Internal Medicine

Comprehensive study resource covering the major subspecialties of clinical medicine. Every diagnosis, every management guideline, every clinical correlation you need to know.

1. Cardiovascular

Heart Failure CAD Hypertension Afib Valvular Pericarditis Aortic Dissection PAD VTE

Epidemiology and Burden

Cardiovascular disease (CVD) is the leading cause of death globally, accounting for ~17. 9M deaths/year.
In the US, ~6. 2M adults have heart failure (HF), with lifetime risk ~20% at age 40.
Coronary artery disease (CAD) affects ~20M Americans; hypertension (HTN) affects ~47% of US adults.
Atrial fibrillation (Afib) prevalence rises sharply with age (0. 1% in > 9% in >= 80).
Valvular disease is present in ~2. 5% of the population, predominantly aortic stenosis (AS) in the elderly and mitral regurgitation (MR).
Venous thromboembolism (VTE) incidence is 1 - 2 per 1,000 person-years.

Pathophysiology

HFrEF involves progressive LV systolic dysfunction driven by neurohormonal activation - RAAS, sympathetic surges, and maladaptive cardiac remodeling (fibrosis, dilation).
HFpEF is dominated by diastolic dysfunction, LV stiffness, and systemic inflammation (linked to obesity, HTN, diabetes).
CAD results from atherosclerotic plaque rupture/erosion causing acute thrombosis; STEMI is transmural (occlusive), NSTEMI is subendocardial.
HTN increases afterload, promoting LV hypertrophy.
Afib arises from ectopic foci (pulmonary veins) with re-entrant circuits sustained by atrial remodeling.
Aortic dissection starts with an intimal tear in the ascending aorta (Type A) or descending (Type B), propagating through the media.
VTE: Virchow triad (stasis, hypercoagulability, endothelial injury).

Clinical Presentation

HF: dyspnea on exertion, orthopnea, PND, peripheral edema, JVD, S3 gallop.
CAD: stable angina (retrosternal pressure, exertion-relieved) vs ACS (prolonged pain, diaphoresis, dyspnea). STEMI: ST-elevation + troponin rise.
NSTEMI: troponin + without ST-elevation.
Afib: palpitations, irregularly irregular pulse, fatigue, dyspnea; can be asymptomatic.
AS: classic triad - angina, syncope, HF (poor prognosis once symptomatic).
MR: holosystolic murmur at apex radiating to axilla.
Pericarditis: sharp pleuritic pain, worse supine, relieved leaning forward.
Aortic dissection: sudden severe tearing chest pain radiating to back, pulse deficit, syncope.
PAD: claudication, rest pain, non-healing ulcers.

Diagnostic Workup

ECG: ischemia, LVH, Afib, pericarditis (diffuse PR depression + concave STE).
Troponin (hs-cTn) for ACS.
BNP/NT-proBNP for HF (exclusion 40 mmHg, area < 1. 0 cm^2).
Coronary angiography with FFR ( < 0. 80 = ischemic).
CT coronary calcium score. CTPA for PE.
ABI ( < 0. 9 = PAD).
Holter for paroxysmal Afib.
CHA„DS„-VASc for stroke risk.
HAS-BLED for bleed risk.

Treatment and Management

HFrEF GDMT: quadruple therapy - ARNI (sacubitril/valsartan) or ACEi/ARB + beta-blocker (bisoprolol, carvedilol) + MRA (spironolactone) + SGLT2i (dapagliflozin). HFpEF: SGLT2i first-line; manage HTN, diuresis.
STEMI: emergent PCI ( early invasive vs conservative.
DAPT (ASA + ticagrelor/prasugrel) 12 months.
HTN: target = 2 (DOACs preferred). AS: SAVR or TAVR for severe symptomatic.
Pericarditis: NSAIDs + colchicine. Aortic dissection: Type A -> emergent surgery; Type B -> medical (HR < 60, SBP 100 - 120).
PAD: exercise, antiplatelet, statin, revascularization. VTE: DOACs 3 - 6 months.

High-Yield Pearls

Wellens syndrome: deeply inverted T-waves in V2 - V3 -> critical proximal LAD stenosis - do NOT stress test.
HFpEF diagnosis requires: LVEF >= 50%, elevated BNP, diastolic dysfunction (E/e′ > 14).
Pulsus paradoxus > 10 mmHg: cardiac tamponade until proven otherwise.
Afib + WPW: avoid AV nodal blockers (verapamil, digoxin) -> risk of VF -> amiodarone or cardioversion.
HIT: check platelets days 5 - 10; stop heparin, start direct thrombin inhibitor (argatroban, bivalirudin).

Red Flags and Complications

STEMI equivalent: new LBBB + chest pain -> activate cath lab immediately.
Type A dissection with tamponade or coronary involvement -> surgical emergency.
Acute MR from papillary muscle rupture -> pulmonary edema, cardiogenic shock -> emergent mitral valve surgery.
Massive PE (SBP < 90): thrombolysis unless contraindicated.
Cardiac tamponade: Beck triad (hypotension, JVD, muffled heart sounds) + pulsus paradoxus -> emergent pericardiocentesis.

2. Respiratory

COPD Asthma Pneumonia ILD PE Pulmonary HTN OSA Pleural Effusion

Epidemiology and Burden

COPD is the 3rd leading cause of death worldwide (~3. 2M deaths/year).
Asthma affects ~262M people globally. Pneumonia: CAP incidence ~5 - 11/1000 adults; HAP ~2 - 5/1000 hospitalizations. ILD: IPF ~3 - 9/100,000; sarcoidosis ~10 - 20/100,000.
PE accounts for ~100,000 US deaths annually.
OSA affects ~25% of adults (substantially underdiagnosed).
Pleural effusion: transudate vs exudate determined by Light's criteria.

Pathophysiology

COPD: chronic inflammation (neutrophils, macrophages, CD8+ T-cells) from smoke -> emphysema (alveolar destruction, loss of elastic recoil) + chronic bronchitis (mucus gland hyperplasia, airway narrowing). Asthma: Th2-driven eosinophilic inflammation, IgE-mediated mast cell degranulation, bronchial hyperresponsiveness, reversible obstruction.
Pneumonia: microbial lung parenchyma invasion - CAP (Strep pneumo most common), HAP (MRSA, Pseudomonas).
IPF: aberrant wound healing -> fibroblast foci -> honeycombing (UIP pattern).
PE: thrombus (usually from DVT) occludes pulmonary artery -> increased dead space, RV pressure overload.

Clinical Presentation

COPD: chronic cough, sputum, dyspnea, wheezing, prolonged expiration, barrel chest.
Asthma: episodic wheezing, cough, chest tightness, nocturnal worsening.
Pneumonia: fever, productive cough, pleuritic pain, crackles, egophony.
IPF: insidious dry cough, exertional dyspnea, Velcro crackles, clubbing.
PE: acute dyspnea, pleuritic pain, hemoptysis, tachycardia, hypoxia; massive PE -> hypotension, syncope, RV strain.
OSA: loud snoring, witnessed apneas, excessive daytime sleepiness, obesity.
Pleural effusion: diminished breath sounds, dullness, decreased tactile fremitus.

Diagnostic Workup

PFTs: FEV1/FVC if +, D-dimer -> if +, CTPA (gold standard).
V/Q if contrast contraindicated.
ABG: hypoxemia, hypercapnia; A-a gradient widened in PE.
Polysomnography for OSA (AHI >= 5 + symptoms). Thoracentesis: Light's criteria (LDH, protein).

Treatment and Management

COPD: smoking cessation (#1). GOLD 2025: LAMA/LABA for group B/D; ICS if eosinophils >= 300.
Pulmonary rehab O„ if PaO&bdq; <= 55.
Exacerbations: bronchodilators, steroids, abx. Asthma: GINA step 1 - 5 - as-needed ICS-formoterol (mild); ICS/LABA + LAMA (severe); biologics (mepolizumab, benralizumab) for T2-high. CAP: CURB-65.
Empiric: macrolide (outpatient) or beta-lactam + macrolide (inpatient).
HAP: antipseudomonal beta-lactam + MRSA coverage.
IPF: antifibrotics (pirfenidone, nintedanib) slow progression. PE: DOACs first-line; thrombolysis for massive PE. OSA: CPAP first-line, weight loss.
Pleural effusion: treat cause; therapeutic thoracentesis if dyspneic.

High-Yield Pearls

A-a gradient: normal = age/4 + 4. Widened in PE, ILD, pneumonia; normal in hypoventilation.
COPD exacerbation: Anthonisen criteria - increased dyspnea + sputum volume + sputum purulence.
PE with RV hypokinesis = submassive (intermediate-risk); consider thrombolysis if deteriorating.
"Golden S sign" on CXR suggests lobar collapse from central mass (e.g., lung cancer).
Aspergillosis: chronic cavitary in pre-existing cavities -> voriconazole.

Red Flags and Complications

Tension pneumothorax: tracheal deviation, hypotension, distended neck veins -> needle decompression.
ARDS: bilateral infiltrates, PaO&bdq;/FiO&bdq; <= 300, not cardiac -> lung-protective ventilation (TV 6 mL/kg PBW).
Massive hemoptysis ( > 200 mL/24h) -> bronchial artery embolization or surgery.
Superimposed bacterial infection post-influenza (S. pneumo, S. aureus) -> empiric coverage.
Pulmonary HTN: right heart catheterization needed for diagnosis; treat underlying group.

