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🫀 CARDIOVASCULAR SYSTEM - Complete Medical Student Guide

Sources: Barash's Clinical Anesthesia 9e, Braunwald's Heart Disease, Fuster & Hurst's The Heart 15e

PART 1: CARDIAC ANATOMY

Gross Anatomy

The heart is a phasic, electrically self-actuated, variable-speed hydraulic pump composed of two dual-component elastic muscular chambers - each with an atrium and a ventricle. It simultaneously delivers equal volumes of blood to the pulmonary and systemic circulations.

The Cardiac Skeleton: The annulus of the valves, the aortic and pulmonary roots, the central fibrous body, and the left/right fibrous trigones form the heart's cartilaginous skeleton. Located at the base of the heart, it:

Supports the four valves
Resists forces of developed pressure and blood flow
Provides insertion sites for superficial subepicardial muscle

An interstitial collagen fiber network + elastin provides structural support, flexibility, and elasticity.

The Four Chambers

Chamber	Wall Thickness	Key Features
Right Atrium (RA)	Thin	Receives SVC, IVC, coronary sinus
Right Ventricle (RV)	~3-5 mm	Crescent-shaped; low-pressure circuit
Left Atrium (LA)	Thin	Receives pulmonary veins
Left Ventricle (LV)	~8-12 mm	Ellipsoid; generates ~120 mmHg systolic

The LV is composed of three myocardial layers:

Outer layer: counterclockwise spiral fibers (from base to apex)
Middle layer: circumferential fibers (responsible for most shortening)
Inner layer: clockwise fibers

This three-dimensional fiber architecture produces both shortening and twisting (torsional) motion during systole - important for efficient ejection.

Cardiac Valves

Valve	Type	Cusps	Separates
Tricuspid	AV	3 leaflets	RA → RV
Pulmonary	Semilunar	3 cusps	RV → Pulmonary artery
Mitral (Bicuspid)	AV	2 leaflets	LA → LV
Aortic	Semilunar	3 cusps	LV → Aorta

Mitral valve apparatus: anterior and posterior leaflets attached to the papillary muscles via chordae tendineae. Rupture of papillary muscles (e.g., after MI) causes acute mitral regurgitation.

Coronary Anatomy

Right Coronary Artery (RCA):

Arises from the right coronary sinus
Supplies SA node (in ~60%), AV node (~80-90%), right ventricle, inferior LV
Terminates as the posterior descending artery (PDA) in right-dominant circulation (~85% of people)

Left Coronary Artery (LCA):

Left main divides into:
- Left Anterior Descending (LAD): supplies anterior LV, anterior septum, apex, right bundle branch, anterior left bundle fascicle
- Left Circumflex (LCx): supplies lateral/posterior LV, SA node in ~40%

Clinical Pearl: LAD occlusion = "widow maker." Presents as anterior STEMI with ST elevation in V1-V4.

Conduction System

SA Node (pacemaker, 60-100 bpm)
    ↓ (via internodal tracts)
AV Node (delay ~0.12 sec, 40-60 bpm backup)
    ↓
Bundle of His
    ↓
Right Bundle Branch + Left Bundle Branch
(Left Bundle → Anterior fascicle + Posterior fascicle)
    ↓
Purkinje Fibers → Ventricular myocardium

Intrinsic rates:

SA node: 60-100 bpm
AV node / junctional: 40-60 bpm
Ventricular (Purkinje): 20-40 bpm

Action Potential (Ventricular):

Phase	Ion movement	Effect
Phase 0	Fast Na⁺ in	Rapid depolarization
Phase 1	K⁺ out	Early repolarization
Phase 2	Ca²⁺ in + K⁺ out	Plateau (unique to cardiac)
Phase 3	K⁺ out	Rapid repolarization
Phase 4	Na⁺/K⁺ ATPase	Resting membrane potential

The plateau phase (Phase 2) is responsible for the long refractory period, preventing tetany.

PART 2: CARDIAC PHYSIOLOGY

The Cardiac Cycle

A coordinated sequence of electrical, mechanical, and valvular events:

Systole (Contraction):

Isovolumetric contraction: AV valves close (S1), pressure rises, no volume change
Ejection phase: Aortic/pulmonary valves open, blood ejected

Diastole (Relaxation): 3. Isovolumetric relaxation: Semilunar valves close (S2), pressure falls, no volume change 4. Rapid filling: AV valves open, blood flows in (70% of filling) 5. Slow filling: Passive filling 6. Atrial kick (presystole): Active atrial contraction adds last ~20-30% of filling

Key: Loss of atrial kick (e.g., atrial fibrillation) reduces CO by 20-30% in patients with stiff ventricles.

Heart Sounds

Sound	Timing	Cause
S1	Start of systole	Closure of mitral + tricuspid valves
S2	End of systole	Closure of aortic + pulmonary valves
S3	Early diastole	Rapid ventricular filling - "ventricular gallop"; normal in children, suggests HF or volume overload in adults
S4	Late diastole (pre-systole)	Atrial contraction into stiff ventricle; always pathological

Splitting of S2:

Physiologic splitting: Widens on inspiration (A2 before P2) - normal
Wide fixed splitting: ASD
Paradoxical splitting: LBBB, severe aortic stenosis (P2 before A2)

Determinants of Cardiac Performance

1. Heart Rate

Cardiac Output (CO) = Heart Rate × Stroke Volume

Normal CO: 4-8 L/min; Cardiac Index = CO/BSA = 2.5-4 L/min/m²

2. Preload

Defined as the ventricular end-diastolic volume/pressure (i.e., the load before contraction begins)
Represented by LVEDP on pressure-volume loop
Governed by the Frank-Starling Law: increased stretch → increased force of contraction (up to a point)
Clinical marker: CVP (right heart preload), PCWP/LVEDP (left heart preload)

3. Afterload

The external resistance to ejection after contraction begins
Left heart: approximated by Systemic Vascular Resistance (SVR)
Right heart: approximated by Pulmonary Vascular Resistance (PVR)
Laplace's Law: Wall tension (T) = Pressure × Radius / (2 × Wall thickness)
- Dilated, thin-walled ventricle → ↑ wall tension → ↑ afterload → worsening failure

4. Myocardial Contractility (Inotropy)

Intrinsic ability of the myocardium to develop force at a given preload and afterload
Quantified by indices from pressure-volume loops (e.g., dP/dt max, ESPVR slope)
Increased by: catecholamines, digoxin, Ca²⁺, sympathetic stimulation
Decreased by: beta-blockers, calcium channel blockers, acidosis, hypoxia, heart failure

Contractile Apparatus - Molecular Mechanism

The sarcomere is the basic contractile unit. Key proteins:

Thick filament:

Myosin: Has globular heads (ATPase) that bind actin. Hinge rotation drives contraction
Titin: Elastic spring anchoring myosin to Z-lines; length sensor; contributes to diastolic stiffness

Thin filament:

Actin: Activates myosin ATPase via reversible binding
Tropomyosin: Inhibits actin-myosin interaction at rest
Troponin complex (TnT, TnI, TnC):
- TnC: Ca²⁺ binding subunit - when Ca²⁺ binds, moves tropomyosin, exposes actin
- TnI: Inhibitory subunit (also the clinical biomarker for MI)
- TnT: Binds to tropomyosin

Excitation-Contraction Coupling:

Action potential → T-tubule depolarization
L-type Ca²⁺ channels open (slow inward Ca²⁺)
Triggers Ca²⁺-induced Ca²⁺ release (CICR) from sarcoplasmic reticulum (ryanodine receptors)
[Ca²⁺] rises from ~0.1 µM to ~10 µM
Ca²⁺ binds troponin C → tropomyosin shifts → actin sites exposed
Myosin heads bind actin → cross-bridge cycling → contraction
Relaxation: Ca²⁺ pumped back into SR (SERCA2a) and out via Na/Ca exchanger

Coronary Blood Flow Physiology

LV receives blood only during diastole (systolic compression occludes intramyocardial vessels)
Normal coronary blood flow: ~250 mL/min (5% of CO)
Coronary Flow Reserve (CFR): ratio of maximal to basal flow (normal ~3-5×)
- Reduced by: flow-limiting stenoses, pressure-overload hypertrophy, microvascular disease

Regulation of coronary blood flow:

Mechanism	Details
Metabolic	CO₂, adenosine, reactive oxygen species → vasodilation (most important)
Endothelium-derived	NO (vasodilator), endothelin (vasoconstrictor)
Autoregulation	Maintains constant flow over perfusion pressures of 60-130 mmHg
Autonomic	α₁: vasoconstriction; β₂: vasodilation; vagal: mild vasodilation
Myogenic	Stretch → vasoconstriction

Key: O₂ extraction by the LV is near-maximal (~70-80%) at rest, so increased demand MUST be met by increased flow (unlike skeletal muscle which can increase extraction).

PART 3: CARDIAC PATHOLOGY

Heart Failure (HF)

Definition: The heart is unable to eject blood sufficient to meet metabolic demands OR cannot fill adequately without elevated filling pressure.

Classification by EF:

Type	EF	Mechanism	Example Causes
HFrEF (systolic)	< 40%	Reduced contractility, dilated ventricle	Ischemic CM, dilated CM, myocarditis
HFmrEF (mildly reduced)	40-49%	Intermediate
HFpEF (diastolic)	≥ 50%	Impaired relaxation/filling, stiff ventricle	HTN, HCM, aging, DM, obesity

Pathophysiology of HF:

Reduced CO → ↓ tissue perfusion
RAAS activation → Na⁺ + H₂O retention → volume overload
Sympathetic activation → ↑ HR, ↑ SVR, ↑ contractility (compensatory initially, then harmful)
Ventricular remodeling: dilation, hypertrophy, fibrosis → worsening function

Clinical Features:

Left HF: dyspnea, orthopnea, PND, pulmonary crackles, S3 gallop
Right HF: JVD, peripheral edema, hepatomegaly, ascites
Both: fatigue, reduced exercise tolerance

NYHA Classification:

Class I: No symptoms with ordinary activity
Class II: Mild symptoms with moderate exertion
Class III: Symptoms with minimal exertion
Class IV: Symptoms at rest

Management of HFrEF (GDMT - Guideline-Directed Medical Therapy):

Drug class	Examples	Benefit
ACE inhibitors / ARBs	Enalapril, Losartan	↓ preload/afterload, antiremodeling
ARNI	Sacubitril-Valsartan	Superior to ACEi; ↓ mortality
Beta-blockers	Carvedilol, Metoprolol, Bisoprolol	↓ HR, antiremodeling, ↓ mortality
MRA	Spironolactone, Eplerenone	↓ fibrosis, diuresis
SGLT2 inhibitors	Dapagliflozin, Empagliflozin	↓ HF hospitalizations, ↓ mortality
Loop diuretics	Furosemide	Symptom relief only (no mortality benefit)
Ivabradine	If HR ≥ 70, sinus rhythm	↓ HR
ICD	EF < 35%	Prevent sudden cardiac death
CRT	EF < 35% + LBBB	Resynchronization

Ischemic Heart Disease (IHD)

Pathogenesis:

Atherosclerosis → plaque formation in coronary arteries
Stable plaque → angina (supply-demand mismatch)
Plaque rupture → thrombosis → ACS (UA/NSTEMI/STEMI)

Atherosclerosis mechanism:

Endothelial injury → LDL oxidation → macrophage foam cells → fatty streak → fibrous plaque → vulnerable plaque (thin cap, lipid core)

Angina Pectoris

Type	Mechanism	ECG	Relief
Stable	Fixed stenosis, demand ↑	ST depression during exertion	Rest/nitrates
Unstable	Plaque rupture, partial occlusion	ST depression/T-wave inversion at rest	Hospitalization, antithrombotic
Variant (Prinzmetal)	Coronary vasospasm	ST elevation at rest	Nitrates/CCB

Acute Coronary Syndrome (ACS)

STEMI (ST-Elevation MI):

Complete occlusion → transmural infarction
ECG: ST elevation in contiguous leads, new LBBB
Hyperacute T waves → ST elevation → pathologic Q waves → T inversion (sequence over hours-days)
Management: Primary PCI within 90 min (door-to-balloon time) or fibrinolysis if PCI unavailable

NSTEMI:

Partial occlusion → subendocardial infarction
ECG: ST depression, T-wave inversion (NO ST elevation, NO new Q waves)
Troponin elevated
Management: antiplatelet, anticoagulation, early invasive strategy

Localization of MI by ECG leads:

Territory	Occluded Vessel	Leads
Anterior	LAD	V1-V4
Lateral	LCx	I, aVL, V5-V6
Inferior	RCA (usually)	II, III, aVF
Posterior	RCA/LCx	ST depression V1-V3 (reciprocal); ST elevation V7-V9
Septal	LAD (septal perforators)	V1-V2

Complications of MI:

Early (hours): Arrhythmias (VF most common cause of death), heart block (especially inferior MI)
Days: Free wall rupture (3-5 days), VSD, papillary muscle rupture → acute MR
Weeks: Pericarditis (Dressler syndrome), LV aneurysm, mural thrombus

Hypertension

Definition: SBP ≥ 130 mmHg and/or DBP ≥ 80 mmHg (AHA 2017); or ≥ 140/90 (WHO/ESH)

Classification (ACC/AHA):

Stage	BP
Normal	< 120/80
Elevated	120-129 / < 80
Stage 1 HTN	130-139 / 80-89
Stage 2 HTN	≥ 140 / ≥ 90
Hypertensive Crisis	> 180 / > 120

Primary (Essential) HTN: ~95% of cases; multifactorial (genetics, RAAS, SNS, Na retention, endothelial dysfunction)

Secondary HTN causes:

Renal: CKD, renovascular (renal artery stenosis)
Endocrine: Primary hyperaldosteronism (Conn syndrome), pheochromocytoma, Cushing syndrome, hyperthyroidism
Obstructive sleep apnea
Drugs: NSAIDs, OCP, cocaine, steroids

