(gastro) appetite Flashcards
how does the body control thirst? (3)
- increase in plasma osmolality
- reduction in blood volume
- reduction in blood pressure
which is the most potent stimulus for thirst control and how?
plasma osmolality increase is the more potent stimulus
= change of 2-3% induces a strong desire to drink
how do changes in plasma osmolality compare to changes in blood volume and arterial pressure?
plasma osmolality = needs to increase by 2-3% maximum to induce strong thirst
but decreases of 10-15% are required in blood volume or arterial pressure to have the same effect
which hormone is responsible for the regulation of osmolality?
ADH (anti-diuretic hormone)
(i.e. vasopressin)
what is ADH and what is it alternatively known as?
anti-diuretic hormone
= alternatively known as vasopressin
where does ADH act in the kidney?
acts on the basolateral membrane of the renal collecting duct cells
(specifically, the V2 receptors)
what is the function of ADH?
regulates the volume and osmolality of urine by stimulating water reabsorption from the renal collecting duct, back into the systemic circulation
= concentrating the urine
what happens as a result of low plasma ADH?
a large volume of urine is excreted (water diuresis)
what happens as a result of high plasma ADH?
a small volume of urine is excreted (anti-diuresis)
where is ADH stored?
posterior pituitary gland
what is water diuresis and when does it occur?
when the plasma ADH levels are low, less water reabsorption occurs so larger volumes of more dilute urine are produced
what is anti-diuresis and when does it occur?
when the plasma ADH levels are high, more water reabsorption occurs so smaller volumes of more concentrated urine are produced
how is the osmolality of the plasma detected?
osmoreceptors (sensory receptors) on the surface of the neurones of the hypothalamus
= detect changes in plasma osmolality
what are osmoreceptors?
sensory receptors that detect changes in plasma osmolality
where are osmoreceptors found?
found on the surface of specific hypothalamic neurones
(in the OVLT, SFO of the hypothalamus)
what are osmoreceptors responsible for?
osmoregulation
= altering ADH secretion into the systemic circulation to either increase or decrease water reabsorption
which two hypothalamic regions contain osmoreceptors?
OVLT (organum vasculosum of the lamina terminalis)
SFO (subfornical organ)
which of the two hypothalamic osmoreceptor regions has a greater effect?
OVLT (organum vasculosum of the lamina terminalis)
explain the process by which osmoreceptors regulate ADH release in a hypertonic environment
hypertonic solution (more concentrated than the intracellular fluid)
= cell shrinkage (as water moves out of the cell via osmosis)
= increased proportion of active cation channels
= increase influx of positive charge
= depolarisation
= increased action potential firing frequency
= increased signals to ADH releasing neurones
= increased ADH secretion
= stimulates fluid retention and invokes drinking
explain the process by which osmoreceptors regulate ADH release in a hypotonic environment
hypotonic solution (less concentrated than the intracellular fluid)
= cell expansion (as water moves into the cell via osmosis)
= reduced proportion of active cation channels
= reduced influx of positive charge
= hyperpolarisation
= reduced action potential firing frequency
= reduced signals to ADH releasing neurones
= reduced ADH secretion
= increased fluid loss
how does the neuronal response differ in a hypertonic environment compared to that of a hypotonic environment?
in a hypertonic environment = cell shrinkage leads to depolarisation and increases stimulation of ADH secretion
in a hypotonic environment = cell expansion leads to hyperpolarisation and decreases stimulation of ADH secretion
when the plasma osmolality is increased, how do the neurones respond?
neurones shrink and the proportion of active cation channels in the membrane increases
why does the proportion of active cation channels increase when plasma osmolality is high?
a hypertonic solution stimulates the movement of water out of the neurone, causing neuronal cell shrinkage
= increases the number of active cation channels in the membrane
how does ADH secretion increase when plasma osmolality is high?
increased plasma osmolality
= cell shrinkage
= increased number of active cation channels in the neuronal membrane
= depolarisation
= increased firing rate to stimulate increased ADH secretion
what does high plasma ADH stimulate?
fluid retention and invokes drinking
when the plasma osmolality is decreased, how do the body cells respond?
neurones expand and the proportion of active cation channels in the membrane decreases
what is the impact of cell expansion on the proportion of active cation channels?
the proportion of active cation channels in the membrane decreases
how does ADH secretion decrease when plasma osmolality is low?