3. Gastroenterology

GERD PUD IBD IBS Hepatitis Cirrhosis NAFLD Pancreatitis Celiac GI Bleeds

Epidemiology and Burden

GERD affects 18 - 28% of North Americans.
PUD prevalence ~5 - 10%; H. pylori in 70 - 90% of duodenal and 50 - 70% of gastric ulcers. IBD: UC ~10 - 20/100,000, Crohn's ~5 - 15/100,000.
IBS affects 10 - 15% globally (Rome IV).
Hep B infects ~257M chronically; Hep C ~58M.
Cirrhosis causes 1. 3M deaths/year.
NAFLD affects ~25% globally - now leading cause of liver transplant in many regions.
Pancreatitis incidence ~30 - 50/100,000.
Celiac disease ~1% prevalence, significant underdiagnosis.

Pathophysiology

GERD: transient LES relaxations, hypotensive LES, hiatal hernia -> acid/pepsin exposure. PUD: H. pylori (urease-producing) or NSAIDs (COX-1 inhibition, reduced prostaglandins) -> mucosal erosion. Crohn's: transmural inflammation, skip lesions, fistulas, granulomas, Th1/Th17.
UC: continuous mucosal inflammation from rectum proximally.
IBS: altered gut-brain axis, visceral hypersensitivity, dysmotility.
Hep B: HBV DNA integration -> chronic hepatitis -> cirrhosis/HCC.
NAFLD: insulin resistance, lipotoxicity -> steatosis -> NASH -> fibrosis.
Pancreatitis: premature trypsinogen activation -> autodigestion. Celiac: HLA-DQ2/DQ8 T-cell response to gliadin -> villous atrophy.

Clinical Presentation

GERD: heartburn, regurgitation, dysphagia, cough.
PUD: epigastric pain - duodenal (relieved by food) vs gastric (worse with food). Crohn's: RLQ pain, diarrhea, weight loss, perianal fistulas.
UC: bloody diarrhea, tenesmus, urgency.
IBS: chronic abdominal pain related to defecation, altered stool (Rome IV >= 1 day/week).
Acute hepatitis: jaundice, RUQ pain, nausea, transaminitis.
Cirrhosis: ascites, spider angiomas, caput medusae, encephalopathy, varices.
NAFLD: usually asymptomatic; hepatomegaly, elevated ALT/AST ( < 2 x ULN).
Pancreatitis: epigastric pain radiating to back, N/V, elevated lipase.
Celiac: diarrhea, bloating, weight loss, iron-deficiency anemia, dermatitis herpetiformis.
GI bleed: hematemesis/melena (upper) vs hematochezia (lower).

Diagnostic Workup

GERD/PUD: EGD with biopsy.
H. pylori: stool antigen, urea breath test, or biopsy urease.
IBD: colonoscopy + ileoscopy with biopsies; CT/MR enterography for Crohn's. IBS: Rome IV clinical diagnosis (exclude alarm features: bleeding, weight loss, age > 50, FHx).
Viral hepatitis: serology (HBsAg, anti-HBc, HBsAb; anti-HCV, HCV RNA).
Cirrhosis: transient elastography (FibroScan), labs (albumin ↓, INR ↑, platelets ↓), MELD-Na. NAFLD: US shows steatosis; FibroScan for fibrosis.
Pancreatitis: lipase > 3 x ULN + typical pain. Celiac: TTG-IgA + total IgA; EGD/biopsy confirms. GI bleed: EGD first (upper), colonoscopy (lower), CT angio if massive.

Treatment and Management

GERD: lifestyle (elevate head, avoid triggers), PPIs. PUD: H. pylori eradication - triple therapy (PPI + amoxicillin + clarithromycin) 14 days; quadruple if resistance. Crohn's: mesalamine -> steroids -> immunomodulators (azathioprine) -> anti-TNF (infliximab).
UC: mesalamine first-line; steroids for flares; anti-TNF or JAKi for refractory.
IBS: fiber, antispasmodics, low-FODMAP, rifaximin for IBS-D.
Hep B: tenofovir or entecavir.
Hep C: pangenotypic DAAs (sofosbuvir/velpatasvir) 12 weeks.
Cirrhosis: diuretics for ascites, beta-blockers for variceal prophylaxis, lactulose/rifaximin for encephalopathy.
NAFLD/NASH: weight loss >= 7%; vitamin E (non-diabetic, biopsy-proven NASH).
Pancreatitis: aggressive IVF, NPO, pain control.
Celiac: strict gluten-free diet lifelong.
GI bleed: resuscitate, PPI drip, restrictive transfusion (Hb < 7), endoscopic therapy (clips, banding for varices).

High-Yield Pearls

Child-Pugh C: 1-year survival ~50% -> refer for transplant evaluation.
H. pylori testing: stop PPI 2 weeks before urea breath test/stool antigen.
Budd-Chiari: hepatic vein thrombosis -> hepatomegaly, ascites; workup for PNH, JAK2.
PSC + UC -> increased cholangiocarcinoma risk; MRCP/MRI screening.
Zollinger-Ellison: gastrinoma -> refractory ulcers + high gastrin.

Red Flags and Complications

Variceal bleed: octreotide + ceftriaxone + urgent EGD banding (PPI insufficient).
Acute cholangitis: Charcot triad (pain, fever, jaundice) + Reynolds pentad (AMS, hypotension) -> ERCP emergency.
Toxic megacolon: transverse colon > 6 cm + systemic toxicity -> surgical consult, IV steroids, avoid antidiarrheals.
Boerhaave syndrome: vomiting + subcutaneous emphysema + mediastinitis -> surgical emergency.
SBP: cirrhotic ascites PMN >= 250/mm^3 -> cefotaxime + albumin.

4. Nephrology and Acid-Base

AKI CKD Glomerulonephritis Electrolytes Acid-Base HTN in CKD

Epidemiology and Burden

AKI occurs in ~15% of hospitalized patients, 50% in ICU.
CKD affects ~15% of US adults (37M); ~2. 5M have ESRD.
Glomerulonephritis accounts for ~10% of ESRD.
Electrolyte disorders are among the most common lab abnormalities.
Acid-base disturbances are universal in critical illness.
Global CKD burden rising, driven by diabetes and hypertension.

Pathophysiology

AKI: pre-renal (hypoperfusion -> RAAS activation), intrinsic (ATN from ischemia/nephrotoxins, AIN from drugs), post-renal (obstruction -> increased intratubular pressure).
CKD: progressive nephron loss -> hyperfiltration -> glomerulosclerosis -> declining eGFR.
Nephrotic: podocyte injury (MCD, FSGS, membranous).
Nephritic: immune complex deposition (post-strep, lupus, IgA, RPGN). Electrolytes: Na via water balance (ADH); K via shifts (insulin, catecholamines) and total body; Ca via PTH, vitamin D. Acid-base: Henderson-Hasselbalch; respiratory (CO&bdq;) vs metabolic (HCO^3−).

Clinical Presentation

AKI: oliguria, fluid overload, uremia, hyperkalemia, metabolic acidosis.
CKD: fatigue, edema, pruritus, nocturia, metallic taste, neuropathy.
Nephrotic: periorbital/peripheral edema, frothy urine.
Nephritic: hematuria (cola-colored), HTN, edema, RBC casts.
Hypernatremia: thirst, confusion, seizures.
Hyponatremia: headache, confusion, seizures (if acute/severe).
Hypokalemia: weakness, cramps, U-waves, arrhythmias.
Hyperkalemia: peaked T, weakness, cardiac arrest.
Hypercalcemia: stones, bones, groans, psychic moans. Metabolic acidosis: Kussmaul respirations, fatigue.

Diagnostic Workup

AKI: BUN/Cr > 20 (pre-renal), FeNa 2% (ATN), urine microscopy (muddy brown casts = ATN; RBC casts = GN; WBC casts = AIN).
Renal US to r/o obstruction.
CKD: eGFR (CKD-EPI), urine ACR, staging (G1 - 5, A1 - 3). GN serology: C3/C4, ANA, ANCA, anti-GBM, dsDNA, SPEP.
Renal biopsy for definitive diagnosis.
Electrolytes: serum + urine levels, osmolality. Acid-base: ABG + BMP -> anion gap (AG = Na − Cl − HCO^3), delta ratio (ΔAG/ΔHCO^3), Winter's formula (PaCO&bdq; = 1. 5 x [HCO^3] + 8 +/- 2).

Treatment and Management

AKI: IVF (pre-renal), hold nephrotoxins, relieve obstruction.
RRT indications: "AEIOU" - Acidosis (pH 6. 5), Ingestion, Overload (pulmonary edema), Uremia (pericarditis, encephalopathy). CKD: BP target 25.
Dietary: low Na, restrict K/PO´/protein. Anemia: iron, ESAs.
MBD: phosphate binders (sevelamer), vitamin D.
GN: nephrotic -> RAAS blockade, diuretics, steroids (MCD); nephritic -> immunosuppression (steroids + cyclophosphamide for RPGN).
Hyponatremia: correct <= 8 mEq/L/24h to avoid ODS; 3% NaCl if seizures. Hyperkalemia: Ca gluconate (cardiac) + insulin/glucose + albuterol + loop diuretic/resins.
Metabolic acidosis: treat underlying; NaHCO^3 if pH < 7. 1.