Target organ damage:

Heart: LVH, diastolic dysfunction, HF, IHD
Brain: Stroke, hypertensive encephalopathy
Kidney: CKD, proteinuria
Eyes: Hypertensive retinopathy (Keith-Wagener classification)
Arteries: Aortic dissection, PAD

Management:

Lifestyle: DASH diet, Na restriction, weight loss, exercise, smoking cessation
Pharmacotherapy:
- First-line: ACEi/ARB, thiazide diuretics, CCBs
- Specific indications: ACEi/ARB in DM/CKD; beta-blockers in IHD/HF; MRA in HF
- Hypertensive emergency: IV nitroprusside, labetalol, nicardipine

Cardiac Arrhythmias

Supraventricular Arrhythmias

Atrial Fibrillation (AF):

Irregularly irregular rhythm; absent P waves; narrow complex (unless aberrant conduction)
Causes: HTN, HF, valve disease, hyperthyroidism, alcohol, lone AF
Risk: Stroke (Virchow's triad in LA appendage)
CHA₂DS₂-VASc score for stroke risk; anticoagulation if score ≥ 2 (men) or ≥ 3 (women)
Management: Rate control (beta-blocker, diltiazem, digoxin) vs. Rhythm control (cardioversion, antiarrhythmics, ablation)

Atrial Flutter:

Regular ~150 bpm; "sawtooth" flutter waves at 300 bpm; usually 2:1 AV block
Management: similar to AF

SVT (AVNRT/AVRT):

Narrow complex, regular, abrupt onset/offset
Treatment: Vagal maneuvers → Adenosine → CCB/beta-blockers → cardioversion

Ventricular Arrhythmias

Arrhythmia	Rate	QRS	Risk	Treatment
PVCs	Variable	Wide, bizarre	Low (unless frequent)	Reassurance; beta-blockers
VT	> 100 bpm	Wide (> 120 ms)	High	Stable: amiodarone; Unstable: DC cardioversion
VF	Chaotic	Irregular	Immediately fatal	Immediate defibrillation + CPR

Torsades de Pointes:

Polymorphic VT; "twisting of the points"
Causes: Long QT (drugs - sotalol, quinidine, antipsychotics, antibiotics), hypokalemia, hypomagnesemia
Treatment: IV Magnesium sulfate; remove causative agent

Heart Block

Degree	Features	Management
1st degree	PR interval > 200 ms; all P waves conduct	None needed
2nd degree Mobitz I (Wenckebach)	Progressive PR lengthening until P wave drops	Observe; treat cause
2nd degree Mobitz II	Constant PR; sudden dropped QRS	Pacemaker (risk of complete block)
3rd degree (Complete)	P waves and QRS dissociated; escape rhythm	Pacemaker

Valvular Heart Disease

Aortic Stenosis (AS)

Obstruction of LV outflow; most common valvular lesion in developed countries
Causes: Bicuspid aortic valve (younger), calcific degenerative (elderly), rheumatic
Classic triad: Syncope, Angina, Heart Failure (SAD)
Murmur: Crescendo-decrescendo systolic ejection murmur, best at right upper sternal border, radiates to carotids
Pulse: Pulsus parvus et tardus (slow-rising, low amplitude)
ECG: LVH
Echo: Valve area < 1.0 cm² = severe; mean gradient > 40 mmHg = severe
Management: TAVR or AVR (surgical) when symptomatic or EF < 50%

Aortic Regurgitation (AR)

Causes: Bicuspid AV, rheumatic, infective endocarditis, aortic root dilation (Marfan, syphilis, HTN)
Murmur: Early diastolic, decrescendo, best at left sternal border, with patient leaning forward
Pulse: Water-hammer pulse (Corrigan's pulse); wide pulse pressure
Signs: De Musset's sign (head bobbing), Quincke's sign (capillary pulsations in nail bed), Duroziez sign, Austin Flint murmur (functional MS due to AR jet)
Management: ACEi/ARBs if symptomatic; surgical when severe/symptomatic

Mitral Stenosis (MS)

Almost always rheumatic in etiology (commissural fusion)
Murmur: Low-pitched diastolic rumble at apex, opening snap (OS), loud S1
Complications: AF, pulmonary HTN, right HF, systemic emboli
Normal MV area: 4-6 cm²; severe MS < 1.5 cm²
Management: Diuretics, rate control (AF), anticoagulation; Percutaneous balloon mitral valvotomy (PBMV) or MVR

Mitral Regurgitation (MR)

Causes: MVP, rheumatic fever, ischemia (papillary muscle dysfunction), IE, dilated CM
Murmur: Holosystolic, high-pitched, best at apex, radiating to axilla
Management: ACEi; surgical when severe with symptoms or LV dysfunction (EF < 60%, LVESD > 40 mm)

Infective Endocarditis (IE)

Duke Criteria (Major/Minor):

Major criteria:

Positive blood cultures (≥2 for typical organisms: viridans strep, Staph aureus, HACEK group)
Echo evidence: vegetation, abscess, new valvular regurgitation

Minor criteria:

Predisposing condition/IV drug use
Fever ≥ 38°C
Vascular phenomena (emboli, Janeway lesions, mycotic aneurysm)
Immunologic phenomena (Osler's nodes, Roth spots, glomerulonephritis, +RF)
Microbiological: single positive blood culture

Definite IE: 2 major, or 1 major + 3 minor, or 5 minor

Organisms by risk group:

Patient	Organism
Native valve (community)	Streptococcus viridans (most common overall)
IV drug user	Staphylococcus aureus, right-sided (tricuspid)
Prosthetic valve (early < 2 months)	Staph epidermidis, Staph aureus
Nosocomial / colon cancer	Streptococcus bovis (S. gallolyticus) → colonoscopy!

Peripheral stigmata of IE:

Janeway lesions: painless, hemorrhagic (palms/soles) - septic emboli
Osler's nodes: painful, nodular (fingers/toes) - immune complex deposition
Roth spots: retinal hemorrhages with pale centers
Splinter hemorrhages under nails

Pericardial Disease

Acute Pericarditis

Causes: Viral (Coxsackie B most common), bacterial, TB, autoimmune, malignancy, post-MI (Dressler)
Clinical: Sharp pleuritic chest pain, relieved by sitting forward; pericardial friction rub
ECG: Diffuse saddle-shaped ST elevation + PR depression (hallmark); no reciprocal changes
Management: NSAIDs + Colchicine (reduces recurrence)

Cardiac Tamponade

Fluid in pericardium → increased pericardial pressure → impaired filling
Beck's Triad: Hypotension + JVD + Muffled heart sounds
Pulsus paradoxus > 10 mmHg (↓ BP on inspiration)
ECG: Electrical alternans (alternating QRS amplitude)
Management: Pericardiocentesis (emergency drainage)

Constrictive Pericarditis

Fibrotic, calcified pericardium limits filling
Causes: TB (most common worldwide), radiation, viral
Features: Kussmaul's sign (JVP rises on inspiration - opposite of normal), pericardial knock, "square root sign" on ventricular pressure tracing
Management: Pericardiectomy

Cardiomyopathies

Type	Pathology	Key Features	Management
Dilated CM	Enlarged, thin-walled ventricles; systolic dysfunction	Most common CM; causes: ischemic, alcoholic, viral, familial, peripartum, drug-induced	GDMT for HFrEF
Hypertrophic CM (HCM)	Asymmetric septal hypertrophy; diastolic dysfunction; LVOT obstruction	Most common cause of sudden death in young athletes; systolic anterior motion (SAM) of mitral valve; Midsystolic murmur that increases with Valsalva/standing	Beta-blockers/CCBs; ICD; surgical myectomy or alcohol ablation
Restrictive CM	Stiff ventricle; normal/small LV cavity	Causes: Amyloidosis (most common in adults), sarcoidosis, hemochromatosis, eosinophilic	Treat underlying cause
ARVC (Arrhythmogenic RV CM)	Fibro-fatty replacement of RV	Epsilon waves on ECG; risk of VT/VF	ICD; beta-blockers

Aortic Diseases

Aortic Dissection

Intimal tear → blood enters media → creates false lumen
Risk factors: HTN (most common), Marfan syndrome, bicuspid aortic valve, cocaine
Stanford Classification:
- Type A: Involves ascending aorta → Emergency surgical repair
- Type B: Involves descending aorta only → Medical management (BP control with beta-blockers + vasodilators); endovascular repair for complications
Clinical: Tearing/ripping chest pain radiating to back, unequal BP in arms, neurologic deficits
Diagnosis: CT angiography (gold standard); TEE

PART 4: CARDIOVASCULAR PHARMACOLOGY

Antihypertensive Drugs

Class	Examples	MOA	Key Uses	Side Effects
ACE Inhibitors	Enalapril, Ramipril, Lisinopril	Block ACE → ↓ Angiotensin II → ↓ vasoconstriction, ↓ aldosterone	HTN, HF, DM nephropathy, post-MI	Dry cough (bradykinin), angioedema, hyperkalemia, teratogenic
ARBs	Losartan, Valsartan, Candesartan	Block AT1 receptor	Same as ACEi; use if ACEi intolerant	Angioedema (rare), hyperkalemia, teratogenic
ARNI	Sacubitril-Valsartan	Neprilysin inhibition + AT1 block	HFrEF (superior to ACEi)	Angioedema (with ACEi), hypotension
Thiazide Diuretics	HCTZ, Chlorthalidone, Metolazone	Block NCC in DCT → ↓ Na reabsorption	HTN, mild HF, hypercalciuria	Hypokalemia, hyperuricemia, hyponatremia, hyperglycemia, hypercalcemia
Loop Diuretics	Furosemide, Bumetanide, Torsemide	Block NKCC2 in TAL of LOH	Acute HF, edema, hypertensive emergency	Hypokalemia, hypomagnesemia, ototoxicity, metabolic alkalosis
Potassium-sparing Diuretics	Spironolactone (MRA), Amiloride	Block aldosterone or ENaC in collecting duct	HF, hyperaldosteronism	Hyperkalemia; spironolactone: gynecomastia
Dihydropyridine CCBs	Amlodipine, Nifedipine	Block L-type Ca²⁺ channels in vascular smooth muscle	HTN, angina, Raynaud	Peripheral edema, reflex tachycardia, flushing
Non-DHP CCBs	Diltiazem, Verapamil	Block Ca²⁺ channels in heart + vessels	HTN, AF rate control, angina	AV block, constipation, heart failure worsening, negative inotrope
Beta-blockers	Metoprolol, Carvedilol, Bisoprolol, Atenolol	Block β1 (and β2 in non-selective)	HTN, HF, post-MI, angina, AF	Bradycardia, bronchospasm, mask hypoglycemia, fatigue

Antiarrhythmic Drugs (Vaughan-Williams)

Class	Mechanism	Drugs	Uses
Ia	Na⁺ channel block (moderate); ↑ QT	Quinidine, Procainamide, Disopyramide	Atrial and ventricular arrhythmias
Ib	Na⁺ channel block (fast kinetics); ↓ QT	Lidocaine, Mexiletine	VT, digoxin toxicity arrhythmias
Ic	Na⁺ channel block (slow kinetics); no QT change	Flecainide, Propafenone	AF/flutter (without structural heart disease)
II	Beta-blockers	Metoprolol, Esmolol	AF, flutter, SVT, post-MI VT
III	K⁺ channel block; ↑ QT	Amiodarone, Sotalol, Dofetilide	VT, VF, AF (amiodarone most effective)
IV	Non-DHP CCBs	Diltiazem, Verapamil	SVT, AF rate control
Misc		Adenosine	SVT (diagnostic + therapeutic); half-life 10 sec
Misc		Digoxin	AF rate control; HFrEF (narrow TI)
Misc		Atropine	Bradycardia, AV block

Amiodarone toxicities (multi-organ, long half-life ~40-55 days):

Pulmonary fibrosis (most serious)
Thyroid (hypo- and hyperthyroidism)
Liver toxicity
Corneal microdeposits (often asymptomatic)
Photosensitivity, blue-grey skin discoloration
Peripheral neuropathy
Bradycardia, prolonged QT

Anticoagulants

Drug	Target	Monitoring	Reversal
Warfarin	Vit K epoxide reductase → ↓ II, VII, IX, X, protein C, S	INR (target 2-3)	Vitamin K, FFP, 4-factor PCC
Heparin (UFH)	Antithrombin → ↑ inhibition of IIa, Xa, IXa	aPTT	Protamine sulfate
LMWH	Mainly anti-Xa	Not routinely needed	Partial reversal: protamine
Fondaparinux	Anti-Xa only	No monitoring	No specific reversal (rFVIIa)
Dabigatran	Direct thrombin (IIa) inhibitor	ECT/dTT	Idarucizumab
Rivaroxaban, Apixaban, Edoxaban	Direct Factor Xa inhibitors	Not routine	Andexanet alfa

Antiplatelets

Drug	MOA	Uses
Aspirin	Irreversible COX-1 inhibition → ↓ TXA2	ACS, stroke prevention, post-PCI
Clopidogrel	ADP receptor (P2Y12) antagonist (pro-drug, CYP2C19)	ACS, post-PCI (DAPT)
Ticagrelor	Reversible P2Y12 antagonist (not prodrug)	ACS (preferred over clopidogrel in PLATO trial)
Prasugrel	Irreversible P2Y12 (prodrug)	ACS with PCI; avoid in stroke history
Abciximab, Eptifibatide, Tirofiban	GP IIb/IIIa inhibitors	ACS with PCI (high-risk)

Statins (HMG-CoA Reductase Inhibitors)

