Cardio

Anatomy
- Primitive heart tube
o Truncus arteriosus -> aorta, pulmonary trunk
o Bulbis cordis -> smooth part of ventricles
o Primitive ventricle -> rough part (trabeculae carnae) of ventricles
o Primitive atrium -> trabeculated part of atria
o Sinus venosus -> smooth part of ventricles, coronary sinus
- Fetal circulation = oxygenated blood from placenta reaches fetus via 1 umbilical vein,
drained back to placenta via 2 umbilical arteries
o Blood circumvents pulmonary circulation via foramen ovale & ductus arteriosus
- Pericardium = outer fibrous (parietal) pericardium and inner visceral epicardium with a
pericardial space
o Pericarditis = inflammation of pericardium (viral, bacterial, Dressler’s)
o Cardiac tamponade = pericardial effusion -> Beck’s triad (distended neck veins,
hypotension, muffle heart sounds)
o Pericardiocentesis = left subxiphoid (15o) or 5/6th left ICS (45o)
- Heart chambers
o Right atrium = crista terminalis (SA node), pectinate muscle, triangle of Koch (AV
node)
o Right ventricle = rough trabeculae carnae, 3 papillary muscles, tricuspid +
pulmonary valves, moderator band (right bundle branch)
o Left atrium = base of heart, pectinate muscle
o Left ventricle = rough trabeculae carnae, 2 papillary muscles, mitral + aortic valve
- Coronary circulation
o RCA = right atrium/ventricle, SA/AV nodes, pos. 1/3 of interventricular septum
▪ Dominance determined by vessel that gives off PDA -> usually RCA
o LCA = left atrium/ventricle, anterior 2/3 of interventricular septum
▪ Gives off LAD and circumflex
o Cardiac sinus = drains great/middle/small cardiac veins into right atrium
▪ Anterior cardiac veins drain directly into right atrium
- Auscultatory areas
o Aortic (R 2nd ICS), pulmonic (L 2nd ICS), tricuspid (L 3/4th ICS), mitral (L 5th ICS)
o 1st heart sound (lub) = tricuspid/mitral closure, 2nd heart sound (dub) =
aortic/pulmonary closure
- Conduction pathway = SA node -> AV node -> bundle of HIS -> Purkinje fibres
Physiology
Cardiac muscle
- Contraction relaxation = depolarization -> Ca influx (L-type channels) -> release of Ca
from SR (ryanodine receptors) -> Ca binds troponin -> muscle contraction -> Ca pumped
back into SR (SERCA) + out of cell (Na/Ca exchanger, CaATPase) -> relaxation
o Strength of contraction proportional to intracellular [Ca]
o Longer AP due to increased Ca and low K conductance (plateau phase)
- Conduction = SA node -> atrial contraction -> AV node (slow conduction) -> bundle of His
-> Purkinje fibres (fast conduction) -> ventricular contraction
o Works as a syncytium via gap junctions and T-tubules for rapid conduction
o Nodal AP = funny pacemaker current (spontaneous depolarization) due to slow
Na influx, AP due to Ca influx
▪ Nodal tissue has long refractory period
- ANS control
o Sympathetic = Gs adrenergic receptor -> increases cAMP -> increased gap
junctions + Na channel stimulation + increased Ca influx and storage -> positive
ionotropy, dromotropy, chronotropy -> shortens refractory period
o Parasympathetic = Gi muscaranic receptor -> decreases cAMP -> negative
ionotropy (atria), dromotropy, chronotropy -> increases refractory period
- Cardiac cycle
o Systole = AV valves close -> isovolumetric contraction -> increase in ventricular
pressure -> semilunar valves open -> ejection
▪ Afterload = pressure the heart works against = aortic pressure
● Afterload is directly related to ventricular size and pressure,
inversely related to ventricular wall thickness
o Diastole = semilunar vales close -> isovolumetric relaxation -> AV valves open ->
ventricular filling
▪ Preload = initial stretching due to ventricle filling = end diastolic volume
● Frank-Starling mechanism = increased preload -> increase muscle
stretch -> increase the force of contraction -> increase CO
● Sympathetic stimulation -> increased ionotropy -> increased
contractility -> decreased end systolic volume -> increased CO ->
ESPVR slope increases and Frank-Starling curve shifts upwards
- Jugular venous pressure = measurement taken to determine right atrial pressure
o Elevated in right ventricular failure, tricuspid regurgitation, SVC obstruction,
constrictive pericarditis, volume overload
- Heart sounds
o S1 = closure of AV valves
o S2 = closure of semilunar valves
o S3 = oscillation of blood in ventricles -> early diastolic ventricular gallop
o S4 = forceful ejection into stiff ventricle -> late diastolic atrial gallop
- Cardiac output = HR x SV = ∆P / R = MAP / TPR
o CO depends on exercise, age, size, Frank-Starling mechanism, SA node stretching,
venous return, Bainbridge reflex (atrial stretch), tissue metabolism
o TPR = MAP – CVP -> CVP usually = 0
o Fick principle -> CO = lung O2 / arteriovenous O2 difference
o Increase in venous return increases CO
 o Increase in venous return increases CO
- Venous return = peripheral venous pressure – central venous pressure / vein resistance
o Lung expansion -> decreased right atrial pressure + increased abdominal venous
pressure -> increased venous return -> increased CO
▪ Valsalva stops venous return
o Muscular contractions pumps venous blood back to heart -> one way valves
o Decreased compliance increases peripheral venous pressure -> C = ∆V / ∆P
- Mean circulatory pressure = equilibrium pressure in absence of flow (7mmHg)
o Infusion or vasoconstriction (SANS) will increase it, hemorrhage or an increase in
blood flow will decrease it
- Coronary circulation = primarily aerobic (FFA B-oxidation) but uses anaerobic glycolysis
in ischemic conditions -> greatest blood flow during diastole
o Active hyperemia = increased blood flow due to metabolic demands (primary
controller of blood flow)
▪ NO (cGMP) & PGI2 (cAMP) induce vasodilation during exercise
▪ Adenosine increases cAMP -> vasodilation in ischemia
▪ Endothelial dysfunction (atherosclerosis) increases endothelin release
which decreases NO/PGI2 release
o Reactive hyperemia = increased blood flow due to vasoconstriction
▪ Myogenic response = increased pressure -> increased vessel diameter and
wall stress -> myogenic vasoconstriction to decrease vessel diameter and
wall stress
o Rate pressure product = indicates myocardial uptake of O2
EKG

- Waves & intervals

o P wave = atrial depolarization
▪ P-R interval = beginning of P wave to beginning of Q wave -> 0.12-0.20s
o QRS complex = ventricular depolarization, <0.12s
▪ Q-T interval = beginning of Q wave to end of T wave -> systole
o T wave = ventricular repolarization
▪ S-T segment = begins with J point -> slow rise to peak of T wave -> can be
horizontal in women
o U wave = Purkinje repolarization -> seen in V3
▪ Prominent in hypokalemia, inverted in MI
- Axis = mean direction of depolarization -> -30o to + 90o
o Tangent of net QRS deflections in lead I and aVF determine axis
Pathophysiology
Congenital abnormalities
- Dextrocardia = heart lies on left side of heart -> left looping of heart tube
- Tetralogy of Fallot = VSD + over-riding aorta + right ventricular hypertrophy + pulmonary
artery stenosis -> cyanosis at birth

- Patent ductus arteriosus = leads to pulmonary hypertension

- Coarctation of aorta = narrowing near PDA -> upper extremity hypertension + lower
extremity hypotension + rib notching
Cardiac cycle abnormalities
- Aortic stenosis = increased afterload -> end systolic volume increases -> decreased CO ->
ESPVR slope decreases
- Mitral stenosis = decreased preload -> end diastolic volume decreases -> decreased CO
- Aortic regurgitation = end diastolic volume increases + increased end systolic volume ->
slightly increased CO
- Mitral regurgitation = end diastolic volume increases + decreased end systolic volume ->
increased CO
- Murmurs = due to increased blood velocity and turbulence
o Systolic murmurs = tricuspid/mitral regurgitation, aortic/pulmonic stenosis, VSD
o Diastolic murmurs = tricuspid/mitral stenosis, aortic/pulmonic regurgitation
o Right sided murmurs louder on inspiration, left sided louder on expiration
Hypertrophy = increase in cell/nuclear size via increased protein synthesis -> due to increased
afterload (hypertension) or preload (valve insufficiency, anemia) -> altered gene expression
(ATII, ET1, I-GF, SERCA, etc.)
- Concentric hypertrophy = thickening of ventricular myocardium with normal or
decreased volume due to pressure overload
o Systemic hypertension will cause left sided hypertrophy while pulmonary
hypertension will cause right sided hypertrophy
- Eccentric hypertrophy = dilation of ventricular myocardium with increased volume due
to volume overload
Heart failure = inability to pump to meet metabolic needs
- Risk factors = CAD, MI, chronic hypertension, valvular diseases, congenital defects,
arrythmias, myocarditis, cardiomyopathies, diabetes, old age, smoking, etc.
- Compensatory mechanisms = increased SANS, Frank-Starling, hypertrophy, RAAS, ADH,
natriuretic peptides, catecholamines -> increase contractility + vasoconstriction +
increase venous return + increase blood volume + increased ventricular compliance ->
prevent blood stasis & maintain TPR
o Angiotensin II -> increased Na/water resorption, vasoconstriction, cardiac
remodelling, interstitial fibrosis