High-Yield Pearls

Delta ratio: < 1 = AG + non-AG metabolic acidosis; > 2 = concurrent metabolic alkalosis.
Winter's formula: if measured PaCO&bdq; > calculated = respiratory acidosis; < = respiratory alkalosis.
Post-streptococcal GN: low C3 (normalizes 6 - 8 weeks); if persistently low, think MPGN or lupus.
ACEi/ARB + SGLT2i + finerenone = "triple therapy" for CKD with T2DM.
FeUrea is more reliable than FeNa if on diuretics.

Red Flags and Complications

RPGN: crescents on biopsy -> pulse steroids + cyclophosphamide urgently.
Hyperkalemia with ECG changes: give IV Ca gluconate IMMEDIATELY.
Osmotic demyelination: overcorrection of hyponatremia -> quadriplegia, locked-in syndrome.
Renal artery stenosis: refractory HTN, flash pulmonary edema, ACEi-induced Cr rise -> CTA/MRA.
Alport syndrome: hereditary nephritis + hearing loss + ocular lesions.

5. Endocrinology

Diabetes Thyroid Adrenal Pituitary Ca/PTH PCOS Dyslipidemia

Epidemiology and Burden

Diabetes affects ~537M adults globally (IDF 2021); T2DM 90 - 95%.
DKA ~100,000 hospitalizations/year US.
Hypothyroidism ~5% hyperthyroidism ~1. 2%.
Adrenal insufficiency ~150 - 300/million.
Cushing ~0. 2 - 5/million/year.
PCOS 6 - 12% of reproductive-age women.
Dyslipidemia ~40% of US adults.
Osteoporosis ~10M Americans over 50.

Pathophysiology

T1DM: autoimmune β-cell destruction (islet cell antibodies, GAD-65) -> absolute insulin deficiency -> ketogenesis.
T2DM: insulin resistance + progressive β-cell dysfunction.
DKA: insulin deficiency -> lipolysis -> ketone bodies -> AG metabolic acidosis.
HHS: hyperglycemia > 600 mg/dL, hyperosmolality, minimal ketosis.
Hypothyroidism (Hashimoto's): autoimmune thyroid destruction.
Hyperthyroidism (Graves'): TSI stimulates TSH receptor. Cushing: ACTH-dependent (pituitary 70%) vs ACTH-independent (adrenal).
Hyperaldosteronism: renin-independent aldosterone excess. Ca metabolism: PTH ↑ Ca^2 +/- (bone resorption, renal reabsorption, vitamin D activation).

Clinical Presentation

T1DM: polyuria, polydipsia, weight loss, DKA.
T2DM: often asymptomatic; polyuria, fatigue, blurred vision, recurrent infections. DKA: N/V, abdominal pain, Kussmaul, fruity odor, AMS.
HHS: profound dehydration, AMS, seizures.
Hypothyroidism: fatigue, weight gain, cold intolerance, constipation, dry skin, bradycardia, delayed reflexes.
Hyperthyroidism: weight loss, heat intolerance, tachycardia, tremor, lid lag, exophthalmos. Cushing: central obesity, moon face, purple striae, easy bruising, proximal myopathy.
Addison: hyperpigmentation, orthostatic hypotension, hyponatremia, hyperkalemia.
Hypercalcemia: nephrolithiasis, bone pain, constipation, short QT.
Hypocalcemia: perioral numbness, Chvostek/Trousseau, prolonged QT, tetany.
PCOS: oligomenorrhea, hirsutism, acne, infertility.

Diagnostic Workup

Diabetes: FBG >= 126, HbA1c >= 6. 5%, OGTT 2h >= 200, or random >= 200 + sx.
DKA: glucose > 250, pH = 3, + AG.
HHS: glucose > 600, osm > 320, no ketones. Thyroid: TSH (screening). Graves: TSI + RAIU (diffuse increased). Thyroid nodules: US + FNA (Bethesda).
Adrenal: ACTH stim test (cosyntropin) for insufficiency; midnight salivary cortisol + DST for Cushing; ARR for aldosteronism.
Ca: corrected Ca = measured + 0. 8(4 − alb).
PTH: low in non-PTH hypercalcemia; high in primary hyperpara. Osteoporosis: DXA T-score <= −2. 5. PCOS: Rotterdam criteria (2 of 3: oligo-anovulation, hyperandrogenism, PCO morphology).
Dyslipidemia: fasting lipid panel + ASCVD risk estimator.

Treatment and Management

T1DM: basal-bolus insulin (MDI/pump), carb counting. DKA/HHS: IVF (0. 9% NS), insulin (0. 1 U/kg bolus + drip), K+ repletion if < 5. 3, dextrose when glucose < 250.
T2DM: metformin first-line; add SGLT2i or GLP-1 RA if ASCVD/HF/CKD.
Hypothyroidism: levothyroxine (1. 6 μg/kg/day); TSH goal 0. 5 - 2. 5.
Hyperthyroidism: methimazole, β-blockers, RAI or surgery.
Adrenal insufficiency: HC 15 - 25 mg/day + fludrocortisone (if primary). Cushing: transsphenoidal surgery (pituitary); adrenalectomy (adrenal source). Conn: spironolactone/eplerenone.
Hyperparathyroidism: parathyroidectomy if symptomatic or meets criteria.
Osteoporosis: bisphosphonates first-line; denosumab, teriparatide for high risk. PCOS: OCPs (hirsutism), metformin (metabolic), letrozole (ovulation).
Dyslipidemia: statins; ezetimibe/PCSK9i if refractory.

High-Yield Pearls

DKA: K+ correction is KEY - insulin drives K+ into cells -> hypokalemia risk.
Pseudohyponatremia: correct Na by 1.6 mEq per 100 mg/dL glucose > 100.
Thyroid storm: β-blocker + PTU/methimazole + SSKI + steroids.
MEN: MEN1 (parathyroid, pituitary, pancreas), MEN2A (MTC, pheo, parathyroid), MEN2B (MTC, pheo, neuromas).
Pheochromocytoma screening: plasma metanephrines (high sensitivity).

Red Flags and Complications

Adrenal crisis: hypotension, AMS, hyponatremia, hyperkalemia -> IV HC 100 mg + IVF STAT.
Myxedema coma: hypothermia, bradycardia, AMS -> IV levothyroxine + steroids (cover adrenal insufficiency).
Thyrotoxic periodic paralysis: Asian male, severe hypokalemia + paralysis -> β-blockers + K+ (non-dextrose).
Diabetic foot: neuropathic + vascular -> ulcer -> osteomyelitis -> amputation risk; examine feet every visit.
ONJ: in patients on bisphosphonates/denosumab having dental procedures -> consider drug holiday.

6. Rheumatology

RA SLE Gout Ankylosing Spondylitis PsA Vasculitis Scleroderma Sjogren Osteoporosis

Epidemiology and Burden

RA affects 0. 5 - 1. 0% globally (2 - 3:1 F:M).
SLE ~20 - 150/100,000 (9: 1 F:M). Gout ~4% US adults.
AS ~0. 1 - 1. 4%, HLA-B27 associated.
PsA ~0. 3 - 1%, in ~30% of psoriasis.
Vasculitides are rare: GPA ~10/million.
Scleroderma ~50 - 300/million.
Sjogren ~0. 1 - 1. 0% (9:1 F:M).
Osteoporosis ~200M women worldwide.

Pathophysiology

RA: autoimmune synovitis (Th17, TNF-α, IL-6, ACPA/RF) -> pannus -> cartilage/bone erosion.
SLE: loss of tolerance -> anti-nuclear antibodies (ANA, dsDNA, Smith) -> immune complex deposition -> multi-organ damage. Gout: MSU crystals activate NLRP3 inflammasome -> IL-1β -> neutrophil influx. Pseudogout: CPPD crystals. AS: HLA-B27 misfolding -> IL-23/IL-17 axis -> enthesitis, sacroiliitis, syndesmophytes.
ANCA vasculitis: necrotizing small-vessel inflammation (GPA, MPA, EGPA).
Scleroderma: endothelial dysfunction (Raynaud's) + fibroblast activation (fibrosis).
Osteoporosis: imbalance of osteoblast vs osteoclast activity.

Clinical Presentation

RA: symmetric small-joint polyarthritis (MCP, PIP, wrists, MTP), morning stiffness >= 30 min, ulnar deviation, swan-neck/Boutonniere deformities, nodules.
SLE: malar rash, DLE, oral ulcers, serositis, arthritis, lupus nephritis, hematologic, CNS.
Gout: acute monoarthritis (1st MTP = podagra), red/hot/swollen/excruciating; tophi in chronic.
AS: < 40 y/o chronic low back pain (improves with exercise), loss of lordosis, Schober +, uveitis. PsA: DIP, dactylitis, enthesitis, nail pitting.
GPA: triad - respiratory granulomas + GN + vasculitis; c-ANCA (PR3+) in 90%.
Scleroderma: CREST + ILD + PAH + renal crisis.
Sjogren: xerophthalmia + xerostomia + parotid enlargement + lymphoma risk.
Osteoporosis: asymptomatic until fragility fracture (hip, wrist, vertebral).

