Pathophysiology of Cardiovascular Diseases PDF

### Correlate the pathophysiology to the clinical evaluation and management of systemic arterial hypertension. (Independent Learning) a. i. SBP \> 130; DBP \> 80 (ACC/AHA) ii. Have 2 qualifying measurements obtained on separate office visits b. iii. Interplay of genetic and environ...

### Correlate the pathophysiology to the clinical evaluation and management of systemic arterial hypertension. (Independent Learning) a. i. SBP \> 130; DBP \> 80 (ACC/AHA) ii. Have 2 qualifying measurements obtained on separate office visits b. iii. Interplay of genetic and environmental factors leading to increased blood volume and/or peripheral resistance iv. c. v. ; identifiable underlying cause d. e. vi. Family history, African American race, high salt intake, alcohol, obesity, low physical activity vii. Sodium intake: eating a high salt meal -\> ­ plasma osmolarity, ­ ADH, ­ reabsorption of H2O to maintain \[Na+\] around 135-145 (which ­ BP) f. viii. Symptoms of target-organ damage: headaches, transient weakness or blindness, loss of visual acuity, chest pain, dyspnea, claudication ix. Hypertensive retinopathy may indicate chronically elevated BP x. Cardiac findings: Laterally displaced PMI in LVH or S4 heart sound g. xi. xii.  a. i. BP ii. Labs: 1. Electrolytes- look for second causes like hyperaldosteronism 2. Serum creatinine- assess kidney function 3. Urinalysis- assess kidney function thru protein or blood detection 4. Fasting glucose and lipid panel to eval CV risk iii. ECG for LVH or ischemic changes iv. Echo for assessment of cardiac fx b. v. Tx: lifestyle modification (DASH, Weight loss, regular physical activity, salt restriction, alcohol moderation, smoking cessation) vi. Pharm: 5. Thiazide diuretics, ACE (lisinopril), ARBs (losartan), Ca channel blockers 6. Beta blockers (heart failure), aldosterone antagonist (spiro), direct vasodilators (hydralazine) c. vii. HBP viii. Clinical signs of organ damage (proteinuria, LV Hypertrophy on ECG) d. e. **Essential hypertension** is generally diagnosed when there are no secondary causes or suggestive symptoms. f. **Secondary hypertension** is indicated by features like sudden onset at a young age, very high blood pressure, resistant hypertension, and symptoms like muscle weakness or episodes of sweating and palpitations (suggestive of pheochromocytoma). ### Correlate the pathophysiology to the clinical evaluation and management of hypertensive vascular disease. a. Define hypertensive vascular disease in pathologic and clinical terms. a. HTN and adverse effects due to increased demands placed on vasculature i. Hyaline= leakage across endothelial cells with increased ECM production ii. Hyperplastic= smooth muscle hyperplasia with wall thickening and luminal narrowing b. Explain the main pathophysiologic mechanisms by which sustained and/or severe elevations of systemic arterial pressure lead to hypertensive vascular disease. b. Brain= lipohyalinosis; thickening of arterioles due to collagen deposits loss of contractility and increased stroke risk c. Eyes= AV nicking, copper wire appearance iii. Hyperplastic arteriosclerosis d. Heart= increased in left ventricle afterload concentric hypertrophy e. Kidney= ischemic change in glomeruli and loss of autoregulation of renal blood flow nephron loss c. Identify the known risk factors for hypertensive vascular disease, including host and environmental factors, along with clinical and comorbid conditions. f. Age, obesity, family history, reduced nephron number, high sodium diet, physical inactivity, smoking, family history d. Describe the main morphologic alterations seen in the blood vessels of patients with hypertensive vascular disease. e. Describe the main pathologic findings in each of the 5 most common target organs affected by hypertensive vascular disease (heart, large arteries, brain, eyes, and kidneys). f. Link the main clinical manifestations of hypertensive vascular disease to the underlying morphology and pathophysiology. g. Outline the principal diagnostic strategies for patients with hypertensive vascular disease, including main types of tests and when they should be used. h. Explain how test results useful in managing patients with hypertensive vascular disease should be interpreted. i. Outline the overall prognosis and main prognostic factors that predict poor outcome in patients with hypertensive vascular disease. j. Determine the affected target organs and most likely pathologic morphology in presented patients with hypertensive vascular disease. ### Apply a step-wise systematic approach to the evaluation and management of patients with resistant hypertension. a. Distinguish resistant hypertension and secondary hypertension in pathophysiologic and clinical terms. a. Resistant= HTN that remains uncontrolled despite treatment with \>3 antihypertensive medications b. Secondary HTN= underlying cause b. Identify the main categories and common examples of pathophysiologic derangements and underlying diseases that give rise to resistant hypertension and secondary hypertension. c. SECONDARY= renal artery stenosis/renal failure, endocrine htn, coarctation of