Cardiorespiratory Pathologies (W11)

Etiology of Thrombosis

Virchow's triad (turbulent or stasis of blood flow, endothelial injury, hypercoagulability)

Virchow's triad in Thrombosis

Arterial thrombi: Via endothelial injury

Cardiac thrombosis: Via endothelial injury

Venous thrombosis: Via stasis of blood

Microscopic Findings of Thrombosis

Lines of Zahn; Post mortem clot - Blood separates into upper plasma layers (translucent, chick-fat like), lower RBC layers (very red, red current jelly).

Fates of Thrombosis

Dissolution

Propagation

Embolisation

Organisation & recanalisation

Etiology of Embolism

Detached mass that is carried by the blood from its point of origin to a distant site, where it causes tissue dysfunction or infarction.

Presentation of Embolism

i. Most pulmonary emboli are clinically silent (small)

ii. Sudden death (large)

iii. Embolic obstruction of medium arteries with vascular rupture can cause pulmonary haemorrhage

iv. Embolic obstruction of small end-arteriolar pulmonary branches cause haemorrhage or infarction

Etiology of Infarction

A condition of tissue necrosis that results from insufficient blood and oxygen supply → tissue death.

Classification of Infarction

Classified according to color - red (haemorrhagic) or white (anaemic); presence (septic) or absence (bland) of infection.

Microscopic Findings of Infarction

Ischemic coagulative necrosis (or fibrinoid necrosis in arteries)

Complications of Infarction

Hypoxia (oxygen deficiency)

schemia (cell injury due to hypoxia, reduced blood flow)

Necrosis (unprogrammed cell death and tissue destruction)

Ischemia-reperfusion injury: Restoration of blood flow to ischemic tissues can promote recovery or exacerbate the injury → cell death

Etiology of Hypertension

Sustained elevation of resting systolic blood pressure (>140 mmHg), diastolic blood pressure (>90mmHg), or both.

Classification of Hypertension

Classified according to cause: systemic hypertension (primary or secondary) or pulmonary hypertension; + Staged hypertension (referring to the severity of blood pressure): elevated → stage 1 → stage 2.

Causes of Secondary Hypertension

Renal, endocrine, CVD, estrogen, treatment, etc

Complications of Hypertension

Complications on heart (LVH, CHF, ischemic HD); Complications on blood vessels (atherosclerosis, aneurysms, dissections).

Etiology of Cardiac Hypertrophy

Increase in the size of cells that results in an increase in the size of heart.

Presentation of Cardiac Hypertrophy

Physiological via exercise: static (concentric), aerobic (eccentric)

Pathological via pressure overload (concentric), volume overload (eccentric)

Microscopic Findings of Cardiac Hypertrophy

Larger cardiomyocytes.

Etiology of Atherosclerosis

Three phases: Initiation, progression and complication

Types of Atherosclerosis

Atherosclerosis, Monckeberg sclerosis, arteriosclerosis (hyaline, hyperplastic)

Microscopic Findings of Atherosclerosis

Foamy macrophages, cholesterol clefts, necrotic lipid core, fibrous cap.

Stability of Atherosclerotic Plaque

Stability determined by fibrous cap strength (ruptured, unstable plaque → thrombi occlusion);

Complications of Atherosclerosis

Critical stenosis, occlusion by thrombus, aneurysm and rupture.

Etiology of Aneurysm

Congenital or acquired dilations of blood vessels or the heart caused by transmural inflammation

Causes of Aneurysm

Important causes include atherosclerosis and hypertension.

Types of Aneurysm

Depending on the layers involved → true, false (extravasation of CT)

Depending on shape → saccular, fusiform

Depending on location (ascending, descending, thoracic aorta, ventricular)

Microscopic Findings of Aneurysm

Degradation of extracellular elastin and collagen

Cystic medial degeneration

Medial and adventitial infiltration by lymphocytes and macrophages

Complications of Aneurysm

Obstruction of vessel, embolism from atheroma or mural thrombus, impingement, abdominal mass, rupture into cavity (haemorrhage).

Etiology of Dissection

Flowing of blood through a tear in the intima with separation of the intima and media → false lumen

Intimal tear may be primary or secondary to haemorrhage in media

Most commonly at areas of high hydraulic stress

Causes of Dissection

Hypertension is an important contributor; Occurs in patients with preexisting degeneration (CT disorders, trauma, atherosclerosis, injury).

