Liver pathology Flashcards
The ____ surface of hepatocytes faces the canaliculi, whereas the ____ surface faces the sinusoids.
Apical; basolateral
In a patient with viral hepatitis, what zone of the liver is first affected?
Zone I, the periportal zone
A patient suffers septic shock and becomes hypotensive. Which zone of the liver is first to suffer necrosis?
Zone III, the pericentral vein zone, which is a watershed area
Drugs metabolized by the P-450 system are most likely to be found in which zone of the liver?
Zone III
List the three parts of the liver that make up the portal triad.
Bile ductule, portal vein, and hepatic artery
Lymph drains from the liver via which histologic structure?
The space of Disse
A teenaged cocaine addict presents with elevated liver enzymes. What zone of the liver is cocaine most likely affecting?
Zone I
During an autopsy, a 52-year-old man from the United States is found to have a shrunken, nodular liver. What is the most likely etiology?
Alcohol (responsible for 60–70% of cirrhosis in the United States)
Esophageal varices and caput medusae are caused by ____ (pathologic state) and are partially alleviated by ____ shunts.
Portal hypertension; portosystemic
A patient with musty-smelling breath presents to the ED with confusion and asterixis. What skin findings do you expect on exam?
Common skin findings in liver failure are jaundice and spider nevi (the musty breath is fetor hepaticus) & may see caput medusae, edema
A patient with melena is found to have esophageal varices. Where else in the GI tract are you concerned for bleeding?
The stomach, due to bleeding peptic ulcers (or may be caused by portal hypertension)
Name at least three direct effects of portal hypertension.
Splenomegaly, caput medusae, ascites, esophageal varices with hematemesis, peptic ulcers, anorectal varices, portal hypertensive gastropathy
An alcoholic has cirrhosis due to liver failure. What do you expect to find on eye exam?
Scleral icterus
While seeing a patient with known cirrhosis, you cannot help but notice his musty breath. What is this called?
Fetor hepaticus
Visible dilated capillary proliferation within the skin secondary to the effects of liver failure and cirrhosis is called what?
Spider nevi
A man with liver failure also complains of gynecomastia and testicular atrophy. How did this likely develop?
Due to an increase in estrogen
A patient with cirrhosis has a coarse, flapping tremor of the hands. What is this called?
Asterixis
A cirrhotic patient should be cautioned about what kind of hematologic abnormality(ies) due to her liver cell failure?
Bleeding tendency (decreased production of clotting factors, increased prothrombin time) and anemia
Why do patients with cirrhosis have an increased tendency to bleed?
Liver cell failure decreases production of prothrombin and clotting factors
Is the bleeding tendency in cirrhosis considered an effect of portal hypertension or an effect of liver cell failure?
Liver cell failure (it is due to the inability to synthesize clotting factors)
Is the ankle edema of cirrhosis considered an effect of portal hypertension or an effect of liver cell failure?
Liver cell failure (it is due to the inability to synthesize albumin resulting in lack of oncotic pressure)
What is cirrhosis?
Cirrhosis is defined as diffuse fibrotic and nodular regeneration that disrupts the normal architecture of the liver
What two gastrointestinal enzymes are markers of injury to hepatocytes?
The aminotransferases, which are alanine aminotransferase and aspartate aminotransferase
A patient has viral hepatitis. What do you expect the ratio of aspartate aminotransferase to alanine aminotransferase to be?
Low (in viral hepatitis, AST
A patient has alcoholic hepatitis. What do you expect the ratio of aspartate aminotransferase (AST) to alanine aminotransferase (ALT) to be?
High (in alcoholic hepatitis, AST > ALT)
A 40-year-old man is intoxicated and not making any sense. Elevated serum γ-glutamyl transpeptidase may indicate which diagnosis?
Chronic alcoholism, along with possible Wernicke encephalopathy
A patient has elevated alkaline phosphatase. To differentiate between bone disease and liver pathology, what marker do you use?
