Week 3 Flashcards
indicate the affected coronary vessel(s) and the alternative route of blood supply to the ischemic area based on ECG as ST elevations in V1-V4, some subtle ST elevations in I, aVL and V5, and reciprocal ST depression in lead III (there are also hyperacute/peaked T waves in V2-4)
predominantly affected area is anteroseptal, which is supplied by the anterior interventricular (IV) branch of the left coronary artery (LCA), commonly referred to as the left anterior descending (LAD).
In the event of occlusion of the anterior IV branch (LAD), blood flow to the ischemic area will increase through the posterior interventricular branch of the right coronary artery (RCA).
The ECG findings and clinical presentation are consistent with acute myocardial infarction, specifically ST-segment elevation myocardial infarction (STEMI). The ST-segment elevation indicates transmural infarct. After 12-24 hours, the infarcted area (the full-thickness) of the heart will appear reddish-blue due to microvascular injury and blood leakage and may begin to show central yellow-tan region(s) of grossly-apparent infarct.
Describe how elevated troponin I indicates the status of the myocardial cells in the ischemic zone.
Troponin I is a cardiac-specific protein that is released from the cardiac myocytes following disruption of the sarcolemmal membrane. This membrane disruption and leakage of intracellular contents into the interstitium and, ultimately, the systemic circulation, is the earliest detectable feature of myocyte necrosis. Therefore, elevated serum troponin I signals the beginning of irreversible damage (time is myocardium!).
Describe the cellular responses that have occurred in the patient’s cardiac myocytes that induced irreversible injury.
The occlusion of the coronary vessel causes oxygen levels to fall inducing a rapid shift from aerobic to anaerobic metabolism. This causes a reduction in ATP and accumulation of lactic acid. The drop in ATP interferes with the Na/K ATPases and calcium ATPases. Increases in intracellular sodium disrupt the osmotic gradient causing cellular edema. The increase in intracellular calcium increases the permeability of the mitochondria inducing mitochondrial swelling. In addition, the increased calcium activates intracellular lipases and proteases causing destruction of the cytoskeleton and cell membranes. The leak of proteolytic enzymes results in the damage of adjacent cells leading to irreversible injury
Angiogram reveals 45% stenosis in the patient’s right coronary artery (RCA), 75% in the left circumflex (LCX), and 100% stenosis of the left anterior descending (LAD). Contrast how the distal arterioles compensate for the stenosis in their respective coronary arteries.
In the RCA, the stenosis is less than 60%, dilation of the distal arterioles provide adequate blood flow to meet the metabolic needs. Thus, the maximal potential blood flow through the artery is not altered.
In the LCX, the stenosis is greater than 70%. Dilation of the distal arterioles can meet the metabolic demands when resting blood flow is normal. However, upon exertion, maximal blood flow is reduced even when resistance vessels are fully dilated. In this situation, the coronary flow reserve is inadequate to meet the metabolic demands during exertion.
In the LAD, the stenosis is complete occlusion and even with maximal dilation of the distal arterioles, blood flow will be inadequate to meet the metabolic needs at rest and exertion.
The physician administers nitroglycerin and metoprolol to the patient experiencing MI. Rationalize why metoprolol was used. Include route of administration and pertinent mechanism(s) of action.
Because the heart is being stimulated by increased sympathetic activity and circulating catecholamines during infarction, drugs such as beta-blockers that inhibit sympathetic activity are commonly given. Cardiac-selective beta1-adrenergic antagonists like metoprolol are administered intravenously for emergent cardiac disturbances. Metoprolol antagonizes catecholamine binding at beta1-adrenergic receptors on cardiac nodal cells to decrease heart rate. They also antagonize beta1-adrenergic receptors on cardiac myocytes to decrease cardiac contractility. The decrease in heart rate and contractility reduces myocardial oxygen demand of the heart and decreases mortality.
