case 5 - jaundice and cirrhosis Flashcards
what does jaundice refer to
the yellowish tint to the body tissues
what is it caused by
large amounts of billirubin in the extracellular fluids
what are the three types of jaundice
pre-hepatic
intra-hepatic
post-hepatic
what is the normal plasma concentration
The normal plasma concentration of bilirubin, which is almost entirely the free form, averages 0.5 mg/dl of plasma.
when will the skin begin to appear jaundiced
when the concentration rises to about three times normal - above 1.5mg/dl
what is pre hepatic jaundice caused by
haemolysis or by congenital hyperbillirubinaemia and is characterised by an isolated raised bilirubin level
what is haemolysis
this is the destruction of RBCs or their precursors in the bone marrow.
this causes increased bilirubin production
therefore the plasma concentration of unconjugated bilirubin rises to above normal levels
why is jaundice due to haemolysis usually mild
because a healthy liver can excrete a bilirubin load six times greater than normal before unconjugated bilirubin accumulates in the plasma
what is intra hepatic jaundice caused by
impaired cellular uptake, defective conjugation or abnormal secretion of bilirubin by hepatocytes, occurring as a consequence of parenchymal liver disease
when can bilirubin transport across the hepatocytes be impaired
at any point between uptake of unconjugated bilirubin into the cells and transport of conjugated bilirubin into the canaliculi
what happens to the levels of both unconjugated and conjugated bilirubin in the blood
they both increase
what can hepatocellular jaundice be due to
acute or chronic liver injury and clinical features of acute or chronic liver disease may be detected clinically
what is jaundice due to parenchymal liver disease associated with
increases in AST, ALT, but increases in other LFTs, including GGT and ALP may occur and suggest specific aetiologies
what does acute jaundice in the present of raised AST suggest
an infectious cause
what is obstructive jaundice due to
Failure of hepatocytes to initiate bile flow.
Obstruction of bile flow in the bile ducts or portal tracts.
Obstruction of bile flow in the extrahepatic bile ducts between the porta hepatis and the papilla of Vater.
what happens to the unconjugated bilirubin
still enters the liver cells and becomes conjugated in the usual way
what happens to this conjugated bile
it is unable to enter the bile canaliculi and passes back into the blood
what is the consequence of this
most of the bilirubin in the plasma becomes the conjugated type rather than the unconjugated type
so why does this cholestatic jaundice occur
because the conjugated bilirubin is unable to enter the bile canaliculi and passes back into the blood
there is a failure of clearance of unconjugated bilirubin arriving at the liver
what happens when there is a total obstruction of bile flow
no bilirubin can reach the intestines to be converted into urobilinogen by bacteria
what happens when this urobilinogen isnt present
no urobilinogen is reabsorbed into the blood, and none can be excreted by the kidneys into the urine (urobilin)
what will the urine test results for TOJ be then
completely negative for urobilinogen
what makes the stools become clay coloured
the lack of stercobilin
what is hepatic cirrhosis characterised by
diffuse hepatic fibrosis and nodule formation
what are the most common causes of cirrhosis
Chronic viral hepatitis (B or C)
Prolonged excessive alcohol consumption
Chronic use of alcohol raises the mean corpuscular volume (MCV) and the enzyme GGT.
what is the most common cause of portal hypertension
cirrhosis
what are the cardinal features of cirrhosis
an increase in fibrous tissue
progressive and widespread death of liver cells
inflammation leading to loss of normal liver architecture
where are stellate cells located
in the space of Disse
what happens to these stellate cells following liver injury
these cells are activated by cytokines produced by Kupffer cells and hepatocytes
what do these cytokines do to the stellate cells
transforms the stellate cell into a myofibroblast-like cell, capable of producing collagen, pro-inflammatory cytokines and other mediators which promote hepatocyte damage and cause tissue fibrosis
what does destruction of liver architecture cause
distortion and loss of normal hepatic vasculature with the development of portosytemic vascular shunts and the formation of nodules
what are the symptoms of cirrhosis
Weakness and fatigue
Muscle cramps
Weight loss
Anorexia
Nausea and vomiting
Upper abdominal discomfort
what are the liver function tests used to diagnosis cirrhosis
Bilirubin
Aminotransferases
Alkaline phosphatase
Gamma-glutamyl transferase
Albumin
what do these tests do
they do not assess the functioning of the liver, but rather provide biochemical markers of liver cell damage
what does the degree of elevation of bilirubin reflect
the degree of severity of liver damage
when does a raised bilirubin often occur
earlier in the natural history of biliary disease
what happens to serum albumin levels in patients with liver disease
they are reduced
what is this due to
the change in the volume of distribution of albumin, as well as reduction in synthesis
what does the plasma half life of albumin of 2 weeks mea
serum albumin levels may be normal in acute liver failure but are almost always reduced in chronic liver failure
what do ALT and AST normally do
transfer the amino group from an amino acid - alanine in the case of ALT
asparate in the case of AST
what does this produce
producing pyruvate (ALT) and oxaloacetate (AST)
where are ALT and AST located
in the cytoplasm of the hepatocyte
where is AST also located
in the cytoplasm of the mitochondria
which enzyme is considered to be more specific for hepatocellular damage
ALT
what is alkaline phosphatase (ALP)
enzymes that are capable of hydrolysing phosphate esters at alkaline pH
where are the main sites of production of ALP
the liver, GI tract, bone, placenta and kidney
where are the ALP enzymes located in the liver
in the cell membranes of hepatic sinusoids and the biliary canaliculi/ducts
what is ALP rise in plasma concentration indicative of
intrahepatic and extrahepatic biliary obstruction and with sinusoidal obstruction, as occurs in infiltrative liver disease.
what is GGT
a microsomal enzyme produced in high concentrations by hepatocytes and by the epithelium lining of the small bile ducts
what is the function of GGT
to transfer glutamyl groups from gamma-glutamyl peptides to other peptides and amino acids
why do you get itchy skin with jaundice
Pruritus is itching of the skin when you are jaundiced. The itch is caused by a build up of bile salts in the blood when the bile ducts are blocked or the liver is not working properly. This can also make the skin feel hot and uncomfortable.
what is endothelum one
a vasodilator peripherally that therefore leads to increased heart rate
mainly released from active stellate cells
what is the consequence of a paracetamol overdose on the liver
In the case of overdose, the sulphate and glucuronide pathways become saturated, and more paracetamol is shunted to the cytochrome P450 system to produce NAPQI. As a result, hepatocellular supplies of glutathione become depleted, as the demand for glutathione is higher than its regeneration. NAPQI therefore remains in its toxic form in the liver and reacts with cellular membrane molecules, resulting in widespread hepatocyte damage and death, leading to acute liver necrosis.