aorta, estrogen, neurological, treatment c. Identify the clinical findings and test results useful in determining the pathophysiologic derangements and underlying diseases in patients with resistant hypertension. d. Outline the stepwise diagnostic evaluation of patients with resistant hypertension. e. Determine the best next step in the diagnostic evaluation and management of patients with resistant hypertension, based on clinical scenarios. f. Summarize the most likely pathophysiology category and underlying disease in patients with resistant hypertension, based on clinical scenarios. g. Select the pathophysiologically appropriate treatment for presented patients with resistant hypertension. ### ### Correlate the pathophysiology to the clinical evaluation and management of vasculitis/ vasculopathy. a. Define vasculopathy and vasculitis in pathophysiologic and clinical terms. b. Classify vasculitis by size of vessel involved (e.g. Chapel Hill Classification), including small, medium, and large vasculitides. c. Identify the main categories and common examples of underlying diseases that cause vasculitis/vasculopathy, including dysfunctional inflammatory mechanisms, immune complex deposition, or direct invasion of vessel wall. d. Contrast the pathophysiology of different antibody-mediated vasculitides including IgA vasculitis, Kawasaki disease, anti-GBM, and ANCAs. e. Explain the immune cell pathophysiology that can promote giant cell arteritis. f. Explain the pathophysiology of drug-induced vasculopathy (hapten-mediated). g. Explain the pathophysiology of infection-mediated vasculopathy (e.g. rickettsia, erythrovirus). h. Describe infectious, inflammatory and non-inflammatory etiologies of aortic vasculopathy. i. Outline the vasculitic diseases with ischemia as a major manifestation (e.g. giant cell arteritis, Takayasu arteritis, polyarteritis nodosa, thromboangiitis obliterans, Kawaski disease). j. Relate clinical findings in the evaluation of vasculitis/vasculopathy to the most likely underlying pathophysiology. k. Outline the principal diagnostic strategies for patients with vasculitis/vasculopathy, including main types of tests and when they should be used. l. Explain how clinical findings and test results should be interpreted when determining the underlying cause of vasculitis/vasculopathy. m. Describe the main treatment strategies for vasculitis/vasculopathy, including their indications for use, mechanisms of action, the main benefits and adverse effects. n. Determine the best next step in the diagnostic evaluation and management of patients with vasculitis/vasculopathy, based on clinical scenarios. ### Apply a step-wise systematic approach to the evaluation of patients presenting with dyslipidemia. (Independent Learning ) a. Define dyslipidemia in pathophysiologic and clinical terms. i. Abnormal amt of lipids in blood such as cholesterol, triglycerides, HDL, and LDL 1. High LDL \> 160; can form plaques in arteries 2. Low HDL \150: plaque formation and artery inflammation contributor 4. High total cholesterol increased heart disease and stroke; \>200 b. Identify the main categories and common examples of pathophysiologic events and underlying diseases that cause dyslipidemia. ii. Primary= genetic mutations that affect lipid metabolism 5. Familial hypertriglyceridemia, apo c2 defic, familial hdl, hepatic lipase defic iii. Secondary= lifestyle factors (sedentary, diabetes, liver disease, CKD, Meds- thiazide, beta-blockers, cyclosporine c. Relate the clinical findings and test results useful in the evaluation of dyslipidemia to the most likely underlying pathophysiology and causative diseases. iv. Typically asymptomatic v. Atherosclerosis, CAD, peripheral artery disease, stroke, heart failure developed vi. Xanthomas on eyelids vii. Arcus senilis- grey/white ring around cornea viii. Liipemia retinalis= milky appearance blood vessels ix. Lower limb ischemia caused by narrowing or artery blockage from atherosclerosis x. Angina xi. TIA and stroke d. Outline the principal diagnostic strategies for patients with dyslipidemia, including main types of tests and when they should be used. xii. Screenings: fasting liipid panel every 5 years for adults 20 yearrs and older e. Explain how clinical findings and test results useful in the management of dyslipidemia should be interpreted. f. Determine the best next step in the diagnostic evaluation and management of patients with dyslipidemia, based on clinical scenarios. xiii. A medical history and health checklist Description automatically generated with medium confidence g. Summarize the most likely pathophysiology and underlying causative disorder in patients with dyslipidemia, based on clinical scenarios. xiv.  xv. A diagram of the internal organs Description automatically generated ### ### Correlate the pathophysiology to the clinical evaluation and management of atherosclerosis. a. Define atherosclerosis in pathologic and clinical terms. a. Pathologic accumulation of LDL within vessel wall that causes narrowing b. Subtype of arteriosclerosis b. Explain the main pathophysiologic mechanisms by which humans are believed to develop atherosclerosis. c. Foam