Block HMG-CoA reductase → ↓ cholesterol synthesis → ↑ LDL receptors → ↓ LDL
Also: Pleiotropic effects (↓ inflammation, plaque stabilization, endothelial function)
High-intensity: Atorvastatin 40-80 mg, Rosuvastatin 20-40 mg
Side effects: Myopathy (↑ CK), rhabdomyolysis (rare; ↑ risk with fibrates/CYP3A4 inhibitors), transaminase elevation

PART 5: CLINICAL SKILLS - CARDIOVASCULAR EXAMINATION

Approach to Cardiac Patient

History: Chest pain (character, radiation, onset, duration, relieving/aggravating factors), dyspnea, palpitations, syncope, edema, prior cardiac history, risk factors (DM, HTN, hyperlipidemia, smoking, family history)
Examination:
- General: Cyanosis (central vs peripheral), pallor, jaundice, clubbing, Marfanoid habitus
- Vital signs: BP (both arms), HR, RR, SpO₂
- Pulse: Rate, rhythm, character (volume, waveform), radiofemoral delay
- JVP: Height (normal < 3-4 cm above sternal angle), waveforms (a, c, x, v, y)
- Precordium: Inspection (apex beat position), palpation (thrills, heaves), auscultation (S1, S2, murmurs, extra sounds)
Investigations: ECG, chest X-ray, echocardiography, troponin, BNP/NT-proBNP, CBC, renal function, lipid profile, coronary angiography

ECG Systematic Reading

Rate → Rhythm → Axis → P-waves → PR interval → QRS → QT → ST/T waves → Overall assessment

Normal values:

HR: 60-100 bpm
PR interval: 120-200 ms
QRS duration: < 120 ms
QTc: < 440 ms (male), < 460 ms (female)
Axis: -30° to +90° (normal)

Axis deviation:

Left axis (-30° to -90°): LBBB, LAHB, LVH, inferior MI, Wolff-Parkinson-White
Right axis (+90° to +180°): RBBB, RVH, pulmonary HTN, lateral MI, normal in children

🫁 RESPIRATORY SYSTEM - Complete Medical Student Guide

Sources: Murray & Nadel's Textbook of Respiratory Medicine, Barash's Clinical Anesthesia

PART 1: RESPIRATORY ANATOMY

Upper Respiratory Tract

Nose/Nasopharynx: Filters, warms, humidifies air; olfaction; paranasal sinuses
Pharynx: Nasopharynx, oropharynx, laryngopharynx; lymphoid tissue (Waldeyer's ring)
Larynx: C3-C6; vocal cords (true and false); epiglottis protects airway during swallowing
Trachea: Starts at C6; 10-15 cm long; bifurcates at carina (T4/sternal angle)

Lower Respiratory Tract - Tracheobronchial Tree

The conducting zone (trachea → bronchi → bronchioles → terminal bronchioles) = anatomical dead space (~150 mL)

The respiratory zone (respiratory bronchioles → alveolar ducts → alveolar sacs → alveoli) = gas exchange

Generation	Structure	Notes
0	Trachea	Cartilaginous, ciliated
1-4	Main, lobar, segmental bronchi	Cartilaginous support
5-16	Smaller bronchi/bronchioles	No cartilage after ~generation 8
17-19	Respiratory bronchioles	Some alveoli in walls
20-22	Alveolar ducts
23	Alveolar sacs

Right bronchus vs Left bronchus:

Right: Shorter, wider, more vertical → Foreign bodies more commonly lodge in right lower lobe
Left: Longer, narrower, more horizontal

Lungs

Right lung: 3 lobes (upper, middle, lower); 10 bronchopulmonary segments Left lung: 2 lobes (upper, lower) + lingula; 8-10 segments

Pleura: Visceral (covers lung) + parietal (lines chest wall); potential pleural space normally contains ~10-20 mL fluid for lubrication.

Alveoli - The Gas Exchange Unit

~300-500 million alveoli; total surface area ~70-80 m²
Type I pneumocytes (~95% of surface): Gas exchange; flat, squamous
Type II pneumocytes (~5% of surface): Produce surfactant (lecithin/dipalmitoylphosphatidylcholine - DPPC), progenitor cells for Type I, produce proteins for host defense
Alveolar macrophages: First line immune defense; phagocytose particles, bacteria

Blood-gas barrier: Alveolar epithelium (Type I) → basement membrane → pulmonary capillary endothelium = ~0.3-0.5 µm thick

PART 2: RESPIRATORY PHYSIOLOGY

Lung Volumes and Capacities

TLC ─────────────────────────────────────
      ↑ IRV
VC  
IC ─  VT (tidal volume ~500 mL)         
      ↓ ERV
FRC ─────────────────────────────────────
      RV
RLC ─────────────────────────────────────

Volume/Capacity	Normal	Definition
Tidal Volume (VT)	500 mL	Volume with each breath
IRV	3000 mL	Max additional inspiration above VT
ERV	1200 mL	Max additional expiration below VT
Residual Volume (RV)	1200 mL	Air remaining after maximal expiration; CANNOT be measured by spirometry
Vital Capacity (VC)	4800 mL	IRV + VT + ERV
FRC	2400 mL	ERV + RV; volume at end of quiet expiration (balance between lung recoil in, chest wall spring out)
TLC	6000 mL	All four volumes; RV + VC
IC	3500 mL	IRV + VT

Note: RV, FRC, and TLC cannot be measured by spirometry alone - require helium dilution, nitrogen washout, or body plethysmography.

Spirometry - Obstructive vs Restrictive

Pattern	FEV1	FVC	FEV1/FVC	TLC	Causes
Obstructive	↓↓	Normal/↓	< 0.70 (< 70%)	Normal/↑	COPD, Asthma, Bronchiectasis
Restrictive	↓	↓↓	Normal or ↑	↓	Pulmonary fibrosis, Pleural effusion, Neuromuscular disease, Obesity
Mixed	↓	↓	< 0.70	↓	Sarcoidosis, some COPD

Respiratory Mechanics

Lung Compliance

Compliance (C) = ΔVolume / ΔPressure

Normal lung compliance: ~200 mL/cmH₂O; Normal total (lung + chest wall): ~100 mL/cmH₂O

↓ Compliance (stiff)	↑ Compliance (floppy)
Pulmonary fibrosis, ARDS, pulmonary edema, neonatal RDS (surfactant deficiency)	Emphysema (destruction of elastic tissue), aging

Surfactant:

Produced by Type II pneumocytes
Lowers surface tension in alveoli (LaPlace's law: P = 2T/r; smaller alveoli have higher pressure → surfactant prevents collapse)
Prevents alveolar collapse at low lung volumes
Deficient in premature infants (<32 weeks) → Neonatal Respiratory Distress Syndrome (NRDS)
Treatment: Antenatal corticosteroids (betamethasone) → stimulate surfactant; exogenous surfactant (beractant/poractant)

Airway Resistance

Poiseuille's Law: Resistance (R) = 8ηL / πr⁴

Resistance is inversely proportional to the 4th power of radius → small changes in airway caliber have enormous effects
Normal airway resistance: ~1-3 cmH₂O/L/s
Medium-sized bronchi (3rd-4th generation) contribute most resistance (not small airways, which have vast total cross-sectional area)
↑ Resistance: bronchospasm, mucosal edema, secretions, foreign body

Laminar vs Turbulent Flow:

Laminar flow: Low velocity, straight tubes, governed by Poiseuille's law
Turbulent flow: High velocity, branch points, described by Reynolds number (Re > 2000 = turbulent)
Turbulent flow requires greater driving pressure for the same flow → relevant in trachea and upper airways

Elastic Recoil

Lung recoil:

Lungs tend to collapse (recoil inward) due to:
1. Elastic tissue (elastin fibers - 70%)
2. Surface tension at air-liquid interface in alveoli (30%)

Chest wall recoil:

Chest wall tends to spring outward
At FRC, lung recoil inward = chest wall recoil outward → equilibrium

Pressure-Volume (P-V) Curve:

Normally shows hysteresis (inflation curve ≠ deflation curve) due to surface tension and recruitment
Compliance = slope of P-V curve
In ARDS: flat P-V curve (very stiff); "baby lung" concept

Gas Exchange

Ventilation-Perfusion (V/Q) Ratio

Normal overall V/Q = 0.8 (alveolar ventilation ~4 L/min; cardiac output ~5 L/min)

Regional V/Q differences (upright position):

Region	V/Q	Cause
Apex	> 1 (West Zone 1)	Low perfusion (gravity); higher O₂, lower CO₂
Middle	~0.8 (West Zone 2)	Normal
Base	< 1 (West Zone 3)	High perfusion, low ventilation (relative); lower O₂, higher CO₂

West Zones of Perfusion:

Zone 1 (apex): PA > Pa > Pv → No flow (collapsed capillaries); not normally present but occurs in hemorrhage or positive-pressure ventilation
Zone 2 (middle): Pa > PA > Pv → Flow depends on Pa - PA
Zone 3 (base): Pa > Pv > PA → Continuous flow; most blood flow

V/Q Mismatch → Hypoxemia:

Low V/Q (shunt-like): blood perfuses poorly ventilated areas → hypoxemia (responds to O₂ supplementation)
True shunt (V/Q = 0): Blood bypasses ventilation entirely (e.g., atelectasis, consolidation, intracardiac shunt) → hypoxemia NOT corrected by 100% O₂
High V/Q (dead space): ventilation with no perfusion → hypercapnia mainly

Causes of Hypoxemia (5 mechanisms):

Hypoventilation: ↑ PaCO₂ displaces O₂; corrected by ↑ FiO₂; A-a gradient normal
Diffusion impairment: e.g., pulmonary fibrosis; worsens on exercise
V/Q mismatch: Most common cause; responds to O₂
True shunt: Does NOT respond to 100% O₂ (anatomic or physiologic shunt)
Low FiO₂: High altitude

A-a gradient = PAO₂ - PaO₂; Normal < 10-15 mmHg; rises with V/Q mismatch, diffusion impairment, shunt; normal in hypoventilation.

Oxygen Transport

Hb-O₂ Dissociation Curve (sigmoidal shape):

P50 = PaO₂ at which Hb is 50% saturated; normal ~26-27 mmHg

Shift RIGHT (↓ O₂ affinity, ↑ O₂ delivery to tissues):

↑ Temperature, ↑ 2,3-DPG, ↑ PCO₂, ↓ pH (Bohr effect), exercise

Shift LEFT (↑ O₂ affinity, ↓ O₂ delivery):

↓ Temperature, ↓ 2,3-DPG, ↓ PCO₂, ↑ pH, fetal Hb (HbF), CO poisoning, methemoglobin

O₂ Content (CaO₂) = (Hb × 1.34 × SaO₂) + (0.003 × PaO₂)

Dissolved O₂ is a minor contributor normally
Oxygen delivery (DO₂) = CO × CaO₂

Carbon Dioxide Transport

70%: As bicarbonate (HCO₃⁻) via carbonic anhydrase in RBCs
- CO₂ + H₂O → H₂CO₃ → H⁺ + HCO₃⁻
- Chloride shift: HCO₃⁻ exits RBC via AE1, Cl⁻ enters
23%: Bound to Hb as carbaminohaemoglobin
7%: Dissolved in plasma

Haldane Effect: Deoxygenated Hb has greater affinity for CO₂ → at tissues, Hb releases O₂ and binds more CO₂.

Control of Breathing

Respiratory Centers (brainstem):

Pre-Bötzinger complex (medulla): Rhythm generator; automatic breathing
Dorsal Respiratory Group (nucleus tractus solitarius): Inspiration
Ventral Respiratory Group: Expiration and forced breathing
Pneumotaxic center (upper pons): Limits inspiration, helps regulate rate
Apneustic center (lower pons): Sustained inspiration (overridden by pneumotaxic)

Central chemoreceptors (ventral medulla):

Respond to ↑ PCO₂ (→ ↓ pH of CSF)
Primary drive to breathe in normal individuals
Slow response (minutes)
Insensitive to PO₂ changes

Peripheral chemoreceptors (carotid and aortic bodies):

Carotid bodies: Most important; CN IX afferents → NTS
Respond to: ↓ PaO₂ (< 60 mmHg), ↑ PaCO₂, ↓ pH
Fast response (seconds)

Clinical: In chronic COPD with chronic CO₂ retention, the central chemoreceptors become desensitized → "hypoxic drive" (peripheral chemoreceptors) becomes the primary drive. High-flow O₂ can suppress this → "CO₂ retention" risk (though the mechanism is multifactorial - mainly V/Q mismatch worsening and Haldane effect).