Diagnostic Workup

RA: RF anti-CCP ( > 95% specificity), ESR/CRP, X-ray (erosions, joint space narrowing).
ACR/EULAR 2010 criteria. SLE: ANA (screening, > 99% sensitive), anti-dsDNA, anti-Smith, anti-Ro/La, low C3/C4. 2019 EULAR/ACR criteria ( >= 10).
Gout: synovial fluid polarized microscopy (negatively birefringent MSU crystals), serum urate > 6. 8. AS: MRI SI joints (sacroiliitis), HLA-B27.
Vasculitis: ANCA (c-ANCA/PR3 for GPA, p-ANCA/MPO for MPA), tissue biopsy (gold). Scleroderma: ANA (nucleolar), anti-Scl-70 (diffuse), anti-centromere (limited/CREST), PFTs, echo PAH. Sjogren: Schirmer test, salivary gland biopsy (focus score), anti-Ro/SSA. Osteoporosis: DXA + FRAX.

Treatment and Management

RA: early DMARD - MTX + folic acid first-line.
Add TNFi (adalimumab) or IL-6i (tocilizumab) or JAKi (tofacitinib) if inadequate response. SLE: HCQ for all (reduces flares, improves survival).
Mycophenolate or cyclophosphamide for lupus nephritis III/IV.
Belimumab for non-renal.
Gout: acute - NSAIDs, colchicine, steroids.
Chronic - allopurinol first-line, goal urate < 6 ( < 5 if tophi). AS: NSAIDs, anti-TNF, IL-17i (secukinumab). PsA: TNFi, IL-17i, IL-23i, PDE4i (apremilast).
Vasculitis: high-dose steroids + rituximab/cyclophosphamide. Scleroderma: MMF for ILD, ERA/PDE5i for PAH, ACEi for renal crisis.
Sjogren: artificial tears, pilocarpine, HCQ.
Osteoporosis: bisphosphonates (alendronate), denosumab, teriparatide, romosozumab; Ca 1200 mg + vit D 800 IU/day.

High-Yield Pearls

Anti-CCP: >95% specificity for RA (RF ~70%). Both + = more aggressive disease.
Lupus nephritis: Class V (membranous) = nephrotic; Class III/IV (proliferative) = nephritic.
Febuxostat: contraindicated in prior MI/stroke (increased CV risk).
Scleroderma renal crisis: abrupt malignant HTN + AKI -> ACEi immediately; steroids can precipitate.
Drug-induced SLE: procainamide, hydralazine, minocycline, isoniazid, TNFi.

Red Flags and Complications

Cauda equina in AS: saddle anesthesia, urinary retention -> surgical emergency.
GPA with RPGN -> urgent steroids + rituximab/cyclophosphamide.
Lupus cerebritis: high-dose steroids + cyclophosphamide.
Macrophage activation syndrome (MAS): fever, hepatosplenomegaly, ferritin >10K, cytopenias.
Avascular necrosis of femoral head: in SLE (steroids) -> groin pain, MRI gold standard.

7. Infectious Disease

Sepsis Respiratory Infections Endocarditis Osteomyelitis CNS Infections TB HIV Antibiotic Stewardship

Epidemiology and Burden

Sepsis: ~49M cases/yr globally, 11M deaths (~20% of all deaths worldwide).
The #1 cause of death in hospitals.
Respiratory tract infections: pneumonia (5th leading cause of death globally), TB (~10M new cases/yr, 1. 5M deaths).
HIV: ~39M living with HIV globally, ~1. 3M new infections/yr.
Antimicrobial resistance (AMR): ~1. 3M direct deaths/yr; could reach 10M/yr by 2050 without action.
Endocarditis: incidence ~15/100,000/yr, increasing; ~30% associated with prosthetic valves/device.
Osteomyelitis: 1-3% of orthopedic surgeries complicated by infection; chronic osteomyelitis in 20% of acute if untreated.

Sepsis and Septic Shock

Sepsis-3: life-threatening organ dysfunction due to dysregulated host response to infection. qSOFA: altered mental status, RR >= 22, SBP = 2 mmol/L + need for vasopressors to maintain MAP >= 65 -> septic shock.
Pathophysiology: pathogen PAMPs -> TLR activation -> pro-inflammatory cytokine storm (TNF-α, IL-1, IL-6) + anti-inflammatory response (immunoparalysis) -> endothelial injury, microvascular thrombosis, mitochondrial dysfunction, multi-organ failure.
Treatment: 1-hr bundle: blood cultures (2 sets), lactate, broad-spectrum ABx (within 1h), 30 mL/kg crystalloid if hypotension/lactate >= 4, vasopressors (norepinephrine first-line) if MAP < 65 after fluids.
Corticosteroids: if refractory shock despite adequate fluids + high-dose vasopressors.
Source control within 6-12h.
EGDT not superior to usual care (ARISE, ProCESS, ProMISe).

Pneumonia

CAP: S. pneumoniae (~40%), H. influenzae, M. pneumoniae, C. pneumoniae, Legionella, viruses (COVID, influenza, RSV).
CURB-65 (confusion, BUN > 20, RR >= 30, BP = 65) -> severity.
Treatment: outpt (no comorbidities): amoxicillin or doxycycline or macrolide.
Outpt (comorbidities): amoxicillin-clavulanate + macrolide or respiratory FQ.
Inpt (non-ICU): beta-lactam + macrolide.
ICU: beta-lactam + macrolide or FQ.
HAP/VAP: consider MDR pathogens (MRSA, Pseudomonas, ESBL).
Duration: 5d (CAP), 7d (HAP/VAP) if responding.
HCAP no longer a distinct category.
Pneumococcal vaccine: PCV15/PCV20 + PPSV23.

Infective Endocarditis

Modified Duke Criteria (definite: 2 major OR 1 major + 3 minor OR 5 minor).
Major: (1) positive blood cultures (typical organism from 2 sets, persistently positive, or Coxiella serology); (2) endocardial involvement (vegetation, abscess, new partial dehiscence of prosthetic valve).
Minor: predisposition, fever, vascular phenomena, immunologic phenomena, microbiologic evidence. Native valve: S. aureus (most common), viridans group strep, Enterococcus, HACEK.
Prosthetic valve: early ( 1yr, similar to native). IV drug use: S. aureus (especially tricuspid).
Treatment: empiric vancomycin + ceftriaxone (native), vancomycin + cefepime + gentamicin (prosthetic).
S. aureus: 6wk nafcillin/cefazolin (MSSA) or vancomycin/daptomycin (MRSA).
Strep: 4wk PCN or ceftriaxone.
Enterococcus: 6wk ampicillin + ceftriaxone (E. faecalis) or vancomycin + gentamicin.
Indications for surgery: heart failure, uncontrolled infection (abscess, persistent bacteremia), prevention of embolism (large mobile vegetation > 10mm after embolus, > 15mm with high embolic risk).

Osteomyelitis

Acute: hematogenous (pyogenic bacteria -> metaphysis in children, vertebral in adults). Vertebral: S. aureus (most common), gram-neg rods (elderly, IVDU), TB (Pott disease).
Diabetic foot: polymicrobial (S. aureus, Strep, anaerobes, Enterobacteriaceae, Pseudomonas). Diagnosis: ESR/CRP elevated; X-ray shows periosteal reaction/lytic lesions after 2-3wk; MRI (best sensitivity ~90%, specificity ~80%); biopsy + culture gold standard.
Treatment: acute hematogenous: 4-6wk IV ABx (nafcillin/cefazolin for MSSA, vancomycin for MRSA).
Vertebral: 6-12wk IV then oral if responding.
Diabetic foot: based on bone culture; typically 6wk.
Debridement required for: abscess, necrotic bone, hardware, chronic.
Chronic: requires surgical debridement + 6-12wk ABx + dead space management.

Tuberculosis

Pulmonary TB: cough > 3wk, hemoptysis, night sweats, fever, weight loss.
CXR: apical infiltrates, cavities. Primary: Ghon focus + lymphadenopathy (Ghon complex).
Reactivation: apical cavitary disease. Diagnosis: AFB smear + NAAT (GeneXpert) + culture (Lowenstein-Jensen, liquid broth).
IGRA (Quantiferon) or PPD for latent TB.
Treatment (drug-sensitive): 2-month intensive: RIPE (rifampin, INH, pyrazinamide, ethambutol) daily; then 4-month continuation: RI.
Miliary TB: diffuse small nodules, treat 9-12mo -> steroids for TB meningitis.
MDR-TB: resistance to R + I; requires 18-24mo BPaL (bedaquiline, pretomanid, linezolid) or longer individualized regimen.
LTBI: 4R (4mo rifampin) or 3HP (3mo weekly INH + rifapentine) or 9H.
BCG: reduces miliary/meningeal TB in children.

HIV/AIDS

Transmission: blood/sexual/perinatal.
Natural history: acute HIV (mononucleosis-like 2-6wk) -> asymptomatic latency (~8-10yr) -> AIDS (CD4 TMP-SMX (PCP); CD4 azithromycin (MAC); CD4 CMV monitoring.
Immune reconstitution inflammatory syndrome (IRIS): paradoxical worsening after ART initiation -> treat OI first, continue ART.

CNS Infections

Meningitis: bacterial (S. pneumoniae, N. meningitidis, H. influenzae, L. monocytogenes, GBS, E. coli), viral (enterovirus, HSV, VZV, West Nile), fungal (cryptococcus).
Empiric ABx: vancomycin + ceftriaxone + ampicillin (elderly/immunocompromised).
Dexamethasone before/with ABx (pneumococcal). Encephalitis: HSV (temporal lobe, acyclovir), VZV, West Nile.
Brain abscess: streptococci (viridans, anginosus), S. aureus, anaerobes, Enterobacteriaceae.
Treatment: empiric ceftriaxone + metronidazole + vancomycin.
N. meningitidis: droplet precautions, rifampin/ceftriaxone/cipro prophylaxis for contacts.
Cryptococcal meningitis (HIV): L-AmB + flucytosine then fluconazole.

