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Advanced Physiology and Patho – Exam 2 V4IVC RA tricuspidvalve RV pulmvalve pulmartery lungs palmveins CA Structure and Function of the Cardiovascular and Lymphatics System mitral LV998...

Advanced Physiology and Patho – Exam 2 V4IVC RA tricuspidvalve RV pulmvalve pulmartery lungs palmveins CA Structure and Function of the Cardiovascular and Lymphatics System mitral LV998 9 1. Detail the anatomy of the heart, including the location of each chamber and surface within the mediastinum. Outline blood flow from the SVC and IVC to the aorta, including chambers, vessels, and valves. a. Anterior to descending aorta, esophagus, and major bronchi from T5-T8 b. Shaped like a blunt cone roughly ⅔ size of clenched fist c. ⅔ to the left of midline d. Projects anterior, superior, and to left e. Heart surfaces mpot.atp8stEeteta i. Sternocostal (anterior): RV, with some LV and RA LA ii. 11 arf Diaphragmatic (inferior): LV, with some RV 111 iii. Base (posterior): LA, with some RA 2. State the location where each heart valve is best auscultated. a. Aortic: Second intercostal space, R sternal border b. Pulmonary: Second intercostal space, L sternal border c. Mitral: Apex or PMI; 5th intercostal space, midclavicular line d. Tricuspid: Right half of the lower end of the sternum 3. Discuss phases of the cardiac cycle and state which valves are open or closed in each phase. Correlate the waves of the ECG I and 1relaxation Larcyde and CVP traces to the events of the cardiac cycle. a. Phases of the Cardiac Cycle contraction i. Phase 1: Atrial systole/ventricular diastole (fast and slow filling) ii. Phase 2: Isovolumetric ventricular systole (passive); all 4 valves closed pressureexceedapsinstn.hn in iii. Phase 3: Ventricular ejection (fast and slow ejection); aortic and pulmonic valves open iv. Phase 4: Isovolumetric ventricular relaxation (S2 heart sound); aortic and pulmonic valves close v. Phase 5: Passive ventricular filling; mitral and tricuspid valves open b. Ventricles as pumps i. Period of isovolumetric relaxation: all 4 valves closed ii. Period of active filling 1. Rapid 2. Diastasis (slow filling) 3. Atrial systole (AV valves open) iii. Period of isovolumetric contraction: AV valves close iv. Period of active ejection (Semilunar valves open) emptyingventricles 1. Rapid ejection (⅓) 2. Slowed ejection (⅔) during vyrtole  Advanced Physiology and Patho – Exam 2 4. List normal cardiac pressures in each chamber. a. RA- Mean: 4 mmHg; range: 0-8 mmHg b. RVESP- Mean: 24 mmHg; range: 15-28 mmHg c. RVEDP- Mean: 4 mmHg; range: 0-8 mmHg d. LA- Mean: 7 mmHg; range: 4-12 mmHg e. LVESP- Mean: 130 mmHg; range: 90-140 mmHg f. LVEDP- Mean: 7 mmHg; range 4-12 mmHg 5. Discuss the layers of the heart wall from the fibrous pericardium to the endocardium. State the function of each layer. Differentiate between atrial, ventricular, and conduction muscle and state the property of each. Discuss how the muscle of the LV differs from that of the RV. a. Fibrous Pericardium: heavy connective tissue attached to diaphragm externalvac i. Fused to connective tissue of great vessels ii. Protective membrane that prevents overdistension and protects the heart iii. Fibrous skeleton: 1. Surrounds heart valves 2. Annulus of each valve 3. Separates muscle mass of atria and ventricles b. Serous Pericardium: thin delicate sac that forms a double layer internalsac i. Parietal layer (under fibrous pericardium) ii. Visceral layer (epicardium) outermostayÉr offñ heart Fluid in pericardial cavity bw visceral and parietallayers heart to move withinpericardial sac Advanced Physiology and Patho – Exam 2 iii. Pericardial cavity 1. 10-50 ml fluid (normally 20 mL) 2. Reduces friction 3. Pericarditis and cardiac tamponade superficial c. Epicardium: same as serous visceral layer d. Myocardium i. 3typer Atrial (contractility) ii. Ventricular (contractility) iii. Conductive (automaticity): SA node, AV node, Bundle of His, Purkinje fibers eightmarickected by It iv. Atria and ventricles separated by fibrous skeleton ÉLp v. Atrial myocardium is relatively thin vi. Myocardium of the LV is 3 x as thick as RV, meaning the RV is more susceptible to ischemia/infarction 1. RV is crescent shaped and moves like a bellow 2. LV requires circumferential shortening to eject against a systemic pressure 4-5 times greater than pulmonary pressure 3. LV is able to maintain stroke volume despite large changes in MAP, but RV decompensates with mild increases in PAP vii. Endocardium: connected to the myocardium by loose connective tissue, blood vessels, terminal conducting branches of nerves 1. Continuous with tunica intima of great vessels 2. Comprised of endothelium and subendothelium 3. Most susceptible to ischemia because the small vessels are exposed to highest pressures (opposes coronary perfusion) 4. Optimal aortic diastolic pressure are critical to perfusing smallest coronary vessels 6. List the common features of the AV valves and semilunar valves. a. AV valves i. Cusps: endocardial folds around fibrous tissue ii. Annular rings attach to fibrous skeleton iii. Free edges attach to chordae tendineae → papillary muscle iv. Prevents regurgitation from ventricles into atria v. Open and close in response to pressure gradients vi. Stenotic when less that 1 cm2 vii. Tricuspid 1. RA/RV 2. Anterior, septal, and inferior cuspsbleaflets viii. 3. 7-10 cm 2 Mitral rupture of a papillary 1. LA/LV muscleor chordae can 2. Anterior and posterior leaflets 2leaflets toleaflet lead prolapse 3. 2-6 cm2 b. Semilunar Valves and regurgitation ofblood i. Pulmonary: separates RV from main pulmonary artery 1. Right, left, and anterior cusps 2. 4 cm2 ii. Aortic: separates LV from ascending aorta 1. Right coronary, left coronary, and noncoronary cusps 2. 3-4 cm2 3. Severe stenosis at PVCs) b. Parasympathetic Stimulation i. Acetylcholine 1. Decreases chronotropy (HR) 2. Decreases dromotropy (speed of contraction) 3. Decreases inotropy (force of contraction) 4. Coronary vasodilation ii. Stimulation from: 1. Chemical (ACH) 2. Strong emotions (vasovagal reflex) 3. Mechanical pressure a. Pressure and volume (valsalva, carotid massage, bainbridge, etc)  Advanced Physiology and Patho – Exam 2 c. Baroreceptor Reflex (pressure receptors) i. Carotid 1. Afferent via Glossopharyngeal (CN IX) ii. Aortic 1. Afferent via Vagus (CN X) iii. Both excite the Cardio Inhibitory Center iv. Major role in short-term regulation of BP d. Bainbridge Reflex i. Sensitive to stretch due to increased volume in right atrium ii. Opposite effect of carotid and aortic reflex iii. Increasing stretch sends signals via Vagus nerve 1. Excite Cardio Accelatory Center 2. Inhibits Cardio Inhibitory Center iv. Increases HR, force of contraction, etc so volume is expelled e. Valsalva Maneuver i. Forced expiration against a closed glottis 1. Increases intrathoracic pressure and CVP 2. Decreases venous return ii. When glottis opens, venous return increases and causes heart to respond by increased contraction and BP → increased PSNS activity and decreased HR 11. Differentiate between myocyte and nodal action potentials stating their location, ion causing contraction, phases, and absoluterefractory period from correlation to the ECG. 11T polarized phase0 3 Pm f o na to leak in so potential rises 65mV that caurer Nachannelsto open Talkingpotent toHenshold absolute refractory period closed Na channels a. Ventricular Myocyte (Fast) F Y briefannelsopen 90mV chargeinsideall of hyperpolarization restoring i. Located in ventricle and atrial tissue period ii. Mediated by Na iii. Phase 0: rapid depolarization (Na in) 1. P wave for atria (PR 0.12-0.2) ii 