Acid-Base - Respiratory Component

Disorder	pH	PaCO₂	HCO₃⁻	Compensation
Respiratory Acidosis	↓	↑	↑ (renal compensation)	HCO₃⁻ ↑ 1 mEq/L per 10 mmHg ↑ CO₂ (acute); 3.5 mEq/L (chronic)
Respiratory Alkalosis	↑	↓	↓ (renal compensation)	HCO₃⁻ ↓ 2 mEq/L per 10 mmHg ↓ CO₂ (acute); 5 mEq/L (chronic)

Causes of respiratory acidosis: Hypoventilation from any cause (COPD, sedatives/opiates, neuromuscular disease, severe asthma, pneumothorax)

Causes of respiratory alkalosis: Hyperventilation (anxiety, pregnancy, salicylate toxicity early, high altitude, mechanical ventilation, sepsis early, hepatic failure)

PART 3: RESPIRATORY DISEASES

Chronic Obstructive Pulmonary Disease (COPD)

Definition: Persistent, largely irreversible airflow limitation; FEV1/FVC < 0.70 post-bronchodilator

Two main phenotypes:

	Chronic Bronchitis ("Blue Bloater")	Emphysema ("Pink Puffer")
Mechanism	↑ mucus secretion, inflammation, airway narrowing	Destruction of alveolar walls, loss of elastic recoil
Cause	Smoking (90%); productive cough ≥3 months/yr for ≥2 years	Smoking; α1-antitrypsin deficiency (young, non-smoker, panacinar)
Hypoxia	Severe early; cyanosis	Mild; hyperventilate to compensate
CO₂ retention	Common	Rare until late
Cor pulmonale	Early	Late

GOLD Classification (by FEV1 % predicted):

GOLD 1 (Mild): FEV1 ≥ 80%
GOLD 2 (Moderate): 50-79%
GOLD 3 (Severe): 30-49%
GOLD 4 (Very Severe): < 30%

Emphysema Types:

Centrilobular (proximal acinar): Smoking; upper lobes predominantly
Panacinar: α1-antitrypsin deficiency; lower lobes; Panlobular
Paraseptal (distal acinar): Young adults; associated with spontaneous pneumothorax

Management:

Stable COPD:

Smoking cessation (most important intervention)
Bronchodilators: SABA (salbutamol), SAMA (ipratropium), LABA (salmeterol, formoterol), LAMA (tiotropium)
Inhaled corticosteroids (ICS): Add for frequent exacerbations; ICS + LABA combination
Triple therapy: ICS + LABA + LAMA (Trelegy/Trimbow)
Pulmonary rehabilitation
O₂ therapy (LTOT): PaO₂ ≤ 55 mmHg (or ≤ 60 mmHg with polycythemia/cor pulmonale) → ≥15 hrs/day → ↓ mortality
Roflumilast (PDE4 inhibitor): Add for severe with chronic bronchitis
Influenza and pneumococcal vaccines
Lung volume reduction surgery / BLVR

COPD Exacerbation:

Controlled O₂: Target SpO₂ 88-92%
Short-acting bronchodilators (nebulized)
Systemic corticosteroids (prednisolone 40 mg × 5 days)
Antibiotics if purulent sputum (amoxicillin/doxycycline/azithromycin)
Non-invasive ventilation (NIV/BiPAP): If pH < 7.35 + PaCO₂ elevated → improves outcome, reduces intubation

Asthma

Definition: Chronic inflammatory airway disease with episodic, reversible airflow obstruction and bronchial hyperresponsiveness

Pathophysiology:

Airway inflammation (eosinophils, mast cells, Th2 cells)
Allergen → IgE-mediated mast cell degranulation → histamine, leukotrienes → bronchoconstriction
Airway remodeling in chronic/severe asthma (sub-epithelial fibrosis, smooth muscle hypertrophy)

Triggers: Allergens, cold air, exercise, NSAIDs (aspirin-exacerbated respiratory disease), beta-blockers, smoke, viral URTI

Classification:

Severity	Daytime symptoms	Night symptoms	FEV1
Intermittent	≤ 2 days/week	≤ 2 nights/month	≥ 80%
Mild Persistent	> 2 days/week but not daily	3-4 nights/month	≥ 80%
Moderate Persistent	Daily	> 1 night/week	60-79%
Severe Persistent	Continuous	Often nightly	< 60%

Step-up Therapy (GINA/NAEPP):

Step	Treatment
1	SABA PRN (salbutamol/albuterol)
2	Low-dose ICS + SABA PRN
3	Low-dose ICS + LABA (or medium ICS)
4	Medium-high ICS + LABA
5	High ICS + LABA ± LAMA ± oral corticosteroids
Severe/Biologic	Anti-IgE (Omalizumab), Anti-IL5 (Mepolizumab), Anti-IL4/13 (Dupilumab)

Acute Severe Asthma (Status Asthmaticus):

Features: Inability to speak in sentences, SpO₂ < 92%, silent chest (very severe - no air entry), PEF < 33% predicted
Life-threatening features: silent chest, bradycardia, confusion, PaO₂ < 8 kPa, normal/↑ PaCO₂ (in asthma, PaCO₂ should be LOW; normal = very severe bronchospasm)
Management: O₂ (target SpO₂ 94-98%), nebulized SABA (every 20 mins), ipratropium, IV/oral corticosteroids, IV magnesium sulfate (2 g over 20 min), IV aminophylline (selected cases), intubation if deteriorating

Pneumonia

Classification:

Type	Common Pathogens
Community-Acquired (CAP)	S. pneumoniae (most common), Mycoplasma, Legionella, H. influenzae, Moraxella, Viruses
Hospital-Acquired (HAP, >48 hrs)	Gram-negatives (Pseudomonas, Klebsiella, E. coli), S. aureus (MRSA)
Aspiration	Anaerobes, mixed flora
Atypical (walking pneumonia)	Mycoplasma, Chlamydophila, Legionella

Typical vs Atypical:

Feature	Typical (S. pneumoniae)	Atypical (Mycoplasma)
Onset	Acute, sudden	Gradual
Fever	High, shaking chills	Low-grade
CXR	Lobar consolidation	Diffuse/patchy, bilateral
Sputum	Purulent, productive	Non-productive
Response	Amoxicillin	Macrolide, Doxycycline

CURB-65 Score (mortality predictor for CAP):

Criterion	Score
Confusion (new)	1
Urea > 7 mmol/L	1
Respiratory rate ≥ 30	1
BP < 90 systolic or < 60 diastolic	1
Age ≥ 65	1

0-1: Outpatient; 2: Inpatient; 3-5: ICU consideration

Management:

CAP (mild): Amoxicillin ± macrolide (or doxycycline)
CAP (severe/ICU): IV ceftriaxone + macrolide (or fluoroquinolone monotherapy)
Legionella/Atypical: Macrolide or fluoroquinolone
HAP: Piperacillin-tazobactam, cefepime, or carbapenem ± vancomycin/linezolid if MRSA risk

Legionella pneumophila (Legionnaires' disease):

Gram-negative intracellular; grows in water (cooling towers, A/C systems)
Features: Pneumonia + GI symptoms + CNS involvement + hyponatremia + elevated LDH/ALT + lymphopenia
Diagnosis: Urinary antigen (serogroup 1), culture (BCYE agar)
Treatment: Macrolide or fluoroquinolone (NOT beta-lactams - intracellular)

Pulmonary Tuberculosis (TB)

Mycobacterium tuberculosis - acid-fast bacillus (Ziehl-Neelsen stain)

Primary TB: First infection; Ghon focus (mid-lung) + hilar lymph node = Ghon complex; usually asymptomatic; heals with calcification

Post-Primary (Reactivation) TB:

Apical/posterior upper lobe and superior lower lobe (high PO₂ areas)
Cavity formation, caseation necrosis
Symptoms: Chronic cough, hemoptysis, weight loss, night sweats, evening fever

Diagnosis:

AFB smear and culture (gold standard; Lowenstein-Jensen medium; 6-8 weeks)
Nucleic acid amplification (GeneXpert MTB/RIF): Fast, also detects rifampicin resistance
Mantoux test (TST): Purified protein derivative (PPD); read at 48-72 hrs; induration ≥10 mm = positive (lower threshold in immunocompromised/HIV: 5 mm)
IGRA (Interferon-Gamma Release Assay): More specific, not affected by BCG vaccination
CXR: Apical infiltrates, cavitation, calcification

Treatment (Standard regimen):

Phase	Drugs	Duration
Intensive (RIPE)	Rifampicin + Isoniazid + Pyrazinamide + Ethambutol	2 months
Continuation	Rifampicin + Isoniazid	4 months
Total		6 months

Drug toxicities:

Drug	Key Side Effects
Rifampicin	Orange urine/tears/sweat, hepatotoxicity, enzyme inducer (↓ OCP, warfarin efficacy)
Isoniazid	Peripheral neuropathy (B6 deficiency - give pyridoxine), hepatotoxicity, SLE-like syndrome
Pyrazinamide	Hyperuricemia (gout), hepatotoxicity
Ethambutol	Optic neuritis (monitor visual acuity monthly)

Pulmonary Embolism (PE)

Risk Factors (Virchow's Triad):

Stasis: Immobility, long-haul flight, post-surgery
Hypercoagulability: Thrombophilia (Factor V Leiden, antiphospholipid syndrome, malignancy, OCP)
Endothelial injury: Trauma, surgery

Clinical Features:

Dyspnea (most common), pleuritic chest pain, hemoptysis, tachycardia
Massive PE: Hypotension, RV failure, syncope, cardiac arrest

Wells Score for PE Probability:

Criterion	Points
DVT symptoms/signs	3
PE more likely than alternative	3
HR > 100	1.5
Surgery/immobility in last 4 weeks	1.5
Prior DVT/PE	1.5
Hemoptysis	1
Active malignancy	1

Score > 4: High probability → CT pulmonary angiography (CTPA)
Score ≤ 4: Low probability → D-dimer first; if negative, PE excluded

Investigations:

ECG: Sinus tachycardia (most common); classic (but not specific) pattern: S1Q3T3 (S wave in I, Q wave and T inversion in III)
CXR: Often normal; Westermark sign (oligemia), Hampton's hump (wedge-shaped infarct)
ABG: Hypoxemia, hypocapnia, respiratory alkalosis, widened A-a gradient
CTPA: Gold standard for diagnosis
V/Q scan: If CTPA contraindicated (CKD, contrast allergy)
Echo: RV dilation, right heart strain, McConnell's sign (apical RV sparing)

Management:

Hemodynamically unstable (massive PE): Systemic thrombolysis (tPA/alteplase); surgical embolectomy if contraindicated
Stable PE: Anticoagulation with DOACs (rivaroxaban, apixaban preferred) or LMWH → warfarin
Duration: 3 months (provoked), ≥ 3 months (unprovoked, recurrent, or malignancy)
IVC filter: Anticoagulation contraindicated or recurrent PE despite anticoagulation

Pleural Diseases

Pleural Effusion

Light's Criteria (exudate vs transudate):

An effusion is an EXUDATE if ANY one of the following is met:

Pleural protein/serum protein > 0.5
Pleural LDH/serum LDH > 0.6
Pleural LDH > 2/3 upper limit of normal serum LDH

Transudate	Exudate
Heart failure (most common)	Pneumonia (parapneumonic)
Cirrhosis (hepatic hydrothorax)	Malignancy
Nephrotic syndrome	TB
Hypothyroidism	Pulmonary embolism
Hypoalbuminemia	Rheumatoid arthritis

Diagnosis: CXR (> 300 mL), ultrasound, thoracocentesis with analysis

Management: Drain if large/symptomatic; treat underlying cause; consider pleurodesis for malignant/recurrent

Pneumothorax

Type	Cause	Features
Spontaneous primary	Young, tall, thin males; Blebs	No underlying lung disease
Spontaneous secondary	COPD (emphysematous bullae), TB, cystic fibrosis, Marfan	Underlying lung disease
Tension	Any cause; valve effect traps air	Medical emergency: tracheal deviation AWAY from side, ↓ breath sounds, hypotension, JVD
Traumatic	Penetrating chest wound, iatrogenic (central line)

Management:

Small primary (< 2 cm): Observe; high-flow O₂ (accelerates absorption 4×)
Large or symptomatic: Needle aspiration or chest tube (intercostal drain)
Tension pneumothorax: Immediate needle decompression (2nd ICS, MCL) → then chest tube

Interstitial Lung Disease (ILD)

Heterogeneous group of diffuse parenchymal lung diseases with fibrosis/inflammation.

Key features: Restrictive pattern, diffusion impairment, ground-glass opacities on HRCT, bibasal crepitations (Velcro crackles), clubbing in IPF

ILD	Key Associations	HRCT Pattern
IPF (Idiopathic Pulmonary Fibrosis)	Elderly male smokers; poor prognosis (median survival 2-3 yr)	UIP: Basal, subpleural honeycombing + traction bronchiectasis
NSIP	Autoimmune diseases (Scleroderma, SLE, PM/DM)	Ground-glass opacities, basal fibrosis
COP (Cryptogenic organizing pneumonia)	Post-infection/drug	Consolidation + ground-glass, peribronchovascular
Sarcoidosis	Young adults, African-American; bilateral hilar lymphadenopathy	Micronodules along lymphatics; upper lobe
HP (Hypersensitivity pneumonitis)	Organic dust exposure (farmer's lung - thermophilic actinomycetes; bird fancier's lung - avian proteins)	Acute: GGO; chronic: fibrosis
Pneumoconioses	Occupational dust	Silicosis (nodules, upper lobe, "eggshell" calcification); Asbestosis (basal fibrosis + pleural plaques; ↑ mesothelioma risk)

Treatment of IPF: Pirfenidone or Nintedanib (anti-fibrotic agents; slow progression, do not cure); lung transplantation

Lung Cancer

Most common cancer worldwide; #1 cause of cancer death

Type	Location	Cell Characteristics	Key Features
Squamous Cell	Central (hilar)	Squamous cells, keratin pearls, intercellular bridges	Cavitates; PTHrP → hypercalcemia; Pancoast tumor; Most commonly associated with smoking
Adenocarcinoma	Peripheral	Glandular, mucin-producing; most common in non-smokers/women	EGFR/ALK mutations (targeted therapy); grows along alveolar walls (lepidic pattern in BAC)
Small Cell (SCLC)	Central	Neuroendocrine; oat cells	Paraneoplastic syndromes (SIADH, ACTH/Cushing, Lambert-Eaton myasthenic syndrome, sensory neuropathy); highly aggressive; responds well initially to chemo
Large Cell	Peripheral	Undifferentiated	Poor prognosis

Non-Small Cell (NSCLC) = Squamous + Adenocarcinoma + Large Cell (~85% of all lung cancers)

Paraneoplastic syndromes:

Syndrome	Association
Hypercalcemia (PTHrP)	Squamous cell carcinoma
SIADH (↓ Na, ↓ serum osmolality)	SCLC
Ectopic ACTH → Cushing syndrome	SCLC
Lambert-Eaton Myasthenic Syndrome	SCLC (anti-VGCC antibodies)
Hypertrophic osteoarthropathy / clubbing	Adenocarcinoma
Trousseau's syndrome (migratory thrombophlebitis)	Adenocarcinoma

Superior Vena Cava Syndrome:

