20: Liver + Some Gallbladder Pathology Flashcards
HBx Ag in Hepatitis B + what it indicates
X protein - is a transcription transactivator - indicates HBV-related HCC
Avg weight of the liver
1500 g
Organization of liver parenchyma
Separated into lobules, composed of six acini, with three zones from exterior to interior (next to central vein)
Two types of blood that mix in the liver
Portal venous blood + hepatic arterial blood
What type of cells are Kupffer cells and stellate cells?
Kupffer: monocytic
Stellate: fat-containing myofibroblastic
Path of bile from hepatocytes to terminal bile ducts
Hepatocytes -> bile canaliculi -> canals of Hering -> bile ductules -> terminal bile ducts
Two causes of direct hyperbilirubinemia (rest of the things are typically indirect)
- Canalicular membrane transporter deficiency (Dubin-Johnson, Rotor syndrome)
- Impaired bile flow from duct obstruction or autoimmune cholangiopathies
Normal range for conjugated and unconjugated bilirubin in blood
- Conjugated: 0.1-0.3 mg/dL
2. Unconjugated: 0.2-0.9mg/dL
What is frequently the first or only sign of liver disease
Abnormal lab tests
If GGT is normal, what is likely?
Liver disease is not likely
Elevated AST:ALT with a 2:1 ratio is classic for what?
Alcoholic hepatitis
Why is GGT important to test for along with ALP?
Bc ALP can be elevated in both liver and bone disease
Testing PT vs albumin gives a picture of what?
PT: acute changes
Albumin: chronic changes
Gamma globulins are increased in acute or chronic liver processes?
Chronic
Four general patterns when assessing liver function tests and what they present with
- Acute hepatitis: elevated ALT/AST
- Cirrhosis: decreased albumin + elevated gamma globulins and PT
- Chronic hepatitis: acute hep + cirrhosis findings
- Obstructive liver disease/cholestasis: elevated ALP and bilirubin
Pattern of death seen in acute toxic or ischemic injuries to the liver
Coagulation necrosis
What does an apoptotic cell on histo look like?
Mass of intensely eosinophilic cytoplasm
Major cell involved in scar deposition in liver
Hepatic stellate cell
What vitamin do hepatic stellate cells store?
Vitamin A
Two major mechanisms of liver regeneration
- Proliferation of remaining hepatocytes
2. Repopulation from progenitor cells
Three types of things that can active stellate cells
- Cytokines like TNF-a
- Altered interaction with ECM
- Toxins and ROS
Two mechanisms of how hepatocyte loss turns into dense fibrous septa in chronic liver disease
- Collapse of reticulin framework
2. Deposition of collagen by myofibroblasts
What type of nodules are a predominant feature in most cirrhotic liver
Regenerative nodules
Most sever type of liver disease
Liver failure (chronic or acute)
What % functional capacity must be lost in liver before failure signs appear?
80-90%
Major zone where necrosis occurs in acetaminophen OD
Zone 3
What cell type produces factor 8?
Liver sinusoidal endothelial cells
Is cirrhosis a diagnosis?
No, its a response to injury
Five things that give points on the Child-Turcotte-Pugh calculator for chronic liver failure
- Bilirubin
- Albumin
- Ascites
- Encephalopathy
- INR
What causes itching?
Cholestasis
Which viral hepatitides can cause chronic infection in order from most to least likely
- Hep C
- Hep B
- Hep D (as a superinfection)
- Hep E (immunocompromised only)
- Hep A: never
Best indicator of chronicity of Hep B
Age at time of infection
RFs for progression in Hep C
- Older age
- Males
- EtOH use
- Immunosuppressive drugs
- Hep B or HIV co-infection
- Insulin resistance, DM, obesity, and metabolic syndrome
Three major sx of a liver abscess
Fever, RUQ pain, tender hepatomegaly
Examples of parasitic infections of the liver
- Malaria
- Schistosomiasis
- Strongyloides
- Cryptosporidium
- Leishmaniasis
- Echinococcus
- Amebiasis
- Flukes like clonorchis sinensis
What pattern of hepatic injury do anabolic steroids, Abx, and ART cause?
