Case Scenario 1:
A 25-year-old man is brought to the emergency room after fasting for 24 hours due to a trek. He feels weak, dizzy, and has mild confusion. On examination, he is pale, sweaty, and has a rapid pulse. His blood glucose is found to be 55 mg/dL.
a) Which metabolic pathways help maintain blood glucose during fasting?
b) Explain how carbohydrates, fats, and proteins are integrated during the fasting state.
c) What hormonal changes regulate metabolism during fasting?
Answer:
a) Metabolic pathways maintaining blood glucose during fasting:
In the fasting state, the body maintains blood glucose through:
- Glycogenolysis: Breakdown of liver glycogen to glucose (early fasting, up to ~12–18 hours).
- Gluconeogenesis: Synthesis of glucose from non-carbohydrate sources like lactate, glycerol, and amino acids (becomes dominant after glycogen stores deplete)
- b) Integration of carbohydrate, fat, and protein metabolism in fasting:
- Carbohydrates:
- Blood glucose decreases → glycogenolysis and gluconeogenesis increase.
- Brain continues to use glucose initially, then shifts partly to ketone bodies.
- Fats:
- Lipolysis in adipose tissue → free fatty acids (FFA) released → oxidized for energy in muscle & liver.
- Liver converts FFA to ketone bodies → used by brain, muscle during prolonged fasting.
- Proteins:
- Muscle proteins broken down → amino acids → used in gluconeogenesis & ketone body production.
- Protein sparing occurs as ketone bodies increase.
- c) Hormonal changes during fasting:
| Hormone | Change | Effect |
| Insulin | ↓ | Decreases glucose uptake, favors lipolysis & gluconeogenesis. |
| Glucagon | ↑ | Stimulates glycogenolysis, gluconeogenesis, lipolysis. |
| Catecholamines (epinephrine) | ↑ | Promote glycogenolysis & lipolysis. |
| Cortisol & GH | ↑ | Support gluconeogenesis & lipolysis. |
Case Scenario 2:
A 30-year-old man is rescued after being stranded on a deserted island without food for 10 days. On examination, he appears thin and weak, with sunken eyes, dry skin, and slow reflexes. Laboratory tests show low blood glucose, elevated ketone bodies, and mild hypoalbuminemia.
a) What are the metabolic changes that occur in the body during starvation?
b) How do different tissues adapt to prolonged starvation?
Answer
a) Metabolic changes during starvation:
Starvation is a state of prolonged nutrient deprivation, where the body shifts to alternate fuels to preserve life.
- Early phase (first 1–2 days):
- Liver glycogen stores are used (glycogenolysis) → maintains blood glucose.
- Gluconeogenesis begins (from lactate, glycerol, amino acids).
- Later phase (after ~3–5 days):
- Glycogen depleted → gluconeogenesis becomes main source of glucose.
- Lipolysis increases → free fatty acids (FFA) and ketone bodies produced.
- Protein catabolism decreases to conserve muscle mass.
- Prolonged starvation:
- Brain adapts to use ketone bodies → reduces glucose requirement.
- b) Tissue adaptations in prolonged starvation:
| Tissue | Fuel used during starvation |
| Brain | Initially glucose → later ketone bodies. |
| Muscle | Uses FFA & ketone bodies → reduces glucose use. |
| Liver | Produces glucose (gluconeogenesis) & ketone bodies. |
| Adipose tissue | Lipolysis → provides FFA & glycerol. |
Case Scenario 3:
A 40-year-old man has been on a hunger strike for 10 days.
a) What metabolic changes occur in carbohydrate metabolism during prolonged starvation?
b) What metabolic changes occur in protein metabolism during prolonged starvation?
Model Answer
a) Changes in carbohydrate metabolism:
- In the first 1–2 days, liver glycogen stores supply glucose through glycogenolysis — but these stores deplete within ~24 hours.
- After glycogen depletion, gluconeogenesis becomes the main source of glucose, using lactate, glycerol, and amino acids.
- Blood glucose levels are maintained at a lower, but steady level.
- To spare glucose for the brain & RBCs, most tissues shift to using fatty acids and ketone bodies for energy.
- By ~10 days, the brain also starts utilizing ketone bodies, reducing its glucose requirement further.
b) Changes in protein metabolism:
- Early in starvation, muscle proteins are broken down to provide amino acids (like alanine & glutamine) for gluconeogenesis.
- As starvation continues, protein breakdown slows down to conserve muscle mass and prevent excessive nitrogen loss.
- Increased use of fatty acids & ketone bodies as fuel reduces the body’s dependence on protein-derived glucose.
- Urea excretion (a marker of protein breakdown) decreases over time due to reduced protein catabolism.