2ms 0.0610s 2. QRS wave for ventricle (QRS 0.06-0.1) iv. Phase 1: initial repolarization (K+ out, Cl- in) v. Phase 2: plateau (Ca+ in, K+ out) againstgradient vi. Phase 3: Rapid repolarization (K+ out, Ca+ in briefly) 3 outzin p rinterval vii. Phase 4: Resting membrane potential (Na out, remains steady d/t Na/K pump) b. SA Nodal (Slow) i. Located in the SA or AV node ii. Mediated by Ca iii. Phase 4: resting membrane potential begins 60mV spontaneously depolarizes (conduction to K slows while Na & Ca start to leak in) iv. Phase 0: depolarization (Ca in) v. Phase 3: repolarization (K out) 12. Discuss the organization of cardiac muscle and detail the structure of a sarcomere, including the actin and myosin filaments. Describe the cross-bridging cycle and excitation contraction coupling. a. Skeletal muscle→ muscle fascicle/fasciculus→ muscle fiber (single muscle cell)→ myofibril→ actin (thin) and myosin (thick) filaments (sarcomere) b. Sarcomere- space b/w each Z-Disc, contain actin and myosin filaments and is the functional unit of contraction ardiac muscle arrangedin branchednetworks I nuclei more mitochondria than skeletal junctionamplifymovement ofAP is a synctium musclecells haveintercalateddiscsgap  9 19 I 1 e d As Advanced Physiology and Patho – Exam 2 i. I Band: light band extending from Z Disc w/ only Actin filaments 1. Shortens during contraction ii. A Band: dark band where actin and myosin overlap 1. Remains constant during muscle contraction iii. H Band/Zone: light area in middle of A band surrounding M line (middle), contains only tails of thick Myosin filament (no heads) 1. Shortens during muscle contraction iv. A band is Always same length v. H and I bands wave HI and go up and down vi. Myosin length never changes, the actin get pulled in to change the length c. Cross-bridging cycle i. Myosin head and arm together are cross-bridges, participate in contraction with actin 1. Troponin I, Troponin T and Tropomyosin on actin filament blocks binding site for myosin head 2. Calcium is released with nerve stimulus, binding to Troponin complex releasing it from actin allowing myosin to bind 3. ATP bound to myosin is hydrolyzed to ADP cocking the myosin head and triggering the power stroke rotating 45 degrees pulling the actin with it 4. If ATP binds again to myosin head, myosin will release the actin bind and return to the relaxed stage d. Excitation contraction coupling i. To spread action potential, it needs to go through T-tubules to communicate with the terminal cisternae of the sarcoplasmic reticulum allowing for release of Ca within the entire muscle fiber ii. 2 types of Calcium channels 1. L-type (long) a. Blocked by calcium channel blocking drugs (verapamil, nifedipine, dilt) b. Reduces force of contraction 2. T-type (transient) impaiment HFwpet MF.it iITfffE free calcium is pumped out of after contraction reticulum ell or taken up into sarcoplasmic concentration of Ca drops troponin relearer bound calcium as Advanced Physiology and Patho – Exam 2 13. Define preload, afterload, contractility, and compliance and discuss the impact that each has on cardiac output and stroke volume. Define ejection fraction and list values that correlate with LV function. a. Preload: volume inside the ventricle at the end of diastole (LVEDV) when preload JV Frankstarling i. Determined by: 1. venous return to the ventricle preload isprimaryfactor 2. Blood left in the LV at the end of systole affectingsv b. Afterload: Resistance to ejection during systole i. Aortic systolic pressure is the most common index of afterload for the LV 1. Decreased afterload = increased force of contraction 951 2. Increased afterload = decreased force of contraction and increased workload c. Cardiac output: HR x SV NSV i. Normally 5 L/min in adults ii. Affected by preload, afterload, contractility, and heart rate d. Stroke volume: amount of blood ejected from the left ventricle during systole i. LVEDV - LVESV ii. Determined by preload, afterload, contractility, and compliance iii. Alterations in nervous system control of ventricles iv. Adequacy of myocardial oxygen e. Ejection fraction: The fraction of the total volume of blood that is in the ventricle at the end of diastole (EDV) which is ejected during systole (SV) i. EDV - ESV/EDV ii. 70-80%: hyperdynamic iii. 52-72%: normal iv. 41-51%: mild dysfunction v. 30-40%: moderate dysfunction vi. 2.2 microns) = no tension 3. Less than 2.0 microns (too much overlap) = decreased tension ii. Preload is the primary determinant of sarcomere length in the heart and therefore the primary determinant of stroke volume 1. Too little preload → no stretch → decreased force of contraction 2. Too much preload → overstretch → decreased force of contraction iii. This is the physiologic basis for the effect that preload has on contraction (Starling Mechanism) b. Relation of velocity of contraction to afterload Advanced Physiology and Patho – Exam 2 basisfor i. Velocity of contraction is greatest when it contracts against no load ii. When load = force of contraction, velocity is 0 Physiologic c. LaPlace’s Law: smaller and thicker chambers → greater force of contraction i. Positive inotropic agents increase force of contraction afterload 1. Epinephrine 2. Norepinephrine ii. Negative inotropic agents decrease force of contraction 1. Ach released from vagus nerve 2. Beta blockers iii. Other factors that decrease force of contraction 1. Hypoxia 2. Ventricular dilation 3. Reduced LV compliance also reduces or 15. Discuss the structure and function of arteries, arterioles, capillaries, venules, and veins. Detail the role of the endothelium. a. Arteries (blood away from heart)→ arterioles → capillaries (exchange fluids b/w blood and interstitial space) → venules → veins (carry blood to heart) b. Endothelium (basement membrane) i. Transport substances 1. Large molecules via vesicular transport 2. Small molecules via opening of tight junctions ii. Coagulation: Antithrombogenesis and fibrinolysis iii. Immune system function: adhesion molecules that support white blood cells iv. Tissue growth and wound healing v. Vasomotion (autoregulation with adenosine) 1. Contraction: Epi, Norepi, angiotensin II, vasopressin 2. Relaxation of vessels: nitric oxide, natriuretic peptides, adrenomedullin, endothelins, prostacyclin 16. Outline the factors that affect blood flow and list substances that cause vasoconstriction and vasodilation. a. Pressure- force exerted on a liquid per unit area b. Resistance- Opposition to blood flow i. Diameter and length of blood vessels contribute to resistance ii. Vessel radius or diameter greatly affects resistance iii. Doubling the diameter of a catheter increases flow x16 c. Velocity- distance blood travels in a unit of time d. Viscosity- internal friction of a moving fluid i. Thick fluids move slowly, cause greater resistance than thin fluids ii. High Hct reduces flow through blood vessels (so dilute blood to increase flow) e. Compliance- increase in volume for given increase in pressure i. Reduced in atherosclerosis ii. Veins more compliant than arteries 17. Define blood pressure, mean arterial pressure, pulse pressure, and cardiac output. List the factors that impact peripheral resistance. a. BP = CO x peripheral resistance b. MAP = (2D)+S/3 or D + (1/3S) c. Pulse pressure = systolic - diastolic i. Effects of total peripheral resistance 1. Primary function of the diameter of the arterioles d. Cardiac output = HR x SV 18. Discuss neuronal control of peripheral resistance and the effect of hormones. a. Baroreceptors i. Reduce blood pressure to normal by decreasing CO and peripheral resistance ii. Can also increase BP