How is the liver connected to the intestine and the great vessels?
The liver is connected to the gallbladder on the inferior side. Also at the hilus is the dual blood supply
- hepatic artery: arterial oxygenated
-portal vein: venous rich nutrient
Which cells form liver lobules?
hepatocytes are arranged into lobules
What are the main functions of the liver?
Metabolic: processing factory for food
Synthetic: major plasma proteins (except immunoglobulins)
What are the consequences of portal hypertension?
1. formation of varicosities d/t increased pressure
2. chronic passive congestion in the spleen (portal vein connects)
3. transudation of fluid >> ascites
How is bilirubin formed and excreted?
Senescent RBCs are taken up by phagocytic cells of the spleen and kupffer cells of the liver. Within these cells, hgb is degraded to heme and globin.
Heme loses the iron and is transformed into yellow pigment = bilirubin. Bilirubin is then bound in the blood by albumin = unconjugated. Unconjugated which is not water soluble is taken up by liver cells and conjugated to glucuronide. Bilirubin bound to glucuronide = water soluble. Bacteria not used in the intestine is converted by bacteria to urobilinogen.
Which enzymes are released into the circulation from damaged liver cells?
AST and ALT are ubiquitous enzymes that are elevated in blood after liver injury (and also other organs).
Alkaline phosphatase is used as marker for bile duct obstruction.
What are three principal forms of jaundice and what causes each of them?
Prehepatic: unconjugated, usually due to excessive bilirubin formation secondary to hemolysis
malaria, Gilbert's disease
Hepatic: mixed conjugated, unconjugated, can be caused by acute or chronic hepatitis, hepatotoxicity, cirrhosis, drug-induced hepatitis and alcoholic liver disease. Cell necrosis reduces the liver's ability to metabolize and excrete bilirubin
Posthepatic: conjugated, disturbance in excretion, usually (gallstones) at the level of the common bile duct.
Compare the biochemical laboratory findings in prehepatic, hepatic, and posthepatic jaundice.
unconjugated >> does NOT cross BBB, does not filter in urine
conjugated >> excreted in urine
What are the causes of viral hepatitis?
Hepatitis A, B, C, D, E
Hepatotropic viruses: mono, epstein-barr, herpes, CMV
Compare viral hepatitis A with viral hepatitis B and C.
Hepatitis A and C and RNA viruses; Hepatitis B is aDNA virus.
Hep A is F/O, while B and C are Par/Sex.
Hep A is NOT associated with a carrier state. Hep B and C are.
A vaccine is available for A and B. NOT for C.
Explain the signficance of serologic tests for the diagnosis of hepatitis.
HBsAg: surface antigen
released early, can be detected 1 week after onset
Persists only in patient who develop CHRONIC
HBcAg: core antigen
Antibodies appear in all infected persons
IGM first, IgG later
HBeAg: e antigen
Appears early, but disappears during ICTERIC stage
*presence in CHRONIC is a marker of INFECTIVITY
Compare the findings in acute and chronic hepatitis.
In hepatitis B there is a preicteric, icteric, and convalescent phase:
Preicteric: weakness, N/V, mild enlargement/tenderness of liver, rash, dark urine
* the more profound jaundice = more likely recovery
mild jaundice = likely transition to chronic
Chronic = intralobular inflammation, portal tract inflammation, disruption of lobular architecture secondary to aggresive inflammation and fibrosis
What is cirrhosis, and how does this disease present clinically?
= chronic liver disease characterized by loss of normal liver structure and function
irreversible and incurable
- thin hair
- facial telangiectasia
- parotid bland enlargement
- spider nevi
- muscle wasting, gynecomastia
- caput medusa
- palmar erythema
- absent of reduced pubic hair, small testes
- edema, purpura
What are the common causes of cirrhosis?
Hepatitis B and C
Hereditary metabolic diseases
- Wilson's disease
- Alpha antitrypsin
- biliary cirrhosis
- primary sclerosing cholangitis
- autoimmune hepatitis
- cystic fibrosis
Compare portal and biliary cirrhosis.
portal >> results from liver cell necrosis followed by ingrowth of fibrous tissue from the portal tracts
fibrous scars increase, incirciling remaining liver parenchyma and inhibiting ability to regenerate.
biliary >> results from diseases of the biliary tree, primary or secondary
primary = autoimmune disease
secondary = develops after prolonged, partial or complete obstruction of bile flow
Describe the gross and microscopic features of a cirrhotic liver.
Alcoholic cirrhosis: fatty, yellow, enlarged
Other forms: shrinks
Histology: liver cells arranged into nodules, separated by dense connective tissue
- if fat: alcoholic
- mallory's hyaline: alcoholic
- cytoplasmic granules: alpha AT deficiency
- iron: hemochromatosis
Why are some cirrhotic livers yellow and some others are rusty brown.