Cell- macrophages eat deposited LDL d. Fatty Streak e. Atheroma- made of SMC, Macrophages, and T Cells; ECM (collagen, elastic fibers, proteoglycans), and LIPIDS f. Rupture c. Explain the known risk factors for atherosclerosis, including host and environmental factors, along with clinical and comorbid conditions. g.  d. Identify the main stages of formation and the corresponding morphology of atherosclerotic plaques seen in the blood vessels of affected patients. e. Identify the most common arterial locations of atherosclerosis (aortic, coronary, carotid & vertebral, renal, and ilio-femoral) and main organs supplied by these vessels. f. For each of the most common arterial locations of atherosclerosis, identify the pathophysiologic events and downstream consequences of ischemia to supplied organs. g. Link the main clinical manifestations of atherosclerosis to the presence or complications of atherosclerosis, such as plaque rupture, thrombosis, and stenosis. h. Outline the principal diagnostic strategies for patients with atherosclerosis, including main types of tests and when they should be used. h. A screenshot of a white sheet Description automatically generated i. Use ASCVD risk assessment to assess risk of cardiovascular disease caused by atherosclerosis (coronary heart disease, cerebrovascular disease, PAD, aortic atherosclerosis) i. Risk factors= demographics, patient history, and clinical info (BP, Cholesterol, etc) j. Low Dose CT scan (adults \>40 yo at intermediate to high risk of ASCVD) i. Explain how test results should be interpreted in the evaluation of atherosclerosis. j. Outline the overall prognosis and main prognostic factors that predict poor outcome for atherosclerosis. ### ### Apply a step-wise systematic approach to the evaluation and management of patients with leg claudication. (Independent Learning) a. Define leg claudication in pathophysiologic and clinical terms. a. Pain, fatigue, discomfort, or cramping deep in muscle due to vascular disease from inadequate blood flow to target muscle group (= supply/demand mismatch) b. Identify the main categories and common examples of pathophysiologic events and underlying diseases that cause leg claudication. b. **Peripheral arterial disease (PAD**)/Peripheral Atherosclerosis c. Aneurysm in abdomen or leg; debris becomes emboli and clogs leg arteries d. Popliteal entrapment syndrome= muscles/cyst compress popliteal artery c. Outline the principal diagnostic strategies for patients with leg claudication and peripheral vascular disease, including main types of tests and when they should be used. d. Explain how clinical findings and test results useful in the evaluation of leg claudication should be interpreted. e. Exertional calf pain; resolves with rest (buttocks, hip, thigh, calf, and foot) f. Diminished or absent pedal pulses; bruit over distal aorta, iliac, or femoral arateries g.  h. i. Physical exam: i. Blood pressure= BLE ii. Pulse: Carotid (amplituide, bruits?), extremities iii. Auscultation and palpation of abdomen (bruit, aortic pulsation, diameter) iv. Auscultation of femoral arteries (check to see if bruits) e. Determine the best next step in the diagnostic evaluation and management of patients with leg claudication, based on clinical scenarios. j. If PAD suspected: v. ankle-brachial index (ratio of systolic pressure of each ankle to either arm's brachial artery 1. ABI \50% of normal i. True= involves all 3 layers ii. Inflammation and proteolytic degeneration of connective proteins (collagen, elastin, smooth muscle cells) causes loss of structural integrity and vessel widening. Mechanical stress acts on weakened wall tissue and causes dilation and rupture. 1. Disruption of blood flow and turbulent flow increases risk of thrombi formation in an aneurysm b. Identify the main categories of underlying disease that are associated with aortic aneurysm. b. Vasculitis: giant cell, takayasu, polyarteritis nodosa, infectious causes c. CT disorders d. Tertiary syphilis (causes obliterative endarteritis of vasa vasorum) or other infection e. Age \F g. Obesity h. DM i. Smoking j. Family hx/genetic factors k. Atherosclerosis l. Cystic medial degeneration c. Distinguish between the pathogenesis of the 3 most common causes of aortic aneurysm. d. Identify the hemodynamic forces acting on arterial walls that determine wall stress and contribute to the pathophysiologic development of aortic aneurysm. e. Explain the known risk factors for aortic aneurysm, including host and environmental factors. f. Describe the range of clinical manifestations of aortic aneurysm. m. Most are asymptomatic n. TAA: dyspnea, stridor, dysphagia, hoarseness, edema; sudden onset chest pain radiating to back= rupture o. AAA: pulsatile mass from xiphoid to umbilicus g. Link the main clinical findings of aortic aneurysm to the underlying abnormalities of structure and function. h. Outline the principal diagnostic strategies for patients with aortic aneurysm, including main types of tests and when they should be used. i. Explain how clinical findings and test results should be interpreted in the evaluation of aortic aneurysm. j. Describe the main treatment strategies for aortic