Hepatic disorders

Liver Function Tests (LFT)

Jaundice

  • Yellowing of oral mucosa, then eyes, then skin

  • Pruritus

  • Hemolysis ➔ Heme + globin

  • Heme ➔ macrophage ➔ Unconjugated Bilirubin (calculated indirectly)

  • Unconjugated Bilirubin ➔ liver ➔ Conjugated Bilirubin (direct)

  • ↑ bilirubin (direct and indirect) ➔ jaundice

  • Pruritus is associated with cholestasis

    • Classically taught that itch is from bile salts but no evidence they play direct role in pathogenesis of itching in jaundiced pts

Pre-hepatic Jaundice

  • ↑ Unconjugated Bilirubin (T.Bili >> D.Bili)

  • Hemolysis or reabsorbed hematoma

Intra-hepatic Jaundice

  • Hepatitis, cirrhosis, Gilbert's

Post-hepatic Jaundice

  • Obstruction ➔ ↑ Conjugated (↑ T.Bili and ↑ D.Bili)

    • Conjugated (water soluble) ➔ dark urine

      • Painful: Gallstones

      • Painless: PSC, PBC, cancer

Neonatal Jaundice

  • Physiologic jaundice (harmless): unconjugated bilirubin

    • Fetal hemoglobin hemolysis and ↓ hepatic metabolism of bilirubin

    • MC between 2-8 days old

  • Pathologic jaundice: unconjugated OR conjugated bilirubin

    • Obstruction, hemolytic anemia, conjugation problem, TORCH

Portal HTN

  • Resistance to portal blood flow (like from cirrhosis)

  • ➔ splanchnic arteriolar vasodilation and angiogenesis ➔ ↑ portal collateral blood flow

  • ➔ shunting of blood (bypassing liver) ➔ ↑ NH3 ➔ encephalopathy

  • ➔ ↑ cardiac output (but output stays in gut) ➔ hypotension ➔ RAAS/sympathetic activation

  • Intrahepatic (MCC): cirrhosis

  • Prehepatic: portal vein thrombosis

  • Posthepatic: right HF, Budd-Chiari

SSX:

  • SX of underlying cause

  • Typically ASX until complications:

    • Esophageal varices, hypertensive gastropathy ➔ bleeding

    • Ascites, spontaneous bx peritonitis

    • Heaptopulmonary syndrome

      • Hepatic hydrothorax (pleural effusion) right side MC, pulmonary HTN

    • Hepatorenal syndrome ➔ ↑ SrCr (↓ GFR) and↓ Na excretion

DX:

  • Clinical DX: known cirrhosis (or other risk factor) and ssx of portal HTN

    • Hepatic venous pressure gradient quantifies

      • Normal HVPG: 1-5mmHg

  • Get EGD to evaluate varices

TX:

  • Treat underlying cause

  • PPX against variceal hemorrhage: NON-SELECTIVE β-blockers - propanolol

Chronic Liver Disease

  • Fibrosis (scarring) of liver ➔ ↓ liver function and ↑ risk of hepatocellular carcinoma

  • Thrombocytopenia (↓ thrombopoietin production by liver and splenic sequestration)

  • ↓ clotting factors (extrinsic) ➔ ↑ PT/INR

  • Hypoalbuminemia (albumin made by liver)

  • Malnutrition (↓ bile ➔ ↓ fat soluble vitamin absorption)

    • ↓ vitamin D (liver converts D3 to active calcidiol) ➔ hypocalcemia ➔ secondary hyperPTH

      • BOLO hypercalcemia when supplementing cirrhotic pt with calcidiol

  • ↑ estrogenic effects ➔ gynecomastia

  • ↓ urea synthesis ➔ ↑ NH3 ➔ encephalopathy

  • ↑ total body water BUT ↓ intravascular volume

Ascites

  • Portal HTN, ↓ albumin ➔ ↓ oncotic pressure, RAAS ➔ ↑ water/Na reabsorption

DX

  • Paracentesis (diagnostic tap), gram stain, culture, cell count and SAAG

    • SAAG (serum-ascitic albumin gradient)

      • ↑ protein in ascitic fluid ➔ < 1.1

      • ↑ hydrostatic pressure ➔ > 1.1

        • Total ascitic protein: < 2.5 means likely cirrhotic origin

        • Total ascitic protein > 2.5 is likely cardiac origin

TX

  • Na and fluid restrict, spironolactone and furosemide

  • Refractory ascites ➔ tx paracentesis (large volume... tap til dry)

