Mod.A. Bio Lec13: Ketosis

Question 1

what are ketone bodies ?

Answer 1

acetone, acetoacetate, b-hydroxybutyrate

Question 2

what is the metabolic significance of ketone bodies ?

Answer 2

1- serve as fuel for extra hepatic tissues

2- brain can utilize them but cannot synthesize them

3- brain utilizes ketone bodies under prolonged starvation (glucose deprivation)

4-liver can synthesize them but cannot utilize them because liver lacks COA TRANSFERASE

Question 3

Pathogenesis of ketosis:

Answer 3

• there is a decrease in insulin/glucagon ration (decreased insulin, high glucagon), so there is a defect in carbohydrate metabolism which makes the body DEPEND ON OXIDATION OF FAT as the main source of energy
• excessive lipolysis occurs in adipose tissues
• FA are oxidized to produce large amounts of acetyl coa that CANNOT ENTER THE CITRIC ACID CYCLE because OA is insufficient.
• Acetyl CoA diverted to ketogenesis thus causing excessive formation of ketone bodies which leads to KETOSIS

Question 4

normal plasma level of ketone bodies:

Answer 4

<1 mg/dl

Question 5

normal urinary level of ketone bodies

Answer 5

<3 mg/24 hour urine

Question 6

Ketonemia

Answer 6

progressive rise of blood concentration of ketone bodies

ketone bodies > 100 mg/dl

Question 7

Ketonuria

Answer 7

increase in ketone body concentration in urine

> 500 mg/dl

Question 8

Ketosis is ….+…..

Answer 8

Ketonemia + Ketonuria

rate of ketone synthesis is higher than rate of utilization

Question 9

What are the causes of ketosis ?

Answer 9

Prolonged starvation
Carbohydrate restriction, dieting
Uncontrolled diabetes
Chronic alcoholism
Von gierke's disease
Heavy exercise

Question 10

Difference between Ketosis and Ketoacidosis

Answer 10

Ketosis:
A metabolic state characterized by increased ketone bodies due to a diet that is very low in carbohydrate.
Is a natural condition.
LOW BLOOD GLUCOSE LEVELS

Ketoacidosis:
A feature of uncontrolled diabetes characterized by A COMBINATION OF ACIDOSIS AND KETOSIS
A disease condition that has to be treated immediately
Occurs in diabetic patients
HIGH BLOOD GLUCOSE LEVELS

Question 11

What is Kussmaul breathing

Answer 11

deep and rapid respiration due to ketoacidosis

Question 12

Pathogenesis of Ketoacidosis

Answer 12

• Hepatic gluconeogenesis and glycogenolysis due to insulin deficiency result in severe HYPERGYLCEMIA
• Lipolysis increases leading to free fatty acids
• Increased proteolysis and decreased protein synthesis as a result of insulin deficiency.
• Hepatic metabolism of FFA lead to accumulation of acidic intermediate of ketogenesis (ketones,ketoacids) with insufficient buffering capacity lead to KETOACIDOSIS

Question 13

Role of acetyl coA in ketoacidosis

Answer 13

• High levels of acetyl coA inhibit pyruvate dehydrogenase complex but activate pyruvate carboxylase thus generating OA which enters gluconeogenesis rather than TCA cycle*****

TCA cycle is inhibited by NADH produced from excessive beta oxidation of FA

Excess acetyl coA is rerouted to ketogenesis.

Question 14

Comparing Starvation Ketosis to Diabetic Ketoacidosis(bl.glucose, HCO3, pH, urine glucose, ketonuria, plasma KB)

Answer 14

SKA:

• Low
• Low
• Low
• NIL
• +
• 3-5 mmol/l

DKA:

• High
• Very low
• Very low
• +++
• +++
• > 12mml/l