Starvation

Question 1

Glucose post-absorption

Answer 1

Once we stop eating, first step will be to start using glycogen stores.

Liver will convert glycogen to glucose and then release it into the blood. This glucose can then be used by other tissues such as the brain.

Muscle will also use its glycogen stores.

Question 2

Glycogen capacity

Answer 2

Using glycogen in early stages of starvation is very short because gycogen storage is only modest.

A mammal at rest, can supply energy for ~20hrs. Active mammal ~6hrs

Question 3

Fat Oxidation Capacity

Answer 3

Fat storage is large, can potentially provide several weeks of survival fuel (20-60 days).

Reason why hibernating animals build up fat storage prior to hibernation

Question 4

Early starvation (after glycogen store)

Answer 4

1. Fat breakdown increases and beta-oxidation becomes primary fuel
2. Gluconeogenesis increased to support energy for brain
3. Ketogenesis- when glucose demand cannot be met. Gluconeogenesis will be using all oxaloacetate in liver so acetyl-CoA will be used to make ketones instead. Ketones enter blood and can be used for TCA cycle in other tissues

Question 5

Effects of ketone utilization

Answer 5

Ketones are rapidly produced and accumulate during starvation.

Ketonemia: 1-2mM (3-4 days) to 6-10mM (week 2)

Ketoacidosis: increased anion gap

Question 6

Starvation Complications

Answer 6

1. Steatosis
2. Ketoacidosis

Question 7

Steatosis during starvation

Answer 7

Lipolysis is greater than capacity to use fatty acids and their export out of liver.

Lipolysis is happening at a much greater rate than aerobic metabolism. Oxygen consumption reduction by 10-15%. The lack of ATP impairs the livers ability to synthesize protein and make VLDLs for export.

Build up of fat on liver results in poor liver function. Unable to breakdown bilirubin.

Question 8

Symptoms of Steatosis

Answer 8

Jaundice- liver unable to process bilirubin because poor liver function from fat build up

Question 9

Ketoacidosis

Answer 9

Surge of ketone production causes a decrease in HCO3- because ketones are acidic and donate H to blood. Donated H decreases pH. Shown by a increased AG

Question 10

Late Stage Starvation

Answer 10

Begins to breakdown tissue proteins using ubiquitin-proteasome system.

1. Digestive enzymes
2. Liver enzymes
3. Muscle

Question 10

Amino Acid destinations

Answer 10

1. Ketogenic amino acids will go straight to liver for ketogenesis
2. Alanine goes to liver for gluconeogenesis
3. Glutamine goes to kidneys for gluconeogenesis

Question 10

How is alanine formed?

Answer 10

Pyruvate + Glutamate –> alanine

Enzyme: alanine aminotransferase

Waste in liver: urea

Question 10

How is glutamine formed?

Answer 10

Glutamate + NH3+ –> Glutamine

Enzyme: Glutaminase

Waste in kidneys: Ammonium NH4+

Question 11

Percentage of alanine and glutamine produced during late stage starvation

Answer 11

60%

Question 12

Role of liver in late stage starvation

Answer 12

Usually shares amino acids between gluconeogenesis, ketogenesis, and protein synthesis. Under starvation, it will prioritize gluconeogenesis and ketogenesis… hindering protein production such as serum albumin.

Question 13

Function of serum albumin

Answer 13

1. Transport protein and fatty acid
2. Maintain plasma colloid osmotic pressure

Question 14

How does decreased liver function effect serum albumin during starvation?

Answer 14

Liver decreases protein synthesis which means decrease of serum albumin. A loss of serum albumin means a decrease in FFA transport and osmotic pressure. The decrease of osmotic pressure results in increased fluid loss from plasma.

Question 15

Late stage starvation consequences (Protein degradation)

Answer 15

1. decreases plasma serum, decreased osmotic pressure, plasma fluid loss leading to edema or ascites
2. Hypovolemia leads to a decrease in oxygen delivery to organs because fluid and pressure loss. Can lead to shock, coma, death
3. Risk of pneumonia. Respiratory muscle proteins are degraded inhibited ability to cough which increases risk of resp. infection.

Question 16

Re-feeding syndrome

Answer 16

Occurs when reintroducing food after periods of prolonged malnutrition.
Driven by electrolyte imbalance.

Question 17

Why does electrolyte depletion not show up on blood tests?

Answer 17

Many key ions are stored intracellularly.

Question 18

What happens when refeeding after starvation?

Answer 18

Increase in glucose and insulin which drives electrolytes intracellularly. Further depleting extracellular electrolytes.

Hypophosphatemia- low levels of phosphate

Question 19

Hypophosphatemia

Answer 19

1. Phosphate needed for 2,3-BPG which releases O2 from hemoglobin. Therefore oxygen not released into tissues= hypoxia
2. Phosphate needed for ATP production therefore there is a stall in glycolysis after prepatory phase which uses ATP. ATP depletion = hemolysis

Together, causes impaired aerobic metabolism

Question 20

Clinical symptoms of Refeeding syndrome

Answer 20

Muscles- general weakness, cardiomyopathy, rhabdomyolysis

CNS- seizure, coma

Hematologic- hemolysis and anemia

Immunity- leukocytes with impaired function, susceptible to infections