Test: Jaundice, Reye Syndrome, & Budd-Chiari Syndrome - NEET PG MCQ

• In patients of obstructive jaundice the value of serum bilirubin plateaus around 25 - 30 mg % since the water soluble bilirubin is excreted via the urine. However in setting of concomitant renal failure the concomitant loss of conjugated bilirubin via the kidney fails and leads to extremely high values.
• Another reason can be a simultaneous overproduction of unconjugated bilirubin due to haemolysis, sepsis and sickle cell anaemia.

• The presence of pruritus with jaundice points to presence of cholestatic component.
• The presence of SAP increasing the credibility of diagnosis of obstetric cholestatis
• HELLP syndrome is ruled out as coagulation profile is normal
• Hepato renal syndrome is ruled out as RFT is normal.
• The closest choice is viral hepatitis which presents with jaundice with marked elevation of AST, ALT and SAP being mostly normal.

Total serum bilirubin is calculated as follows:

• Direct bilirubin
• Indirect bilirubin
• Delta bilirubin

Delta bilirubin refers to the portion of direct-reacting (conjugated) bilirubin that is covalently bonded to albumin and is often called the delta fraction or bili-protein. Due to its strong attachment to albumin, the rate at which albumin-bound bilirubin is cleared from the serum closely resembles the half-life of albumin, which is approximately 12-14 days, rather than the brief half-life of bilirubin, which is around 4 hours. This fraction plays a significant role in the overall serum bilirubin levels for patients with cholestasis and hepatobiliary disorders. The extended half-life of albumin-bound conjugated bilirubin accounts for several observations:

• Some patients experiencing conjugated hyperbilirubinemia may not show bilirubinuria during their recovery phase, as the bilirubin is covalently attached to albumin and thus not filtered by the renal glomeruli.
• In certain patients who seem to be recovering well, the decline in elevated serum bilirubin levels may occur more gradually than anticipated.
• Later in the recovery phase of hepatobiliary disorders, it is possible that all conjugated bilirubin exists in the albumin-linked form, resulting in a slow decrease in its serum value due to the prolonged half-life of albumin.

• Urobilinogen is formed by bacterial metabolism in the gut from conjugated bilirubin. Following secretion into bile, conjugated bilirubin reaches the duodenum and passes down the gastrointestinal tract without reabsorption by the intestinal mucosa.
• Hence it is absent in urine in obstructive jaundice.
• Urinary Urobilinogen is increased in haemolytic jaundice and decreased in hepatitis.
• Absence indicates post hepatic cause which from the above four choices arc peri-heaptic obstruction.

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The most effective method for diagnosing biliary atresia is the percutaneous liver biopsy, as it yields the most dependable discriminatory results. Since this option is not available, hepatobiliary scintigraphy emerges as the best alternative. This test is sensitive but lacks specificity. Hepatobiliary scintigraphy, which employs technetium-labeled imino­diacetic acid derivatives, helps distinguish biliary atresia from non-obstructive causes of cholestasis.

• While uptake may be reduced in cases of neonatal hepatitis, excretion into the bowel will eventually take place.
• Ultrasound (USG) reveals a small or absent gall bladder, with no visualization of the common duct and the presence of the triangular cord sign.

• GGTP is not specific to alcohol and is elevated in all forms of fatty liver
• Gamma glutamyl transferase is found in many different tissues including: Kidney, Pancreas, Spleen and heart.

The production of vitamin K-dependent clotting factors is reduced due to a decline in hepatic mass. In such situations, the administration of parenteral vitamin K does not enhance the clotting factors or the prothrombin time.

Alkaline phosphatase serves as a marker for cholestasis; that is, an increase in alkaline phosphatase levels is observed in over 90% of individuals with cholestasis, indicating a decrease in bile flow.

• Due to the presence of isozymes in the liver, bone, placenta, leukocytes, and small intestine,
• An elevated alkaline phosphatase level does not specifically indicate issues with the biliary tract.
• Alkaline phosphatase levels exceeding four times the normal range are considered significant.

The occurrence of biliary atresia is approximately 1 in 10,000 to 15,000 live births. This condition is defined by the obstruction or discontinuation of the extrahepatic biliary system. It is the second most frequent surgically correctable cause of cholestasis observed during the neonatal phase.

