Zonation
What percentage of the blood in liver sinusoids is arterial?
Approximately 75% of the afferent lobule blood is venous blood that drains from the intestine, with only 25% of the perfusion originating from highly oxygenated arterial blood
Which 2 diseases are caused by deficiency of canalicular membrane transporters?
Dubin-Johnson syndrome, Rotor syndrome
A patient with compensated cirrhosis is admitted with altered mental status. Which of the following is most likely contributing to his current symptoms?
A) Hypokalemia
B) Use of lactulose
C) High albumin levels
D) Increased hepatic protein synthesis
E) Beta-blocker therapy
Hypokalemia, a common result of diuretic therapy, and alkalosis promote intracellular shift and renal generation of ammonia, worsening HE. Lactulose helps, not harms.
Which enzyme is a typical marker of cholestasis along with serum alkaline phosphatase?
γ-glutamyl transpeptidase
Gluconeogenesis is carried out by which hepatocytes?
periportal hepatocytes - since gluconeogenesis is an energy-consuming process.
Which genetic defect is revealed in Crigler-Najjar syndrome?
Genetic deficiency of UGT1A1 activity
rapid extension-flexion movements of the head and extremities, best seen when the arms are held in extension with dorsiflexed wrists.
A 58-year-old man with a history of alcoholic cirrhosis presents with increasing abdominal distension and mild shortness of breath. Physical examination shows a fluid wave and shifting dullness. Paracentesis yields clear yellow fluid. Labs show:
Serum albumin: 2.8 g/dL
Ascitic fluid albumin: 1.0 g/dL
Total protein in ascitic fluid: 0.9 g/dL
WBC in ascitic fluid: 230/µL (80% lymphocytes)
SAAG: ?
Which of the following is the most likely cause of this patient’s ascites?
A) Peritoneal carcinomatosis
B) Cirrhosis with portal hypertension
C) Tuberculous peritonitis
D) Pancreatic ascites
E) Nephrotic syndrome
SAAG is >1.1, therefore, Cirrhosis with portal hypertension
A 38-year-old man presents to the emergency department with nausea, right upper quadrant pain, and confusion after intentionally ingesting a large quantity of acetaminophen tablets. Laboratory tests show elevated liver transaminases, prolonged prothrombin time, and metabolic acidosis. A liver biopsy is performed and reveals extensive necrosis around the central veins of hepatic lobules.
Which of the following best explains the regional susceptibility of this area of the liver to acetaminophen toxicity?
A) Higher expression of albumin mRNA in central hepatocytes
B) Increased oxygen tension near the central vein
C) High expression of cytochrome P450 enzymes in pericentral hepatocytes
D) Dominance of gluconeogenesis over glycolysis in pericentral hepatocytes
E) Enhanced urea cycle activity in zone 3 hepatocytes
Pericentral hepatocytes (zone 3, near the central vein) express CYP2E1 and CYP1A2, key enzymes responsible for converting acetaminophen into the toxic metabolite NAPQI.
This region has lower oxygen tension, and detoxification relies heavily on glutathione, which gets depleted in overdose situations.
Histologically, the centrilobular zone is most vulnerable to hypoxia and drug-induced liver injury, particularly from acetaminophen
A 43-year-old previously healthy woman has noted bouts of sharp upper abdominal pain along with nausea for 3 weeks. On physical examination she has tenderness to palpation of the right upper quadrant. She has scleral icterus. A liver biopsy is performed and on microscopic examination shows only intracanalicular cholestasis. There is no necrosis and no fibrosis. Which of the following is the most likely diagnosis?
A Chronic passive congestion
B Hepatitis B viral infection
C Acetaminophen overdose
D Choledocholithiasis
E Alcohol abuse
Choledocholithiasis
Why periportal hepatocytes take up glutamine and produce glutamate
Glutaminase activity
Periportal hepatocytes express glutaminase (GLS2), which catalyzes:
Glutamine→Glutamate+NH3This liberates free ammonia (NH₃) from glutamine.
2. Feeding the urea cycle
The released ammonia enters the urea cycle in the same periportal cells, where it's converted to urea:
2 NH3+CO2→UreaUrea is water-soluble and excreted by the kidneys.
3. Oxygen requirement
The urea cycle is energy-intensive, consuming 4 ATP equivalents, so it must occur in well-oxygenated periportal zones.