- Signs = dilated ventricles & pulmonic vessels, Kerley lines (fluid between lung lobes),
heart failure cells (hemosiderin laden macrophages in alveoli)
 - Diagnosis = ECG (blocks, arrythmias), echocardiogram (ejection fraction), exercise
testing, coronary arteriography
- NYHA classification = I (no limitations in activity), II (slight limitation), III (marked
limitation), IV (no physical activity)
- HFrEF = systolic dysfunction due to decreased contractility -> poor pumping -> decreased
SV and EF < 50%
o Symptoms = paroxysmal nocturnal dyspnea, orthopnea, hemoptysis, chest pain,
fatigue, nocturia, elevated HR/respirations, diaphoresis, left sided hypertrophy,
systolic murmurs (mitral regurgitation – S3 gallop), pulmonary edema, etc.
- HFpEF = diastolic dysfunction due to decreased ventricular compliance -> poor
ventricular relaxation and filling -> decreased EDV -> decreased SV but EF remains > 50%
o Usually due to left sided heart failure or hypertension
o Isolated right heart failure = in patients with lung parenchymal or vasculature
disease (cor pulmonale)
o Symptoms = systemic edema, right sided hypertrophy, portal hypertension,
hepatosplenomegaly, nutmeg liver, hepatic centrilobular necrosis, ascites
- Decompensation = increased fluid retention and cardiac remodelling -> arrythmias,
valve failure -> low CO + high venous pressure -> decreased tissue perfusion -> low renal
fluid excretion -> edema and congestion
o Cytokines mediate cardiomyocyte cell death in heart failure = TNFa, IFNy, Il-1, Il-6
release -> NFkB -> inflammation pathway -> apoptosis -> fibrosis
- Hypertensive heart disease = left ventricular diastolic dysfunction + left ventricular
hypertrophy + heart failure due to systemic hypertension
o Normotensive = no hypertension in any situation
o Sustained hypertension = hypertension in all situations
o Masked hypertension = no hypertension in clinic, hypertension at home
o White coat hypertension = hypertension in clinic, no hypertension at home
o Isolated systolic hypertension = increased systolic BP, normal diastolic BP -> in
elderly secondary to increased CO
EKG abnormalities
- Left ventricular hypertrophy = left axis deviation, ST depression and T inversion (I, aVL,
V5, V6)
- Right ventricular hypertrophy = right axis deviation, ST depression and T inversion (III,
V1-4)
- Wave abnormalities
o Tall P wave = right atrial hypertrophy (cor pulmonale, tricuspid stenosis)
o Bifid P wave = left atrial hypertrophy (mitral stenosis)
o Small QRS = old MI, myocarditis, pericardial effusion
o Tall T wave = hyperkalemia, MI, pericarditis (notched)
- Dysrhythmias
o Sinus bradycardia = <60bpm, prolonged PR interval
o Sinus tachycardia = >100bpm, short PR interval
 o Sick sinus syndrome = SA node dysfunction due to drugs, scarring, CAD, etc. in
patients >50 years -> bradycardia, tachycardia, bradycardia-tachycardia
syndrome, sinus arrest
o Sinus arrythmia = variant R-R interval due to breathing -> increases during
inspiration, decreased during expiration
o Sinus arrest = cardiac standstill due to failure of SA node firing
o Premature atrial contraction = due to ectopic pacemaker -> irregular rhythm,
may have compensatory pause
o Atrial flutter = consistent re-entry pathway causing saw-tooth appearance, no PR
interval, ventricular rate can be regular or irregular
o Atrial fibrillation = patients >75 years with hypertension, atrial hypertrophy,
diabetes, CHF, left ventricular dysfunction, thyrotoxicosis, etc. -> multiple
re-entry pathways, no P waves, irregularly irregular ventricular rhythm -> chest
pain, exercise intolerance, risk of thrombus formation (stroke) -> control rate
(defibrillator or drugs) + give anticoagulants + ablative therapy + pacemaker
▪ Wolf-Parkinson-White syndrome = re-entry via bundle of Kent causing
atrial flutter or fibrillation -> short PR interval, delta wave (slurred QRS
upstroke), prolonged QRS
o Paroxysmal supraventricular tachycardia = due to re-entry pathway between
ventricles and atria -> regular tachycardic ventricular rhythm with narrow
(orthodromic) or wide (antidromic) QRS complexes -> defibrillation if unstable,
vagal maneuvers (carotid massage, Valsalva, cold water to face) if stable
o Premature ventricular contraction = ectopic impulse within ventricle, QRS >0.12s
o V-tach = >3 QRS complexes at a rate of >100bpm, due to ectopic pacemaker or
re-entry, no P waves, QRS >0.12s, can be monomorphic or polymorphic
▪ Torsades de Pointes = polymorphic V-tach due to re-entry in long QT
syndrome -> can degenerate into V-fib -> shorten QT interval with
magnesium
o V-fib = changing re-entry pathways, no rhythm or discernible waves, no
contraction, lethal -> defibrillator
o Asystole = no waves, fatal -> do not use defibrillator
- Conduction blocks
o AV block = PR >0.20s
▪ 1st degree = consistent, generally benign (high vagal tone) -> seen in
inferior MI, hypokalemia, hypomagnesia -> reduced exercise tolerance,
syncope, decreased first heart sound
▪ Mobitz I (2nd degree) = PR interval progressively increases until it is not
conducted to ventricles -> irregular ventricular rhythm -> seen in AV node
ischemia, hyperkalemia, etc. -> atropine or exercise removes condition
▪ Mobitz II (2nd degree) = consistent PR interval until it is not conducted to
ventricles at least twice consecutively -> irregular ventricular rhythm ->
requires pacemaker
 ▪ 3rd degree = no conduction to ventricles via atria, ventricles assume AV
pacemaker rhythm -> regular slow ventricular rhythm (<50bpm) ->
pacemaker required
o Bundle branch block = QRS >0.12s
▪ LBBB = left deviation of axis, progression of W to M QRS complex from
lead V4 to V6
▪ RBBB = normal axis or right deviation, progression of M to W QRS
complex from lead V1 to V5
- MI = ST depression (subendocardial) or elevation + tombstoning (transmural) within the
first few hours -> T wave inversion hours to days after -> permanent Q wave in stable
chronic phase -> axis deviates away from site of injury
Ischemic heart disease
- Causes = coronary atherosclerosis, emboli or vasospasms
- Angina
o Chronic stable = due to ischemia (atherosclerosis) -> occurs on exertion -> ST
depression (1mm in exercise ECG) -> resolution on rest or medication
▪ Pain threshold decreased after meals,
o Unstable = due to thrombus -> can occurs during sleep/rest/exertion, gets worse
over time
o Prinzmetal = coronary vasospasm -> occurs at rest -> ST elevation
- MI = Lack of blood flow -> ischemia -> tissue recovery or death (depletion of ATP) ->
dead tissue replaced by fibrous scar
o Acute response = ATP depletion (first 10 seconds) -> loss of contractility (<2min)
-> reversible changes (1-10min) -> irreversible damage (>20min)
o Causes of death = arrythmia (immediate) -> cardiogenic shock (1-3 days) ->
rupture (3-7 days) -> cardiac failure (>7 days)
o Morphologic changes = no change (<6hrs) -> wavy fibre change (<2 days) ->
coagulative necrosis + neutrophils (2-4 days) -> macrophages (5-7 days) ->
granulation tissue (7-10 days) -> organization of infarct (1-6 weeks) -> collagen
deposition (1-3 months)
o Types
▪ Transmural = due to thrombus/plaque change -> ST elevation
● Can be cause by cocaine
▪ Subendocardial = most susceptible to infarct -> due to atherosclerosis,
global ischemia, quick reperfusion -> ST depression
o Coronary steal phenomenon = dilation of vessels to non-ischemic myocardium
thereby decreasing blood flow to ischemic myocardium
▪ Dilation can be due to exercise or drugs
o Diagnostics
▪ CKMB = falls by 3rd day -> used to diagnose secondary MI
▪ Troponin = falls by 7th day -> used to determine myocardial necrosis
o Complications = arrythmias, reinfarction, Dressler’s syndrome (autoimmune
pericarditis), aneurysm and rupture, cardiac tamponade, heart failure
- Myocardial stunning = reversible contractile impairment due to ischemia
 o Hibernation = cumulative stunning due to recurrent bouts of ischemia
- Contraction band necrosis = due to reperfusion in persistent myocardial ischemia (dead
myocytes) -> neutrophil influx, free radicals, Ca overload, membrane disruption
Arteriosclerosis
- Atherosclerosis = buildup of atherosclerotic plaque -> narrowing of arteries
o Injury = hyperlipidemia, HT (shear stress), tobacco, inflammation, infections ->
effects = lipid accumulation/free radicals, cytokines, necrosis, apoptosis,
thrombosis -> repair = fibrosis
o Risk factors = age, gender, genetics, diabetes, hyperlipidemia, HT, smoking
(primary preventable risk factor), homocysteine, metabolic syndrome
o Hyperlipidemia -> increased circulating LDL -> acylated or oxidized (LOX1) ->
taken up by macrophages (scavenger receptor) -> foam cells -> fatty streak ->
increased adhesion + inflammation -> extracellular lipid accumulation -> fibrous
plaque (lipid core + fibrous cap) -> complicated lesion (intima + media) ->
unstable plaque -> rupture -> thrombus
▪ Oxidized LDL is chemotactic (inflammation), toxic, increases adhesion
▪ Risk of rupture = large lipid core, thin cap, decreased SMCs, increased
macrophages, inflammation, metalloprotease
▪ Statins -> downregulate LOX1, inhibit HMG-CoA reductase, reduce CRP
o Clinical presentation = angina, TIA, intermittent claudication, renovascular HT,
mesenteric ischemia
- Monckeberg medial calcific sclerosis = dystrophic calcification of tunica media in the
lower limb arteries (pipe stem rigidity) or breast (railroad track) of elderly patients -> no
luminal narrowing, usually asymptomatic
- Myocardial bridges = burrowing of coronary vessels into myocardium -> usually
asymptomatic -> prone to coronary steal if given vasodilators
o Proximal segment prone to atherosclerotic plaques
o Diagnosis = half-moon sign (ultrasound), fingertip phenomenon (doppler
measurements), milking effect
Circulatory shock = imbalance between blood supply and demand -> nonprogressive (normal
compensatory mechanisms) -> progressive (therapy required) -> irreversible (end organ
damage) -> death
- Cardiogenic = due to arrythmia, HF, MI, cardiomyopathy, etc.
- Obstructive = cardiac tamponade, tension pneumothorax
- Neurogenic = loss of sympathetic outflow due to spinal injury
- Septic = due to infection
- Anaphylactic = IgE mediated allergic reaction
- Hypovolaemic = hemorrhage, burns, dehydration, etc.
Pharmacology
Antihypertensives
- a1 blockers = Prazosin, tamsulosin -> cause vasodilation and decrease TPR
o Therapeutic uses = hypertension with BPH + good lipid profile
▪ Combined with B-blockers or diuretic
o ADR = first dose syncope, reflex tachycardia, postural hypotension
- B-blockers = decrease CO (negative ionotropy/chronotropy) + renin release
o Therapeutic uses = performance anxiety, glaucoma, hypertension, MI,
pheochromocytoma (with a1 blockers first), arrythmias, migraines
o ADR = bronchospasm, sedation, masks hypoglycemia (insulin drugs), poor lipid
profile, sexual dysfunction, precipitate vasospasm (Prinzmetal angina, PVD),
additive depression (digitalis, verapamil), decreased effectiveness with NSAIDs,
rebound angina
o Non-selective B blockers = propranolol, timolol -> also used in glaucoma
o B1 blockers = atenolol, esmolol, metoprolol -> safe for asthmatics/COPD patients
▪ Esmolol is short acting -> acute SVT
o B-blockers with ISA = pindolol, acebutolol -> useful in HTN with DM, PVD,
asthma/COPD, abnormal lipid profile
o Mixed B blocker = labetalol (pheochromocytoma) and carvedilol (congestive
heart failure, pregnancy)
- a2 agonists = clonidine, methyldopa -> reduce sympathetic flow from vasomotor center
o Therapeutic uses = hypertension in pregnant/renal failure patients (methyldopa),
opiate withdrawal
o ADR = sedation, increased prolactin/positive Coombs test (methyldopa), edema,
rebound hypertension
- Ganglionic blockers = trimethaphan
- Hormone synthesis inhibitors = reserpine, guanethidine (blocked by cocaine), bretyllium
- Calcium channel blockers -> block L-type Ca channels in arteries
o Therapeutic uses = HTN patients with asthma/DM/PVD/angina, arrythmia,
cerebral vasospasm (nicardipine)
o ADR = constipation (verapamil), reflex tachycardia/ginigival hyperplasia (dipines),
peripheral edema
o Verapamil, diltiazem = cardiac vasodilators
▪ Contraindicated in CHF/AV block
o Dihydropyridine = nimodipine -> vascular vasodilators
▪ Increased risk of MI (reflex tachycardia) with short acting nifedipine
- Direct acting vasodilators
o Hydralazine = release NO -> arteriolar dilation -> pregnancy induced HTN -> can
cause edema, reflex tachycardia, Lupus like syndrome
o Nitroprusside = release NO -> vasodilation -> hypertensive emergencies ->
tolerance resistant -> can cause CN poisoning
▪ CN poisoning treatment = nitrite + sodium thiosulfate/B12
o Minoxidil/diazoxide = open K channels -> arteriolar dilation -> HTN, baldness
 - D1 agonist = fenoldopam -> arteriolar dilator -> increases renal perfusion -> HTN with
renal insufficiency -> can cause glaucoma
- ACE inhibitors = captopril -> blocks ATII formation -> vasodilation, decrease aldosterone
o Therapeutic uses = HTN, protects against diabetic nephropathy, CHF (decreases
preload AND afterload + blocks heart remodelling), post MI
o ADR = dry cough (bradykinin), hyperkalemia, angioedema, teratogenic, not used
in bilateral renal artery stenosis
- ARBs = losartan -> blocks ATI receptor -> same effects as ACE inhibitors WITHOUT dry
cough
- Renin inhibitor = aliskiren -> can cause diarrhea and acute renal failure
- CA inhibitors = acetazolamide -> block Na/H exchanger in PCT
o Therapeutic uses = glaucoma, acute mountain sickness, metabolic alkalosis,
alkalinize urine, epilepsy
o ADR = acidosis, hypokalemia, renal stones
- Loop diuretics = furosemide, bumetanide, ethacrynic acid -> block Na/K/2Cl transport in
ALH + increased PG synthesis (vasodilation)
o Therapeutic uses = acute pulmonary edema (CHF), HTN, edema
o ADR = alkalosis, NSAIDs block vasodilation, hypokalemia, hypomagnesia,
hypovolemia, HSR (furosemide = sulfa drug), hyperuricemia, ototoxicity (don’t
use with aminoglycosides)
- Thiazide diuretics = chlorothiazide -> blocks Na/Cl symporter in DCT + enhances Ca
resorption + opens K channels (vasodilation)
o Therapeutic uses = HTN, edema, nephrogenic diabetes insipidus, kidney stones
o ADR = alkalosis, hypokalemia, hyperuricemia, hyperglycemia, hypercalcemia,
hyperlipidemia
- K sparing diuretics = spironolactone, eplerenone-> blocks aldosterone induced proteins
in collecting duct
o Amiloride/triamterene does not depend on aldosterone
o Therapeutic uses = hyperaldosteronism, prevents cardiac remodelling
(spironolactone), nephrogenic diabetes insipidus (amiloride)
o ADR = acidosis, hyperkalemia, gynecomastia/dysmenorrhea
- Osmotic diuretics = mannitol -> water excretion along entire tubule -> used for
glaucoma, increase ICP
IHD/angina drugs
- Nitrates = release NO -> increased cGMP -> dephosphorylation of MLC -> SMC relaxation
-> decrease preload (venodilation) + increase collateral circulation + relieve vasospasm
o Therapeutic uses = acute angina, stable angina (+ B blockers), Prinzmetal angina
(+ Ca channel blockers), CN poisoning, esophageal spasm, biliary colic
o ADR = tachyphylaxis (overcome via nitrate free period), postural hypotension,
reflex tachycardia, methemoglobinemia, severe hypotension if given with Viagra
- Dipyridamole = coronary vasodilator -> worsens angina (coronary steal)
- Ca channel blockers = verapamil, diltiazem, dipines = arteriolar/coronary vasodilation ->
decrease afterload -> used for all angina, especially Prinzmetal angina
 - B blockers = decrease force of contraction and HR -> decreased O2 demand + blocks
reflex tachycardia -> increased exercise tolerance (stable angina)
o Pindolol/acebutolol (ISA) contraindicated
- Ranolazine = reduces late Na current -> reduced Ca concentration -> less diastolic
tension
- Trimetazidine = pFOX inhibitor -> inhibits b-oxidation pathway in cardiomyocytes
- Ivabradine = inhibits funny Na channel -> bradycardic drug
- Aspirin = low dose inhibits TXA2 -> decreased platelet aggregation
- Morphine = decreases preload and HR
CHF drugs
- Low salt diet, avoid NSAIDs/B-blockers/Ca channel blockers (verapamil, diltiazem)
- Ionotropic agents = increase contractility
o Digoxin/digitoxin = inhibit Na/K pump -> blocks Na/Ca exchanger -> more
intracellular Ca -> increased contractility without increased O2 demand +
increased vagal activity + decreased sympathetic activity
▪ ADR = narrow TI (excreted in urine), GI distress, vision disturbance,
▪ Toxicity = causes arrythmias -> exacerbated by quinidine, hypokalemia,
verapamil -> treat with atropine or digibind (anti-digoxin Abs)
o Dobutamine = B1 agonist -> acute heart failure
▪ ADR = tachyphylaxis
o Dopamine = D1 agonist -> cardiogenic shock in MI
o Amrinone/milrinone = PDE3 inhibitor -> increased cAMP -> increase contractility
+ decrease afterload (vasodilation)
- Diuretics = decrease preload and afterload
o Spironolactone -> prevents cardiac remodelling
▪ ADR = endocrine abnormalities -> use eplerenone
- Vasodilators = decrease preload and afterload
o Captopril = ACE inhibitor -> vasodilation + reduced Na retention + prevents
cardiac remodelling
▪ ADR = dry cough, hyperkalemia, teratogenic
o Losartan = ARB -> patients intolerant to ACE inhibitors (no dry cough)
o Sacubitril = inhibits neprilysin -> increased natriuretic peptide release
o Nesiritide = recombinant BNP -> vasodilation -> acute decompensated HF
o Hydralazine/nitrates = NO -> decreases afterload/preload -> decompensated
refractory HF
- B blockers = decrease cardiac remodelling -> for chronic HF management
Antiarrhythmics
- Class Ia = block open/activated Na channels -> increase AP duration + ERP
o Quinidine = used for a-fib
▪ ADR = proarrhythmic due to muscarinic/a1 block, cinchonism (tinnitus, GI
distress, etc.), prolonged QRT/QT interval, hypokalemia
o Procainamide = also blocks K channels -> less autonomic effects
▪ ADR = Lupus like syndrome, hematotoxicity
- Class Ib = block inactivated Na channels -> decrease AP duration + ERP
 o Lidocaine = DoC for post-MI ventricular arrythmia
▪ ADR = seizures
- Class Ic = non-selective Na channel block
o Flecainide = very proarrhythmic -> last resort
- Class II = B blockers -> decrease SA/AV node activity -> prolong ERP -> used for V-fib
o Therapeutic uses = pheochromocytoma/halothane arrythmia, SVT (esmolol),
prophylaxis in post-MI
- Class III = K channel blockers -> increased AP duration + ERP
o Amiodarone = used for all arrythmias
▪ ADR = pulmonary fibrosis, blue skin
- Class IV = Ca channel blockers -> decrease nodal activity
o Verapamil/diltiazem = used for SVT
▪ ADR = AV block, constipation
- Unclassified
o Adenosine = decrease nodal activity -> DoC for PSVT/AV nodal arrythmias
▪ ADR = bronchospasm, higher dose in tea drinkers
o Magnesium = used in torsades
Drugs for dyslipidemia
- Statins = HMG-CoA reductase inhibitors -> decrease LDL
o ADR = rhabdomyolysis when combined with niacin, fibrates, verapamil or
amiodarone, hepatotoxicity
- Niacin = decrease HSL in adipose tissue -> increase HDL
o ADR = flushing/pruritis (take aspirin), hyperuricemia, acanthosis nigricans
- Fibrates = activate PPARa + LPL -> decreases TAG
o ADR = gallstones, myopathy
- Cholestyramine/colestipol/colesevelam = bile acid sequestrants -> used in isolated
increases of LDL
- Ezetimibe = inhibits intestinal cholesterol absorption -> decreased LDL
- EPA/DHA = fish oils -> decreased TAG
- Alirocumab/evolocumab = PSCK9 inhibitors -> improves LDL clearance
Cardio
Pathophysiology
Inflammatory heart disease
- Endocarditis
o Infectious = usually bacterial and left sided -> fever, Janeway lesions, splinter
hemorrhage, Roth’s spots, Osler nodes (red tender blanchable nodules on
fingers/toes), large irregular vegetations on valve cusps that extend into chordae
▪ Prosthetic valve endocarditis with metallo-B-lactamase producing
pseudomonas
▪ Predisposing factors = endothelial injury, turbulent flow, bacteremia,
IVDU, dental procedures, cardiac surgery, etc.
● Right sided seen in IVDU (S. aureus, pseudomonas)
o Give Nafcillin -> vancomycin in MRSA
▪ Prophylaxis (vancomycin + rifampin + gentamycin) given in patients with
prosthetic heart valves, previous infective endocarditis, congenital heart
diseases, transplant patients
o Non-infective = seen in patients with malignancy (mucinous adenocarcinoma),
hypercoagulability, scarred valves
▪ Nonbacterial thrombotic/marantic endocarditis = small vegetations
attached to lines of closure -> seen in hypercoagulability states
(paraneoplastic syndromes)
▪ Liebman-Sacks endocarditis = seen in SLE -> eosinophilic vegetations on
both sides of AV valves, fibrosis and deformity
- Myocarditis = causes dilated cardiomyopathy, patchy necrosis
o Infectious
▪ Chagas (T. cruzi) -> dilated myocardiopathy

