36 - Hepatobiliary System II Flashcards
Describe alcoholic liver disease
- Pathologic changes in patients with alcohol-induced liver disease
- Develops in man who consumes > 80 g/day & woman > 40 g/day
- There is no one type of person that develops alcoholism
Describe the types of liver disease progression
Hepatitis
- Liver cell necrosis
- Inflammation
- Mallory bodies
- Fatty change
Cirrhosis
- Fibrosis
- Hyperplastic nodules
Steatosis
- Fatty change
- Perivenular fibrosis
Describe the gross appearance of alcoholic hepatic steatosis
This alcoholic fatty liver (hepatic steatosis) is enlarged, soft, and yellow. It has a greasy texture.
Neutrophils will be present, fatty accumulation, lyced hepatocytes
Describe focal lytic necrosis and mallory bodies
Mallory bodies
- Proteins that cannot be broken down
- Not only in alcoholic liver disease, but is present here
Focal lytic necrosis
Pericellular fibrosis, Mallory bodies (black arrows) and small round red megamitochondria (red arrow) are typical findings in alcoholic steatohepatitis.
Alcoholic Hepatitis Longer Abuse - Chicken Wire Fibrosis
- Stop eating
- Only drinking
- Malnutrition
What determines full blown alcoholic cirrhosis?
Nodules
- In alcoholic cirrhosis, nodules of regenerating hepatocytes consist of disordered cords of cells of irregular thickness.
Describe Alcoholic Steatohepatitis clinical presentation
- Fever
- Leukocytosis
- Jaundice
- Increase in AST - ALT 2 (still drinking)
- Increased AP
- Ultrasonography
What develops with alcoholic cirrhosis?
- Severe portal hypertension
- Ascites
- Large veins
Can also effect brain, anemia, stocking glove neuropathy (nutritional aspect)
Describe the five year survival of patients who stop drinking
Five-year survival approaches 90% in abstainers who are free of jaundice, ascites, or hematemesis; it drops to 50% to 60% in those who continue to drink.
What are the proximate causes of death in end-stage alcoholics?
- Hepatic coma
- Massive GI hemorrhage
- Infection
- Hepatorenal syndrome following a bout of alcoholic hepatitis
What are the types of steatohepatitis?
- Alcoholic steatohepatitis (ASH)
- Nonalcoholic steatohepatitis (NASH)
Describe the causes of Nonalcoholic steatohepatitis (NASH)
Insulin resistance/metabolic syndrome
- Obesity
- Diabetes
- Hyperlipidemia
Drug hepatotoxicity
- Tamoxifen
- Nifedipine
Pregnancy
- Small droplet fat
- Very serious condition during pregnancy
Describe alcoholics who quit drinking and need a liver transplant
- They go on the list if they stop drinking
- Sometimes just the stopping of drinking is enough to improve their condition enough to take them off the list
What are the three inborn errors of metabolism?
- Hereditary hemochromatosis
- Wilson disease
- 1-antitrypsin deficiency
Describe hereditary hemochromatosis
- Hereditary hemochromatosis is an inherited disorder that increases the amount of iron that the body absorbs from the gut.
- Symptoms are caused by this excess iron being deposited in multiple organs of the body.
What causes hereditary hemochromatosis?
Many mutations in the body’s iron transport system can cause hemochromatosis; however, most cases are caused by mutations in the HFE gene
The treatment is giving blood - phlebotomy to get rid of excess iron
What tests results will you see in hereditary hemochromatosis?
- High Serum Fe >300 mg/dL
- High Transferrin saturation >2X
- High Serum ferritin >2X
- High Hepatic Fe index >2
Describe the transferrin and ferritin increases seen in hemochromatosis
If transferrin saturation and ferritin concentration are high, genetic testing for hemochromatosis is warranted.
Patients who are either homozygous for C282Y or heterozygous for C282Y and H63D have hereditary hemochromatosis.
