6.2 Appetite Flashcards
What are the three factors that regulate thirst?
1) Plasma osmolarity
2) Hypovolaemia
3) Hypotension
Where is vasopressin released from?
Herring bodies of the posterior pituitary gland i
Which types of neurones release vasopressin?
Magnocellular hypothalamic neurones
Which hypothalamic nuclei release vasopressin?
Supraoptic and paraventricular nuclei
Which receptors are stimulated by vasopressin?
V2 receptors on tubule cells of the collecting duct and distal convoluted tubule
Which types of channels are synthesised in response to vasopressin?
Aquaporin-2 channel expression to increase water permeability and reabsorption
What is the effect of low plasma ADH?
Water diuresis
What is the effect of high plasma ADH?
Anti-diuresis
Small volume of concentrated urine
Where are osmoreceptors found?
Circumventricular residing within the organum vasculosu, and the subfornical organ
How do osmoreceptors induce ADH release?
- Detection of increased plasma osmolarity.
- Osmoreceptor cell shrinkage (due to water diffusing into extracellular environment).
- Conformational change increases proportion of cation channels expressed on the cell surface membrane.
- Increased influx of cations Membrane depolarisation.
- Transmits action potentials to ADH producing magnocellular hypothalamic neurones
- Improved fluid retention
What happens to the osmoreceptor when there is an increase in plasma osmolarity?
Cell shrinkage, due to water diffusing into extracellular environment.
What happens to the osmoreceptors when there is conformational change?
Causes an increase in the expression of cation channels expressed on the cell surface membrane
-influx of cations, causing membrane depolarisation
What effect does ADH do in hypertonic conditions?
increased fluid retention, by stimulating water reabsorption
What happens in hypotonic conditions to ADH>
In hypotonic conditions, osmoreceptor cells maintain their structural shape, and cation channels are inhibited Reduced cation influx induces a state of hyperpolarisation to inhibit firing.
Where are thirst receptors located?
Mouth, pharynx, and oesophagus
What is the effect of the stimulation of thirst receptors?
They are stimulated by detecting water consumption, and relieve the sensation of thirst in the short-term
How is thirst sensation completely satisfied?
• Thirst sensation is completely satisfied once plasma osmolarity is corrected or blood volume/arterial pressure is restored to normal.
What is the response to low renal perfusion pressure by JG cells?
Renin is secreted (increased sympathetic activity by stimulating beta-1 receptors).
What is the effect of renin?
Converts angiotensinogen into angiotensin-I
What is the effect of ACE?
Converts angiotensin-I to angiotensin-II
What is the effect of angiotensin-II?
A potent vasoconstriction to increase systemic blood pressure and increases sympathetic activity.
- Promotes thirst
- Promotes ADH secretion
- Promotes aldosterone synthesis
- Increased sodium reabsorption
What effect does aldosterone have on tubule cells of the distal convoluted tubule?
Sodium reabsorption
Potassium secretion
What is the effect of ACE-inhibitors?
Inhibit the conversion of angiotensin -I to angiotensin-II
reduces vasoconstrictive properties of angiotensin-II
vasodilator
What is an ARB?
Angiotensin-receptor blocker
Where is aldosterone synthesised?
In the zona glomerulosa of the adrenal cortex
What is the mechanism of an ARB?
• Angiotensin-II receptor blockers are receptor antagonists which prevent angiotensin-II from exerting hypertensive effects.
What is adipose tissue expansion?
Reduces food intake and increases energy expenditure.
What happens to energy expenditure when there is a reduction in fat mass?
Reduction in fat mass - Increased
What is the ventromedial nucleus?
Ventromedial nucleus is associated with inducing a state of satiety, a lesion to the ventromedial nuclei increases the sensation to intake food contributing to severe obesity.
What is the impact to a lesion to the ventromedial nucleus?
Increases the sensation of food intake - leading to severe obesity
What is the role of the ventromedial nucleus?
Induces a state of satiety
What type of factor is released from the lateral hypothalamic nucleus?
Releases orexigenic factors
What is an orexigenic factor?
Behaves as an appetite stimulant
Which structure includes both orixgenic and anorexigenic neurones?
Arcuate nucleus
What are orexigenic neurones?
are appetite stimulating – releasing neuropeptide Y and agouti-related peptides. (LHN)
Which peptides are released from orexigenic neurones?
