U1iii: Physiology of starvation
Definition
- Starvation = totally absent/inadequate nutrition when the body has depleted its own stores
Early Starvation
- Circulating blood glucose adequate for 4 – 6hrs
- Glycogenolysis (24 – 48hrs)
- Liver stores 100g & skeletal m. 400g glycogen
- α & β cells pancreas detect ↓BSL
- ↓insulin & ↑glucagon secretion & ↑adrenaline activates GLYCOGEN PHOSPHORYLASE
- ↑glucose release from liver (GLUCOSTAT)
- Skeletal m. do not have G6Pase & ∴ cannot release into blood
- → exhausted in 24 – 48hrs
Late Starvation
- ↑ Gluconeogenesis (1 – 2 weeks)
- α – acid from proteolysis
- Glycerol from lipolysis
- Lactate* & pyruvate^ from anaerobic glycolysis
→ all substrates for gluconeogenesis in liver
CORI CYCLE: glucose → pyruvate → lactate → glucose
- All due to further ↓insulin, ↑glucagon, ↑adrenaline, ↑GH, ↑cortisol
- RBC & renal medulla also produce lactate because obligate glucose substrate requirements
* Lactate = produced from reduction of pyruvate in AnO2 conditions (i.e. pyruvate can’t enter Kreb’s)
^ Pyruvate = end product of glycolysis
- Ketogenesis
- CHO supply depleted
- ↑reliance on hepatic oxidation of FFA as E source
- ∴↑ketogenesis with ↑duration of fasting
Ketone production
Acetyl CoA + Acetyl CoA
↓
Acetoacetyl CoA
↓
NMG CoA
↓
Acetoacetate
↓
β – hydroxybutarate = 1° ketone body
- Ketones = freely diffusible
- Oxidised to provide E. for brain:
β – hydroxybutarate
↓
Acetoacetyl CoA
↓
Acetyl CoA + Acetyl CoA
↓
Enters KREBS
- Normal ketone = 0.2 mol/L
- Starvation = 6 – 7 mol/L
Hormonal Changes
- ↓ Insulin
- ↑ Glucagon
- ↑ Adrenaline
- ↑ Cortisol
- ↓ T3 → ↓BMR