2014A14. Compare and contrast the physiological effects of a six hour fast of food and fluid with a twenty four hour fast in a healthy adult.
List:
· Phases of fasting
· Energy stores
· Metabolic pathways and key enzymes
· Food fast
· Fluid fast
Phases of fasting:
|
Absorptive |
· 0-6 hours |
|
Glycogenolytic |
· 6-24 hours |
|
Gluconeogenic |
· 1-7 days |
|
Protein conservation |
· 7 days + |
Energy stores:
|
Absorbed meal |
· e.g. 8000/3 = 2600kJ |
|
Glycogen |
· 50-100g liver, 300-400g skeletal muscle · Enough for ~24 hours (but some hepatic glycogen always preserved in case of emergency) |
|
Protein |
· 6kg = 96,000kJ · Enough for ~12 days (but vital lean tissue) |
|
Fat |
· >200,000kJ · Enough for ~4 weeks |
Metabolic pathways and key enzymes:
|
Glycolysis (GL) |
· Hexokinase |
|
Gluconeogenesis (GNG) |
· From pyruvate, lactate, fructose, amino acids, glycerol · Note glucose 6 phosphatase mainly expressed in liver > renal cortex |
|
Glycogenolysis (GGL) |
· Glycogen phosphorylase |
|
Glycogenesis (GG) |
· Glycogen synthase |
|
Lipolysis (LL) |
· Hormone-sensitive lipase |
|
De novo lipogenesis (DNL) |
· Lipoprotein lipase, acetyl-CoA carboxylase, fatty acid synthase |
|
Ketogenesis (KG) |
· Acetyl-CoA thiolase |
Food fast:
|
|
6 hours |
24 hours |
|
Overall |
· Well tolerated · Exception: children (faster MR), diabetics (poor glucose homeostasis) |
· Poorly tolerated · Hunger, lethargy, irritability · Brain and RBC are obligate glucose users and stores are limited · High rate of protein breakdown · Increase risk of wound breakdown, infection |
|
Hormonal profile |
· ↑Insulin, ↓glucagon |
Progressive changes: · ↓Insulin, ↑glucagon · ↑Catecholamines: if ↓BGL (? >24 hours) · ↑Cortisol, growth hormone: if significant and prolonged ↓BGL (?>24 hours) |
|
Liver |
· (GL), (GG), (DNL) |
· (GGL) > (LL) > (KG) · (LL) upregulated over days 1-3 · (KG) upregulated over days 1-7 |
|
Muscle |
· (GL), (GG) |
· (GGL) -> Cori cycle >> (LL)
· Proteolysis -> glucose-alanine cycle
|
|
Adipose |
· (DNL) |
· (LL) upregulated over days 1-3 |
|
Brain |
· Uses glucose only |
·
Uses glucose >> ketones |
Fluid:
|
|
6 hours |
24 hours |
|
Overall |
· Well tolerated (e.g. overnight) · Exceptions: children (faster MR) |
· Poorly tolerated · Thirst, lethargy, dry mouth, postural dizziness · Increased blood viscosity · Increased risk of organ dysfunction e.g. AKI |
|
% Volume lost |
· 1.5% |
· Resp 0.4L · Skin 0.4L · GIT 0.2L · Kidneys 1.5L · Total 2.5L = 6% water loss |
|
RAAS response |
· ↓ |
· ↑ (↓afferent arteriolar stretch, ↓NaCl load to macula densa) |
|
ADH response |
· ↓ |
· ↑ · Due to ↑osmolality (sensitive to ↑1-3%) · Not due to ↓volume (sensitive to ↓10%) |
|
ANP response |
· ↑ (right atrial stretch) |
· ↓ |
|
Urine |
· Dilute |
· Increasingly concentrated, max 1200mOsmol/L |
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