CVS - Patho

Transudate vs. exudate?

Transudate = protein-poor (↑ hydrostatic pressure).

Exudate = protein-rich (↑ permeability, inflammation).

Virchow’s triad

Endothelial injury, abnormal blood flow, hypercoagulability

4 main pathophysiologic categories of edema

1. Increased Hydrostatic Pressure (e.g., heart failure, venous obstruction)

2. Reduced Plasma Osmotic Pressure (e.g., nephrotic syndrome, cirrhosis)

3. Lymphatic Obstruction (e.g., filariasis, post-surgical)

4. Sodium and Water Retention (e.g., renal failure)

Hyperemia

Active process from arteriolar dilation; tissue is red (erythema) due to increased oxygenated blood (e.g., inflammation).

Congestion

Passive process from reduced venous outflow; tissue is blue-red (cyanosis) due to deoxygenated blood accumulation.

3 stages of hemostasis

1. Transient Vasoconstriction (neurohumoral factors)

2. Primary Hemostasis (platelet adhesion, activation, aggregation forming a plug)

3. Secondary Hemostasis (coagulation cascade activation, fibrin polymerization to stabilize the plug)

Role of von Willebrand factor (vWF) and GpIb in primary hemostasis

vWF acts as a bridge, binding to exposed subendothelial collagen and to the GpIb receptor on platelets, mediating platelet adhesion.

Lines of Zahn

Laminated layers in thrombus → formed in flowing blood (antemortem).

Most common embolus source

DVT of lower extremities → pulmonary embolism

Types of shock

Cardiogenic, hypovolemic, distributive (septic, anaphylactic, neurogenic).

Septic shock mechanism

Cytokine storm → vasodilation, endothelial injury, DIC, multiorgan failure.

Petechiae vs. hemarthrosis

Petechiae = platelet/vWF defect (primary hemostasis).

Hemarthrosis = clotting factor defect (secondary hemostasis).

Heparin-induced thrombocytopenia syndrome (HIT) mechanism

Antibodies to heparin-PF4 complex → platelet activation + thrombocytopenia

Hyaline arteriolosclerosis

Pink hyaline thickening (benign HTN, diabetes). Plasma protein leakage

Hyperplastic arteriolosclerosis

“Onion skin” thickening (malignant HTN)

Atherosclerosis earliest lesion

Fatty streak (lipid-filled macrophages/foam cells)

Vulnerable plaque features

Thin fibrous cap, large lipid core, inflammation → prone to rupture

True vs. false aneurysm

True = all 3 vessel layers.

False = extravascular hematoma contained by surrounding tissue.

Most common aneurysm causes

Atherosclerosis (AAA), hypertension (ascending aorta).

Aortic dissection type A vs. B

Type A = involves ascending aorta (surgical emergency).

Type B = spares ascending (medical mgmt).

Giant cell arteritis vs. Takayasu

GCA >50yo, temporal artery, blindness.

Takayasu <50yo, pulseless disease.

Granulomatosis with polyangiitis (GPA) triad

Upper/lower respiratory granulomas, necrotizing vasculitis, glomerulonephritis. c-ANCA (PR3) 95%

Polyarteritis nodosa (PAN) hallmark

Necrotizing arteritis, spares lungs, fibrinoid necrosis at branch points

Most common vascular tumor in adults

Hemangioma (capillary, cavernous). Angiosarcoma = malignant

HFrEF vs. HFpEF

HFrEF = systolic dysfunction, ↓EF.

HFpEF = diastolic dysfunction, stiff ventricle, normal EF.

Pressure overload hypertrophy

Sarcomeres in parallel → concentric hypertrophy (e.g., HTN, aortic stenosis)

Most common congenital heart defect

Ventricular septal defect (VSD)

Tetralogy of Fallot components

VSD, RV outflow obstruction, overriding aorta, RV hypertrophy.

(Mnemonic: V.O.A.R.)

Stable vs. unstable angina

Stable = demand ischemia, relieved by rest.

Unstable = crescendo, at rest → pre-MI

Time to irreversible myocyte injury in MI?

20–40 minutes

Earliest histologic change in MI

Myocyte waviness (30 min–4 hr)

MI rupture risk window

3–7 days post-MI.

Most sensitive/specific MI marker

Cardiac troponins (cTnT, cTnI)

Most common cause of mitral stenosis

Rheumatic heart disease.

Mitral valve prolapse histology

Myxomatous degeneration of spongiosa layer

Aschoff bodies & Anitschkow cells

Pathognomonic for rheumatic fever.

