case 5 - jaundice and cirrhosis Flashcards

1
Q

what does jaundice refer to

A

the yellowish tint to the body tissues

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2
Q

what is it caused by

A

large amounts of billirubin in the extracellular fluids

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3
Q

what are the three types of jaundice

A

pre-hepatic
intra-hepatic
post-hepatic

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4
Q

what is the normal plasma concentration

A

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

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5
Q

when will the skin begin to appear jaundiced

A

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

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6
Q

what is pre hepatic jaundice caused by

A

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

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7
Q

what is haemolysis

A

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

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8
Q

why is jaundice due to haemolysis usually mild

A

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

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9
Q

what is intra hepatic jaundice caused by

A

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

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10
Q

when can bilirubin transport across the hepatocytes be impaired

A

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

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11
Q

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

A

they both increase

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12
Q

what can hepatocellular jaundice be due to

A

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

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13
Q

what is jaundice due to parenchymal liver disease associated with

A

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

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14
Q

what does acute jaundice in the present of raised AST suggest

A

an infectious cause

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15
Q

what is obstructive jaundice due to

A

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.

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16
Q

what happens to the unconjugated bilirubin

A

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

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17
Q

what happens to this conjugated bile

A

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

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18
Q

what is the consequence of this

A

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

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19
Q

so why does this cholestatic jaundice occur

A

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

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20
Q

what happens when there is a total obstruction of bile flow

A

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

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21
Q

what happens when this urobilinogen isnt present

A

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

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22
Q

what will the urine test results for TOJ be then

A

completely negative for urobilinogen

23
Q

what makes the stools become clay coloured

A

the lack of stercobilin

24
Q

what is hepatic cirrhosis characterised by

A

diffuse hepatic fibrosis and nodule formation

25
Q

what are the most common causes of cirrhosis

A

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

26
Q

what is the most common cause of portal hypertension

A

cirrhosis

27
Q

what are the cardinal features of cirrhosis

A

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

28
Q

where are stellate cells located

A

in the space of Disse

29
Q

what happens to these stellate cells following liver injury

A

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

30
Q

what do these cytokines do to the stellate cells

A

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

31
Q

what does destruction of liver architecture cause

A

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

32
Q

what are the symptoms of cirrhosis

A

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

33
Q

what are the liver function tests used to diagnosis cirrhosis

A

Bilirubin
Aminotransferases
Alkaline phosphatase
Gamma-glutamyl transferase
Albumin

34
Q

what do these tests do

A

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

35
Q

what does the degree of elevation of bilirubin reflect

A

the degree of severity of liver damage

36
Q

when does a raised bilirubin often occur

A

earlier in the natural history of biliary disease

37
Q

what happens to serum albumin levels in patients with liver disease

A

they are reduced

38
Q

what is this due to

A

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

39
Q

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

A

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

40
Q

what do ALT and AST normally do

A

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

41
Q

what does this produce

A

producing pyruvate (ALT) and oxaloacetate (AST)

42
Q

where are ALT and AST located

A

in the cytoplasm of the hepatocyte

43
Q

where is AST also located

A

in the cytoplasm of the mitochondria

44
Q

which enzyme is considered to be more specific for hepatocellular damage

A

ALT

45
Q

what is alkaline phosphatase (ALP)

A

enzymes that are capable of hydrolysing phosphate esters at alkaline pH

46
Q

where are the main sites of production of ALP

A

the liver, GI tract, bone, placenta and kidney

47
Q

where are the ALP enzymes located in the liver

A

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

48
Q

what is ALP rise in plasma concentration indicative of

A

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

49
Q

what is GGT

A

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

50
Q

what is the function of GGT

A

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

51
Q

why do you get itchy skin with jaundice

A

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.

52
Q

what is endothelum one

A

a vasodilator peripherally that therefore leads to increased heart rate

mainly released from active stellate cells

53
Q

what is the consequence of a paracetamol overdose on the liver

A

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.