when needed b. Arterial receptors (chemoreceptors) i. Sensitive to oxygen, carbon dioxide, pH ii. Also play a lesser role in regulation of BP c. Hormones i. Epinephrine and norepinephrine 1. Vasoconstriction Advanced Physiology and Patho – Exam 2 2. Increased myocardial HR and contractility ii. ADH: increased blood volume by resorption of H2O from DCT and collecting ducts iii. RAAS 1. Aldosterone: stimulates reabsorption of Na, Ca, Cl, and H2O to increase blood volume and stimulate thirst 2. Angiotensin II: vasoconstrictor iv. Natriuretic peptides (ANH, BNP): cause loss of Na, Cl, and H2O through their effects on kidney function, decreasing blood volume v. Adrenomedullin: powerful vasodilatory activity vi. NO, prostaglandins, endothelium-derived relaxing factor: cause vasodilation 19. Outline the structure and function of the lymphatic system. fluid and returns lymphaticsystem picks excess up a. Right lymphatic duct venouscirculations moves i. Drains right head and neck (so prefer to place RIJ lines over LIJ) to lymphocytes and leukocyte b. Left lymphatic duct Thoracicduct bw different components i. Drains everything else- Left IJ and subclavian, rest of body c. Afferent lymphatic vessels carry lymph to the nodes d. Efferent lymphatic vessels carry lymph away from nodes 20. Generally discuss tests used to evaluate cardiac function. bothducts draininto subclavian a. Chest x-rays: contour of heart and related structures b. Echo: most effective and widely used noninvasive modality, esp in valvular disease c. Stress testing i. Exercise vs. chemical (dobutamine) ii. S & S of CAD do not appear at rest iii. Injection of a radiotracer d. Technetium scanning: provides “hot spots” using nuclear scanning e. CT: evaluation of CAD and ischemia during stress testing f. Dipyridamole Thallium Scintigraphy (coronary vasodilator): looking for coronary steal g. MRI: anatomy and physiology of great vessels and myocardium in 3D h. EKG: myocardial ischemia/infarction or conduction defects, dysrhythmias i. Electrophysiology: electrical conduction of heart, looking for accessory pathways j. Catheterization with angiography 21. Outline the prevalence of cardiac disease and the physiologic changes that occur with aging. a. Prevalence of CV disease i. #1 cause of mortality ii. Affects 48% of adults b. Physiologic changes with aging i. Myocardial and blood vessel stiffening ii. Changes in neurogenic control over vascular tone iii. Increased occurrence of atrial fibrillation iv. Loss of exercise capacity v. LV hypertrophy and fibrosis vi. Arterial stiffening 1. Cross-linking of collagen 2. Increased collagen 3. Changes in elastin 4. Decreased baroreceptor activity vii. Improving cardiovascular health 1. Active risk reduction 2. Physical activity 3. Disease management Alterations in Cardiovascular Function Objectives 1. Outline the etiology, clinical presentation, diagnosis, complications, and treatment of varicose veins, chronic venous insufficiency, deep vein thrombosis (DVT), Heparin-Induced Thrombocytopenia (HIT), and Superior Vena Cava Syndrome. Advanced Physiology and Patho – Exam 2 a. Varicose vein i. Blood pools in the veins from a leakage, increased intravascular hydrostatic pressure, and inflammation of veins. ii. Caused by incompetent valves, venous obstruction, muscle pump dysfunction or a combination iii. or Altered ratio of prostacyclin top thromboxane A2 with potential for clotting, increased fibroblast growth factor, and increased transforming growth factor B in vein walls. b. Chronic venous insufficiency i. Persistent ambulatory venous hypertension ii. Treatment 1. Weight loss 2. Decrease time standing/sitting 3. Leg elevation, compression stockings, and physical exercise 4. Endovenous ablation (radiofrequency and laser) or foam sclerotherapy) 5. Vein stripping 6. Prevention better than treatment will come back c. DVT i. Prevention crucial ii. Predisposing factors include: malignancy, recent surgery, head injury, medical illness, and pregnancy iii. Mobilization soon after surgery, illness, injury iv. Prophylactic low–molecular-weight heparin or direct thrombin inhibitors v. Tests: D-dimer and Doppler vi. Treatment vii. Low–molecular-weight heparin viii. Direct-Acting Oral Anticoagulants (Apixaban (Eliquis®), Dabigatran (Pradaxa®), Rivaroxaban (Xarelto®) ix. Direct thrombin inhibitors (bivalirudin) x. Aspirin therapy xi. Catheter directed thrombolytic therapy xii. Pharmacomechanical treatment xiii. IVC Filter-only good for 6 months d. HIT i. Occurs in.1-5% of patients receiving therapeutic heparin ii. iii. 4 Caused by antibodies directed toward heparin-platelet protein platelet factor 4 (PF$) complexes Hallmark is thrombocytopenia, temporally related to heparin exposure iv. Paradoxically, HIT is a prothrombotic state, with thromboembolic complications occurring in approximately 33-50% of patients e. Super Vena Cava (SVS) Syndrome i. Very high risk with lung cancer and large thoracic aneurysms, usually develop blue face and papilledema from venous congestion ii. Recurrent laryngeal nerve compression causes hoarseness iii. Tumor can occlude airway, usually do awake intubation iv. Progressive occlusion of the SVC that leads to venous distention in the upper extremities and head v. Leading cause: nonsmall cell lung cancer, small cell lung cancer, lymphoma vi. Also caused by large thoracic aneurysms vii. Symptoms 1. Edema 2. Venous distention in face, neck, trunk, upper extremities 3. Cyanosis 4. Dyspnea, dysphagia, hoarseness, stridor, cough, and chest pain 5. CNC changes 6. Respiratory distress viii. Treatment 1. Radiation 2. Chemo 3. Surgery 2. List risk factors for hypertension (HTN). Differentiate between essential and secondary HTN and state the causes of secondary HTN. Classify the HTN and outline the treatment for each class. Detail the pathophysiology including the role of the sympathetic nervous system and RAAS. Discuss how HTN impacts cerebral autoregulation. a. HTN: Defined as SBP over 140 or DBP over 90 b. Affects the entire cardiovascular system i. Systolic HTN most significant factor in cause target organ damage c. Increases risk for MI, kidney disease and stroke d. Risk factors i. Non-modifiable Advanced Physiology and Patho – Exam 2 1. Family history 2. Advancing age 3. Gender: Female >70 years of age; male 5.5 cm ascending 2. > 6.5 cm for descending 3. Expanding > 0.5 cm/yr. 4. 4-4.5 cm Marfan or connective tissue disease i. Stanford Type A/B i. A 1. Involves ascending aorta → Surgical emergency ii. B, below subclavian no tissueischemia 1. Uncomplicated descending dissections managed medically and repaired electively 2. Medical therapy a. Smoking cessation b. Beta blocker therapy i. Goal is to get HR down to 50-60 c. Statins d. ACEI, ARB e. Docyclicine → matrix metalloproteins (MMPs) suppresses proteases involved in extracellular matrix degradation 4. Discuss arterial thrombus formation and outline the types of embolisms encountered in practice. a. Atherosclerosis leads to roughening of the tunica intima, which in turn activated the coagulation cascade b. Bolus of matter circulates in the bloodstream and then lodges, obstructing blood flow c. Types of emboli: DVT, air embolism, amniotic fluid, fat aggregate, bacteria, cancer cells, foreign substance d. Treatment i. Heparin, warfarin, thrombin inhibitors, thrombolytic agents ii. Balloon angiography iii. Drug/catheter therapies (EKOS) 5. List the causes, clinical presentation, diagnosis and treatment of peripheral vascular disease including: a. Thromboangiitis obliterans (Buerger Disease) i. Occurs mainly in smokers ii. Inflammatory disease of the peripheral arteries which occurs mainly