aneurysm, including their indications for use, mechanisms of action, the main benefits and adverse effects. p. If \>5 cm or symptomatic or rapid rate of expansion (0.5 cm in 6 months repair q. Asymptomatic= surveillance or elective repair iii.  k. Outline the overall prognosis and main prognostic factors that predict poor outcome for aortic aneurysm. l. Recognize the presence and complications of aortic aneurysm, distinguishing it from other disorders, in presented patients. ### ### Correlate the pathophysiology to the clinical evaluation and management of aortic dissection. a. Define aortic dissection in pathophysiologic and morphologic terms. b. Differentiate aortic dissection from aortic aneurysm. c. Identify the main categories of underlying disease that are associated with aortic dissection. d. Distinguish the pathogenesis of the 3 most common causes of aortic dissection. e. Identify the hemodynamic forces acting on arterial walls that determine wall stress and contribute to the pathophysiologic development of aortic dissection. a. Blood pressure of blood in the artery= intraluminal pressure; greater pressure= greater stress on arterial wall b. Wall tension= wall tension proportional to pressure within the vessel and radius of the vessel i. T= P x r ii. Larger aorta diameters increase wall tension increased wall tension c. Shear stress= blood flow creates shear stress on endothelial cells lining arteries d. Vascular compliance= ability of arterial wall to stretch and accommodate blood volume changes and pressure affects wall stress (decreased compliance- aging or atherosclerosis increased wall stress) e. Pulsatile flow induces chyclic stress on arterial walls f. Collagen and elastin weakening aorta dissection g. HTN, atherosclerosis, CT disorders alters balance iii. Htn leads to sustained high wall stress iv. Degenerative changes weaken wall f. Explain the known risk factors for aortic dissection, including host and environmental factors. g. Describe the range of clinical manifestations of aortic dissection. h. Link the main clinical findings of aortic dissection to the underlying abnormalities of structure and function. i. Outline the principal diagnostic strategies for patients with aortic dissection, including main types of tests and when they should be used. h. j. Explain how clinical findings and test results should be interpreted in the evaluation of aortic dissection. k. Describe the main treatment strategies for aortic dissection, including their indications for use, mechanisms of action, the main benefits and adverse effects. l. Outline the overall prognosis and main prognostic factors that predict poor outcome for aortic dissection. m. Recognize the presence and complications of aortic dissection, distinguishing it from other disorders, in presented patients. ### Apply a step-wise systematic approach to interpreting a Chest X-Ray (CXR), identifying common abnormalities seen on a CXR. a. Recall the five key aspects used to evaluate CXR quality. a. Airway b. Bones c. Cardio/Mediastinum d. Diaphragm e. Effusion f. Filtrates b. Use a systematic approach to interpreting CXRs. c. Identify abnormal processes that might be seen on CXR. d. Identify medical devices that might be seen on CXR. ### Summarize the main categories of nonpharmacologic or 'indirect' (i.e. for comorbid conditions) treatments for patients with hypertension. a. Describe the dietary modifications (i.e. restriction of sodium, increased potassium, DASH diet, reduced alcohol intake) used in the non-drug treatment of hypertension. i.  b. Outline the role of non-drug treatments for hypertension, including weight loss, aerobic exercise conditioning, and smoking cessation. ii. iii. Smoking most impactful! c. Outline the role of optimization of both non-drug and drug treatment for other comorbid conditions that also elevate the risk for atherosclerosis, e.g. hyperlipidemia and DM. iv. Hyperlipidemia= using a statin in populations at risk (patients with clinical ASCVD, Familial hyperlipidemia; Diabetes with LDL \>= 70; Patients with 10 year ascvd risk \>= 7.5.) can prevent CVD 1. Exetimbe- adjunct 2. PCSK 9 inhibitors 3. Fibrates for triglycerides v. Diabetes= lifestyle modification d. Outline the role of selective antithrombotic treatment for existing atherosclerosis (e.g. antiplatelet drug) in the treatment of hypertension. e. Outline the main indications and contraindications for each non-drug or 'indirect' treatment used in patients with hypertension. f. Outline the main expected benefits and adverse effects of each non-drug or 'indirect' treatments for hypertension. g. Outline potentially hazardous interactions with other treatments for each non-drug or 'indirect' treatments used in patients with hypertension. ### ### Explain the basic pharmacology of the main classes of drugs used to treat hypertension and rationale for use in different clinical settings. a. List the main classes of drugs used to treat hypertension, including important examples of each (e.g. beta adrenergic antagonists - carvedilol and diuretics - hydrochlorothiazide). b. Identify the main indications for the use of different antihypertensives. c. Summarize