Download Pertubation of metabolism in IDD Q3-5 Joe - PBL-J-2015

3. Indicate the mechanisms by which beta ketoacid production is increased in
response to oversupply of fatty acid to the liver, including the steps of the
pathways of fatty acid metabolism that are up regulated
The oversupply of fatty acids in the liver cells (in the absence of insulin) leads to the up
regulation of the β-oxidation of these fatty acids in the mitochondrial cells of the liver.
This is initiated when excess supply of fatty acids triggers the activation and increase in the
Carnitine transport mechanism that is responsible for transporting fatty acids to the
mitochondria. As a result, large amounts of acetyl-CoA are produced due to the the β-oxidation
reaction. These large amounts of acetyl-CoA are then condensed into acetoacetic acid, and
released into the circulation. Most of this passes to the peripheral cells where it is again reconverted into acetyl-CoA and used as an energy source. However, in a diabetic patient with
the absence of insulin, this acid is not converted and utilized by cells but accumulates. Its
buildup in the plasma increases body fluid acidosis.
Acetoacetic acid is also converted into β-hydroxybutyric acid and acetone, and along with
acetoacetic acid these three compounds are called ketone bodies. The presence of ketone
bodies in large quantities in body fluid causes metabolic ketoacidosis..
4. Outline how hyperglycaemia causes polyuria
Urine is produced in the nephrons of the kidney by a process called filtration. In filtration, water
and small molecules (such as glucose, AA’s) in the blood plasma enter Bowman’s capsule for
filtration and then into the tubules for reabsorption before be excreted as urine. Many of these
small molecules (namely glucose) are transferred out of the forming urine and back into the
extracellular fluid by reabsorption.
Under normal conditions, 100% of the glucose that is filtered is reabsorbed by specific transport
proteins. In a diabetic that has hyperglycaemia, the amount of glucose that is filtered can
exceed the capacity of the kidney tubules to reabsorb glucose, because the transport proteins
become saturated. Glucose (being a solute) draws water into the urine by osmosis. Thus,
hyperglycaemia causes a diabetic to produce a high volume of glucose-containing urine. This
then leads to a state of polyuria and diuresis, ultimately leading to dehydration and loss of fluid
volume. Important electrolytes are also lost in the urine resulting in osmotic disturbances
throughout the body.
5. Describe how hyperglycaemia can disrupt normal acid-base balance.
In hyperglycaemia resulting from insulin deficiency, glucose is not available to the cells and the
body may attempt to provide an alternative energy source. One way is by metabolizing free
fatty acids from lipid stores which encourages the production of ketoacids in the liver/. This
creates a buildup of acid (known as metabolic acidosis) disturbing the normal acid-base
balance.