B57, Cholestasis, PSC, PBC, cholelithiasis, jaundice Flashcards
What is PSC and PBC?
Primary sclerosing cholangitis
Prib=mary biliary cirrhosis
What are the causes of cholestasis? (8)
- PSC
- PBC
- Tumor - tumor of the head of the pancreas, tumor of the duct of gall bladder
- Gallstones
- Biliary atresia
- Biliary trauma
- Congenital abnormalities of bile tract
- Drugs
Describe the general pathology and etiology of primary sclerosing cholangitis
Destruction of both the intrahepatic ducutles and extrahepatic bile duct.
Causes patches of sclerosis that produce beading and strictures along the biliary tree, visible by radiology.
Highly associated with IBD, especially Ulcerative Colitis. Occuring in as many as 70% of UC patients.
2:1 male preference
Idiopathic cause - ie Primary sclerosing cholangitis
Describe the histology of liver biopsies from primary sclerosing cholangitis
Histology:
- Circumferential fibrosis, aka Onion skinning. around the intrahepatic bile ducts.
- This progresses to total occlusion of the duct, leaving behind a tombstone scar which is unique and diagnostic for PSC.
What are the clinical consequences of PSC?
- Duct loss and occlusion
- compensatory bile duct proliferation
- Portal-portal septal fibrosis
- Cirrhosis and all of its consequences
- End stage liver that is cirrhotic and green from bile
- Biliary intraepithelial neoplasia, a precursor lesion to
- Cholangiocarcinoma seen in ~15% of patients, with onset about 5 years after PSC diagnosis.
What is the basic pathogenesis and etiology of Primary biliary cirrhosis?
- It is an autoimmune disease of middle aged women.
- Hallmark autoantibodies are anti-mitochondrial
- Causes inflammation and destruction of small, intrahepatic bile ducts.
- Eventually leads to cirrhosis and liver failure, but the liver failure may occur prior to overt cirrhosis, and end stage PBC occurs over 10-20 years.
Describe the histopathology of PBC
- Idiopathic development, insidiously with long asymptomatic period.
- Causes nonsuppurative destruction of intrahepatic bile ducts. The ducts will have inflammatory infiltrate with lymphocytes and plasma cells, in a somewhat granulomatous reaction around the duct, called a florid duct lesion
- The ductal inflammation eventually causes portal-to-portal fibrous septum formation.
- Destruction of the ducts causes upstream proliferation of the healthy duct tissue.
- The upstream proliferation of the healthy regions causes the gross feature of nodular regenerative hyperplasia, and overall, the liver is larger than normal rather than shrunken and contracted, as seen in cirrhosis.
- Importantly, the degeneration is periportal, and not peri-central as in alcholic hepatitis, congestive, or sepsis induced degeneration.
What is the clinical course/consequences of PBC?
How can it be treated?
Slowly progressing, 10-20yrs eventually leading to cholestasis and portal hypertension.
May or may not cause overt cirrhosis.
With or without cirrhosis, it progresses to hepatic decompensation and liver failure, causing hepatic encephalopathy and variceal bleeding/ascites and cholestasis.
It is important to treat with ursodeoxycholic acid early in the disease to dramatically slow its progression. Unkown mechanism.
Has associated extrahepatic conditions,
- Sjogren syndrome.
- Scleroderma
- Reumatoid arthritis
- Celiac disease
- Raynaud phenomenon.
What are the kinds of gall stones?
Cholesterol stones and pigment stones, and mixed
Cholesterol stones:
- 80% of gall stones
- formed by free cholesterol or bile salts
Pigment stones:
- Formed by unconjugated, insoluble bilirubin, in the form of Calcium bilirubinate salts.
How are cholesterol stones formed?
Requires:
- Supersaturation of bile with cholesterol/bile salts
- Nucleation site on a calcium salt precipitate
- Stasis
- Mucous hypersecretion, trapping the stones
What are pigment stones composed of and when do they form?
Composed of unconjugated bilirubin salts, form during hemolytic anemia and infection of the biliary tree.
Two types of pigment stones:
Black or Brown Pigment stones - 10%, are crystals of unconjugated bilirubin and calcium-bilirubin salts.
- Hemolytic anemias
- Biliary infection
- GI disorders such as Crohn’s disease, or ileal resectoin
- Cystic fibrosis with pancreatic insufficiency.
Black pigment stones
- form in sterile gall bladder.
- usually small and crumble easily
- 50-75% are radiodense
Brown pigment stones
- Form in infected bile
- can be large or small
- are greasy and soft from fatty acids
- are radiolucent (clear)
What are the risk factors for gall stone development?
Main ones, the four F’s
- Age over Forty
- Female gender, about twice as high (because of estrogen)
- Familial disorders of impaired bile salt secretion
- Fatness, hypercholesterinemia
- Estrogen, oral contraceptives
- Decreased gall motility/stasis
- pregnancy
- spinal cord injury
- rapid weight loss
- Any of the other cholestasis causes:
- PSC
- PBC
- Tumor - tumor of the head of the pancreas, tumor of the duct of gall bladder
- Gallstones
- Biliary atresia
- Biliary trauma
- Congenital abnormalities of bile tract
- Drugs
What are the 3 types of jaundice
Prehepatic, Hepatic, and Post-hepatic
At what level of serum bilirubin does jaundice occur?
2mg/dL
What are the congenital disorders that cause jaundice?
Gilbert syndrome, decreased hepatic expression of UDP glucuronosyltransferase
Criggler-Najjar syndrome,
- Type 1: Total lack of glucuronosyltransferase. High neonatal mortality
- Type 2: Reduced activity of the enzyme
Dublin-Johnson syndrome, defect in the ABCC2 gene, impairing excretion of conjugated bilirubin into bile. Backup and conjugated hyperbilirubinemia
Transient hemolytic jaundice of the newborn.