in smokers iii. T-cell activation and lack of endothelial precursor cells → blood vessel lining damage →obliteration of small to medium sized arteries iv. Pain and tenderness, sluggish blood flow, rubor, cyanosis v. Treatment: smoking cessation, sympathectomy, exercise, immunomodulation, spinal cord stimulation, bone marrow transplantation b. Raynaud's phenomenon/disease i. Episodic vasospasm in the arteries/arterioles of the fingers, less commonly the toes ii. Raynaud Disease is primary vasospastic disorder. iii. Endothelial dysfunction with imbalance of vasoconstrictors and vasodilators iv. Changes in skin color/sensation v. Raynaud phenomenon: caused by other diseases or medications vi. Treatment: avoidance of cold, emotional stress, smoking cessation c. Detail the pathophysiology of atherosclerosis. i. Thickening and hardening caused by the accumulation of lipid-laden macrophages in the arterial wall ii. Endothelial injury → inflammation of endothelium →cytokine release → cellular proliferation → macrophage migration → LDL oxidation → foam cell formation with oxidative stress → fatty streak → fibrous plaque → complicated plaque iii. Collagen cap rupture → clot → vessel occlusion iv. Leading cause of CAD and CVD Advanced Physiology and Patho – Exam 2 v. Treatment: 1. Reduce risk factors 2. Removal initial cause of vessel damage 3. Prevent lesion progression 4. Exercise, smoking cessation, controlling HTN, DM, reducing LDL d. PAD/PVD i. Prevalent in smokers and diabetics ii. Intermittent claudication, frequent infections iii. Medical à vasodilators, antiplatelet/antithrombotic mediations, cholesterol lowing medications iv. Surgical treatment includes embolectomy, thromboembolectomy, endarterectomy, bypass grafts, debridements, amputations 6. Outline the risk factors for coronary artery disease. a. Any vascular disease that narrows or occludes the coronary arteries – most common cause is atherosclerosis b. Results in an imbalance between coronary blood supply and myocardial demand for oxygen and nutrients – reversible myocardial ischemia or irreversible infarction may result c. Heart rate and LVEDP affect both supply and demand. Non Modifiable Modifiable Nontraditional Risk Factors Advanced age Dyslipidemia Inflammatory markers Family history HTN CKD Genetics Cigarette smoking Adipokines Male gender Diabetes/insulin resistance Medications Postmenopausal Obesity, sedentary lifestyle Microbiome women Atherogenic diet Air pollution, ionizing radiation Coronary artery calcification, carotid wall thickness LDL – lousy cholesterol; most associated with risk of atherosclerotic disease HLDis an indicator of risk coronary 7. HDL – happy cholesterol returns excess cholesterol to liver Differentiate between the 5 types of myocardial infarctions (MI) and state the criteria for Type I and Type II MI. a. Occurs over a spectrum and proceeds from endocardium à epicardium Goal q b. Ischemic changes in 10-15 mins – ST depression and T wave inversion (increase supply/decrease demand) c. Injury results in troponin release – ST elevation (PCI/cath lab) d. Complete necrosis takes 2-4 hrs – noted as Q waves e. Silent ischemia is especially prevalent in women and diabetics; 70% is silent f. Prinzmetal angina – causes unpredictable chest pain that may occur at rest due to coronary vasospasm – if you have Raynaud’s you are more likely to have Prinzmetal angina g. Type 1: Coronary Clot (ACS) i. Plaque Rupture/erosion with occlusive thrombus ii. Could be STEMI or NSTEMI iii. Transmural injury – full thickness of heart iv. PCI often needed v. Criteria: 1. Rise and/or fall of cardiac troponin (cTn) with at least 1 value > 99% of upper reference limit with evidence of ischemia and 1 or more of the following: a. Sx of ischemia b. New ST changes or new LBBB c. New pathologic Q wave Advanced Physiology and Patho – Exam 2 d. Imaging revealing new loss of viable myocardium or new wall motion abnormality e. Identification of a coronary thrombus on imaging/autopsy h. Type 2: Supply/Demand: - mostly seen in post-op period i. In presence or absence of CAS (no plaque rupture) ii. More common in women, higher mortality 2/2 more comorbidities iii. Potential causes 1. CAD with imbalance 2. Vasospasm 3. Coronary dissection/embolism 4. Acute aortic dissection 5. Tachy/brady arrhythmia, hypo/hypertension, anemia, LVH iv. Criteria 1. Rise and/or fall of cTn with at least 1 value > 99% of URL, evidenced of an imbalance between myocardial O2 supply and demand unrelated to acute coronary atherothrombosis, requiring at least one of the following: a. Sx of ischemia b. ST/LBBB EKG changes c. Pathological Q wave d. Imaging evidencing new loss of viable myocardium or wall motion abnormality i. Type 3: Sudden death i. Symptoms of ischemia, EKG changes, V-fib ii. Death before biomarkers of MI on autopsy j. Type 4: PCI/Stent i. cTn > 5x 99% URL ii. 4a: within 48 hours of PCI iii. 4b: Stent/scaffold thrombus iv. 4c: Restenosis after PCI k. Type 5: CABG (cTn >10 x 99% URL) 8. Discuss acute coronary syndrome and differentiate between a. ST elevation MI (STEMI): transmural b. Non-STEMI: subendocardial c. Unstable angina: reversible myocardial ischemia and a harbinger of impending infarction (troponins are NOT elevated) 9. Define myocardial stunning, hibernation, preconditioning, and reperfusion injury. Stunning Hibernation Preconditioning Reperfusion Injury Occurs when an acute Chronic reduction in blood Occurs before, during, or Stunned or hibernating vessel occlusion flow after the insult myocardium is suddenly subsequently reopens and restored with high blood flow reperfuses the myocardium Myocardial function is Cellular signaling, cascades, decreased to match blood and amplification leads to Cell damage, swelling, Wall motion abnormalities flow immediate cardioprotection leaking Reversible Function returns when Genetic reprogramming later May be reversible but coronary perfusion is offers further protection progress to irreversible Myocardium less responsive restored damage to drugs Inhaled anesthetics and Viable myocardium some IV meds may contribute Infarction leads to remodeling – process that occurs in the myocardium after an MI Heart dilates to compensate for reduced systolic function Eccentric hypertrophy with series addition of sarcomeres Advanced Physiology and Patho – Exam 2 List other cardiac and systemic causes for elevated troponin. Cardiac Causes of Elevated cTn Myocardial Injury Causes of Elevated Non-cardiac Causes of Elevated cTn cTn Heart Failure Plaque disruption with thrombosis Sepsis, infection Myocarditis CKD Cardiomyopathy Reduced myocardial perfusion Stroke, SAH Takotsubo (broken heart syndrome) (embolism, vasospasm, aortic PE, pulmonary HTN Coronary revascularization dissection, etc.) Amyloidosis, sarcoidosis Cardiac procedures Chemo drugs Catheter ablation Increased myocardial O2 demand Critical illness Defibrillation Strenuous exercise Cardiac contusion 10. Discuss the etiology, clinical presentation, diagnosis and treatment of: Condition Etiology Clinical Presentation Diagnosis/Treatment Pericarditis Inflammation of the Fever, myalgia, malaise; Rest pericardium sudden, severe chest pain Salicylates, NSAIDS Diffuse ST elevation in all leads Nonsteroidals, colchicine Friction rub Pericardial Effusion Accumulation of fluid in the Beck’s Triad: Pericardiocentesis pericardial cavity 1. HTN 2. Distant heart Pericardial window Tamponade →emergency sounds 3. JVD Pulsus Paradoxus: 10 mmHgtoooooo increase in SBP on spontaneous inspiration or PPV Constrictive Pericarditis Fibrous scarring with Exercise intolerance Sodium restriction occasional calcification of the