Pathology-Liver and Gallbladder Path Flashcards
A mother brings her 2 month old baby in because his skin is yellow. A CT scan showed biliary atresia. What are causes of this in such a young baby and what complications is he at risk for?
This can be due to congenital failure to form OR early destruction of the extra-hepatic biliary tree from infection. This can progress to liver cirrhosis.
A mother brings her 2 month old baby in because his skin is yellow. A CT scan showed biliary atresia. What type of bilirubin is causing the jaundice?
Conjugated, it has already passed through the liver.
A patient presents with RUQ pain. Ultrasound of his gallbladder is shown below. Name 3 ways gallstones can form.
Stasis can promote bacterial infection which deconjugate the bilirubin and cause bilirubin stones. A high concentration of cholesterol or bilirubin could cause stone precipitation in the bile. Decreased phospholipids (lecithin) or bile acids could also cause stone formation because they function to solubilize the cholesterol.
A 55 year old man presents to the clinic with colicky RUQ pain. He has a history of high cholesterol and is on cholestyramine to manage it. How could the medication be causing his symptoms?
Cholestyramine forms insoluble complexes with bile acids, preventing reabsorption and they are secreted in the feces. This lowers the concentration of bile acids and can thus promote formation of cholesterol gallstones due to lower solubility.
Why do we typically use ultrasound to look for these in the West?
The most common type of gallstones in the West are cholesterol stones, which are radiolucent.
Why are women at higher risks for gallstones than men?
Estrogen increases the activity of HMG-CoA reductase, increasing cholesterol synthesis. Estrogen also increases expression of LDL-R, increasing the amount of cholesterol available to put into the bile.
Risk factors for development of gallstones.
Fat, fertile, female in her forties with a family history and flatulence. Native American & hyperlipidemia too.
How does Clofibrate increase your risk for gallstones?
1) Increases HMG-CoA reductase activity, increasing cholesterol synthesis 2) Decreases bile acid synthesis, decreasing solubility of bile cholesterol.
Why are you at increased risk for gallstones if you have Crohn’s disease or liver cirrhosis?
Crohn’s: damage to terminal ileum -> decreased uptake of bile salts -> decreased bile cholesterol solubility. Cirrhosis: decreased synthesis of bile salts -> decreased bile cholesterol solubility
What are the major risk factors for the condition shown below?
Risk factors for bilirubin stones are: 1) Extravascular hemolysis: large production of unconjugated bilirubin is produced by the splenic macrophages (reticuloendothelial system), this increases the concentration of conjugated bilirubin in the bile. 2) Biliary tract infection: bacteria deconjugate the bilirubin and decreases bilirubin solubility
How do RBCs contribute to bilirubin concentration in the bile?
Hemoglobin -> haem + globin -> Haem goes to Fe2+ and protoporphyrin, globin goes to A.A. -> Fe is recycled, protoporphyrin is converted to unconjugated bilirubin -> unconjugated bilirubin binds albumin and heads to liver -> liver conjugates bilirubin -> Sent out in bile canaliculi -> Bile duct -> Gallbladder
What organisms can deconjugated bilirubin and increase risk for precipitation and bilirubin gallstone formation?
E. coli, ascaris lumbricoides and clonorchis sinesis
What is the most common symptom of people with gallstones?
They are typically asymptomatic.
A patient presents with waxing and waning colicky RUQ pain. Suddenly the pain goes away. If he had a gallstone, what was causing the pain? What may he be at risk for now?
He has biliary colic due to contraction and relaxation of the gallbladder while the stone is blocking the cystic duct. The pain went away once the stone passed. If the stone is now blocking the ampulla of Vater, he is at risk for obstructive jaundice and pancreatitis.
An overweight 40 year old Native American woman presents with RUQ pain radiating to her right scapula, nausea and vomiting. She has a fever of 102 and an elevated WBC. What is likely causing her condition?
