Introduction to Liver Cirrhosis Flashcards
what ligaments divides the right and left lobes
falciform ligament
5 functions of the liver
detoxification
synthesis of digestive enzymes
protein production
storage of nutrients
metabolism
functions of periportal zone
gluconeogenesis
bile salt formation
functions of perivenous/pericentral zone
glycolysis
lipolysis
glucuronidation
what is the cholangiole
the bile channels/bile cannaliculi
what % of the liver is hepatocytes
80%
what are pit cells
natural killer cells of the liver
what cell types are found in the perisinuosoidal space
stellate cells
dendritic cells
what substances can be used to make glucose in gluconeogenesis
lactate
pyruvate
glucogenic amino acids
glycerol
describe the steps of lipid metabolism
- bile digests lipids in the gut
- chylomicrons are formed
- these travel in the lymphatic system to the liver
- chylomicrons are metabolised by lipoprotein lipase to cholesterol, phospholipids, triglycerides and free fatty acids
how does the liver metabolise proteins
via the citric acid cycle
function of vitamin k
required for post translational modification of many of the clotting factors
key protein made in the liver
albumin
what is a cause of brain damage in liver disease
the blood is diverted past the liver due to cirrhosis
which means ammonia is not removed from the blood
the ammonia damages the astrocytes in the brain
what is ammonia a waste product of
protein metabolism
what does the liver do to ammonia
detoxifies it by converting it to urea in the urea cycle
what are the three phases of drug metabolism
- oxidation, reduction and hydrolysis
- conjugation in cytoplasm of hepatocytes
- secretion into the bile
what enzymes control phase 1 (oxidation, reduction and hydrolysis) of drug metabolism and where are these found
CYP450
in endoplasmic reticulum of the liver
what control excretion of metabolised drugs into bile
ATP
how much bile is made in a day
1-2L
what are the constituents of bile
bile acids
phospholipids
cholesterol
conjugated drugs
electrolytes (Na+, Cl-, HCO3-, Cu)
bilirubin
what’s the difference between primary and secondary bile acids
primary - made in liver
secondary - absorbed
what contributes to the brown colour of stool
stercobilin
a form of urobilinigon
where is heme broken down into unconjugated bilirubin
spleen
what vitamin are stored in the liver
A
D
B12
K
what minerals are stored in the liver
copper
iron (as ferritin and haemosiderin)
how much vitamin K is stored in the liver and how quickly does it deplete with decreased dietary intake
small
quickly
what does the liver do to vitamin D
metabolises from inactive form (cholecalciferol vitamin D3) to active form (25-hydroxyl vitamin D)
what mechanisms does the liver have for immune regulation
filters all blood from gut
kupffer cells phagocytose pathogens from gut
supply chemokines
prime T cell responses
what chemokines are supplied by the liver
interleukins
tumour necrosis factor
what mediates resolution from early fibrosis back to normal liver
macrophages
cirrhosis without treatment leads to
hepatocellular carcinoma
what two proteins/peptides are released when hepatocytes are damaged
TGF alpha
IGF1
what follows stellate cell activation in hepatocyte injury
cells transform into myofibroblast like cells
this causes increased collagen and proinflammatory factors
what follows stellate cell activation in hepatocyte injury
cells transform into myofibroblast like cells
this causes increased collagen and proinflammatory factors
an autocrine loop is formed where stellate cells activate themselves
steps of liver cirrhosis
- stellate cells transform into myofibroblasts and increase collagen production
- metabolite and oxygen exchange decrease across the space of disse
- hepatocytes disfunction
- new blood vessels are formed and sinusoid is remodelled
- sinusoidal resistance increases causing portal hypertension
what metabolic diseases can cause cirrhosis
haemochromatosis
wilson disease
why is sodium and water retention a feature of liver cirrhosis
portal hypertension causes splanchnic (abdominal) vessels to vasodilate
which causes hypotension in the rest of the body
so the RAAS is activated
which causes vasocontriction and Na+ and water retention
difference between compensated and decompensated stage of liver disease
compensated - asymptomatic
decompensated - symptomatic
median survival of compensated liver disease
12 years
median survival of decompensated liver disease
2 years
what signs can be seen on the hands of someone with liver cirrhosis
xanthoma
duputren’s contracture
clubbing
liver palms
symptoms of decompensated liver cirrhosis
neurological (disorientation, drowsy, coma)
hepatic flap
variceal bleeding
jaundice
ascites
oedema
caput medusae
how does albumin change in liver cirrhosis
decreased in end stage due to decreased function
how does prothrombin time change in liver cirrhosis
increases due to decreased synthesis of clotting factors
what PT time is an indicator of liver dysfunction
> 12s
how does bilirubin change in liver cirrhosis
increase due to decreased clearance
how does platelets change in liver cirrhosis
decreased
increased consumption due to splenomegaly
investigations to diagnose fibrosis and cirrhosis
liver biopsy
serum markers
transient elastography (fibroscan)
advantages of liver biopsy
quantitative
can detect cause of cirrhosis
disadvantages of liver biopsy
prone to sampling error
risk of bleeding and others
advantages of serum markers
cheap
widely available
disadvantages of serum markers
nonspecific
grey zone for intermediate fibrosis
advantages of transient elastography
non invasive
quick
disadvantages of transient elastography
machine cost
user and patient experience
what does the fibroscan detect
liver stiffness and (some machines) fat
what score can be used for prognosis of liver disease
child-pugh score