γ-glutamyl transpeptidase (like ALP, GGT is elevated in liver and biliary disease, but unlike ALP, it is not elevated in bone disease)
Alkaline phosphatase, in addition to being a marker of liver disease, is also a marker of ____ disease.
Bone
Which two gastrointestinal enzymes are used as markers for acute pancreatitis? Which one is more specific?
Amylase and lipase; lipase is more specific
A patient has epigastric abdominal pain radiating to the back, fever, and nausea. What two enzymes will likely be elevated on lab studies?
Amylase and lipase will likely be elevated (the patient has acute pancreatitis)
Which serum protein is decreased in Wilson disease?
Ceruloplasmin
A patient has bronze rings in the irises, liver cirrhosis, muscle rigidity, and dystonia. What serum protein is most useful to check?
Ceruloplasmin is decreased, because this patient likely has Wilson disease (the bronze rings are Kayser-Fleischer rings)
A boy who has never received any vaccines comes to the ED with an elevated amylase level (lipase is normal). Name a likely diagnosis.
Mumps
A 5-year-old boy with seasonal flu is given aspirin for his fever and develops altered mental status and elevated LFTs. Diagnosis?
Reye syndrome
What pathologic liver change is associated with Reye syndrome?
Microvesicular fatty changes and, later on, hepatomegaly
A 7-year-old girl is thought to have Reye syndrome. What metabolic disturbance do you check for (it shows up on a basic metabolic panel)?
Hypoglycemia
A mother brings in her son for lethargy and vomiting. A week ago he had a viral infection treated with a drug. What was he likely given?
Aspirin or salicylates (the boy likely developed Reye syndrome, which can occur in children with viral infections treated with aspirin)
List two viral infections that are strongly associated with Reye syndrome.
Varicella zoster virus, influenza B
A mother asks if she can give her 4-year-old son aspirin for his fever of 101°F. What drug would you recommend instead?
Acetaminophen or ibuprofen
How does aspirin cause Reye syndrome in young infants?
Aspirin metabolites reversibly inhibit mitochondrial enzymes and cause a decrease in β-oxidation
What potentially reversible liver pathology can be seen with moderate alcohol intake?
Macrovesicular fatty changes of the liver (hepatic steatosis)
A patient with chronic alcoholism develops hepatitis. What microscopic changes do you expect to see on liver biopsy?
Swollen and necrotic hepatocytes with neutrophilic infiltration and Mallory bodies (he likely has alcoholic hepatitis)
You test the AST and ALT levels of a long-term alcoholic with sustained alcohol consumption. What do you expect them to be?
AST > ALT (the ratio is usually >1.5) (make a toast with alcohol)
A 48-y/o woman with chronic alcoholism crashes her car and lacerates her liver. She goes to the OR. How do you expect her liver to appear?
She will likely have a micronodular, irregularly shrunken liver (also called hobnail appearance) (this is alcoholic cirrhosis)
An alcoholic patient has jaundice, a “hobnail” liver, and hypoalbuminemia. If the patient quits drinking, will these symptoms go away?
No, as this describes a micronodular, shrunken liver appearance indicating alcoholic cirrhosis, which is irreversible
What is the AST:ALT ratio in non-alcoholic fatty liver disease?
ALT > AST (ALT = Lipids)
A non-alcoholic, type II diabetic patient has cirrhosis and a high ALT:AST ratio. What pathologic changes are associated with this disease?
Insulin resistance = fatty infiltration of hepatocytes & cellular ballooning on pathology (as seen in non-alcoholic fatty liver disease)
What type of syndrome is associated with non-alcoholic fatty liver disease?
Metabolic syndrome (insulin resistance)
A non-alcoholic man with a high ALT:AST ratio and metabolic syndrome should be advised that he is at risk for what type(s) of liver disease?
Cirrhosis and HCC (he has non-alcoholic fatty liver disease)
What are some triggers of hepatic encephalopathy?
Increased NH3 production (protein intake, GI bleeding, constipation, infection), decreased NH3 removal (renal failure, diuretics, TIPS)
A patient with hepatic encephalopathy is prescribed lactulose. He is also a medical student who wonders what lactulose does. You say?