Other Key Infections

UTI: uncomplicated vs complicated -> TMP-SMX or nitrofurantoin (uncomplicated); FQ or carbapenem (complicated, ESBL). Pyelonephritis: FQ or ceftriaxone 14d.
C. difficile: mild-moderate -> vancomycin 125mg PO QID 10d or fidaxomicin 200mg BID 10d; severe/fulminant -> vancomycin PO + IV metronidazole.
Cellulitis: beta-hemolytic strep + S. aureus; treat cephalexin or clindamycin.
Necrotizing fasciitis: polymicrobial or GAS, urgent surgical debridement + broad spectrum ABx.
Catheter-related BSI: remove line, treat 7-14d, S. aureus/Tx candida -> TEE to rule out endocarditis.

Antibiotic Stewardship

Right drug right dose, right duration, right indication.
De-escalate based on cultures. Shorten duration: CAP 5d, HAP 7d, UTI 3-5d (uncomplicated), pyelo 7d (if responding).
Avoid FQ for uncomplicated infections unless no alternative.
Use procalcitonin to guide ABx discontinuation in respiratory infections (PCT stop).
Stewardship reduces C. diff, AMR, costs, length of stay.

High-Yield Pearls

Sepsis 1-hr bundle: blood cultures, lactate, broad-spectrum ABx, 30mL/kg crystalloid, vasopressors PRN.
Duke Criteria: 2 major or 1 major + 3 minor or 5 minor = definite IE.
LTBI: 4R (4mo rifampin) or 3HP (3mo INH + rifapentine weekly) preferred over 9H.
ART regardless of CD4; INSTI + 2 NRTIs first-line; U=U.
Pneumococcal vaccine: PCV15/PCV20 + PPSV23 for all >= 65 and high-risk 19-64.

Red Flags and Complications

S. aureus bacteremia -> always order TEE to exclude endocarditis.
Necrotizing fasciitis: pain out of proportion, crepitus, rapid progression -> immediate surgery.
Meningococcemia: petechiae/purpura, shock -> empiric ABx + droplet precautions + contact prophylaxis.
C. diff: severe colitis, toxic megacolon, ileus, perforation -> vancomycin PO + IV metronidazole, consider vancomycin PR if ileus.
IRIS: paradoxical worsening after ART -> treat OI, continue ART, consider steroids.

8. Allergy and Immunology

Anaphylaxis Asthma Allergic Rhinitis Drug Allergy Food Allergy Uticaria Angioedema Primary Immunodeficiencies

Epidemiology and Burden

Allergic diseases affect ~30% of the global population.
Asthma: ~300M people worldwide; 5-10% severe (uncontrolled despite high-dose ICS/LABA).
Allergic rhinitis: ~15-30% prevalence; costs ~$5B/yr in lost productivity and treatment.
Food allergy: 6-8% children, 3-4% adults; 150-200 deaths/yr from anaphylaxis in US.
Drug allergy: 10-15% of hospitalized patients report a drug allergy; most common = beta-lactams (10% of patients) but > 90% of these tolerate PCN on testing.
Primary immunodeficiencies (PIDs): prevalence ~1:1,200 live births; CVID most common symptomatic PID (1:25,000).
Anaphylaxis: lifetime risk ~0. 5-2%; fatality rate ~0. 3-0. 7/100,000 cases.

Anaphylaxis

Definition: severe, life-threatening, generalized or systemic hypersensitivity reaction with rapid onset.
Diagnostic criteria (NIAID/FASE): acute onset (min-hr) with involvement of skin/mucosa AND at least one of: respiratory compromise, reduced BP, end-organ dysfunction. Or: 2+ of: skin/mucosa, respiratory, BP, GI. Or: known allergen + hypotension alone.
Triggers: food (peanut, tree nut, shellfish, egg, milk), medications (ABx, NSAIDs, biologics), insect venom (Hymenoptera), latex, exercise-induced, idiopathic.
Pathophysiology: mast cell/basophil degranulation -> histamine, tryptase, PAF, leukotrienes -> vasodilation, bronchospasm, edema, urticaria, hypotension.
Treatment: IM epinephrine (1:1000, 0. 01 mg/kg, max 0. 3-0. 5 mg) anterolateral thigh, repeat q5-15min.
No death from anaphylaxis is ascribable to epinephrine; death is due to delayed epinephrine. Adjuncts: H1/H2 blockers, steroids, albuterol.
Observation: 4-6h (biphasic reaction in ~5%).
Discharge: auto-injector, action plan, allergy referral.
Indications for ICU: severe biphasic, need for epinephrine drip, severe airway compromise.

Asthma

Variable airway obstruction due to chronic airway inflammation + bronchial hyperresponsiveness.
Phenotypes: allergic (early-onset, IgE, eosinophilic, Th2-high), non-allergic (late-onset, neutrophilic, Th2-low), eosinophilic (adult-onset, severe, high FeNO/eos), exercise-induced (bronchoconstriction during exertion).
Diagnosis: spirometry with bronchodilator (FEV1/FVC = 12% >= 200mL improvement).
Alternative: bronchial challenge (methacholine) if suspicion persists.
Exhaled NO (FeNO) > 50 ppb = eosinophilic inflammation.
Treatment (GINA): Step 1: as-needed low-dose ICS-formoterol.
Step 2: low-dose ICS-formoterol maintenance + reliever (MART).
Step 3: medium-dose ICS-formoterol MART.
Step 4: high-dose ICS-formoterol MART + add-on (LAMA, LTRA, theophylline).
Step 5: add-on biologic (anti-IgE omalizumab, anti-IL5 mepolizumab/benralizumab/reslizumab, anti-IL4R dupilumab, anti-TSLP tezepelumab) + oral corticosteroids (lowest dose possible).
Severe asthma: >= 50% of exacerbations prevented with biologics.
Non-pharmacologic: allergen avoidance, smoking cessation, influenza/COVID/SARS2 vaccine, PAP for OSA, exercise, weight loss.

Allergic Rhinitis (Hay Fever)

Seasonal vs perennial.
Symptoms: sneezing, rhinorrhea, nasal congestion, itchy nose/eyes/palate, postnasal drip.
Diagnosis: clinical + skin prick (prick/puncture) + sigE (ImmunoCAP).
Treatment: intranasal corticosteroids (INCS) first-line (fluticasone, mometasone, triamcinolone).
Intranasal antihistamines (azelastine, olopatadine).
Oral antihistamines: 2nd gen (cetirizine, levocetirizine, fexofenadine, loratadine, desloratadine).
Montelukast: add-on for nocturnal symptoms (but boxed warning for neuropsychiatric events).
Allergen immunotherapy (AIT): SCIT or SLIT, for moderate-severe uncontrolled with medications.
Other: saline irrigation, allergen avoidance.

Drug Allergy

Type I (immediate, IgE-mediated): urticaria, angioedema, anaphylaxis within 1-6h.
Type II (cytotoxic): hemolytic anemia, thrombocytopenia (e. g. , PCN, cephalosporins, methyldopa).
Type III (immune complex): serum sickness, DRESS, vasculitis.
Type IV (delayed, T-cell-mediated): MPE, SJS/TEN, AGEP, DRESS.
Penicillin allergy: 10% report, > 90% tolerate; no cross-reactivity with cephalosporins except 1st gen (1-2% cross).
If severe IgE-mediated (anaphylaxis, angioedema) -> skin testing (PPL + MDM, then full-dose challenge if negative).
If negative -> de-label.
Cephalosporin cross-reactivity: 30% (TEN); -> stop all drugs, ICU burn unit, IVIG/cyclosporine, supportive wound care.
SCORTEN predicts mortality.

Food Allergy and Urticaria/Angioedema

IgE-mediated food allergy: most common triggers = peanut, tree nut, shellfish, fish, egg, milk, soy, wheat, sesame, finned fish.
Diagnosis: sIgE + skin testing, oral food challenge (gold standard).
Treatment: strict avoidance; auto-injector for all IgE-mediated food allergy (especially if prior anaphylaxis).
OIT (oral immunotherapy) available for peanut (Palforzia) after skin testing.
Chronic urticaria: spontaneous (CSU, autoimmune, > 6wk) vs inducible (physical).
First-line: 2nd gen H1 (up to 4x dose).
Second-line: add H2, montelukast.
Third-line: omalizumab (anti-IgE, ~70% complete response).
Fourth-line: cyclosporine.
Angioedema: histaminergic (urticaria + angioedema = treat with H1/H2/steroids) vs bradykinin-mediated (HAE: C1-inhibitor deficiency, ACEi-induced).
HAE: no urticaria, no pruritus, often GI + laryngeal; treat with C1-INH replacement (Berinert, Cinryze), ecallantide (kallikrein inhibitor), icatibant (bradykinin B2 antagonist).
ACEi-AE: stop ACEi; consider ARB (safe to switch).