He has acute cholecystitis. This is due to stone impaction -> gallbladder dilation -> pressure ischemia on vessels in gallbladder wall -> bacterial overgrowth -> inflammation of the gallbladder wall.
An overweight 40 year old Native American woman presents with RUQ pain radiating to her right scapula, nausea and vomiting. She has a fever of 102 and an elevated WBC. What other lab value may be elevated if she has acute cholecystitis?
Serum alkaline phosphatase. The epithelium in the gallbladder have this enzyme and would be releasing it as they die off.
An overweight 40 year old Native American woman presents with RUQ pain radiating to her right scapula, nausea and vomiting. She has a fever of 102, an elevated WBC and serum alkaline phosphatase. What is the major complication this patient is at risk for?
Rupture of the gallbladder wall.
An overweight 40 year old Native American woman presents with vague RUQ pain after meals. She has a history of gallstones and works in a textile factory. Gallbladder biopsy is shown below. What is causing her pain?
This patient has chronic cholecystitis due to chronic inflammation of the gallbladder. The inflammation was likely caused by chemical irritation or longstanding cholelithiasis. Note the Rokitansky-Aschoff sinus formation (outpouching of gallbladder sinuses in the smooth muscle).
An overweight 40 year old Native American woman presents with vague RUQ pain after meals. She has a history of gallstones and works in a textile factory. What is a late complication of the condition she currently has?
Porcelain gallbladder is a late complication of chronic cholecystitis. This is because chronic inflammation causes dystrophic calcification of the gallbladder, as shown in the radiograph below.
An overweight 40 year old Native American woman presents with vague RUQ pain after meals. She has a history of gallstones and works in a textile factory. How do you treat her?
Cholecystectomy, especially if porcelain gallbladder is present because it is a risk factor for gallbladder cancer.
An overweight 40 year old Native American woman presents with jaundice and abdominal pain. She is also septic. She has a history of choledocolithiasis. What is causing her condition?
This patient has ascending cholangitis. This is due to bacterial infection of the bile ducts, typically by enteric gram-negative bacteria. Choledocolithiasis can cause this because it blocks bile flow out of the duct, decreasing the “washing out” of bacteria from the duct by normal flow. Bacteria walk up the duct and cause an ascending infection.
An overweight 40 year old Native American woman presents with a long history of recurrent RUQ pain. She presents today because she had an acute onset of colicky abdominal pain and abdominal distention. What could be causing her condition?
This patient has gallstone ileus. This happens when inflammation of the gallbladder wall causes rupture and fistula formation with the small bowel. Now the large stones can enter the small bowel and obstruct it.
An 80 year old woman presents with vague RUQ pain after meals that sometimes radiates to her right scapula. She has a history of gallstones, but has not felt like this in 20 years. What is likely causing her condition?
An elderly woman with a history of gallstones, especially porcelain gallbladder, presenting with cholecystitis, a condition of middle-aged women, could likely have gallbladder carcinoma.
What cells does the tumor shown below arise from?
Gallbladder adenocarcinoma arises from glandular epithelium in the gallbladder wall.
What is the earliest presentation of jaundice?
Scleral icterus
What causes jaundice?
Disturbances in bilirubin metabolism that increases serum bilirubin levels > 2.5mg/dL.
How long do RBCs typically live for and what marks the end of their lives?
120 days. The macrophages of the reticuloendothelial system in the spleen gobble them up.
You eat a meal and CCK causes gallbladder contraction and release of bile into the small bowel. What happens to the conjugated bilirubin present within the bile?
Intestinal flora convert it to urobilinogen. This is what makes the stool brown. It is also partially reabsorbed into the blood, filtered by the kidney, making the urine yellow.
A 40 year old man presents with colicky RUQ pain that waxes and wanes. He also has jaundice. UA reveals darkened urine. Name 2 conditions that could cause him to have jaundice.
