12) Liver function Flashcards
what makes the liver unique?
only organ in mammals that can regenerate
divides liver’s lobes
falciform ligament
liver receives —% of blood per minute
30
explain dual blood supply of liver
Portal vein: Carries blood from GI tract (nutrient rich) and spleen
Hepatic artery: a branch of celiac axis (well-oxygenated)
liver lobule
Basic microscopic unit
contains four to six portal triads
portal triad has branches of…
Portal vein
Hepatic artery
Bile duct
acinus
Functional anatomical unit of the liver
Diamond-shaped mass of liver parenchyma
kupffer cells
phagocytes that engulf bacteria, old red blood cells (RBCs), toxins, and cellular debris from the blood flowing through the sinusoids
The ———— and ———– flow in opposite directions.
bile in the bile canaliculi
blood in the sinusoids
space of disse
Space between the endothelial cells and hepatocytes where nutrient uptake occurs
5 major categories of liver function
- Metabolism
- Excretion
- Detoxification
- Storage
- Immunologic
liver’s metabolism functions
- Most of plasma proteins, except gamma globulins, vWF, and hemoglobin
- Produces, stores, and breaks down glycogen
- Lipid and lipoprotein synthesis
- Synthesis of Urea
liver’s excretion functions
Bile acids
Cholesterol
Bilirubin
bile functions
- Fatty acid metabolism by provide surface-active detergent molecules that facilitate excretion of cholesterol and solubilization of the lipids for intestinal absorption.
- Excretion of waste products.
- Kill off bad microbes.
- Blood sugar metabolism
liver’s detox functions
Bilirubin conjugated to direct bilirubin
Drugs
Alcohol dehydrogenase
liver’s storage functions
Glycogen
Iron
Copper
Vit A, D, E, K
liver’s immunologic functions
Phagocytosis of bacteria and other substances by Kupffer cells
Secretion of I g A
Approximately 200 to 400 mg of bilirubin produced daily, 80% of which is produced from…
hemoglobin released from old RBCs.
Degradation of RBCs occurs in the…
macrophages of the reticuloendothelial system (spleen, liver, and bone marrow).
what happens to hemoglobin’s porphyrin ring?
- Converted to biliverdin (green bilirubin) by the action of heme oxidase
- Biliverdin is reduced to unconjugated bilirubin by biliverdin reductase in the macrophages
- Unconjugated bilirubin is transported to the liver by plasma albumin
unconjugated bilirubin has an affinity for…
nervous tissue
kernicterus
Unconjugated bilirubin reaches liver
albumin is removed in the sinusoidal space
enters the hepatocyte by binding to ——- or passive diffusion.
ligandin
Unconjugated bilirubin is conjugated to glucuronic acid by …
UDP-glucuronyl transferase
3 types of conjugated bilirubin found in plasma
Bilirubin monoglucuronide
Bilirubin diglucuronide
Delta bilirubin
unconjugated is found in serum
conjugated bilirubin is bound to —— acid
glucaronic
Seen only in cases of significant hepatic obstruction
delta bilirubin
pathway of conjugated bilirubin
Bile canaliculi → larger bile ducts → hepatic ducts → gallbladder → duodenum
Conjugated bilirubin is metabolized into ———-, ———-, and ———- by bacteria enzyme.
urobilinogen
stercobilinogen
mesobilinogen
————- is accountable for more symptoms of jaundice than ———— because it is more easily absorbed into the tissues
conjugated
unconjugated
types of prehepatic jaundice
- increased production of bilirubin (hemolysis, dyserythropoiesis)
- decreased delivery to hepatocytes
most common cause of unconjugated hyperbilirubinemia
neonatal jaundice
examples of posthepatic jaundice
- Common bile duct stones, gallbladder stones (most common)
- Cancer of the bile ducts, pancreas, or ampulla of Vater
- Bile duct stricture or stenosis
↑ total bilirubin
N conj. bilirubin
↑ unconj. bilirubin
↑ urine urobilinogen
N or ↑ fecal urobilinogen
N urine bilirubin
prehepatic jaundice
↑ total bilirubin
↑ conj. bilirubin
↑ unconj. bilirubin
↑ or N urine urobilinogen
N or ↑ fecal urobilinogen
↑ urine bilirubin
hepatic jaundice
↑ total bilirubin
↑ conj. bilirubin
↑ unconj. bilirubin
↓ urine urobilinogen
↓↓ fecal urobilinogen
↑ urine bilirubin
posthepatic jaundice
Benign condition manifested by mild unconjugated hyperbilirubinemia
gilbert’s syndrome
Rare disorder caused by complete absence of UDP-glucuronyl transferase
Crigler-Najjar Syndrome (CNS)
Most patients die of severe brain damage caused by kernicterus within the first year of life.
type 1 CNS
Milder form, partial deficiency of enzyme, 10% of enzyme activity.
type 2 CNS
Defect in canalicular excretion of the conjugated bilirubin into the bile.