Primary Immunodeficiencies

CVID (Common Variable Immunodeficiency): onset 20-40yr, low IgG + IgA +/- IgM, impaired antibody response, recurrent sinopulmonary infections, autoimmune manifestations (ITP, AIHA, IBD), lymphoproliferation (lymphoma risk 30-50x). Treatment: IVIG/SCIG replacement q3-4wk.
Bruton agammaglobulinemia (XLA): onset normal/high IgM, low IgG/A/E, Pneumocystis + Cryptosporidium + neutropenia; IVIG + HSCT.
Wiskott-Aldrich syndrome: X-linked, eczema + thrombocytopenia (small platelets) + recurrent infections + autoimmune + lymphoma; HSCT curative.
Ataxia-telangiectasia: ATM mutation -> cerebellar ataxia + telangiectasias + IgA/IgE deficiency + radiosensitivity + lymphoma risk; avoid radiation.
DiGeorge (22q11. 2 deletion): thymic aplasia -> low T cells, hypocalcemia, conotruncal heart defects; if complete: thymus transplant or HSCT.

9. Hematology

Anemia Sickle Cell Thalassemia VWD Hemophilia DIC TTP/HUS Leukemia Lymphoma Myeloma MDS Transfusion

Epidemiology and Burden

Anemia ~1. 9B globally (iron deficiency #1).
SCD ~100K Americans, ~20M globally.
Thalassemia: α-thal (Asia/Africa), β-thal (Mediterranean).
VWD ~1% (most common inherited bleeding disorder).
Hemophilia A ~1/5000 males.
DIC common in sepsis/trauma/malignancy. TTP ~4/million.
Leukemia: AML ~20K/yr, CLL most common adult, CML ~8K, ALL ~6K. Lymphoma: HL ~8. 5K, NHL ~77K/yr. Myeloma ~35K/yr.
MDS ~10 - 15K/yr US.

Pathophysiology

Microcytic anemia: Fe deficiency (low ferritin, low Fe, high TIBC), thalassemia (microcytosis out of proportion), ACD (high ferritin, low Fe, low TIBC). Macrocytic: B12 def (demyelination + anemia), folate def (anemia only), MDS, alcohol.
Hemolytic: intrinsic (spherocytosis, G6PD, SCD) vs extrinsic (AIHA, MAHA). SCD: HbS polymerizes -> sickling -> vaso-occlusion -> hemolysis -> organ damage.
Thalassemia: ↓ globin chain -> ineffective erythropoiesis + iron overload.
VWD: quantitative/qualitative VWF deficiency.
Hemophilia A/B: X-linked FVIII/FIX deficiency.
DIC: systemic coagulation activation -> microthrombi + factor consumption. TTP: ADAMTS13 deficiency -> uncleaved VWF multimers -> microthrombi. HUS: Shiga toxin -> endothelial damage.
Leukemia: clonal proliferation with maturation arrest (AML = Auer rods; CML = BCR-ABL; CLL = CD5+; ALL = lymphoblasts). Lymphoma: HL = Reed-Sternberg (CD15+, CD30+); NHL = heterogeneous (DLBCL, FL, MALT).
Myeloma: clonal plasma cells -> M-protein -> lytic lesions, hyperCa, renal failure, anemia.

Clinical Presentation

Anemia: fatigue, pallor, DOE, palpitations, glossitis (Fe/B12), koilonychia (Fe).
SCD: acute pain crises, acute chest syndrome, aplastic crisis (parvovirus B19), autosplenectomy, stroke.
Thalassemia major: severe anemia, failure to thrive, skeletal deformities, hepatosplenomegaly, iron overload.
VWD: easy bruising, epistaxis, menorrhagia, prolonged surgical bleeding.
Hemophilia: hemarthroses, deep hematomas, muscle bleeds.
DIC: concurrent bleeding and thrombosis. TTP: MAHA + thrombocytopenia + fever + neuro sx + renal (pentad). HUS: MAHA + thrombocytopenia + AKI (post-diarrheal).
Leukemia: cytopenias (fatigue, infection, bleeding), fever, bone pain, lymphadenopathy, gum hypertrophy (AML M4/M5).
CML: incidental WBC elevation, splenomegaly.
Lymphoma: painless LAD, B-symptoms (fever, night sweats, weight loss). Myeloma: CRAB - hyperCalcemia, Renal failure, Anemia, Bone lesions.
MDS: cytopenias with hypercellular marrow.

Diagnostic Workup

CBC + indices (MCV, MCH, RDW), reticulocyte count.
Fe studies, B12, folate. Hemolysis: LDH ↑, haptoglobin ↓, bili ↑, DAT (Coombs).
Smear: schistocytes (TTP/HUS, DIC), spherocytes (AIHA), sickle cells, target cells, tear drops (myelofibrosis).
Hb electrophoresis for SCD/thal. VWD: VWF Ag, ristocetin cofactor, FVIII, multimers.
Hemophilia: FVIII/FIX activity, prolonged PTT (corrects).
DIC: platelets ↓, PT/PTT ↑, D-dimer ↑, fibrinogen ↓. TTP: ADAMTS13 < 10%.
BMB: essential for leukemia, myeloma, MDS. Cytogenetics: BCR-ABL (CML), FLT3/NPM1 (AML).
SPEP + immunofixation + free light chains (myeloma).
Skeletal survey: lytic lesions.

Treatment and Management

Fe deficiency: oral ferrous sulfate (reticulocytosis day 7 - 10, Hb +1 g/dL q2 - 3wk).
IV Fe if intolerant. B12: IM/SC 1000 μg monthly. SCD: HU first-line (↓ crises); L-glutamine, crizanlizumab, voxelotor.
Transfusion for acute chest syndrome/stroke.
Penicillin ppx + vaccines. β-thal major: regular transfusions + chelation (deferasirox). VWD: DDAVP (type 1); VWF concentrates (type 2/3). Hemophilia A: FVIII concentrates; emicizumab for ppx (with/without inhibitors).
DIC: treat cause; platelets if bleeding, cryo if fibrinogen < 100, FFP if INR ↑. TTP: PLEX + steroids + rituximab; avoid platelets.
AML: 7+3 induction + consolidation; targeted (FLT3i, IDHi, venetoclax + HMA). CML: TKI (imatinib, dasatinib, nilotinib).
CLL: watchful waiting (early); ibrutinib, venetoclax.
ALL: multi-agent chemo + CAR-T for refractory. HL: ABVD x 2 - 4 + RT. NHL: R-CHOP (DLBCL), R-bendamustine (FL).
Myeloma: VRd (bortezomib, lenalidomide, dex) + daratumumab; auto SCT.
MDS: supportive; lenalidomide (del5q); HMA (azacitidine); transplant for eligible.

High-Yield Pearls

Mentzer index (MCV/RBC): < 13 = thal trait; > 13 = Fe deficiency.
TTP: MAHA + thrombocytopenia without other cause. ADAMTS13 < 10%. Start PLEX immediately.
Auer rods = pathognomonic for AML.
HL staging: early (IA - IIA favorable) -> ABVD x 2 + RT; advanced -> ABVD x 6.
Daratumumab (anti-CD38) causes DAT+ but not true hemolysis.

Red Flags and Complications

Tumor lysis syndrome: hyperuricemia, hyperK, hyperPhos, hypoCa -> allopurinol/rasburicase + aggressive IVF.
Hyperleukocytosis (WBC > 100K): in AML/CML -> leukostasis -> emergent leukapheresis.
Spinal cord compression (myeloma): back pain + leg weakness/bladder sx -> MRI + steroids + RT.
Acute chest syndrome (SCD): new pulmonary infiltrate + fever -> abx, transfusion, bronchodilators.
Priapism in SCD: urologic emergency -> hydration, analgesia, exchange transfusion; urology if > 4h.

10. Oncology

Lung Breast Colorectal Prostate Palliative Care

Epidemiology and Burden

Cancer is the 2nd leading cause of death globally (~10M deaths/yr).
Lung cancer is the leading cancer killer (1. 8M deaths/yr).
NSCLC 85%, SCLC 15%.
Breast cancer is the most common cancer in women (~2. 3M cases/yr).
CRC is 3rd most common (~1. 9M cases/yr).
Prostate cancer is 2nd most common in men (~1. 4M cases/yr).
Effective screening (USPSTF) reduces mortality for breast, cervical, colorectal, and lung cancers.

Pathophysiology

Lung: NSCLC subtypes - adenocarcinoma (most common, peripheral, non-smokers), squamous (central, cavitating), large cell.
SCLC (neuroendocrine, rapid, paraneoplastic). Driver mutations: EGFR, ALK, ROS1, KRAS, BRAF, MET, RET, NTRK. Breast: HR+ (ER/PR+), HER2+, triple-negative.
BRCA1/BRCA2 -> familial.
CRC: adenoma-carcinoma sequence (APC -> KRAS -> TP53) vs MSI (Lynch).
Prostate: androgen-dependent growth; Gleason grading (3+4, 4+3, etc. ). Paraneoplastic: SCLC (SIADH, LEMS), squamous (hypercalcemia/PTHrP).

Clinical Presentation

Lung: cough, hemoptysis, dyspnea, chest pain, hoarseness (recurrent laryngeal), Horner (Pancoast), SVCS, post-obstructive pneumonia.
Breast: painless mass, axillary LAD, peau d'orange, nipple retraction, bloody discharge.
CRC: change in bowel habits, hematochezia, weight loss, IDA (right colon).
Prostate: often asymptomatic; urinary obstruction, hematuria, bone pain (mets).
Palliative: pain, nausea, dyspnea, constipation, fatigue, depression, existential distress.