the principal mechanisms and targets of action of each of the main classes of antihypertensive drugs. d. Describe the route of administration for different drugs used to treat hypertension. e. Explain the type and magnitude of clinical benefits derived from different antihypertensive treatments. f. Describe the types and frequencies of common and serious adverse drug effects associated with the use of antihypertensives. g. Compare the potential drug interactions that can occur following administration of antihypertensive medications. h. Outline the main strategies for selecting and combining agents to achieve good control of blood pressure. i. Select the best antihypertensive treatment option, given different clinical case scenarios. ### ### Explain the basic pharmacology of the main classes of drugs used to treat primary and secondary dyslipidemias and the rationale for use in different clinical settings. a. List the main classes of drugs used to treat dyslipidemia, i.e. statins, adjuncts to statins and other non-statins, including important examples of each. b. Describe the mechanism of action of statins and their effect on cholesterol and lipid transport. c. Discuss the main indications for initiating treatment with statins at appropriate therapeutic intensities. d. Describe the types and frequencies of common and serious adverse drug effects associated with the use of statins. e. Identify the potential drug interactions that can occur following administration of statins. f. Outline the appropriate follow-up and monitoring of statins. g. Compare and contrast pharmacokinetic profiles of various statins. h. Summarize the principal mechanism of action of drugs that reduce intestinal cholesterol absorption (e.g. NPCILI inhibitor; ezetimibe and bile acid sequestrants). i. Compare and contrast potential adverse effects of ezetimibe and bile acid sequestrants. j. Identify potential contraindications to the use of ezetimibe and bile acid sequestrants. k. Summarize the actions of adjuncts to statin therapy that reduce activity of PCSK9 (e.g. evolocumab; inclisiran) and ATP citrate lyase (e.g. bempedoic acid). l. Discuss the potential adverse effects associated with the adjuncts that target PCSK9 and ATP citrate lyase. m. Describe the type and magnitude of clinical benefits derived by the addition of adjuncts to stain therapy. n. Describe the effects of non-statins such as fibrates (e.g gemfibrozil), niacin, omega 3-acid ethyl esters on lipid and cholesterol transport. o. Discuss the main indications for the use of non-statin classes of drugs. p. Identify the potential adverse effects and contraindications for the use of non-statin classes of drugs. q. Outline the main strategies for selecting and combining agents to lower cholesterol and lipid levels. r. Select the best treatment option for dyslipidemia, given different clinical case scenarios. ### ### Explain the basic pharmacology of the main classes of drugs used to treat angina pectoris and rationale for use in different clinical settings. a. List the main classes of drugs used to treat angina, including important examples of each (e.g., calcium channel blockers - amlodipine, nitrates - nitroglycerin, ranolazine). b. Identify the main indications for the use of different antianginals. c. Summarize the principal mechanisms and targets of action of each of the main classes of antianginal drugs. d. Describe the route of administration for different drugs used to treat angina. e. Explain the type and magnitude of clinical benefits derived from different antianginal treatments. f. Describe the types and frequencies of common and serious adverse drug effects associated with the use of antianginals. g. Compare the potential drug interactions that can occur following administration of antianginal medications. h. Select the best antianginal treatment option, given different clinical case scenarios. ### Apply a step-wise systematic approach to the evaluation and management of patients with medication nonadherence. (Independent Learning) a. Define medication nonadherence in neutral and non-judgmental clinical terms. b. Identify biological, psychological, and social and structural determinants of health that contribute to medication nonadherence, giving examples of each category. c. Identify direct and indirect methods for measuring medication adherence and identify advantages and disadvantages of these methods. d. Identify the presence of medication nonadherence and the most likely contributing factors in presented patients, based on clinical scenarios. ### Demonstrate the ability to take a brief history and deliver bad (serious) news using the SPIKES framework during an encounter with a standardized patient. a. Define the 6 steps in giving bad (serious) news as represented in the SPIKES framework. b. Describe common pitfalls and strategies for success in delivering bad (serious) news, i.e. setting, time, support, honesty, and simplicity. c. Demonstrate delivering bad (serious) news to a patient using the SPIKES framework.  A table of medical information Description automatically generated  A close-up of a medical report Description automatically generated