▪ Candida -> micro abscesses in myocardium -> pseudo hyphae/germ tubes

in biopsy
▪ Toxoplasma -> bradyzoites inside of a pseudocyst and free tachyzoites in
the myocardium
▪ Coxsackie B -> lymphocytic myocarditis
o Non-infectious = due to HSR (eosinophilia), rheumatic fever, sarcoid
- Pericarditis = can cause pericardial effusion and cardiac tamponade
o Acute = primarily viral (infectious) -> chest pain, palpitations, fever, dyspnea,
pericardial friction rub, non-specific EKG (reciprocal ST depression and PR
elevation ONLY in aVR and V1)
 o Pericardial effusion = hoarseness, dyspnea, cough, dysphagia, muffled heart
sounds, no apical impulse, low voltage QRS, QRS alternans, water bottle
appearance/displaced epicardial fat pad on CXR -> treat with pericardiocentesis
▪ Fast rate can cause cardiac tamponade
o Cardiac tamponade = obstruction of ventricular diastolic filling due to pericardial
effusion -> low CO -> dyspnea, chest pain, weakness, drowsiness, oliguria,
paradoxical pulse -> sudden death or shock
▪ Becks triad = absent heart sounds, distended jugular veins, hypotension
o Dressler’s syndrome = inflammation of pericardium/pleura due to autoimmune
response following surgery, blunt trauma or MI -> chest pain/fever weeks to
months after -> can cause pleural effusion (used echo), cardiac tamponade,
restrictive pericarditis, hemorrhagic pericarditis (don’t give anticoagulants)
o Chronic pericarditis = fibrosis/adhesions leads to loss of pericardial sac -> normal
cardiac function
o Chronic constrictive pericarditis = thickened/scarred/contracted pericardium ->
impaired ventricular filling -> low CO -> exercise intolerance, malaise, pericardial
knock, muffled heart sounds -> can progress to left/right sided heart failure ->
only treatment is pericardiotomy
- Rheumatic heart disease = 2-3 weeks after pharyngitis in children 5-15 years ->
antibodies against GAS M protein that attacks heart glycoproteins -> causes pancarditis
-> pericarditis (fibrinous) + myocarditis (multinucleated Aschoff bodies) + endocarditis
(small warty vegetations due to fibrinoid necrosis along lines of closure of mitral/aortic
valves) -> can lead to congestive heart failure
o Chronic RHD -> thickened valve leaflets, fused chordae tendinae, thickened
leaflets with commissural fusion (fish mouth/buttonhole) -> leads to mitral
stenosis/insufficiency and left atrial dilation -> TEE is best diagnostic tool
o Jones criteria = 2 major + 1 minor symptom
▪ Major = migratory polyarthritis, carditis, subcutaneous nodules, erythema
marginatum, Sydenham chorea
▪ Minor = fever, arthralgias, elevated liver enzymes, increased ESR,
prolonged PR interval
Congenital heart diseases -> usually have chromosomal anomalies (NOTCH, trisomy)
- Left-to-right shunts -> NO cyanosis -> right sided volume overload -> irreversible
pulmonary hypertension -> RVH -> reversal of flow @ 40 years (Eisenmenger syndrome)
causes cyanosis, exertional dyspnea, arrythmia, etc. -> treatment before shunt reversal
o ASD = defect in atrial septum (primum, secundum, sinus venosus) -> rumbling
mid diastolic murmur (large ASD), fixed wide split S2
▪ Osteum primum can present with mitral insufficiency
o VSD = large VSD usually membranous -> RVH/pulmonary hypertension present at
birth -> holosystolic murmur, recurrent pulmonary infections (large VSD)
 o PDA = connection between aorta and pulmonary trunk -> wide pulse pressure,
enlarged heart, continuous harsh machinery like murmur -> give indomethacin
o AVD = endocardial cushion defect -> communication between atria and ventricles
-> variable cyanosis
o Gerbode defect = shunt between left ventricle and right atrium -> enlarged right
heart -> load harsh pansystolic murmur, elevated jugular venous pressure,
peripheral edema -> heart failure and death
▪ Can be acquired due to surgery/PCI (iatrogenic) or infection (GAS, staph)
- Right-to-left shunt -> cyanosis -> associated with polycythemia, hypertrophic
osteoarthropathy, paradoxical emboli -> requires left-to-right shunt to survive
o Persistent truncus arteriosus = failure of aorta and pulmonary trunk to separate
-> pulmonary volume overload
o Tetralogy of Fallot = VSD + Right ventricular hypertrophy + Overriding Aorta +
Pulmonary stenosis -> boot heart -> maintain PDA with prostaglandin E1
▪ Pink tet = minor pulmonary stenosis -> left-to-right shunt instead

▪ Tet spells = cyanosis/syncope on crying/fever/exercise -> squatting

compensates by increasing TPR
o Transposition of great vessels = RVH + thin LV -> maintain PDA with prostaglandin
▪ Situs inversus = mirror image of situs solitus

▪ Kartagener syndrome = primary ciliary dyskinesia -> mirror image

dextrocardia, immotile sperm
o Total anomalous venous return = pulmonary arteries drain into right atrium ->
hypoplastic left atrium, normal left ventricle, large right atrium
o Pulmonary stenosis/atresia = hypoplastic right ventricle -> increasing cynosis with
increased stenosis
o Aortic stenosis = obstructs LV outflow tract -> left ventricular hypertrophy
▪ Aortic atresia = left ventricular hypoplasia

▪ Severe cases require PDA

o Hypoplastic left heart syndrome = left ventricular/aortic hypoplasia ->
immediate death with cyanosis
o Coarctation of aorta
▪ Infantile/preductal form = with PDA -> cyanosis in lower extremities, RVH,
death in infancy
▪ Adult/postductal form -> no PDA -> hypotension in lower extremities,
hypertension in upper extremities, LVH, rib notching, seen in Turners
o Ebstein’s anomaly = tricuspid valve displaced downwards -> large right atrium +
small right ventricle -> S3, S4, pansystolic murmur, WPW (bundle of Kent)
 o Truncus arteriosus = single vessel from heart -> associated with VSD
Cardiomyopathies -> leads to monomorphic VT/a-fib due to scarring/fibrosis (re-entry) -> death
- Dilated cardiomyopathy = can be genetic mutation in all myocyte proteins
(cytoskeleton, sarcomere, membrane, etc.), or due to viral infection, alcohol
consumption, pregnancy -> dilation of all heart chambers -> lack of force generation ->
systolic dysfunction -> heavy/flabby/ovoid heart, patchy fibrosis, arrythmias, mural
thrombi, decreased ejection fraction (echo) -> B-agonists/ACE inhibitors
- Hypertrophic cardiomyopathy = always AD genetic mutation in sarcomeres (myosin)
with no history of hypertension -> hypertrophic left ventricle/atrium (>1.5cm) AND
intraventricular septum + systolic anterior motion of the mitral valve -> myofiber
disarray + fibrosis -> decreased compliance/diastolic filling + left ventricular outflow
tract obstruction + mitral regurgitation (SAM) -> transient hypotension/near syncope,
dilated/double apical impulse, sudden death in young athletes -> B-blockers
o Yamaguchi’s disease = left ventricular outflow tract obstruction due to contact
between hypertrophied intraventricular septum and ventricular wall

