Pathology - Liver and Pancreas Flashcards
What is hepatorenal syndrome?
What is the presumed pathophysiology?
Hepatorenal syndrome refers to the appearance of renal failure in patients with cirrhosis and ascites where there is no identifiable cause for renal failure. It occurs in 8% of such patients per year.
Decreased renal perfusion, due to systemic vasodilation, leads to activation of the RAAS system and increased renin and sodium retention. Prognosis is poor; 2 weeks to 6 months.
How much function does the liver lose prior to hectic failure being manifest?
80-90%
Mortality from hepatic failure is approximately 80%
What is hepatopulmonary syndrome?
Intrapulmonary vascular dilatation (due to increased NO) causing shunting in the lung.
Cirrhosis as the end stage of chronic liver disease is defined by three histological characteristics:
Bridging fibrous septae (linking portal tracts to each other)
Parenchymal nodules (proliferating hepatocytes encircled in fibrosis)
Disruption of the hepatic parenchymal architecture.
What is the main source of fibrosis in cirrhosis?
Although portal fibroblasts also contribute collagen, the predominant source of fibrosis is proliferation and activation of stellate cells via PDGF beta.
What triggers activation and proliferation of fibroblasts and stellate cells in cirrhosis?
Proinflammatory cytokines (TNF-a, IL-1b)
Cytokines (PDGF-b, TGF-b)
Disruption of ECM
Direct toxin stimulation
How common are oesphageal varices in patients with cirrhosis?
40% of patients with advanced cirrhosis get OV.
Each bleed has a 30% mortality.
Describe the metabolism of peripheral haemoglobin to bilirubin in the hepatocyte:
After 120 days RBC cell membranes rupture and haemoglobin in phagocytozed by the reticuloendothelial system.
Haemoglobin is then split giving free iron and biliverdin. Biliverdin is quickly reduced to unconjugated bilirubin which is released by the macrophages.
This combines with plasma albumin and is taken back to the liver…
Describe the intra-hepatocyte metabolism of bilirubin:
Once the unconjugated bilirubin has passed into the liver, it is released from plasma albumin and thereafter conjugated about 80% with glucoronic acid to form bilirubin glucoronide, about 10% with sulfate to form bilirubin sulfate, and 10% other.
In these forms, bilirubin is excreted from the hepatocytes by an active transport process into the bile canaliculi and then into the intestines.
Describe the post-hepatocyte metabolism of bilirubin:
Once in the intestine, about half of the conjugated bilirubin is converted by bacterial action into urobilinogen, which is highly soluble. Some of this is reabsorbed and re-excreted back by the liver back into the gut; 5% is excreted by the kidneys.
Further down the GI tract, urobilinogen becomes oxidised and altered to become stercobilin.
Which hepatic endoplasmic transferase conjugates bilirubin to glucoronic acid?
UGT1A1
Glucoronosyltransferase 1 polypeptide A1
Name the unconjugated hereditary hyperbilirubinameias:
Crigler-Najjar Types 1 and 2:
Autosomal recessive and dominant respectively. Loss of UGT1A1
Gilbert syndrome:
30% reduction in UGT1A1
Name the conjugated hereditary hyperbilirubinameias:
Dubin-Johnson syndrome
Rotor syndrome
Features of HAV?
ssRNA virus
Indirectly cytopathic (via CD8 T cell response)
Accounts for 25% of acute hepatitis, fecal-oral route of spread
Acute infection demonstrated by IgM anti-HAV
IgG anti-HAV confers immunity.
Features of HBV?
dsDNA virus
Indirectly kills via CD8 cytotoxicity
Capable of integrating into genome, constituting a pathway for cancer development
What are potential outcomes of HBV infection?
80-90% get either acute hepatitis or have subclinical disease. Most of these people recover with incident.
5-10% will become healthy “carriers”
4% will get persistent infection, some 20-50% of whom will get chronic hepatitis, some 10% of whom will get HCC
What is the HBV carrier state?
The HBV carrier state is defined by the presence of HBsAG in the serum for 6 months or longer after the initial detection.
Some patients will exhibit HBsAG and HBeAg, and HBV DNA, usually with Anti-HBc and occasionally with Anti-HBs. These patients are susceptible to progressive liver damage.
Features of HCV?
ssRNA virus
Substantial genomic variability makes vaccination difficult, hence characteristic ebb and flow of infection
Like HBV cellular damage is immune mediated, though the virus is not effectively killed!
Potentially curable with IFN-y and Ribovarin
Features of HDV?
RNA virus which can only develop in conjunction with HBV.
Co infection with HBV leads to hepatitis which ranges from mild to fulminant, but rarely becomes chronic.
Vaccination against HBV is therefore protective.
Features of HEV?
ssRNA virus
Enterically transmitted, endemic in India
High rate (20%) of fulminant hepatitis in pregnant women
Features of hepatic cysts?
Usually bacterial or candidal in developed countries
Mortality ranges from 30-90%, early recognition improves survival
Rupture of echinococcal cysts may cause severe immune mediated shock.
What is the characteristic histological finding in AIH?
Clusters of peri-portal plasma cells.
Features of AIH?
Autoimmune hepatitis is a chronic, progressive hepatitis attributable to T-cell mediated autoimmunity (CD8 T cells and IFN-y) Female preponderance (78% cases)
May be triggered by AIDisorders, drugs, or viruses.
Type 1 and 2 based on autoantibodies.
Untreated 6 month mortality is 40%, and 40% of survivors develop cirrhosis
Which drugs may cause fatty liver?
Ethanol, methotrexate, amiodarone, diltiazem, glucocorticoids, tetracycline.
What are the nutritional and metabolic causes of hepatic steatosis?
Metabolic:
Pregnancy, storage disorders, diabetes, metabolic syndrome
Nutritional:
TPN, malnutrition, gastric bypass, severe weight loss.