Neuropeptide Y and agouti-related peptides (LHN)
What are anorexigenic neurones?
POMC/CART neurones are appetite suppressive – releasing MSH. (VHN). These neurones are directly innervated and inhibited by the NPY neurones.
Which peptides are released from anorexigenic neurones?
Alpha-MSH
What directly inhibits POMC neurones?
NPY neurones
Where do the neuronal projections terminate at?
Paraventricular nucleus of the hypothalamus, adjacent to the third ventricle.
What does the paraventricular nucleus secrete?
Oxytocin and ADH
How does the arcuate nucleus receive hormonal stimulation?
There is an incomplete blood brain barrier - enabling access for the arcuate nucleus to interact with circulating hormones
Which hormones inhibit orexigenic neurones?
Leptin, peptide YY, and insulin
Which hormone stimulates orexigenic neurones?
Ghrelin
What is the hunger reflex?
Hunger:
- Decreased stimulation of mechanoreceptors within the stomach
- Decreased firing frequency of the vagal nerve to the solitary nucleus.
- Solitary nucleus relays information to the arcuate nucleus within the hypothalamus
- Activates the lateral hypothalamic nucleus via orexigenic factors
- Supresses the ventromedial nucleus via the anorectic factors.
Which nucleus relays information to the arcuate nucleus?
Solitary nucleus
Which nucleus is activated during hunger?
Lateral hypothalamic nucleus
Which factors are released during hunger from the lateral hypothalamic nucleus?
Orexigenic factors
Which centres are suppressed during hunger?
Ventromedial nucleus
Which hormone is released during hunger?
Ghrelin - stimulates the arcuate nucleus
What effect does leptin have on appetite sensation?
Inhibits appetite sensation (binds to leptin receptors on both NPY and POMC neurones)
Which peptide is released from POMC neurones?
POMC neurones of the arcuate nucleus release alpha-MSH peptides which induce an anorexigenic effect
What type of effect is exerted by alpha-MSh neurones?
Anorexigenic effect on the paraventricular nucleus
What type of receptors does alpha-MSH bind to?
MC-4, triggers the sensation of satiety
What happens in an NPY and Agrp mutation?
This is associated with reduced appetite.
What is the effect of a POMC deficiency or MC4-R mutation?
Cause obesity given that the induction of satiety is lost
Which cells release leptin and circulating hormones?
Adipocytes
Which tissue synthesises leptin?
White adipose tissue
What is the effect of leptin?
Regulate intake and thermogenesis by inhibiting orexigenic neurones (NPY, AGRP) within the arcuate nucleus and lateral hypothalamic area
Stimulates the anorexigenic neurones
What is congenital leptin deficiency?
There is a significant reduction in circulating leptin, thus the inhibitory effect on orexigenic neurones is lost - promoting feeding behaviour and intake
Manifests as severe early age obesity
What is the treatment of congenital leptin deficiency?
Leptin injections can reduce body weight
What is the relationship between serum leptin and body fat?
Serum leptin is higher in comparison to baseline patients in obesity, suggesting that hypothalamus is insensitive to endogenous leptin production
What is the effect of Ghrelin?
Stimulates appetite and increases gastric emptying
- Directly modulates neurones in the arcuate nucleus. Stimulates NPY/Agrp neurones.
- Inhibits POMC neurones.
- Increases appetite
- Regulation of reward, taste sensation memory, circadian rhythm
What is the relationship between plasma ghrelin and pre-prandial?
Plasma ghrelin increases twofold pre-prandially
Decreases thereafter post-prandially
What rhytmn is exhibited by ghrelin inter-prandially?
Diurnal
Which cells secrete peptide YY?
Enteroendocrine L cells, throughout the mucosa of the terminal ileum, colon and rectum
What is the effect of peptide YY?
Increases post-prandially, to reduce appetite and food intake
Inhibits NPY orexigenic release
Stimulates POMC anorexigenic releases
N.B: Also reduces intestinal motility, gall bladder contractions and inhibits pancreatic exocrine secretion.
-Can cause nausea.
What comorbidities are associated with obesity?
Depression Sleep apnoea Bowel cancer Stroke Osteoarthritis Gout Peripheral vascular disease Diabetes Hypertension MI
