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CHAPTER 1: Clinical Pathology: Clinical chemistry > Clinical patholgy:clinical chemistry-(iv)Evaluation of the liver > Flashcards

Clinical patholgy:clinical chemistry-(iv)Evaluation of the liver Flashcards

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1
Q

Enzymes in the liver

List all the 4 main leakage enzymes and the 2 main induced enzymes.

A

A.Leakage enzymes:alanine aminotransferase(ALT), aspartate aminotransferase(AST), sorbitol dehydrogenase(SDH) and glutamate dehydrogenase(GLDH)
B.Induced enzymes: alkaline phosphatase(ALP), GGT(gamma glutamyl transpeptidase)

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2
Q

Which tests are performed for hepatocyte injury?

What were the previous names of the first two enzymes mentioned?

A

(i) Alanine aminotransferase(previously known as serum pyruvic transaminase)
(ii) Aspartate aminotransferase(previously called serum glutamic oxaloacetic transaminase)
(iii) Sorbitol dehydrogenase
(iv) Glutamate dehydrogenase

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3
Q

Which ones are liver specific and which ones are not?

A

ALT and AST are not liver specific: they are leakage emzymes.
SDH and GLDH are liver specific: they are leakage enzymes as well

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4
Q

When can there be an increase in ALT levels in dogs and cats?

A

in dogs and cats, ALT is present mostly in hepatocytes, but increases can be seen with muscle injury(especially extensive injury).

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5
Q

What does an elevation in ALT levels indicate in horses and ruminants?

A

Horses and ruminants have little ALT in hepatocytes, so elevations of ALT usually indicate muscle damage.

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6
Q

Where is AST usually present?

A

AST is present in hepatocytes and in skeletal and cardiac muscle cells.

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7
Q

What can lead to increased AST?

A

Increased AST can be due to hepatocyte death, hepatocyte injury, muscle cell death and muscle cell injury.

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8
Q

Compare the specificity of AST to that of ALT in the dogs, cats, horses and ruminants.

A

Not as specific in the dog and cat as ALT; more specific than ALT in horses and ruminants.

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9
Q

What does an increase in SDH indicate?

A

An increase in SDH indicate hepatocyte death or injury.

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10
Q

Comment on the half-life of sorbitol dehydrogenase.

A

SDH has a very short half-life and values return to normal within a few days.

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11
Q

Comment on the stability of SDH.

A

Not very stable in serum samples; stable for about 48 hours if frozen.

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12
Q

In horses and ruminants, which enzyme is preferably checked when detecting injury to hepatocytes.

A

In horses and ruminants, SDG is preferable to AST for detecting injury to hepatocytes.

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13
Q

What does an increase in GLDH indicate?

A

An increase in GLDH indicates hepatocytes death or injury.

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14
Q

Compare the stability of GLDH to that of SDH.

A

GLDH is more stable than SDH but still not very stable.

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15
Q

Give the three different origins of ALP?

A
  1. Bone origin(BALP)
  2. Liver origin(LALP)
  3. Corticosterois-induced(CiALP)
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16
Q

What does a mild increase in bone ALP(BALP) suggest?

A

Mild increase associated with increased osteoblast acitivty

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17
Q

Are these values usually higher or lower in younger animals?

A

Will be higher in young growing animals?

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18
Q

When can BALP be elevated?

A

May be elevated in association with primary or secondary hyperparathyroidism(effects of PTH on bone).

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19
Q

What does an increase in LALP suggest?

A

An increase is associated with cholestasis.

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20
Q

Does LALP usually increase before or after an increase in bilirubin with cholestasis?

A

LALP usually increases before an increase in bilirubin with cholestastis.

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21
Q

What induces the release of CiALP?

A

Induced by corticosteroids and also anticonvulsants

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22
Q

What other condition can induce CiALP?

A

Chronic disease(including chronic cholestasis) can iduce CiALP).

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23
Q

Comment on the half-life of ALP in cats and the resulting effect on ALP levels during cholestatic disease.

A

In cats, the half-life of ALP is very short(about 6 hours); thus the increase of ALP in cholestasis disease is significantly less than in other species.

