Ch.18 Flashcards
What are the serum measurements of hepatocyte integrity
AST
ALT
Lactate dehydrogenase (LDH)
What are the tests that look for biliary excretory fxn
Serum bilirubin
- Total: unconjugated and conjugated
- Direct: conjugated only
Urine bilirubin
Serum bile acids: plasma membrane enzymes from damage to bili canaliculus
Serum alkaline phosphatase
Serum y-glutamyl transpeptidase (GGT)
What are the tests that look for damage to the bile canaliculus
Serum alkaline phosphatase
Serum gamma-glutamyl transpeptidase (GGT)
What are the tests that look for hepatocyte synthetic function
Serum albumin
Coagulation factors: PT, PTT, Fibrinogen, prothrombin, factors V, VII, IX, X
Hepatocyte metabolism: serum ammonia, aminopyrine breath test
Cholestasis
Accumulation of bilirubin in liver
Cytokine released by kupffer cell
TGF-beta
Liver hilum is called
Porta hepatis
Characteristic sign of acute hepatic failure (2)
Asterixis (Encephalopathy)
Nonrhythmic, rapid extension-flexion of the head and extremities
Coagulopathy: impaired clotting due to lack of production of Vit K dep factors
- Easy bruising early sign
Acute hepatic failure is associiated with (3)
1) Disseminated intravascualr coagulation
- liver removes activated coagulation factors
2) Portal HTN (leads to ascites and encephalopathy)
3) Hepatorenal syndrome
- kidneys normal
- hyponuria, elevated BUN and creatine
Chronic liver failure is associated with
Hepatitis B and C
NAFLD
Alcoholic fatty liver disease
Signs of chronic liver failure (4)
- Palmar erythema
- Spider angiomata
- Hypogonadism
- Gyencomastia
Ultimate cause of death from liver failure
- Encephalopathy
- Bleeding from esophageal varices
- Bacterial infections
Cirrhosis leads to risk of developing
Hepatocellualr carcinoma
Hepatitis without chronic or carrier state
Hepatitis A virus
Hepatitis that is ds-DNA
Hepatitis B virus
Chronic liver failure w/ hepatitis seen inperson who is 20 or 30 years old
Hepatitis B virus
Chronic liver failure hepatitis
Hepatitis B virus
Hepatitis C virus
Hepatitis that is precursor for hepatocellular carcinoma
Hepatitis B virus
Liver biopsy shows finely granular “ground glass” hepatocytes
Chronic Hepatitis B virus
Associated with metabolic syndrome
HCV
HAV
- type
- family
- transmission
- chronic
- diagnosis
- Sudden hepatitis
ssRNA
Hepatovirus (picornavirus)
Fecal-oral (contaminated H2O)
Chronic= never
Diagnosis= serum IgM Ab
Acute hepatitis: Yes
HBV
- type
- family
- transmission
- chronic
- diagnosis
- Sudden hepatitis
dsDNA
hepaDNAvirus
parenteral, sexual contact, perinatal
Chronic: 5-10%
Diagnosis: HBsAg, antiHBcAg; PCR for DNA
Acute hepatitis: Yes
HCV
- type
- family
- transmission
- chronic
- diagnosis
- Sudden hepatitis
ssRNA
flaviviridae
Parenteral, intranasal cocaine
Chronic: >80%
PCR for DNA, Elisa for Ab
Acute hepatitis: NO
Hallmark for increased portal chronic inflammation
Portal tract expansion
Fatty changes indicate what hepatitis
Chronic HCV
Interface hepatitis (piecemeal necrosis)
associated iwth lymphocytic infiltrate into adjacent parenchyma (beyond limiting plate) with destruction of individual hepatocytes along edges
Feature of chronic viral hepatitis
(as well as autoimmune hepatitis & steatophepatitis)
Hallmark of progressive chronic liver damage
Scarring
Cholangiocarcinoma
Liver flukes
Fasciola hepatica
Thorotrast
Acetaminophen involves what mechanism
CYP450
Oral contraceptives and anabolic steroids –>
hepatocellualr adenoma
Vinyl chloride –>
Angiosarcoma
DRB1 alleles
Autoimmune hepatitis
Type 1 autoimmune hepatitis
Middle aged older individuals
ANA (anti-nuclear)
ASMA (anti smoot muscle)
Prognosis better
Type 2 autoimmune hepatitis
Children, teenagers
Anti-LKM1 (anti-liver kidney microsome-1) antibodies against CYP2D6
Clinical features
1) Steatosis
2) Steatohepatitis
3) Steatofibrosis/ cirrhosis
1) Hepatomegaly
Mildly elevated bilirubin
Mildly elevated alk phos
2) Tender hepatomegaly
Hyperbilirubinemia
AST:ALT 2:1 levels (<300-400)
Elevated Alk phos
3) Hypoproteinemia
