intro clinical biochem

Question 1

list the 3 categories of things we can routinely measure in clinical biochemistry

Answer 1

• substrates/products
• enzymes
• hormones

Question 2

What 2 substrate/outputs could be easily measured in blood to monitor the function of the glucose pathways of an animal?

Answer 2

• glucose
• ketone bodies

not glycogen because it isnt measured in blood - stored in tissues

Question 3

Why are different substrates/outputs measured in ruminants and mono-gastrics?

Answer 3

The reliance of ruminants on a large microbial rumen population means that e.g., glucose and carbohydrate that would be available from the GI tract of will be consumed by GI bacteria and the ruminant has a metabolic system adapted to utilise the metabolic products of the bacteria

Question 4

What 2 substrates/outputs could easily measured in blood to monitor the function of the lipid pathways in animals

Answer 4

• triglycerides
• cholesterol

Question 5

what are the 2 categories of liver enzymes and which liver enzymes fall into each

Answer 5

hepatocellular: these enzymes are contained inside the liver cells (hepatocytes) and if cell damage occurs (eg physical, necrosis), then enzymes will leak out of the cells. These enzymes when increased in the circulation are indicators of liver cell damage . These include the enzymes asparate aminotransferase (AST) and alanine aminotransferase (ALT)
cholestatic: these are enzymes which are situated on the cell membrane of the cells which line the bile ducts (these transport bile to the small intestine which is needed for fat digestion) and these enzymes are increased in concentration in the blood a lot if there is an issue with the flow of bile through the liver. These include the enzymes alkaline phosphatase (ALKP) and gamma glutamyl transpeptidase (GGT).

Question 6

what is the function of aspartate aminotransferase and where is it found

Answer 6

important enzyme in amino-acid metabolism allowing for entrance to krebs cycle
- found in liver, skeletal muscle, heart, kidney and brain

Question 7

what is the function of alanine aminotransferase and where is it found

Answer 7

important enzyme in amino acid metabolism allowing for entrance to krebs cycle
- found mainly in liver

Question 8

what is the function of alkaline phosphatase and where is it found

Answer 8

enzyme that transports metabolites across cell membranes. is present in the bile duct epithelial cells therefore biliary stasis = release of enzyme
- found in liver, bone > intestine, placenta and kidney

Question 9

what is the functions of gamma glutamyl transpeptidase and where is it found

Answer 9

catalyzes the transfer of a gamma glutamyl group between amino acids. important for the synthesis and breakdown of glutathione
- found in hepatocytes, biliary epithelial cells and renal tubules

Question 10

what is the function of bilirubin and where is it found

Answer 10

catabolic product of hemoglobin which is released in the unconjugated form and conjugated to a water soluble product by hepatic cells
- found in serum and liver. comparison of conjugated and unconjugated bilirubin elevations will determine wether intraheptaic

Question 11

are hormones routinely measured as part of routine biochemistry

Answer 11

no but can be measured if we think the result would give us better indication of what is happening to the animal

Question 12

what is the most likely cause of an elevated PCV in a rabbit who appears dehydrated

Answer 12

dehydration

Question 13

a rabbit has the following blood results. interpret the findings

Answer 13

Elevated bile acids - indicative of liver dysfunction; Decreased glucose - indicative of anorexia/not eating; Increased GGT - indicative of liver damage; Increased AST - indicative of liver damage; Increased urea - indicative of dehydration affecting kidney perfusion; Increased creatinine - indicative of dehydration affecting kidney perfusion. OVERALL: The lab results support anorexia and dehydration as well as liver damage.

Question 14

discuss the pathophysiology of a rabbit with anorexia getting secondary liver damage

Answer 14

Reduced glucose absorption from the gut due to anorexia is followed by reduced production of volatile fatty acids. The anorexia is most likely related to the stress of the house move. Anorexia also results in ileus of the large intestine due to changes in gastric motility and gastric function leading to loss of liquid from ingesta by intestinal absorption resulting in dehydrated and compacted masses of gastrointestinal contents that are difficult to pass.
b) The hypoglycaemia stimulates lipolysis and mobilisation of free fatty acids from adipose tissue that are transported to the liver, causing fat accumulation in hepatocytes. The accumulation of triglycerides in the liver reflects an imbalance between the process is that cause lipid mobilisation, those that lead to fatty acid oxidation and dispatch (VLDL transportation processes) and those that encourage storage in adipose tissue. One or more mechanisms may be involved and these include
Increased activation of hormone sensitive lipase by catecholamines released in response to stress
Failure to produce sufficient insulin in diabetes results in uncontrolled hormone sensitive lipase activity
Excessive lipid mobilisation induced by anorexia starvation or illness partly under the influence of glucagon on hormone sensitive lipase
c) The use of fatty acids in the liver as the energy substrate only undergoing partial oxidation
d) Fat accumulation in the hepatocytes results in cholestasis, which means that the bile does not flow from the gall bladder in the liver into the small intestine this means that there will be elevated bile acids in the blood stream.
e) Fat accumulation the hepatocytes (liver cells) reduces the function of the liver cells, including causing the death of hepatocytes

Question 15

what is prodcut of partial oxidation of fatty acids in the liver could be tested in the urine as part of the monitoring process

Answer 15

ketones

Question 16

this histological image taken from the liver indicates what disease

Answer 16

hepatic lipidosis:
- liver cells show accumulation of fat within them

Question 17

you see the following results from a biochemistry of a horse with yellow gums, ataxia and acute blindness. interpret the results

Answer 17

Increased GGT, AST and ALKP: liver damage; Increased ammonia and decreased urea: the liver is unable to perform the urea cycle. The urea cycle is the removal of toxic ammonia by conversion of ammonia to the less toxic substance urea in the liver. Ammonia is produced by bacteria within the gastrointestinal tract (see urea metabolism lecture later in the course). Here it indicates that the liver is not functioning correctly; Decreased glucose: gluconeogenesis is not occurring in this anorexic horse

Question 18

what is hepatic encephalopathy

Answer 18

Central nervous system dysfunction that has a liver condition as its cause. Ammonia (and other metabolites) that accumulate in these particular liver conditions alter/disrupt CNS function.

Question 19

what substance contained in ragwort makes it toxic to horses

Answer 19

Pyrrolizidine alkaloids (toxic to hepatocytes leading to necrosis)

Question 20

explain the biochemical process that occurs when blood glucose levels are low

Answer 20

Glucagon is released from pancreatic islet alpha cells in response to low blood glucose levels. The secretion of insulin is inhibited.
Glucagon results in glycolysis to increase the glucose levels in the short term.
In the medium term lipolysis occurs (via the hormone sensitive lipase in adipose tissue) to mobilise fatty acids, which are transported to the liver for partial beta oxidation to ketone bodies and energy. This will continue long term

Question 21

explain the pathophysiology in the case of a horse with severe liver damage in response to low glucose levels

Answer 21

the liver is so broken that it cannot correctly function due to pathology in more than 75% of the organ (basically less than 25% of the organ contains functioning hepatocytes which can do anything useful!). This means that despite the fatty acids appearing to be used as substrates, the hepatocytes are unable to carry out gluconeogenesis. Therefore there is no/limited energy including for the brain cells