• Progressive familial intrahepatic cholestasis type 1 (PFIC 1), previously referred to as Byler disease, is a severe variant of intrahepatic cholestasis.
• Individuals affected by this condition typically exhibit steatorrhea, intense itching, vitamin D-deficient rickets, and progressively worsening cirrhosis.

The key distinguishing factor between this disorder and Alagille syndrome is the lack of bile duct paucity and extrahepatic characteristics. Alagille syndrome, also known as arteriohepatic dysplasia, is the most prevalent syndrome associated with intrahepatic bile duct paucity.

Bile duct paucity refers to a deficiency or significant decrease in the number of interlobular bile ducts within the portal triads, while the branches of the portal vein and hepatic arteriole remain of normal size.

The process that leads to bilirubinuria involves the transport of conjugated bilirubin to the bile canaliculi. If this transport is defective, bilirubin accumulates in the urine, resulting in bilirubinuria. This issue primarily occurs when the liver cannot effectively move conjugated bilirubin into the bile ducts, causing it to leak into the bloodstream and subsequently be excreted through the urine.

• Conjugated bilirubin is water-soluble, so when it enters the bloodstream, it can be filtered by the kidneys.
• Normal transport to bile canaliculi is essential for proper bilirubin elimination.
• Disruption in this process can indicate liver dysfunction or biliary obstruction.

• Several factors contribute to the onset of hepatogenous insulin resistance or diabetes, including:
• Damage to hepatic parenchymal cells
• Portal-systemic shunting
• Infection with the hepatitis C virus

An SGOT: SGPT ratio >2:1 indicates a possibility, while a ratio >3:1 strongly suggests alcoholic liver disease. In cases of alcoholic liver disease, the AST is seldom >300 U/L, and the SGPT tends to be within normal limits. The reduced level of SGPT in the serum results from an alcohol-induced deficiency of pyridoxal phosphate.

A symmetrical and slightly warm area of erythema located on the thenar and hypothenar eminences of the palm in patients with chronic liver disease is known as palmar erythema.

• It may exhibit a mottled appearance or blanch when pressed.
• There is no association with pain, itching, or scaling.
• It can affect the palmar surface of the fingers and the proximal nail folds.

Causes of palmar erythema include:

• Primary causes (where no pathological processes can be identified):
  • Hereditary - rare
  • Pregnancy - common
  • Senile
• Secondary causes:
  • Chronic liver disease
  • Autoimmune conditions (e.g. rheumatoid arthritis)
  • Endocrinological issues - hyperthyroidism
  • Neoplastic conditions

Gilbert syndrome is defined by mild unconjugated hyperbilirubinaemia, normal liver enzyme levels, and typical hepatic histology, apart from a slight rise in lipofuscin pigment in certain patients. Serum bilirubin levels are usually below 3 mg/dl, though both higher and lower values are commonly seen.

• Bilirubin levels can vary significantly in any individual.
• At least 25% of patients will show temporarily normal values during extended follow-up.
• Higher bilirubin levels are linked to stress, fatigue, alcohol consumption, decreased caloric intake, and concurrent illnesses.
• In contrast, increased caloric intake or the use of enzyme-inducing agents leads to lower bilirubin levels.

Typically, Gilbert syndrome is identified at or shortly after puberty or in adulthood during routine check-ups that involve multichannel biochemical assessments. UGT1A1 activity is generally diminished to 10-35% of the normal range, and bile pigments display a notable increase in bilirubin monoglucuronides. A defect in the hepatic uptake of certain organic anions, which partially share an uptake mechanism with bilirubin—such as sulfobromophthalein and indocyanine green—is noted in a small number of patients.

• Significant weight loss
• Midepigastric pain: A common symptom, sometimes radiating to the mid-back or lower back
• Persistent pain: Nighttime pain is often a major complaint
• Painless obstructive jaundice: The most characteristic sign of cancer located in the head of the pancreas
• Pruritus: Frequently the symptom that causes the most distress for the patient
• Migratory thrombophlebitis (known as Trousseau's sign) and venous thrombosis: These may be the initial presentation
• Palpable gallbladder (referred to as Courvoisier's sign)

The sign and symptoms of Reye syndrome include protracted vomiting, with or without clinically significant dehydration: hepatomegaly in 50%; minimal or absent jaundice; and lethargy progressing to encephalopathy, obtundation, coma, seizures, and paralysis. Notably, patients are afebrile.
The CDC developed the following diagnostic criteria for Reye syndrome:

