KINESIOL 1Y03 Chapter Notes - Chapter 12: Histopathology, Hepatocyte, Alkaline Phosphatase
22 Jun 2018
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Assessment of hepatic functional reserve
Normal liver function involves:
1. Intermediary metabolism
-Glycogen storage
-Glucose synthesis only this relevant in acute liver failure where hypoglycaemia is
v.rapid
-Fatty acid synthesis
-Lipoprotein metabolism
2. Protein synthesis
-albumin has a longer t1/2 than most other factors hence drops more slowly in acute
liver failure
-those in red are acute phase proteins, hence raised in inflammatory response, which
can scupper diagnosis in patients with inflammatory conditions
-Prothrombin is vitK dependant so it can be unclear whether low levels are truly due
to reduced liver function or fat malabsoprtion (e.g. due to cholestasis) can give
vitamin K to clarify this
3. Xenobiotic metabolism
-conjugation via glucuronate and sulphate
-chemical modification via P450, acetylation/deacetylation and oxidation/reduction
-excretion via bile
hence liver failure causes changes to drug metabolism
4. Hormone metabolism
-Vitamin D hydroxylation and absorption
-Steroid hormone conjugation and excretion
gynaecomastia and testicular atrophy only in chronic liver failure
-Peptide hormone catabolism e.g. insulin, growth hormone, glucocorticoids, PTH
5. Bile synthesis
-Involved in excretion, micelle formation and digestion
6. Reticulo-endothelial function
-Kupffer cells in sinusoids are the key player in RE function: they absorb bacteria /
bacterial products (LPS) and IgA receptors before systemic inflammation response
begins
pertinent in acute liver failure where function is lost very quickly, where many
patients die of sepsis
-Erythropoiesis
-Destruction of exhausted red cells (120 day lifespan), also occurs in bone marrow
and spleen: haemolysis unconjugated bilirubin conjugated to glucuronic acid and
excreted to biliary system bacterial proteases convert to urobilinogen excretion
in faeces
Liver function is localized:
-there is a central vein
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-there are triads around the
outside (hepatic artery, portal
vein, bile duct)
-hence, zone 1 is the most
oxygenated, zone 3 is the least
-carbohydrate and protein
metabolism occur in all zoned c.f.
cytochrome P450 function, which
occurs in zone 3; hence
paracetemol OD is toxic to
central zone (3) where P450
metabolises it
Encephalopathy
= stimulation of the reticular system followed by terminal depression of brainstem function
toxicity due to ammonia, and other toxic metabolites
early: personality change, anti-social behaviour, nightmares, headaches + dizziness,
delirium / mania, fits, asterixis, hepatic foetor
late: decerebrate rigidity (spasticity, extension and hyperpronation of amrs, hyperextension
of legs), dysconjugate eye movements, respiratory + circulatory failure due to brainstem
failure
grading:
By grade 3 should be on ITU
Complications of liver failure
LIVER FUNCTION COMPLICATION AS RESULT OF LOSS
Intermediary metabolism Hypoglycaemia
Protein synthesis Coagulopathy
Xenobiotic metabolism Drug toxicity
Bile synthesis (bile acid excretion, bilirubin
metabolism)
Jaundice (steatorrhoea, pruritis – more
common in cholestasis than liver failure)
Reticulo-endothelial infection
Assessment of liver function
LFTs
-Transaminases are cytosolic enzymes; ALT more liver-specific than AST. Increases
reflect hepatocyte necrosis but are non-specific
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Document Summary
Glucose synthesis only this relevant in acute liver failure where hypoglycaemia is v. rapid. Hence liver failure causes changes to drug metabolism: hormone metabolism. Gynaecomastia and testicular atrophy only in chronic liver failure. Peptide hormone catabolism e. g. insulin, growth hormone, glucocorticoids, pth: bile synthesis. Involved in excretion, micelle formation and digestion: reticulo-endothelial function. Kupffer cells in sinusoids are the key player in re function: they absorb bacteria / bacterial products (lps) and iga receptors before systemic inflammation response begins. Pertinent in acute liver failure where function is lost very quickly, where many patients die of sepsis. Destruction of exhausted red cells (120 day lifespan), also occurs in bone marrow and spleen: haemolysis unconjugated bilirubin conjugated to glucuronic acid and excreted to biliary system bacterial proteases convert to urobilinogen excretion in faeces. By grade 3 should be on itu. Jaundice (steatorrhoea, pruritis more common in cholestasis than liver failure) infection. Transaminases are cytosolic enzymes; alt more liver-specific than ast.