Coagulation abnormalities
Intracellualr eosinophilic aggregates of intermediate filaments (keratin) in ballooning hepatocytes
Mallory-Denk bodies
Mallory Denk seen in
Alcohol hepatitis
NAFLD
Wilson
Chronic biliary tract disease
Scarring in a chicken wire fence pattern
Alcohol steatofibrosis
Laennec cirrhosis
aka micronodular
Chicken wire
alcoholic steatofibrosis
Mutation for alcohol intolerance
Homozygous ALDH2 (asians) Flusing nausea lethargy
Most common in
- alcoholic liver disease
-NAFLD
-
1) Africans
2) Hispanics
NAFLD has an increased risk of
HCC
Pathogenesis of NAFLD
1) Insulin resistance leads to hepatic steatosis (fat deposition in liver)
2) Oxidative injury –> liver cell necrosis
Non-alcoholic steatohepatitis (NASH)
–> NASH cirrosis –> Decompensatin or HCC
Metabolic syndrome:
dysfunctional adipose tissue (endocrine organ)
Decreased production of adiponectin
Increased TNF-alpha, IL-6
=hepatocyte apoptosis
What also gets activated in NAFLD
Stellate cells via SHH
Levels of SHH correlated to stage of fibrosis of NAFLD
NAFLD vs Alcohol liver disease
Mononuclear cells more prominent
Portal fibrosis more prominent
Mallory Denk less common
Death of NAFLD most common by
Cardiovascular death
Alcohol liver disease death by (5)
Hepatic coma Massive GI hemorrhage Intercurrent infection Hepatorenal syndrome Hepatocelluarl carcinoma
“A 45-year-old man has had a fever and a productive cough for the past 3 days. On physical examination there is dullness to percussion over the right upper lung. His temperature is 37.9°C. A chest radiograph reveals right upper lobe consolidation. Laboratory findings include serum total protein of 6.0 g/dL, albumin 2.7 g/dL, AST 185 U/L, ALT 98 U/L, total bilirubin 1.0 mg/dL, alkaline phosphatase 31 U/L, and prothrombin time 20 sec. An abdominal CT scan shows hepatomegaly with decreased hepatic attenuation. Which of the following conditions is the most likely underlying cause of death?”
Diabetes Mellitus
NAFLD is associated w/ obesity and diabetes mellitus
Metabolic syndrome criteria
One of: DM, impaired glucose tolerance, impaired fasting glucose, insulin resistance
Two of:
- BP >140/90
- TGs ?1.695 and HDL
Only metabolic liver disease not AR
NAFLD
Hemochromotosis: AR
Wilson disease: AR
Alpha1-AT: AR
Excessive iron absoprtion
Hemochromatosis
HFE mutation
Hemochromatosis
C282Y
Juvenile hemochromastosis
HJV or HAMP
More severe
Prussian blue stain
Small shrunken liver w/ micronodules
Dark brown black liver
Hemochromastosis
Pancreas fill w/ brown pigment Bronze skin DM Hypogonadism Cardiac dysfunction
Hemocrhomatosis
Hemochromatosis risk of
Hepatocellular carcinoma 200x
Prussian blue stains for
iron
Mutation ATP7B
Wilson disease
Impaired cooper excretion in bile
Wilson disease
Parkinsonism movement
Elevated direct bilirubin
Elevated bilirubin = hemolytic anemia due to copper toxicity to RBC membranes
PiZZ
Alpha 1- AT def
A1-AT leads to
- age
- mutation causes accumulation of
infants and children
Pulmonary emphysema
Hepatic disease
Accumulation of protein in liver
Magenta granules inside hepatocytes
Alpha 1- AT
Hereditary hyperbilirubinemias (5)
(Extrahepatic)
Crigler Najjar Type 1 Crigler Najjar type 2 Gilbert syndrome Dubin-johnson syndrome Rotor syndrome
Autopsy baby
Unconjugated hyperbilirubinemia
- inheritence
- missing
Crigler-Najjar type I
AR
No UGT1A1 activity
Clinic baby Hyperbilirubinemia Kernicterus -inheritence -missing
Crigler Najjar type II
AD
Decreased UGT1A1
Stressed student with yellow eyes
hyperbilirubin- indirect
Gilbert
Decreased UGT1A1
Autopsy
black liver
Dubin johnson syndrome
AR
MDR protein 2 (MRP2)
conjugated hyperbilirubinemia
18 y.o
hyperbilirubin- direct
Rotor syndrome
AR
Infant to pediatrician, yellow skin. Tired weak, floppy arms. Parents first cousins
Crigler Najjar type II
Elevated GTT and alk phosphatase
Cholestasis
(impaired bile flow)
Accumulation of bile pigment in hepatic parenchyma
Fever, RUQ pain, jaundice
Charcot's triad Ascending cholangitis (gallstones)
Primary hepatolithiasis