Initally virally infected livers appear normal and have a smooth surface on gross examintaiton. In such livers, the signs of liver cell injury can be seen only microscopically. Alcohol abuse leads to fatty transformation of the liver, which appears yellow.
What is the pathogenesis of ascites and splenomegaly in chronic liver disease?
Backpressure in brances of the portal vein results in the transudation of fluid from the serosal surfaces of the intestines, liver, and peritoneal surfaces lining the abdominal cavity. REduced oncotic pressure of the plasma secondary to hypoalbuminemia facilitates the passage of fluids from the circulation to the abdominal cavity. This results in relative hypovolemia, which triggers the release of aldosterone from the adrenal cortex. Aldosterone causes sodium and water retention >> anuria = hepatorenal syndrome.
What is the pathogenesis of hepatic encephalopathy, and how does it present clinically?
= clouded mentation and neurologic symptoms
thought to be caused by ammonia. Shows edema and altered astrocytes.
What is hepatorenal syndrome?
REduced oncotic pressure of the plasma secondary to hypoalbuminemia facilitates the passage of fluids from the circulation to the abdominal cavity. This results in relative hypovolemia, which triggers the release of aldosterone from the adrenal cortex. Aldosterone causes sodium and water retention >> anuria = hepatorenal syndrome.
Which endocrine abnormalities are found in patients with cirrhosis?
Sex hormones: impotence, gynecomastia, anovluation
Abn Vit D: osteodystrophy
Abn metabolism of thyroid hormones: hypothyroidism
Why do patients with cirrhosis bleed?
Decreased synthesis of coagulation proteins.
Compare predictable and unpredictable liver injury caused by drugs.
predictable = dose related
eg. tylenol (necrosis, >15g), tetracycline (fatty changes)
unpredictable = those without obvious explanation
eg. halothane (viral like), chlorpromazine (cholestasis), methyldopa (chronic), phenybutazone (granuloma), estrogens (tumor), isoniazid (mild hepatitis)
How does alcohol affect the liver?
Fatty liver: increases fatty acid sythesis, decreased oxidation, decreased export of lipoproteins, dose dependent fatty changes
alcoholic hepatitis: fever, leukocytosis, abd pain, jaundice. Focal necrosis of liver cells associted with leukocytic infiltrates and bile stasis. OFten contain eosinophilic aggregates of intermediate cyoskeletal filamens = mallory's hyaline.
What is Gilbert's disease?
Autosomal dominant disorder
- intermittent jaundice
- after puberty
- unconjugated hyperbilirubinemia
Compare hereditary hemochromatosis and Wilson's disease.
- both autosomal recessive
- hemochromatosis = iron, pigmentary cirrhosis, bronze diabetes
- wilson's = copper, cirrhosis, eyes and brain
How does alpha 1 antitrypsin deficiency affect the liver?
- accumulates in the form of cytoplasmic globules
- >> cholestasis, chronic hepatitis
What is autoimmune hepatitis?
- affects young women
- serology: high Ig, ANA
- inflammatory infiltrates of plasma cells and lymphocytes
Compare primary biliary cirrhosis and primary sclerosing cholangitis.
Primary biliary cirrhosis
- destruction of intrahepatic bile ducts and progression >> cirrhosis
- type IV hypersensitivity?
- antibodies to mitochondria
- fatigue, itching, jaundice
- xanthomas = infiltrates of macrophages full of lipids
Primary sclerosing cholangitis
- destruction of intra and extra hepatic ducts
- cell mediated
- segmental, beaded appearance
- often have Crohn's, UC
How do bacteria protozoa, and parasites infect the liver?
Infections can reach the liver through the bile ducts, blood flowing from hepatic artery/portal vein, wounds, extension from adjacent abdominal organs.
- Typically bacterial resistant: pylphlebitic abcess, ascending cholangitis, e coli, proteus, strep fecalis
What is the difference between cholangitic and pylephlebitic abscesses?
Cholangitic: mostly assoc with biliary obstruction
Pylephlebitic: entry from portal vein
Compare cholesterol stones with pigmentary gallstones.
Cholesterol stones = supersaturated bile, decreased bile acids, lecithin, solitary
Pigmentary = calcium bilirubinate, multiple
What is the pathogenesis of cholecystitis?
Gallstones may mechanically injure the mucosa.
- cause chronic inflammation
- obstruction >> mecrosis
- inflamed serosa >> adhesion >> fistula
List the most important primary tumors of the hepatobiliary tract.
Hepatocellular carcinomas = most important
Compare hepatocellcular carcinoma with cholangiocarcinoma.
Compare cholangiocarcinoma with gallbladder carcinoma.
Compare the pathology of primary and metastatic liver tumors.
Metastatic = typically multiples, nodules, central softened or indented necrotic areas
What are the indications for liver transplantation?
- all forms of cirrhosis
- acute liver necrosis
- metabolic disorders (wilson's, at deficiency, hemochromatosis)