Medicine Marrow Pg No 1005-1014 (Hepatology)

Hepato Pulmonary Syndrome (HPS)

• Treatment:
  • Pre-HPS:
    • Terlipressin: 1 mg IV every 4-6 hours, max 12 mg/day
    • Octreotide + Midodrine: s/c Octreotide + oral α agonist (midodrine)
    • Norepinephrine: IV infusion
  • Definitive: Liver transplantation
• Pathogenesis:
  • Liver disease leads to increased nitric oxide (NO) production.
  • NO causes intrapulmonary capillary dilatation (from 8-15 μm to 50-500 μm).
  • This leads to a decrease in oxygenation, causing hypoxia and hypoxemia due to a ventilation/perfusion (V/Q) mismatch.
  • Arteriovenous (AV) shunts develop.
• Clinical Features:
  • Platypnea: Dyspnea (shortness of breath) on standing due to increased AV shunt activation.
  • Orthodeoxia: Drop in SpO2 (oxygen saturation) >3% on standing.
• Investigations:
  • Echocardiography: Bubble or Contrast Transthoracic echocardiography.

Lactulose Bowel Wash Treatment

• Administration: 4 times a day.
• Other Medications:
  • Rifaximin: 400 mg three times a day or 550 mg twice a day.
  • Acarbose: Oral medication.
  • LOLA (Branched Chain AA): Oral medication.
  • Sodium Benzoate: Oral medication.
• Mechanism of Action (MOA):
  • Lactulose is fermented by colonic bacteria producing Hydrogen gas (H₂) and Volatile Fatty Acids (VFAs).
  • Bacteria use VFAs as a substrate, reducing ammonia production.
  • Ammonia (NH₃) is incorporated into the stool.
  • NH₃ excretion: secondary to laxative effect.
  • Decreased pH: Ammonia (NH₃) + H+ → Ammonium (NH₄⁺)
  • Volatile fatty acid formation: Stimulates bowel movement.
  • Laxative effect: Promotes stool passage.

Ascites

• Definition: Free fluid in the peritoneal cavity.
• First sign of decompensation: Indicates worsening liver disease.
• Onset:
  • Portal hypertension (PHTN): 90% of cases.
    • Cirrhosis: Most common underlying cause.
  • Peritoneal causes: 10% of cases.
    • Fulminant Hepatitis: Ascites without a prior history of PHTN or cirrhosis.
      • Causes: Paracetamol poisoning, alcohol abuse, mushroom poisoning, rat killer poisoning.
• SAAG (Serum Ascites Albumin Gradient):
  • SAAG: Serum albumin - Ascitic fluid albumin (AFA).
  • High SAAG ascites (≥1.1): 90% of cases, indicates PHTN as the primary cause.
    • High SAAG, high protein: Indicates decreased AFA and increased protein in the ascitic fluid (e.g., Budd-Chiari syndrome).
    • High SAAG, low protein: Indicates decreased AFA and decreased protein in the ascitic fluid.
• Ascitic Fluid Detection:
  • < 100 ml: Ultrasound (USG).
  • 500 ml: Shifting dullness on percussion of the abdomen.
  • 1.5 L: Fluid thrill (vibration felt when tapping the abdomen).
• Refractory Ascites: No response to maximum doses of diuretics.
  • Large volume paracentesis: Should be followed by albumin replacement (expensive).

Spontaneous Bacterial Peritonitis (SBP)

• Cause: Gram-negative bacteria (e.g., E. coli).
• Criteria:
  • Ascitic fluid white blood cell count (WBC) ≥ 500 cells/ml OR polymorphonuclear neutrophils (PMNs) ≥ 250 cells/ml.
  • Positive ascitic fluid culture.
  • No surgically treatable source of infection.
• Differentials:
  • CNNA (Culture Negative Neutrocytic Ascites): Only criterion 1 and 3 present, criterion 2 absent.
  • MNNA (Monobacterial Non Neutrocytic Ascites): Only criterion 2 and 3 present, criterion 1 absent. (Gram-positive organisms are more common than Gram-negative organisms).
• Surgical peritonitis:
  • Protein > 1 g/dl.
  • Sugar < 50 mg/dl.
  • Increased lactate dehydrogenase (LDH).
• Treatment: Inj Ceftriaxone IV three times a day for 5 days.
• Prophylaxis:
  • Prior SBP, Child's score 29, Ascitic fluid protein < 1.5 g/dl (cirrhosis).
  • Upper gastrointestinal (UGI) bleed: Tab Norfloxacin 400 mg twice a day for 7 days.
  • Tab Norfloxacin 400 mg once a day for life.