reduced plasma osmolality
= cell expansion
= reduced number of active cation channels in the neuronal membrane
= hyperpolarisation
= reduced firing rate to reduce ADH secretion
what does low plasma ADH stimulate?
fluid loss = diuresis
how does a hypotonic environment lead to hyperpolarisation of neurones?
hypotonic = cell expansion = reduced number of active cation channels = reduced influx of positive charge = hyperpolarisation
what is the impact of hyperpolarisation on ADH secretion?
reduced neuronal firing rate
= reduce stimulation of ADH secretion
= reduced plasma ADH
what is the impact of depolarisation on ADH secretion?
increased neuronal firing rate
= increased stimulation of ADH secretion
= increased plasma ADH
how quickly are changes in osmolality corrected by drinking water?
not rapidly
= delay in absorption of water in GI tract and subsequent correction of osmolality
how is thirst decreased? (2)
1) partial decrease in thirst = osmoreceptors in the mouth, pharynx and oesophagus detect water intake and decrease thirst partially
2) complete decrease in thirst = once plasma osmolality returns to normal or blood volume/arterial pressure
explain how thirst is partially decreased
osmoreceptors in the mouth, pharynx and oesophagus detect water intake and decrease thirst partially
= relief of thirst sensation via these receptors is short-lived
explain how thirst is fully decreased
only when plasma osmolality returns to normal or blood volume or arterial pressure is corrected, thirst is fully decreased
which receptors are involved in the partial decrease of thirst?
receptors in mouth, pharynx, oesophagus
= thirst relief from these receptors in short-lived (partial)
when and how is thirst fully decreased?
thirst is only completely satisfied once plasma osmolality is decreased or blood volume or arterial pressure corrected
explain what happens when the blood pressure decreases, in the context of RAAS
blood pressure decreased
= renal afferent arteriole hypoperfusion
= increased renin secretion from the juxtaglomerular cells (of renal afferent arteriole)
= increased conversion of angiotensinogen to angiotensin I in the liver
= angiotensin I conversion into angiotensin II via ACE in the lungs
= angiotensin II increases aldosterone secretion, stimulates sympathetic activation and arteriole vasoconstriction among other things
which cells respond to the decrease in blood pressure and why?
juxtaglomerular cells of renal afferent arteriole
= detect hypotension due to hypoperfusion of the renal afferent arteriole
how do the juxtaglomerular cells respond to hypotension?
increased renin secretion into the systemic circulation
what is renin and what is it alternatively known as?
renin is an enzyme secreted by the kidneys and is responsible for converting angiotensinogen into angiotensin I in the liver
(also known as an angiotensinogenase)
which cells release renin and why?
juxtaglomerular cells of renal afferent arteriole
= response to the renal hypoperfusion
what is the function of renin?
responsible for converting angiotensinogen into angiotensin I in the liver
where is angiotensin I produced?
in the liver
how is angiotensin I produced?
renin cleaves angiotensinogen in the liver to form the physiologically inactive precursor, angiotensin I
where is angiotensin II produced?
capillary blood vessels/vascular tissue of the lungs
(site of most ACE expression and most angiotensin II production in the body)
how is angiotensin II produced?
the enzyme ACE in the lung vascular tissue is responsible for converting angiotensin I into angiotensin II in the lung capillaries
what converts angiotensinogen into angiotensin I?
renin (angiotensinogenase)
what converts angiotensin I into angiotensin II?
ACE (angiotensin-converting enzyme)
where is angiotensinogen found?
produced in the liver and is found continuously circulating in the plasma
what are the impacts of increased angiotensin II secretion?
neurovascular effects
- increased sympathetic activation
- increased arteriole vasoconstriction
endocrine effects
- increased ADH secretion from the PPG
- increased aldosterone secretion from the zona glomerulosa of the adrenal cortex
renal effects
- (increased aldosterone) results in increased Na+ retention and K+ excretion
- increased salt retention results in increased H2O retention
how does angiotensin II impact aldosterone secretion?
increased aldosterone secretion from the zona glomerulosa of the adrenal cortex
where does angiotensin II act in the adrenal cortex and why?
acts on the zona glomerulosa of the adrenal cortex
= to increase aldosterone production to then increase Na+ reabsorption and K+ excretion
what are the impacts of increased aldosterone secretion?
increase Na+, Cl- reabsorption and K+ excretion
= to stimulate H2O retention to increase blood volume
what impact does angiotensin II have on the renal collecting duct?
