appetite & disorders of appetite

Question 1

What are the 3 mechanisms that control thirst and which one is the strongest?

Answer 1

1. plasma osmolarity increase 2. blood volume reduction 3. blood pressure reduction. Strongest stimulus is plasma osmolarity increase

Question 2

What is the mechanism of ADH? Where is it stored?

Answer 2

Acts on V2 receptor on collecting duct signalling for aquaporin 2 channels to increase water reabsorption. ADH high - more water reabsorbed, less excreted. ADH stored in posterior pituitary gland (but produced in hypothalamus)

Question 3

What do osmoreceptors do? Where are they located? How do they work?

Answer 3

• Sensory receptors in hypothalamus. Organum vasculosum & subfornical organ.
• Hypertonic solution, increases number of cation channels and membrane depolarised in osmoreceptors, increasing neuronal firing and signalling ADH producing cells to make ADH.
• Hypotonic solution, loss of cation influx causes hyperpolarisation, inhibiting firing.

Question 4

How is the sensation of thirst decreased short term and long-term?

Answer 4

Short term by receptors in mouth, pharynx & oesophagus. Long-term when plasma osmolarity/blood volume/pressure is corrected

Question 5

What happens when there is a decrease in blood pressure?

Answer 5

Juxtaglomerular cells secrete renin, which activates renin-angiotensin system, cleaving angiotensin II by ACE in lung. ANGII induces thirst, binds to intraglomerular mesangial cells causing them to contract, releases aldosterone from zona glomerulosa of adrenal cortex (to increase sodium/water reabsorption) and increases ADH secretion.

Question 6

How is body weight homeostasis achieved?

Answer 6

• Reduction in fat mass increases food intake and reduces energy expenditure by decreasing sympathetic activity, decreasing thyroid actions, increasing hunger and food intake.
• Adipose tissue expansion reduces food intake & increases energy expenditure by increasing sympathetic activity to favour return to original weight

Question 7

How is appetite regulated and by what? What signals are given to hypothalamus and what does it respond with?

Answer 7

Mostly regulated in hypothalamus. Peripheral hormonal and neuronal stimuli like ghrelin, PYY, gut hormones signal via vagus nerve to hypothalamus, which receives these triggers and sensitises responses to increase/decrease energy expenditure and to regulate food intake.

Question 8

What does arcuate nucleus do?

Answer 8

Produces both appetite increasing (orexigenic) or suppressive (anorexigenic) peptides.

Question 9

What other hypothalamic factors are involved in appetite regulation?

Answer 9

Endocannabinoids, AMP, protein tyrosine phosphatase

Question 10

What does paraventricular nucleus of hypothalamus do?

Answer 10

Contains neurones that project to posterior pituitary where ADH stored, to secrete oxytocin ADH affecting osmoregulation, appeitite and stress.

Question 11

What does lateral hypothalamus do?

Answer 11

Produces orexigenic peptides

Question 12

What does ventromedial hypothalamus do?

Answer 12

Associated with satiety

Question 13

What do lesions in appetite areas of the hypothalamus lead to?

Answer 13

severe obesity

Question 14

What is the arcuate nucleus involved in? what does it do? What type of cells does it have?

Answer 14

Regulation of food intake. BBB incomplete so acess to peripheral signals - integrates peripheral/central signals. Has 2 populations: stimulatory NPY/Agrp neurones, and inhibitory POMC neurones.

Question 15

What do NPY/agrp neurones do?

Answer 15

NPY/agrp make peptides that stimulate food intake by increasing neuropeptide Y signalling and reducing melanocortin singalling via release of agrp (endogenous melanocortin receptor antagonist). Also express receptors for leptin & insulin (decrease of these by fasting or genetic leptin deficiency) increase food intake.

Question 16

How does the melanocortin system work? What is it stimulated by and what does it lead to?

Answer 16

Melanocortins are products of POMC chain (eg. A-MSH). Central regulator of energy balance. Melanocortin-4 expressed in paraventricular nucleus. Stimulated by serotonin & lead to reduction in appetite & weight by decreasing food intake.

Question 17

What CNS mutations lead to morbid obesity?

Answer 17

POMC deficiency and MCR-4 (melanocortin-4) mutations

Question 18

What is role of amygdala in appetite?

Answer 18

(reward/motivation) affect appetite

Question 19

What is the adipostat and how does it work?

Answer 19

Keeps fat in range. Hormone produced by adipose tissue (more tissue, more hormone), hypothalamus senses hormone concentration and alters neuropeptides to increase or decrease food intake.

Question 20

What is leptin? Where is it produced? What is its role?

Answer 20

Hormone made by adipose tissue and small intestine. Involved in regulation of energy balance, suppressing food intake & inducing weight loss. Role in atherosclerosis via innate system. Acts on hypothalamus to regulate appetite & thermogenesis

Question 21

What conditions is leptin low in?