pericardium →visceral Dyspnea on exertion Diuretics and parietal layers adhere Fatigue Anti-inflammatories Can occur after someone has radiation Anorexia Surgical excision of pericardium if not successful Diastolic HF Advanced Physiology and Patho – Exam 2 11. Discuss the pathophysiologic difference between the following, including the associated conditions, alterations in wall thickness, volume, compliance, and contractility, and heart failure Type Associated Chamber Chamber Myocardial Dysrhythmias Heart Failure Conditions Volume Compliance Contractility Dilated Pregnancy, EtOH, Increased Increased Decreased in Sinoatrial Left (Eccentric) IHD, infections, left ventricle tachycardia; nutritional atrial and deficiencies, systolic ventricular Fastfull toxins, regurgitant dysfunction dysrhythmias valvular disease, forward DM, renal failure, hyperthyroid Volume overload Series addition of new sarcomeres Hypertrophic Untreated HTN, Decreased Decreased, Normal or Atrial and Left (Concentric) inherited defect of especially in supernormal ventricular muscle growth and LV (Increased dysrhythmias development EF%) (mutation of slow myocin) Diastolic dysfunction Pressure overload systemic Parallel addition of new sarcomeres May have HOCM, LVOT obstruction, or SAM → MR Restrictive Infiltrative disease Normal to Decreased, None Tachycardia Right (amyloidosis, decreased especially in myocardium sarcoidosis) LV becomes Iatrogenic: rigidand radiation, chemo noncompliant Idiopathic: endomyocardial filling fibrosis, Loeffler pressures endomyocarditis during diastole 12. State the law that relates to ventricular wall tension. a. Law of Laplace wall thickness pressure Advanced Physiology and Patho – Exam 2 13. List hemodynamic goals in treating the various types of heart failure. Type Clinical Manifestations Treatment Hemodynamic Goals Dilated (Eccentric) Dyspnea, fatigue, pedal Reduce blood volume, “Full, Fast, & Forward” edema increase contractility, reverse underlying disorder Maintain high-normal HR Lower SVR Need adequate preload but avoid afterload Hypertrophic (Concentric) Angina, syncope, B-blockers, Ca-channel “Slow, Sinus, Systemic” Hypertensive or stenotic palpitations, symptoms of blockers, ACE-I valvular MI, symptoms of LV failure, Slow-normal HR especially with exercise IVCD in high risk individuals Adequate preload Leading cause of death in Surgical resection of septum athletes Adequate coronary PP Septal ablation (higher BP) Treat hypotension and dysrhythmias promptly – want Neo HR slow) Cardiovert early! Restrictive RV failure with systemic Correct the underlying Correct the underlying cause venous congestion cause, diuretics, transplant, palliative Palliative care Myocardium becomes rigid and noncompliant, impeding Diuretics ventricular filling and raising filling pressures during Transp;ant diastole Ex: Amylodisis, sarcodisis, after radition/chemo, and endomyocardial fibrosis Advanced Physiology and Patho – Exam 2 14. For each valvular defect (AS, MS, AI, MR) list the causes, clinical presentation, pathophysiologic changes and hemodynamic goals of management. overloadocentric stenosis pressure overfed regurg volume Valve Disorder Causes Clinical Manifestation Pathophysiologic Hemodynamic Goals Changes Aortic Stenosis Degeneration with Angina (5 years) Valve orifice is Slow, sinus, aging Syncope (3 years) constricted and systemic Bicuspid aortic valve SOB/CHF (2 years) narrowed in younger patients Midsystolic ejection Results in high Keep BP and preload 25% inflammatory murmur 2nd ICS RSB velocity jet stream and up (RA, chest radiation, Pulsus tardus, narrow pressure drop across etc.) PP the valve Maintain sinus rhythm Concentric LV and cardiovert early hypertrophy Graded on valve CPR ineffective area 4cm severe Mitral Stenosis Rheumatic fever (esp Dyspnea LV underloaded (only Slow, sinus, in women and valvular disease that pulmonary underdeveloped A-fib 2/2 atrial has this manifestation) countries) enlargement Rate control for a-fib Severe when valve Avoid hypoxia, Degenerative RV failure area less than 1 cm2 hypercarbia, acidosis calcification (elderly) Avoid pure Diastolic rumbling LA hypertrophy vasoconstrictor and Inflammatory disease murmur choose meds with (RA, radiation) Graded on valve alpha and beta effects Pulmonary HTN area (avoid pulm HTN!) Avoid T-burg and abdominal insufflation May need to support RV Aortic Regurgitation Acute endocarditis or Loss of isovolumetric Increased LVEDV and Full, fast, forward aortic dissection relaxation eccentric hypertrophy High-normal HR Rheumatic heart Bounding pulse with disease rapid upstroke and Lower SVR enhances wide PP forward flow Degenerative aging and HTN Decrescendo diastolic murmur at 2nd ICS Connective tissue RSB disorders Mitral Regurgitation MVP or myxomatous Holosystolic “blowing” Eccentric hypertrophy Full, fast, forward degeneration murmur at apex of LA and LV Vasodilators may Rheumatic fever Loss of isovolumetric improve contraction LV dysfunction hemodynamics Dilated cardiomyopathy Dyspnea 2/2 High-normal HR pulmonary edema MI, endocarditis A-fib 2/2 atrial dilation Reduced PVR, SVR Advanced Physiology and Patho – Exam 2 15. Differentiate between systolic and diastolic, right and left heart failure. Heart Failure Pathophysiology Clinical Manifestations Treatment Systolic (HFrEF) Decreased inotropy, increased compliance and Subject to supply ischemia Apply O2 dilation Decreased EF Nitrates, morphine, Caused by CAD, MI, dilated cardiomyopathy diuretics, ACE-I, Increased diastolic volume aldosterone blockers, Pressure overload, volume overload, eccentric beta-blockers hypertrophy, regurgitant valves Dyspnea, orthopnea, frothy sputum Increase contractility Increased catecholamines Fatigue Reduce preload and RAAS, ADH, ANP, BNP, TNF-alpha, IL-6 afterload Decreased UOP Myocyte calcium transport Edema Insulin resistance and DM Diastolic Decreased myocardial relaxation, decreased Demand ischemia Physical training (HFpEF) compliance of LV (aerobic and weight Abnormal relaxation, training) EF preserved increased LVEDP Beta blockers IHD, HTN, AS, HOCM Dyspnea on exertion ACE-I Myocardial edema, fibrosis, concentric Fatigue hypertrophy, age, pressure overload, obesity ARBS LA pressure increases to compensate for LV Aldosterone blockers filling Left Inability of heart to generate adequate cardiac Pulmonary edema Same as HFrEF output to perfuse vital tissues Dyspnea, orthopnea, frothy sputum Right Inability of the heart to provide adequate blood Peripheral edema Same as Left flow into the pulmonary circulation at a normal CVP JVD, hepatosplenomegaly Increase in LV filling pressure that is reflected back into pulm circulation Advanced Physiology and Patho – Exam 2 16. Compare the ACC/AHA stages of heart failure to the NYHA classes of heart failure 17. Outline the treatment of heart failure. 