Metabolic 3: Metabolic response to sepsis/ injury vs starvation

Question 1

Simple starvation

Answer 1

Metabolic adaptation

Lean tissue conserved

Question 2

Catabolic weight loss

Answer 2

No adaptation

Lean tissue breakdown continues despite nutrient intake

Question 3

Anorexia nervosa

Answer 3

Nutritional deficiency, severe

Severe restriction of nutritional intake
- despite extremely low body weight

Glucose: low

• starvation ketosis
• physiological response for alternative energy supply

Question 4

Normal glucose metabolism

Answer 4

Postprandial increase blood glucose

Stimulates insulin release

Insulin mediates glucose uptake into skeletal muscle, fat tissue

Suppresses hepatic gluconeogenesis

Question 5

Ketoacidosis causes

Answer 5

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

Question 6

Ketoacidosis

Answer 6

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

Question 7

Where does ketone synthesis occur?

Answer 7

Liver

Question 8

Ketone bodies metabolism

Answer 8

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

Question 9

Ketone bodies

Answer 9

Acetone

Acetoacetate

B-hydroxybutyrate

Question 10

Fasting ketosis

Answer 10

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

Question 11

3 mechanisms of stabilisation in fasting ketosis

Answer 11

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

Question 12

Ketones

Answer 12

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

Question 13

Nutritional support in critical illness

Answer 13

Catabolism exceeds anabolism

Carbohydrates are preferred energy

Fat mobilisation is impaired

Protein administration to decrease breakdown of muscle protein

Question 14

Sepsis 6

Answer 14

1. Give O2 to keep sats above 94%
2. Take blood cultures
3. Give IV antibiotics
4. Give a fluid challenge
5. Measure lactate
6. Measure urine output

Question 15

Sepsis- Lactic acidosis

Answer 15

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

Question 16

Hypermetabolic response to injury: trauma, surgical, critically ill

Answer 16

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

Question 17

High glucose in critically ill due to

Answer 17

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

Question 18

Altered protein and lipid metabolism in starvation

Answer 18

Lipolysis and ketosis provide energy, protect muscle reserves

Question 19

Altered protein and lipid metabolism in illness

Answer 19

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

Question 20

Consequences of altered protein and lipid metabolism

Answer 20

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

Question 21

Starvation- endocrine complciations

Answer 21

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

Question 22

Endocrine complications- adrenal

Answer 22

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

Question 23

Endocrine complications- thyroid

Answer 23

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