    • Follow up with 5g of albumin per L fluid removed (with 25% albumin - 25g in 100cc)

Spontaneous Bacterial Peritonitis

DX

  • Low volume paracentesis

    • DON'T PULL OFF TOO MUCH VOLUME (can push into hepatorenal)

    • > 250 PMN ➔ ceftriaxone

Bleeding esophageal varices

DX/TX

  • STOP β-blockers

  • Transfuse to Hb of 7 (don't over-transfuse cirrhotic bleeders)

  • Protect airway and stop uncontrolled bleeding with balloon tamponade

  • EGD (for band ligation or sclerotherapy)

  • Octreotide ➔ splanchnic vasoconstriction

  • ABX (ceftriaxone)

  • Multiple episodes of bleeding varices, refractory ascites, or acute portal vein thrombosis ➔ TIPS (Transjugular Intrahepatic Portosystemic Shunt)

Encephalopathy

  • ↑ NH3 ➔ altered mental status with asterixis (hand flaps down while pt tries to keep it up)

    • Coma/severely altered ➔ ICU

    • NH3 levels don't correspond with severity

TX

  • Lactulose titrated to ~3 bowel movements/day

Acute Liver Failure

  • Patients WITHOUT hx of liver disease

  • Acute liver failure ➔ ↑ NH3 and ↓ coagulation factors

  • Tylenol (MCC)

  • Commonly idiopathic

  • ABX, antifungals, antivirals

  • Anti-convulsants

  • EtOH

  • Hepatitis, CMV, toxoplasmosis

SSX

  • Acute encephalopathy

  • Cerebral edema ➔ AMS, papilledema, Cushing triad (bradycardia, HTN with wide pulse pressure, irregular breathing)

  • Jaundice

DX

  • INR > 1.5

  • Encephalopathy

  • ↑ transaminases

  • ↑ bilirubin

  • ↓ platelets

  • ABD US to investigate cause

  • Biopsy if can't find etiology

TX

  • ICU management

    • Needs liver transplant - use MELD score to risk stratify

    • N-acetylcysteine for tylenol OD

    • ↓ systemic vascular resistance and ↓ intravascular volume

      • Hypotensive: resuscitate with NS, if acidotic give 1/2 NS with 75 mEq/L NaHCO3, add dextrose if hypoglycemic

        • BOLO overhydration (may worsen cerebral edema)

        • Norepinephrine preferred pressor if needed (less tachycardia, better splanchnic blood flow)

    • Avoid catabolism ➔ ↑ nitrogenous waste

      • Enteral feeding preferred

Acute on chronic liver failure

  • Patients WITH hx of liver disease

  • ↑ TBW but ↓ intravascular volume

    • Resuscitate with 500cc 5% albumin (NS/LR wont stay intravascular and may worsen ascites)

  • Look for infection: diagnostic paracentesis (not therapeutic), blood/urine cultures

  • Monitor CBC, CMP, INR

  • REQUIRES LIVER TRANSPLANT

Hepatorenal syndrome

  • Hyper-dynamic circulation ➔ intravascular depletion ➔ renal vasoconstriction & RAAS activation

DX

  • Sr Cr doubles or CrCl ↓ by half (< 2weeks)

  • Confirm pre-renal:↑ Na reabsorption ➔ urine Na < 10

TX

  • Octreotide and midodrine while looking for transplant

Heaptopulmonary

  • Pulmonary vasodilation ➔ hypoxemia

SSX

  • Platypnea - SOB while standing/sitting, improves while supine

PSC & PBC

Primary Sclerosing Cholangitis

  • Inflammation of intra and extra-hepatic ducts

  • Associated with ulcerative colitis > Crohn

SSX

  • Cholestasis ➔ jaundice, pale stool, pruritus

  • Can present with acute cholangitis

DX

  • p-ANCA

  • MRCP ducts have beaded-appearance (strictured and dilated segments)

TX

  • Ursodeoxycholic acid ± cholestyramine for pruritus

  • ERCP dilation of stenotic ducts (liver transplant only cure for cirrhosis)

Primary Biliary Cholangitis

  • ♀ >> ♂

  • Granulomatous inflammation of small intra-hepatic ducts

  • Associated with Hasimoto thyroiditis

SSX

  • Cholestasis ➔ jaundice, pale stool, pruritus

  • Liver can't convert cholesterol ➔ dyslipidemia ➔ xanthelasma

DX

  • AMA or ANA

  • MRCP (biopsy if clinical picture matches without AMA)

TX

  • Ursodeoxycholic acid slows progression (liver transplant is only tx for cirrhosis)