Lactulose increases NH4+ generation, which decreases NH3 that can contribute to hepatic encephalopathy
What two viral diseases are associated with an increased incidence of hepatocellular carcinoma?
Hepatitis B and C
Excessive exposure to what two substances is associated with an increased incidence of hepatocellular carcinoma?
Alcohol (alcoholic cirrhosis) and carcinogens such as aflatoxin
A 47-y/o man’s friend is diagnosed with hepatocellular carcinoma. The man asks what factors might increase his risk for this disease.
Hepatitis B and C, Wilson disease, hemochromatosis, α1-antitrypsin deficiency, alcoholic cirrhosis, carcinogens (e.g., aflatoxins)
A 52-y/o man comes in with RUQ abdominal pain and is convinced that this could be liver cancer. What signs/symptoms could you check for?
Jaundice, tender hepatomegaly, ascites, polycythemia, anorexia
A doctor suspects hepatocellular carcinoma in a patient. She orders what lab, expecting it to be elevated?
α-fetoprotein, because it is elevated in hepatocellular carcinoma
How might a hepatocellular carcinoma predispose a patient to Budd-Chiari syndrome?
Via polycythemia (a hypercoagulable state leading to thrombosis in the hepatic vein) or by direct compression of the hepatic vein
A woman with hemochromatosis develops jaundice and ascites and is found to have elevated serum α-fetoprotein levels. What is the diagnosis?
Hepatocellular carcinoma
Under what circumstances would a liver biopsy for a patient with a liver tumor be contraindicated?
If the tumor is thought to be a cavernous hemangioma due to potential aspiration causing a life-threatening hemorrhage
A liver mass is incidentally discovered in a 34-year-old man with no risk factors for carcinoma. Do go you straight to biopsy?
No, as this may be a cavernous hemangioma, commonly occurring in people 30–50 y/o for whom biopsy is dangerous due to bleeding risk
A patient on oral contraceptives is discovered to have a benign liver tumor. What is she most likely to have?
Hepatic adenoma
A patient often works with arsenic and polyvinyl chloride. He is found to have a malignant liver tumor. What liver tumor do you suspect?
Angiosarcoma
A woman has a liver mass seen on ultrasound, and you are concerned that this could be a metastasis from a malignancy of which organs?
GI, lung, and breast tumors (metastases are the most common liver tumors)
Blood backup to liver, commonly caused by right-sided heart failure and Budd-Chiari syndrome, leads to what liver finding?
Nutmeg liver (mottled liver appearance)
The liver of your patient with hepatic vein thrombosis is mottled, similar to nutmeg. If this condition persists, what outcome might occur?
Centrilobular congestion and necrosis can be expected, possibly leading to cirrhosis if it persists (this is Budd-Chiari syndrome)
In Budd-Chiari syndrome, there is occlusion of the ____ vena cava and/or the ____ veins.
Inferior; hepatic
What liver region becomes congested and necrotic in Budd-Chiari syndrome?
The centrilobular region
A patient with polycythemia vera develops new-onset ascites, abdominal pain, and elevation of liver enzymes. What do you suspect?
Congestive liver failure secondary to Budd-Chiari syndrome
What medical conditions are often associated with Budd-Chiari syndrome?
Polycythemia vera, pregnancy (postpartum state), hypercoagulable states, hepatocellular carcinoma
A patient with known hypercoagulability has developed ascites with visible abdominal and back veins. What exam finding can rule out HF?
Absence of JVD would support Budd-Chiari syndrome (the occlusion is distal) instead of HF
In your patient with prolonged expiratory time, what type of emphysema is more consistent with α1-antitrypsin deficiency than with COPD?
Panacinar emphysema caused by breakdown of elastic fibers of the lungs (as opposed to centriacinar [centrilobular] emphysema in COPD)
α1-antitrypsin deficiency can be diagnosed histologically by seeing what in liver biopsy samples?
PAS-positive globules
A patient has panacinar emphysema and a liver tumor. He has a certain protein deficiency. What is the pattern of inheritance of this trait?
