1. Portal Hypertension

• Lower esophagus (esophageal varices - most dangerous)
• Around umbilicus (caput medusae)
• Rectum (anorectal varices)
• Retroperitoneum

• Esophageal/gastric varices - life-threatening hemorrhage
• Ascites
• Hepatic encephalopathy (see below)
• Splenomegaly

• Sclerotherapy (injection of sclerosing agents) - complications: perforation, stricture, infection
• TIPS (Transjugular Intrahepatic Portosystemic Shunt) - catheter via jugular vein into liver; stent placed between hepatic vein branch and portal vein branch
• Distal splenorenal shunt - now preferred surgical option; diverts only splenic blood away from liver, so lower incidence of encephalopathy vs. portacaval shunts
• Medical Physiology, p. 3828-3832

2. Hepatic Encephalopathy

• Grade 1: Mild confusion, euphoria, irritability
• Grade 2: Lethargy, disorientation
• Grade 3: Somnolent but arousable, gross disorientation
• Grade 4: Coma

• Lactulose (reduces NH₃ production and absorption)
• Rifaximin (non-absorbable antibiotic)
• Treat precipitants: infection, GI bleeding, constipation, sedatives, electrolyte imbalance
• Sleisenger and Fordtran's GI and Liver Disease, p. 3657; Medical Physiology, p. 3837

3. Whipple's Triad

1. Symptoms consistent with hypoglycemia (sweating, tremor, confusion, palpitations)
2. Low plasma glucose level (< 50 mg/dL / 2.8 mmol/L) during symptomatic episode
3. Relief of symptoms upon administration of glucose

• Maingot's Abdominal Operations, p. 4094-4100; Harrison's Principles of Internal Medicine 22E

4. Acute Pancreatitis

1. Abdominal pain consistent with pancreatitis
2. Serum amylase or lipase > 3x upper limit of normal
3. Characteristic findings on abdominal imaging

1. Gallstones / biliary sludge / microlithiasis (>50%)
2. Alcohol (~30%)
3. Others (<15%): hypertriglyceridemia (TG > 1000 mg/dL), trauma, medications, ERCP, neoplasm, viral infection, idiopathic

• Aggressive IV hydration - 250-500 mL/hr isotonic crystalloid; most critical management step; prevents pancreatic necrosis if given in first 12-24 hours
• Goal: decrease BUN
• ERCP within 24h only if concurrent acute cholangitis
• CECT/MRI reserved for unclear diagnosis or failure to improve at 48-72 hours
• Medical therapy is primarily supportive

• Textbook of Family Medicine 9e, p. 1803-1848

5. Pellagra (Niacin/Vitamin B3 Deficiency)

• Diet of corn/maize (bound niacin unavailable without alkaline hydrolysis)
• Alcoholism
• Carcinoid syndrome (tryptophan diverted to serotonin, ~60% instead of normal 1%)
• Hartnup disease (autosomal recessive; defective neutral amino acid transporter - malabsorption of tryptophan)
• Isoniazid use (competitive inhibitor of NAD; also impairs pyridoxine)
• Other drugs: 5-fluorouracil, 6-mercaptopurine, phenytoin

1. Dermatitis - photosensitive, erythematous, painful rash in sun-exposed areas; "gauntlet" on dorsum of hands; "Casal's necklace" around neck; butterfly distribution on face
2. Diarrhea
3. Dementia (neuropsychiatric manifestations)
4. Death (if untreated)

• Fitzpatrick's Dermatology, p. 2585-2596; Harrison's 22E

6. Vitamin B12 Deficiency

• Pernicious anemia (autoimmune: anti-intrinsic factor antibodies, anti-parietal cell antibodies) - most common in developed world
• Dietary (strict vegans)
• Gastrectomy / gastric surgery (loss of intrinsic factor)
• Ileal disease or resection (site of B12-IF complex absorption)
• Metformin use (impairs absorption)
• Tapeworm (Diphyllobothrium latum)

1. Methionine synthase: homocysteine → methionine (↑ homocysteine in deficiency)
2. Methylmalonyl-CoA mutase: methylmalonyl-CoA → succinyl-CoA (↑ methylmalonic acid in deficiency)