18. Discuss the neurohumoral changes associated with the failing heart. a. Increased catecholamines b. Increased angiotensin II, aldosterone Advanced Physiology and Patho – Exam 2 c. Increased ADH d. Increased ANP, BNP e. Increased TNF-alpha, IL-6 Alterations in Cardiovascular Function in Children (1 Question) 1. Outline fetal circulation including the role of the foramen ovale, ductus arteriosus, and ductus venosus. a. Foramen ovale: opening between the atria b. Ductus arteriosus: joins the pulmonary artery to the aorta c. Ductus venosus: connects the inferior vena cava to the umbilical vein 2. Discuss the changes that occur at birth and postnatal development of the circulation. a. Receives blood-carrying oxygen and nutrients from the placenta through the umbilical vein b. Blood travels to the liver, where a portion enters the portal and hepatic circulation i. ½ of the flow is diverted away from the liver through the ductus venosus and into the IVC c. Fetal circulation: i. Most of the blood bypasses the lungs by flowing through the ductus arteriosus and into the descending aorta ii. Blood from the descending aorta returns to the placenta through two umbilical arteries that branch from the internal iliac arteries d. Transitional Circulation: i. With clamping of the umbilical cord, SVR increases dramatically and circulatory changes take place after birth ii. Gas exchange shifts from the placenta to the lungs iii. Fetal shunts close (ductus venous, foramen ovale, and ductus arteriosus) e. Postnatal Development and Circulation: i. Changes in position of the heart; changes in the size of the right ventricle ii. Decreased PVR, increased SVR – helps the left ventricular myocardium to become thicker and more dominant, heart ranges from 100-180 bpm iii. Blood flow follows the same pathway as adults 3. Categorize each congenital heart defect as primarily a lesion that increases pulmonary flow, decreases pulmonary flow, obstructs left or right outflow, or as a mixed lesion. – do not need to memorize a. Prenatal, environmental, and genetic risk factors: i. Maternal: Rubella, lupus, insulin-dependent diabetes, alcoholism, illicit drug use, age >40, PKU, hypercalcemia b. Lesions increasing pulmonary blood flow (defect that shunt from high pressure left side to low pressure right side with pulmonary congestion and cyanosis) i. Patent ductus arteriosus (PDA) – ii. Atrial septal defect – dx by murmur iii. Ventricular septal defect (VSD) iv. Atrioventricular canal defect (AVC) c. Lesions decreasing pulmonary blood flow (generally complex with right-to-left shunt and cyanosis) i. Tetralogy of Fallot (TOF) ii. Tricuspid atresia d. Obstructive lesions (right or left-sided outflow tract obstruction that prohibit blood flow out of the heart; no shunting) i. Coarctation of the aorta ii. Aortic stenosis iii. Pulmonary stenosis iv. Hypoplastic left heart syndrome e. Mixed Lesions (desaturated blood and saturated blood mix in the chambers or great arteries of the heart) i. Transposition of the great veins ii. Total anomalous pulmonary venous connect (TAPVC) iii. Truncus arteriosus iv. Hypoplastic left heart syndrome (HLHS) Advanced Physiology and Patho – Exam 2 4. Discuss Eisenmenger syndrome and list congenital defects that are associated with hypoxia and cyanosis. a. Eisenmenger syndrome – increased PVR that exceeds or equals vascular resistance, resulting in a reversal of shunting b. Defects that cause hypoxemia and cyanosis: i. Lesions that cause obstruction and shunting grom the right side of the heart to the left side of the heart, as in tetralogy of Fallot ii. Defects involving the mixing of saturated and unsaturated blood, as in the univentricular heart iii. Transposition of the great arteries 5. List the 4 defects in Tetralogy of Fallot and outline the defects in hypoplastic left heart. a. Defects of TOF: i. Large VSD ii. Overriding aorta straddles the VSD iii. Pulmonary stenosis iv. Right ventricle hypertrophy v. S/S: Cyanosis, hypoxia, clubbing, feeding difficulty, dyspnea, restlessness, squatting. Hypercyanotic spell or “test spell” that occurs with crying and exertion. b. Hypoplastic left heart i. Left sided cardiac structures develop anormally ii. Obstruction to blood from the left ventricular outflow tract iii. Left ventricle, aorta, and aortic arch are underdeveloped; mitral atresia or stenosis is observed iv. As the ductus closes, systemic perfusion is decreased, resulting in hypoxemia, acidosis, and shock Advanced Physiology and Patho – Exam 2 Pulmonary Physiology A. Pulmonary Volumes a. Tidal Volume (TV) - Volume of air inhaled and exhaled with each normal breath. Equal to about 500 mL. i. Minute TV – volume of air inhaled and exhaled during 1 minute. Calculated by multiplying the TV by the respiratory rate. Equal to 8L ii. Alveolar volume – TV minus the dead space volume. Equal to about 350 mL (500-150 dead space) iii. Average minute alveolar volume is about 5600 mL (500-150 dead space x 16 breaths per minute) b. Inspiratory Reserve Volume (IRV) – extra volume of air that can be inhaled beyond the normal tidal volume. Equal to about 3000 mL. i. Measure of effectiveness of pulmonary compliance and inspiratory muscle strength. ii. A decrease in IRV is associated with disorders that reduce lung compliance, weaken inspiratory muscle, or both. 1. Restrictive disorders and end-stage COPD may have reduced IRV c. Expiratory Reserve Volume (ERV) – volume of air that can be forcefully exhaled after a normal tidal inhalation. Equal to 1100 mL. i. Indicator of airway patency and expiratory muscle strength ii. Increased ERV is an indication of improved respiratory muscle strength iii. Decreased ERV is associated with weaker musculature, airway obstruction, and restrictive disorders d. Residual Volume (RV) – volume of air still remaining in the lungs after the most forceful exhalation. Equal to 1200 mL. i. Indicator of airway patency and effectiveness of elastic recoil ii. Increased RV occurs with aging à effectiveness of ventilation is reduced e. Forced Expiratory Flow (FEF) or Peak Expiratory Flow (PEF/PEFR) – flow rate/speed of air being exhaled during the middle portion of a forced expiration i. Indicator of airway patency ii. Usually the only PFT is clinical setting. Reductions greater than 25% of a person’s PEFR is an early indicator of obstructive disorders. f. Forced Expiratory Volume 1 (FEV1) – maximum amount of air that a person can forcefully expel during the first second of exhalation after a maximal inhalation. Normal is 80% of an individual’s normal average. i. Most sensitive clinical and rapid test for the need for intervention r/t to airway obstruction, especially acute asthma g. Diffusing capacity of lung carbon monoxide (DLCO) – how well gas moves from the alveoli into the erythrocytes in pulmonary circulation. i. Helpful in determining alveolar dysfunction – test is near normal in people with asthma or bronchitis and is greatly reduced in the presence of emphysema, pneumonia, and pulmonary edema B. Pulmonary Capacities a. Inspiratory Capacity (IC) – composed of the tidal volume and inspiratory reserve volume. Equal to 3500 mL. i. Maximum amount of air that can be inspired ii. Reduction=restrictive, especially fibrosing disorders b. Functional residual capacity (FRC) – composed of the expiratory reserve volume and the residual volume. Equal to 2300 mL. i. Amount of air remaining in the lungs at the end of normal tidal respiration ii. Increased in obstructive disorders (can’t get it all out). c. Vital capacity (VC) – composed of inspiratory reserve volume + tidal volume + expiratory reserve volume. Equal to 4600 mL. i. Maximum amount of air that can be expelled from the lungs after filling the lungs to the maximum extent d. Total lung capacity (TLC) – composed of tidal volume, inspiratory reserve volume, expiratory reserve volume, and the residual volume. Equal to 6L. i. Maximum volume that the lung can hold with the greatest inspiratory effort ii. Reduced in restrictive disorders iii. Increased in severe long standing COPD e. Forced Vital Capacity (FVC) – maximum amount of air that can be exhaled as quickly as possible after maximal inhalation. i. Indicates respiratory muscle strength and ventilatory reserve ii. Average VC for men = 4800 mL, Average VC for women = 3500 mL iii. Reduced in both obstructive and restrictive disease C. Pulmonary Functions a. Regulation of oxygenation and gas exchange b. Protection (macrophages, surfactant) c. Maintenance