increase tubular Na+, Cl- reabsorption and K+ excretion
= to stimulate H2O retention to increase blood volume
what impact does angiotensin II have on the posterior pituitary gland?
stimulates ADH secretion from the posterior pituitary gland
what impact does angiotensin II have on the arterioles and why?
stimulates arteriole vasoconstriction
= to increase blood pressure
what impact does angiotensin II have on the autonomic nervous system?
stimulates sympathetic nervous system activation
which two drugs are used to treat hypertension that affect RAAS?
direct renin inhibitors and ACE inhibitors
how do variations in fat mass affect food intake and energy expenditure?
reduction in fat mass increases food intake and reduces energy expenditure
increases in fat mass (i.e. adipose tissue expansion) decreases food intake and increases energy expenditure
what happens to food intake and energy expenditure when fat mass reduces?
reduction in fat mass increases food intake and reduces energy expenditure
what happens to food intake and energy expenditure when adipose tissue expands?
adipose tissue expansion reduces food intake and increases energy expenditure
how does the body respond to the overfed, weight augmented state?
increased sympathetic activation
increased energy expenditure
reduced hunger and food intake
= weight loss
how does the body respond to the underfed, weight reduced state?
reduced sympathetic activation
reduced energy expenditure
increased hunger and food intake
(reduced thyroid function)
= weight gain
which cerebral structure is responsible for appetite regulation?
hypothalamus
which hormones are responsible for appetite regulation?
short-term
- ghrelin
- peptide YY (PYY)
long-term
- leptin
explain how gut hormones have an effect on higher brain structures
ghrelin + PYY
= peripheral stimulation that travels via vagus nerve to the brainstem
= then onto the hypothalamus
= then onto the higher CNS centres of brain e.g. amygdala
how does the hypothalamus regulate appetite?
- receives all trigger (ghrelin, PYY, leptin, neural input from the periphery)
- synthesises response to them by regulation food intake or increasing/decreasing energy expenditure
which factors does the hypothalamus alter to regulate appetite?
food intake
energy expenditure
where is the arcuate nucleus found?
located at the base of the hypothalamus on either side of the third ventricle
(in the medial-basal part of the brain)
what is the arcuate nucleus?
aggregation of neurones in the medial-basal part of the
adjacent to 3rd ventricle
= involved in the regulation of food intake
what is the most important terminal field of the arcuate nucleus and why is this important?
most important terminal field is the paraventricular nucleus (also adjacent to the third ventricle)
= has neurones that project onto the posterior pituitary gland where ADH is stored
what is the paraventricular nucleus and why is this important?
adjacent to the third ventricle
many of its neurons project to the posterior pituitary + secrete oxytocin and a smaller amount of ADH
where is the paraventricular nucleus found?
the hypothalamus, adjacent to the third ventricle
what is the orexigenic effect?
appetite-increasing
what is the anorexigenic effect?
appetite-reducing
what do posterior pituitary gland neurones release?
oxytocin and ADH
what are the two divisions of the hypothalamus that are important in appetite regulation?
lateral hypothalamus
ventromedial hypothalamus
what is the function of the lateral hypothalamus?
only produces orexigenic peptides
= appetite-increasing effect
what is the function of the ventromedial hypothalamus?
associated w satiety
what is likely to happen if there is a lesion to the ventromedial hypothalamus?
lesions in this region can lead to severe obesity (seen in rats)
name some hypothalamic factors implicated in appetite regulation
endocannabinoids
AMP-activated protein kinase
protein tyrosine phosphatase
how is the arcuate nucleus adapted to interact with peripheral hormones?
has an incomplete blood-brain barrier
= allows access to peripheral hormones
how many neuronal populations are there in the arcuate nucleus and what are they called?
two: one stimulatory population, one inhibitory population
- stimulatory = NPY/Agrp neurone
- inhibitory = POMC neurone
what is the stimulatory neuronal population in the arcuate nucleus?
NPY/Agrp neurone
(neuropeptide Y/Agouti-related peptide)
what is the inhibitory neuronal population in the arcuate nucleus?
