Vascular Pathology, Arrhythmias, and Cardiac Drugs

Vascular And Rhythm Reasoning Map

Atherosclerosis is an intimal disease of large and medium arteries driven by endothelial dysfunction and chronic inflammation. Hypertension, smoking, diabetes, hyperlipidemia, and turbulent flow at branch points increase permeability and leukocyte adhesion. LDL enters the intima, becomes oxidized, and is taken up by macrophage scavenger receptors, forming foam cells. Fatty streaks can be seen early, but clinically important plaques add smooth muscle migration from the media to the intima, extracellular matrix deposition, and a fibrous cap over a lipid necrotic core.

Stable angina usually comes from a plaque with a thick cap and fixed luminal narrowing. Acute coronary syndromes more often come from rupture or erosion of a vulnerable plaque with a thin cap, large lipid core, abundant macrophages, and high tissue factor exposure. Platelets bind exposed collagen and von Willebrand factor, activate, release ADP and thromboxane A2, and aggregate through glycoprotein IIb/IIIa binding to fibrinogen. The coagulation cascade adds thrombin and fibrin.

In the aorta or peripheral arteries, plaque can cause aneurysm, emboli, renal artery stenosis, mesenteric ischemia, claudication, or gangrene depending on location. Hypertension causes endothelial injury and promotes both atherosclerosis and arteriolosclerosis. Benign hypertension classically produces hyaline arteriolosclerosis from plasma protein leakage and smooth muscle wall thickening, narrowing small vessel lumens in kidneys, retina, and brain. Diabetes produces similar hyaline change through nonenzymatic glycosylation of basement membranes.

Malignant hypertension produces hyperplastic arteriolosclerosis, an onion-skin pattern of concentric smooth muscle proliferation and basement membrane duplication, often with fibrinoid necrosis. Chronic hypertension drives left ventricular concentric hypertrophy through sarcomeres added in parallel; chronic volume overload, such as regurgitation, produces eccentric hypertrophy through sarcomeres added in series. Aneurysm mechanisms depend on wall weakness.

Abdominal aortic aneurysm is often atherosclerotic and infrarenal because vasa vasorum are limited and the wall is exposed to chronic inflammation and protease activity. Thoracic aortic aneurysm and dissection are associated with hypertension, connective tissue disorders, bicuspid aortic valve, and cystic medial degeneration, meaning fragmentation of elastic tissue with basophilic ground substance in the media. Dissection begins with an intimal tear and blood tracking through the media; pain is abrupt and tearing, and complications depend on branch vessel obstruction, aortic regurgitation, tamponade, or rupture.

Vasculitis questions are solved by vessel size and immune pattern. Large-vessel granulomatous disease includes giant cell arteritis and Takayasu arteritis. Giant cell arteritis affects older adults, often branches of the carotid artery, and can cause headache, jaw claudication, vision loss, polymyalgia rheumatica, elevated erythrocyte sedimentation rate, and granulomatous inflammation with giant cells.

Takayasu arteritis affects younger patients, classically women, with granulomatous inflammation of the aortic arch branches causing weak upper extremity pulses, limb claudication, blood pressure discrepancies, and ocular or neurologic symptoms. Medium-vessel vasculitis includes polyarteritis nodosa and Kawasaki disease. Polyarteritis nodosa is transmural necrotizing inflammation with fibrinoid necrosis, segmental lesions at different stages, renal and mesenteric involvement, neuropathy, livedo reticularis, testicular pain, and association with hepatitis B; it typically spares pulmonary arteries.

Kawasaki disease is an acute febrile childhood vasculitis with mucocutaneous inflammation and risk of coronary artery aneurysms; immune activation damages medium arteries. Small-vessel vasculitis includes immune complex and ANCA-associated patterns. IgA vasculitis causes palpable purpura, abdominal pain, arthralgia, and renal disease from IgA immune complex deposition. Granulomatosis with polyangiitis is c-ANCA or proteinase 3 associated and causes necrotizing granulomas of upper and lower respiratory tract plus glomerulonephritis.

Microscopic polyangiitis is p-ANCA or myeloperoxidase associated and causes pulmonary-renal disease without granulomas. Eosinophilic granulomatosis with polyangiitis has asthma, eosinophilia, neuropathy, p-ANCA association, and granulomatous small-vessel disease. Thromboangiitis obliterans affects small and medium vessels in smokers, with segmental thrombosing inflammation and extremity ischemia. Arrhythmias reflect altered automaticity, conduction, repolarization, or circuit geometry.