Describe the trend in patients with hemochromatosis
There is an exponential increase in the levels of serum ferritin concentration
By age 30 it causes progressive tissue injury and by 40 we see cirrhosis with organ failure
What are all the complications of hemochromatosis?
Slide 57
Describe the histological cahnges in hemochromatosis
X
Describe WIlson disease
- Wilson’s disease is a hereditary disease that causes the body to retain copper.
- Patients have decreased ceruloplasmin and excessive deposition of copper.
- The copper buildup leads to damage in the kidneys, brain, and eyes. If not treated, Wilson’s disease can cause severe brain damage, liver failure, and death.
- Symptoms usually appear between the ages of 6 and 20 years, but can begin as late as age 40.
Describe the clinical appearance of Wilson disease
Children
- Hepatitis
- Acute/chronic/fulminant
Adults
- Neurologic/psychiatric disease
- Untreated: fatal
How do you diagnose Wilson disease?
- Low serum ceruloplasmin (250 μg/g tissue)
- Urinary copper (Levels above 100μg/24h – NL is 10-30 μg/24h)
- Kaiser-Fleischer rings
What are Kaiser-Fleischer rings?
Brown rings around the eye
Describe cirrhosis seen in Wilson disease
x
WHat is the treatment for Wilson disease?
Chelating agents
What is alpha 1 antitrypsin deficiency?
- Autosomal recessive
- Primary liver metabolic disease
- Primary genetic liver disease in children
- 2nd cause of liver transplantation in children
Describe the clinical picture of alpha 1 antitrypsin deficiency
- Neonatal hepatitis/cholestasis
- Adults: chronic hepatitis /cirrhosis
- Hepatocellular carcinoma
- Liver transplantation
Describe the diagnosis of alpha 1 antitrypsin deficiency
- Low serum α1AT
- Abnormal electrophoretic α1AT
- Liver biopsy
Describe the protein buildup in alpha 1 antitrypsin
X
Describe liver cell adenoma
- Young women
- Oral contraceptives
- Glycogen storage disease
- May rupture in pregnancy
- May harbor hepatocellular carcinoma
Describe the treatment for liver cell adenoma
- Remove the tumor
- It is usually well-defined, so not that hard to remove
- We don’t want it to rupture so we take them out
- Usually benign
Describe hepatocellular carcinoma
- MUCH worse
- This one is malignant
What are the risk factors for hepatocellular carcinoma?
- Cirrhosis
- Alcoholism
- HBV, HCV
- Hereditary hemochromatosis
- α1AT deficiency
Describe the clinical appearance of hepatocellular carcinoma
- Painful hepatomegaly
- Abdominal mass
- Weight loss
- Portal/hepatic vein thrombosis
- Hemorrhagic ascites
- Hepatic failure
- Massive bleeding
How do you diagnose hepatocellular carcinoma?
- Ultrasound
- Angiography
- CT
- MRI
- Elevated AFP >1000
Describe the formation of hepatocellular hepatocellular carcinoma
- Differentiation
- Not going to test you on oncogenes
Describe the tumor of a hepatocellular carcinoma
- ## Large mass with smaller masses around it throughout the liver
Describe cholangiocarcinoma
Malignant primary tumor of the bile duct epithelium
What are the risk factors for cholangiocarcinoma?
Risk factors
- Primary sclerosing cholangitis
- Thorotrast
- Liver flukes
Note: a thorotrast is a colloidal suspension of thorium dioxide that was used until the 1950s as an intravascular contrast agent.
Describe the tumor of a cholangiocarcinoma
Slide 81
Describe metastatic tumors that go to the liver
- The most common malignant tumor of the liver
- Common primary site: GI tract, breast, lung, pancreas, melanoma
- Multiple, nodular
- Hepatomegaly
- Jaundice
- High liver enzymes
What are the three types of gall stones?
Cholelithaisis
- Cholesterol stones
- Pigmented stones
- Mixed
Describe cholesterol stones
Biliary hypersecretion of Cholesterol/supersaturation of bile with cholesterol
Describe pigmented stones
Predominantly bilirubin calcium salts
What are the four contributing factors for cholelithiasis?