Diagnostic Workup

Lung: CT chest + PET-CT.
Tissue via bronchoscopy/EBUS/CT-guided. Molecular: EGFR, ALK, ROS1, PD-L1, NGS.
Breast: mammogram + US + core biopsy. ER/PR/HER2/ki-67.
CRC: colonoscopy + biopsy; CT CAP; MSI/MMR testing.
Prostate: PSA (shared decision); MRI before biopsy; Gleason scoring; PSMA-PET for mets. General: TNM staging determines treatment.
ECOG performance status critical.

Treatment and Management

NSCLC: I - III -> surgery +/- chemo.
III unresectable -> chemoradiation + durvalumab.
IV -> targeted if driver (osimertinib for EGFR, alectinib for ALK, entrectinib for NTRK).
IO (pembrolizumab) if PD-L1 >= 50% or + chemo.
SCLC: etoposide + platinum + atezolizumab/durvalumab; PCI for limited-stage.
Breast: lumpectomy + SLNB + RT vs mastectomy.
Adjuvant: endocrine (tamoxifen/AI) if HR+; trastuzumab if HER2+; neoadjuvant chemo for TN/HER2+.
CRC: surgical resection; FOLFOX/CAPOX for stage III/high-risk II.
Stage IV: FOLFOX/FOLFIRI + bevacizumab or anti-EGFR (RAS wt, left). IO for MSI-H.
Prostate: active surveillance (low risk); prostatectomy or RT (intermediate/high).
ADT for advanced; abiraterone/enzalutamide for CRPC; docetaxel, radium-223. Palliative: WHO ladder (acetaminophen -> NSAIDs -> weak -> strong opioids).
Nausea: ondansetron, metoclopramide, dexamethasone, olanzapine.
Bowel regimen with opioids.

High-Yield Pearls

Osimertinib first-line for EGFR-mutant NSCLC (best CNS penetration); T790M resistance check.
Trastuzumab (Herceptin) cardiotoxicity: serial ECHO monitoring.
Bevacizumab: avoid within 4 weeks of surgery (wound healing); risk of perforation, hemorrhage.
FOLFOX: oxaliplatin neuropathy (cold sensitivity). FOLFIRI: irinotecan diarrhea.
ADT ↑ CV risk, bone loss, metabolic syndrome -> manage proactively.

Red Flags and Complications

SVCS: SCLC/lymphoma -> head/neck swelling, dyspnea -> urgent RT + stenting.
Febrile neutropenia (ANC < 500 + fever >= 38.3) -> blood cultures + empiric broad abx (cefepime).
Spinal cord compression: MRI STAT + dexamethasone + RT/surgery (irreversible if delay > 24 - 48h).
Hypercalcemia of malignancy: IVF + bisphosphonates (zoledronic acid) + calcitonin.
irAE from checkpoint inhibitors: colitis, pneumonitis, hepatitis, thyroiditis, myocarditis -> hold IO, steroids.

11. Neurology

Stroke/TIA Seizures Dementia Parkinson's Headache MS GBS MG

Epidemiology and Burden

Stroke is the #1 cause of disability globally. ~795K strokes/yr US (87% ischemic, 10% ICH, 3% SAH).
Epilepsy ~50M worldwide.
Dementia ~55M globally (Alzheimer's 60 - 80%).
Parkinson's ~1% over age 60.
Migraine ~12% of adults. MS ~2. 8M globally.
GBS ~0. 5 - 2/100K/yr.
MG ~20 - 40/100,000.

Pathophysiology

Ischemic stroke: thrombotic (large/small vessel), embolic (cardioembolic, cryptogenic).
Hemorrhagic: hypertensive (basal ganglia, thalamus), amyloid angiopathy (lobar), aneurysm (SAH), AVM.
Seizures: abnormal synchronous neuronal discharge (focal vs generalized).
Alzheimer's: amyloid plaques (Aβ42) + neurofibrillary tangles (tau).
Parkinson's: substantia nigra dopamine neuron loss -> Lewy bodies (α-synuclein). Migraine: CSD -> trigeminovascular activation -> CGRP release. MS: CNS demyelination (T-cell mediated).
GBS: molecular mimicry -> anti-ganglioside antibodies -> peripheral demyelination/axonal. MG: AChR antibodies (80 - 90%) -> impaired neuromuscular transmission.

Clinical Presentation

Stroke: sudden focal deficit (FAST). NIHSS score.
Anterior: hemiparesis, hemisensory, aphasia (dominant), neglect (non-dominant).
Posterior: vertigo, diplopia, ataxia, visual field cuts.
Seizures: focal aware -> focal impaired -> generalized tonic-clonic -> absence; post-ictal confusion.
Alzheimer's: insidious short-term memory loss -> progressive cognitive decline. Parkinson's: TRAP - Tremor (resting, pill-rolling), Rigidity (cogwheel), Akinesia/bradykinesia, Postural instability (asymmetric onset).
Migraine: unilateral throbbing 4 - 72h, N/V, photo/phonophobia +/- aura.
Cluster: severe orbital pain + autonomic features (lacrimation, rhinorrhea, miosis).
Tension: bilateral band-like tightness.
MS: relapsing-remitting (optic neuritis, transverse myelitis, sensory/motor).
GBS: ascending symmetric flaccid paralysis, areflexia; Miller-Fisher (opthalmoplegia, ataxia, areflexia, anti-GQ1b).
MG: fluctuating weakness - ptosis, diplopia, dysphagia, proximal limbs; improves with rest, worsens with use. Myasthenic crisis.

Diagnostic Workup

Stroke: non-contrast CT (r/o hemorrhage), CTA (LVO), MRI DWI (acute infarct).
NIHSS, Carotid Dopplers, ECHO, telemetry. TIA: ABCD^2 score. Seizures: EEG (interictal epileptiform), MRI brain, labs (Na, glucose, Ca, Mg).
Dementia: MoCA ( CT/MR, LP, ESR. MS: MRI (demyelinating lesions, Dawson fingers), CSF (oligoclonal bands, elevated IgG), evoked potentials. GBS: LP (cytoalbuminologic dissociation), EMG/NCS (demyelinating). MG: AChR antibodies (80%), RNS (decremental), SFEMG (most sensitive), chest CT for thymoma.

Treatment and Management

Acute ischemic stroke: IV tPA within 4. 5h (r/o hemorrhage, strict criteria).
Mechanical thrombectomy for LVO within 6 - 24h (perfusion imaging). Stroke unit.
DAPT 21d for minor stroke/TIA.
Secondary ppx: antiplatelet + high-intensity statin + BP control +/- anticoagulation. ICH: BP fosphenytoin/valproate/levetiracetam -> anesthetics.
Alzheimer's: donepezil, rivastigmine (mild-moderate); memantine (moderate-severe).
Parkinson's: carbidopa/levodopa (most effective), DA agonists, MAO-Bi, DBS.
Migraine acute: triptans, NSAIDs, gepants, ditans.
Prevention: β-blockers, topiramate, amitriptyline, CGRP mAbs (erenumab). Cluster: O&bdq; 12 - 15 L/min, sumatriptan SC; verapamil for prevention.
MS: relapse -> IV methylprednisolone. DMT: IFN, GA, fingolimod, dimethyl fumarate, natalizumab, ocrelizumab. GBS: IVIG or PLEX; ICU monitoring (FVC, NIF).
MG: pyridostigmine + steroids/azathioprine/MMF.
Thymectomy if thymoma or generalized AChR+ MG.
Myasthenic crisis -> IVIG/PLEX + ICU.

High-Yield Pearls

tPA exclusions: > 4.5h, ICH, recent surgery/stroke, INR > 1.7, plt < 100K, BP > 185/110.
Status epilepticus: continuous seizure > 5 min or 2+ without recovery. ABC -> benzodiazepine.
Myasthenic crisis: NIF < −20, VC < 15 mL/kg -> intubation, IVIG/PLEX.
Migraine + aura: avoid estrogen-containing OCPs (↑ stroke risk).
Cholinergic crisis: excessive pyridostigmine -> fasciculations, miosis, sweating. Differentiate with edrophonium test.

Red Flags and Complications

SAH: thunderclap "worst headache of life" -> non-contrast CT (best < 6h); if negative, LP for xanthochromia.
Malignant MCA syndrome: large infarct with midline shift -> hemicraniectomy.
NMS: rigidity + fever + AMS + autonomic instability from antipsychotics -> dantrolene, bromocriptine.
Serotonin syndrome: clonus, hyperthermia, hyperreflexia from serotonergic agents -> cyproheptadine.
GBS: monitor for autonomic instability (arrhythmias, BP lability) and respiratory failure (serial NIF, VC).

12. Geriatrics

Frailty Polypharmacy Falls Delirium vs Dementia Elder Abuse Pressure Injuries

Epidemiology and Burden

Older adults ( > 65) are the fastest-growing population (1. 5B by 2050).
Frailty ~10 - 15% of community-dwelling older adults.
Polypharmacy ( >= 5 meds) in 40%; potentially inappropriate medications in 25 - 50% (Beers Criteria).
Falls: ~30% of older adults fall each year; 10% serious injury.
Delirium ~30% of hospitalized older adults (50% ICU).
Pressure injuries ~2. 5M/yr US ($9 - 11B cost).
Elder abuse ~10% (often unrecognized).