Compression/invasion of SVC
Features: Facial/neck edema, arm edema, JVD, dilated chest wall veins, headache, Pemberton's sign
Most common cause: SCLC, lymphoma
Treatment: SVCS stenting, radiotherapy

Pancoast Tumor (Superior Sulcus Tumor):

Apex of lung → invades brachial plexus, subclavian vessels, stellate ganglion
Horner's syndrome: Ptosis, miosis, anhidrosis, enophthalmos (stellate ganglion invasion)
Shoulder/arm pain radiating down ulnar nerve distribution (C8/T1/T2)
Treatment: Combined chemoradiation → surgery

Staging and Treatment:

NSCLC Stages I-II: Surgery (lobectomy); adjuvant chemotherapy
NSCLC Stage III: Concurrent chemoradiation
NSCLC Stage IV: Platinum-based chemotherapy; targeted therapy (EGFR: erlotinib/osimertinib; ALK: crizotinib); Immunotherapy (PD-L1 inhibitors - pembrolizumab)
SCLC Limited: Chemo + radiation (cisplatin/etoposide); prophylactic cranial irradiation (PCI)
SCLC Extensive: Chemotherapy + immunotherapy (atezolizumab)

Cystic Fibrosis (CF)

Autosomal recessive mutation in CFTR gene (chromosome 7q); most common lethal AR disease in Caucasians

Most common mutation: ΔF508 (deletion of Phe 508)
CFTR = ABC transporter Cl⁻ channel; defect → thick, viscous secretions

Clinical features (multi-system):

System	Manifestations
Respiratory	Chronic productive cough, bronchiectasis, recurrent pneumonias (Pseudomonas aeruginosa hallmark), pneumothorax, respiratory failure
GI/Pancreatic	Meconium ileus (newborn), pancreatic exocrine insufficiency (malabsorption, steatorrhea), CF-related diabetes, distal intestinal obstruction
Hepatic	Focal biliary cirrhosis
Reproductive	Male infertility (congenital bilateral absence of vas deferens - CBAVD); female ↓ fertility
Other	Sinusitis, nasal polyps, clubbing, salt depletion

Diagnosis:

Newborn screening: Immunoreactive trypsinogen (IRT) + CFTR mutation analysis
Sweat chloride test (gold standard): Cl⁻ > 60 mmol/L = diagnostic; 40-60 = borderline

Management:

Airway clearance: Chest physiotherapy, hypertonic saline, dornase alfa (DNase - cleaves DNA in sputum)
Antibiotics: Prophylactic/therapeutic; chronic Pseudomonas → inhaled tobramycin/aztreonam; exacerbations: IV antipseudomonal antibiotics
Pancreatic enzyme replacement (Creon)
Fat-soluble vitamin supplementation (A, D, E, K)
CFTR modulators (targeted therapy):
- Ivacaftor (potentiator): G551D mutation
- Lumacaftor + Ivacaftor: ΔF508 homozygous
- Elexacaftor + Tezacaftor + Ivacaftor (Trikafta/Kaftrio): ΔF508 (one copy) - most effective; transforms outcomes
Lung transplantation (bilateral): End-stage

Obstructive Sleep Apnea (OSA)

Repetitive upper airway obstruction during sleep → apnea/hypopnea
Risk factors: Obesity (↑ neck circumference > 40 cm), male sex, age, retrognathia, tonsillar hypertrophy
Symptoms: Snoring, witnessed apneas, daytime sleepiness (Epworth Sleepiness Scale), morning headaches
Complications: HTN (most common), AF, pulmonary HTN, RV failure (cor pulmonale), cognitive impairment, road traffic accidents
Diagnosis: Polysomnography (gold standard); AHI (Apnea-Hypopnea Index): mild 5-14, moderate 15-29, severe ≥ 30
Management: CPAP (first-line, most effective) - maintains positive airway pressure to keep airway patent; weight loss; mandibular advancement device (mild-moderate); surgery (UPPP, tonsillectomy) in select cases

Mechanical Ventilation Basics

Indications: Apnea, respiratory failure (type I or II), impending respiratory arrest

Types:

NIV (BiPAP/CPAP): Non-invasive; avoids intubation; used in COPD exacerbation, cardiogenic pulmonary edema, OSA, type II respiratory failure
Invasive mechanical ventilation: Via ETT or tracheostomy

Ventilator modes:

VCV (Volume Control): Set tidal volume delivered regardless of pressure
PCV (Pressure Control): Set pressure; volume varies
SIMV: Synchronized mandatory + spontaneous breaths
PSV (Pressure Support): Patient-triggered; supplements spontaneous breaths
CPAP: Continuous positive pressure; patient breathes spontaneously

Lung Protective Ventilation (ARDSnet Protocol):

Tidal volume: 6 mL/kg ideal body weight (reduces barotrauma)
Plateau pressure: < 30 cmH₂O
PEEP: Adequate to prevent alveolar collapse
Permissive hypercapnia: Accept pH > 7.20, PaCO₂ up to 55-60 mmHg
Prone positioning: 16 hrs/day in severe ARDS (PaO₂/FiO₂ < 150) → ↓ mortality

QUICK REVISION SUMMARY

CVS Key Facts

Topic	Key Point
Most common cause of heart failure	IHD/ischemic cardiomyopathy
HFrEF EF threshold	< 40%
4 pillars of HFrEF GDMT	ACEi/ARNI + Beta-blocker + MRA + SGLT2i
STEMI treatment	Primary PCI < 90 min door-to-balloon
Most common valvular disease in developed world	Aortic stenosis
AS classic triad	Syncope, Angina, Heart Failure
Most common cause of MS	Rheumatic fever
HCM murmur increases with	Valsalva / standing (↓ preload)
Most common IE organism	Streptococcus viridans
Aortic dissection Type A	Emergency surgery
Antidote for amiodarone toxicity	No specific antidote
Dabigatran reversal	Idarucizumab

Respiratory Key Facts

Topic	Key Point
Cannot be measured by spirometry	RV, FRC, TLC
Obstructive pattern	FEV1/FVC < 0.70
Most common cause of hypoxemia	V/Q mismatch
Hypoxemia NOT corrected by 100% O₂	True shunt
COPD first-line mortality benefit	Smoking cessation
COPD LTOT indication	PaO₂ ≤ 55 mmHg
COPD NIV indication	pH < 7.35 with ↑ CO₂
Most common CAP organism	Streptococcus pneumoniae
Atypical pneumonia treatment	Macrolide/doxycycline
TB standard duration	6 months (2 RIPE + 4 RI)
Ethambutol toxicity	Optic neuritis
PE massive treatment	Systemic thrombolysis
IPF treatment	Pirfenidone or Nintedanib
Most common mutation in CF	ΔF508
CF CFTR modulator for ΔF508	Elexacaftor/Tezacaftor/Ivacaftor (Trikafta)
OSA first-line treatment	CPAP
ARDS protective ventilation tidal volume	6 mL/kg IBW

Sources: Barash, Cullen, Stoelting's Clinical Anesthesia 9e (Cardiac Anatomy & Physiology, Respiratory Mechanics) | Braunwald's Heart Disease 2-Vol Set | Fuster & Hurst's The Heart 15e | Murray & Nadel's Textbook of Respiratory Medicine | Katzung's Basic & Clinical Pharmacology 16e

---That is your complete, structured medical-student-level guide to both systems. Here is a quick orientation to what was covered:

What Was Covered

🫀 Cardiovascular System (Part 1)

PART 1 - Anatomy: Gross anatomy, cardiac skeleton, chambers, valves, coronary anatomy (RCA, LAD, LCx), conduction system (SA → AV → His-Purkinje), action potential phases

PART 2 - Physiology: Cardiac cycle (systole/diastole), heart sounds (S1-S4), Frank-Starling law, preload/afterload/contractility, Laplace's law, excitation-contraction coupling, molecular sarcomere proteins (myosin, actin, troponin complex), coronary blood flow regulation

PART 3 - Pathology:

Heart failure (HFrEF vs HFpEF, GDMT - ARNI, beta-blockers, MRA, SGLT2i)
Ischemic heart disease / ACS (STEMI/NSTEMI, ECG localization, MI complications)
Hypertension (classification, target organ damage, management)
Arrhythmias (AF, VT/VF, heart blocks, Torsades de Pointes)
Valvular disease (AS, AR, MS, MR - murmurs, signs, management)
Infective endocarditis (Duke criteria, organisms, peripheral signs)
Pericardial disease (pericarditis, tamponade, constrictive)
Cardiomyopathies (dilated, HCM, restrictive, ARVC)
Aortic dissection (Stanford A vs B)

PART 4 - Pharmacology: Antihypertensives (ACEi, ARB, ARNI, diuretics, CCBs, beta-blockers), antiarrhythmics (Vaughan-Williams classification), anticoagulants (warfarin, heparin, DOACs with reversals), antiplatelets, statins

PART 5 - Clinical Skills: History-taking, examination approach, ECG reading

🫁 Respiratory System (Part 2)

PART 1 - Anatomy: Upper/lower tract, tracheobronchial tree generations, right vs left bronchus differences, alveolar structure (Type I vs II pneumocytes, surfactant), blood-gas barrier

PART 2 - Physiology: Lung volumes/capacities (VT, TLC, FRC, RV), spirometry (obstructive vs restrictive), compliance, surfactant/LaPlace's law, airway resistance (Poiseuille's law), V/Q matching (West zones), 5 mechanisms of hypoxemia, A-a gradient, Hb-O₂ dissociation curve (shifts), CO₂ transport, control of breathing (central/peripheral chemoreceptors), acid-base

PART 3 - Diseases:

COPD (Blue Bloater vs Pink Puffer, GOLD classification, emphysema types, step-up therapy, exacerbation management, LTOT)
Asthma (pathophysiology, triggers, step-up therapy, biologics, status asthmaticus)
Pneumonia (CAP/HAP/atypical, CURB-65, antibiotic regimens, Legionella)
Tuberculosis (primary vs reactivation, RIPE regimen, drug toxicities)
Pulmonary embolism (Wells score, S1Q3T3, CTPA, thrombolysis)
Pleural diseases (Light's criteria, pneumothorax types, tension pneumothorax management)
ILD/IPF (UIP pattern, pirfenidone/nintedanib)
Lung cancer (SCLC/NSCLC, paraneoplastic syndromes, Pancoast/Horner's, SVC syndrome, targeted therapy)
Cystic fibrosis (ΔF508, Trikafta, management)
OSA (CPAP)
Mechanical ventilation (ARDSnet protocol, lung protective ventilation)

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🫀 CVS - Scroll up to find:

Anatomy - Gross anatomy, valves, coronary arteries, conduction system
Physiology - Cardiac cycle, heart sounds, preload/afterload, sarcomere proteins
Pathology - Heart failure, ACS/STEMI, hypertension, arrhythmias, valvular disease, IE, pericarditis, cardiomyopathies, aortic dissection
Pharmacology - Antihypertensives, antiarrhythmics, anticoagulants, antiplatelets, statins
Clinical - ECG reading, cardiac examination

🫁 Respiratory - Scroll up to find:

Anatomy - Airways, alveoli, Type I/II pneumocytes
Physiology - Lung volumes, spirometry, V/Q matching, O₂/CO₂ transport, control of breathing
Diseases - COPD, Asthma, Pneumonia, TB, PE, Pleural diseases, ILD/IPF, Lung cancer, CF, OSA, Mechanical ventilation

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🫀 CARDIOVASCULAR SYSTEM - Complete Medical Student Guide

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🫀 CARDIOVASCULAR SYSTEM - Complete Medical Student Guide

PART 1: CARDIAC ANATOMY

Gross Anatomy

Supports the four valves
Resists forces of developed pressure and blood flow
Provides insertion sites for superficial subepicardial muscle

An interstitial collagen fiber network + elastin provides structural support, flexibility, and elasticity.

The Four Chambers

Chamber	Wall Thickness	Key Features
Right Atrium (RA)	Thin	Receives SVC, IVC, coronary sinus
Right Ventricle (RV)	~3-5 mm	Crescent-shaped; low-pressure circuit
Left Atrium (LA)	Thin	Receives pulmonary veins
Left Ventricle (LV)	~8-12 mm	Ellipsoid; generates ~120 mmHg systolic

The LV is composed of three myocardial layers:

Outer layer: counterclockwise spiral fibers
Middle layer: circumferential fibers (responsible for most shortening)
Inner layer: clockwise fibers

This three-dimensional fiber architecture produces both shortening and twisting (torsional) motion during systole.

Cardiac Valves

Valve	Type	Cusps	Separates
Tricuspid	AV	3 leaflets	RA → RV
Pulmonary	Semilunar	3 cusps	RV → Pulmonary artery
Mitral (Bicuspid)	AV	2 leaflets	LA → LV
Aortic	Semilunar	3 cusps	LV → Aorta

Mitral valve apparatus: anterior and posterior leaflets attached to papillary muscles via chordae tendineae. Rupture of papillary muscles (e.g., post-MI) causes acute mitral regurgitation.

Coronary Anatomy

Right Coronary Artery (RCA):

Supplies SA node (~60%), AV node (~80-90%), RV, inferior LV
Terminates as PDA in right-dominant circulation (~85% of people)

Left Coronary Artery (LCA):

Left main → divides into:
- LAD: anterior LV, anterior septum, apex, RBB, anterior LBB fascicle
- LCx: lateral/posterior LV, SA node in ~40%

Clinical Pearl: LAD occlusion = "widow maker" → anterior STEMI, ST elevation V1-V4.

