Appetite Regulation Flashcards
(36 cards)
what are the stimuli for thirst
which is the most potent
increase in plasma osmolality
reduction in blood volume
reduction in blood pressure
increased plasma osmolality is the most potent
a 2-3% increase in plasma osmolality induces strong desire to drink
a 10-15% decrease in blood volume or blood pressure is needed to induce the same strong desire to drink
how is plasma osmolality regulated
plasma osmolality increases → osmoreceptors in organum vasculosum and subfornical organ (in hypothalamus) shrink → increases the proportion of active cation channels on cell membrane → +ve charge influx → membrane depolarises
osmoreceptors send APs which stimulate ADH release from posterior pituitary
ADH enters blood → travels to kidney
ADH binds to V2 receptor on collecting duct → triggers vesicles of Aquaporin 2 channels to insert themselves into apical membrane
increased water reabsorption → small volume of concentrated urine is released
plasma osmolality decreases → osmoreceptors swell → cation channels inactive → hyperpolarisation → no APs can be generated → no ADH is released
less water reabsorbed in collecting duct → large volume of dilute urine is produced
Note: cation channels are inactivated by stretch
what is important to note about the reasons someone may feel thirst
not always physiological → e.g. not always due to high plasma osmolality/low blood pressure/low blood volume
can be prompted by habit, alcohol, caffeine, drugs, wanting warming or cooling drinks
what is the issue that arises surrounding being relieved of thirst after drinking
how is this overcome
there is a delay between the absorption of water in the GI tract and the correction of plasma osmolality (takes time for the water absorbed to then circulate around the body) → therefore there needs to be a mechanism in place to prevent over drinking
therefore thirst is decreased by drinking before sufficient water has been absorbed by the GI tract to correct plasma osmolality
receptors in mouth, pharynx, oesophagus provide short lived relief of thirst sensation when you drink
however thirst is only completely satisfied once plasma osmolality/blood volume/blood pressure has been corrected
where are the receptors which provide relief from thirst
why are they necessary
mouth, pharynx, oesophagus
time delay between the absorption of water in the GI tract and the correction of plasma osmolality/blood volume/blood pressure which stops the person feeling thirsty anymore/complete satisfaction of thirst
the receptors provide short lived relief of thirst to prevent over drinking/ fluid overload because that can interfere with nutrient absorption as it can cause hyponatremia (and much of the nutrient transport is driven by sodium) and it is a waste of energy for the kidneys to filter all the excess fluid
how are changes in blood pressure or blood volume corrected
via the renin-angiotensin-aldosterone system
reduced blood pressure/blood volume → reduction in renal perfusion pressure → detected by baroreceptors → juxtaglomerular cells release renin
(NOTE: renin release can also be stimulated by reduced Na+ delivery to DCT and this is detected by macula densa or increased sympathetic stimulation of JGA cells via B1 adrenergic receptors)
renin cleaves angiotensinogen (produced by liver) → angiotensin I
angiotensin I is cleaved by Angiotensin Converting Enzyme (ACE is mainly produced by lungs and this process occurs in lungs) → angiotensin II
angiotensin II:
induces thirst
stimulates ADH secretion → increased H2O reabsorption
stimulates sympathetic nervous system → vasoconstriction → increased blood pressure
stimulates release of aldosterone from zona glomerulosa in adrenal cortex
aldosterone acts on cells n DCT → increased Na+ reabsorption and K+ excretion → water retention
blood pressure/blood volume increases
what is the clinical importance of RAAS
ACE inhibitors, ARBs and direct renin inhibitors are used to treat hypertension
describe weight homeostasis
changes to adipose tissue activate responses which favour the return to their previous/original weight
if fat mass reduces or person is underfed → activates systems which:
reduce energy expenditure
reduce sympathetic activity
reduce energy expenditure
increase hunger/food intake
decrease thyroid function
in order to cause subject to gain weight
if fat mass increases or person is overfed → activates systems which:
increase energy expenditure
increase sympathetic activity
increase hunger/food intake
in order to cause weight loss
outline how peripheral stimuli influence appetite
through the hypothalamus
hypothalamus links higher brain centres e.g. amygdala and peripheral neuronal input and hormones e.g. leptin, ghrelin and PYY
peripheral neuronal input is via the vagus nerve to brainstem → brainstem communicates with hypothalamus → hypothalamus communicates with higher brain centres
nuclei in hypothalamus have incomplete blood brain barrier → hormones from the periphery in the systemic circulation can act on hypothalamic neurons
hypothalamus generates a response to the information from peripheral stimuli to influence food intake and energy expenditure
what are the different areas of the hypothalamus involved in appetite regulation
what do they contain