- Restrictive cardiomyopathy = seen in amyloidosis, hemochromatosis, sarcoidosis,

doxorubicin toxicity, glycogen storage diseases -> dilation of both atria but not ventricles
-> patchy fibrosis -> decreased diastolic filling
o Endomyocardial fibrosis = idiopathic fibrosis of endocardium/subendocardium in
African children
o Loeffler endomyocarditis = eosinophilic fibrosis in 50 year old men
o Endocardial fibroelastosis = fibroelastosis of endocardium of left ventricle in
children <2 years -> associated with congenital heart defects
o Amyloidosis = deposition of amyloid -> stiffening of ventricles -> amorphous pink
glassy substance (Congo red stain) and yellow-brown amyloid deposits (grossly)
▪ Types of deposition = amyloid light chain (multiple myeloma), amyloid
fibril protein/SAA (autoimmune, NSAIDs), transthyretin (neuropathies),
B-amyloid (Alzheimer’s, Downs), B2-microglobulin (chronic renal failure)
o Naxos syndrome = arrhythmogenic right ventricular cardiomyopathy ->
plakoglobin mutation -> hyperkeratosis of soles
- Takotsubo cardiomyopathy = sudden temporary weakening of the heart (apical
hypokenisis) due to stress induced catecholamine release -> common in
postmenopausal women -> elevated BNP/catecholamines, microcirculation dysfunction,
apical ballooning
 - Ischemic cardiomyopathy = CAD -> myocardial stunning (ATP depletion), hibernation
(glycogen plaques) -> cardiac remodelling (dilation -> scarring) and impaired left
ventricular function
Aneurysms
- True aneurysm = all 3 layers -> fusiform (circumferential) or saccular (outpouching)
atherosclerotic weakening of aortic wall -> pulsatile mass, widening of mediastinum
o Thoracic aortic aneurysm = ascending aorta due to Marfan (cystic medial
necrosis), aortic arch/descending aorta due to atherosclerosis
o Abdominal aortic aneurysm = usually below renal arteries in older men with CVD
or who smoke -> use ultrasound
- False aneurysm = cavity lines by a blood clot
- Dissecting aneurysm = seen in hypertension (40-60 years), trauma, Marfan syndrome
(fibrillin gene mutation in younger aged patients, cystic medial degeneration) ->
tearing/stabbing pain radiating to back, cardiac tamponade, double-barrel aorta ->
perform repair if aneurysm is >5.5cm
o Atherosclerosis and scarring prevents dissection
o Type A = ascending aorta, type B = arch and/or descending aorta
- Syphilitic (3o) aneurysm = obliterative endarteritis of vasa vasorum -> tree barking of
ascending aorta, cor bovinum (LVH)
- Berry aneurysm = congenital defect (ADPKD) in cerebral vasculature (ACA and AcommA)
with thickened hyalinized intima -> rupture due to stress -> thunderclap headache
Degenerative valvular diseases
- Mitral stenosis = seen in rheumatic heart disease (more common in women),
calcification in elderly -> normal left ventricle -> left atrial dilation + fibrosis + myocyte
disarray (a-fib) -> opening snap
o Ortner’s syndrome = compression of left recurrent laryngeal nerve due to left
atrial dilation -> hoarseness
- Calcific aortic stenosis = deterioration and heaped up calcification of aortic valves due to
wear and tear in patients >65 years -> leads to outflow obstruction and LV concentric
hypertrophy -> recurrent angina/syncope, dyspnea
o Congenital bicuspid aortic valve presents earlier with calcifications
o RHD can cause an even earlier presentation (30-60 years)
- Mitral valve prolapse = seen in Turners, ADPKD, connective tissue disorders ->
myxomatous degeneration of mitral valve -> midsystolic click, ballooning of valve leaflets
- Artificial valve complications = calcification/stenosis of porcine valve = life threatening ->
emergency valve replacement
o Cardiac transplant rejection = lymphocytic infiltrate + intact internal elastic
lamina/media
o Mechanical heart valve -> thrombi due to stasis -> give warfarin
Neoplastic cardiac diseases – most common is due to lung metastases -> pericardial effusion
- Rhabdomyoma = benign (hamartoma) white masses in myocardium of children with
tuberous sclerosis -> PAS+ (glycogen vacuoles), HMB45+
 - Cardiac myxoma = benign hemorrhagic tumor with mononuclear infiltrate occurring in
left atria (fossa ovalis) of adults -> can cause cerebral emboli & extend into mitral valve
- Carcinoid heart disease = endocardia fibrotic lesions involved right ventricle/tricuspid

Respi
Anatomy
- Thoracic wall = made up of 12 ribs, sternum and vertebrae
o Movement = anteroposterior (rib 1-6 pump handle), transverse (rib 7-10 bucket
handle), vertical (diaphragm)
- Pleura = parietal (pain sensitive) and visceral (pain insensitive)
o Recesses = costomediastinal and costodiaphragmatic

o
- Alveoli = type I pneumocytes (endoderm) for gas exchange, type II pneumocytes
(splanchnic mesoderm) secrete surfactant
Physiology
Pulmonary system
- Pulmonary functions = ventilation, gas transfer, acid-base balance, enzymes (NO, ACE),
phonation, defense mechanisms (mucocilliary apparatus)
- Gas flow = convection/mass flow in airways/blood, diffusion across membranes in
alveoli/target tissues
- Respiratory apparatus = trachea -> bronchi -> bronchioles -> alveolar ducts -> alveoli
o No cartilage bronchioles onward -> more prone to obstruction
o Respiratory membrane = lipid soluble gases (O2/CO2) readily diffuse through
alveolar/capillary membranes
- Mechanics of breathing
o Inspiration = descent of diaphragm + elevation of ribs -> chest cavity expansion
▪ Forced inspiration -> external intercostals + accessory muscles
o Expiration = passive relaxation of diaphragm + elastic recoil
▪ Forced expiration -> internal intercostals + abdominal muscles
- Lung volumes
o Vt = normal breathing (500mL)
o IRV = maximal inhalation above Vt (3000mL)
o ERV = maximal exhalation below Vt (1100mL)
o RV = volume remaining in lung after maximal exhalation (1200mL)
o IC = Vt + IRV
o FRC = IRV + RV
o VC = Vt + IRV + ERV
 o TLC = Vt + IRV + ERV + RV
- Pulmonary circulation = right atrium -> pulmonary arteries (deoxygenated) -> respiratory
exchange -> pulmonary veins (oxygenated) -> left atrium
- Bronchial circulation = bronchial arteries from aorta carry oxygenated blood to lung
parenchyma -> drain into pulmonary veins (venous admixture)
- Pulmonary hemodynamics = equal flow to system circulation but lower resistance and
arterial pressure due to increased compliance
o Exercise = increased CO -> recruitment of nonperfused capillaries + distension
o Hemorrhage = decrease in CO -> decruitment of capillaries + vasoconstriction
o Regional blood flow = greater blood flow/perfusion at base of lungs due to
gravity
o Net filtration pressure = greater in pulmonary system -> compensated by
increased lymphatic drainage
▪ Pulmonary edema -> increased capillary pressure (left sided heart
failure), capillary permeability, interstitial colloid oncotic pressure,
alveolar surface tension (decreased surfactant) OR decreased plasma
colloid oncotic pressure
▪ Pleural effusion = accumulation of fluid in pleural cavity -> blockage of
lymphatic drainage, right heart failure, decreased plasma colloid oncotic
pressure, increased capillary permeability
- Pulmonary vascular resistance = lowest at FRC
o On inspiration -> alveolar vessel are compressed (increased resistance) and
extra-alveolar vessels are relaxed (decreased pressure) -> opposite on inspiration
o PVR increased -> compression of vessels, increased blood viscosity
o PVR decreased -> increased pulmonary pressure/blood volume, increased left
atrial pressure, gravity (hydrostatic)
o Hypoxic pulmonary vasoconstriction = hypoxia/hypercapnia/low pH induce
vasocontraction in pulmonary vessels increasing PVR (opposite for systemic
vascular resistance)
▪ Regional hypoxia -> diversion of blood to well ventilated areas

▪ Global hypoxia -> generalized increase in PVR -> can lead to pulmonary
hypertension
Mechanics of ventilation
- Respiratory pressures = lungs tend to collapse, chest well tends to expand -> balance
between collapsing and expanding pressures at FRC
o Intrapleural pressure = negative at rest due to lymphatic suction and lung/chest
elastic forces -> decreases during inspiration
o Alveolar pressure = 0 at rest -> decreases on inspiration
o Transpulmonary pressure = alveolar pressure – intrapleural pressure
▪ Transpulmonary pressure = lung elastic recoil = increases with inspiration
- Lung compliance = ∆V / ∆P -> distensibility
o Lung expansion -> compliance decreases and elasticity increases -> both lung and
chest wall tend to recoil inward at high lung volume
o Hysteresis = separation of curves in the lung pressure-volume loop
- Lung elasticity = tendency for lung to recoil -> determined primarily by alveolar surface
tension then elastic properties of lung parenchyma
o Alveolar surface tension = collapse prevented by surfactant and alveolar
interdependence
▪ Preterm infants lack surfactant (lecithin:sphingomyelin < 2:1) -> smaller
alveoli tend to drain into larger one and collapse -> atelectasis
- Airflow = Q = ∆P / R
o Laminar flow = slow velocity in small airways
o Turbulent flow = fast velocity in large airways
- Airway resistance = resistance to airflow mainly due to friction
o Greatest total resistance in medium sized bronchi, smaller airways more prone
to occlusion
o Increased lung volume -> increased tension in alveolar walls -> pulling open
airways (traction effect) -> decreased airway resistance
o Sympathetic stimulation decreases airways resistance -> bronchodilation (B2),
decreased mucus secretion while
- Equal pressure point = level in airway where intrapleural pressure equals airway
pressure -> above EPP is compressing force by higher intrapleural pressure
o EPP lowers towards alveoli during forced expiration -> increased airway
resistance and airway limitation
o EPP is on larger airways at high lung volumes -> no airway limitation -> airflow
rate is effort dependent
▪ At lower lung volumes -> airflow rate is effort independent
- Work of breathing = decreased lung compliance + increased airflow resistance ->
increased work of respiration
- Alveolar ventilation = (Vt – Vd) x breaths/min
o Physiological dead space = air that does not participate in gas exchange =
anatomical dead space + alveolar dead space
o End of expiration -> anatomic dead space filled with alveolar air
▪ Air sample near end of inspiration is alveolar air
o End of inspiration -> anatomic dead space filled with atmospheric air
o Base of lung has better alveolar ventilation as the apex is less compliant
- Alveolar gas equation – PAO2 = PiO2 – (PaCO2/R)
- Closing capacity = lung volume at which airways begin to collapse -> less than FRC
- PFT = use spirometry and diffusion capacity of CO to determine pulmonary function
o Advanced PFTs = arterial blood gas, exercise oximetry, 6 minute walk test, peak
flow, maximal inspiratory/expiratory pressures
 o Spirometry = measurement of lung volumes
▪ FEV1 = forced expired volume in 1 second -> indicative of expiratory
resistance
● FEV25-75% = scooping seen in obstructive lung diseases
▪ RV/FRC/TLC cannot be measured via spirometry

▪ Supine -> decreased chest recoil -> decreased ERV/FRC

o DLCO = measure of membrane functionality
▪ Decreased -> decreased surface area (emphysema), increased membrane
thickness (fibrosis), pulmonary hypertension, anemia
▪ Increased = exercise, asthma, pulmonary hemorrhage, polycythemia,
mild left heart failure
Pathophysiology
- Thoracentesis = 9th ICS midaxillary
- Chest tube = 5/6th ICS midaxillary
- Pancoast tumor = lung apex tumor -> compression on sympathetic chain -> Horner’s
syndrome
- Pneumothorax = air in pleural cavity with collapsed lung
- Pulmonary function tests =
- Obstructive lung disease = COPD, asthma, bronchiectasis, CF -> increased compliance
o FEV1 AND FVC are decreased, FEV1/FVC < 70%, FVC < SVC, increased
RV/FRC/TLC/CC, decreased VC with compensatory increase in Vt -> compliance
curve shifts to the left
o Emphysema = loss of alveolar walls -> decrease in lung elasticity and increased
lung compliance -> overinflated lungs, barrel chest
▪ Decreased FEV1 -> lost alveolar elasticity moves EPP downwards -> forced
expiration moves EPP further towards alveoli -> air trapping
● Expire slowly through pursed lips
▪ Higher ventilation at the lung apex

▪ Decreased DLCO
o Aging = increased lung compliance and decreased elastic recoil -> slight increase
in RV/FRC
o Asthma = reversible increase in airway resistance due to bronchospasm and
increased mucus secretion
▪ FEV1 improved with bronchodilators