of cardiac output and blood pressure d. Immunity e. Fluid, electrolyte, and acid-base balance Advanced Physiology and Patho – Exam 2 D. Processes Involved with Pulmonary Function a. Ventilation – movement of atmospheric air into and out from lungs for gas exchange b. Perfusion – circulation of blood through tissues and organs for gas exchange c. Diffusion for gas exchange – movement of O2 and CO2 molecules across permeable membranes from an area of higher partial pressures to areas of lower partial pressures E. Pulmonary Anatomy a. Easier for things to be aspirated into right bronchus because it is shorter and more vertical b. Most respiratory function in right because it is larger; left lung is smaller due to heart leaning left. c. By adulthood, 500 million alveoli; alveoli amount depends on how active they are – alveoli development stops at older adolescence d. Goblet cells produce mucus e. Cilia beat towards throat f. Dead Spaces i. Anatomic dead space: anatomic areas (beyond the larynx – conducting airways) where normal structures are too thick for gas diffusion. Average=150 mL ii. Physiologic dead space (includes anatomic dead space – do not add): all areas (beyond the larynx) in which gas diffusion does not occur 1. Includes normal anatomic structures and areas of pathology (pulmonary embolism) iii. In health, physiologic and anatomic dead spaces are equal. Advanced Physiology and Patho – Exam 2 F. Airway Pressure and Flow a. Resistance is the reciprocal of flow (anything resistant to flow, slows flow) b. Factors that affect airway resistance include: airway length (increased length, increased resistance), airway radius (decreased radius, slows flow), and flow rate. i. Trachea and bronchi have least impedance to flow c. Boyle’s Law i. Mass and temperature are constant – pressure is increased or decreased – volume of gas will vary inversely is with the pressure ii. Inhalation: atmospheric air>intrathoracic pressure (air will go from area of low pressureàhigh pressure). Mew iii. Exhalation: intrathoracic pressure> atmospheric pressure O O airs ew G. Perfusion: Pulmonary Circulation a. Two separate systems, one smaller to oxygenate pulmonary structures and one larger to provide gas exchange for systemic circulation b. 9% of total blood volume c. Low pressure, high flow system d. Small increases in pulmonary capillary pressure can result in transudation and edema e. Serves as reservoir with great compliance f. Pulmonary artery (away from heart, towards lungs) g. Pulmonary veins (away from lungs, toward heart) Advanced Physiology and Patho – Exam 2 H. Ventilation and Perfusion a. Gas exchange depends on both ventilation and perfusion b. Ratio unequal in different areas of the normal lungs (position and gravity, blood vessel distribution, and unequal alveolar filling) c. When ventilation is 0, there is no ventilation i. Alveolar pressure=capillary gas pressure (no exchange) d. When perfusion is 0, Va/Q=infinity i. No perfusion and alveolar gas pressure = those of atmospheric air e. High V/Q = >ventilation than blood flow (pulmonary embolism, wasting ventilation) f. Low V/Q = > blood flow than ventilation (wasting blood flow – pulmonary edema, pneumonia, asthma) I. Diffusion and Gas Exchange a. Rate of gaseous diffusion depends on: i. Pressure gradient ii. Amount of diffusible surface area iii. Degree of gas solubility iv. Thickness of the diffusing membrane b. Higher altitudes à pressure changes (Ex: In Denver, atmospheric pressure is 655 mmHg – harder to inhale) c. CO2 has a high solubility and diffusiblity coefficient i. Crosses easier into alveoli vs O2 into capillary à will see hypoxia before hypercarbia ii. Hypercarbia is a sign that disease has been going on for awhile J. Surfactant and Surface Tension a. Family of lipoproteins secreted by type II pneumocytes, starting late in fetal life b. Reduce surface tension by preventing the formation of an air-water interface with a very high surface tension c. Surfactant is between water molecules to keep them separate so alveoli won’t collapse – decreased surface tension, especially in smaller alveoli d. Smaller alveoli are inherently unstable – greater tendency to collapse (Surface tension is inversely proportional to the radius of the alveoli) e. Surfactant increases the compliance of each alveolus so less work or effort is needed to expand the entire lung and reduces the risk of pulmonary edema by preventing transudation f. Law of LaPlace Advanced Physiology and Patho – Exam 2 K. Compliance – how much lung can expand a. Expandability/distensibility of lungs and thorax b. Volume increases in the lungs for each unit increase in intra-alveolar pressure c. How much volume increases depends on the compliance of chest wall and alveoli d. When alveolar pressure increases by 0.7 mmHg (0.95 cm H2O), lung volume expands by 130 mL e. Compliance = change in volume/change in pressure L. Elastance – ability of lungs to go back to normal shape after expansion a. Interaction between the recoil of the lung (alveoli) and the recoil of the chest b. Resistance and elastance are the reciprocal of compliance c. Tendency of the lung and chest wall to spring back to their original shape after expansion M. Gaseous Transport a. Hemoglobin is an allosteric molecule meaning the process by which oxygen binding to one subunit of hemoglobin affects the binding of oxygen to other subunits. The binding of oxygen to one subunit causes conformational changes that are relayed to other subunits, increasing their affinity for oxygen. b. 02activelyunloading c. Haldane Effect – increased O2 binding to Hgb, decreased Hgb affinity for CO2 (facilitates CO2 release from lungs) d. Bohr Effect – decreased pH = increased CO2, decreased Hgb affinity for O2 (facilities O2 to be released into tissues) e. Carbon Dioxide Transport i. CO2 is always transported more easily and in greater quantities in the blood than is O2 ii. Mostly as bicarbonate (70%), in combination with plasma proteins (23%) f. Carbon Monoxide Transport i. CO binds competitively at the same site on Hgb where O2 binds ii. CO binds 200x more tightly than O2; Hgb will selectively bind with CO over O2 iii. Patient will not be cyanotic with CO poisoning N. Autonomic Regulation of Ventilation (occurs in brainstem) a. Dorsal Respiratory Group (DRG) i. Responsible for basic rhythms of ventilation ii. Contains both inspiratory and expiratory areas in separate but interconnected oscillatory circuits that are mutually inhibitory to prevent simultaneous inspiration and expiration iii. Primarily inspiratory, does not vary in rhythm, only in pattern b. Ventral Respiratory Group (VRG) i. Only acting during overdrive to augment both inspiratory and expiration ii. Activates abdominal muscles for more effective expiation during heavy exercise iii. VRG is not needed during quiet ventilation Advanced Physiology and Patho – Exam 2 c. Inspiratory “Ramp” – progressive excitation in inspiratory neurons, increasing firing rate and numbers firing. The purpose of the ramp is to allow smooth, progressive filling of the lungs instead of “gasps” d. Central Chemoreceptor Regulation (responsive to increased CO2 and H+) e. Peripheral Chemoreceptors (more responsive to decreased O2/hypoxia) i. Located in highly metabolic/active tissues such as aortic arch and carotid sinus Obstructive Pulmonary Problems A. General Pathology a. Pathology reduces airway lumen resulting from an increase in resistance to air flow at any level of the bronchia tree b. Anatomic airway narrowing, deceased elastic recoil c. Chronic airflow limitation B. PFT Abnormalities w/ Disease a. Restrictive