4. Glutamate fate
The glutamate formed may:
Be transaminated to form α-ketoglutarate (entering TCA cycle)
Be used for glutathione synthesis
Be passed downstream to pericentral hepatocytes, where it's converted back to glutamine by glutamine synthetase (a key scavenger pathway)
A 34-year-old Caucasian male is found to have biliary stones on abdominal ultrasonography one year after ileal resection. Which of the following is most likely responsible for the stone formation in this patient?
Which zone of the lobule most actively expresses Hamp and Hamp2 genes, which encode hepcidin?
Unlike many other functions, which are mostly active at periportal or pericentral hepatocytes, some are most active at mid-lobule hepatocytes.
A 72-year-old woman notes generalized itching, increasing jaundice and nausea for the past month. On physical examination she is afebrile, but scleral icterus is present. There is no abdominal pain on palpation. Laboratory findings include total protein 6.1 g/dL, albumin 3.3 g/dL, alkaline phosphatase 410 U/L, AST 49 U/L, ALT 40 U/L, total bilirubin 7.2 mg/dL, and direct bilirubin 6.3 mg/dL. Which of the following conditions is she most likely to have?
A Gilbert syndrome
B Autoimmune hemolysis
C Chronic active hepatitis C
D Primary biliary cirrhosis
Primary biliary cirrhosis
A previously healthy, 38-year-old woman has become increasingly obtunded in the past 4 days. On physical examination, she has scleral icterus, abdominal fluid wave, and asterixis. She is afebrile, and her blood pressure is 110/55 mm Hg. Laboratory findings show a prothrombin time of 38 seconds (INR 3.1), serum ALT of 1854 U/L, AST of 1621 U/L, albumin of 1.8 g/dL, and total protein of 4.8 g/dL. Serum or blood levels of which of the following will most likely be abnormal in this patient?
A Alkaline phosphatase
B Ammonia
C Amylase
D Anti-HCV
E Antinuclear antibody (ANA)
The history points to an acute liver failure from fulminant hepatitis with massive hepatic necrosis. The loss of hepatic function from destruction of 80% to 90% of the liver results in hyperammonemia from the defective hepatocyte urea cycle, and this leads to hepatic encephalopathy within 2 weeks of the onset of jaundice.
A patient with ascites has SAAG>1.1.
What additional measurement helps differentiate cirrhosis from right-sided heart failure?
Ascitic protein. Less than 2.5 confirms cirrhosis.
Increased alcohol consumption caused an increase in AST levels. What is the likely mechanism?
Pathological conditions that increase hepatocyte oxygen consumption, such as increased alcohol consumption, lead to pericentral hypoxia
A patient is hospitalized for evaluation of a medical condition. A liver biopsy is taken and light microscopy shows extensive lymphocyte infiltration and granulomatous destruction of interlobular bile ducts. The biopsy was most likely taken from which of the following patients?
A. A 3-week-old boy with high levels of unconjugated bilirubin and signs of encephalopathy
B. A 10-year-old girl loss of appetite, nausea, jaundice, and elevated levels of ALT and AST
C. A 42-year-old woman with a long history of pruritus and fatigue who has pale stools and xanthelasma
D. A 55-year-old obese woman prolonged episode of severe right upper abdominal pain after fatty meal ingestion
E. A 75-year-old man with weight loss abdominal discomfort, jaundice and an epigastric mass
A 42-year-old woman with a long history of pruritus and fatigue who has pale stools and xanthelasma
A 48-year-old man with alcoholic cirrhosis and grade II HE is started on treatment. Which of the following drugs acts by acidifying colonic contents and promoting ammonia excretion?
A) Rifaximin
B) Neomycin
C) Lactulose
D) L-carnitine
E) Metronidazole
Lactulose is a non-absorbable disaccharide fermented by colonic bacteria, producing acidic metabolites that trap NH₃ as NH₄⁺, reducing absorption.
A 47-year-old man presents with fatigue and mild jaundice. He takes no medications and denies alcohol use. Physical exam shows scleral icterus but no ascites or asterixis. Labs reveal:
AST: 89 U/L, ALT: 101 U/L, ALP: 410 U/L
Total bilirubin: 3.7 mg/dL Direct bilirubin: 2.9 mg/dL
Albumin: 4.0 g/dL
PT 13 seconds
Which of the following patterns of liver injury is most consistent with these findings?
A) Hepatocellular injury
B) Cholestatic injury
C) Mixed hepatocellular-cholestatic pattern
D) Isolated hyperbilirubinemia
E) Synthetic liver failure
Mixed hepatocellular-cholestatic pattern