▪ Increased DLCO
- Restrictive lung disease = intrapulmonary (fibrosis, sarcoidosis, atelectasis, ) or
extrapulmonary (obesity, scoliosis, kyphosis, neuromuscular disorders, pneumothorax)
-> decreased compliance
o FEV1 and FVC are proportionately decreased, FEV1/FVC is normal or above
normal, all lung volumes/capacities are decreased -> compliance curve shifts to
the right
o Pneumothorax = intrapleural pressure equalizes with atmospheric pressure ->
chest wall springs out and lungs collapse -> decreased lung compliance
▪ Tension pneumothorax = mediastinal shift, decreased venous return/CO
Respi
Physiology
- Cell types = type I pneumocytes (gas exchange), type II pneumocytes (surfactant,
replace type I pneumocytes), alveolar macrophages
o Pores of Kohn equalize pressure between alveoli
o Canals of Lambert form bronchoalveolar connections
- Gas flows according to pressure gradients (high to low)
o Tissue gas pressure determined by rate of blood flow and tissue consumption
o Increased O2 demand -> PaO2 maintained by better V/Q matching + increased
O2 extraction -> PvO2 is decreased
o Increased CO2 production -> PaCO2 maintained by increased blood flow +
alveolar excretion
- O2 delivery = determined by ventilation, perfusion and V/Q matching and O2 carrying
capacity (dissolved O2 + Hb concentration + Hb affinity)
o Hb = 4 binding sites for O2 (ferrous form) -> increased affinity as more O2 binds
▪ Ferric Hb = methemoglobin -> cannot bind O2
▪ Hb binding capacity = 1.34mL O2 / g Hb
- O2 dissociation curve
o Left shift = increased O2 affinity -> fetal Hb, Hbs (sickle cell), CO poisoning
▪ CO poisoning = CO binds with much higher affinity to Hb than O2 -> [Hb]
and PaO2 are normal + blood is cherry red (no cyanosis) -> no feedback
mechanism -> use CO oximetry
o Right shift = decreased O2 affinity -> increased PCO2/H+/2,3-BPG/temp
(exercise) -> increased O2 delivery to tissues
▪ Increased 2,3-BPG in prolonged hypoxia -> further shift to right
- CO2 transport = mainly carried as bicarbonate from tissues to lungs
o Chloride enters RBC in exchange for bicarbonate at tissues -> increase venous pH
o Haldane effect = binding of O2 displaces CO2 -> CO2 excretion from lungs
- Myoglobin = 1 higher affinity O2 binding site -> greater concentration in slow twitch
muscles -> used at low PO2 (decreased perfusion)
- A-a gradient = PAO2 – PaO2 -> usually 5-15mmHg
o PAO2 = [(Pb – H2O) x FiO2] – [PaCO2 / 0.8]
o PaO2 decreases with aging -> increased gradient
- Fick’s law of diffusion = diffusion directly proportional to pressure gradient + surface
area + solubility, inversely proportional to membrane thickness
- Diffusion capacity = amount of gas that will diffuse per minute per mmHg
o DLO2 determined via DLCO -> O2 1.23x more diffusible than CO
o DLO2 increases during exercise due to increased blood flow/ventilation + V/Q
matching
o Diffusion limitation = equilibration NOT achieved between alveolar and capillary
gas pressure -> CO, O2 (thick membrane -> fibrosis)
o Perfusion limited = equilibration achieved (PAGas = PaGas) between alveolar
and capillary gas pressure -> CO2, O2 (normal)
▪ O2 still equilibrates in heavy exercise due to large O2 diffusion reserve
- V/Q = usually is 0.8 giving a PaO2 of 100mmHg & PaCO2 of 40mmHg
o Apex -> low V (high pleural pressure, larger alveoli, less compliant) and low Q ->
higher V/Q ratio -> blood from apex is more oxygenated
o Base -> high V (small alveoli, more compliant, gravity) and high Q (distended
veins) -> lower V/Q ratio -> blood from base contributes to physiologic shunt
o Despite O2 equilibration, PaO2 is always less than PAO2 due to physiologic
shunts -> bronchial venous blood + thebesian veins + low V/Q at base
- Respiratory center = primarily in the medulla
o Dorsal respiratory group = quiet respiration -> repetitive inspiratory ramp
signals that increase in intensity -> diaphragmatic contraction -> abrupt cessation
of signal (inspiratory off switch) -> diaphragmatic relaxation
▪ Respiratory rate controlled by altering slope of ramp signal (apneustic
center in lower pons) and inspiratory off switch (pneumotaxic center in
dorsolateral pons)
o Ventral respiratory group = inspiratory and expiratory signals -> inactive during
quiet respiration
- Respiratory receptors
o Pulmonary stretch receptors = slow adapting, sense airway stretch/lung volume
▪ Hering-Breuer reflex = excitation of pulmonary off switch + prolongation
of expiration -> prevent lung over inflation
o Irritant receptors = stimulated by irritants -> causes coughing, gasping,
prolonged inspiration
o J receptors = stimulated by lung injury
o Chest wall proprioceptors = stimulated when breathing movements are opposed
o Central chemoreceptors = sensitive to acute increase H+ (due to increased
PCO2) -> increases respiratory drive
▪ Chronic increase in CO2 is compensated by the kidneys
o Peripheral chemoreceptors = carotid/aortic bodies -> sensitive to low PaO2
(strong stimulus) + high PCO2 (rapid stimulus) + reduced pH
- Respiration during exercise = PaO2/PaCO2 are normal during exercise due to
compensatory increase in ventilation and perfusion + better V/Q matching
- Types of respiration
o Voluntary hyperventilation = decreased PaCO2, increased pH
▪ Hyperventilation syndrome -> vasoconstriction -> cardiac/cerebral
symptoms + alkalosis -> hypocalcaemia (Trousseau/Chvostek sign) +
hypokalemia (weakness)
o Voluntary hypoventilation = decreased PaO2, increased PaCO2 -> break point
where breathing can no longer be inhibited
o Cheyne-Stokes respiration = cyclic hyperpnea and apnea
o Kussmaul’s respiration = rapid deep breathing to compensate for metabolic
acidosis
- Altitude acclimatization = decreased PiO2 -> decreased PAO2 -> decreased PaO2 ->
peripheral chemoreceptors triggered -> hyperventilation -> decreased PaCO2 ->
 respiratory alkalosis -> decreased ventilation -> increased excretion of bicarbonate and
H+ retention (renal compensation) -> decreased pH -> increased ventilation
o Acute mountain sickness = headache, nausea, vomiting, fatigue within first week
o Chronic mountain sickness = increased RBCs + pulmonary hypertension ->
enlarged right heart -> heart failure
o High altitude cerebral edema = hypoxia induce vasodilation of cerebral vessels
causing fluid leak into brain tissue
o High altitude pulmonary edema = unequal hypoxic vasoconstriction of
pulmonary vessels causing fluid leak into lung tissue
Pathophysiology
- Anemia = decrease in Hb concentration
o PaO2 and SaO2 are normal -> in severe anemia 2,3-BPG increases to maintain O2
delivery to tissues
o Cyanosis ≥ 5g/dL deoxygenated Hb -> in anemia cyanosis appears at much lower
SaO2/PaO2
- Hypoxemia = decreased blood O2 content
o Normal A-a = hypoventilation, low Pi (high altitude), anemia, ischemia,
methemoglobinemia
▪ Low PCO2 at high altitudes (compensatory hyperventilation) vs high PCO2
in hypoventilation
o Increased A-a = V/Q mismatch, congenital R-L shunt, impaired diffusion (fibrosis,
edema, pneumonia, emphysema), aging
▪ V/Q = 0 -> ventilation defect with normal perfusion (severe obstructive
lung disease, atelectasis, blocked airway) -> alveolar gas = venous gas =
low PO2, high PCO2 -> wasted blood/shunt
▪ V/Q = ∞ -> perfusion defect with normal ventilation (pulmonary
embolism) or excess ventilation (hyperventilation) -> capillary gas =
alveolar gas = atmospheric gas = high PO2, low PCO2 -> wasted air
- Hypoxia = failure of O2 delivery or use at the tissue level
o Hypoxic hypoxia = hypoxemia -> decrease PaO2
o Anemic hypoxia = decreased [Hb] -> decreased O2 carrying capacity -> decreased
deliver of O2 -> PaO2 is normal
o Ischemic hypoxia = decreased blood flow to tissue
o Histotoxic hypoxia = tissue cannot make use of O2
- Nitrogen
o Inert gas narcosis = nitrogen dissolves into fatty tissue (brain) at increasing
depths -> altered ionic conductance reducing neuronal excitability
o Decompression sickness = quick ascent from the sea precipitates nitrogen
bubbles in the blood -> ischemia and death
Congenital disorders
- Peribronchiolar metaplasia = bronchial injury -> bronchiolar metaplasia in alveoli
- Pulmonary agenesis = complete absence of one or both lungs
- Pulmonary aplasia = absence of lung parenchyma, blind ended bronchus present
 - Pulmonary hypoplasia = incomplete small lungs -> seen in congenital diaphragmatic
hernia or oligohydramnios
- Foregut cysts = abnormal detachment of primitive foregut -> usually in bronchus
(mediastinal) -> can also be in esophagus or upper GI
- Pulmonary sequestration = part of lung supplied by extrapulmonary blood flow
o Extralobular = infantile mass lesion usually left sided, covered by separate pleura
o Intralobular = in older children with recurrent infection/bronchiestasis
- Bronchial atresia = distal lung tissue hyperinflates and fills with mucus
- Lobar hyperinflation = lack of bronchial cartilage -> progressive over inflation in male
neonates -> obstruction/air trapping
- Congenital pulmonary airway malformation = bronchial development failure ->
harmatomatous proliferation of lung tissue -> multi cystic masses, absence of cartilage
and bronchial glands
- Primary ciliary dyskinesia = abnormal ciliary movement due absence of inner/outer
dynein arms (DNAH5 mutation) -> recurrent pulmonary infections, sinusitis, otitis media,
male infertility -> associated with situs inversus totalis (Kartagener syndrome)
Lung disorders
- Atelectasis = incomplete expansion (loss of surfactant, ARDS) or collapse of previously
expanded lung (acquired atelectasis) -> hypoxemia and infections
o Acquired atelectasis = complete obstruction (mucus, foreign body -> mediastinal
shift towards collapse), compression (tumor, pneumothorax -> mediastinal shift
away from collapse) contraction (fibrosis)
▪ Obstruction due to tumors/enlarge lymph nodes more common in right
middle lobe
▪ Catamenial pneumothorax = right sided in women 30-40 years 2-3 days
after menstruation
- Pulmonary edema = due to imbalance between hydrostatic and oncotic pressures
o Increased capillary hydrostatic pressure (impaired venous return) + interstitial
oncotic pressure + vascular permeability + sodium retention OR decreased
capillary oncotic pressure (hypoproteinemia) + interstitial hydrostatic pressure +
lymphatic drainage -> accumulation of fluid in interstitial space
▪ CHF -> increased venous pressure + sodium retention -> heart failure cells
(hemosiderin laden macrophages)

- Acute interstitial pneumonia = Hamman-Rich syndrome -> idiopathic lung injury in

elderly usually preceded by an URT infection
 - Acute respiratory distress syndrome = non-cardiogenic pulmonary edema seen in
pulmonary infections, sepsis, gastric aspiration, trauma -> dyspnea, cyanosis, bilateral
infiltrates, respiratory acidosis
o Acute phase = endothelial injury (TNFa) -> neutrophil invasion -> increased
vascular permeability -> diffuse alveolar damage + surfactant abnormalities +
hyaline membranes
o Proliferative/organizing phase = phagocytosis (macrophages) + regeneration
(type II pneumocytes) OR fibrosis (TGFB, PDGF)

- Sleep related disorders = insomnia, parasomnia, hypersomnia, narcolepsy, Kline-Levine

syndrome, restless leg syndrome, snoring, etc.
o Sleep apnea = daytime hypersomnolence/fatigue + disordered respiration in
sleep (snoring, apnea, thrashing movements) + hypoxemia (arrythmias) + other
complications (arterial/pulmonary hypertension, impotence)
▪ Treatment = nasal continuous positive airway pressure (first line), oral
appliance (maintains tongue/jaw anteriorly), uvulopalatopharyngoplasty
(eliminates snoring), nasal septoplasty
Obstructive lung diseases = increased airway resistance, air trapping, increased lung compliance
-> decreased FEV1 + FVC + FEV1/FVC ratio, increased RV/TLC
- Emphysema = destruction of alveolar walls without fibrosis -> irreversible enlargement
of airways -> pink puffers = dyspnea, coughing, weight loss, hunched over, barrel chest,
hyperlucent lung fields, flattened diaphragm, respiratory acidosis
o Centriacinar = effects proximal portion of acinus with distal sparing in upper
lung, black pigment due to smoking, seen in chronic bronchitis
o Panacinar = effects entire length of respiratory bronchiole to alveolus in lower
lung, due to a1-antitrypsin deficiency
o Paraseptal = primarily effects distal acinar, can cause spontaneous
pneumothorax (rupture of subpleural bullous due to old TB scars)
o Irregular = airway enlargement due to previous scarring
- Chronic bronchitis = chronic irritation (smoking) -> gland/goblet cell hyperplasia (gland
thickening) + mucus hypersecretion -> airflow obstruction + inflammation + productive
cough + increased Reid index (>0.5) + fibrosis -> blue bloaters = seen in obese
hypoxemic patients with pulmonary hypertension, polycythemia and frequent infections
o Smoking = causes fibrosis (TGFB) + alveolar wall destruction + increased mucus
- Asthma = hyperreactivity of airways -> bronchoconstriction + edema + mucus secretion
-> reversible airway obstruction due to mucus plugs, lung hyperinflation -> can lead to
airway remodelling (thickening, fibrosis) -> tested via methacholine/exercise challenge,
skin test, fractional NO test -> forward leaning in severe asthma
o Non-atopic asthma = non-allergic, normal IgE
 ▪ Samter’s triad = non-atopic asthma + aspirin sensitivity + nasal polyposis
o Atopic asthma = type I HSR to allergen = sensitization (IgE production) -> early
phase (antigen induce IgE cross linking on mast cell) -> late phase (mast cell
degranulation -> LTs, ACh, histamine, cytokines, chemokines, eosinophilia)
▪ Imaging -> Charcot-Leyden crystals (red crystals inside eosinophils),
Curschmann’s spirals (basophilic mucinous fibrils), thickened basement
membrane, eosinophilic/lymphocytic infiltrate

