Gastro - Pathology Part 2 Flashcards
Familial adenomatous polyposis involves mutation of the ____ gene on chromosome ____.
APC; 5q
You are going to perform a colonoscopy on a patient with familial adenomatous polyposis. What do you expect to find?
Pancolonic involvement, including the rectum
A patient is found to have thousands of polyps on colonoscopy; he has a history of bone and soft-tissue tumors. What syndrome do you suspect?
Gardner’s syndrome
Turcot syndrome describes the combination of FAP and what other finding?
Glioma and medulloblastoma (remember: TURcot = TURban)
Hereditary nonpolyposis colon cancer, or Lynch syndrome, involves mutations of DNA ____ ____ genes.
Mismatch repair
True or False? Hereditary nonpolyposis colon cancer rarely involves the proximal colon.
False; the proximal colon is always involved
A patient presents with fever, low blood pressure, and new murmur. Blood cultures grow Streptococcus bovis and he is started on appropriate antibiotics. After he is stabilized, what is the most appropriate next step in management?
Streptococcus bovis bacteremia is associated with colorectal cancer; this patient needs a colonoscopy when he is stable
Iron-deficiency anemia is particularly concerning for colon cancer in which patient population?
Men and postmenopausal women
What is the prognosis for a patient found to have familial adenomatous polyposis?
100% of patients will develop colon cancer if the colon is not removed
What are the two major molecular pathways that lead to colorectal cancer?
The microsatellite instability and chromosomal instability pathways
In the microsatellite instability pathway, what type of mutation is responsible for carcinogenesis in colonic epithelium?
DNA mismatch repair mutation
Loss of function of which gene leads to decreased intracellular adhesion in the colonic epithelium?
APC
KRAS gene mutation leads to dysregulation of what cellular function?
Signal transduction; the cell will respond abnormally to growth factors, contributing to tumorigenesis
True or False? Loss of the APC gene will lead to adenoma formation.
False. Both APC and KRAS gene mutation must be present for adenoma formation
Sporadic mutation leading to loss of function of which tumor suppressor gene is often the last step in malignant transformation of colonic epithelial cells?
p53
Carcinoid tumors are malignancies of which type of cell?
Carcinoid tumors are derived from endocrine cells
What percentage of small bowel tumors are carcinoid tumors?
50%
What is the most common site of a carcinoid tumor?
The small intestine
What are the presenting symptoms of carcinoid tumor confined to the small intestine?
None; carcinoid syndrome only occurs once the tumor metastasizes to the liver
What are the classic presenting symptoms of carcinoid syndrome?
Flushing, wheezing, diarrhea, right-sided heart murmurs
What finding is seen on electron microscopy in carcinoid tumors?
Dense core bodies; these are secretory vesicles containing serotonin
Explain why a patient does not present with carcinoid syndrome when a carcinoid tumor is confined to the gastrointestinal tract.
The patient would not present with carcinoid syndrome because the liver metabolizes serotonin on the first pass and it does not reach systemic circulation
Describe the pathogenesis of cirrhosis.
Destruction of hepatocytes results in diffuse fibrosis; cells regenerate in nodular pattern, destroying normal architecture
Cirrhosis can be further characterized as being either _____ or _____, depending on the etiology of the liver injury.
Micronodular; macronodular
Micronodular cirrhosis is often the result of what category of liver damage?
Metabolic insult such as from alcohol, hemochromatosis, or Wilson’s disease
Macronodular cirrhosis is usually the result of significant liver injury leading to _____ _____.
Hepatic necrosis
Give two examples of disease processes that typically lead to macronodular cirrhosis.
Postinfectious hepatitis and drug-induced hepatitis
Which form of cirrhosis is most associated with an increased risk of hepatocellular carcinoma: micronodular or macronodular?
Macronodular
A surgical portacaval shunt allows blood to flow between the _____ _____ and the _____ _____ _____.
Splenic vein; left renal vein
In patients with cirrhosis and portal hypertension, melena may be the result of bleeding from either _____ _____ or _____ _____.