24
Q

What do increases in ALP suggest in ruminants?

A

In ruminants, increases in ALP are usually due to cholestasis or osteoblastic activity.
NOTE: Increases in horses with cholestasis are not well documented.

25
Q

What can lead t elevations in the level of GGT?

A

Considered to be an induced enzyme; however, acute injury can cause elevations of GGT.

26
Q

What is the primary cause of elevation of GGT? What are the other causes?

A

Elevated primarily in cholestasis. May also be induced by glucocorticoidsand anticonvulsants.

27
Q

Compare the usefulness of GGT to that of ALP in detecting cholestasis in horses and ruminants.

A

GGT is superior to ALP in horses and ruminants fo the detection of cholestasis.

28
Q

Comment on the level of GGT in the colostrums of cattle and sheep.

A

GGT is present in very high levels in cattle and sheep colostrums, resulting in very high levels of serum GGT in calves and sheep that have consumed colostrum.

29
Q

What are 9 different components that are usually checked when testing liver function?

A 
1/Bilirubin
2/Bile acids
3/Ammonia
4/Albumin
5/Globulins(may be increased, especially in horses)
6/Glucose
7/Urea
8/Cholesterol
30
Q

Describe how bilirubin is normally formed in the body.

A

Normal metabolism
The heme portion of haemoglobin is split into iron and protoporphyrin.
Protoporphyrin is converted to biliverdin, then to bilirubin,

31
Q

What do we mean by the term ‘unconjugated’ or indirect bilirubin.

A

Unconjugated or indirect bilirubin is circulating bilirubin which is released from macrophages, attached to albumin or other globulins, transported to the liver, released from albumin or globulins and enters the hepatocytes.

32
Q

What does the term ‘conjugated’ bilirubin mean?

A

Once in hepatocytes, bilirubin is conjugated and most of it secreted into bile. A small amount passes through the sinusoidal side back into the blood. Conjugated bilirubin is also termed as direct bilirubin.

33
Q

What can lead to an increase in the level of bilirubin?(3)

A

Bilirubin is increased when there is :

(i) increased haemoglobin production(increased RBC destruction)
(ii) decreased uptake and conjugation of bilirubin by hepatocytes
(iii) decrease in outflow of conjugated bilirubin(cholestasis)

34
Q

For measuring the level of bile acids, which samples are usually preferred in digs and cats?

A

Fasting and postprandial samples are usually collected in dogs and cats.

35
Q

What usually leads to an exaggerated value of postprandial bile acids?

A

The postprandial bile acid concentration is usually greatly exaggerated with portosystemic shunt.

36
Q

What may lead to an increase in the level of bile acids in fasting, postprandial or both samples?(9)

A

Increases in fasting, postprandial or both samples may occur with:

(i) portosystemic shunts
(ii) cholestasis
(iii) cirrhosis
(iv) necrosis
(v) necrosis
(vi) hepatitis
(vii) hepatic lipidosis
(viii) steroid hepatopathy
(ix) neoplasia

37
Q

How many samples are usually collected in horses and ruminants and what does an increase in the level of bile acids usually suggest?

A

One sample is collected in horses and ruminants and an increase in bile acids suggest hepatic disease.

38
Q

When is ammonia concentration usually increased?(2)

A

Ammonia concentration is usually increased in those with portosystemic shunts or if more than 60% if liver mass is lost.

39
Q

What can lead to a decrease in the level of albumin?

A

Albumin decreases when 60-80% of liver function is lost.

40
Q

When can the level of glucose be:

(i) increased and
(ii) decreased?

A

The liver converts glucose to glycogen.
Glucose may be increased if there is decreased glucose uptake by the liver.
Glucose may be decreased if there is decreased gluconeogenesis or glycogenolysis.

41
Q

What is the relation between urea and ammonia and what can lead to a:

(i) decrease in blood urea nitrogen
(ii) blood ammonia concentration

A

Urea is synthesised in the liver from ammonia.

  1. Blood urea nitrogen decreases with liver failure.
  2. Blood ammonia concentration increases with liver failure.
42
Q

What can lead to an:

(i) increase in the level of cholesterol
(ii) decrease in the level of cholesterol?