POMC neurone
(pro-opiomelanocortin)
how do NPY/Agrp neurones stimulate appetite?
make peptides that stimulate food intake
increased NPY signalling and reduced melanocortin signalling
= more stimulation and less inhibition of appetite
which two hormones can affect the arcuate nucleus neuronal populations?
leptin and insulin
how does leptin affect the arcuate nucleus neurones?
leptin stimulates the POMC neurones (increased inhibition of appetite)
leptin inhibits the NPY/Agrp neurones (reduced stimulation of appetite)
how does leptin affect POMC neurones and what is the effect of this?
stimulates the POMC neurones
= increased inhibition of appetite
how does leptin affect NPY/Agrp neurones and what is the effect of this?
inhibits the NPY/Agrp neurones
= reduced stimulation of appetite
which conditions can cause food intake to increase by affecting the arcuate neuronal populations?
fasting, uncontrolled diabetes, general leptin deficiency
explain the impact of general leptin deficiency
leptin deficiency
= less stimulation of POMC (so less inhibition of appetite)
= less inhibition of NPY/Agrp (so more stimulation of appetite)
= collectively act to increase appetite and food intake
how do circulating factors control appetite?
circulating factors arrive at the arcuate nucleus
can penetrate into the arcuate nucleus via the incomplete blood-brain barrier
- factors stimulate the POMC neurones (to decrease appetite)
OR - factors stimulate the NPY/Agrp neurones (to increase appetite)
how can circulating factors decrease appetite?
circulating factors arrive at the arcuate nucleus and penetrate via the incomplete blood-brain barrier
= act on POMC neurones stimulating them to decrease appetite
how can circulating factors increase appetite?
circulating factors arrive at the arcuate nucleus and penetrate via the incomplete blood-brain barrier
= act on NPY/Agrp neurones stimulating them to increase appetite
explain how the melanocortin system works in terms of POMC neurones
melanocortins (e.g. aMSH) are products of POMC neurones
melanocortins will bind to MC4R, expressed in the paraventricular
= leads to reduction in appetite, weight and decreased food intake
what happens if there is a mutation in the MC4R?
fewer melanocortins will bind to the MC4R
= so less stimulation to decrease food intake
= so the opposite happens (i.e. food intake increases = fat mass increases)
how do the POMC neurones act on the MC4Rs?
POMC neurones release melanocortins such as aMSH that bind to the MC4Rs of the paraventricular nucleus and stimulate a decrease in food intake
how do the Agrp neurones act on the MC4Rs?
Agrp neurones bind to the MC4Rs of the paraventricular nucleus and inhibit the decrease in food intake (reduced inhibitory signal)
= consequently, food intake increases
which CNS mutations are known to affect appetite?
no NPY or Agrp mutations associated with appetite have been discovered in humans = so no lack of stimulation of appetite
POMC deficiency and MC4-R mutations cause morbid obesity = lack of inhibition of appetite
what is the implication of the following statement?
no NPY or Agrp mutations associated with appetite discovered in humans
no lack of/impaired stimulation of appetite
= food intake remains intact
what is the implication of the following statement?
POMC deficiency and MC4-R mutations cause morbid obesity
lack of inhibition of appetite
= food intake increases hugely
why is the amygdala important in appetite?
controls rewards and motivation pathways = strong effect on appetite
what is the lateral hypothalamus associated with?
appetite-stimulant (orexigenic) peptides produced
what is the ventromedial hypothalamus associated with?
associated with satiety
how is neuronal information carried from the GI tract to the brain?
neuronal info from GI tract carried to the brainstem via the vagus nerve and then to hypothalamus and then to amygdala
what is the adipostat mechanism?
keep an individual’s fat mass in a very narrow range despite changes in physical activity and diet
explain how the adipostat mechanism works
- adipose tissue produces circulating hormone
- hypothalamus senses the concentration of circulating hormone present
- hypothalamus then alters neuropeptides to increase or decrease food intake
how do variations in adipose tissue alter the adipostat mechanism?
= more adipose tissue
= more hormone being produced
= neuropeptides production altered to (increase or) decrease food intake
where is leptin produced?
made by adipocytes in white adipose tissue
what are the two types of adipose tissue?
white adipose tissue
brown adipose tissue
what is the function of white adipose tissue?
stores energy
what is the function of brown adipose tissue?
dissipates energy, less common
differentiate between white and brown adipose tissue
white adipose tissue = stores energy
brown adipose tissue = dissipates energy, less common
where is leptin found?
in adipose tissue
what is the function of leptin?
signals to the hypothalamus to control food intake and energy expenditure over the long term
(not from meal to meal = unlike ghrelin and PYY that act short-term)
what is the function of leptin?