• Macrocytic (megaloblastic) anemia (MCV > 100 fL)
• Hypersegmented neutrophils (>5 lobes) - hallmark smear finding
• Pancytopenia
• Elevated LDH, indirect bilirubin (ineffective erythropoiesis)

• Subacute Combined Degeneration of the Spinal Cord (SACD): degeneration of dorsal and lateral columns
• Paresthesias (hands and feet), loss of vibration sense and proprioception
• Spastic weakness, ataxia
• Loss of deep tendon reflexes
• Neuropsychiatric: "megaloblastic madness," memory disturbance, irritability

• IM cyanocobalamin 1000 mcg weekly x 4 weeks, then monthly (for pernicious anemia or malabsorption)
• Oral B12 1000-2000 mcg/day (for dietary deficiency or when absorption is adequate)

7. Heat Stroke vs. Heat Syncope

• Core temp >40°C is hallmark
• CNS collapse distinguishes from heat exhaustion
• Best cooling: ice-water immersion
• Until proven otherwise, consider heat stroke as the diagnosis in any heat casualty with altered mental status
• Textbook of Family Medicine 9e, Table 29-7; Washington Manual of Medical Therapeutics

8. Hypercalcemia

• C - Calcium supplementation
• H - Hydrochlorothiazide (thiazide diuretics)
• I - Iatrogenic, Immobilization
• M - Multiple myeloma, Milk-alkali syndrome, Medications (lithium)
• P - Parathyroid adenoma/hyperplasia (primary hyperparathyroidism - most common outpatient cause)
• A - Alcohol
• N - Neoplasm (PTHrP; bone mets - most common inpatient cause)
• Z - Zollinger-Ellison syndrome
• E - Excessive vitamin D
• E - Excessive vitamin A
• S - Sarcoidosis (and other granulomatous diseases)

• Bones: Osteitis fibrosa cystica, pathological fractures
• Stones: Renal calculi, nephrocalcinosis
• Groans/Thrones: Nausea, vomiting, constipation, peptic ulcers, pancreatitis
• Moans: Fatigue, weakness, myalgia
• Psychiatric overtones: Confusion, depression, psychosis, coma

• Short QT interval (most characteristic)
• Prolonged PR interval
• Widened QRS
• In severe: Osborn (J) waves, VF risk

• Mild/asymptomatic: Oral hydration, treat cause
• Moderate-Severe: IV 0.9% NS (volume expansion + calciuresis), furosemide (after adequate hydration)
• Bisphosphonates (pamidronate/zoledronate) for malignancy-related
• Calcitonin (rapid onset, short-lived)
• Steroids (for granulomatous disease, vitamin D toxicity)
• Dialysis for refractory cases

9. Hyperkalemia

• Impaired renal excretion (most common cause of sustained hyperkalemia): renal failure, hypoaldosteronism, amiloride/spironolactone
• Transcellular shift: acidosis (H+ enters cells, K+ exits), beta-blockers, digoxin toxicity (inhibits Na-K pump)
• Massive cell breakdown: hemolysis, rhabdomyolysis, burns, tumor lysis syndrome, GI bleeding

1. Peaked/tall tented T waves (earliest)
2. Widened PR interval
3. Loss of P waves
4. Widened QRS
5. Sine wave pattern → VF/asystole

• C - Calcium gluconate IV (membrane stabilization; works in minutes; does NOT lower K+)
• B - Bicarbonate IV (if acidotic; shifts K+ into cells)
• G - Glucose + Insulin (shifts K+ intracellularly; insulin 10 units + 50 mL 50% dextrose)
• D - (Diuretics) + Sodium polystyrene sulfonate (Kayexalate) or patiromer/sodium zirconium - removes K+ from body via GI tract (takes hours)
• Dialysis - for renal failure or refractory cases (definitive)
• Medical Physiology, p. 2159-2165

10. H. pylori Eradication Regimens

• Harrison's Principles of Internal Medicine 22E, p. 2327-2342; Rosen's Emergency Medicine

11. Budd-Chiari Syndrome

• Myeloproliferative disorders (40-50%; especially polycythemia vera, essential thrombocythemia) - most common
• Antiphospholipid syndrome (10-12%)
• Paroxysmal nocturnal hemoglobinuria (PNH) (7-12%)
• Factor V Leiden mutation (8%)
• Protein C deficiency (5%), Protein S deficiency (4%), Antithrombin III deficiency
• Factor II mutation (3%)
• Oral contraceptive pills
• Pregnancy
• Malignancy, trauma, IBD
• Idiopathic (20%)

