intro to liver and cirrhosis W5 Flashcards
what defines segments of the liver?
venous drainage - branches of the hepatic vein
parenchymal cells of the liver?
hepatocytes
bile duct epithelia (cholangiocytes)
function of hepatocytes?
synthetic and metabolic activity
function of bile duct epithelia (cholangiocytes)
contribute to bile secretion
sinusoidal cells of the liver?
endothelial cells
Kupffer cells
function of endothelial cells? (liver)
allow transfer of substances to hepatocytes
function of Kupffer cells?
specialised tissue macrophages
perisinusoidal cells of the liver?
stellate cells
pit cells
function of stellate cells?
maintain homeostasis in sinusoids
involved in development of fibrosis
function of pit cells?
NK cells of the liver
features of protein metabolism in the liver?
catabolism of circulating protein/peptides
interconversion of amino acids
deamination of amino-acids allowing gluconeogenesis
synthesis of amino acids
catabolism of hepatic (stored) proteins in fasted state
protein synthesis
what proteins are synthesised in the liver?
albumin
transport proteins
ferritin
protease inhibitors
CRP
AFP
complement
coagulation factors
ammonia/ium metabolism in the liver?
absorbed from the gut
synthesised in the liver
detoxified in liver by conversion to urea in the urea cycle
3 phases of drug metabolism?
1 - oxidation, reduction, hydrolysis. CYP450 in liver
2 - conjugation in cytoplasm of hepatocytes
3 - secreted into the bile
constituents of bile?
bile acids
phospholipids
cholesterol
conjugated drugs
electrolytes
bilirubin
what causes jaundice?
bilirubin
where does bilirubin come from
breakdown product of haemoglobin
which vitamins are stored in the liver in large amounts?
vitamin A, D, B12
which vitamins are stored in the liver in small amounts? when are these rapidly depleted?
vitamin K, folate
depleted with decreased dietary intake
what minerals are stored in the liver?
iron (stored in ferritin and haemosiderin)
copper
immune regulation in the liver?
filters all blood from the gut
Kupffer cells phagocytose pathogens
supply of important chemokines/cytokines
priming T cell responses
what is the precursor to cirrhosis? how does this occur?
fibrosis
chronic injury causes:
-inflammatory damage
-parenchymal cell death
-angiogenesis
what types of chronic injury cause early fibrosis?
viral infection
alcohol
NASH
autoimmune disorders
cholestatic disorders
metabolic diseases
what causes early fibrosis to develop into cirrhosis?
disrupted architecture
loss of function
aberrant hepatocyte regeneration
how does hepatocyte injury lead to fibrosis?
hepatocytes injured, release substances, communicates to stellate cells, stellate cells activate macrophages leading to inflammation and fibrosis
what can cirrhosis lead to
portal hypertension
ESLD
what is cirrhosis?
development of regenerative nodules surrounded by fibrous bands in response to chronic liver injury
causes of cirrhosis?
toxin/drugs - alcohol
metabolic (non alcohol related) fatty liver disease
viral hepatitis (B, C)
immune-mediated disorders
inherited diseases
physical signs of cirrhosis? (maybe?)
jaundice
fever
loss of body hair
neuro - disorientation, drowsy, coma
ascites
how to diagnose fibrosis/cirrhosis?
liver biopsy
serum markers
transient elastography
liver biopsy features
gold standard
prone to sampling error, morbidity
serum markers features
cheap widely available
non-specific, grey zone for intermediate fibrosis
transient elastography features?
non-invasive, quick
machine costs, user experience, patient factors
serum markers of liver function?
albumin
prothrombin time
bilirubin
platelets
albumin features?
decreases in end stage liver disease due to decreased synthesis
prothrombin time features
decreased synthesis of clotting factors leads to increased prothrombin time
bilirubin features
increased in cirrhosis due to decreased clearance
platelets features
decreased in cirrhosis
increased consumption due to splenomegaly
decreased thrombopoietin production