signals to the hypothalamus to decrease food intake and energy expenditure over the long term (+ increase thermogenesis)
(not from meal to meal = unlike ghrelin and PYY that act short-term)
explain the pathophysiology of congenital leptin deficiency
condition that causes severe obesity beginning in the first few months of life
= reduced leptin levels
= reduced stimulation of the inhibitory POMC neurones + reduced inhibition of the stimulatory NPY/Agrp neurones
= collective effect to increased food intake
= can lead to obesity
(despite adipose tissue expanding, leptin levels do not proportionally increase)
how do serum leptin levels vary in obesity?
would expect them to be high leptin with a high amount of adipose tissue, as part of the normal physiological mechanisms BUT
= leptin production is high instead because most obese people are insensitive to endogenous leptin production
why does the body stop responding to leptin and what is the impact of this?
leptin receptor signalling defective
= decreased sensitivity to leptin
(obese people have reduced sensitivity to endogenous leptin production)
results in increased food intake
what are normal leptin levels in an individual with low body fat?
low body fat = low leptin
what are normal leptin levels in an individual with high body fat?
high body fat = high leptin
how do leptin levels vary with body fat?
leptin circulates in plasma in concentrations proportional to fat mass
what are gastrointestinal hormones?
hormones at are secrete into the GI tract to control various functions of digestive organs
where are gastrointestinal hormones produced?
secreted by enteroendocrine cells in the stomach, pancreas & small intestine
which two gastrointestinal hormones are involved in appetite regulation?
ghrelin
peptide YY
what is the function of ghrelin?
stimulates appetite, increases gastric emptying
what is the function of peptide YY?
inhibits food intake
when are ghrelin levels highest and why?
blood levels of ghrelin are highest before meals
= help prepare for food intake by increasing gastric motility and acid secretion
how does ghrelin work?
- increases appetite
- regulates reward, taste sensation, memory, circadian rhythm
where does ghrelin act?
directly modulates neurons in the arcuate nucleus
- stimulates NPY/Agrp neurons
- inhibits POMC neurons.
explain the pattern of ghrelin secretion
plasma ghrelin levels increase almost twofold before each meal time
preprandial rise and post prandial fall in ghrelin concentration
what does the preprandial rise and postprandial fall in ghrelin concentration indicate?
physiological role of ghrelin in meal initiation via increasing gastric motility and gastric acid secretion
what does the following graph indicate?
food intake increases with ghrelin dose
= associated with weight gain and increasing adiposity
what does the following graph indicate?
increased appetite and energy intake for those given a dose of ghrelin
what is PYY?
peptide YY (peptide tyrosine tyrosine)
released into the terminal ileum and colon to inhibit food intake (by acting on the hypothalamus)
when and where is PYY released?
released in the terminal ileum (TI) and colon in response to feeding
what is the function of PYY?
reduces appetite (can be digested or injected IV)
where does PYY act?
acts on the arcuate nucleus of the hypothalamus
specifically
- inhibits NPY/Agrp neurones
- stimulates POMC neurones
(bu initially released into the terminal ileum and colon)
how does ghrelin increase appetite?
ghrelin stimulates NPY/Agrp neurones and inhibits POMC neurones
how does PYY decrease appetite?
PYY inhibits NPY/Agrp and stimulates POMC
compare the mechanism of action of ghrelin to that of PYY
ghrelin stimulates NPY/Agrp neurones and inhibits POMC neurones whereas PYY does the opposite by inhibiting NPY/Agrp and stimulating POMC
what does the following graph indicate?
the more PYY released in the GI tract, the greater the reduction in food intake and the more weight reduces
what is the relationship between postprandial PYY release and calorie intake?
postprandial PYY release is proportional to the calorie intake
(greater calorie intake, greater PYY release postprandially)
what is the effect of PYY on food intake and hunger?
PYY reduces food/calorie intake
name some comorbidities associated with obesity
what are some conclusions that can be drawn from this graph?
healthy environment
- subjects who are genetically prone to obesity BUT in a healthy environment = very few will develop obesity
- subjects that are genetically resistant + in a healthy environment = very unlikely to develop obesity
toxic environment
- subjects that are genetically prone and in a toxic environment = highest risk of severe obesity
- but those genetically resistant in a toxic environment = likely unaffected
= genes + environment both affect obesity
how do ghrelin and peptide YY differ compared to leptin?
leptin = long term appetite regulation
ghrelin and peptide YY = immediate appetite regulation