Conduction System

SA Node (pacemaker, 60-100 bpm)
    ↓ internodal tracts
AV Node (delay ~0.12 sec; backup 40-60 bpm)
    ↓
Bundle of His
    ↓
Right Bundle Branch + Left Bundle Branch
(LBB → Anterior fascicle + Posterior fascicle)
    ↓
Purkinje Fibers → Ventricular myocardium

Action Potential (Ventricular):

Phase	Ion movement	Effect
Phase 0	Fast Na⁺ in	Rapid depolarization
Phase 1	K⁺ out	Early repolarization
Phase 2	Ca²⁺ in + K⁺ out	Plateau (unique to cardiac muscle)
Phase 3	K⁺ out	Rapid repolarization
Phase 4	Na⁺/K⁺ ATPase	Resting membrane potential

The plateau phase (Phase 2) creates a long refractory period, preventing tetany.

PART 2: CARDIAC PHYSIOLOGY

The Cardiac Cycle

Systole:

Isovolumetric contraction - AV valves close (S1), pressure rises, no volume change
Ejection phase - semilunar valves open, blood ejected

Diastole: 3. Isovolumetric relaxation - semilunar valves close (S2), pressure falls, no volume change 4. Rapid filling - AV valves open; 70% of filling occurs here 5. Slow filling - passive 6. Atrial kick (presystole) - active atrial contraction adds last 20-30%

Loss of atrial kick (e.g., AF) reduces CO by 20-30% in stiff ventricles.

Heart Sounds

Sound	Timing	Cause
S1	Start of systole	Closure of mitral + tricuspid valves
S2	End of systole	Closure of aortic + pulmonary valves
S3	Early diastole	Rapid ventricular filling; normal in children; suggests HF in adults
S4	Late diastole	Atrial contraction into stiff ventricle; always pathological

Splitting of S2:

Physiologic: Widens on inspiration (normal)
Wide fixed splitting: ASD
Paradoxical splitting: LBBB, severe AS (P2 before A2)

Determinants of Cardiac Performance

CO = Heart Rate × Stroke Volume (Normal: 4-8 L/min)

1. Preload - LVEDV/LVEDP; Frank-Starling Law: increased stretch → increased force 2. Afterload - SVR (left heart); Laplace's Law: T = P × r / (2 × wall thickness) 3. Contractility - Increased by catecholamines, Ca²⁺; decreased by beta-blockers, acidosis, hypoxia

Contractile Apparatus - Molecular Mechanism

Sarcomere proteins:

Myosin (thick filament): Globular heads with ATPase activity; hinge rotation drives contraction
Titin: Elastic spring anchoring myosin to Z-lines; contributes to diastolic stiffness
Actin (thin filament): Activates myosin ATPase via reversible binding
Tropomyosin: Inhibits actin-myosin interaction at rest
Troponin complex:
- TnC: Ca²⁺ binding - when Ca²⁺ binds, moves tropomyosin, exposes actin
- TnI: Inhibitory subunit (clinical biomarker for MI)
- TnT: Binds to tropomyosin

Excitation-Contraction Coupling:

Action potential → T-tubule depolarization
L-type Ca²⁺ channels open
Ca²⁺-induced Ca²⁺ release (CICR) from SR via ryanodine receptors
Ca²⁺ binds TnC → tropomyosin shifts → actin exposed
Myosin-actin cross-bridge cycling → contraction
Relaxation: Ca²⁺ pumped back into SR (SERCA2a) + Na/Ca exchanger

Coronary Blood Flow Physiology

LV receives blood only during diastole (systolic compression occludes vessels)
Normal flow: ~250 mL/min (5% of CO)
O₂ extraction by LV is near-maximal (~70-80%) at rest → increased demand MUST be met by increased flow

Regulation:

Mechanism	Details
Metabolic	CO₂, adenosine → vasodilation (most important)
Endothelium	NO (vasodilator), endothelin (vasoconstrictor)
Autoregulation	Constant flow over 60-130 mmHg perfusion pressure
Autonomic	α₁: vasoconstriction; β₂: vasodilation

PART 3: CARDIAC PATHOLOGY

Heart Failure (HF)

Definition: Unable to eject blood sufficient to meet metabolic demands OR unable to fill adequately without elevated filling pressure.

Classification by EF

Type	EF	Mechanism	Causes
HFrEF (systolic)	< 40%	Reduced contractility, dilated ventricle	IHD, dilated CM, myocarditis
HFmrEF	40-49%	Intermediate
HFpEF (diastolic)	≥ 50%	Impaired relaxation, stiff ventricle	HTN, HCM, aging, DM, obesity

Pathophysiology:

↓ CO → ↓ tissue perfusion
RAAS activation → Na⁺/H₂O retention → volume overload
Sympathetic activation → compensatory initially, then harmful (remodeling)
Ventricular remodeling: dilation, hypertrophy, fibrosis

Clinical Features:

Left HF: Dyspnea, orthopnea, PND, pulmonary crackles, S3 gallop
Right HF: JVD, peripheral edema, hepatomegaly, ascites

NYHA Classification:

I: No symptoms with ordinary activity
II: Mild symptoms with moderate exertion
III: Symptoms with minimal exertion
IV: Symptoms at rest

GDMT for HFrEF (4 pillars):

Drug class	Examples	Benefit
ACEi / ARB	Enalapril, Losartan	↓ preload/afterload, antiremodeling
ARNI	Sacubitril-Valsartan	Superior to ACEi; ↓ mortality
Beta-blockers	Carvedilol, Metoprolol succinate, Bisoprolol	↓ HR, antiremodeling, ↓ mortality
MRA	Spironolactone, Eplerenone	↓ fibrosis, diuresis
SGLT2i	Dapagliflozin, Empagliflozin	↓ HF hospitalizations, ↓ mortality
Loop diuretics	Furosemide	Symptom relief only
ICD	EF < 35%	Prevent sudden cardiac death
CRT	EF < 35% + LBBB	Resynchronization

Ischemic Heart Disease (IHD)

Pathogenesis: Endothelial injury → LDL oxidation → macrophage foam cells → fatty streak → fibrous plaque → vulnerable plaque (thin cap, lipid core) → rupture → thrombosis → ACS

Angina Pectoris

Type	Mechanism	ECG	Relief
Stable	Fixed stenosis, demand ↑	ST depression on exertion	Rest/nitrates
Unstable	Plaque rupture, partial occlusion	ST depression/T-inversion at rest	Hospitalization, antithrombotic
Variant (Prinzmetal)	Coronary vasospasm	ST elevation at rest	Nitrates/CCB

Acute Coronary Syndrome (ACS)

STEMI:

Complete occlusion → transmural infarction
ECG: ST elevation in contiguous leads; new LBBB
Sequence: Hyperacute T waves → ST elevation → Q waves → T inversion
Management: Primary PCI within 90 min (door-to-balloon time)

NSTEMI:

Partial occlusion → subendocardial infarction
ECG: ST depression, T-wave inversion (no ST elevation, no Q waves)
Troponin elevated
Management: Antiplatelet + anticoagulation + early invasive strategy

Localization by ECG:

Territory	Vessel	Leads
Anterior	LAD	V1-V4
Lateral	LCx	I, aVL, V5-V6
Inferior	RCA	II, III, aVF
Posterior	RCA/LCx	ST depression V1-V3; confirm V7-V9
Septal	LAD (septal perforators)	V1-V2

Complications of MI:

Hours: Arrhythmias (VF - most common early death), heart block (inferior MI)
Days (3-5): Free wall rupture, VSD, papillary muscle rupture → acute MR
Weeks: Dressler syndrome, LV aneurysm, mural thrombus

Hypertension

Classification (ACC/AHA 2017):

Stage	BP
Normal	< 120/80
Elevated	120-129 / < 80
Stage 1 HTN	130-139 / 80-89
Stage 2 HTN	≥ 140 / ≥ 90
Hypertensive Crisis	> 180 / > 120

Secondary HTN causes:

Renal artery stenosis, CKD
Primary hyperaldosteronism (Conn syndrome)
Pheochromocytoma, Cushing syndrome
OSA, hyperthyroidism
Drugs: NSAIDs, OCP, cocaine, steroids

Target organ damage: LVH, diastolic dysfunction, HF, IHD, stroke, CKD, hypertensive retinopathy, aortic dissection

Management:

Lifestyle: DASH diet, Na restriction, weight loss, exercise
First-line drugs: ACEi/ARB + thiazide diuretics + CCBs
Hypertensive emergency: IV nitroprusside, labetalol, nicardipine

Cardiac Arrhythmias

Supraventricular

Atrial Fibrillation (AF):

Irregularly irregular; absent P waves; narrow complex
Causes: HTN, HF, valve disease, hyperthyroidism, alcohol
Risk: Stroke (LA appendage thrombus)
CHA₂DS₂-VASc for stroke risk; anticoagulate if ≥ 2 (men) / ≥ 3 (women)
Rate control: Beta-blocker, diltiazem, digoxin
Rhythm control: Cardioversion, antiarrhythmics, ablation

SVT (AVNRT/AVRT):

Narrow complex, regular, abrupt onset/offset
Treatment: Vagal maneuvers → Adenosine → CCB/beta-blocker → cardioversion

Ventricular

Arrhythmia	Rate	QRS	Treatment
PVCs	Variable	Wide, bizarre	Beta-blockers if symptomatic
VT	> 100 bpm	Wide > 120 ms	Stable: amiodarone; Unstable: DC cardioversion
VF	Chaotic	Irregular	Immediate defibrillation + CPR

Torsades de Pointes:

Polymorphic VT; causes: Long QT (drugs), hypokalemia, hypomagnesemia
Treatment: IV Magnesium sulfate + remove causative agent

Heart Block

Degree	Features	Management
1st	PR > 200 ms; all P waves conduct	None
2nd Mobitz I	Progressive PR lengthening until P drops	Observe
2nd Mobitz II	Constant PR; sudden dropped QRS	Pacemaker
3rd (Complete)	P and QRS dissociated	Pacemaker

Valvular Heart Disease

Aortic Stenosis (AS)

Classic triad: Syncope, Angina, Heart Failure (SAD)
Murmur: Crescendo-decrescendo systolic ejection murmur; right upper sternal border; radiates to carotids
Pulse: Pulsus parvus et tardus
Severe: Valve area < 1.0 cm², mean gradient > 40 mmHg
Management: TAVR or surgical AVR when symptomatic or EF < 50%

Aortic Regurgitation (AR)

Causes: Bicuspid AV, rheumatic, IE, Marfan, syphilis
Murmur: Early diastolic decrescendo; left sternal border; leaning forward
Signs: Water-hammer pulse, wide pulse pressure, De Musset's sign, Quincke's sign, Austin Flint murmur
Management: ACEi/ARBs; surgery when severe/symptomatic

Mitral Stenosis (MS)

Almost always rheumatic
Murmur: Low-pitched diastolic rumble at apex; opening snap; loud S1
Severe: MV area < 1.5 cm²
Complications: AF, pulmonary HTN, right HF, emboli
Management: Diuretics, rate control, anticoagulation; PBMV or MVR

Mitral Regurgitation (MR)

Causes: MVP, rheumatic, ischemia, IE, dilated CM
Murmur: Holosystolic high-pitched at apex; radiates to axilla
Surgery: When severe with EF < 60% or LVESD > 40 mm

Infective Endocarditis (IE)

Duke Criteria - Major:

Positive blood cultures (≥2 typical organisms)
Echo: vegetation, abscess, new valvular regurgitation

Duke Criteria - Minor:

Predisposing condition/IVDU
Fever ≥ 38°C
Vascular phenomena (Janeway lesions, emboli)
Immunologic phenomena (Osler's nodes, Roth spots, +RF)
Single positive blood culture

Definite IE: 2 major / 1 major + 3 minor / 5 minor

Organisms:

Patient	Organism
Native valve (community)	Streptococcus viridans (most common)
IV drug user	Staphylococcus aureus; right-sided (tricuspid)
Prosthetic valve (early)	Staph epidermidis, Staph aureus
Colon cancer	Streptococcus bovis → do colonoscopy!

Peripheral signs:

Janeway lesions: Painless, hemorrhagic (palms/soles) - septic emboli
Osler's nodes: Painful, nodular (fingers/toes) - immune complex
Roth spots: Retinal hemorrhages with pale centres
Splinter hemorrhages

Pericardial Disease

Acute Pericarditis

Causes: Viral (Coxsackie B), TB, autoimmune, post-MI (Dressler)
Clinical: Sharp pleuritic pain, relieved sitting forward; friction rub
ECG: Diffuse saddle-shaped ST elevation + PR depression (no reciprocal changes)
Management: NSAIDs + Colchicine (reduces recurrence)

Cardiac Tamponade

Beck's Triad: Hypotension + JVD + Muffled heart sounds
Pulsus paradoxus > 10 mmHg
ECG: Electrical alternans
Management: Emergency pericardiocentesis

Constrictive Pericarditis

Causes: TB (most common worldwide), radiation, viral
Features: Kussmaul's sign, pericardial knock, "square root sign"
Management: Pericardiectomy

Cardiomyopathies

Type	Pathology	Key Features	Management
Dilated CM	Enlarged, thin-walled; systolic dysfunction	Most common CM; causes: ischemic, alcoholic, viral, peripartum	GDMT for HFrEF
HCM	Asymmetric septal hypertrophy; diastolic dysfunction; LVOT obstruction	Most common cause of SCD in young athletes; SAM of MV; murmur increases with Valsalva/standing	BB/CCB; ICD; myectomy or alcohol ablation
Restrictive CM	Stiff ventricle; normal cavity	Causes: Amyloidosis, sarcoidosis, hemochromatosis, eosinophilic	Treat underlying cause
ARVC	Fibro-fatty RV replacement	Epsilon waves on ECG; VT/VF risk	ICD; beta-blockers

Aortic Dissection

Intimal tear → blood enters media → false lumen
Risk: HTN (most common), Marfan, bicuspid AV, cocaine
Stanford A: Ascending aorta → Emergency surgery
Stanford B: Descending only → Medical management (BB + vasodilators); endovascular if complicated
Clinical: Tearing/ripping chest pain radiating to back; unequal BP in arms
Diagnosis: CT angiography (gold standard)