ADAMTS13 levels are found to be low in this patient, and ADAMTS13 antibodies are detected. Relate the ADAMTS13 levels to the patient’s other laboratory values and peripheral blood smear findings, then rationalize the recommended acute intervention for this patient
ADAMTS13 is a metalloprotease that is responsible for cleaving ultra-large multimers of von Willebrand Factor. When decreased or absent, the result is large “sticky” circulating forms of vWF that are capable of triggering spontaneous platelet thrombus formation. As these platelet thrombi form in the microcirculation, platelets are consumed (thrombocytopenia). One of the other consequences of the platelet thrombi is high sheer stress in the microvasculature that leads to RBC hemolysis (anemia) and the formation of schistocytes (peripheral blood smear).
In patients with rapid hemolysis secondary to antibody-mediated acquired TTP, therapeutic plasmapheresis/plasma exchange should be performed early in management to remove the ADAMTS13 autoantibodies and to replace functioning ADAMTS13 enzymes.
A 16-year-old male soccer player is in the locker room when he faints after standing up suddenly. After a few minutes, he recovers and reports that he felt “light-headed” before losing the ability to stand. He has just completed a two-hour soccer practice on a very hot, late August afternoon with limited hydration. . His skin appears diffusely flush and diaphoretic. Further questioning reveals that he skipped breakfast that morning and that his family recently moved to Texas from Minnesota. When asked about his urine output, he states he has not used the restroom since he woke this morning.
Indicate the cause of the patient’s hypotension and explain the short-term compensatory mechanisms that occur in the vasculature in response to it.
The patient’s hypotension is a result of reduced circulating blood volume from dehydration.
In an attempt to compensate for the patient’s hypotension, the body will increase cardiac output (heart rate x stroke volume) and vascular resistance to increase mean arterial pressure (MAP). In the vasculature, the increase in sympathetic tone will increase vascular resistance and vascular tone.
In the arterioles, activation of the alpha-adrenergic receptor (Gq) stimulates the influx of calcium (binds to calmodulin to activate myosin light chain kinase) to initiate constriction of the vessels. This reduces the radius to increase the resistance (total peripheral resistance) helping to increase MAP.
Similarly, in the veins, alpha-adrenergic activation and venoconstriction results in an increased venous tone. This increases venous return (preload) and subsequent stroke volume via the Frank-Starling mechanism to increase cardiac output and MAP.
Correlate the patient’s urine output to the long-term compensatory response that occurs with dehydration
In a state of dehydration, the renin-angiotensin-aldosterone system (R-A-A-S) is activated to reduce urine output and increase circulating blood volume. Renin released from the kidneys (juxtaglomerular cells in the kidney) converts angiotensinogen to angiotensin I, which is then converted to angiotensin II by the angiotensin converting enzyme (ACE).
ANG II stimulates the release of aldosterone (from the adrenal cortex) which directly effects the kidney (at the collecting ducts) by increasing the reabsorption of sodium into the plasma.
ANG II along with the increase plasma osmolarity due to dehydration stimulates the release of vasopressin (from the posterior pituitary). This in turn stimulates the upregulation of aquaporins in the kidney (collecting duct) to increase water reabsorption.
This results in an increase in circulating blood volume and a reduction in urine output.
Describe one dietary modification and one medicinal food or supplement that would benefit this patient’s blood pressure
- The DASH Diet was specifically designed for hypertension (by the National Heart, Lung, and Blood Institute) and shares many similarities with the Mediterranean diet, including recommendations for whole grains, vegetables, fruits, and nuts/seeds. The DASH diet also emphasizes dietary salt reduction to less than 1 teaspoon (2.4 grams) of sodium per day and low-fat dairy products, and it has been shown to significantly reduce blood pressure (by ~11/5mmHg) in people with hypertension.
- Dark chocolate, which is high in polyphenols known as flavanols at concentrations of >70% cacao. A meta-analysis reported significant (~5/3 mmHg) reductions of blood pressure in patients with hypertension / pre-hypertension.
Discuss how a high LDL/HDL ratio contributes to the formation of foamy, calcified atherosclerotic plaques in the patient.
A high LDL/HDL ratio is indicative of dyslipidemia (other markers include elevations of the abnormal lipoprotein(a) variant of LDL and the ApoB:ApoA-I ratio), in which high levels of LDL become trapped within the walls of blood vessels. Concomitantly, endothelial injury and dysfunction attracts monocytes to the vessel wall, where the monocytes become activated to macrophages.