Esophageal varices; peptic ulcers
Name six direct effects of portal hypertension.
Splenomegaly, caput medusae, ascites, hemorrhoids, esophageal varices, peptic ulcers
What condition may be noted on the eye examination of patients with cirrhosis as a result of the effects of liver cell failure?
Scleral icterus; caused by increased serum bilirubin
The foul-smelling breath of patients with cirrhosis is referred to as what?
Fetor hepaticus
Visible dilated capillary proliferation within the skin secondary to the effects of liver failure and cirrhosis is called what?
Spider naevi
What physical signs are seen in male patients as a result of the hyperestrogenic state seen in liver failure?
Gynecomastia, testicular atrophy
What physical signs are seen in patients with liver failure as a result of the buildup of bilirubin in the body?
Jaundice, icterus
What is the name for the coarse ‘flapping’ tremor of the hands that may occur in patients with cirrhosis?
Asterixis
List two hematologic abnormalities that may result from liver cell failure in patients with cirrhosis?
Bleeding tendency and anemia
Why do patients with cirrhosis have an increased tendency to bleed?
Liver cell failure leads to the decreased production of prothrombin and clotting factors
What physical findings in liver failure patients are seen as a result of the inability of the liver to make adequate albumin?
Edema, ascites
Is the bleeding tendency of cirrhosis considered to be an effect of portal hypertension or an effect of liver cell failure?
An effect of liver cell failure; it is due to the inability to synthesize clotting factors
Is the ankle edema of cirrhosis considered to be an effect of portal hypertension or an effect of liver cell failure?
An effect of liver cell failure; it is due to the inability to synthesize albumin resulting in lack of oncotic pressure
What two gastrointestinal enzymes are markers of injury to hepatocytes?
Alanine aminotransferase and aspartate aminotransferase
Which aminotransferase is the strongest marker of viral hepatitis?
Alanine transaminase
Which aminotransferase is the strongest marker of alcoholic hepatitis?
Aspartate transaminase
Which serum marker of hepatocyte necrosis can also be elevated after myocardial infarction?
Aspartate transaminase
Elevated serum γ-glutamyl transpeptidase may indicate which diagnoses?
Chronic alcoholism or biliary tree disease
What enzyme is a marker of obstructive liver disease?
Alkaline phosphatase, γ-glutamyl transferase
Alkaline phosphatase is a marker of _____ _____ as well as of obstructive liver disease.
Bone disease
Which two gastrointestinal enzymes are used as markers for acute pancreatitis?
Amylase and lipase
Which serum protein is decreased in Wilson’s disease?
Ceruloplasmin
Which enzyme marker is elevated in bile duct disease?
Alkaline phosphatase
A child with seasonal influenza is given aspirin to treat his fever and subsequently develops a deterioration in mental status and elevated hepatic enzymes. What is your diagnosis?
Reye’s syndrome
What liver pathology is associated with Reye’s syndrome?
Microvesicular fatty changes
What metabolic disturbance is often found in children with Reye’s syndrome?
Hypoglycaemia
A mother brings in her son for lethargy. A week ago he broke out in a vesicular rash and had a slight fever. After giving him some medicine, his mental status deteriorates. What medication did she likely give him?
Salicylates
List two specific viral infections that are especially associated with Reye’s syndrome.
Varicella-zoster virus and influenza B
Because aspirin is associated with Reye’s syndrome in children, what drug is instead recommended for this age group for treatment of fever?
Acetaminophen
How does aspirin cause Reye’s syndrome?
Aspirin metabolites decrease β-oxidation by inhibiting mitochondrial enzymes
What potentially reversible liver pathology can be seen with moderate alcohol intake?
Macrovesicular fatty changes of the liver (hepatic steatosis)
What microscopic changes are seen on liver biopsy of a patient with alcoholic hepatitis?
Hepatocytes become swollen and necrotic; Mallory bodies (intracytoplasmic inclusions) and neutrophilic infiltration are often present
In alcoholic hepatitis, what is the pattern of transaminase elevation?