• Acute/subacute: Sudden onset ascites, abdominal pain, jaundice, hepatomegaly, hepatic encephalopathy, renal failure
• Chronic (most common): Progressive ascites, absent jaundice, hepatosplenomegaly

• Doppler USS: First line; shows reversed/absent hepatic vein flow (often diagnostic alone)
• CT/MRI: Caudate lobe hypertrophy (drains separately into IVC - spared), peripheral liver atrophy
• Ascitic fluid: protein >2 g/dL, WBC <500/µL, SAAG >1.1
• ↑LFTs (25-50% cases); ↑INR, ↓albumin with chronicity

• Anticoagulation (warfarin/direct Xa inhibitors) - all patients, even without identified cause
• Treat underlying cause (e.g., hydroxyurea for polycythemia vera)
• Beta-blockers for variceal prophylaxis
• Diuretics for ascites
• TIPS (Transjugular Intrahepatic Portosystemic Shunt) for refractory cases
• Liver transplant - definitive for end-stage disease
• Sources: StatPearls - Budd-Chiari Syndrome; Cleveland Clinic

12. Metabolic Acidosis and HAGMA (High Anion Gap Metabolic Acidosis)

AG = Na⁺ - (Cl⁻ + HCO₃⁻) Normal AG = 10-12 mEq/L (corrected for albumin; add 2.5 for every 1 g/dL albumin below 4 g/dL)

1. Get ABG + electrolytes simultaneously
2. Verify calculated HCO₃⁻ (ABG) matches measured HCO₃⁻ (electrolytes) within ±2
3. Calculate AG (correct for albumin)
4. If high AG present → identify cause
5. Compare Delta-Delta: Δ AG vs Δ HCO₃⁻ (detects mixed disorders)
6. Estimate compensatory response

• GI bicarbonate loss: diarrhea, fistula, ostomy
• Renal tubular acidosis (RTA)
• Carbonic anhydrase inhibitors (acetazolamide)
• Adrenal insufficiency (Type IV RTA)

• <1: High AG + normal AG acidosis (mixed)
• 1-2: Pure high AG metabolic acidosis

• 2: High AG metabolic acidosis + metabolic alkalosis

Expected PaCO₂ = 1.5 × HCO₃⁻ + 8 ± 2 (If actual PaCO₂ lower than expected → additional respiratory alkalosis) (If actual PaCO₂ higher than expected → additional respiratory acidosis)

• Harrison's Principles of Internal Medicine 22E, p. 664-703; Brenner and Rector's The Kidney

• Harrison's Principles of Internal Medicine 22E (2025)
• Goldman-Cecil Medicine
• Sleisenger and Fordtran's GI and Liver Disease
• Brenner and Rector's The Kidney
• Bailey and Love's Surgery
• Adams and Victor's Principles of Neurology
• Braunwald's Heart Disease
• Robbins & Cotran Pathologic Basis of Disease
• Washington Manual of Medical Therapeutics
• Medical Physiology (Boron & Boulpaep)
• Rosen's Emergency Medicine
• Fitzpatrick's Dermatology
• ...and others

1. Cover all your original topics using Harrison's 22E + Goldman-Cecil as the primary sources?
2. Focus on specific topics you haven't covered yet?

1. Portal Hypertension

1. Increased intrahepatic resistance to blood flow (due to cirrhosis, regenerative nodules, microthrombi)
2. Increased splanchnic blood flow secondary to vasodilation within the splanchnic vascular bed

• In advanced stages: neurohumoral activation → sodium and water retention → increased blood volume → hyperdynamic circulation → worsens portal hypertension

• 5-10 mmHg: Compensated cirrhosis - asymptomatic, can last ≥10 years
• ≥10 mmHg: Clinically Significant Portal Hypertension (CSPH) - substantial risk of decompensation
• Decompensation: median mortality <2 years

2. Hepatic Encephalopathy

• Note: Ammonia-encephalopathy correlation is often poor; most hepatologists do not rely on ammonia levels alone for diagnosis or monitoring.