- supersaturation
- gallbladder hypomotility
- crystal nucleation
- accretion within the gallbladder mucous layer
What are the clinical features of cholelithiasis
- 70 to 80% of gallstone patients remain asymptomatic throughout life
- Symptoms include – spasmodic, colicky pain owing to obstruction of bile ducts by passing stones
- Gallbladder obstruction causes right upper abdominal pain
- Pain after fatty meal
Describe the use of US and ERCP in the diagnosis of cholethiasis
Slide 89
Describe the microscopic appearance of acute cholecystitis
Slide 90
Describe chronic cholecystitis
Both gross and microscopic morphology is highly variable!
Usually GB is somewhat thickened and fibrotic but it may be normal in thickness although it is usually less pliable.
Usual Microscopic Appearance
- Collagen in wall (scarring)
- Lymphocytes
- Plasma cells
- Macrophages
The amount of inflammation varies from a heavy infiltration to just a few inflammatory cells.
Describe the appearance of chronic cholecystitis
Slide 92
Describe carcinomas of the gallbladder
- Fifth most common cancer of the digestive tract
- Slightly more common in women, presents in patients in their sixties
- Gallstones coexist in 60 to 90% of patients
- Most are adenocarcinomas, rarely squamous cell carcinoma
- Tumors are usually unresectable when discovered
Describe the clinical features of a carcinoma of the gall bladder
- Clinical features: Symptoms are insidious and indistinguishable from those caused by cholelithiasis; prognosis is poor
If the gall bladder becomes porcalinized (calcified) it needs to be removed
What are the types of pancreatitis
Group of disorders characterized by inflammation of pancreas
- Acue pancreatitis
- Chronic pancreatitis
What are the etiologies of acute pancreatitis?
Metabolic
- Alcoholism, hypercalcemia
Mechanical
- Gallstones, Trauma
Vascula
- Shock, Atheroembolism
Infectious
- Mumps, Coxasackievirus, Mycoplasma pneumoniae
Drugs
What is the clinical course of acute pancreatitis?
- Acute epigastric pain with radiation to the back
- Shock
- Mortality rate high, about 10 to 15%
- Full blown acute pancreatitis is a medical emergency
Describe the laboratory findings in acute pancreatitis
- Elevation of serum amylase during first 24 hrs
- Rising serum lipase levels within 72 to 96 hrs (more specific)
- Hypocalcemia may result from precipitation of calcium soaps in fat necrosis—poor prognosis
- Radiographic images: enlarged inflamed pancreas——pancreatic pseudocyst
Describe the gross and microscopic appearance of acute pancreatitis
Slide 99
- Dark red to black hemorrhage
- Chalky white necrosis of interstitial and peripancreatic fat
Describe chronic pancreatitis
Progressive inflammatory disease of the pancreas
Characterized by the clinical triad of:
- diabetes
- steatorrhea
- calcifications on radiographs
Describe the morphological changes seen in chronic pancreatitis
Along with PERMANENT impairment of function and IRREVERSIBLE morphologic changes
Causes
- most common cause = alcohol ingestion (70% of cases)
- next most common cause = idiopathic
- n.b. gallstone disease causes
Describe the gross and microscopic appearance of chronic pancreatitis
Slide 104
Give a summary of acute and chronic pancreatitis
Slide 105
Describe carcinoma of the pancreas
- 60% arise in the head; 10% in the body; and 10% in the tail; in 20% the tumor diffusely involves the entire gland
- All are adenocarcinomas arising from ductal epithelium
- Some may secrete mucin and may have abundant fibrous stroma
VERY AGGRESSIVE - very low survival - once you find it, the patient usually already have mets
What are the complications of pancreatic carcinoma?
Primary effects
- Mets to lung, liver peritoneum
- Pancreatic carcinoma
- Abdominal pain (perineural lymphatic invasion)
Secondary effects
- Weight loss
- Obstructive jaundice
- Courvoisier gallbladder
- Migratory thrombophlebitis