1) Extravascular hemolysis: massive digestion of RBCs by splenic macrophages. 2) Ineffective erythropoiesis: death of RBCs within bone marrow results consumption by bone marrow macrophages. In both cases, excessive production of UCB results in a high serum concentration of UCB that exceeds the conjugating ability of the liver. This causes jaundice due to high serum levels of UCB.
A 40 year old man presents with colicky RUQ pain that waxes and wanes. He also has jaundice. UA reveals darkened urine. Why is his urine dark and why does he have colicky pain?
Once the liver catches up conjugating the UCB in the blood, you have excessive amounts of conjugated bilirubin in the bile. The results in increased amounts of urine urobilinogen, making the urine dark. Increased concentration of conjugated bilirubin in the bile also can cause pigmented bilirubin gallstones, which would be responsible for his colicky pain.
Why is the dark urine seen in patients with jaundice not due to high levels of unconjugated bilirubin?
Unconjugated bilirubin is not water soluble and is absent in the urine. The urine is dark because the liver is on overdrive conjugating bilirubin. The conjugated bilirubin is converted to urobilinogen by normal flora, filtered by the kidneys and excreted in the urine, making it dark.
Why do you put a newborn baby by a window with good sunlight?
Uridine glucuronyl transferase (UGT) activity is low in newborns and thus ability to conjugate UCB is initially low, increasing serum UCB levels and causing jaundice. This is important because UCB is fat soluble, can deposit in the basal ganglia and cause neurological deficits or death in the newborn.
Treatment to prevent kernicterus
Kernicterus happens in newborns as a result of UCB deposition in the basal ganglia. Phototherapy makes serum UCB water soluble. Water soluble UCB can now leak out in the urine.
A 30 year old woman is pregnant and has a miscarriage. On delivery of the fetus, it was very jaundiced. What similar genetic condition allows people to live without clinical symptoms?
The child had Crigler-Najjar syndrome, due to absence of UGT causing high serum UCB levels and fatal kernicterus. The more mild form that only causes jaundice with stress is Gilbert syndrome, which is an autosomal recessive disorder characterized by mildly low UGT activity.
A surgeon enters the abdomen for a cholecystectomy. On visualization of the liver, it is dark black. Labs reveal elevated serum conjugated bilirubin levels. The patient does not have any clinical symptoms of jaundice or liver disease. What is his condition and what similar condition presents without a dark liver?
Dubin-Johnson syndrome is a result in deficiency of bilirubin canalicular transport protein, causing conjugated bilirubin to leak out into the blood and build up in hepatocytes, making the liver black. A similar condition that happens without liver discoloration is Rotor syndrome.
A 40 year old overweight Native American woman presents with jaundice, pruritus, xanthomas, dark urine and pale stools. She has a history of gallstones and pancreatic carcinoma. What would you expect to see on lab values in this patient?
She has biliary tract obstruction causing obstructive jaundice. This results in back up of bile content into the blood, causing elevation in serum conjugated bilirubin (hence the dark urine), decreased urobilinogen (from decreased bile in intestine) and increased alkaline phosphatase (gallbladder epithelium death).
A 40 year old overweight Native American woman presents with jaundice, pruritus, xanthomas, dark urine and pale stools. She has a history of gallstones and pancreatic carcinoma. What is causing her to have pale stools, pruritus and xanthomas?
Pale stools: no bile is being secreted to emulsify the fat due to biliary tract obstruction. This results in steatorrhea and fat-soluble vitamin malabsorption. Pruritus: increased plasma bile acids. Xanthomas: hypercholesterolemia from decreased bile secretion.
Name 5 ways you can get obstructive jaundice.
Gallstones, pancreatic carcinoma, cholangiocarcinoma, parasites and liver fluke (C. sinensis)
A patient presents with dark urine and jaundice. Labs reveal increased serum conjugated bilirubin and unconjugated bilirubin. What would you expect urobilinogen levels to be in this patient?