Classification of Dissection

Stanford type A (ascending aorta +/- descending aorta & origin at sinotubular junction)

Stanford type B (descending aorta & origin at left subclavian artery)

Microscopic Findings of Dissection

Haemorrhage between intima and media

Imaging Findings of Dissection

CXR - Widened mediastinum

CT angiography - Intimal flap

Complications of Dissection

Aortic insufficiency, cardiac tamponade, aortic rupture, ischemia, stroke

Etiology of Acute Coronary Syndrome

Term for conditions suddenly blocking blood flow to the heart causing ischaemia

Overview of Stable angina

Chest pain, claudication or discomfort triggered by exertion or emotional stress due to heart ischaemia

Types of Acute Coronary Syndrome

Unstable angina, NSTEMI, STEMI

Overview of Unstable angina

Plaque rupture → incomplete occlusion → no infarction + no ST elevation or cardiac biomarker elevation

Overview of NSTEMI

Non-transmural/subendocardial infarction + no ST elevation or cardiac biomarker elevation

Overview of STEMI

Transmural infarction + ECG [peaked T waves → ST elevation (minutes) → deep Q-waves (hours)] + may have elevated cardiac biomarkers

Etiology of Myocardial Infarction

Complete occlusion of coronary vessel

Classification of Myocardial Infarction

Transmural (whole thickness of myocardium)

Non-transmural/subendocardial (inner ⅓ of myocardium where blood is vulnerable to changes)

Multifocal (only in smaller intramural vessels)

Findings of 1-2 days Post-MI

Increased opacity of tissue, coagulative necrosis, neutrophils, wavy fibres (risk of ventricular arrhythmia, papillary muscle rupture, interventricular septal rupture)

Findings 3-10 days Post-MI

Macrophage, neutrophil inflammatory response (risk of pericarditis, papillary muscle rupture, interventricular septal rupture)

Findings 2 weeks Post-MI

Granulation tissue, collagen deposition (risk of tamponade, mural thrombus)

Findings months Post-MI

Scar tissue (risk of LV aneurysm, Dressler syndrome, reinfarction)

Findings of Reperfused infarcts

Contraction band necrosis

Complications of Myocardial Infarction

Ventricular rupture, papillary muscle rupture, arrhythmias, tamponade, acute heart failure

Testing of Myocardial Infarction

Measuring macromolecules leaked out of injured myocardial cells → myoglobin, troponins (TnT, TnI), CK-MB (re-infarction), lactate dehydrogenase.

List 8 HF Medications

ACE inhibitors

Angiotensin Receptor Blockers

Mineralocorticoid receptor antagonists

Beta-blockers

Neprilysin inhibitors

Loop duiretics

Thiazide diuretics

Digoxin

ACE Inhibitors

Inhibition of ACE → ↓ angiotensin II

Effects of ACE Inhibitors

Decrease vasoconstriction and blood pressure

Adverse Effect of ACE Inhibitors

Dry cough (bradykinin), hyperkalemia (worsening kidney function), angioedema

Angiotensin Receptor Blockers (ARBs)

Receptor blockade of angiotensin II type 1 receptor

MoA of ARBs

RAAS; allows the production of Angiotensin II but blocks interaction with AI receptors

Use of ARBs

Used if ACE inhibitors are not well tolerated

Adverse effects of ARBs

Elevated K+, low blood pressure, worsening kidney function, diarrhea

Mineralocorticoid receptor antagonists

Aldosterone antagonists → Increase sodium and water excretion → weak diuretics

Adverse effects of Mineralocorticoid receptor antagonists

Increase risk of hyperkalemia, particularly in renal impairment

Neprilysin Inhibitors

Neprilysin is a metalloproteinase that inactivates ANP, BNP, and AT-II

Effects of Neprilysin Inhibitors

↑ ANP, ↑ BNP, ↑ AT-II

Use of Neprilysin Inhibitors

Used with angiotensin-II receptor blocker

Loop Diuretic (Furosemide)

Inhibition of Na/K/Cl transporter in ascending limb of loop of Henle

Effect of Loop Diuretic

Increased ion concentration in the tubule → reduce water resorption in collecting duct → diuresis

Primary use of Loop Diuretic

Fluid retention and pulmonary edema; used in combination with ACE-inhibitor

Thiazide Diuretic (Metolazone)

Inhibition of Na/Cl transporter in distal tubule

Effect of Thiazide Diuretic

Potentiation of loop diuretic effect

Digoxin

Inhibition of Na+/K+-ATPase in myocytes

Effects of Digoxin

↑ Vagal activity to nodal cells → ↑ Ionotropic agent; ↑ intracellular calcium concentration in ventricular myocytes

Toxicity of Digoxin

Disturbed color perception, GI symptoms, arrhythmias; precipitated by hypokalemia