PART 4: CARDIOVASCULAR PHARMACOLOGY

Antihypertensives

Class	Examples	MOA	Side Effects
ACE Inhibitors	Enalapril, Ramipril, Lisinopril	Block ACE → ↓ AngII	Dry cough (bradykinin), angioedema, hyperkalemia, teratogenic
ARBs	Losartan, Valsartan	Block AT1 receptor	Angioedema (rare), hyperkalemia, teratogenic
ARNI	Sacubitril-Valsartan	Neprilysin inhibition + AT1 block	Angioedema (DO NOT combine with ACEi), hypotension
Thiazides	HCTZ, Chlorthalidone	Block NCC in DCT	Hypokalemia, hyperuricemia, hyperglycemia, hypercalcemia
Loop Diuretics	Furosemide, Bumetanide	Block NKCC2 in TAL	Hypokalemia, ototoxicity, metabolic alkalosis
K-sparing Diuretics	Spironolactone, Amiloride	Block aldosterone/ENaC	Hyperkalemia; spironolactone: gynecomastia
DHP CCBs	Amlodipine, Nifedipine	L-type Ca²⁺ block (vessels)	Peripheral edema, reflex tachycardia, flushing
Non-DHP CCBs	Diltiazem, Verapamil	Ca²⁺ block (heart + vessels)	AV block, constipation, worsens HF
Beta-blockers	Metoprolol, Carvedilol, Atenolol	Block β1 (±β2)	Bradycardia, bronchospasm, masks hypoglycemia

Antiarrhythmics (Vaughan-Williams)

Class	Mechanism	Drugs	Uses
Ia	Na⁺ block (moderate); ↑ QT	Quinidine, Procainamide	AF, VT
Ib	Na⁺ block (fast); ↓ QT	Lidocaine, Mexiletine	VT, digoxin toxicity
Ic	Na⁺ block (slow); no QT change	Flecainide, Propafenone	AF (no structural heart disease)
II	Beta-blockers	Metoprolol, Esmolol	AF, SVT, post-MI
III	K⁺ block; ↑ QT	Amiodarone, Sotalol	VT, VF, AF
IV	Non-DHP CCBs	Diltiazem, Verapamil	SVT, AF rate control
Misc	-	Adenosine	SVT (half-life 10 sec)
Misc	-	Digoxin	AF rate control; narrow TI

Amiodarone toxicities (long t½ ~40-55 days): Pulmonary fibrosis, thyroid (hypo/hyper), hepatotoxicity, corneal microdeposits, photosensitivity, blue-grey skin, peripheral neuropathy, bradycardia, ↑ QT

Anticoagulants

Drug	Target	Monitoring	Reversal
Warfarin	Vit K epoxide reductase → ↓ II,VII,IX,X	INR (target 2-3)	Vitamin K, FFP, 4-factor PCC
UFH	Antithrombin → inhibits IIa, Xa, IXa	aPTT	Protamine sulfate
LMWH	Mainly anti-Xa	Not routine	Partial: protamine
Dabigatran	Direct thrombin (IIa) inhibitor	ECT/dTT	Idarucizumab
Rivaroxaban/Apixaban	Direct Factor Xa inhibitors	Not routine	Andexanet alfa

Antiplatelets

Drug	MOA	Uses
Aspirin	Irreversible COX-1 inhibition → ↓ TXA2	ACS, stroke prevention, post-PCI
Clopidogrel	P2Y12 ADP antagonist (prodrug, CYP2C19)	ACS, post-PCI (DAPT)
Ticagrelor	Reversible P2Y12 (not prodrug)	ACS (PLATO trial - preferred over clopidogrel)
Prasugrel	Irreversible P2Y12 (prodrug)	ACS with PCI; avoid in prior stroke

Statins

Block HMG-CoA reductase → ↓ LDL synthesis + ↑ LDL receptors
Pleiotropic: ↓ inflammation, plaque stabilization
High intensity: Atorvastatin 40-80 mg, Rosuvastatin 20-40 mg
Side effects: Myopathy, rhabdomyolysis (rare), transaminase ↑

PART 5: CVS CLINICAL SKILLS

ECG Systematic Reading

Rate → Rhythm → Axis → P waves → PR → QRS → QT → ST/T → Assessment

Normal values:

HR: 60-100 bpm
PR interval: 120-200 ms
QRS: < 120 ms
QTc: < 440 ms (M), < 460 ms (F)
Axis: -30° to +90°

Axis deviation:

Left axis: LBBB, LAHB, LVH, inferior MI
Right axis: RBBB, RVH, pulmonary HTN, lateral MI

🫁 RESPIRATORY SYSTEM - Complete Medical Student Guide

PART 1: RESPIRATORY ANATOMY

Upper Respiratory Tract

Trachea: Starts at C6; 10-15 cm; bifurcates at carina (T4/sternal angle)
Larynx: C3-C6; vocal cords; epiglottis protects airway during swallowing

Tracheobronchial Tree

Zone	Generations	Purpose
Conducting (dead space ~150 mL)	0-16	Air conduction only; no gas exchange
Respiratory	17-23	Gas exchange (respiratory bronchioles → alveolar sacs)

Right bronchus: Shorter, wider, more vertical → foreign bodies lodge in right lower lobe
Left bronchus: Longer, narrower, more horizontal

Lungs:

Right: 3 lobes (upper, middle, lower); 10 bronchopulmonary segments
Left: 2 lobes (upper, lower) + lingula; 8-10 segments

Alveoli - Gas Exchange Unit

~300-500 million alveoli; surface area ~70-80 m²
Type I pneumocytes (~95% surface area): Gas exchange; flat, squamous
Type II pneumocytes (~5%): Produce surfactant (DPPC/lecithin); progenitor cells; host defense proteins
Alveolar macrophages: First-line immune defense
Blood-gas barrier: Alveolar epithelium → basement membrane → capillary endothelium = ~0.3-0.5 µm

PART 2: RESPIRATORY PHYSIOLOGY

Lung Volumes and Capacities

Volume/Capacity	Normal	Definition
Tidal Volume (VT)	500 mL	Volume per breath
IRV	3000 mL	Max extra inspiration above VT
ERV	1200 mL	Max extra expiration below VT
Residual Volume (RV)	1200 mL	Air after maximal expiration
Vital Capacity (VC)	4800 mL	IRV + VT + ERV
FRC	2400 mL	ERV + RV; end-quiet-expiration volume
TLC	6000 mL	All volumes combined

RV, FRC, and TLC cannot be measured by spirometry - need helium dilution, N₂ washout, or body plethysmography.

Spirometry - Obstructive vs Restrictive

Pattern	FEV1	FVC	FEV1/FVC	TLC	Causes
Obstructive	↓↓	Normal/↓	< 0.70	Normal/↑	COPD, Asthma, Bronchiectasis
Restrictive	↓	↓↓	Normal or ↑	↓	IPF, Pleural effusion, NMD, Obesity
Mixed	↓	↓	< 0.70	↓	Sarcoidosis, some COPD

Respiratory Mechanics

Compliance

C = ΔVolume / ΔPressure (Normal lung ~200 mL/cmH₂O)

↓ Compliance (stiff)	↑ Compliance (floppy)
Pulmonary fibrosis, ARDS, pulmonary edema, NRDS	Emphysema, aging

Surfactant:

Produced by Type II pneumocytes
Lowers surface tension (LaPlace's law: P = 2T/r; prevents alveolar collapse)
Deficient in premature infants (<32 weeks) → NRDS
Treatment: Antenatal betamethasone; exogenous surfactant (beractant)

Airway Resistance

Poiseuille's Law: R = 8ηL / πr⁴ (resistance inversely proportional to 4th power of radius)

Medium bronchi (3rd-4th generation) contribute most resistance
↑ Resistance: bronchospasm, mucosal edema, secretions, foreign body

Gas Exchange

V/Q Ratio

Normal overall V/Q = 0.8 (ventilation ~4 L/min; CO ~5 L/min)

Regional differences (upright):

Region	V/Q	Features
Apex (Zone 1)	> 1	Low perfusion; high O₂, low CO₂
Middle (Zone 2)	~0.8	Normal
Base (Zone 3)	< 1	High perfusion; low O₂, high CO₂

West Zones:

Zone 1: PA > Pa > Pv → No flow (not normally present; occurs in hemorrhage or PPV)
Zone 2: Pa > PA > Pv → Flow = Pa - PA
Zone 3: Pa > Pv > PA → Continuous flow (most blood flow)

V/Q Mismatch → Hypoxemia:

Low V/Q: Hypoxemia (responds to O₂)
True shunt (V/Q = 0): Hypoxemia NOT corrected by 100% O₂ (atelectasis, consolidation)
High V/Q: Dead space → mainly hypercapnia

5 Mechanisms of Hypoxemia:

Hypoventilation - ↑ CO₂ displaces O₂; A-a gradient normal
Diffusion impairment - IPF; worsens on exercise
V/Q mismatch - Most common; responds to O₂
True shunt - Does NOT respond to 100% O₂
Low FiO₂ - High altitude

A-a gradient = PAO₂ - PaO₂; Normal < 10-15 mmHg; elevated in V/Q mismatch, shunt, diffusion impairment; normal in hypoventilation.

Hb-O₂ Dissociation Curve

Shift RIGHT (↓ O₂ affinity, ↑ delivery to tissues): ↑ Temperature, ↑ 2,3-DPG, ↑ CO₂, ↓ pH (Bohr effect), exercise

Shift LEFT (↑ O₂ affinity, ↓ delivery): ↓ Temperature, ↓ 2,3-DPG, ↓ CO₂, ↑ pH, HbF, CO poisoning, methemoglobin

O₂ Content: CaO₂ = (Hb × 1.34 × SaO₂) + (0.003 × PaO₂)

CO₂ Transport

70%: As HCO₃⁻ (carbonic anhydrase in RBCs) - Chloride shift
23%: Carbaminohaemoglobin (bound to Hb)
7%: Dissolved in plasma

Haldane Effect: Deoxygenated Hb binds more CO₂ → facilitates CO₂ unloading at lungs.

Control of Breathing

Respiratory centres (brainstem):

Pre-Bötzinger complex (medulla): Rhythm generator
Dorsal Respiratory Group (NTS): Inspiration
Pneumotaxic centre (upper pons): Limits inspiration
Apneustic centre (lower pons): Sustained inspiration (overridden by pneumotaxic)

Central chemoreceptors (ventral medulla):

Respond to ↑ PCO₂ → ↓ CSF pH
Primary drive to breathe in normal individuals
Slow response; insensitive to PO₂

Peripheral chemoreceptors (carotid + aortic bodies):

Carotid bodies most important (CN IX → NTS)
Respond to: ↓ PaO₂ (< 60 mmHg), ↑ PCO₂, ↓ pH
Fast response (seconds)

COPD Clinical Pearl: Chronic CO₂ retention desensitizes central chemoreceptors → "hypoxic drive" via peripheral chemoreceptors. High-flow O₂ suppresses this → CO₂ retention risk.

Acid-Base - Respiratory Component

Disorder	pH	PaCO₂	HCO₃⁻	Compensation
Respiratory Acidosis	↓	↑	↑	Acute: +1 mEq/L per 10 mmHg ↑ CO₂; Chronic: +3.5 mEq/L
Respiratory Alkalosis	↑	↓	↓	Acute: -2 mEq/L per 10 mmHg ↓ CO₂; Chronic: -5 mEq/L

Causes Respiratory Acidosis: COPD, sedatives/opioids, NMD, severe asthma, pneumothorax

Causes Respiratory Alkalosis: Anxiety, pregnancy, salicylates (early), high altitude, mechanical ventilation, sepsis (early)

PART 3: RESPIRATORY DISEASES

COPD

Definition: Persistent, largely irreversible airflow limitation; FEV1/FVC < 0.70 post-bronchodilator

	Chronic Bronchitis ("Blue Bloater")	Emphysema ("Pink Puffer")
Mechanism	↑ mucus, airway inflammation, narrowing	Alveolar wall destruction, ↓ elastic recoil
Cause	Smoking; cough ≥3 months/yr for ≥2 yrs	Smoking; α1-antitrypsin deficiency (young, panacinar)
Hypoxia	Severe, early cyanosis	Mild; compensatory hyperventilation
CO₂ retention	Common	Rare until late

Emphysema subtypes:

Centrilobular: Smoking; upper lobes
Panacinar: α1-antitrypsin deficiency; lower lobes
Paraseptal (distal acinar): Young adults; associated with spontaneous pneumothorax

GOLD Classification (FEV1 % predicted):

GOLD 1 (Mild): ≥ 80%
GOLD 2 (Moderate): 50-79%
GOLD 3 (Severe): 30-49%
GOLD 4 (Very Severe): < 30%

Stable COPD Management:

Smoking cessation (most important - only intervention reducing mortality)
Bronchodilators: SABA → SAMA → LABA → LAMA (tiotropium)
ICS: Add for frequent exacerbations; ICS + LABA combination
Triple therapy: ICS + LABA + LAMA
Pulmonary rehabilitation
LTOT: PaO₂ ≤ 55 mmHg (or ≤ 60 mmHg with polycythemia/cor pulmonale) → ≥ 15 hrs/day → ↓ mortality
Influenza + pneumococcal vaccines
Roflumilast (PDE4 inhibitor): Severe + chronic bronchitis

COPD Exacerbation Management:

O₂: Target SpO₂ 88-92%
Nebulized SABA + ipratropium
Systemic corticosteroids (prednisolone 40 mg × 5 days)
Antibiotics if purulent sputum
NIV (BiPAP): If pH < 7.35 + ↑ CO₂ → ↓ intubation, ↓ mortality

Asthma

Definition: Chronic inflammatory airway disease with episodic, reversible airflow obstruction and bronchial hyperresponsiveness