Pathophysiology

Frailty: multi-system decline - sarcopenia, neuroendocrine dysregulation (↓ IGF-1, ↑ cortisol), immune dysfunction (↑ IL-6, CRP).
Phenotype: weight loss, exhaustion, weakness, slow gait, low activity.
Polypharmacy: altered PK (↓ renal/hepatic clearance, ↓ Vd, ↓ albumin) + altered PD (↑ sensitivity to CNS drugs, anticholinergics) -> ↑ ADEs, drug interactions, prescribing cascade.
Falls: multifactorial - age-related changes + environment + medications (especially psychotropics, antihypertensives).
Delirium: acute brain dysfunction - neurotransmitter imbalance (↓ ACh, ↑ DA, ↑ 5-HT) + neuroinflammation.
Dementia pathology discussed above.
Pressure injuries: unrelieved pressure -> ischemia -> necrosis.
Elder abuse: risk factors - caregiver stress, dependency, social isolation, cognitive impairment.

Clinical Presentation

Frailty: Fried phenotype >= 3 of 5 - unintentional weight loss >= 10 lb/yr, exhaustion, weak grip, slow gait ( > 5s/15ft), low activity. Polypharmacy: ADEs (falls, hypotension, bleeding, delirium), drug interactions, prescribing cascade.
Falls: assess cause, gait, balance, orthostatics, vision, medications.
Delirium: acute, fluctuating, inattention, disorganized thinking, AMS (hyperactive vs hypoactive = missed).
Delirium vs dementia: acute vs chronic, fluctuating vs stable, reversible vs progressive.
Dementia: chronic progressive cognitive decline. Pressure injuries: Stage I (non-blanchable) -> II (partial) -> III (full, visible fat) -> IV (bone/muscle) -> Unstageable (eschar).
Common sites: sacrum, heels, trochanters.
Elder abuse: physical (bruises, fractures), emotional, financial, neglect (poor hygiene, untreated conditions, malnutrition).

Diagnostic Workup

Geriatric assessment: medical, functional (ADLs/IADLs), cognitive (MoCA), mobility (TUG), nutrition (MNA), vision/hearing, social, advance care planning.
Polypharmacy: medication reconciliation (brown bag), Beers Criteria, STOPP/START. Delirium: CAM - acute + fluctuating + inattention + disorganized thinking or AMS.
Workup: CBC, BMP, glucose, Ca, Mg, TSH, B12, UA, tox, cultures, ABG, EEG.
Falls: postural BP, vision, neuro exam, TUG ( > 12s = high risk), ECG, medication review. Pressure injury: NPUAP staging; labs (albumin, wound culture if infected).
Elder abuse: screen (EASI), mandatory reporting, imaging for occult fractures, social work/APS.

Treatment and Management

Frailty: resistance + aerobic exercise, protein >= 1. 2 g/kg/d, vitamin D 800 IU + Ca 1200, deprescribe.
Polypharmacy: systematic deprescribing - taper benzodiazepines, PPIs, anticholinergics, antihistamines, avoid tight glycemic control.
BP target: individualize (SBP flap closure.
Elder abuse: mandatory reporting, safety plan, legal interventions, caregiver support/respite, placement if needed.

High-Yield Pearls

"One fall is never just a fall" - assess balance, gait, orthostatics, vision, meds, home safety.
Hypoactive delirium > dangerous than hyperactive - often missed, higher mortality.
Beers: avoid benzodiazepines, anticholinergics, muscle relaxants, sulfonylureas, NSAIDs, long-term PPIs.
TUG > 12s = high fall risk.
Antipsychotic for delirium: start low, go slow, re-evaluate daily for discontinuation.

Red Flags and Complications

Anticholinergic toxicity: confusion, urinary retention, constipation, hyperthermia -> identify and remove.
Hip fracture: surgery within 24 - 48h; pre-op optimization; start bisphosphonate post-op.
Dehydration -> hypernatremia, prerenal AKI, orthostasis, falls.
Aspiration pneumonia: in dementia/PD/stroke -> swallowing assessment, thickened liquids/NPO, PEG if needed.
Elder abuse: suspicious injuries, delay in seeking care, caregiver refuses to leave -> mandatory reporting.

13. Preventive Medicine

USPSTF Screening Vaccinations Lifestyle Genetic Screening

Epidemiology and Burden

Preventive medicine reduces cancer mortality by 30 - 50% for screened cancers.
Only ~50% of eligible US adults receive recommended preventive services.
CVD + cancer = ~50% of all deaths (both modifiable).
Vaccine-preventable diseases still cause ~50K adult deaths/yr US. ~40% of US adults have obesity (BMI >= 30).
Tobacco is the #1 preventable cause of death (480K/yr).
Genetic screening identifies 5 - 10% with hereditary cancer syndromes.

Pathophysiology of Prevention

Primary: prevent before disease (vaccines, lifestyle, chemoprevention).
Secondary: early detection of asymptomatic disease (screening).
Tertiary: prevent progression/complications of established disease.
Health behaviors shaped by social determinants.
The 5Ms guide geriatric prevention: Mobility, Mind, Medications, Multicomplexity, Matters Most.
Vaccines work through humoral/cell-mediated immunity; herd immunity at 80 - 95% coverage.
Genetic screening identifies heritable mutations for targeted prevention.

USPSTF Screening (Grade A/B)

Breast: biennial mammography 50 - 74 (shared decision 40 - 49). Cervical: Pap q3y 21 - 65; HPV co-test q5y 30 - 65. CRC: FIT q1y or colonoscopy q10y 45 - 75. Lung: LDCT 50 - 80, >= 20 pk-yr, current/quit = 65.
AAA: one-time US men 65 - 75 ever smoked.
T2DM: screen 35 - 70 with overweight/obesity.
HTN: screen at any age.
Lipids: men >= 35, women >= 45 with risk.
HIV: screen 15 - 65 (once; annually if high risk).
Hep C: one-time 18 - 79. Syphilis: at-risk.
Depression: all adults (PHQ-9).
Anxiety: adults = 30).
Aspirin primary ppx: age 40 - 59 with 10-yr ASCVD >= 10%, low bleed risk.

Adult Vaccination Schedule (CDC 2025)

Influenza: annually ( >= 6mo; high-dose/adjuvanted for >= 65).
Tdap: one dose then Td/Tdap q10y; Tdap each pregnancy 27 - 36wk.
HPV: 2-dose at 11 - 12 (catch-up through 26; shared decision 27 - 45). Pneumococcal: PCV15/PCV20 + PPSV23 (if PCV15) for >= 65 or high-risk. Zoster: RZV 2-dose at >= 50.
COVID-19: annual updated 2025 - 26 vaccine ( >= 6mo; >= 65: 2 doses/season).
RSV: one dose for >= 75 or >= 60 with chronic conditions.
HepA: at-risk.
HepB: all >= 19 (catch-up).
MMR: 1 dose if no immunity (born >= 1957).
Varicella: 2 doses if no immunity (born >= 1980).
Meningococcal ACWY: if asplenia, complement deficiency, MSM, HIV, college.
MenB: shared decision 16 - 23.
Travel vaccines: per destination.

Lifestyle Counseling and Genetic Screening

Tobacco: 5 As (Ask, Advise, Assess, Assist, Arrange).
Varenicline most effective pharmacotherapy. Diet: Mediterranean (Level A for CVD prevention) - fruits, veg, whole grains, fish, olive oil, nuts.
Activity: 150 min/wk moderate or 75 vigorous + 2d strength.
Weight: intensive behavioral interventions; GLP-1 RA (semaglutide, tirzepatide) if BMI >= 30 or >= 27 + comorbidity; bariatric surgery if BMI >= 40 or >= 35 + comorbidity.
Alcohol: enhanced screening, RRSO 35 - 40 (BRCA1) or 40 - 45 (BRCA2), PARPi for treatment.
Lynch -> colonoscopy q1 - 2y starting 20 - 25, prophylactic hysterectomy.
FH -> high-intensity statin + ezetimibe + PCSK9i; cascade screening.
Hemochromatosis -> HFE (C282Y) -> phlebotomy.
FAP -> APC mutation -> prophylactic colectomy.
Always genetic counseling before/after testing.

High-Yield Pearls

NNS for CRC (colonoscopy) to prevent 1 death: ~150; breast: ~1500; lung: ~320.
Varenicline: most effective single smoking cessation pharmacotherapy (NNT < 10). Avoid bupropion if seizure hx.
Mediterranean diet = only diet with Level A evidence for CVD prevention.
Statin primary ppx: ASCVD risk >= 7.5% -> moderate-to-high intensity statin.
BRCA1 ovarian cancer risk ~40% lifetime; RRSO at 35 - 40. BRCA2 ~15%; RRSO at 40 - 45.

Red Flags and Complications

Not screening is the biggest gap - order age-appropriate cancer screening at every preventive visit.
Missed vaccination opportunity: assess immunization status at every visit; strongly recommend co-administration.
Aspirin for primary ppx: only in select 40 - 59 yo with ASCVD risk >= 10% AND low bleeding risk; no longer routine >= 70.
BRCA+ with current cancer: PARP inhibitors (olaparib, niraparib) improve survival.
Lynch syndrome: annual colonoscopy starting 20 - 25; associated endometrial, ovarian, gastric, urothelial, brain, pancreatic cancers - comprehensive surveillance.

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