• Volume depletion
• GI bleeding
• Hyponatremia
• Infection (always tap ascites to rule out SBP)
• Constipation
• Sedatives/opiates
• Electrolyte imbalance

• Confusion, personality change, somnolence
• Asterixis ("liver flap") - extension of arms + dorsiflexion of wrists → sudden forward flap of wrist

• Correct precipitating factors; correct electrolytes; hydration often sufficient
• Lactulose (mainstay) - nonabsorbable disaccharide → colonic acidification → catharsis → eliminates nitrogenous products. Goal: 2-3 soft stools per day
• Rifaximin 550 mg twice daily - replaced neomycin/metronidazole due to toxicity; very effective adjunct for recurrent episodes
• Dietary protein restriction is strongly discouraged (negative impact on nutrition outweighs benefit)

3. Whipple's Triad

1. Symptoms consistent with hypoglycemia (autonomic: sweating, tremor, palpitations; neuroglycopenic: confusion, visual changes, seizures)
2. Low plasma glucose (<50 mg/dL / 2.8 mmol/L) documented during the symptomatic episode
3. Relief of symptoms with administration of glucose

4. Acute Pancreatitis

• Gallstones + alcohol account for 80-90%
• Gallstones (30-60%) - most common; stones <5 mm carry 4x higher risk
• Alcohol (15-30%) - second most common
• Severe hypertriglyceridemia
• ERCP (especially after therapeutic intervention)
• Drugs: azathioprine, 6-MP, sulfonamides, estrogens, tetracycline, valproic acid, DPP-4 inhibitors
• Hypercalcemia, pancreatic cancer, trauma, infections (mumps, CMV, coxsackievirus), autoimmune, hereditary, cystic fibrosis, idiopathic

• Risk factors for increased severity: Age >60, obesity (BMI >30), comorbid disease
• SIRS criteria (≥2 of): Temp <36 or >38°C, HR >90, RR >20 or PaCO₂ <32, WBC >12,000 or <4,000 or >10% bands
• APACHE II ≥8 at 24h
• Hemoconcentration (Hct >44%)
• BUN >20 mg/dL on admission
• BISAP score ≥3: BUN >25, Impaired mental status, SIRS ≥2, Age >60, Pleural effusion

• Early aggressive IV fluid resuscitation - the single most important intervention
• Lactated Ringer's preferred over normal saline (reduces systemic inflammation, lower CRP)
• Initial bolus ~15-20 mL/kg, then 2-3 mL/kg/hr; maintain urine output >0.5 mL/kg/hr
• Recent RCT caveat: A less aggressive strategy (10 mL/kg bolus then 1.5 mL/kg/hr) showed no worse outcomes, with less risk of fluid overload
• Serial assessment every 6-8h; monitor Hct and BUN every 8-12h
• NPO initially; IV analgesics; supplemental O₂
• ERCP within 24h only if concurrent acute cholangitis

5. Pellagra (Niacin/Vitamin B3 Deficiency)

• Corn/maize-based diets (bound niacin unavailable) - China, Africa, India
• Alcoholism (most common in North America)
• Hartnup disease - autosomal recessive; defective intestinal/renal absorption of neutral amino acids including tryptophan
• Carcinoid syndrome - increased tryptophan → serotonin conversion
• Isoniazid - structural analogue of niacin; precipitates pellagra (also mass scale-up of TB preventive therapy)
• Famine/population displacement (deficiency of cofactors: iron, riboflavin, pyridoxine needed for tryptophan → niacin conversion)

1. Dermatitis - Photosensitive, pigmented, scaling rash in sun-exposed areas; Casal's necklace (ring around the neck in advanced cases); bright red glossitis (early)
2. Diarrhea (partly from proctitis, partly from malabsorption)
3. Dementia - Depression, seizures, dementia
4. Death (if untreated)

• Also: loss of appetite, weakness, irritability, abdominal pain, vomiting, vaginitis, esophagitis

• Oral nicotinamide or nicotinic acid 100-200 mg three times daily for up to 4 weeks

6. Vitamin B12 (Cobalamin) Deficiency

• Cobalamin exists mainly as deoxyadenosylcobalamin (in mitochondria - cofactor for L-methylmalonyl-CoA mutase) and methylcobalamin (in plasma/cytoplasm - cofactor for methionine synthase)
• Body stores: 2-3 mg → sufficient for 3-4 years if intake completely cut off
• Daily requirement: 1-3 μg; daily losses: 1-3 μg (~0.1% of stores)
• Dietary source: exclusively animal-origin foods (meat, fish, dairy); vegetables/fruits contain none