Aspartate aminotransferase > alanine aminotransferase (ratio usually > 1.5) (remember: You’re toASTed with alcoholic hepatitis)
______ _____ are intracytoplasmic eosinophilic inclusions that are often seen in alcoholic hepatitis.
Mallory bodies
In alcoholic cirrhosis, sclerosis may be noted around the central vein in zone _____ on liver histology.
Zone III
In alcoholic hepatitis, which is typically elevated more: aspartate aminotransferase or alanine aminotransferase levels?
Aspartate aminotransferase levels
In viral hepatitis, which is typically elevated more: aspartate aminotransferase levels or alanine aminotransferase levels?
Alanine aminotransferase levels
What is the appearance of a liver with alcoholic cirrhosis on gross pathology?
Micronodular, irregularly shrunken liver (also called “hobnail” appearance)
What two infectious 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 B1
Name seven risk factors for hepatocellular carcinoma.
Infectious diseases and exposures, Wilson’s disease, hemochromatosis, and a1-antitrypsin deficiency
What are typical signs and symptoms of hepatocellular carcinoma?
Tender hepatomegaly, hypoglycemia, ascites, and/or polycythemia
What is the mode of metastasis of hepatocellular carcinoma?
Hematogenous spread
What laboratory finding is sometimes used as a marker for hepatocellular carcinoma?
Elevated α-fetoprotein level
What symptom of hepatocellular carcinoma predisposes a patient to Budd-Chiari syndrome?
Hepatocellular carcinoma can cause polycythemia, which, in turn, results in a hypercoagulable state leading to Budd-Chiari syndrome
A patient with hemochromatosis presents with jaundice, tender hepatomegaly, ascites and is found to have elevated serum AFP. What diagnosis do you suspect?
Hepatocellular carcinoma
What are the two common causes of nutmeg liver?
Right-sided heart failure and Budd-Chiari syndrome (backup of blood into the liver)
What type of damage occurs in nutmeg liver?
Centrilobular congestion and necrosis, possibly leading to cirrhosis
In Budd-Chiari syndrome, there is occlusion of the _____ _____ _____ or of the _____ veins.
Inferior vena cava; 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 can predispose a patient to Budd-Chiari syndrome?
Budd-Chiari syndrome is associated with polycythemia vera, pregnancy, and hepatocellular carcinoma
How can you differentiate Budd-Chiari syndrome from cardiac cirrhosis?
There is absence of jugular venous distention (JVD) in Budd Chiari syndrome
α1-Antitrypsin deficiency leads to the accumulation of misfolded proteins in which cells?
In the endoplasmic reticulum of hepatocytes
What effect does α1-antitrypsin deficiency have on the lungs?
Leads to increased breakdown of elastic fibers of the lungs, causing panacinar emphysema
α1-Antitrypsin deficiency can be diagnosed histologically by seeing what in liver biopsy samples?
Periodic acid-Schiff-positive globules
A newborn baby is found to have a yellowish hue 12 hours after birth. What is the molecular basis of this condition?
Immature UDP-glucuronyl transferase, which leads to increased unconjugated bilirubin and jaundice
What is the treatment for physiologic neonatal jaundice?
Phototherapy, which converts the unconjugated bilirubin into a water-soluble form that can be excreted in the urine
What organ performs the function of converting unconjugated bilirubin into conjugated bilirubin?
The liver
What form of bilirubin is water soluble?
Direct bilirubin
How can direct bilirubin be excreted from the body?
Urine, bile, feces
What organ excretes bilirubin as bile?
The liver
After being excreted into bile by the liver, direct bilirubin is then converted by _____ _____ into _____.
Gut bacteria; urobilinogen
In addition to the bacterial conversion of bilirubin, how else is urobilinogen formed?
Directly from heme metabolism
Is the hyperbilirubinemia of hepatocellular jaundice conjugated, unconjugated, or both?
Both
Is the hyperbilirubinemia of obstructive jaundice conjugated, unconjugated, or both?
Conjugated
Is the hyperbilirubinemia of hemolytic jaundice conjugated, unconjugated, or both?