Disease Decreased VC, FEV1, PERF, FRC, RV, and TLV Normal FEV1/FVC b. Severe Obstructive Disease Decreased VC, FEV1, FEV1/FVC, PERF Increased FRC, RV, TLC C. Emphysema - trouble getting air out a. Patho Permanent enlargement of acini and destruction of alveolar walls without fibrosis Enzymatic degradation of elastin in alveoli and airways 1. Alveoli lose elasticity and recoil 2. Small airways collapse or narrow 3. Alveoli become large and flabby – air becomes trapped in the lungs 4. Alveolar destruction 5. Air-filled spaces (bullae) Decreased area for functional gas exchange – retaining CO2 Primary pathological changes – loss of lung elasticity and lung hyperinflation Collapse/narrowing of smaller bronchioles b. S/S Increased WOB Dyspnea and increased RR Advanced Physiology and Patho – Exam 2 Hyperinflated lung flattens diaphragm – additional muscles (accessory muscles) in the neck, chest wall, abdomen needed to inhale/exhale Air hunger sensation due to increased effort which increases the need for O2 and metabolic nutrients Inhalation begins before exhalation is completed, resulting in dyspnea with an uncoordinated breathing pattern D. Bronchitis/Bronchiolitis – trouble getting air in a. Patho Inflammation of the bronchi and bronchioles from continuous exposure to infectious or noninfectious irritants, especially tobacco smoke and vaping chemicals Irritants cause an inflammatory response, vasodilation, congestion, mucosal edema, and bronchospasm Affects airways rather than alveoli Chronic inflammation results in mucous gland hypertrophy and hyperplasia, which produces large amount of thick mucus Bronchial walls thicken and impair airflow – small airways affected before large airways PaO2 decreases and PaCO2 increases respiratory acidosis E. COPD a. Risk factors Deficiency of alpha 1 antitrypsin (AAT) 1. Mutated gene – cannot get rid of proteases, which will destroy elastin in lungs Cigarette smoking Chronic exposure to inhalation irritants Air pollution Vaping b. Complications Hypoxemia and acidosis Advanced Physiology and Patho – Exam 2 Respiratory infections Cardiac failure (Cor pulmonae) Cardiac dysrhythmias Activity limitations Premature death c. S/s General: Thin, decreased muscle mass (except lung muscles) Slow moving, slightly stooped “tripod position” Reduced hunger, nutritional deficits Fatigue (short on O2, fatigue will be a huge symptom) d. S/s Respiratory: Rapid, shallow respirations Use of accessory muscles Abnormal breathing patterns Decreased excursion, decreased fremitus, hyperresonant Crackles Dyspnea Barrel chest (increased anterior- posterior ratio) Non-cyanotic “pink puffer” – emphysema dominates with CO2 retention Cyanotic, blue tinged, dusky appearance (chronic bronchitis dominates, “Blue bloater” Excessive sputum Clubbing of the fingers Decreased capillary refill Acute respiratory acidosis 1. Decreased pH – 7.25 2. Normal-ish HCO3 – 22 mEq/L 3. Increased PCO2 – 70 mmHg 4. Decreased PO2 – 55 mmHg e. Compensation for Respiratory Acidosis Process in which the body uses its three regulatory mechanisms to correct for changes in the pH of body fluids If a lung problem causes retention of CO2, the healthy kidney compensates by increasing the amount of bicarbonate that is produced and retained 1. The kidney is the best at getting rid of H+ 2. Renal compensation/Increased Bicarb = longer or chronic problem Partial Compensation 1. Decreased pH – 7.26 2. Increased HCO3 -- 30 mEq/L 3. Increased PCO2 – 80 mmHg 4. Decreased PO2 – 65 mmHg Full compensation (complete) 1. Decreased pH – 7.33 phis hearingnormal 2. Increased HCO3 – 38 mEq/L 3. Increased PCO2 – 85 mmHg 4. Decreased PO2 – 68 mmHg F. Asthma a. Pathology Condition of intermittent, reversible airflow limitation from narrowed airways Constriction of bronchiolar smooth muscle (allergen, irritants) 1. Exercise 2. Upper respiratory infections 3. Genetic factors Edema of luminal mucosa inflammation (obstructed lumen), eosinophilia (75% of asthmatics release IL-5), reactive mast cells, neutrophilia Advanced Physiology and Patho – Exam 2 1. Specific allergens include: cold, dry air; fine airborne particle microorganisms, air pollution, chemical fumes, GERD, aspirin Increased pulmonary secretions Bronchoconstriction alone triggers receptors in airway mucosa, activating a protective response of reducing airway diameter to limit exposure to the trigger Inflammatory response 1. Early – acute bronchoconstriction on trigger exposure caused by mucosal responses of inflammation a. Begins within 30 mins with release of inflammatory mediators causing increased capillary permeability, edema, increased mucous, bronchoconstriction, and airway narrowing b. Can resolve in 1-3 hours 2. Late a. Usually 4-8 hours after early response b. Increased airway hyperresponsiveness c. Latent release of initial mediators and increased synthesis of more mediators, especially from eosinophils which induce tissue damage d. Crystals and debris from cells further obstruct the airway, injure cilia, hypertrophy of goblet cells e. Over time, airways remodel and fibrose 3. Presence of chronic inflammation leads to damage and hyperplasia of bronchial cells and of smooth muscle 4. With frequent attacks, exposure even to reduced levels of triggering agent/event stimulate attacks 5. Severe chronic asthma can result in such bronchial tissue damage that cor pulmonale results b. S/s (may not have symptoms between attacks) Chest tightness Shortness of breath Audible wheeze (1st on exhalation) Cough (often nonproductive early) Increased RR Use of accessory muscles Difficulty talking Activity intolerance Sleep interruption with cough/wheeze Barrel chest (late with severe disease) Hypoxia – decreased pulse ox, cyanosis, tachycardia, altered LOC Labs: acute respiratory acidosis, elevated eosinophils, elevated IgE levels, sputum may have Curschman spiral and/or Charcot-Leyden crystals (fragmentation of eosinophils) G. Obstructive Sleep Apnea (OSA) a. Pathology Disordered breathing pattern during sleep with intermittent cessation of ventilation Not associated with disruption of CNS or brainstem stimulation for ventilation Purely mechanical problem and very under diagnosed – bidirectional disorders b. Risk factors Obesity Male Large uvula Enlarged tonsils/adenoids Short neck Oropharyngeal edema Smoking/vaping Oral cavity/pharyngeal malformations Increasing age Diabetes, HTN, allergies, other obstructive disorders, stroke Advanced Physiology and Patho – Exam 2 c. Diagnostic Criteria Apnea only during sleep, each episode lasts at least 10 seconds, pattern repeats a minimum of 5x each hour Hypopnea and relaxation of oral and neck muscles displaces tongue, soft palate, and uvula Snoring precedes complete airway obstruction Ventilation and gas exchange are inhibited, O2 falls, CO2 rises, stimulating central receptors Increased effort wakens person Pulmonary Problems: Infectious Disorders - lungs are very susceptible to infection due to anatomic location to outside world A. Acute Epiglottitis a. Pathophysiology Inflammation of epiglottis (may also include supraglottic structures) – edema and swelling Most common causes are viral (RSV) and bacterial (Strep) infection Also caused by thermal, smoke inhalation, chemical injuries, traumatic intubation Life-threatening with airway obstruction 1. Nonverbal children and adults are most at risk for death because you cannot tell change in voice quality 2. Non- ambulatory children and adults are also at more risk for death Most common in younger children 1. Children under 12 months are most at risk for death b. S/s: Fever (more with bacterial) Sore throat (bacterial and viral) Change in voice