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

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

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

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

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

INR > 1.5
Encephalopathy
↑ transaminases
↑ bilirubin
↓ platelets
ABD US to investigate cause
Biopsy if can't find etiology

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

Sr Cr doubles or CrCl ↓ by half (< 2weeks)
Confirm pre-renal:↑ Na reabsorption ➔ urine Na < 10

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

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

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

AMA or ANA
MRCP (biopsy if clinical picture matches without AMA)

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

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