Disease of intrahepatic gallstone formations
Leads to repeat bouts of ascending cholangitis, progressive inflammatory destruction of hepatic parenchyma, and predisposes to biliary neoplasia
Hepatolithiasis
gallstones in bilary ducts of liver
Cholestasis
flow of bile stops
Panlobular giant-cell transformation of hepatocytes
Neonatal hepatitis
Most common form of biliary atresia
Perinatal form
Rotavirus, CMV, autoimmune
Jaundice longer than 2 weeks
Acohlic stools
Biliary atresia
Inflammatory destruction of intrahepatic ducts
primary biliary cirrhosis (PBC)
Inflammatory destruction of intrahepatic adn extrahepatic bile ducts
Priamry sclerosing cholangitis (PSC)
FLorid duct lesions
Primary biliary cirrhosis (PBC)
Antimitochondrial Ab
Primary biliary cirrhosis (PBC)
Beading on X ray
Primary sclerosing cholangitis (PSC)
PANCA
atypical perinuclear anti-neutrophilic cytoplasmic antibodies
PSC
Onion skin fibrosis
PSC
PSC associated with
IBD
Pancreatitis
PBC associated with
Sjogren syndrome
Scleoderma
Thyroid disease
AMA positive
ANA positive
PBC
Choledochal cysts
congenital dilations of the common bile duct
Females before age 10
Jaundice
Recurring abdominal pain
Cysts may form segmental or cylindric dilations
Von Meyen complexes
indicative of fibropolycystic disease FPD
Caroli disease
biliary cysts that occur w/ congenital hepatic fibrosis
indicative of fibropolycystic disease FPD
Congenital hepatic fibrosis
portal tracts enlarged by irregular broad bands of collagenous tissue that form septa to divide liver into irregular islands
indicative of fibropolycystic disease FPD
Schistosomiasis
parasitic worm
Obstruction of two or more hepatic veins leads to hepatomegaly, pain ascites
Budd-Chiari syndrome
Liver is swollen red-purple
Budd-chiari syndrome
Obstruction two or more hepatic veins
Obliteration of terminal hepatic venules by subendothelial swelling and collagen depostiion
-Causes
Sinusoidal obstruction syndrome
(Veno-occlusive disease)
- Jamaican bush tea drinkers
- 3 weeks after stem cell transplant
Hemolysis
Elevated liver enzymes
Low platelets
Pregnant
HELLP
Preeclampsia
Maternal HTN
Proteinuria
Peripheral edema
Coagulation problems
Preeclampsia
Becomes eclampsia w/
- hyperreflexia convulsons occur
Third trimester
Elevated serum aminotransferases
Bleeding, nausea vomiting
Jaundice
Acute fatty liver disease
Pregnant 3rd trimester Dark urine Light acholic stools Jaundice Bile salt level increased greatly
-risk (3)
Intrahepatic cholestasis of pregnancy
- fetal distress
- stillborn
- prematurity
Autopsy
Plump hepatocytes are surrounded by rims of atrophic hepatocytes
Multiple nodules on liver
No fibrosis
Nodular regenerative hyperplasia (NRH)
Single well demarcated lesion with central scar on liver
Focal nodular hyperplasia FNH
Blood vessel tumor of liver
Cavernous hemangioimas
Red blue nodules under capsule
Cavernous hemangiomas
Tumor of liver associated with oral contraceptives
Hepatocellualr adenoma
- beta-catenin
3 types hepatocellular adenomas
1) HNF1-alpha
-inactive
no risk
2) Beta-Catenin
- active
- high risk
- oral contraceptives
3) Inflammatory
- small risk
Assoc w/ NAFLD
Single large scirrhous tumor with fibrous bands coursing through it
<35
well differentiated cells rich in mitochondria in cords separated by parallel lamellae of dnse collagen bundles
Fibrolamellar carcinoma
Perihilar tumors located at junction of hepatic ducts
Klatskin tumors
Cholangiocarcinoma (CCA)
Liver flukes
Opisthorchis
Clonorchis
Cholangiocarcioma CCA
Most common gallbladder anomaly
Phrygian cap
Fundus that folded inward
Cholelithiasis
Gallstones
Family history, female, fat, fourty, fertile, fair risk factors for
Cholelithasis gallstones
Pigment stones
Stones of unconjugated bilirubin
Bacterial contamination
Brown stones
Cholesterol stones
only in gallbladder
pale yellow –> black (sterile bile duct)
Carcinoma of gallbladder
adenocarcinoma
women
risk factor gallstones
ERBB2 (HER2) oncoprotein overexpressed
Carcinoma of gallbladder
Adenocarcinoma
