Appetite Flashcards
Control of thirst caused by
Body Fluid Osmolality (increasing increases thirst) - change of 2/3% to induce thirst
-Blood volume (reduction increases thirst) - change of 10-15% to induce thirst
-Blood pressure (reduction increases thirst) - change of 10-15% to induce thirst
Regulation of osmolality
ADH- acts on kidneys
Low ADH= large volume of urine, water diuresis
High ADH= low diuresis
Released and stored from posterior pituitary
Osmoreceptors
Measure osmolality
Found in hypothalamus:
- Organum Vasculosum of the Lamina Terminalis (OVLT)
- Subfornical Organ (SFO)
Small proportion of active cation channels in the osmoreceptors, so in hypotonic conditions the cells shrink, and therefore the proportion of active cation channels increases. This therefore increases positive charge influx and therefore membrane depolarisation occurs, resulting in signals being send to ADH producing cells. This causes fluid retention and increases thirst
Sensation of thirst
- Thirst is decreased by drinking even before there is sufficient water absorption in the GI tract to correct the plasma osmolality
- This is because there are receptors in the mouth, pharynx and oesophagus
- Thirst is only fully satisfied once plasma osmolality has decreased or blood volume / pressure are corrected
Renin-angiotensin-aldosterone system
- Blood pressure falling leads to excretion of renin from juxtaglomerular cells of renal afferent arteriole
- Angiotensinogen converted to angiotensin I by renin
- ACE from lungs cleaves angiotensin I into angiotensin II
- Angiotensin II increases ADH secretion, increases thirst
- Angiotensin II also causes influx of potassium and efflux of sodium from the zona glomerulosa of the adrenal cortex, resulting in aldosterone release, which then promotes systemic H2O retention due to Na+ and Cl- absorption, alongside K+ excretion
Angiotensin II also causes vasoconstriction and increases sympathetic activity
Homeostasis
- Neuman 1902 - noticed maintaining body weight didn’t need active input
- Passmore 1971 - noticed most adults maintain stable weight
- Reduction in fat mass increases food intake and reduces energy expenditure
- Adipose tissue expansion reduces food intake and increases energy expenditure
System underpinning rapid weight loss is well understood, but there is no knowledge of what prevents rapid weight gain
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Appetite regulation and the hypothalamus
- Neural input from the periphery and other brain regions
- Ghrelin, PYY, other gut hormones
- Leptin
Hypothalamus alters food intake and energy expenditure
Arcuate nucleus produces orexigenic and anorectic peptides
Has an incomplete blood brain barrier, allowing access to peripheral hormones
Integrates peripheral and central feeding signals
Two neuronal populations:
STIMULATORY (NPY/AGRP neurone) [neuropeptide Y and Agouti-related peptide]
- NPY stimulates directly whilst AGRP disinhibits
INHIBITORY (POMC neurone)
Ventromedial hypothalamus - responsible for feelings of satiety
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Melanocortin system
POMC > a-MSH stimulates MC4R in the paraventricular Nucleus
POMC and MC4R mutations associated with human obesity
Amygdala, latera hypothalamus, vagus nerve all transmit signals about hunger
Adipostat mechanism
Fat produces a circulating hormone, the concentration of which can be detected by the hypothalamus
The hypothalamus then alters neuropeptides to alter food intake on the basis of hormone concentration
Leptin
Made by adipocytes in white adipose tissue and enterocytes
Circulates in the plasma
Acts on the hypothalamus to regulate appetite and thermogenesis, so energy intake and energy expenditure
Low body fat = low leptin, vice versa
Congenital leptin deficiency = constantly hungry
Mechanism of action of leptin
- Absence of leptin
- Regulatory defect of leptin
- Leptin resistance
Leptin is ineffective as a weight control drug due to leptin resistance
Gut hormones
Cause feelings for satiety
Secreted by enteroendocrine cells in the stomach, pancreas and small bowel
Ghrelin - stimulates appetite, increases gastric emptying
- Levels highest before a meal
- Helps prepare for food intake as it increases gastric motility and acid secretion
- Directly modulates neurons in the arcuate nucleus, stimulates NPY/AGRP, inhibits POMC
- Involved in regulation of reward, taste sensation, memory and circadian rhythm
Peptide YY (PYY) - inhibits food intake
-released in the terminal ileum and colon in response to feeding
-short (36 amino acids)
-stimulates POMC neurones
-inhibits NPY release
Comorbidities of obesity
- Depression
- Sleep apnoea
- Bowel cancer
- Osteoarthritis
- Gout
- Peripheral vascular disease
- Diabetes
- Hypertension
- Myocardial infarction
- Stroke
Epidemiology
Overweight - least = camden, most = rotherham
Obese - most = Bolton
Obesity and related comorbidities are increasing worldwide