Anitschkow = “caterpillar” nuclei.

Janeway lesions vs. Osler nodes

Janeway = septic emboli (non-tender palms/soles).

Osler = immune complex (tender finger pads)

Most common primary cardiac tumor in adults

Myxoma (left atrium, “ball-valve” obstruction)

Most common cause of sudden death in young athletes

Hypertrophic cardiomyopathy (HCM)

Edema categories

↑ hydrostatic pressure (CHF, venous obstruction), ↓ plasma oncotic pressure (nephrotic syndrome, cirrhosis), lymphatic obstruction (filariasis, tumor), sodium/water retention (renal failure)

Causes of increased hydrostatic pressure

Impaired venous return (CHF, constrictive pericarditis, ascites, venous thrombosis), arteriolar dilation (heat, neurohumoral), lower extremity inactivity.

Causes of reduced plasma oncotic pressure

Protein-losing glomerulopathies (nephrotic syndrome), liver cirrhosis, malnutrition, protein-losing gastroenteropathy.

What is lymphedema? Causes?

Interstitial fluid accumulation due to lymphatic obstruction. Causes: trauma, fibrosis, tumor, infection (filariasis → elephantiasis).

Normal hemostasis: three major stages

1. Transient vasoconstriction.

2. Primary hemostasis (platelet plug).

3. Secondary hemostasis (fibrin polymerization).

Platelet aggregation mechanism

Activated platelets change shape, release ADP & TxA₂, recruit more platelets. Fibrinogen bridges GpIIb/IIIa receptors.

Endothelial antithrombotic mechanisms

Prostacyclin (PGI₂) & NO inhibit platelets; thrombomodulin activates protein C; heparin-like molecules activate antithrombin III; t-PA promotes fibrinolysis.

Endothelial prothrombotic mechanisms

vWF (adhesion), tissue factor (initiates coagulation), plasminogen activator inhibitor (PAI, inhibits fibrinolysis).

Inherited hypercoagulable states

Factor V Leiden (resistance to activated protein C), prothrombin G20210A mutation, antithrombin III deficiency, protein C/S deficiency.

Acquired hypercoagulable states

Prolonged immobilization, cancer, OCP/pregnancy, heparin-induced thrombocytopenia (HIT), antiphospholipid antibody syndrome (APS)

Antiphospholipid antibody syndrome (APS) features

Autoantibodies (anti‑cardiolipin, lupus anticoagulant) → arterial/venous thrombosis, recurrent miscarriages.

Postmortem clot vs. thrombus

Postmortem clot = gelatinous, “chicken fat” top, dark “currant jelly” bottom, not attached to wall.

Thrombus = attached, laminated.

Saddle embolus

Pulmonary embolus that lodges at the bifurcation of the main pulmonary artery.

Paradoxical embolism

Venous embolus crosses an intracardiac defect (e.g., patent foramen ovale) to enter systemic circulation.

Fat embolism syndrome: classic setting and timing

Long bone fractures; symptoms 1–3 days later: tachypnea, dyspnea, neurologic symptoms, petechial rash.

Decompression sickness: “the bends” vs. “the chokes”

Bends = nitrogen bubbles in joints/muscles → pain.

Chokes = bubbles in pulmonary vessels → respiratory distress.

Amniotic fluid embolism: findings at autopsy

Squamous cells, lanugo hair, vernix, mucin in maternal pulmonary microvasculature.

Disseminated intravascular coagulation (DIC)

Widespread microvascular thrombosis with simultaneous consumption of platelets and clotting factors → bleeding and thrombosis.

Red infarct vs. white infarct

ed (hemorrhagic) → loose tissue, dual circulation (lung, bowel), venous occlusion.

White (anemic) → solid organ with end‑arterial supply (heart, kidney, spleen).

Septic infarct

Infarct with bacterial infection → converts to abscess (e.g., from infected cardiac vegetation).

Septic shock pathogenesis

Pathogen-associated molecular patterns (PAMPs) activate innate immunity → cytokine storm, vasodilation, endothelial injury, DIC, multiorgan failure.

Stages of shock

1. Non‑progressive (compensated).

2. Progressive (tissue hypoperfusion, acidosis).

3. Irreversible (cellular damage irreversible even after correction).

Two principal mechanisms of vascular pathology

Narrowing/obstruction (atherosclerosis, thrombosis) vs. weakening/dilation/rupture (aneurysm).