- Bronchiectasis = chronic necrotizing infections -> SMC/elastic tissue destruction ->

permanent bronchi dilation + lymphoid hyperplasia + thickened bronchial arteries ->
severe/persistent cough, foul-smelling sputum, hemoptysis, chest pain, cyanosis, etc.
o Also seen in cystic fibrosis, rheumatoid arthritis, foreign body obstruction, etc.
Restrictive interstitial fibrosing diseases = cause chronic inflammation/interstitial fibrosis ->
septal thickening, reduced lung compliance, decreased FEV1 + FVC but normal FEV1/FVC ratio
- Pneumoconiosis = inhalation of particles (exacerbated by smoking due to impaired
mucociliary clearance) -> interstitial fibrosis
o Coal workers pneumoconiosis = inhalation of carbon -> black pigment in
macrophages (dust cells)
▪ Simple CWP = coal macules (no fibrosis) & nodules (fibrosis) in upper lung
▪ Complicated CWP = large fibrotic opacities -> black lung disease ->
pulmonary hypertension
o Silicosis = inhalation of silicon -> intra-alveolar lipoprotein material (acute) ->
nodules with concentric layers of collagen, hilar lymph node eggshell calcification
(chronic) -> pulmonary hypertension, fibrosis, risk of TB infection/cancer
o Asbestosis = asbestos inhalation -> large fibrocalcific plaques on diaphragmatic
pleura -> asbestos/ferruginous bodies (ferritin coated asbestos fibers) ->
interstitial fibrosis of lower lobe and honeycomb lung
o Berylliosis = beryllium inhalation (aerospace, nuclear industry, etc.) -> diffuse
alveolar damage (acute) -> non-caseating granulomas (chronic) -> interstitial
fibrosis and honeycomb lung
o Caplan’s syndrome = pneumoconiosis (CWP, silicosis, asbestosis) + rheumatoid
arthritis
CWP Silicosis Asbestosis Berylliosis
- Idiopathic pulmonary fibrosis = usual interstitial pneumonia -> progressive fibrosis in
older male smokers with patchy necrosis (heterogenous lung parenchyma) -> firm
rubbery white areas along interlobular areas of lower lobes (cobblestone appearance)
-> clubbing, cyanosis, Velcro like crackles, non-productive cough -> honeycomb lung,
pulmonary hypertensive changes (intimal fibrosis + medial hypertrophy)
o Endothelin -> activated by angiotensin II/TGFB -> activates fibroblasts -> ECM
remodelling (fibrosis) + myofibroblast proliferation (bronchoconstriction)
- Nonspecific interstitial pneumonia = diffuse uniform interstitial thickening with
lymphoblastic infiltrate in female non-smokers with type II pneumocyte hyperplasia ->
minimal fibrosis/honeycombing
- Cryptogenic organizing pneumonia = subpleural/peri bronchial patchy areas with
Masson bodies (plugs of loose connective tissue) -> normal lung architecture
IPF NSIP COP

- Drug induced lung injury = bleomycin & amiodarone cause fibrosis, methotrexate &
nitrofurantoin cause HSR pneumonitis, aspirin & B blockers cause bronchospasms
- Radiation induced lung injury = can acutely cause lymphocytic alveolitis/HSR
pneumonitis, fever, pleural effusion -> chronically cause fibrosis, foam cells, atypia
- Sarcoidosis = systemic granulomatous disease in black women <40 years ->
noncaseating granulomas compressing alveoli, giant cells with Schumann/asteroid
bodies -> sudden shortness of breath, cough, chest pain, night sweats, fever, erythema
nodosum, lupus nernio, hypercalcemia, hyperIgG

- Hypersensitivity pneumonitis = NO IgE or eosinophilia -> inhalation of antigenic dust ->

dyspnea, cough, pulmonary infiltrate (type III HSR) -> chronic cough, lower lobe fibrosis,
noncaseating granulomas, honeycomb lung (type IV HSR) -> seen in
farmers/millers/pigeon breeders lung
- Pulmonary eosinophilia = eosinophilic infiltrate (Il-5) -> fever, night sweats, diffuse
alveolar damage -> seen in Loeffler’s (Ascaris lumbricoides)
- Lymphoid interstitial pneumonia = associated with HIV (children), EBV, Sjogren’s,
hyperIgG -> interstitial expansion due to WBC infiltrate
 - Smoking related pneumonitis
o Desquamative interstitial pneumonia = ground glass opacities, dry cough,
thickened alveoli, pigmented macrophages with lamellar bodies (surfactant)
o Respiratory bronchiolitis associates pneumonitis = pigmented intraluminal
macrophages
- Langerhans cell histiocytosis = eosinophilic granulomas or diffuse cysts primarily in
upper lobe of smokers -> Langerhans cells with Birbeck granules

- Lymphangioleiomyomatosis = mainly in reproductive age females with tuberous

sclerosis -> immature SMC proliferation, perivascular epithelioid cells -> can cause
pneumothorax/chylothorax
- Pulmonary alveolar proteinosis = accumulation of surfactant derived lipoproteins due to
macrophage failure (Anti GM-CSF abs, mutated GM-CSF receptors, silicosis) -> bright
pink alveolar protein infiltrate
Pulmonary vascular disorders
- Pulmonary hypertension = due to increased pulmonary blood flow or vascular resistance
(atherosclerosis in larger vessels, medial hypertrophy in medium vessels)
o Idiopathic PHT -> in 20-40 year old females -> dyspnea, fatigue, RVH -> death due
to cor pulmonale, thromboembolism, pneumonia
▪ Familial type -> AD mutations in TGFB pathway (BMPR)
▪ Secondary PHT -> mutations in serotonin transport
o Causes = precapillary (congenital R-L shunt, scleroderma, drugs), left sided heart
failure (mitral stenosis), chronic lung disease (COPD/ILD -> vascular remodelling),
chronic thromboembolism
o Morphologic changes
▪ Reversible = medial hypertrophy -> intimal proliferation -> intimal fibrosis
▪ Irreversible = plexiform lesion -> dilation -> fibrinoid necrosis

- Embolism = seen in prothrombic states (hypercoagulability, immobilization, fractures,

surgery, etc.) -> decreased perfusion (increased V/Q) + D-dimer + leukocytosis ->
pleuritic chest pain, hemorrhagic wedge shaped infarct (tip facing in), swollen leg (DVT)
o Large embolus -> pulseless electrical activity (S1Q3T3, RBBB), raised JVP,
tachycardia -> can cause sudden death -> CT in hemodynamically stable patients,
IV heparin + echo in hemodynamically unstable patients -> can do
thrombectomy or IVC filter
 ▪ Thrombus formed in flowing blood will show lines of Zahn (interchanging
layers of RBCs and platelet/fibrin deposits)
▪ Lack of D-dimer rules out embolism
o Chronic embolus -> many small emboli -> pulmonary hypertension
- Goodpasture syndrome = anti basement membrane Abs of lungs and kidneys in males
between 20-40 years -> necrotic + hemorrhagic lung (intra-alveolar and diffuse) + type II
pneumocyte hyperplasia + fibrosis + pulmonary consolidations + hemoptysis +
progressive renal failure
- Idiopathic pulmonary hemosiderosis = in children -> intermittent episodes of alveolar
hemorrhage
- Wegner’s granulomatosis = cANCA+ (proteinase3) -> vasculitis + poorly formed
granulomas + necrosis -> cavitating lesions in upper airways/lungs/kidneys + sinusitis +
saddle nose + hearing loss + hoarseness
o pANCA is targeted to myeloperoxidase
Pulmonary infections
- Pneumonia = community acquired (post viral bacterial infection), healthcare associated
(MRSA, pseudomonas, etc.), hospital acquired (pseudomonas, MRSA, strep
pneumoniae, etc.)
o Lobar pneumonia = diffuse consolidation
o Bronchopneumonia = patchy consolidation with suppurative exudate
o Interstitial/atypical pneumonia = no consolidation, interstitial inflammation,
thick septa -> fever, headache, myalgia
o Aspiration pneumonia = in impaired swallowing/gag reflex -> right sided,
polymicrobial (actinomyces -> sulfur granules), necrotizing abscesses with
malodorous sputum
▪ Lung abscesses also seen in patients with poor oral hygiene
o Lipid pneumonia = exogenous (aspiration -> lipid vacuoles) or endogenous
(foamy macrophages, cholesterol crystals)
o Ventilator associated pneumonia = colonization of oropharynx by
microorganisms -> quantitative culture approach used to determine infectious
agent
o Pneumonia severity score = Confusion, Urea elevated, Respiration elevated,
Blood pressure decreased, 65 years or older -> ICU admission if score ≥ 4
- Bacterial
o Strep pneumoniae = gram+ lancet shaped diplococci -> upper lobar pneumonia,
rust colored sputum,
▪ Congestion (fluid + bacteria) -> red hepatization (neutrophils + RBCs ) ->
gray hepatization (neutrophils + lysed RBCs) -> resolution (macrophages,
fibroblasts)

-> -> ->

 o Klebsiella = gram- encapsulated -> lobar pneumonia in alcoholics, currant jelly
sputum
o Legionella = gram- aerosolized bacteria -> bronchopneumonia OR lobar
pneumonia, watery diarrhea, confusion, hyponatremia, bradycardia -> tested via
urine antigen test
o H. influenza = pleomorphic gram- with pili/IgA protease -> bronchopneumonia,
otitis, meningitis, epiglottitis
o Moraxella = gram- diplococci -> respi infection, otits
o Staph aureus = gram+ -> post-viral nosocomial lobar pneumonia, abscesses,
endocarditis in IVDU
o Pseudomonas = gram- rod -> nosocomial necrotizing pneumonia in patients with
cystic fibrosis
o Walking pneumonia = mycoplasma (cold agglutination, military recruits),
chlamydia, Coxiella (vets)
o Nocardia = weakly acid-fast gram+ filamentous rod -> pneumonia with abscesses
in immunocompromised
- Viral -> cause atypical pneumonia -> diffuse alveolar damage + hyaline membranes
o Influenza (A, B, C) = HA and NA (antigenic drift/shift) -> can cause secondary
bacterial infection
o Parainfluenza = giant cell pneumonia -> croup
o RSV/metapneumovirus = pediatric pneumonia with multinucleated giant cells
o Adenovirus = in children and immunocompromised -> necrotizing pneumonia
with smudge cells
o Measles = giant cell pneumonia with Warthin-Finkeldey cells + Koplik spots +
exanthema
- Fungal -> cause chronic pneumonia (granulomas)
o Histoplasmosis = bird/bat dropping in Ohio/Mississippi river -> buckshot
calcification (acute), caseating granulomas with tree bark appearance (chronic)
▪ No granulomas in disseminated histoplasmosis
o Blastomycosis = broad based budding yeast from central/southeastern US
o Coccidioides = infective arthroconidia from Southwestern US (San Juan valley)
o Paracoccidioides = mariners wheel yeast from south America -> attack mucosa of
mouth, nose, and lungs
o Aspergillus = allergic bronchopulmonary aspergillosis (IgE, eosinophils,
granulomas in patients with asthma/cystic fibrosis), aspergilloma (fungal ball in
pre-existing cavity), invasive aspergillosis (air crescent sign on CXR, granulomas),
aspergillus niger (pigmented spores + calcium oxalate crystals)
o Mycormycosis/zygomycosis = large angle hyphae -> hemorrhagic necrosis seen
in diabetic patients
o Candida = pseudohyphae -> multiple micro abscesses
- Tuberculosis
o Primary = asymptomatic or fever/pleural effusion -> Il-12 causes Th1
differentiation -> Th1 cells produce INFy -> macrophages secretes TNFa and form
 caseating granulomas in lower lobes (Gohn focus + hilar lymphadenopathy +
Langhans cells)
▪ Can also have empyema, scrofula, Potts disease (vertebral involvement)
o Secondary = previously sensitized host -> weight loss, caseating granulomas in
upper lobes, mucoid cough, pleuritic chest pain, hemoptysis, amyloidosis
o Miliary TB = hematogenous spread to all organs
o PPD test = positive if zone of induration if >5mm (HIV), >10mm (at risk), >15mm
(healthy patients)
- HIV pneumonia
o Pneumocystis jirovecii = intra-alveolar cotton candy eosinophilic exudate, cup
shaped/crushed ball cysts
o Cryptococcus = thick capsule
o CMV = bilateral symmetrical infiltrate, owl’s eye inclusion bodies
o HSV/VSV = Cowdry bodies + multinucleated giant cells
o MAC = miliary granulomatous inflammation
- Lung transplant rejection = leukocyte infiltrate (acute) -> fibrosis, bronchiolitis
obliterans, vascular rejection (intimal fibrosis + medial hypertrophy)
Lung tumors -> will have weight loss, cough, chest pain, dyspnea, may cause obstruction
- Squamous cell carcinoma = firm grayish centrally located tumor that may cavitate seen
in male smokers with loss of p53/Rb/p16 -> keratin pearls, intercellular bridges, tadpole
cells -> can secrete PTHrP (hypercalemia)

- Adenocarcinoma = peripherally located that spreads along alveolar walls in non-smoking

women with gain of function tyrosine kinase mutation -> lepidic/butterfly, acinar,
papillary or micropapillary pattern