• Acute noninflammatory encephalopathy with an altered level of consciousness
• Hepatic dysfunction with a liver biopsy showing fatty metamorphosis without inflammation or necrosis or a greater than 3-fold increase in alanine aminotransferase (ALT), aspartate aminotransferase (AST), or ammonia levels
• No other explanation for cerebral edema or hepatic abnormality
• Cerebrospinal fluid with a white blood cell count of 8 cells/ μL.
• Brain biopsy with findings of cerebral edema without Inflammation or necrosis

Causes of Hepatic Steatosis
Macrovesicular steatosis

• Excessive alcohol consumption
• Hepatitis C (genotype 3)
• Wilson's disease
• Lipodystrophy
• Starvation
• Parenteral nutrition
• Abetalipoproteinemla
• Medications (e.g. tamoxifen, amiodarone, methotrexate, corticosteroids)

Microvesicular steatosis

• Reye's syndrome
• Medications (valproate, anti-retroviral medicines)
• Acute fatty liver of pregnancy
• HELLP syndrome
• Inborn errors of metabolism (e.g. LCAT deficiency, cholesterol ester storage disease, Wolman disease)

The most prevalent secondary mitochondrial hepatopathy is Reye syndrome. Recurrent Reye-like syndrome is observed in children with genetic disorders affecting fatty acid oxidation, including:

• Deficiencies in the plasmalemmal carnitine transporter
• Carnitine palmitoyl transferase I and II
• Carnitine acylcarnitine translocase
• Medium- and long-chain acyl-CoA dehydrogenase
• Multiple acyl-CoA dehydrogenase
• Long-chain L-3 hydroxyacyl-CoA dehydrogenase or trifunctional protein

Venous collaterals develop as a result of portal hypertension and necessitate time for their formation. Therefore, they are typically not observed in Budd-Chiari syndrome.

• Alkaline phosphatase (ALP): in females 42-98 U/L and males 53-120 U/L
• Since alkaline phosphatase is normal, obstructive jaundice is ruled out.
• A membrane-bound enzyme localized to the bile canalicular pole of hepatocytes, ALP is markedly elevated in persons with biliary obstruction.
• Elevated direct reacting bilirubin as well as elevated unconjugated bilirubin indicates hepato cellular jaundice. In hemolytic jaundice > 85% is due to indirect factions.

Budd-Chiari syndrome occurs due to the blockage of the hepatic veins.

• Most cases arise from spontaneous thrombosis of the hepatic veins or neoplastic enlargements from other organs.
• The syndrome is also linked to polycythaemia and the use of oral contraceptives.
• A few instances, likely congenital, result from obstruction of the suprahepatic section of the inferior vena cava due to a membranous web.

Mild to moderate increases in alkaline phosphatase levels and prolonged prothrombin time may sometimes be observed.

• The AST level is generally mildly elevated but can become very high temporarily after significant systemic hypotension (shock liver).
• In such cases, the clinical presentation may resemble acute viral or drug-induced hepatitis.

Occlusion of a single hepatic vein typically goes unnoticed. In contrast, overt Budd-Chiari syndrome usually necessitates the blockage of at least two hepatic veins.

• Venous congestion within the liver leads to hepatomegaly, which can stretch the liver capsule and result in significant pain.
• It is common for the caudate lobe to enlarge, as blood is redirected through it directly into the inferior vena cava (IVC).

Budd-Chiari syndrome is a rare condition caused by either thrombotic or non-thrombotic obstruction of hepatic venous outflow, and is marked by hepatomegaly, ascites, and abdominal pain.

In approximately half of the cases, the cause of the disease remains unidentified. The types of Budd-Chiari syndrome include:

• Primary Budd-Chiari syndrome (75%): characterised by thrombosis of the hepatic vein.
• Secondary Budd-Chiari syndrome (25%): caused by compression of the hepatic vein due to an external structure (for instance, a tumour).

Hepatic vein thrombosis is linked to the following conditions, listed in order of decreasing prevalence:

• Polycythemia vera
• Pregnancy
• Postpartum state
• Use of oral contraceptives
• Paroxysmal nocturnal haemoglobinuria
• Hepatocellular carcinoma
• Lupus anticoagulants