Definition: fibrosis and nodular regeneration resulting from hepatocellular injury

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1 Cirrhosis Understanding the liver: Patterns of LFT Abnormalities - Hepatocellular/Transaminitis: o Ratio of AST: ALT >2:1 ETOH (keep in mind AST is also produced by red cells, heart muscle) o If Aminotransferases >1,000: severe viral hepatitis, toxin, ischemia - Cholestatic: Elev TB/DB, Elev Alk Phos o Intrahepatic: meds, sepsis, PBC, post-op o Extrahepatic: PSC, pancreatic ca, cholangiocarcinoma, choledocholithiasis - Infiltrative: elev AlkPhos/GGT o Malignancy: HCC, Mets, lymphoma o Granulomas: TB, Sarcoid, Histo o Abscess - Isolated Hyperbilirubinemia o Conjugated: Dubin-Johnson, Rotor s o Unconjugated: overproduction, defective conjugation Definition: fibrosis and nodular regeneration resulting from hepatocellular injury Severity of Disease: two scoring systems - Child-Pugh (A-C) - MELD o Combination of TB, INR, Creatinine o MELD predicts short-term mortality post-tips o Used for liver transplant listing Complications of Cirrhosis Portal Hypertension - defined as hepatic venous pressure gradient >10-12 mmhg o wedge catheter from the IJ into the hepatic veins and measure pressure gradient between free hepatic vein and wedged pressure - non-invasively: Doppler US with reversal of flow Ascites

2 SAAG >1.1 <1.1 Portal Hypertension Non-Portal HTN Protein >2.5 Protein <2.5 Pancreatitis Carcinomanosis Post-Sinusoidal (e.g. CHF, Budd-Chiari) Sinusoidal Pre-Siinusoidal Tuberculosis Nephrotic Syndrome Management of Ascites - Sodium Restriction - Diuretics: Lasix/Spironolactone to maintain normokalemia - Serial LVPs Spontaneous Bacterial Peritonitis - Definition: PMN >250 in ascetic fluid, positive culture - Microbiology: E coli, Klebsiella, strep species - Management o ABX: cephalosporin, quinolone o Albumin: on days 1 and 3 to prevent HRS GE Varices - Diagnosis: endoscopy - Management: o Acute Bleed: IV access Serial CBC ABX (GI Bleed with Ascites) Octreotide or Vasopressin Emergent Endoscopic Ligation/Sclerotherapy Balloon Compression TIPS Mental Status Checks o Prevention Non-specific beta blocker (propranolol, nadolol)

3 Hepatic Encephalopathy - Pathophysiology: o Inability to metabolize toxins from the bowel that affect the CNS o Ammonia is the detectable representative neurotoxin but not the sole neurotoxin - Stages of encephalopathy o changes in behavior with changes in sleep wake cycle (stage 1) o comatose (stage 4) - Precipitants: o Increased Nitrogen: GI Bleed, constipation, high protein diet, renal failure o Electrolyte Abnormalities: hypoxemia, hypokalemia, hyponatremia, dehydration o Drugs: opiates, benzos, ETOH o Infection: systemic or SBP - Treatment o Treat precipitant o Lactulose o Rifaximin Hepatorenal Syndrome - Pathophysiology o Decreased circulating volume 2/2 ascites o Increased circulating vasodilators (particularly NO) with resulting splanchnic vasodilation with decreased SVR o Heart compensates with increased CO o Ultimately production of vasodilators overcomes increase in CO and you get activation of RAS, sympathetic nervous system, vasopressin with renal vasoconstriction - Diagnostic Criteria o Cirrhosis with ascites o Serum Cr >1.5 o No improved in Cr after fluid challenge o Absence of shock or intrinsic renal disease o No current or recent use of nephrotoxic agents - Types o Type 1: rapidly progressive o Type 2: indolent - Precipitants o GI Bleeding o Overdiuresis o Infection (SBP) o Paracentesis - Treatment o Albumin o Peripheral Vasoconstriction: midodrine, terlipressin

4 o Splanchnic Vasoconstriction: octreotide Hepatopulmonary - Pathophysiology: pulmonary vascular dilations with intrapulmonary shunting - Clinical Manifestations: orthodeoxia, platypnea - Diagnosis: TTE with late bubbles Portopulmonary Hypertension - Clinical Manifestations: sx of RH failure - Diagnosis: PAP > 35 mmhg on RHC - Management: use same therapies as in portal HTN, no improvement posttransplant Hepatic Hydrothorax - Pathophys: microperforations in diaphragm with movement of ascitic fluid into pleural space - Clinical Manifestations o Effusion on CXR (R>L) - Management o Reaccumulates rapidly post-thora or chest tubes o Difficult to treat diuretics or TIPS Lab and Exam Findings Labs: - ALT >AST - Elevated Bilis - Elevated Coags - Low Albumin - Cell Line Deficiencies: 2/2 marrow suppression, hypersplenism, iron/folate deficiency, decreased TPO production o Anemia o Thrombocytopenia Physical Exam Cirrhosis - Decreased hepatocellular mass: o Jaundice: frenular jaundice, scleral icterus o Ecchymosis - Decreased Hepatic Metabolism of Androstenedione Increased Estrogen o Spider Angioma: arteriole with surrounding small radiating vessels, blanching, most frequently found in distribution of SVC o Palmar Erythema o Gynecomastia o Testicular Atrophy - Portal Hypertension

5 o Splenomegaly o Ascites o Caput Medusae o Encephalopathy and asterixis - Dupuytren s contracture - Terry s Nails: white lines on proximal nail beds - Fevor hepaticus - Hypertrophic Osteoarthropathy References Udell et al. Does this patient with liver disease have cirrhosis? Journal of the American Medical Association, 2012; 307(8):

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