Answer 21

alzheimers and depression

Question 22

What does congenital leptin deficiency lead to?

Answer 22

Severe obesity very early in life.

Question 23

What do leptin levels usually correlate with?

Answer 23

Body fat. More body fat, more leptin usually.

Question 24

What are the 3 mechanisms by which leptin can be dysfunctional?

Answer 24

1. insufficient production
2. receptor signalling/regulatory signalling defective so reduce leptin levels despite high fat tissue
3. leptin resistance - decreased sensitivity to leptin so cant detect satiety despite high energy stores

Question 25

What is leptin resistance?

Answer 25

Hormone is present but doesn’t signal effectively.

Question 26

Can leptin be used as weight control drug?

Answer 26

no

Question 27

What hormones are involved in short term regulation of appetite? Where are they produced?

Answer 27

Gut hormones - ghrelin & PYY, secreted by enteroendocrine cells in stomach, pancreas, small intestine

Question 28

What does ghrelin do? When is it high and when is it low? How does it modulate appeitite?

Answer 28

Increases gastric motility/acid before meal to prepare for food intake, increases food intake, increases appetite, role in reward, taste sensation, memory, circadian rhythm, meal initiation.

• Hunger hormone that directly modulates neurones in arcuate nucleus stimulating NPY/agrp and inhibiting POMC to increase appetite.
• Highest before meals (double amount) and fall 1h after eating (diurnal rhythm). Correlate positively with age

Question 29

What is PYY, where is it released? What does it do? What induces the best response of PYY?

Answer 29

Encoded by PYY gene released in terminal ileum in response to food.

• Best response from dietary fibres, wholegrains & crude fish proteins.
• Acts to reduce appetite and induce satiety by inhibiting NPY/agrp and stimulating POMC neurones.

Question 30

What does PYY infusion in humans result in? side effects?

Answer 30

Reduction of food intake/calorie intake/fluid ingestion. Side effects: nausea, fullness, less hunger, early fullness

Question 31

How do genetics affect obesity?

Answer 31

Genetically prone to obesity with healthy environment little obesity manifestation. In toxic environment, genetically prone will suffer while genetically resistant will not as much.

Question 32

Want are causes of primary polydipsia?

Answer 32

Mental illness (psychogenic polydipsia) - schizophrenia, mood disorders, anorexia, drug use. Brain injuries & organic brain damage

Question 33

What are causes of secondary polydipsia?

Answer 33

More common, any disruption in steps of osmoregulation can alter ADH.

1. chronic conditions: diabetes insipidus, diabetes mellitus, kidney failure, conn’s syndrome, addison’s syndrome, sickle cell anaemia.
2. medications: diuretics, laxatives, anti-depressants.
3. dehydration: acute illness, sweating, fever, vomiting, diarrhoea, underhydration

Question 34

What is diabetes inspidus?

Answer 34

Impaired ADH production. Treated with desmopressin

Question 35

What is diabetes mellitus?

Answer 35

High blood sugar.

Question 36

What can overhydration lead to, why is polydipsia a problem?

Answer 36

Electrolyte imbalance. Kidney/bone damage, headache, nausea, cramps, slow reflexes, seizures, low energy, confusion, slurred speech

Question 37

What is adipsia and the different types? Which is most common?

Answer 37

Inappropriate lack of thirst. Type A-D (A is most common).

Question 38

What is the mechanism underlying adipsia?

Answer 38

Increases osmolarity of urine, stimulates secretion of ADH, water retention, sensation of thirst decreases

Question 39

What are eating disorders? Examples?

Answer 39

Abnormal eating habits. Include BED, anorexia, bulimia, pica, rumination syndrome, avoidant/restrictive disorder. They have increased (doubled)

Question 40

What are symptoms, signs of anorexia? What is the mechanism and the types?

Answer 40

Low BMI, weight loss, amenorrhea, halitosis (bad breath), mood swings, dry skin, hair thinning. Mechanism is serotonin. Causes biopsychosocial. Can be mild, moderate, severe depending on BMI.

Question 41

What are comorbidities associated with obesity?

Answer 41

Depression, stroke, MI, hypertension, cancer, osteoarthritis, sleep apnoea, gout

Question 42

Why is obesity increasing?

Answer 42

Increased fast food, cheap.

Question 43

What lifestyle modification most efficient for obesity?

Answer 43

Diet + exercise

Question 44

What are surgeries for obesity? Who are they indicated for? What do they lead to?

Answer 44

Gastric bypass & sleeve gastrectomy. BMI> 30 or 35+ comorbidities. Reduction in all cause mortality and morbidity after surgery. Remission of comorbidities like diabetes and osteoarthritis

Question 45

What are hormonal changes after bariatric surgery?

Answer 45

Decrease in ghrelin (hunger hormone that increases appetite), increase in GLP-1, GLP2 (stimulate insulin release & reduce glucagon release) and PYY (satiety, anorexogenic)