Pathophysiology:

Allergen → IgE-mediated mast cell degranulation → histamine, leukotrienes → bronchoconstriction
Th2 inflammation (eosinophils, mast cells)
Airway remodeling in chronic/severe asthma

Triggers: Allergens, cold air, exercise, NSAIDs (aspirin-exacerbated), beta-blockers, smoke, viral URTI

Step-up Therapy:

Step	Treatment
1	SABA PRN
2	Low-dose ICS + SABA PRN
3	Low-dose ICS + LABA
4	Medium-high ICS + LABA
5	High ICS + LABA ± LAMA ± oral corticosteroids
Severe (Biologic)	Anti-IgE (Omalizumab), Anti-IL5 (Mepolizumab), Anti-IL4/13 (Dupilumab)

Acute Severe Asthma (Status Asthmaticus):

Life-threatening signs: Silent chest, bradycardia, confusion, normal/↑ PaCO₂ (should be LOW in asthma - if normal = very severe)
Management: O₂ (SpO₂ 94-98%), nebulized SABA q20 min, ipratropium, IV/oral steroids, IV Magnesium sulfate 2g over 20 min, IV aminophylline, intubation if deteriorating

Pneumonia

Classification:

Type	Common Pathogens
CAP	S. pneumoniae (most common), Mycoplasma, Legionella, H. influenzae
HAP (> 48 hrs)	Gram-negatives (Pseudomonas, Klebsiella), S. aureus (MRSA)
Aspiration	Anaerobes, mixed flora
Atypical ("walking")	Mycoplasma, Chlamydophila, Legionella

Typical vs Atypical:

Feature	Typical (S. pneumoniae)	Atypical (Mycoplasma)
Onset	Acute, sudden	Gradual
Fever	High, rigors	Low-grade
CXR	Lobar consolidation	Diffuse/bilateral patchy
Sputum	Purulent, productive	Non-productive
Treatment	Amoxicillin	Macrolide, Doxycycline

CURB-65 (mortality predictor):

Criterion	Score
Confusion (new)	1
Urea > 7 mmol/L	1
RR ≥ 30	1
BP < 90 systolic or < 60 diastolic	1
Age ≥ 65	1

0-1: Outpatient | 2: Inpatient | 3-5: ICU consideration

Legionella pneumophila:

Gram-negative intracellular; grows in water systems (cooling towers)
Features: Pneumonia + GI + CNS + hyponatremia + ↑ LDH + lymphopenia
Diagnosis: Urinary antigen (serogroup 1); culture on BCYE agar
Treatment: Macrolide or fluoroquinolone (NOT beta-lactams)

Pulmonary Tuberculosis (TB)

Mycobacterium tuberculosis - acid-fast bacillus (Ziehl-Neelsen stain)

Primary TB: Ghon focus (mid-lung) + hilar node = Ghon complex; usually asymptomatic; heals with calcification

Post-Primary (Reactivation): Apical/posterior upper lobes; cavitation, caseation necrosis; symptoms: cough, hemoptysis, weight loss, night sweats, evening fever

Diagnosis:

AFB smear and culture (Lowenstein-Jensen medium; 6-8 weeks)
GeneXpert MTB/RIF: Fast + detects rifampicin resistance
Mantoux (TST): ≥10 mm = positive; ≥5 mm in immunocompromised/HIV
IGRA: More specific, unaffected by BCG vaccination
CXR: Apical infiltrates, cavitation, calcification

Standard Regimen:

Phase	Drugs	Duration
Intensive (RIPE)	Rifampicin + Isoniazid + Pyrazinamide + Ethambutol	2 months
Continuation	Rifampicin + Isoniazid	4 months
Total		6 months

Drug toxicities:

Drug	Key Side Effects
Rifampicin	Orange urine/secretions, hepatotoxicity, enzyme inducer (↓ OCP, warfarin)
Isoniazid	Peripheral neuropathy (B6 deficiency → give pyridoxine), hepatotoxicity, drug-induced SLE
Pyrazinamide	Hyperuricemia (gout), hepatotoxicity
Ethambutol	Optic neuritis (monitor visual acuity monthly)

Pulmonary Embolism (PE)

Risk Factors (Virchow's Triad):

Stasis: Immobility, post-surgery, long flights
Hypercoagulability: Factor V Leiden, antiphospholipid syndrome, malignancy, OCP
Endothelial injury: Trauma, surgery

Wells Score:

Criterion	Points
DVT symptoms/signs	3
PE more likely than alternative	3
HR > 100	1.5
Surgery/immobility last 4 weeks	1.5
Prior DVT/PE	1.5
Hemoptysis	1
Active malignancy	1

Score > 4: High probability → CTPA
Score ≤ 4: Low probability → D-dimer first

Investigations:

ECG: Sinus tachycardia (most common); S1Q3T3 (classic but not specific)
CXR: Often normal; Westermark sign, Hampton's hump
ABG: Hypoxemia, hypocapnia, respiratory alkalosis, ↑ A-a gradient
CTPA: Gold standard
V/Q scan: If CTPA contraindicated

Management:

Massive PE (hemodynamically unstable): Systemic thrombolysis (alteplase); surgical embolectomy if contraindicated
Stable PE: Anticoagulation with DOACs (rivaroxaban/apixaban preferred)
Duration: 3 months (provoked); ≥ 3 months (unprovoked/malignancy)

Pleural Diseases

Pleural Effusion - Light's Criteria

Exudate if ANY one met:

Pleural protein / serum protein > 0.5
Pleural LDH / serum LDH > 0.6
Pleural LDH > 2/3 upper limit of normal serum LDH

Transudate	Exudate
Heart failure (most common)	Pneumonia (parapneumonic)
Cirrhosis	Malignancy
Nephrotic syndrome	TB
Hypoalbuminemia	PE, RA, SLE

Pneumothorax

Type	Cause	Features
Primary spontaneous	Young, tall, thin males; blebs	No underlying disease
Secondary spontaneous	COPD (bullae), TB, CF, Marfan	Underlying lung disease
Tension	Valve effect traps air	Emergency: trachea deviates AWAY, ↓ breath sounds, hypotension, JVD

Management:

Small primary (< 2 cm): Observe; high-flow O₂ (4× absorption rate)
Large/symptomatic: Needle aspiration or chest tube (ICD)
Tension: Immediate needle decompression (2nd ICS, MCL) → then chest tube

Interstitial Lung Disease (ILD)

Key features: Restrictive pattern, diffusion impairment, bibasal Velcro crackles, ground-glass opacities on HRCT, clubbing (IPF)

ILD	Associations	HRCT Pattern
IPF	Elderly male smokers; poor prognosis (median 2-3 yrs)	UIP: Basal, subpleural honeycombing + traction bronchiectasis
NSIP	Autoimmune (scleroderma, SLE, PM/DM)	Ground-glass opacities, basal fibrosis
COP	Post-infection/drug	Consolidation + GGO, peribronchovascular
Sarcoidosis	Young adults; bilateral hilar lymphadenopathy	Micronodules along lymphatics; upper lobe
Hypersensitivity Pneumonitis	Organic dust (farmer's lung - thermophilic actinomycetes; bird fancier's lung)	Acute: GGO; Chronic: fibrosis
Asbestosis	Occupational; ↑ mesothelioma risk	Basal fibrosis + pleural plaques
Silicosis	Occupational; mining, sandblasting	Upper lobe nodules; "eggshell" calcification of hilar nodes

Treatment of IPF: Pirfenidone or Nintedanib (anti-fibrotic; slow progression); lung transplant for end-stage

Lung Cancer

Most common cause of cancer death worldwide

Type	Location	Key Features
Squamous Cell	Central (hilar)	Cavitates; PTHrP → hypercalcemia; Pancoast tumor
Adenocarcinoma	Peripheral	Most common in non-smokers/women; EGFR/ALK mutations; lepidic growth pattern
Small Cell (SCLC)	Central	Neuroendocrine; oat cells; paraneoplastic syndromes; highly aggressive
Large Cell	Peripheral	Undifferentiated; poor prognosis

Paraneoplastic syndromes:

Syndrome	Cancer
Hypercalcemia (PTHrP)	Squamous cell
SIADH (hyponatremia)	SCLC
Ectopic ACTH → Cushing	SCLC
Lambert-Eaton Myasthenic Syndrome (anti-VGCC)	SCLC
Hypertrophic osteoarthropathy / clubbing	Adenocarcinoma
Trousseau's syndrome (migratory thrombophlebitis)	Adenocarcinoma

SVC Syndrome:

Compression/invasion of SVC
Features: Facial/arm/neck edema, JVD, dilated chest wall veins, Pemberton's sign
Most common cause: SCLC, lymphoma

Pancoast Tumor (Superior Sulcus):

Apex of lung → invades brachial plexus, subclavian vessels, stellate ganglion
Horner's syndrome: Ptosis, miosis, anhidrosis, enophthalmos
Shoulder/arm pain (C8/T1/T2 distribution)
Treatment: Chemoradiation → surgery

Treatment:

NSCLC I-II: Surgery (lobectomy) ± adjuvant chemo
NSCLC III: Concurrent chemoradiation
NSCLC IV: Platinum chemo; targeted (EGFR: osimertinib; ALK: crizotinib); Immunotherapy (pembrolizumab if PD-L1 +)
SCLC Limited: Chemo + radiation (cisplatin/etoposide) + PCI
SCLC Extensive: Chemotherapy + atezolizumab

Cystic Fibrosis (CF)

Autosomal recessive; CFTR gene (chromosome 7q); most common lethal AR disease in Caucasians
Most common mutation: ΔF508 (deletion Phe 508)
CFTR = Cl⁻ channel; defect → thick viscous secretions

Clinical features:

System	Manifestations
Respiratory	Chronic cough, bronchiectasis, recurrent pneumonias (Pseudomonas aeruginosa), pneumothorax, respiratory failure
GI/Pancreatic	Meconium ileus, pancreatic exocrine insufficiency, CF-related diabetes
Reproductive	Male infertility (CBAVD); ↓ female fertility
Other	Sinusitis, nasal polyps, clubbing, salt depletion

Diagnosis:

Newborn screening: IRT + CFTR mutation
Sweat chloride test (gold standard): Cl⁻ > 60 mmol/L = diagnostic

Management:

Airway clearance: Chest physiotherapy, hypertonic saline, dornase alfa (DNase)
Antibiotics: Inhaled tobramycin/aztreonam (chronic Pseudomonas); IV for exacerbations
Pancreatic enzyme replacement (Creon); fat-soluble vitamins (A, D, E, K)
CFTR modulators:
- Ivacaftor (G551D mutation)
- Elexacaftor + Tezacaftor + Ivacaftor (Trikafta/Kaftrio): ΔF508 - transforms outcomes
Lung transplant (bilateral): End-stage

Obstructive Sleep Apnea (OSA)

Repetitive upper airway obstruction during sleep
Risk factors: Obesity, male, age, retrognathia, tonsillar hypertrophy
Symptoms: Snoring, witnessed apneas, daytime sleepiness, morning headaches
Complications: HTN (most common), AF, pulmonary HTN, cor pulmonale, cognitive impairment
Diagnosis: Polysomnography; AHI: mild 5-14, moderate 15-29, severe ≥ 30
Management: CPAP (first-line, most effective)

Mechanical Ventilation

Lung Protective Ventilation (ARDSnet):

Tidal volume: 6 mL/kg ideal body weight
Plateau pressure: < 30 cmH₂O
Adequate PEEP
Permissive hypercapnia (pH > 7.20 acceptable)
Prone positioning 16 hrs/day for severe ARDS (PaO₂/FiO₂ < 150) → ↓ mortality

NIV (BiPAP) indications:

COPD exacerbation (pH < 7.35 + ↑ CO₂)
Cardiogenic pulmonary edema
Type II respiratory failure
OSA (CPAP)

QUICK REVISION TABLES

CVS Key Facts

Topic	Key Point
Most common cause of HF	IHD/ischemic cardiomyopathy
HFrEF EF threshold	< 40%
4 pillars GDMT	ARNI + Beta-blocker + MRA + SGLT2i
STEMI treatment	Primary PCI < 90 min
Most common valvular disease (developed world)	Aortic stenosis
AS classic triad	Syncope, Angina, Heart Failure
Most common cause of MS	Rheumatic fever
HCM murmur increases with	Valsalva / standing (↓ preload)
Most common IE organism (native valve)	Streptococcus viridans
Aortic dissection Type A	Emergency surgery
Dabigatran reversal	Idarucizumab
Xa inhibitor reversal	Andexanet alfa

Respiratory Key Facts

Topic	Key Point
Cannot measure by spirometry	RV, FRC, TLC
Obstructive spirometry	FEV1/FVC < 0.70
Most common cause of hypoxemia	V/Q mismatch
Hypoxemia NOT corrected by 100% O₂	True shunt
COPD most important intervention	Smoking cessation
COPD LTOT indication	PaO₂ ≤ 55 mmHg
COPD NIV indication	pH < 7.35 + ↑ CO₂
Most common CAP organism	Streptococcus pneumoniae
Atypical pneumonia treatment	Macrolide/doxycycline
TB total duration	6 months (2 RIPE + 4 RI)
Ethambutol toxicity	Optic neuritis
Massive PE treatment	Systemic thrombolysis (alteplase)
IPF treatment	Pirfenidone or Nintedanib
CF most common mutation	ΔF508
CF CFTR modulator for ΔF508	Elexacaftor/Tezacaftor/Ivacaftor (Trikafta)
OSA first-line treatment	CPAP
ARDS protective ventilation TV	6 mL/kg IBW

Sources: Barash's Clinical Anesthesia 9e | Braunwald's Heart Disease | Fuster & Hurst's The Heart 15e | Murray & Nadel's Textbook of Respiratory Medicine | Katzung's Basic & Clinical Pharmacology 16e

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