A
  1. Cholesterol can be decreased if there is decreased synthesis of cholesterol with liver failure
  2. Cholesterol can be increased if cholestasis is present, which prevents excretion of cholesterol in bile.
43
Q

What can lead to a decrease in coagulation factors?

A

Coagulation factors are commonly decreased in dogs with liver failure.

44
Q

CHANGES IN SELECTED LIVER DISEASES

What changes to the liver can be seen in the case of portosystemic shunts?

A

If portosystemic shunts occur because of severe cirrhosis, then changes as seen in the end-stage liver disease are expected.

45
Q

Are leakage enzymes usually elevated in the case of early portosystemic shunts?

A

Early portosystemic shunts do not cause much active hepatocyte damage; thus leakage enzymes are usually not elevated.

46
Q

What other components may be elevated with an early portosystemic shunt?(2)

A

(i)Typically occurs in young, growing animals, so ALP may be elevated(BALP).
(ii)Bile acids are markedly elevated.
NOTE: Induced enzymes are not elevated because there is little cholestasis.

47
Q

What other condition may be typical with early portosystemic shunt?

A

Microcytic anaemia with low iron concentration is typical.

48
Q

HEPATIC NECROSIS
What happens to the level of leakage enzymes in the case of focal hepatic necrosis?
What bout diffuse necrosis?

A

If focal, leakage enzymes may be normal or mildly elevated.

Diffuse necrosis more often results in elevations in both leakage and induced enzymes.

49
Q

With hypoxia or mild toxic damage, what happens to the level of leakage enzymes, induced enzymes, bilirubin and bile acids?

A

This process is diffuse, so leakage enzymes are usually mildly to moderately elevated.
Induced enzymes and bilirubin are not typically elevated.
Bile acids may be mildly increased.

50
Q

With focal lesions, what happens to the level of leakage enzymes, induced enzymes?

A

FOCAL LESIONS
Leakage enzymes may be normal to mildly increased.
Induced enzymes are usually normal unless bile flow is significantly impaired.

51
Q

In hepatic lipidosis, what happens to the level of leakage enzymes in cats?
What about the level of ALP, GGT, serum bilirubin and bile acids?

A

HEPATIC LIPIDOSIS
Leakage enzymes are increased in most cats.
ALP is also elevated in most, but GGT is elevated in only a small number.
serum bilirubin is usually elevated, and bile acids are commonly increased.

52
Q

What happens to the level of leakage enzymes, induced enzymes and bilirubin with steroid hepatopathy?

A

NOTE: Steroid hepatopathy most common in dogs.

  1. Leakage enzymes are mildly increased
  2. Induced enzymes are markedly increased
  3. Bilirubin may be mildly increased.
53
Q

With biliary disorders, what happens to the level of induced enzymes, leakage enzymes, bilirubin and bile acids?

A

BILIARY DISORDERS

  1. Induced enzymes are markedly increased.
  2. Leakage enzymes may be mildly increased as a result of hepatocyte injury from the cholestasis.
  3. Bilirubin and bile acids are also typically increased.
54
Q

With chronic liver disease, what happens to the level of induced enzymes, leakage enzymes, bilirubin

A
  1. Leakage enzymes may be increased, depending on the extent and rate of progression of the disease
  2. Induced enzymes are usually mildly to moderately increased.
  3. Bilirubin concentration is normal to mildly increased in those with more advanced disease.
55
Q

With how much loss of liver function does end-stage liver disease occur?
What happens to the different parameters: induced enzymes, leakage enzymes, bilirubin, bile acids, ammonia, BUN, albumin and coagulation test?

A

End-stage liver disease occurs when 60-80% of liver mass has been lost.
Leakage enzymes may be normal to mildly increased because of the overall loss of liver mass.
Induced enzymes are moderately to markedly increased as are bilirubin and bile acid concentration.
Many have increased ammonia, decreased BUN, decreased albumin and abnormal coagulation tests.

CHAPTER 1: Clinical Pathology: Clinical chemistry (11 decks)

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