- Small cell carcinoma = centrally located malignant neuroendocrine tumor (sheets of

dark blue cells, chromogranin/synaptophysin+) in smokers with loss of p53/Rb or
increased Myc -> can produce ACTH (Cushing’s) or ADH (SIADH), cause SVC syndrome
(distended neck veins + facial/upper arm edema)
 - Large cell carcinoma = solid tumor with large polygonal anaplastic cells
- Solitary pulmonary nodule = hamartoma or old granuloma (coin lesion)
- Pancoast tumor = type of squamous cell carcinoma -> Horner’s syndrome, thoracic
outlet syndrome
- Carcinoid tumor = occurs <40 years in patients with MEN I mutation -> secretes
serotonin/bradykinin -> causes diarrhea, flushing -> salt and pepper chromatin,
chromogranin/synaptophysin+
- Pulmonary metastases = from breast, kidneys, etc. -> cannon ball metastases
Pharmacology
Respiratory drugs
Bronchodilators -> short term relief
- B2-agonists = albuterol (short acting), salmeterol (long acting), indacaterol (ultra-long
acting) -> inhibit histamine release + decrease edema + increase mucociliary transport +
inhibit ACh release + smooth muscle relaxation
o Uses = acute attacks (short acting), prophylaxis and nocturnal attacks (long
acting), COPD (ultra-long acting daily), improved lung function (+ magnesium
sulfate)
o ADR = tremors, tachycardia, hypokalemia, tolerance
- Muscarinic antagonists = ipratropium, triotropium -> block Vagus induced
bronchoconstriction + enhance B2 effect -> used in COPD with cardiac issues -> causes
atropine like effects (blurred vision, etc.)
- Methylxanthines = theophylline -> blocks PDE3 + adenosine receptors + Ca influx ->
bronchodilation
o Uses = asthma, COPD, recurrent apnea in preemies
o ADR = nausea, anorexia, arrythmias, seizures, narrow TI
- PDE4 inhibitors = roflumilast -> increases cAMP -> bronchodilation for COPD -> can
cause GI distress and suicidal thoughts
Anti-inflammatory agents
- Corticosteroids = beclomethasone -> inhibit phospholipase A2 -> inhibit inflammation +
increased B2 sensitivity
o Uses = long term asthma control (inhaled), COPD (with B2 agonist)
o ADR = oral thrush (prevented by spacer or valve), hoarseness, cough
▪ Ciclesonide can be used instead to prevent oral thrush
- Mast cell stabilizer = cromolyn sodium/nedocromil -> used for asthma, allergic rhinitis
- Montelukast = LT receptor antagonist -> inhibit bronchoconstriction and inflammation
o Uses = aspirin sensitive asthma, allergic rhinitis
o ADR = hepatotoxic, Churg-Strauss, increased warfarin
- Zileuton = inhibits lipoxygenase -> block LT production
o Uses = asthma, rheumatoid arthritis, UC
o ADR = hepatotoxic, inhibits CYP450 (elevated theophylline, warfarin)
- Mepolizumab/reslizumab = anti Il-5 monoclonal Ab
- Benralizumab = anti Il-5 receptor Ab
- Omalizumab = anti IgE monoclonal Ab -> refractory asthma
Cough drugs
- Pharyngeal demulcents = menthol, benzocaine, dyclonine, pectin -> soothing film over
inflamed mucosa reducing afferent impulses -> for dry cough
- Antitussives = anesthetize afferent fibres + act on cough center -> for dry severe coughs
o Codeine = can cause constipation, respiratory depression (not used in asthma)
o Dextromethorphan = NMDA + 5HT receptor antagonist -> can cause serotonin
syndrome
o Benzonatate = block stretch/cough receptors in the lung
o H1 antihistamines = diphenhydramine, fexofenadine
- Expectorants = increase clearance (mucokinetic) or break down sputum (mucolytic) ->
used for productive coughs in COPD, cystic fibrosis, bronchiectasis
o Guaifenesin = mucokinetic -> enhance mucociliary action
o Acetylcysteine = mucolytic -> breaks down sputum
o Bromhexine = mucokinetic + mucolytic -> can cause rhinorrhea
- Neuromodulators = gabapentin/pregabalin -> used for chronic idiopathic cough
- Allergic rhinitis drugs = H1 antihistamines, a1/2 agonists (oxymetazoline), a agonists
(phenylephrine), intranasal corticosteroids, mast cell stabilizers, antimuscarinics, LTR
blockers, omalizumab
TB drugs
- Rifampin = inhibits RNA polymerase (mutated in resistant strains) -> used for TB,
leprosy, serious staph infections, prophylaxis of meningitis
o ADR = red bodily fluids, hepatitis, induces CYP450
- Isoniazid = converted to active form by KatG (mutated in resistant strains) -> inhibits
mycolic acid synthesis
o ADR = peripheral neuropathy (slow acetylators -> treated with B6),
hepatotoxicity (fast acetylators)
- Pyrazinamide = converted to pyrazinoic acid by pncA (mutation in resistant strains)
o ADR = hyperuricemia, hepatitis, myalgias, phototoxicity
- Ethambutol = inhibits arabinosyl transferase (embB mutation in resistant strains) ->
bacteriostatic -> can be used for TB and MAC
o ADR = optic neuritis, hyperuricemia
- Secondary drugs = streptomycin, fluoroquinolones
- MAC treatment = ethambutol + macrolide (+ rifabutin for severe cases)
- Leprosy treatment = dapsone + rifampin + clofazimine
o Dapsone = inhibits folate synthesis -> can cause hemolytic anemia in G6PD
deficiency
o Clofazimine = can cause Gi distress, red discoloration
Respi
Pathology
Pleural diseases
- Pleuritis = sudden intense pleuritic chest pain on breathing due to infection, pneumonia,
pneumothorax, etc.
- Pleural effusion = due to increased hydrostatic pressure (CHF) + vascular permeability
(pneumonia, infarct) OR decreased oncotic pressure (nephrotic syndrome) + lymphatic
drainage (obstructive tumor) -> dyspnea, chest pain, non-productive cough
o Transudate = due to disturbed starling forces -> clear, <1.015 specific gravity
o Exudate = due to vascular disturbance (inflammation) -> protein rich, cloudy,
>1.024 specific gravity, increased LDH
- Parapneumonic pleural effusion = effusion associated with bacterial pneumonia (staph,
pneumococcus, klebsiella, pseudomonas, etc.)
o Uncomplicated (exudative) -> neutrophilic exudate -> resolves with antibiotics
o Complicated (fibrinopurulent) -> bacterial invasion -> neutrophils, pleural
acidosis, increased LDH, decreased glucose -> requires drainage
o Empyema thoracis (organized) -> pleural thickening + pus in pleural cavity ->
requires drainage
- Hydrothorax = water in pleural cavity due to CHF (elevated BNP) or liver disease (ascites)
- Hemothorax = blood in pleural cavity due to trauma, aortic dissection, etc.
- Chylothorax = lymph in pleural cavity due to lymphatic obstruction, tumors, trauma, etc.
-> elevated TAGs
- Pyothorax = purulent foul-smelling pleural fluid due to bacterial colonization
- Pneumothorax = air in pleural cavity -> tympanic percussion + absent breath sounds
o Spontaneous pneumothorax = bleb rupture in tall thin males smokers or patients
with distal acinar emphysema
o Tension pneumothorax = penetrating trauma causing atelectasis -> hypotension +
distended jugular veins + crisp heart sounds + chest pain + dyspnea
▪ Also occurs in patients on mechanical ventilation
o Catamenial pneumothorax = right sided in women in their 30s 2-3 days after
menstruation
- Atelectasis = collapse of alveoli due to obstruction (aspiration -> mediastinal shift
towards)or compression (tension pneumothorax -> mediastinal shift away) or
contraction (fibrosis)
Lung tumors -> smoking is #1 risk factor -> review all previous CXRs then cytology to confirm
diagnosis (VATS for peripheral lesions) -> stage 1 (no lymph involvement) and stage II (lymph
involvement) tumor resection, stage 4 (metastases) chemotherapy
- Central = small cell + squamous cell carcinoma (smoking associated)
- Peripheral = adenocarcinoma + benign tumors (non-smoking associated), large cell
carcinoma
- Paraneoplastic syndromes = Cushing’s (ACTH) + SIADH (ADH) + Lambert-Eaton with small
cell carcinoma, hypercalcemia (PTHrP) with squamous cell carcinoma, clubbing with
non-small cell carcinomas
 - Bronchial carcinoid tumor = neuroendocrine (chromogranin+) tumor with no necrosis ->
can precipitate carcinoid syndrome (flushing, wheezing, diarrhea)
- Pulmonary metastases = multiple masses (cannonball)
- Solitary pulmonary nodule = well defined round tumor <30mm
- Mesothelioma = yellow malignant pleural tumor due to asbestos exposure -> dyspnea,
weight loss, night sweats, unilateral pleural effusion/thickening, lung invasion ->
epithelioid (like adenocarcinoma) or sarcomatoid (spindle cells) or biphasic (epithelioid
and sarcomatoid) -> calretinin/cytokeratin+ -> chemotherapy

Renal
Anatomy
- Kidney = nephron (functional unit), cortex (contains all glomeruli), medulla, papilla,
columns, calyces, pelvis, ureter (constricted at pelvic junction, pelvic brim, bladder)
o Uteric bud/mesenephric duct = forms collecting system (collecting duct + calyces
+ renal pelvis + ureter)
o Metanephric duct = forms excretory system (glomerulus + Bowman’s capsule +
PCT + loop of Henle + DCT)
▪ Basement membrane (negatively charged heparan sulfate) + slit
diaphragms (space between podocyte foot processes) + nephrin/podocin
molecules keep proteins out of Bowman’s capsule
▪ PCT has a brush border while DCT does not
- Urinary bladder = detrusor muscle (SMC of bladder -> forms internal urethral sphincter),
- Autonomics = pelvic parasympathetic splanchnic (S2-4) + sacral sympathetic splanchnic
(T12-L2) supply inferior hypogastric plexus -> innervate all smooth muscle + glands
Physiology
Renal circulation
- Hemodynamics = main method of altering RBF is by changing afferent/efferent arteriolar
resistance
o Greatest drop in renal pressure is in the afferent and efferent arterioles
o Increasing afferent or efferent resistance -> decreased RBF
o Increasing afferent resistance -> decreased glomerular pressure (GFR)
o Increasing efferent resistance -> increased GFR
- RBF/GFR control
o Sympathetic -> afferent vasoconstriction more than efferent -> decreased RBF
and GFR
o Angiotensin II -> afferent and efferent vasoconstriction + glomerular mesangium
constriction (decreased Kf) -> decreased RBF and GFR
o ANP -> afferent dilation + efferent vasoconstriction + + glomerular mesangium
relaxation (increased Kf) -> RBF remains the same but increased GFR
o Prostaglandin -> afferent dilation -> increased RBF and GFR
o NO -> afferent dilation -> increased RBF and GFR
 - Tubuloglomerular feedback = when RBF/GFR are high -> increase Na delivery to macula
densa in DCT via NK2Cl transporter -> adenosine release -> afferent vasoconstriction ->
decreased RBF/GFR
o High protein/glucose diet -> increased Na coupled AA/glucose resorption ->
decreased Na in macula densa -> increased RBF/GFR
- GFR = NFP x Kf
o Net filtration pressure = glomerular hydrostatic pressure – [Bowman’s capsule
hydrostatic pressure + glomerular oncotic pressure)
o Filtration coefficient = depends on permeability and surface area
▪ GBM resists water movement, negatively charged glycocalyx prevent
protein movement
- Excretion = filtration + secretion – reabsorption
o Filtration fraction = GFR / RBF -> increasing filtration fraction increases capillary
colloid oncotic pressure
▪ Renal circulation passes 2 capillary beds progressively increasing the
capillary colloid oncotic pressure during filtration
o Filtered load = plasma concentration x GFR -> if no reabsorption/secretion then
urine excretion = filtered load

- Na transport ->
o Reabsorbed in PCT -> Na/H exchanger -> reduced H availability with CA inhibitors
o Reabsorbed in loop of Henle -> NaK2Cl transporter -> blocked by loop diuretics
o Reabsorbed in DCT -> NaCl symporter -> blocked by thiazide diuretics
o Reabsorbed in collecting tubule -> electrogenic Na channel -> blocked by K
sparing diuretic amiloride)
Urine formation
- Tubular transport = either passive (paracellular) or active (transcellular) but overall
coupled with Na transport
o Creatinine is mostly filtered (steady state production = excretion) -> creatinine
plasma concentration can be used to calculate GFR
o Inulin is fully filtered -> excretion = filtered load = GFR
o Glucose = transcellular reabsorption in PCT coupled to Na transport (SGLT)
o Amino acids = transcellular reabsorption in PCT coupled to Na transport
o Water = paracellular and transcellular (AQP) reabsorption
o Cl = transcellular reabsorption with sodium in TAL/DCT (NaCl/NaK2Cl) and
paracellular reabsorption
o PAH = transcellular -> fully secreted
 o
- Transport ATPases
o Na/K -> Na reabsorption throughout nephron
o H/K -> H secretion in collecting tubules
o H-ATPase -> H secretion in PCT
o Ca-ATPase -> Ca reabsorption in DCT
- Ion channels
o K channels throughout nephron
o Aldosterone sensitive electrogenic Na channels in distal nephron for reabsorption
(blocked by amiloride/K sparing diuretics)
o PTH sensitive TRPV5 Ca channels in DCT (reabsorption)
- Exchangers
o Na/H exchanger -> acid-base regulation throughout the nephron
o Na/bicarbonate symporter -> acid-base regulation in PCT and TAL
o Cl/bicarbonate antiporter -> acid-base regulation in PCT and collecting duct
o NaK2Cl symporter -> reabsorption in the TAL -> primary effect on macula densa
in DCT (blocked by loop diuretics/furosemide)
o Na/PO3 symporter -> PO3 reabsorption in PCT
o Na/Cl symporter -> Cl reabsorption in the DCT (blocked by thiazide diuretics)

