clinical path - liver Flashcards
functions of the liver
metabolism of body fuels storage functions detoxification synthesis of most coagulation proteins excretory function
what does the liver metabolize
- protein metabolism: albumin, globulin (not immunoglobulin)
- carbohydrate metabolism: remove glucose from portal blood
- lipid metabolism: make fatty acids, triglycerides, cholesterol, and apolipoproteins
when does serum enzyme activity increase
when the rate an enzyme enters plasma exceeds the rate of enzyme inactivation or removal from plasma
when do you see an increase in enzymes
when there are damaged cells,
induction of enzyme synthesis
cell proliferation (neoplasia)
decreased enzyme clearance (decreased renal blood flow)
or ingestion and absorption (GGT from cholesterol, ALP from bones)
what enzymes are released from damaged hepatocytes
ALT
AST
SDH
GLDH
What enzymes are associated with cholestasis
ALP
GGT
what are the four liver products
urea, glucose, albumin, cholesterol
what are some hepatobiliary causes of increased liver enzymes
hypoxia, metabolic disease, toxicoses, inflammation, neoplasia, trauma, or intrahepatic/extrahepatic bile duct obstruction
what are some extrahepatic causes of increased liver enzymes
endocrine disease, Gi disorders, systemic infections, or drug indication
ALT
sensitive indicator of hepatocellular injury, but not specific (found in small amounts of muscle too)
what species can you use ALT
Useful in cats and dogs
not useful in ruminants and horses
AST
an unspecific enzyme produced by the liver, muscle, and erythrocytes during hemolysis
SDH
primary liver enzyme for horses. can also use in ruminants. unstable in vitro, need to run sample immediately
GLDH
liver-specific enzymes helpful in detecting hepatocellular injury/necrosis of large animals/ dogs
explain cholestasis
interruption or obstruction of the bile flow or excretion. can be intrahepatic (bile caniliculi and bile ducts) or extrahepatic (gall bladder and common bile duct)
may result in release of ALP and GGT
what are the three types of ALP
- B-ALP: bone ALP
- L-ALP: liver ALP
- C- ALP: corticosteroid induced ALP (only in dogs)
what can increase B-ALP
- bone growth (young healthy dogs)
- bone fractures (10 days after fracture starts to heal)
- bone lesions that increase osteoblastic activity (osteosarcoma)
- hyperthyroid in cats
L-ALP
sensitive indicator of cholestasis in dogs
increased intrabiliary pressure cause increase ALP production by hepatocytes
often seen in conjunction with GGT and bilirubin
what enzyme do you use to detect cholestasis in horses and cattle
GGT
why is GGT liver sensitive
it is predominately associated with the brush border or microvilli of hepatocytes, biliary epithelial cells, renal tubular epithelial cells or mammary cells
GGT detection in different species
- horses: GGT is more sensitive for detecting cholestasis than ALP
- cattle: GGT is more sensitive than ALP for detecting cholestasis
dogs: ALP is more sensitive than GGT
cats: GGT may be normal with hepatic lipidosis, but ALP increased
explain hepatic insufficiency
pathophysiologic state in which the number of functioning hepatocytes is markedly reduced
what are the two disorders causing hepatic failure
- disorders that destroy hepatocytes
2. PSS causing hyperplasia or atrophy of liver due to decreased nutrients
what are the three liver function tests
- bile acids
- ammonia
- bilirubin
explain the general physiology of bile acids
bile is synthesized in the liver from cholesterol, conjugated, and secreted into the gall bladder. After a meal, the gall bladder contracts, releasing bile into the intestines. it solubilizes lipids and aids in fat digestion in the intestine
when bile acids reach the ileum, it is transported back into the portal circulation and extracted by hepatocytes
where are bile acids found?
95% in enterohepatic circulation
5% in the systemic circulation
–> increase in systemic concentration indicates a problem somewhere in enterohepatic circulation
causes for increased serum bile acids
1) decreased clearance from portal blood
- -> decreased heaptic uptake
- -> PSS
2) decreased bile acid excretion
- -> obstructive choleostasis
- -> functional choleostasis
bile acid concentrations suggesting liver dysfunction
cats: >20um/l
dogs: >25um/l
horses: >18um/l
cattle: ineffective test
ammonia physiology
produced in the GIT by the breakdown of AA and urea by GI microflora, where it’s then transported by the portal circulation to the liver and converted into urea. urea is then excreted into the GIT and into the urine
where is ammonia found
80-90% is shunted into the urea cycle
10-20% metabolized by peripheral tissues (kidneys, brain, heart)
explain the physiology of bilirubin
bilirubin is a pigment that is produced by the degradation of the heme portion of hemoglobin, mainly by macrophages.
it is then transported to the liver where it is conjugated before being excreted into the bile
two types of bilirubin
1) unconjugated: not water-soluble, transported in the blood bound to albumin
2) conjugated: water soluble, conjugated to glucuronide
what are the three types of hyperbilirubinemia
1) pre hepatic
2) hepatic
3) post hepatic
explain pre hepatic hyperbilirubinemia
due to RBC breakdown (haemolysis), resulting in an increase in unconjugated bilirubin that exceeds the hepatic uptake capacity
this can cause secondary cholestasis as the liver becomes overwhelmed
explain hepatic hyperbilirubinemia
caused by a decreased hepatic uptake or conjugation within the liver
can be of a hypoxic, anomalous, metabolic, neoplastic, inflammatory, or inheritated nature
explain post hepatic hyperbilirubinemia
extrahepatic disruption of bile causing a partial or complete blockage
can be due to neoplasia, cholelithiasis, cholangitis, or inflammation of an adjacent organ, i.e pancreas