The SA node phase 4 pacemaker current depends on funny sodium influx, T-type and L-type calcium currents, and declining potassium efflux. Sympathetic beta-1 stimulation increases cAMP, steepens phase 4, increases heart rate, increases AV nodal conduction, and increases contractility. Parasympathetic M2 stimulation lowers cAMP and increases potassium conductance, slowing SA rate and AV nodal conduction. A narrow QRS tachycardia usually originates above the ventricles and travels through the His-Purkinje system.

A wide QRS rhythm suggests ventricular origin, aberrant conduction, bundle branch block, hyperkalemia, or sodium channel blockade. Atrial fibrillation has irregularly irregular rhythm and absent discrete P waves; risk rises with atrial dilation, mitral stenosis, hyperthyroidism, alcohol use, and pulmonary disease. Atrial flutter often has a sawtooth pattern from a macroreentrant right atrial circuit. AV nodal reentrant tachycardia uses dual AV nodal pathways and often terminates with vagal maneuvers or adenosine because the AV node is part of the circuit.

Wolff-Parkinson-White syndrome uses an accessory pathway that bypasses the AV node, producing a short PR interval and delta wave; atrial fibrillation in this setting can conduct rapidly to ventricles, so isolated AV nodal blockade can be dangerous. Long QT predisposes to torsades de pointes, a polymorphic ventricular tachycardia often triggered by early afterdepolarizations; causes include low potassium, low magnesium, congenital channel defects, and many drugs. Antiarrhythmics map to channels and ECG intervals. Class I drugs block fast sodium channels in phase 0.

Class IA, such as quinidine, procainamide, and disopyramide, moderately slows conduction and prolongs repolarization, increasing QRS and QT. Class IB, such as lidocaine and mexiletine, weakly blocks sodium channels and shortens repolarization, especially in ischemic ventricular tissue. Class IC, such as flecainide and propafenone, strongly slows conduction and widens QRS with little effect on QT; they can be proarrhythmic in structural heart disease. Class II beta blockers slow phase 4 and AV nodal conduction, reducing rate and renin release.

Class III potassium channel blockers, such as amiodarone, sotalol, dofetilide, and ibutilide, prolong phase 3 and QT. Amiodarone has multi-class effects and toxicities involving lung, thyroid, liver, cornea, skin, and nerves. Class IV non-dihydropyridine calcium channel blockers, verapamil and diltiazem, slow AV nodal conduction. Adenosine opens potassium channels and transiently blocks AV nodal conduction; flushing, chest pressure, bronchospasm, and a very short half-life are characteristic. Heart failure pharmacology combines hemodynamics and remodeling.

Loop diuretics reduce congestion but mainly improve symptoms. ACE inhibitors, angiotensin receptor blockers, angiotensin receptor-neprilysin inhibitor therapy, evidence-based beta blockers, mineralocorticoid receptor antagonists, and SGLT2 inhibitors reduce adverse remodeling and improve outcomes in systolic heart failure through neurohormonal and renal effects. Hydralazine plus nitrates can reduce afterload and preload, useful in selected patients.

Digoxin inhibits Na/K ATPase, increasing intracellular sodium, reducing sodium-calcium exchange, increasing intracellular calcium, and raising contractility; it also increases vagal tone at the AV node. Toxicity causes gastrointestinal symptoms, visual disturbance, confusion, hyperkalemia in acute overdose, and arrhythmias, and is worsened by hypokalemia because potassium competes with digoxin for pump binding. Autonomic drug questions often ask about reflexes. Alpha-1 agonism constricts arterioles and veins, raising systemic vascular resistance and venous return.

Baroreceptors then increase vagal tone and can cause reflex bradycardia. Arteriolar vasodilators such as hydralazine and dihydropyridine calcium channel blockers can cause reflex tachycardia. Beta-1 blockade lowers heart rate, contractility, AV nodal conduction, and renin. Beta-2 stimulation relaxes vascular and bronchial smooth muscle and drives potassium into cells. Muscarinic blockade increases SA rate and AV nodal conduction by reducing vagal tone.