• Pernicious anemia (PA) - autoimmune destruction of parietal cells; anti-IF antibodies; anti-parietal cell antibodies → most common in developed world
• Strict vegans / dietary deficiency
• Gastrectomy / gastric surgery (loss of IF)
• Terminal ileal disease or resection (Crohn's disease)
• Metformin (impairs absorption)
• Fish tapeworm (Diphyllobothrium latum)

• Serum B12: Normal = 118-148 to ~738 pmol/L; in deficiency usually <74 pmol/L (100 ng/L); borderline: 74-148 pmol/L
• Serum methylmalonic acid (MMA) - raised in B12 deficiency (most specific); also elevated in renal failure
• Serum homocysteine - raised in both B12 and folate deficiency (less specific)
• Caution: commercial assays may give false normal B12 in up to 50% of PA patients with intrinsic antibodies → if PA strongly suspected, check MMA even if B12 seems normal
• Tests for cause: serum gastrin (raised in PA), anti-IF antibodies

• Macrocytic megaloblastic anemia (MCV >100)
• Hypersegmented neutrophils (pathognomonic)
• Pancytopenia

• Subacute Combined Degeneration (SCD) of spinal cord - posterior + lateral column degeneration
• Paresthesias of hands and feet (first symptom)
• Loss of vibration and proprioception (posterior column)
• Progressive spastic + ataxic weakness (lateral column)
• Loss of reflexes + Babinski signs simultaneously (key diagnostic clue)
• Optic atrophy, cognitive changes, irritability in advanced cases
• Romberg sign positive

• IM vitamin B12 1000 μg daily for 5-7 days → then weekly for 4-8 weeks → then monthly maintenance
• Oral maintenance: cyanocobalamin 1-2 mg daily (even in PA, small amounts absorbed passively) - suitable for maintenance
• Nitrous oxide (laughing gas) irreversibly inhibits B12 → identical SCD picture; seen in dental/surgical settings or recreational "whippets"

7. Heat Stroke vs. Heat Syncope

• Orthostatic/postural dizziness at cessation of exercise or prolonged standing
• Normal body temperature; consciousness returns promptly when supine
• This return to normal when supine distinguishes it from heat stroke
• Management: rest supine, legs elevated, oral fluids, cooling

• Hallmark: elevated core temperature + altered mental status
• Key rule (Harrison's): "Until proven otherwise, heat stroke should be the initial working diagnosis in anyone who is a heat casualty and has an altered mental status"
• Types: Classic (non-exertional; elderly, chronically ill) and Exertional (young, athletes)
• Management: immediate aggressive cooling (ice-water immersion best), hospitalization, IV fluids, treat complications (rhabdomyolysis, DIC, AKI)

8. Hypercalcemia

• Bones: osteitis fibrosa cystica, fractures
• Stones: renal calculi, nephrocalcinosis
• Groans/Thrones: nausea, vomiting, constipation, pancreatitis, peptic ulcer
• Moans: fatigue, weakness
• Psychiatric: confusion, depression, psychosis, coma

• Volume expansion with IV 0.9% NS (first step - increases urinary calcium excretion)
• Furosemide (after adequate rehydration)
• Bisphosphonates (IV pamidronate or zoledronate) for malignancy
• Calcitonin (rapid but short-lived; 4U/kg IM/SC)
• Steroids for granulomatous disease or vitamin D toxicity
• Cinacalcet for hyperparathyroidism
• Denosumab for refractory/malignancy cases

9. Hyperkalemia

• Cellular efflux in thrombocytosis, erythrocytosis, leukocytosis, in vitro hemolysis
• Hereditary RBC membrane transport defects

• Acidosis
• Hyperosmolality (radiocontrast, hypertonic dextrose, mannitol)
• β₂-adrenergic antagonists (non-cardioselective)
• Digoxin and related glycosides (yellow oleander, foxglove)
• Hyperkalemic periodic paralysis
• Succinylcholine; thermal trauma, neuromuscular injury, immobilization
• Rapid tumor lysis; lysine, arginine, ε-aminocaproic acid

