  
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Why does transmural pressure decrease from smaller to larer airways during expiration?   1) energy loss to overcome friction. 2) transition from laminar to turbulent flow. 3) decreased radial tethering. 4) lower intra-airway pressure (faster velocity)  
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Determinant of alveolar PO2 & PCO2   V/Q ratio!  
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COPD   low-grade inflammation (asthma = high). small airways 60% degraded, low IRC, FEV1<1L -> diff. breathing. 20% smokers = susceptible. cough/sputum/dyspnea/infection/wheezing. >10 pack-years. FEV1<80%, FEV1/FVC<70%, cor pulmonale, holes in lung on CT  
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airway resistance   from medium-sized to 7th generation airways (small airways have laminar flow). small airways <25% resistance (in parallel)  
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"pink puffer"   COPD: V/Q ratio still matched b/c capillaries destroyed @ same rate as alveoli  
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"blue bloater"   Chronic Bronchitis. mucous plugging in large airways --> V/Q mismatch. barrel-chest (can't get air out) + flat diaphragm (doesn't work as well)  
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bronchodilator challenge   COPD patients don't improve long-term with bronchodilators, but show short-term symptom relief (due to hyperconstricted bronhchi). helps most during exercise.  
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Pulmonary Function Testing   D(subL) of CO = diffusion capacity to CO. CO taken-up proportional to lost surface area. Deep breath of 0.3% CO, hold in, measure [CO breathed out]. low values = COPD/obstruction/fluid buildup/loss of capillaries/fibrosis/anemia/chronic CO (smoking)  
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Ulcerative Colitis   colon. starts @ rectum, extends up. neutrophils collected in crypt (microabscess), macroulceration, bloody diarrhea. inflammation in mucosa ONLY.  
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Crohn's Disease   can occur in colon/ileum/combination. ulcers through entire wall. Granulomas (instead of neutrophil microabscesses). FISTULAS (holes in GI tract fuse), scarring -> obstruction. eye & arthritis problems, bloody diarrhea.  
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Indeterminate colitis   cannot be distinguished b/tw Ulcerative Cholitis & Crohn's  
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ileum in irritable bowel diseases   impaired intrinsic factor & B12 absorbtion. impaired bile salts & fat-soluble vitamins absorption (D, A, K). no fat absorption b/c no bile -> diarrhea & gall stones. Ca (bound by free FAs) not absorbed. Kidney stones.  
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IBD (irritable bowel disease) susceptibility   Genes: IRGM, ATG1601, immune & LRR domain for bacterial recognition, Nod2 protein, Tol-like R. environment: smoking risk for Crohn's (protective for ulcerative colitis), appendectomy protective for u.c., G.I. flora autophagy & antigen presentation.  
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osmotic vs. secretory diarrhea   Osmotic = e.g. lactase deficiency. Secretory = when intestinal crypt cells move H2O w/Na & Cl.  
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cell turnover in GI crypts   3-5 days  
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PepT1   oligopeptides absorbed w/H+ coport. (Na/H pump also in apical membrane). works best w/tripeptides. ~2ndary active Na transport (others use Na coport directly). Chopped up -> single aa's in cell ->basolateral transport.  
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Hartnup Disease   protein deficient, mutation in B-transport system -> tryptophan deficiency import (only as single aa). Cystinuria = kidney stones, no cysteine through s.i.  
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lipase   TAG -> 2-monoglyceride + 2 free FA's  
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phospholipid break down   Lecithin -> Lysolecithin + free FA (PLA2)  
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