Unconjugated
Describe the level of urine bilirubin in the case of hepatocellular jaundice, obstructive jaundice, and hemolytic jaundice.
Elevated; elevated; absent
Describe the level of urine urobilinogen in the case of hepatocellular jaundice, obstructive jaundice, and hemolytic jaundice.
Normal or low; depressed; elevated
A college student comes to health services during finals for yellowing of the skin. He is found to have an elevated indirect bilirubin but is otherwise asymptomatic. What is the likely diagnosis?
Gilbert’s syndrome
What are the potential complications of Gilbert’s syndrome?
Gilbert’s syndrome has no clinical consequences other than jaundice
What is the cause of Gilbert’s syndrome?
It is either due to decreased UDP glucuronyl transferase activity or decreased bilirubin uptake by hepatocytes
Which levels are elevated in Gilbert’s syndrome: conjugated bilirubin, unconjugated bilirubin, or both?
Unconjugated bilirubin
True or False: Gilbert’s syndrome is associated with hemolysis.
False; however, it causes an unconjugated hyperbilirubinemia
In what condition is the activity of UDP-glucuronyl transferase absent?
Crigler-Najjar syndrome type I
When in life does Crigler-Najjar syndrome type I typically present?
Early; death occurs in childhood
List three findings that are associated with Crigler-Najjar syndrome type I.
Jaundice, kernicterus, and high unconjugated bilirubin
Which levels are elevated in patients with Crigler-Najjar syndrome type I: conjugated bilirubin, unconjugated bilirubin, or both?
Unconjugated bilirubin
What is kernicterus?
Bilirubin deposition in the brain that can cause cerebral palsy
What treatments are used for Crigler-Najjar syndrome type I?
Plasmapheresis and phototherapy
Which is more severe: Crigler-Najjar syndrome type I or type II?
Type I
Crigler-Najjar syndrome type II responds to what treatment?
Phenobarbital, which increases liver enzyme synthesis
Which levels are elevated in patients with Dubin-Johnson syndrome: conjugated bilirubin, unconjugated bilirubin, or both?
Conjugated bilirubin
What process is defective in patients with Dubin-Johnson syndrome?
The hepatocyte’s excretion of bilirubin from the cell
What finding is characteristic of Dubin-Johnson syndrome on gross pathology?
The liver is black
What are the clinical consequences of Dubin-Johnson syndrome?
There are no clinical consequences, this condition is benign
What disease is similar to Dubin-Johnson syndrome but does not involve the finding of a grossly black liver?
Rotor’s syndrome
Unconjugated bilirubin is formed from _____ by Kupffer cells and other parts of the mononuclear phagocyte system.
Haem
What cells found within the liver are part of the mononuclear phagocyte system and therefore aid in the conversion of heme to unconjugated bilirubin?
Kupffer cells
True or False? The bilirubin that enters hepatocytes is water soluble.
False; the bilirubin that enters hepatocytes is water insoluble and must be bound to albumin to be transported in blood
True or False: The bilirubin that exits hepatocytes is water-soluble.
True
What enzyme within the hepatocyte converts bilirubin to its water-soluble form?
Glucuronyl transferase (specifically UDP-glucuronyl transferase)
What process is defective in patients with Wilson’s disease?
Hepatic copper excretion
Copper enters blood circulation in what form?
Ceruloplasmin
What five organs accumulate copper in patients with Wilson’s disease?
Liver, brain, cornea, kidneys, and joints
Wilson’s disease is characterized by what tremor?
Asterixis, due to liver failure
Which region of the brain is particularly vulnerable to degeneration in patients with Wilson’s disease?
The basal ganglia
In Wilson’s disease, basal ganglia degeneration results in what neurological symptoms?
Parkinsonian symptoms
What is the classic laboratory finding in patients with Wilson’s disease?
Low serum ceruloplasmin level
What processes occur in the liver of patients with Wilson’s disease?
Cirrhosis, hepatocellular carcinoma
What is the classic ocular finding in Wilson’s disease?
The cornea; these are called Kayser-Fleisher rings