• Inhibition of RAAS (ACE inhibitors, ARBs, renin inhibitors, spironolactone/eplerenone, amiloride/triamterene, trimethoprim, pentamidine)
• Decreased distal delivery: CCF, volume depletion
• Hyporeninemic hypoaldosteronism: diabetes, NSAIDs, β-blockers, CKD
• Advanced renal failure

1. Peaked (tented) T waves - earliest sign
2. Prolonged PR interval
3. Loss of P waves
4. Widened QRS
5. Sine wave → VF / asystole

• Ca gluconate IV - membrane stabilization; does NOT lower K+; works within minutes
• Glucose + Insulin - shifts K+ intracellularly
• NaHCO₃ - if acidotic; shifts K+ into cells
• Sodium polystyrene sulfonate (Kayexalate) or patiromer / sodium zirconium cyclosilicate - removes K+ via GI tract (takes hours; definitive excretion)
• Dialysis - for renal failure or refractory cases

10. H. pylori Regimens

• Prevpac: Pre-packaged lansoprazole + clarithromycin + amoxicillin (twice daily x 14 days)
• Clarithromycin triple therapy should be avoided where H. pylori resistance to clarithromycin >15% or patient had recent macrolide exposure → use bismuth quadruple as first-line instead
• Vonoprazan (potassium-competitive acid blocker, P-CAP) - FDA-approved with amoxicillin ± clarithromycin; may be superior to PPIs
• Side effects reported in 20-30% on triple therapy
• Most common cause of treatment failure: antibiotic resistance (especially clarithromycin)
• Compliance is key: simplifying to twice-daily dosing helps

11. Budd-Chiari Syndrome

• Myeloproliferative disorders: polycythemia vera, essential thrombocythemia (40-50%)
• Antiphospholipid syndrome
• PNH (paroxysmal nocturnal hemoglobinuria)
• Factor V Leiden, Protein C/S deficiency, Antithrombin III deficiency, Prothrombin gene mutation
• OCP, pregnancy
• Malignancy, trauma
• Idiopathic (20%)

• Doppler USS: first line - reversed/absent hepatic vein flow
• CT/MRI: caudate lobe hypertrophy (spared because it drains separately into IVC)
• Ascitic fluid: protein >2g/dL, SAAG >1.1 (portal HTN pattern)
• ↑LFTs (25-50%), ↑INR, ↓albumin (chronic)

• Anticoagulation (all patients; warfarin/direct factor Xa inhibitors)
• Treat underlying cause (e.g., hydroxyurea/ruxolitinib for MPN)
• TIPS for refractory cases
• Liver transplant for end-stage disease

12. Metabolic Acidosis and HAGMA

AG = Na⁺ - (Cl⁻ + HCO₃⁻); Normal = 10-12 mEq/L Correct for albumin: add 2.5 mEq/L for every 1 g/dL drop in albumin below 4 g/dL

1. Increased endogenous acid production (lactic acid, ketoacids)
2. Loss of bicarbonate (diarrhea)
3. Accumulation of acids due to low renal net acid excretion (CKD)

• Characteristic increase in ventilation (Kussmaul breathing)
• Intrinsic cardiac contractility may be depressed
• Peripheral arterial vasodilation + central venoconstriction → pulmonary edema risk
• CNS depression: headache, lethargy, stupor, coma
• Glucose intolerance

Glycols (ethylene/propylene glycol), Oxoproline, Lactate, D-lactate, Methanol, Aspirin (salicylates), Renal failure, Ketoacidosis

1. Draw ABG + electrolytes simultaneously
2. Verify HCO₃⁻ calculated (ABG) matches measured (electrolytes) within ±2
3. Calculate AG; correct for albumin
4. If high AG: identify cause (Table 58-4)
5. If normal AG (hyperchloremia): GI HCO₃⁻ loss or RTA
6. Estimate compensatory response; check Delta-Delta

• Alkali therapy (NaHCO₃) reserved for severe acidemia except when no "potential HCO₃⁻" in plasma
• Non-AG (hyperchloremic) acidosis or uremic acidosis: give NaHCO₃ PO or IV to target [HCO₃⁻] ~22 mmol/L
• In DKA: Bicarbonate only for severe acidemia (pH <7.00) and/or shock; target pH ~7.20 / HCO₃⁻ ~10-12 mmol/L; avoid bolus; watch for hypokalemia