Cholestatic
What pattern of injury does acetaminophen cause?
Hepatocellular necrosis
What pattern of injury is caused by: ethanol, corticosteroids, methotrexate, total parenteral nutrition, aspirin (Reye syndrome)
Fatty liver disease
What neoplasm is caused by vinyl chloride?
Angiosarcoma
What % of alcoholics will develop cirrhosis?
10-15%
What CYP is involved with alcohol breakdown at high concentrations?
CYP2E1
Main enzyme that breaks down alcohol
Alcohol dehydrogenase
Most common cause of chronic liver disease in the US
HAFLD
NASH
Non-alcoholic steatohepatitis; NAFLD with steatohepatic injury similar to those seen in alcoholic hepatitis
Fibrosis on liver histo
Spider web of peri cellular collagen around the central vein
Histo differences in pediatric NAFLD
More diffuse steatosis, portal fibrosis (rather than central), no ballooned hepatocytes
Typical Fe stores in humans vs when hemochromatosis starts to manifest
Typical: 2-6g
Hemochromatosis: 20g+
What gene encodes hepcidin?
HAMP
Function of a1-antitrypsin
Inhibits proteases - particularly neutrophil elastase, cathespin G - neutrophil things
Most commonly diagnosed inherited hepatic disorder in infants and children
A1-antitrypsin deficiency
Lymphocytic infiltrate in liver in AIH
CD4 and CD8 T cells -> activate B cells to produce autoAbs
Combination of which four features helps lead to diagnosis of autoimmune hepatitis
- Exclude other etiologies
- AutoAbs
- Elevation of serum IgG
- Supportive histo findings on liver biopsy
Specific Abs in PBC
Anti-mitochondrial Abs against E2 component of pyruvate dehydrogenase complex
In diagnosing PBC, two of the following must be present (3 things)
- Elevated ALP for 6+ months
- Anti-mitochondrial Abs
- Characteristic histological findings
Classic Ab found in PSC
pANCA
What condition often occurs in association with fibropolycystic disease of the liver?
Poly cystic renal disease
Caroli disease
Multi focal cystic dilation of large intrahepatic bile ducts
Caroli syndrome
Caroli disease + congenital hepatic fibrosis
Classic triad seen in Budd-Chiari syndrome
Hepatomegaly + abd pain + ascites
Common site of complication from transplant of BM, kidney, and other solid organs
Liver, as a graft-vs-host reaction
Most common cause of jaundice in pregnancy
Viral hepatitis
Why are liver infarcts pretty rare?
Dual blood supply thru hepatic artery and portal vein
Most common cause of small portal vein branch obstruction
Schistosomiasis
Most common benign neoplasm of the liver
Cavernous hemangioma of the liver
Most common liver tumor of early childhood
Hepatoblastoma
Most common primary malignancy of hepatocytes
HCC
Biliary adenocarcinoma
Tumor arising from extrahepatic bile ducts
Metastatic liver malignancy
Far more common than primary hepatic neoplasia
Common primary sources that metastasize to the lungs
Colon, breast, lung, pancreas
What part of the embryo gut do the gallbladder and biliary system come from?
Foregut
How much bile can the liver secrete per day?
1L
Capacity of the gallbladder
50 mL
What hormone causes gallbladder to contract and release bile + cause sphincter of Oddi to relax?
CCK
Most common gallbladder anomaly
Folded fundus -> creates a Phrygian cap
Gallstone ileus / Bouveret syndrome
Large gallstone erodes directly into an adjacent loop of SI -> intestinal obstruction
Are gallbladder gangrene and perforation ore common in calculous or acalculous cholecystitis
Acalculous
Complications of both acute and chronic cholecystitis
- Bacterial superinfection
- Gallbladder perforation
- Gallbladder rupture
- Biliary fistula
- Aggravation of pre-existing medical illness
Most common malignancy of extrahepatic biliary tract
Carcinoma of the gallbladder
Other names for idiopathic retroperitoneal fibrosis
- Sclerosing retroPeritonitis
- Ormond disease
- IgG4 disease
Three major tumors of peritoneum
- Mesothelioma**
- Desmoplastic small round cell tumor
- Metastases