Layers of artery and vein

Intima (endothelium, IEL), media (SMC, elastin), adventitia (connective tissue, vasa vasorum). Veins have thinner media and valves.

Vasa vasorum

Small vessels that supply the walls of large arteries and veins, located in adventitia and outer media.

Berry aneurysm: location and risk

Circle of Willis; risk of fatal subarachnoid hemorrhage.

Arteriovenous fistula (AVF): consequence

Direct artery–vein connection bypassing capillaries → high‑output cardiac failure

Fibromuscular dysplasia: appearance and complication

Focal irregular thickening of medium/large arteries (renal, carotid) → “string of beads” on angiography; can cause renovascular hypertension.

Endothelial cell basal functions

Maintain barrier, antithrombotic (PGI₂, NO, thrombomodulin, t‑PA), regulate blood flow.

Mönckeberg medial sclerosis

Calcification of media of muscular arteries (elderly) → not clinically significant.

Atherosclerosis: earliest visible lesion

Fatty streak – lipid‑filled macrophages (foam cells) in intima.

Four components of atheromatous plaque

Cells (SMC, macrophages, T cells), ECM (collagen, elastin), lipids (intra‑ and extracellular), calcification.

Vulnerable plaque characteristics

Thin fibrous cap, large lipid core, abundant inflammation → prone to rupture and thrombosis.

Stable plaque characteristics

Thick collagenous cap, minimal inflammation, less lipid → less likely to rupture.

Major modifiable risk factors for atherosclerosis

Hyperlipidemia, hypertension, smoking, diabetes, inflammation (elevated CRP).

Non‑modifiable risk factors for atherosclerosis

Genetic variation, increasing age, male gender.

Response‑to‑injury hypothesis

Chronic endothelial injury → inflammation, lipid accumulation, SMC proliferation → atherosclerosis.

True aneurysm

Involves all three layers of vessel wall (intima, media, adventitia). Types: saccular (focal outpouching) or fusiform (diffuse dilation).

False aneurysm (pseudoaneurysm)

Defect in vessel wall → extravascular hematoma contained by surrounding tissue, not by vessel layers.

Classic presentation of aortic dissection

Sudden, severe “tearing” chest pain radiating to back, migrating downward.

Giant cell (temporal) arteritis

>50 years, granulomatous inflammation of temporal artery, risk of blindness; T‑cell mediated.

Takayasu arteritis

<50 years, granulomatous vasculitis of aorta and branches → “pulseless disease.

Kawasaki disease

Acute vasculitis in young children; can cause coronary artery aneurysms; treated with IVIg and aspirin.

Thromboangiitis obliterans (Buerger disease)

Segmental, thrombosing vasculitis of small/medium arteries in young male smokers; strongly linked to smoking.

Granulomatosis with polyangiitis (GPA)

c‑ANCA (PR3) positive; triad: upper/lower respiratory granulomas, necrotizing vasculitis, glomerulonephritis.

Eosinophilic granulomatosis with polyangiitis (EGPA, Churg‑Strauss)

p‑ANCA (MPO) positive; asthma, eosinophilia, necrotizing vasculitis, extravascular granulomas.

Microscopic polyangiitis

p‑ANCA (MPO) positive; necrotizing vasculitis of small vessels (capillaries, venules); pauci‑immune glomerulonephritis

IgA vasculitis (Henoch‑Schönlein purpura)

Immune complex vasculitis (IgA deposits); palpable purpura, arthralgia, abdominal pain, renal involvement.

Varicose veins

Dilated, tortuous superficial veins due to incompetent valves; prolonged standing, obesity, pregnancy.

Esophageal varices

Portosystemic collaterals in cirrhosis; risk of massive upper GI hemorrhage.

Superior vena cava (SVC) syndrome

Obstruction of SVC (often by bronchogenic carcinoma or lymphoma) → facial/upper extremity edema, cyanosis.

Lymphedema causes

Primary (Milroy disease, congenital) or secondary (tumor, surgery, radiation, filariasis, postinflammatory).

Bacillary angiomatosis

Vascular proliferation in immunocompromised; caused by Bartonella henselae (cat‑scratch) or B. quintana (trench fever).

Kaposi sarcoma

HHV‑8 associated; forms in classic (older Mediterranean), endemic (African), iatrogenic (transplant), or epidemic (AIDS) types.

Angiosarcoma

Malignant endothelial tumor; associated with lymphedema, radiation, vinyl chloride, arsenic; poor prognosis.