Dubin-Johnson Syndrome (DJ)
Dark brown pigment, lipofuscin, in hepatocytes and Kupffer cells
Dubin-Johnson Syndrome (DJ)
Defect in hepatic uptake and storage of bilirubin
rotor syndrome
Rapidly progressive encephalopathy with hepatic dysfunction
Often begins several days after apparent recovery from a viral illness, especially varicella or influenza A or B
Salicylate use identified as a risk factor in kids with varicella or influenza A or B
Reye’s syndrome
Vomiting and confusion, rapidly evolving to seizures and coma.
Reye’s syndrome
causes of hepatitis
Infections (viral hepatitis)
Toxic (alcohol-related disease)
Genetic (hemochromatosis)
Immune (autoimmune hepatitis and primary biliary cirrhosis)
Neoplastic (hepatocellular carcinoma)
picornavirus
HAV
hepadnavirus
HBV
also Dane particle
Persistent HbsAg without clinical hepatitis
chronic carrier
Always present once infected with HBV
HBcAb
Indicates recovery from HBV infection or immunity status
HBsAb
core window
Brief interval between disappearance of HBsAg and appearance of HBsAb during HBV infection
flaviviridae
HCV
75% acutely infected individuals fail to clear the virus and develop a chronic infection
HCV
coinfection vs superinfection
Coinfection: Infections with two virus at the same time;
Superinfection: HDV infection occurs in the presence of persistent HBV infection
Infection when HBsAb is present but observe clinical deterioration of the patient
suspect HDV
80%-90% develop chronic hepatitis, leading to cirrhosis or hepatic cancer
HDV coinfection
herpesvirus
HEV
Devastating to pregnant women (20% mortality rate for both mom & baby)
HEV
hepatitis with no vaccine
HCV
HEV
most common causes of chronic hepatitis
hepatitis B
hepatitis C
autoimmune disease
Wilson disease
α1-antitrypsin deficiency
suspect ALD in these pts
> 15 drinks per week for men and >10 drinks per week for women over at least a two-year period
Fat accumulation in the hepatocytes.
steatosis
Occur within two weeks of regular alcohol ingestion and resolves rapidly with abstinence
alcoholic steatosis
Fatty accumulation in the hepatocytes and inflammation
alcoholic steatohepatitis
Follows 6 months to a year of moderate alcohol consumption
alcoholic steatohepatits
Symptoms caused by the loss of functioning hepatocytes, increased resistance to hepatic blood flow or portal hypertension, ascites, and hepatic encephalopathy
cirrhosis
leading cause of both chronic hepatitis and cirrhosis
HCV
cirrhosis complications
- Portal hypertension
- Varices formed in the stomach and esophagus
- Edema and ascites
- Bruising
- Itching
- Hepatic encephalopathy
Child-Turcotte-Pugh cirrhosis stages
Class A: score <7 points
Class B: 7-9 points
Class C: 10-15 points
3 blood tests used to get Model for End-Stage Liver Disease (MELD) stage
Bilirubin
Prothrombin time
Creatinine
3 inherited liver diseases that present as chronic hepatitis
Hereditary hemochromatosis (HH)
Wilson disease
α1-antitrypsin deficiency (AAT)
Mutations in the HH gene (HFE), increased intestinal iron absorption can lead to total-body iron overload.
hereditary hemochromatosis
Associated with lung (emphysema) and liver disease
AAT deficiency
Impairment in the excretion of bile
cholestasis
T-lymphocyte-mediated attack on small interlobular bile ducts.
Primary biliary cirrhosis (PBC)
Chronic inflammatory disease of unknown origin
Inflammation, fibrosis and obliteration of the intrahepatic and extrahepatic bile ducts
Primary sclerosing cholangitis (PSC)
associated with IBD
Primary sclerosing cholangitis (PSC)
The presence of hepatic steatosis in the absence of excessive alcohol consumption.
Nonalcoholic fatty liver disease (NAFLD)
Fat accumulation and inflammation and/or fibrosis
ALT level is ≥ AST (De Ritis ratio <1)
Nonalcoholic steatohepatitis (NASH)
Jendrassik-Grof Test
bilirubin method
Jendrassik-Grof Test
Bilirubin pigments react with a —– reagent
———- is added (stops reaction by destroying excess sulfanilic acid)
———– promotes the displacement of bilirubin from albumin and increases the reaction rate.
———– buffers the solution.
Results in formation of ———– Azobilirubin
diazo
ascorbic acid
caffeine
sodium benzoate
blue-green
Converts purple azobilirubin to blue azobilirubin.
Alkaline tartrate
2 possible results of PT test with injected vitamin K
PT corrects: Malabsorption of vitamin K in cholestasis
PT doesn’t correct: Hepatocellular disease
ammonia elevated in…
advanced liver disease
renal failure
ammonia sample
arterial blood preferred
avoid tourniquettes, fist clenching if venous
heparinized
on ice, centrifuged, separated w/i 15 mins
Berthelot reaction
ammonia method
glutamate dehydrogenase
ammonia method