arcuate nucleus - aggregation of neurons in medial basal area of hypothalamus (adjacent to 3rd ventricle) → has orexigenic neurons and anorectic neurons which project to paraventricular nucleus
paraventricular nucleus - contains neurons which project to posterior pituitary and secrete oxytocin and ADH from posterior pituitary
lateral hypothalamus - only contains orexigenic neurons
ventromedial hypothalamus - associated with satiety
define orexigenic
appetite stimulant
define anorectic
appetite suppressant
what do lesions in this area cause
why
ventromedial hypothalamus
lesions in rats cause obesity as the ventromedial hypothalamus is associated with inducing satiety
melanocortins here regulate feeding behaviour
debate about role in humans
how is the arcuate nucleus involved in appetite regulation
integrates central and peripheral feeding signals (from within and outside CNS) to coordinate an appropriate feeding response
contains orexigenic and norectic neurons which project into the paraventricular nucleus
the blood brain barrier is incomplete here → allows peripheral hormones in systemic circulation to access the arcuate nucleus
orexigenic neurons (stimulatory) → neuropeptide Y and AGRP neurons → increase food intake by releasing neuropeptide Y and by releasing AGRP which is a melanocortin receptor antagonist they are inhibited by leptin, insulin and peptide YY (stimulated by low insulin + leptin levels)
anorectic neurons (inhibitory) → POMC neurons → decrease food intake by releasing alpha-MSH they are stimulated by leptin and insulin and inhibited by NPY
what conditions would stimulate orexigenic neurons
why
conditions which decrease leptin and or insulin levels as leptin and insulin inhibit orexigenic neurons
diabetes, fasting, genetic leptin deficiency
label the neurons and stimulus and location
what are the main roles of the arcuate nucleus
feeding
cardiovascular regulation
fertility
explain the role of the melanocortin system in feeding
central regulator of energy balance → involved in feeding behaviours + energy expenditure
melanocortin-4 receptors are expressed in paraventricular nucleus
when POMC neurons from arcuate nucleus are stimulated they release alpha-MSH (breakdown product of POMC) which binds to MC4 receptors
produces anorectic effect by triggering sensation of satiety
(AGRP/NPY neurons when stimulated release NPY → inhibits POMC and AGRP is MC4 receptor antagonist )
serotonin also upregulates alpha MSH
what genetic mutations will affect appetite
what effect will these have
there are no NPY or AGRP mutations associated with appetite in humans
POMC deficiency + melanocortin-4 receptor mutations → morbid obesity (as there is no appetite inhibition)
however the high prevalence of obesity in the population is not due to mutations
how are regions in the brain (other than the arcuate nucleus) involved in appetite
higher centres → amygdala control reward motivation pathways which has strong effect on appetite (hypothalamus is linked to amygdala)
other parts of the hypothalamus → lateral hypothalamus containing orexigenic neurons, ventromedial hypothalamus involved in satiety, paraventricular hypothalamus contains neurons which project to other brain areas and where arcuate nuclei neurons terminate
brain stem → receives neuronal information from the periphery via the vagus nerve e.g. when stomach is stretched when full
what is the adipostat mechanism
circulating hormones e.g. leptin are released into blood by the adipocytes in adipose tissue
the arcuate nucleus detects the level of these circulating hormones and alters appetite levels using neuropeptides accordingly and alters energy expenditure
energy expenditure refers to thermogenesis
increased levels of circulating hormones → decreased appetite + increased energy expenditure (thermogenesis)
aims to keep fat mass within tight range despite changes to diet or daily activity
where is leptin produced
where does it act
what are it functions
produced in white adipose tissue and small intestinal enterocytes
more adipose tissue = more leptin
circulates in plasma
hypothalamus → binds to receptors in arcuate nucleus and ventromedial hypothalamus → in arcuate nucleus it inhibits NPY/AGRP neurons and stimulates POMC neurons → reduced appetite and leptin binds to receptors in ventromedial hypothalamus → satiety
mainly role is to decrease appetite and increase thermogenesis through acting on the hypothalamus
involved in atherosclerosis due to its effects on macrophages particularly
low levels of leptin found in people with depression + alzheimer’s
what effect does congenital leptin deficiency have on the body
very rare mutation
babies are born at normal weight
don’t produce leptin → no inhibitory effect on orexinergic neurons or stimulatory effect on anorectic neurons → constantly have an appetite and don’t feel satiated → become severe early age obesity
increasing their levels of leptin with injections helps them lose weight
how would you be able to tell if someone was obese due to complete leptin deficiency or not
obese individuals have more adipose tissue → very high levels of leptin in their blood
but people who have complete leptin deficiency → have very low/no leptin in their blood compared to what would be expected
also complete leptin deficiency is very rare
