Liver Disease = Drug selection/dosing Flashcards
What does the liver do?
Production of plasma proteins
synthesis of clotting factors
Production of bile = req for absorption of fat, fat soluble vitamins, lipophilic drugs
Enterohepatic (re)circulation of bile salts and some drugs
Conjugation and excretion of bilirubin
Hormone inactivation
Metabolism and excretion
Do LFTs always indicate liver disease?
No, some liver disease can present in the presence or absence of abnormal LFT
What is Alanine transferase used to measure?
ALT = Cell death
What is aspartate transferase used to measure?
AST = cell death
What is alkaline phosphatase used to measure?
Alk phos or ALP = biliary problems
What is gamma GT/GGT used to measure?
Biliary problems
Helps clarify if raised alk phos is from liver
What do altered liver aminotransferase levels indicate about liver health?
(GENERALLY)
Indicate inflammation and necrosis (hepatocyte damage and death)
NOT RELIABLE MEASURE OF DYSFUNCTION
Explain the De Ritis Ratio
Ratio of AST:ALT
> 1 = damage is probably alcohol related
<1 = probably non alcoholic liver disease
What do altered liver ALT levels indicate?
Inc = hepatocellular damage
Also = muscle damage, acute MI, renal infarction
Haemolysis = falsely elevated levels
What do altered liver AST levels indicate?
Found in: liver, heart, kidney, pancreas
Raised = hepatocellular damage, acute MI, musculoskeletal disease, intestinal injury, haemolysis, hypothyroidism, pulmonary embolism, necrotic tumours
Dec = Vit B6 def, preg
What do altered liver Alk phos levels indicate?
Found in: liver, bone, placenta, biliary tract
Raised = hepatobiliary obstruction (+ other liver disease, associated w/ cholestasis), bone disease, children, preg, over 50
Dec = Vit D tox, milk-alkali syndrome, scurvy, hypophosphatasemia, hypothyroidism
What do altered liver GGT/gammaGT levels indicate?
One of the only LIVER SPECIFIC LFT!
Clarify if inc ALT is liver origin
Raised in = Cholestasis, diabetes, alcohol abuse, enz inducing meds
What do altered bilirubin levels indicate?
Raised = intravascular haemolysis, failure of conjugation in hepatocytes, biliary obstruction
- direct hyperbilirubinemia = biliary obstruction, cholestasis, hepatocellular injury - indirect hyperbilirubinemia = inc bilirubin production --> haemolysis
What is total bilirubin?
Conjugates + unconjugated + delta
What is direct bilirubin?
conjugated + delta
Explain the movement/breakdown of bilirubin in the liver
Bilirubin is bound to albumin in blood, taken up by hepatocytes
In hepatocytes = bilirubin conjugated with glucuronic acid
Conjugated (direct) bilirubin = secreted into bile (allows plasma albumin to stay low)
Cumulatively, what does bilirubin, ALP, and aminotransferases indicate?
Whether jaundice is pre-hepatic due to:
- intrahepatic damage
- intrahepatic cholestasis
- post-hepatic
What do altered serum albumin levels indicate?
Dec (due to dec synth) = chronic hepatitis, severe acute hepatitis, cirrhosis, malnutrition
Dec (due to inc loss of albumin) = burns, crohn’s disease, nephrotic syndrome
Dec (Due to inc catabolism) = infection, trauma, thyrotoxicosis
What are signs of severely low serum albumin?
Ascites (inc volume of dist, reduces absorption of water soluble meds)
Peripheral oedema
Pulmonary oedema
Reduced protein binding of drugs
In what liver conditions can you seen jaundice in?
cholestasis
severe cirrhosis
end stage liver failure
What are some clinical signs of compensated cirrhosis?
Xanthelasmas
Parotid enlargement
Spider naevi
Gynecomastia
Small/large liver
Splenomegaly
What are some clinical signs of general cirrhosis?
Jaundice
Fever
Loss of body hair
What are some clinical neurological signs of decompensated cirrhosis?
(neurological)
Disorientated
Drowsy
Hepatic flap
fetor hepaticus
Generally, what is the appearance of someone with liver disease?
Jaundice
Thin/skinny
Muscle wasting
Ascites =portal HTN, low plasma albumin, enhanced renal retention of Na
Gynaecomastia
Spider naevi
easily bruised/bruising
