Metabolic response to starvation

Question 1

Simple starvation response

Answer 1

metabolic adaptation

lean tissue conserved

Question 2

Catabolic weight loss

Answer 2

no adaptation

lean tissue breakdown n continues despite nutrient intake

Question 3

Early metabolic responses to fasting

Answer 3

In simple starvation decreased basal metabolic rate, low glucose, limited glucose use, increased gluconeogenesis which decreases after 5-7 days, low protein catabolism, high fat catabolism, increased ketone use, present ketosis and ketosuria

Question 4

Early metabolic responses to starvation superimposed on to injury or stress

Answer 4

Decreased or normal BMR initally, high glucose levels, increased glucose use, increased gluconeogenesis, high protein catabolism, low/no fat catabolism, decreased ketone use, no ketosis or ketosuria

Question 5

Starvation - Anorexia nervosa

Answer 5

Nutritional deficiency, severe
Severe restriction of nutritional intake
Despite extremely low body weight
Glucose: Low
Starvation ketosis 
Physiological response for alternative 				energy supply

Question 6

What does high urea indicate?

Answer 6

muscle breakdown

Question 7

Muscle energy

Answer 7

Muscles adapt to ketones & spare further protein breakdown
Low insulin does not allow glucose uptake, ketones used

Question 8

Fat tissue

Answer 8

High glucagon activate hormone sensitive lipase

Breakdown of TG to FFA

Question 9

Treatment and prognosis of anorexia

Answer 9

psychotherapy, antidepressants, diet 1800 cal
Survival time depends on fat stores
After depletion of fat stores
Only source energy is protein
Protein degradation accelerates
Death from loss of heart, liver or kidney function

Question 10

Normal glucose metabolism

Answer 10

Postprandial increase blood glucose
Stimulates insulin release
Insulin mediates glucose uptake into skeletal muscle, fat tissue
Suppresses hepatic gluconeogenesis

Question 11

Ketoacidosis

Answer 11

Diabetes: Most common cause - Glucose high, but cannot be utilised so ketones used instead
Fasting ketosis
Alcoholic ketoacidosis;
Especially if malnourished
Ethanol metabolised to acetic acid(ketone)
Nor-adrenaline & cortisol amplify fasting lipolysis (Trigs-FFA-ketones)

Question 12

Alcoholic ketoacidosis characteristics

Answer 12

characterized by

hyperketonemia and metabolic acidosis without significant hyperglycemia

Question 13

What happens during ketoacidosis?

Answer 13

Liver production of ketones
Stimulated by low insulin & high glucagon
Secondary to low glucose: fasting, low carbohydrate diet, diabetes
Lipase activated
Fat stores - triglycerides - long chain fatty acids & glycerol
Fatty acids transported to liver

Question 14

How are ketones synthesised?

Answer 14

Ketones synthesis occurs in the Liver
Fatty acids enter mitochondria
Fatty acids oxidised to acetyl-CoA
Either enter 
Krebs cycle generate ATP
Generate ketones (Acetone, Acetoacetate, beta-hydroxybutyrate) FFA, cholesterol

Question 15

Ketones

Answer 15

B-hydroxybutyric acid and acetoacetic acid.

Acetoacetic acid is unstable and either turns into acetate or b-hydroxybuyric acid

Question 16

Fasting ketosis

Answer 16

Liver generation of ketones is the physiological response to fasting
Mild ketosis ~1mmol/L after 12h fast
Fasting for 20 days: 8 - 10mmol/L
β-hydroxy butyrate is major ketone
Synthesis matches utilization : in brain, muscle, kidney etc
s-bicarbonate falls by 7 - 8mmmol/L

Question 17

ketone body stabilization

Answer 17

Stabilization:3 mechanisms:
Stimulation insulin release, despite low glucose
Increased sensitivity of adipose tissue to insulin inhibitory effect on fatty acid release
Direct inhibition of lipolysis by ketones
No adverse effects with fasting ketosis.

Question 18

Properties of ketones

Answer 18

Water-soluble
Fat-derived fuel
Used when glucose low
Brain especially dependent when serum glucose levels low
Neurologic manifestations hypoglycemia plasma glucose

Question 19

metabolic response to starvation

Answer 19

decreased metabolic rate and urinary nitrogen, slow weight loss and conserved body fuels and protein

Question 20

Metabolic response to trauma or disease

Answer 20

significantly increased metabolic rate and urinary nitrogen, wasted body fuels and body proteins, rapid weight loss

Question 21

Sepsis

Answer 21

Sepsis is a spectrum of disease

Systemic inflammatory response syndrome (SIRS): fever, tachycardia, tachypnoea, respiratory compromise

Question 22

Lab assessment for sepsis

Answer 22

Lab assessment: blood gas, lactate, Glucose, blood culture; FBC; CRP; Na+, K+, Cl–, HCO3– , eGFR, AKI staging, also, phosphate, calcium, albumin, magnesium, coagulation, LFT,

Question 23

Nutritional support in critical illness

Answer 23

Catabolism exceeds anabolism
Carbohydrates are preferred energy
Fat mobilization is impaired
Protein administration to decrease breakdown of muscle protein

Question 24

Sepsis six

Answer 24

oxygen
IV atnibiotics
fluid challange
measure lactate
measure urine
take blood cultures

Question 25

Lactic acidosis

Answer 25

Usual cause is Tissue hypoperfusion Impaired tissue oxygenation, leading to increased anaerobic metabolism Hypovolemia Cardiac failure Sepsis Cardiopulmonary arrest Most common cause of metabolic acidosis in hospitalized patients

Question 26

Hypermetabolic response to injury: trauma, surgical, critically ill

Answer 26

``` Increased blood pressure & heart rate Peripheral insulin resistance Increased protein and lipid catabolism Increased resting energy expenditure Increased body temperature Total body protein loss Muscle wasting Acute-phase protein response ```

Question 27

Glucose is high in critical illness due to

Answer 27

Stress mediators oppose anabolic actions of insulin Enhanced Adipose tissue lipolysis Skeletal muscle proteolysis, Gluconeogenic substrates (glycerol, alanine, lactate) increased glucose production Suppressive effect of insulin on hepatic glucose release is attenuated High catecholamines, cortisol Increased gluconeogenesis Catecholamines: Enhance glycogen breakdown Impair glucose disposal via alterations of the insulin-signaling pathway; & GLUT4 translocation in muscle & adipose tissue, resulting in peripheral insulin resistance

Question 28

Altered protein and lipid metabolism

Answer 28

In starvation, lipolysis & ketosis provide energy, protect muscle reserves Illness: lean-muscle protein breakdown due to: Pro-inflammatory cytokines: tumor necrosis factor (TNF) Reduces ability to use lipids as energy Skeletal muscle is major source of substrate for glucose production

Question 29

Endocrine complications of starvation

Answer 29

Hypothalamic-pituitary abnormalities-multiple Suppression hypothalamic-pituitary-ovarian axis Hypogonadotropic hypogonadism Low GnRH, LH, FSH, estradiol Amenorrhea, infertility Due to energy deficit, low fat mass, leptin low Bone loss - severe