This patient has viral hepatitis, which causes inflammation that disrupts hepatocytes and small bile ductules. Consequently, less bilirubin gets conjugated (due to hepatocyte damage) and less conjugated bilirubin gets secreted (due to damage to small bile ductules). This results in less conjugated bilirubin in the intestine where urobilinogen is formed = slight decrease in urobilinogen.
3 causes of viral hepatitis
Hepatitis virus, EBV and CMV.
What is responsible for the unconjugated bilirubinemia seen in people with acute hepatitis?
If the hepatocytes are infected with hepatitis virus, they present viral proteins on their MHC-I that activate CD8+ T-cells. This results in cytotoxic killing of hepatocytes by apoptosis. Note the inflammatory infiltrate around the hepatocytes shown below.
A 40 year old man presents with jaundice, dark urine, fever, malaise and nausea. He has had these symptoms for about 6 months. Where would you most likely see inflammation in the patient’s liver biopsy?
In chronic hepatitis, inflammation is predominately located around portal tracts (shown below).
Phases of acute hepatitis to resolution
1) Acute phase: + HBsAG (marks infection) and IgM HBcAB (marks body fighting off infection) 2) Window phase: IgM HBcAB is still present, but knocked out HBsAG. 3) Resolved phase HBsAG is still gone, and protective IgG HBsAB and IgG HBcAB are present on serology.
Phases of chronic hepatitis
Chronic: 6+ months w/+ HBsAB, presence of IgG HBcAB, absence of IgG HBsAB
What liver condition is shown below?
Cirrhosis, note the broad bands of fibrosis with nodules of regenerating hepatocytes.
A patient has been an alcoholic for the past 15 years. He starts to show symptoms of edema, decreased blot clotting and esophageal varices. What would you expect gross examination of his liver to look like? What about histologic examination?
The first change in Alcohol-Related Liver Disease is fatty liver. This is reversible with abstinence, and grossly presents as a heavy, greasy liver. Microscopically you see fat accumulation within the hepatocytes.
A 61 year old man presents with painful hepatomegaly. Labs reveal an elevated ALT and an even higher AST. He has a long history of alcohol abuse. What would you expect to see on liver biopsy?
He likely has alcoholic hepatitis. Swelling, ballooning of the hepatocytes, necrosis, inflammation and Mallory bodies would be seen on biopsy.
A 70 year old man presents with bronze skin and diabetes. He came in today because he had a cardiac arrhythmia the night before. He also notes gonadal dysfunction. Labs reveal increased ferritin, high serum Fe, increased percent saturation and decreased TIBC. What is causing this patient’s condition?
This patient has hemochromatosis that deposited Fe in his skin, pancreas, heart and testicles and caused organ damage. Excess Fe depositing in tissues causes organ damage by Fe-induced free radical damage (via the Fenton reaction).
Which biopsy is from a patient suffering from hemochromatosis?
The top image is hemosiderin from Fe deposition. The bottom image is lipofuscin in hepatocytes, a “wear and tear” brown pigment that piles up in the lysosomes from peroxidized lipids. You differentiate the two with a Prussian blue stain (shown below), which will stain the hemosiderin and not the lipofuscin.
A 37 year old woman presents with a history of ulcerative colitis. She also has obstructive jaundice and cirrhosis. Labs reveal p-ANCA. What is causing her condition?
He has primary sclerosing cholangitis. This is from inflammation and fibrosis of intrahepatic and extrahepatic bile ducts, note the periductal fibrosis with an ‘onion-skin’ appearance on biopsy.
A 37 year old woman presents with a history of ulcerative colitis. She also has obstructive jaundice and cirrhosis. Labs reveal p-ANCA. What would you expect imaging of the bile ducts to look like in this patient?
Uninvolved regions of the bile duct in primary sclerosing cholangits are dilated and result in a beaded appearance on imaging.
How might you be able to delineate between metastatic liver cancer and primary liver cancer on physical exam?
Metastatic liver cancer will have multiple nodules on the free edge on the liver when you palpate it.