Hepatic Encephalopathy (HE)

• Precipitating Factors:
  • NH3 (Ammonia) increasing factors:
    • Alkalosis
    • Acidosis
  • Factors causing Acidosis and Alkalosis:
    • Dietary protein overload
    • Constipation
    • GI hemorrhage
    • Sepsis
    • Blood transfusion
    • Hypokalemia
    • Hypovolemia
    • Hyponatremia
    • Dehydration
• TIPSS (Transjugular Intrahepatic Portosystemic Shunt): Can cause HE.
• Uremia: Renal symptoms can contribute to HE.
• Clinical Features:
  • West Haven Criteria:
    • Covert HE: Normal patient (tests for evaluation: Psychometric test or Number connection test).
    • Grade I HE: Anxious, altered sleep pattern, short attention span.
    • Grade II HE: Personality changes, behavioral abnormalities, disorientation, impaired speech, Asterixis (hand tremor).
    • Grade III HE: Semi-stupor, gross disorientation, bizarre behavior, responsive only to painful stimuli.
    • Grade IV HE: Coma, decorticate posture, triphasic waves on EEG.
• Number connection test: A test used for early detection of HE. The patient is asked to connect numbers in a particular order.
• Asterixis: Hand tremor, a characteristic sign of HE.
• EEG: EEG tracing with triphasic waves is a characteristic finding in HE.

Refractory Ascites

• Types: - Diuretic-resistant ascites: No response to full dose diuretics (40 mg spironolactone + 160 mg furosemide). Progresses to Hepato Renal Syndrome (HRS). - Diuretic-intractable ascites: Unable to administer full dose diuretics due to other medical complications (e.g., electrolyte imbalances (hypo/hyperkalemia), renal failure).

Hepato Renal Syndrome (HRS)

• Pathogenesis:
  • Splanchnic vasodilation (stimulated by ADH) which stimulates the sympathetic nervous system (SNS) and renin-angiotensin-aldosterone system (RAAS), resulting in renal vasoconstriction over time.
  • Leads to pre-renal failure.
• Diagnosis:
  • Diagnosis of exclusion in a patient with:
    • Cirrhosis
    • Portal hypertension
    • Ascites
  • Rule out:
    • Pre-renal: Diuretic excess, low serum albumin, UGI bleed.
    • Intra-renal: Proteinuria, hematuria.
    • Diagnostic imaging (USG): Rule out structural abnormalities.
• HRS-AKI (Acute Kidney Injury): Serious complication with poor prognosis. 100% mortality without transplantation.
• Management:
  • TIPSS

Chylous vs Pseudochylous Ascites

Hepatic Encephalopathy (HE)

• AKA: Porto systemic encephalopathy.
• Major complication of: Portal hypertension or advanced liver failure.
• Reversible encephalopathy: Abnormal brain function.
• Types:
  • Type A HE: Fulminant hepatic failure- producing HE. Increased cerebral edema (most common cause of death).
  • Type B HE: TIPSS-associated HE.
  • Type C HE (most common): Cirrhosis with portal hypertension, producing HE.
• Etiology:
  • Ammonia (NH3) (most common), mercaptan, phenol, aromatic amino acids, manganese (Mn), gamma-aminobutyric acid (GABA), octopamine, free fatty acids, bacteria in the colon, increased protein intake (high-protein diet).
• Pathophysiology:
  • Urea cycle dysfunction: Due to liver damage.
  • Portosystemic shunting: Blood bypasses the liver.
  • Glutamine accumulation: Due to increased glutaminase activity.
• Astrocytes: Alzheimer's type-α astrocytes:
  • NH3 + Glutamate → Glutamine (Toxic)
  • Glutamine is absorbed by non-ionic diffusion, damaging astrocytes.
  • Glutamine: Increased in cerebrospinal fluid (CSF).
• Note:
  • Glutamate: Decreased in blood, increased in CSF.
  • Alzheimer's type-1 cells: Aggressive multifocal leukoencephalopathy (PMLE).

Wilson'sDisease

• Inheritance: Autosomal recessive disease.
• Gene: ATP7B (Wilson ATPase) on chromosome 13q.
• Pathophysiology:
  • Copper (Cu²⁺): Absorbed mainly in the duodenum, daily intake is 2-5 mg, high copper foods include chocolates and nuts.
  • Molecular Defect: Copper is not incorporated into ceruloplasmin.
  • Decreased Ceruloplasmin degradation: Screening test: Decreased Serum Ceruloplasmin (normal range is 20-35 mg/dl).
  • Presentation:
    • Fulminant hepatic failure: Coombs-negative hemolytic anemia, and low alkaline phosphatase (ALP) (due to Zn²⁺ and Cu²⁺ competing for ALP)
    • Chronic presentation: Fatigue and elevated liver enzymes (ALT > AST).
• Signs and symptoms:
  • Hemoatocrit:
    • Decreased hematocrit can be a sign of anemia in advanced stages.
  • Copper Levels:
    • Liver biopsy: Demonstrates increased copper levels.
    • Serum: Elevated serum copper levels.
    • Urine: Elevated urinary copper levels (24-hour urine test).
  • Brain:
    • Neurological signs: Dystonia, tremor, rigidity, ataxia, dysarthria, psychiatric problems.
    • MRI/CT scan: Imaging may reveal basal ganglia lesions.
  • Kayser-Fleischer rings: Characteristic brown-green rings around the cornea.
• Treatment:
  • Chelation therapy: Penicillamine, Trientine, Tetrathiomolybdate.
  • Zinc: Increases copper absorption and reduces copper levels.
  • Liver transplantation: In severe cases.