case 5 - jaundice and cirrhosis

Question 1

what does jaundice refer to

Answer 1

the yellowish tint to the body tissues

Question 2

what is it caused by

Answer 2

large amounts of billirubin in the extracellular fluids

Question 3

what are the three types of jaundice

Answer 3

pre-hepatic
intra-hepatic
post-hepatic

Question 4

what is the normal plasma concentration

Answer 4

The normal plasma concentration of bilirubin, which is almost entirely the free form, averages 0.5 mg/dl of plasma.

Question 5

when will the skin begin to appear jaundiced

Answer 5

when the concentration rises to about three times normal - above 1.5mg/dl

Question 6

what is pre hepatic jaundice caused by

Answer 6

haemolysis or by congenital hyperbillirubinaemia and is characterised by an isolated raised bilirubin level

Question 7

what is haemolysis

Answer 7

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

Question 8

why is jaundice due to haemolysis usually mild

Answer 8

because a healthy liver can excrete a bilirubin load six times greater than normal before unconjugated bilirubin accumulates in the plasma

Question 9

what is intra hepatic jaundice caused by

Answer 9

impaired cellular uptake, defective conjugation or abnormal secretion of bilirubin by hepatocytes, occurring as a consequence of parenchymal liver disease

Question 10

when can bilirubin transport across the hepatocytes be impaired

Answer 10

at any point between uptake of unconjugated bilirubin into the cells and transport of conjugated bilirubin into the canaliculi

Question 11

what happens to the levels of both unconjugated and conjugated bilirubin in the blood

Answer 11

they both increase

Question 12

what can hepatocellular jaundice be due to

Answer 12

acute or chronic liver injury and clinical features of acute or chronic liver disease may be detected clinically

Question 13

what is jaundice due to parenchymal liver disease associated with

Answer 13

increases in AST, ALT, but increases in other LFTs, including GGT and ALP may occur and suggest specific aetiologies

Question 14

what does acute jaundice in the present of raised AST suggest

Answer 14

an infectious cause

Question 15

what is obstructive jaundice due to

Answer 15

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.

Question 16

what happens to the unconjugated bilirubin

Answer 16

still enters the liver cells and becomes conjugated in the usual way

Question 17

what happens to this conjugated bile

Answer 17

it is unable to enter the bile canaliculi and passes back into the blood

Question 18

what is the consequence of this

Answer 18

most of the bilirubin in the plasma becomes the conjugated type rather than the unconjugated type

Question 19

so why does this cholestatic jaundice occur

Answer 19

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

Question 20

what happens when there is a total obstruction of bile flow

Answer 20

no bilirubin can reach the intestines to be converted into urobilinogen by bacteria

Question 21

what happens when this urobilinogen isnt present

Answer 21

no urobilinogen is reabsorbed into the blood, and none can be excreted by the kidneys into the urine (urobilin)

Question 22

what will the urine test results for TOJ be then

Answer 22

completely negative for urobilinogen

Question 23

what makes the stools become clay coloured

Answer 23

the lack of stercobilin

Question 24

what is hepatic cirrhosis characterised by

Answer 24

diffuse hepatic fibrosis and nodule formation

Question 25

what are the most common causes of cirrhosis

Answer 25

Chronic viral hepatitis (B or C) Prolonged excessive alcohol consumption Chronic use of alcohol raises the mean corpuscular volume (MCV) and the enzyme GGT.

Question 26

what is the most common cause of portal hypertension

Answer 26

cirrhosis

Question 27

what are the cardinal features of cirrhosis

Answer 27

an increase in fibrous tissue progressive and widespread death of liver cells inflammation leading to loss of normal liver architecture

Question 28

where are stellate cells located

Answer 28

in the space of Disse

Question 29

what happens to these stellate cells following liver injury

Answer 29

these cells are activated by cytokines produced by Kupffer cells and hepatocytes

Question 30

what do these cytokines do to the stellate cells

Answer 30

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

Question 31

what does destruction of liver architecture cause

Answer 31

distortion and loss of normal hepatic vasculature with the development of portosytemic vascular shunts and the formation of nodules

Question 32

what are the symptoms of cirrhosis

Answer 32

Weakness and fatigue Muscle cramps Weight loss Anorexia Nausea and vomiting Upper abdominal discomfort

Question 33

what are the liver function tests used to diagnosis cirrhosis

Answer 33

Bilirubin Aminotransferases Alkaline phosphatase Gamma-glutamyl transferase Albumin

Question 34

what do these tests do

Answer 34

they do not assess the functioning of the liver, but rather provide biochemical markers of liver cell damage

Question 35

what does the degree of elevation of bilirubin reflect

Answer 35

the degree of severity of liver damage

Question 36

when does a raised bilirubin often occur

Answer 36

earlier in the natural history of biliary disease

Question 37

what happens to serum albumin levels in patients with liver disease

Answer 37

they are reduced

Question 38

what is this due to

Answer 38

the change in the volume of distribution of albumin, as well as reduction in synthesis

Question 39

what does the plasma half life of albumin of 2 weeks mea

Answer 39

serum albumin levels may be normal in acute liver failure but are almost always reduced in chronic liver failure

Question 40

what do ALT and AST normally do

Answer 40

transfer the amino group from an amino acid - alanine in the case of ALT asparate in the case of AST

Question 41

what does this produce

Answer 41

producing pyruvate (ALT) and oxaloacetate (AST)

Question 42

where are ALT and AST located

Answer 42

in the cytoplasm of the hepatocyte

Question 43

where is AST also located

Answer 43

in the cytoplasm of the mitochondria

Question 44

which enzyme is considered to be more specific for hepatocellular damage

Answer 44

ALT

Question 45

what is alkaline phosphatase (ALP)

Answer 45

enzymes that are capable of hydrolysing phosphate esters at alkaline pH

Question 46

where are the main sites of production of ALP

Answer 46

the liver, GI tract, bone, placenta and kidney

Question 47

where are the ALP enzymes located in the liver

Answer 47

in the cell membranes of hepatic sinusoids and the biliary canaliculi/ducts

Question 48

what is ALP rise in plasma concentration indicative of

Answer 48

intrahepatic and extrahepatic biliary obstruction and with sinusoidal obstruction, as occurs in infiltrative liver disease.

Question 49

what is GGT

Answer 49

a microsomal enzyme produced in high concentrations by hepatocytes and by the epithelium lining of the small bile ducts

Question 50

what is the function of GGT

Answer 50

to transfer glutamyl groups from gamma-glutamyl peptides to other peptides and amino acids

Question 51

why do you get itchy skin with jaundice

Answer 51

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.

Question 52

what is endothelum one

Answer 52

a vasodilator peripherally that therefore leads to increased heart rate mainly released from active stellate cells

Question 53

what is the consequence of a paracetamol overdose on the liver

Answer 53

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.