Codominant (this patient has α1-antitrypsin deficiency, which is a codominant trait)
Is the hyperbilirubinemia of an intrahepatic process (such as hepatitis or cirrhosis) conjugated, unconjugated, or mixed?
This is mixed (direct and indirect) hyperbilirubinemia
Lab results show high direct and indirect bilirubin levels. Is this process conjugated, unconjugated, or mixed?
This is mixed (direct and indirect) hyperbilirubinemia
Is the hyperbilirubinemia of biliary tract obstruction conjugated, unconjugated, or mixed?
This is conjugated (direct) hyperbilirubinemia
Labs show high direct bilirubin and normal indirect bilirubin levels. What types of biliary disease process might cause this?
Obstructive processes such as primary sclerosing cholangitis or biliary cirrhosis (this is a conjugated [direct] hyperbilirubinemia)
A 5-day-old infant has persistent hyperbilirubinemia despite phototherapy. Is it likely conjugated, unconjugated, or mixed?
This is unconjugated (indirect) hyperbilirubinemia, likely due to hemolysis
Labs show high indirect bilirubin levels. Does this represent a conjugated, unconjugated, or mixed hyperbilirubinemia?
Unconjugated (indirect) hyperbilirubinemia
A patient with Dubin-Johnson syndrome comes in to your office. What type of hyperbilirubinemia does she have?
Conjugated (direct) (Dubin-Johnson is a defect of bile excretion)
A patient presents with Crigler-Najjar syndrome. What sort of hyperbilirubinemia does she have?
Unconjugated (indirect) (Crigler-Najjar is a defect of conjugation)
Name some causes of an unconjugated (indirect) hyperbilirubinemia.
Hemolysis, physiologic (newborns), Crigler-Najjar syndrome, Gilbert syndrome
Name some causes of a conjugated (direct) hyperbilirubinemia that are due to biliary tract obstruction.
Gallstones, cholangiocarcinoma, pancreatic or liver cancer, liver flukes
Name some causes of a conjugated (direct) hyperbilirubinemia that are due to biliary tract disease but are not obstructive.
Primary sclerosing cholangitis, primary biliary cirrhosis
Name some causes of a conjugated (direct) hyperbilirubinemia that are due to bile excretion defects.
Dubin-Johnson syndrome, Rotor syndrome
A newborn has a yellowish hue for 12 hours after birth. The doctor says it is a benign condition. What is its molecular basis?
Immature UDP-glucuronosyltransferase in the infant, leading to increased unconjugated bilirubin levels and jaundice
A newborn has a yellow hue for 10 hours after birth. The doctor says it is due to immature UDP-glucuronosyltransferase. Treatment?
Phototherapy, which converts the unconjugated bilirubin into a water-soluble form that can be excreted in urine
A newborn has severe physiologic neonatal jaundice. A doctor wants to start phototherapy to “protect the brain.” What does he mean by this?
Untreated unconjugated hyperbilirubinemia can cause kernicterus (bilirubin deposition in the brain, particularly in the basal ganglia)
A college student with no prior medical history presents with scleral icterus during final exams. What is the likely diagnosis?
Gilbert syndrome, likely precipitated by fasting or stress secondary to studying
The parents of a child with Gilbert syndrome want to know what complications to expect. What do you tell them?
Gilbert syndrome has no clinical consequences other than jaundice
A woman occasionally has jaundice instigated by stress that goes away without treatment. What is the pathogenesis of this benign condition?
Slightly decreased UDP-glucuronosyltransferase activity or decreased bilirubin uptake by hepatocytes (this is Gilbert syndrome)
Which levels are elevated in Gilbert syndrome: conjugated bilirubin, unconjugated bilirubin, or both?
Unconjugated bilirubin (since UDP-glucuronosyltransferase activity is decreased)
A 1-y/o girl has a new unconjugated hyperbilirubinemia with no laboratory indications of hemolysis. What asymptomatic condition is likely?
