Metabolic 3: Metabolic response to sepsis/ injury vs starvation Flashcards
Simple starvation
Metabolic adaptation
Lean tissue conserved
Catabolic weight loss
No adaptation
Lean tissue breakdown continues despite nutrient intake
Anorexia nervosa
Nutritional deficiency, severe
Severe restriction of nutritional intake
- despite extremely low body weight
Glucose: low
- starvation ketosis
- physiological response for alternative energy supply
Normal glucose metabolism
Postprandial increase blood glucose
Stimulates insulin release
Insulin mediates glucose uptake into skeletal muscle, fat tissue
Suppresses hepatic gluconeogenesis
Ketoacidosis causes
Diabetes: most common cause
- glucose high, but cannot be utilised
- ketones alternative energy supply
Fasting ketosis
Alcoholic ketoacidosis
- hyperteoneamia and metabolic acidosis without significant hyperglycaemia
- especially if malnourished
- ethanol metabolised to acetic acid
Ketoacidosis
Liver production of ketones
Stimulated by low insulin and high glucagon
Secondary to low glucose: fasting, low carb diet, diabetes
Lipase activated
Fat stores- triglycerides, long chain fatty acids and glycerol
Fatty acids transported to liver
Fatty acids enter mitochondria, oxidised to acetyl-CoA
Enter krebs cycle or generate ketones
Where does ketone synthesis occur?
Liver
Ketone bodies metabolism
Ketone synthesis in the liver
During prolonged starvation, oxaloacetate is depleted in liver due to gluconeogenesis
Impedes entry of acetyl-CoA into krebs cycle
Acetyl-CoA in liver mitochondria converted to ketone bodies
Ketone bodies
Acetone
Acetoacetate
B-hydroxybutyrate
Fasting ketosis
Liver generation of ketones is physiological response to fasting
Mild ketosis 1mmol/L after 12h fast
Fasting for 20 days: 8-10mmol/L
B-hydroxybutyrate is major ketone
Synthesis matches utilisation: in brain, muscle, kidney etc
Stabilisation: 3 mechanisms
No adverse effects
3 mechanisms of stabilisation in fasting ketosis
Stimulation of insulin release, despite low glucose
Increased sensitivity to adipose tissue to insulin inhibitory effect on fatty acid release
Direct inhibition of lipolysis by ketones
Ketones
Water soluble
Fat derived fuel
Used when glucose low
Brain especially dependent when serum glucose levels low
Neurological manifestations hypoglycaemia, plasma glucose <2.8mmol/L, in ketoacidosis much lower glucose
Nutritional support in critical illness
Catabolism exceeds anabolism
Carbohydrates are preferred energy
Fat mobilisation is impaired
Protein administration to decrease breakdown of muscle protein
Sepsis 6
- Give O2 to keep sats above 94%
- Take blood cultures
- Give IV antibiotics
- Give a fluid challenge
- Measure lactate
- Measure urine output
Sepsis- Lactic acidosis
Usual cause is tissue hypoperfusion
Impaired tissue oxygenation, leading to increased anaerobic metabolism
- hypovolaemia
- cardiac failure
- sepsis
- cardiopulmonary arrest
Most common cause of metabolic acidosis in hospitalised patients
Hypermetabolic response to injury: trauma, surgical, critically ill
Increased BP and HR
Peripheral resistance to insulin
Increased protein and lipid catabolism
Increased resting energy expenditure
Increased body temperature
Total body protein loss
Muscle wasting
Acute phase protein response
High glucose in critically ill due to
Stress mediators oppose anabolic actions of insulin
Enhanced
- adipose tissue lipolysis
- skeletal muscle proteolysis
- gluconeogenic substrates increase glucose production
Suppressive effect of insulin on hepatic glucose release attenuated
High catacholamines, cortisol
Increased gluconeogensis
Altered protein and lipid metabolism in starvation
Lipolysis and ketosis provide energy, protect muscle reserves
Altered protein and lipid metabolism in illness
Lean muscle protein breakdown due to
- pro-inflammatory cytokines: TNF
- reduces ability to used lipids as energy
- skeletal muscle is major source of substrate for glucose production
Skeletal muscle responsible for 75% of whole body insulin stimulated glucose uptake
- decrease in muscle contribute to persistent insulin resistance
- catecholamines initiate adipose tissue browning after injury, may facilitate hypermetabolic response and cachexia
Consequences of altered protein and lipid metabolism
10% loss in lean body mass
- increase in infection
- delays wound healing
- muscle weakness
- prolongs mechanical ventilatory utilisation
- inhibits cough reflexes
- delays mobilisation
- contributing to mortality
Starvation- endocrine complciations
Hypothalamic- pituitary abnormalities- multiple
Suppression hypothalamic pituitary ovarian axis
Hypogonadotropic hypogonadism
Low GnRH, LH, FSH, oestradiol
Amenorrhoea, infertility
Due to energy deficit, low fat mass, leptin low
Bone loss- severe
Endocrine complications- adrenal
Increased hypothalamic pituitary adrenal activity
Stress of chronic starvation
High cortisol (glucocorticoid): - breakdown of protein to glucose and urea
Loss of collagen: osteopeania
Loss of muscle: weakness
Endocrine complications- thyroid
Sick euthyroid pattern
- TSH low-normal, FT4 low-normal, FT3 low
Due to chronic undernutrition
- decreased metabolic rate
Decreased conversion FT4 to FT3
TSH and FT4 levels: low normal or low
Reduced metabolic rate