- Peritubular reabsorption = depends on starling forces, permeability and electrochemical

gradient
o Peritubular capillary oncotic pressure increases with increased filtration fraction
o Glomerulotubular balance = tubular transport is adjusted to GFR/filtered load to
maintain homeostasis
▪ Decreased efferent arteriolar resistance -> decreased GFR -> decreased
peritubular capillary oncotic pressure (due to decreased filtration
fraction) + increased peritubular capillary hydrostatic pressure ->
decreased Na reabsorption to match decreased GFR

Control of blood pressure

- ADH = increase in blood osmolality (Na) sense in hypothalamus by osmoreceptors ->
increased aquaporins in collecting tubules -> increased water reabsorption -> increase
blood volume and BP
o Pressure natriuresis -> kidney compensates for increased BP by increasing Na
excretion
 - RAAS system = increased sympathetic stimulation + decreased BP + decreased Na
delivery to macula densa -> renin secretion by juxtaglomerular cells converting
angiotensinogen to angiotensin I -> angiotensin I converted to angiotensin II at the lungs
-> increased Na reabsorption directly (Na/K exchanger) and indirectly (aldosterone)
o Aldosterone increases electrogenic Na channels + Na/K exchanger activity
▪ Excess aldosterone due to unilateral renal artery stenosis or localized
intrarenal ischemia can lead to HTN

Pathology
Glomerular diseases
- Nephrotic syndromes – T-cell mediated glomerular injury causing proteinuria ->
hypoalbuminemia (causes hypocalcaemia and 2o hyperparathyroidism), generalized
edema, increased renin (2o hyperaldosteronism), decreased ANF, infections due to loss
of IgG, microcytic hypochromic anemia (loss of transferrin), thrombosis and
hypercoagulability due to decreased anticoagulants/antiplasmins, hyperlipidemia
o Minimal change disease = normal looking glomeruli but uniform/diffuse
podocyte foot process effacement in children -> protein/lipid laden PCT, selective
proteinuria (albumin) -> proteinuria stops with corticosteroids (biopsy children
that don’t respond)
o Focal segmental glomerulosclerosis = segmental sclerosis of glomeruli with
podocyte effacement -> non-selective proteinuria, deposition of
IgM/C3/anti-CD40 Abs, hyaline masses/lipid deposition, increase BUN ->
associated with HIV (collapsing FSFS w/ cystic tubular dilation) & heroin use,
more hematuria and HTN compared to MCD -> treated with RAAS inhibitors
▪ Congenital FSGS -> NPHS1/2 mutation (nephrin/podocin), a-actinin4
mutation, TRPC6A mutation
o Membranous nephropathy = subepithelial spike and dome deposits of
autoantibodies (HepB, SEL, etc.) in GBM in middle aged patients -> uniform
capillary thickening, nonselective proteinuria -> risk of DVT, renal vein thrombosis
and pulmonary embolism -> prophylactic anticoagulants
o Membranoproliferative glomerulonephritis = due to circulating immune
complexes (type I) or anti-C3 Abs (type II) -> proliferation of mesangial cells,
thickened GBM (tram track appearance)
MCD FSGS MN MPGN
- Nephritic syndromes – glomerular injury causing cell proliferation + inflammatory
infiltrate characterized primarily by hematuria with RBC casts -> oliguria & azotemia
(elevated BUN + creatinine) due to decreased GFR, HTN, variable proteinuria/edema
o Post strep glomerulonephritis = IgG/complement immune complex deposition
(subendothelial hump) + hypercellularity + neutrophil infiltrate 1-4 weeks post
GAS infection in children -> gross hematuria (smoky brown urine) -> can progress
to rapidly progressive GN
o IgA nephropathy (Berger’s diseases) = IgA deposition in mesangium due to
defective production/clearance after a GI/respi infection -> episodic gross
hematuria in children/young adults -> also seen in patients with Celiac disease
and liver disease (decreased clearance), responds to plasmapheresis
▪ Henoch-Schoenlein purpura = systemic IgA deposition (purpuric rash +
abdominal pain + nephropathy)
o Hereditary nephritis/Alport syndrome = X-linked dominant mutation of type IV
collagen a-chains, usually in males -> nephritis + ocular disorder + deafness ->
foamy interstitial cells, thick and thin basket weave GBM
▪ Female carriers present with persistent hematuria
o Thin membrane disease = diffuse thinning of GBM -> benign familial
asymptomatic hematuria
o Rapidly progressive glomerulonephritis = severe glomerular injury causing loss
of renal function for days to weeks microscopic -> hematuria with RBC casts,
severe oliguria, azotemia, crescents (proliferation of parietal cells in Bowman’s
capsule + fibrin deposition)
▪ Anti-GBM crescentic GN -> linear IgG/C3 deposits on GBM (type II HSR) ->
smooth GBM
● Seen in Goodpasture syndrome (also effects lungs)
▪ Immune complex GN with crescents -> seen in PSGN, SLE, Henoch
Schoenlein purpura, IgA nephropathy -> lumpy bumpy GBM
 ▪ Pauci-immuno crescentic GN = seen in Wegner’s and polyarteritis nodosa
(C/P-ANCA)
Alport Thin Membrane RPGN crescents

- Systemic associated glomerular lesions

o Diabetic nephropathy = hyperglycemia -> increased type IV collagen + decreased
proteoglycan + increased glycosylation products + increased GFR (hyaline
arteriosclerosis of both efferent/afferent arterioles) -> proteinuria, nodular
glomerulosclerosis (Kimmelsteil Wilson disease) -> eventual loss of GFR (renal
failure) and HTN
o Renal amyloidosis = amorphous pink deposits (Congo red stain)
o Lupus nephritis = anti-DNA Abs deposits (wire looping) -> nephritic-nephrotic
syndrome with lumpy bumpy glomerulus
o Scleroderma nephritis = vessel injury + vasospasm -> severe HTN -> renal crisis
(onionskin vessels, thrombotic microangiopathy, vessel adventitial fibrosis)

- Chronic GN = symmetric disease usually do to RPGN (also FSGN, MPGN, MN) ->
accumulation of hyaline masses transforming glomerulus into acellular eosinophilic mass
+ diffuse granularity on kidney surface -> proteinuria, HTN, azotemia, uremia (and
associated complications)
 - Benign proteinuria = can be due to dehydration, stress, inflammation, intense activity
o Orthostatic proteinuria = increased proteinuria when upright but normal when
lying down -> annual BP and urinalysis to monitor patients
Tubulointerstitial diseases
- Tubulointerstitial nephritis = involves tubules/interstitium and spares glomerulus
o Acute pyelonephritis = suppurative ascending bacterial upper UTI usually in
sexually active women due to E. Coli or other enteric gram- rods (multifocal
infection due to hematogenous staph infection) -> fever, nausea, sudden
costovertebral tenderness, dysuria -> PMN infiltrate, yellow abscesses, renal
papillary necrosis, bacteriuria, pyuria (WBC casts)
▪ Risk factors = bladder/urinary tract obstruction (BPH in men, uterine
prolapse in women), diabetes, drug abuse, CAUTI, vesicoureteral reflux (in
children), pregnancy, etc.
o Chronic pyelonephritis = chronic interstitial inflammation -> asymmetric
pelvicalyceal scarring (flattened calyces underlying cortical scars) due to chronic
obstruction (unilateral) or chronic vesicoureteral reflux (bilateral) -> colloid casts
in tubules (thyroidisation)
o Xanthogranulomatous pyelonephritis = nephrolithiasis and obstruction due to
proteus infection in females -> accumulation of foamy macrophages + giant cells
+ large yellow nodular kidney
o Drug-induced interstitial nephritis = eosinophilia and rash (type I HSR) or
neutrophilia or granulomas (type IV HSR)
▪ NSAIDs cause concomitant MCD + interstitial nephritis
o BK infection = tubulointerstitial nephritis in kidney transplant patients -> large
homogenous inclusions in infected cells (decoy cells that look like cancer cells)
- Acute tubular injury = damaged tubular cells due to glomerular diseases, renal vascular
diseases or drug induced allergic interstitial nephritis -> redistribution of membrane
proteins -> decreased GFR + oliguria -> dirty brown casts
o Ischemic ATI = inadequate blood flow to kidneys due to shock/hypotension
(trauma, pancreatitis, septicemia) -> proteinaceous casts (Tamm-Horsfall protein,
hemoglobin) in distal nephron, tubular necrosis
o Nephrotoxic ATI = due to toxins, organic solvents, drugs (gentamicin), contrast
agents -> primarily effect PCT
Renal stones
- Renal calculi = struvite stones (alkaline pH, proteus), urate stones (acidic pH), cystine
stones (cystinuria) -> renal colic, hematuria, hydronephrosis
- Urate nephropathy = acute injury seen in chemotherapy, chronic injury causes gout ->
can progress to urate stones (nephrolithiasis)
- Myeloma nephropathy = Bence-Jones proteins & Tamm-Horsfall proteins form tubular
casts and induce granulomatous inflammation
- Hydronephrosis = urine flow obstruction -> dilation of renal pelvis/calyces -> cortical
thinning + renal atrophy
Renal vascular diseases
- Benign nephrosclerosis = due to chronic HTN (≥180/120) -> hyaline arteriosclerosis +
medial/intimal thickening -> bilateral leathery granular kidneys
- Malignant nephrosclerosis = due to malignant HTN (≥200/120) superimposed on
essential HTN/2oHTN/scleroderma/pheochromocytoma -> sudden increase in HTN
causes endothelial injury and increased permeability (protein leak) -> fibrinoid necrosis +
necrotizing vasculitis + thrombosis + onion skinned hyperplastic arteriosclerosis -> flea
bitten kidney
- Renal artery stenosis = due to atheromatous plaque (older men) or fibromuscular
dysplasia (younger women) -> chronically ischemic kidney causes constant renin release
-> HTN (surgically correctable) that eventually causes hyperplastic arteriosclerosis in
contralateral kidney
o Fibromuscular dysplasia can also cause strokes, MI, aneurysm and dissection ->
renal artery will have string of beads appearance
- Thrombotic microangiopathy = microangiopathic hemolytic anemia (schistocytes) +
thrombocytopenia (platelet-fibrin thrombi) + renal failure (cortical necrosis)
o HUS = EHEC (O157:7) or Shigella infection in children -> rapidly progressive renal
failure + hemorrhagic diarrhea
o TTP = ADAMTS13 deficiency -> altered mental status + fever + purpura
- Diffuse cortical necrosis = bilateral/symmetrical cortical necrosis due to conditions that
cause ischemia and DIC (HUS, TTP, abruptio placenta, etc.)
- Renal infarct = due to emboli from left heart -> flank pain, fever, leukocytosis,
proteinuria, hematuria -> wedge shaped pale
Congenital anomalies
- Fetal lobulation of kidney = normal renal function
- Horseshoe kidney = fusion of lower poles (ascent blocked by the IMA) -> seen in Turners
Cystic kidney diseases
- ADPKD = PKD gene (polycystin) mutation on chromosome 16 -> variably massive cysts
the only appear in the 4-5th decades -> HTN, hematuria, pain, polyuria, proteinuria and
eventual renal failure -> associated with Berry aneurysms, polycystic liver disease, cystic
spleen/pancreas/lung, colonic diverticulosis, mitral valve prolapse
- ARPKD = PKHD gene (fibrocystin) mutation on chromosome 6 -> bilateral multiple small
cysts (cuboidal cells) occurring in utero or childhood-> associated with Patau, Potters
sequence, hepatic fibrosis, portal HTN
- Multicystic renal dysplasia = abnormal differentiation of metanephric bud -> enlarged
kidney with multiple small cysts, primitive ducts, islands of cartilage
- Medullary sponge kidney = cystic dilatations of medullary collecting ducts in adults ->
risk of nephrolithiasis, infections, hematuria
- Familial juvenile nephronophthisis/uremic medullary cystic disease = shrunken kidneys
(cortical atrophy + interstitial fibrosis) with corticomedullary cysts -> renal failure,
polyuria, tubular acidosis, anemia
- Acquired cysts = associated with renal dialysis and renal cell carcinoma -> cysts
containing calcium oxalate crystals
Acute kidney injury = can be due to glomerular/interstitial/vascular/tubular injury ->
oliguria/anuria, azotemia

Chronic kidney disease = progressive kidney scarring -> signs of uremia

UTIs = can be pyelonephritis (upper UTI in kidney) or cystitis (lower UTI in bladder)

Bartter syndrome = polyuria -> hypercalciuria, hypokalemia, metabolic alkalosis, hypotension

Gitelman’s syndrome = hypomagnesemia, hypokalemia, hypercalciuria
Liddle syndrome = hypertension, hypokalemia

Pharmacology