Gilbert syndrome, which can be triggered by fasting and stress in predisposed individuals
A newborn has defective activity of UDP-glucuronosyltransferase, usually resulting in death within a few years of birth. Diagnosis?
Crigler-Najjar syndrome type I
A 2-week-old boy is diagnosed with Crigler-Najjar syndrome type I. What do you tell the parents about the prognosis?
Death occurs in childhood
A patient has jaundice, kernicterus, and high unconjugated bilirubin levels. He dies at age 3 years. What enzyme is missing in his disease?
UDP-glucuronosyltransferase (the patient has Crigler-Najjar syndrome type I)
The parents of a jaundiced newborn are concerned that he has Crigler-Najjar syndrome. What type of bilirubinemia would rule this out?
Conjugated hyperbilirubinemia (as Crigler-Najjar causes impaired conjugation, leading to an unconjugated hyperbilirubinemia)
What is kernicterus?
Bilirubin deposition in the brain
What would a neonate with absent UDP-glucuronosyltransferase and cerebral palsy be treated with?
Plasmapheresis and phototherapy (this is Crigler-Najjar syndrome)
A baby has hyperbilirubinemia from low UDP-glucuronosyltransferase. How can a drug-enhancing liver enzyme synthesis help you prognosticate?
Phenobarbital enhances enzyme synthesis in Crigler-Najjar syndrome type II (less severe/a better prognosis), but has no effect for type I
A newborn has persistent hyperbilirubinemia despite phototherapy. What type of bilirubinemia supports a diagnosis of Dubin-Johnson syndrome?
Conjugated hyperbilirubinemia (Dubin-Johnson is a defect of hepatic excretion of bile)
What physiologic process is defective in patients with Dubin-Johnson syndrome?
Excretion of bilirubin from hepatocytes
A patient has defective excretion of direct bilirubin. Gross pathology shows a black liver. Diagnosis?
Dubin-Johnson syndrome, which has the characteristic black liver on gross pathology
You diagnose Dubin-Johnson syndrome in a neonate with conjugated hyperbilirubinemia. How do you explain the prognosis to the parents?
There are no clinical consequence, as this condition is benign
A patient has disease symptoms similar to Dubin-Johnson syndrome, but you do not find a grossly black liver. Does the prognosis change?
No (this is Rotor syndrome, which is a milder form of Dubin-Johnson syndrome)
A 22-year-old new to your practice has a history of benign unconjugated hyperbilirubinemia. Which hepatic enzyme is likely affected?
Glucuronosyltransferase (specifically UDP-glucuronosyltransferase in the case of Gilbert syndrome)
Unconjugated bilirubin is formed from ____.
Hemoglobin
What cells within the liver are part of the mononuclear phagocyte system, aiding in the conversion of hemoglobin to unconjugated bilirubin?
Kupffer cells
Describe the properties of circulating bilirubin (in normal healthy individuals). What allows it to be transported through the bloodstream?
Circulating bilirubin is unconjugated and water-insoluble; must be bound to albumin for transport
To enter hepatocytes for processing, what two spaces must circulating bilirubin pass through?
Junctions between endothelial cells in the hepatic sinusoid, followed by the space of Disse
A man has a rare mutation that slightly inhibits passage of bilirubin through the space of Disse. This presents similarly to what syndrome?
Gilbert syndrome (can consider this to be a form of impaired bilirubin uptake)
Within hepatocytes, what enzyme is tasked with converting unconjugated bilirubin into conjugated bilirubin? What function does it perform?
UDP-glucuronosyltransferase, it conjugates the bilirubin
After being acted on by UDP-glucuronosyltransferase, how does bilirubin differ from a previously circulating form?
It is now conjugated (bilirubin diglucuronide) and is more water soluble
Conjugated bilirubin is secreted into what structure so that it may become a part of bile?
The lumen of the bile canaliculus
A patient has jaundice and RUQ pain. A common bile duct gallstone is detected. This most directly impairs what step of bilirubin metabolism?