The trapped LDL undergoes (non-enzymatic) oxidative modification by free radicals and is ingested by the macrophages (as well as other components of the vessel walls, such as recruited smooth muscle cells). However, the oxidized LDL cannot be fully degraded and thus accumulates into lipid-laden foam cells.
These foam cells aggregate into atherosclerotic plaques (atheromas) in the walls of the blood vessels, which can be further modified by extracellular matrix (from smooth muscle cells), cell death (which releases lipids and necrotic debris), and eventual calcification (which can be detected through arterial calcium scanning).
. Justify how the patient’s hypertension would alter the vascular reactivity of his coronary vessels resulting in exertional angina
Hypertension is associated with an increase in sheer stress and turbulent blood flow in the vessels, which can result in endothelial dysfunction and vascular injury. Endothelial dysfunction (as a result of activated endothelial cells) can promote (1) an uncoupling in the regulation of vascular tone in response to metabolic demands (impaired release of endothelial-derived vasodilators) and (2) a stimulation in the recruitment and proliferation of the vascular smooth muscle cells.
The uncoupling of vascular tone leaves the catecholamine response (as seen with exertion) unopposed which can result in inappropriate vasoconstriction.
In addition, stimulation of the vascular smooth muscle cells is associated with synthesis of extracellular matrix, leading to intimal thickening which can impede vascular flow.
The patent’s exertional angina is a result of an imbalance of myocardial supply when his oxygen demand is increased (i.e., during exercise).
Describe the effect of rosuvastatin on atherosclerotic plaques.
Atherosclerotic plaques cause narrowing of arteries that reduce blood flow (and may rupture and embolize). Statins exert their major observable effect, the reduction of LDL levels, via competitive inhibition of HMG-CoA reductase. By reducing the conversion of HMG-CoA to mevalonate, statins inhibit an early and rate-limiting step in cholesterol biosynthesis. Statins therefore regulate blood cholesterol levels by inhibiting hepatic cholesterol synthesis, which results in increased expression of the LDL receptor gene, reduced circulating cholesterol levels, and reduced plaque formation. Statins also appear to exert cholesterol-independent or “pleiotropic” effects, including improved endothelial function, enhanced stability of atherosclerotic plaques, decreased oxidative stress and inflammation, and an inhibited thrombogenic response.
Relate the extracardiac effects of amlodipine to the patient’s vascular function. Include the drug subclass and site of action in your answer
Dihydropyridine calcium channel blockers, such as amlodipine, act as potent vasodilators to reduce peripheral resistance and blood pressure (e.g. extracardiac effects). As a first-line treatment for hypertension, dihydropyridine calcium channel blockers specifically antagonize L-type calcium channels located on arterial smooth muscle cells. The inhibition of calcium influx attenuates vascular smooth muscle contractions which induces vasodilation and subsequent decreases in vascular resistance and blood pressure.
Detail the etiology of the patient’s heart failure due to chronic HTN
- Heart failure with a preserved ejection fraction (HFpEF) occurs when systolic function is preserved (EF > 50%), but symptoms of heart failure are secondary to diastolic dysfunction with impaired relaxation of the affected ventricle(s). This leads to an inability of the heart to provide adequate forward output to maintain peripheral tissue perfusion and oxygenation
Explain how lisinopril is beneficial
Lisinopril, an angiotensin converting enzyme inhibitor (ACEi), is considered beneficial for heart failure patients because it slows the progression of adverse cardiac remodeling (collagen deposition) resulting from cardiac load and/or injury. ACEi prevent the cleavage of angiotensin I to angiotensin II (AII) by inhibiting angiotensin-converting enzymes. Reduced AII activation of AT1 receptors attenuates AII-mediated vasoconstriction, aldosterone-mediated sodium/water retention, and sympathetic activity. ACEi reduce vasoconstriction and enhance bradykinin-mediated vasodilation to decrease blood pressure. Moreover, inhibition of aldosterone signaling decreases blood volume (preload and afterload) to further reduce cardiac load.