Secretion of conjugated bilirubin into the lumen of the bile canaliculus due to obstruction/stasis
opper normally enters the blood circulation in what form?
As ceruloplasmin
In a patient with Wilson disease, which metal tends to accumulate in the liver, brain, cornea, kidneys, and joints?
Copper
Why would a patient with Wilson disease have asterixis?
Wilson patients eventually develop liver failure, which can present with asterixis because the liver cannot metabolize ammonia
A man with a defective ATP7B gene is seen by a neurologist for parkinsonian symptoms. What portion of the brain is most likely degenerated?
The basal ganglia (due to copper deposition from Wilson disease)
You suspect Wilson disease in a patient referred to your neurology practice. What substance is classically decreased in lab studies?
Ceruloplasmin
A man has Wilson disease. His physician informs him that which hepatic changes will likely occur?
Liver failure, cirrhosis, hepatocellular carcinoma
What cancer is associated with Wilson disease?
Hepatocellular carcinoma
A patient with Wilson disease presents with choreiform movements. This is due to copper deposition in which area of the brain?
The basal ganglia
The parents of a child with Wilson disease ask about the chances that their future children also having the disease. How do you respond?
There is a 25% chance, as Wilson disease has autosomal recessive inheritance
What type of anemia is associated with Wilson disease?
Hemolytic anemia
A 30-year-old patient has new-onset dementia, elevated liver function tests, and discolored rings around his irises. Diagnosis?
Wilson disease
A patient has new dementia, high liver function tests, and discolored rings around his irises. What other lab result confirms the diagnosis?
Low serum ceruloplasmin levels (the patient has Wilson disease)
Copper is normally excreted into bile by a hepatocyte copper transporting ____, which is coded by the ____ gene on chromosome ____.
ATPase, ATP7B, 13
A patient with Wilson disease that affects the kidneys will present with what syndrome?
Fanconi syndrome
How does the mnemonic “Copper is Hella BAD” help you remember the classic features of Wilson disease?
Ceruloplasmin, Cirrhosis, Corneas, Copper Carcinoma (HCC), Hemolysis, Basal ganglia, Asterixis, Dementia Dyskinesia, Dysarthria
Hemochromatosis classically affects which three organs, causing which three classic symptoms?
Liver (symptom of micronodular cirrhosis), skin (pigmentation), and pancreas (bronze diabetes)
A man recently diagnosed with insulin-dependent diabetes mellitus has pigmented skin and elevated LFTs. What does liver biopsy show?
Liver biopsy will diagnose it with a positive Prussian blue stain (this is hemochromatosis)
A 42-year-old woman with HLA-A3–related iron disease could be at risk of what cardiac complication? How?
Congestive heart failure; secondary to cardiomyopathy (caused by iron deposition in the heart, from hemochromatosis)
A patient new to your practice has known hemochromatosis. For which cancer should you be vigilant because of this?
Hepatocellular carcinoma
What is the pattern of inheritance of primary hemochromatosis?
Autosomal recessive
Primary hemochromatosis is due to ____ or ____ mutation on the HFE gene.
C282Y, H63D
Primary hemochromatosis is associated with this type of human leukocyte antigen (HLA).
HLA-A3
Secondary hemochromatosis is mainly caused by what?
Chronic transfusion therapy, which can occur in the setting of disorders such as β-thalassemia major
Describe ferritin levels, iron levels, total iron-binding capacity, and transferrin saturation in patients with hemochromatosis.
High, high, low, high
A patient has a C282Y mutation on the HFE gene that causes symptoms. What are some of his treatment options?
Repeated phlebotomy, chelation with deferasirox, deferoxamine, deferiprone (oral) (this is hereditary hemochromatosis)
A woman undergoing menstruation notices that her “bronze” diabetes is not as severe. Skin pigmentation is also decreased. Why?
Iron is lost through menstruation, slowing the progression of hemochromatosis in women
A man with liver disease triggers a metal detector while passing through airport security, but no metal is found on him. Explain.
He likely has hemochromatosis with a total body iron level >50 g, which can set off metal detectors at airports
