Appetite Flashcards
What are the three stimulus for the control of thirst?
Body fluid osmolality
Blood volume reduction
Blood pressure reduction
What is the most potent stimulus for the control of thirst?
Body fluid osmolality, change by 2-3% in comparison to 10-15%
When plasma ADH is high what is the effect on the volume of urine excreted?
A small volume of urine is excreted
When plasma ADH is low what is the effect on the volume of urine that is excreted?
A large volume of urine is excreted
How does ADH act to regulate osmolality?
Acts on kidneys to regulate the volume and osmolality of urine by upregulation/down regulation of Aquaporin2 channels in the collection duct
Where is ADH stored?
Posterior pituitary
What type of receptors are osmoreceptors, what is their function and where are they found?
They are sensory receptors, involved in osmoregulation and found in the hypothalamus
Cell shrinkage due to a high plasma concentration causes fluid retention and invokes drinking, how?
The cells shrink meaning the proportion of cation channels increases causing the membrane to depolarise, this sends signals to the ADH producing cells to increase ADH secretion
How is the sensation of thirst satisfied?
Receptors in mouth, pharynx and oesophagus are involved before water has been absorbed by the GI tract and relief of the thirst sensation via these receptors is short lived.
Thirst is only completely satisfied once plasma osmolality is decreased or blood volume/ arterial pressure is corrected
How does a decreased blood pressure result in H20 retention? (RAAS )
A low blood pressure is detected by the juxtaglomerular cells of the renal afferent arteriole
Juxtaglomerular cells secrete renin
Renin acts on angiotensin -> angiotensin 1
ACE from the vascular endothelium of lungs and kidneys act on angiotensin1 -> angiotensin2
Angiotensin2 acts to increase Na+/H exchange, increasing sodium reabsorption, increasing osmolarity of the blood
Angiotensin2 acts on zona glomerulosa cells of the adrenal cortex to stimulate aldosterone release which causes H2O retention
How does aldosterone secretion result in H2O retention?
Via Na+ Cl- absorption and K+ excretion
Where is ACE found?
In the vascular endothelium of the kidneys and lungs
Where is angiotensin produced?
The liver
The conversion of angiotensin1 to angiotensin2 is catalysed by which enzyme?
Angiotensin converting enzyme (ACE)
How does angiotensin2 exert its affects?
By binding to angiotensin 2 type 1 and angiotensin2 type 2 receptors in the brain, kidney, adrenal cortex, and arterioles
How does aldosterone work?
By stimulating the insertion of luminal Na channels and basolateral Na-K ATPase proteins
What mechanisms are there to manage excessive fluid intake?
Receptors in mouth, pharynx and oesophagus relieve thirst sensation initially to avoid overload
Weight homeostasis favours ________ weight
Stable weight
If weights reduces:
> ↓ sympathetic activity
↓ energy expenditure
↓ thyroid activity
↑ hunger/foot intake
If weight increases?
> ↑ sympathetic activity
↑ energy expenditure
↓ hunger/food intake
How does the central circuit defend against reduction in body fat?
Via leptin
The regulation of appetite occurs in _____, peripheral input for appetite reaches the brain via ______
The hypothalamus
The vagus nerve
What are the key gut hormones in appetite regulation?
Ghrelin and PYY
How does the hypothalamus regulate appetite through the arcuate nucleus?
Arcuate nucleus produces orexigenic and anorectic peptides
The hypothalamus regulates appetite as the paraventricular nucleus produces what hormone?
ADH
the lateral hypothalamus produces what to regulate appetite?
Orexigenic factors
The ventromedial hypothalamus is associated with satiety due to what?
Melanocortins
What is the arcuate nucleus?
Collection of neurones in the medial-basal part of the hypothalamus
Where is the arcuate nucleus located?
In the hypothalamus adjacent to the 3rd ventricle
What is the function of the arcuate nucleus?
Production of orexigenic and anorectic peptides
What are orexigenic peptides?
Appetite stimulant peptides
What are anorectic peptides?
Appetite suppressant peptides
What is the paraventricular nucleus?
Collection of neurons around the third ventricle in the hypothalamus
What hormones are produced in the paraventricular nucleus?
ADH and oxytocin
What happens to food intake when pro-opiomelanocortins are activated?
Decreases
What 3 other hypothalamic factors are involved in appetite?
Cannabinoids, AMP activated protein kinase, protein thyrosine phosphatase
The arcuate nucleus blood brain barrier has what adaptation and why?
Is incomplete, allows access to peripheral hormones
What are the two neuronal populations in the arcuate nucleus?
Stimulatory - NPY , AGRP neurone
Inhibitory - POMC neurone
From which gene are melanocortins produced?
POMC
The melanocortin system is a __________ of energy balance?
Central regulator - feeding behaviours and energy balance
What molecule is expressed by the paraventricular nucleus in the melanocortin system and what effect does this have?
Serotonin stimulus causes expression of MC4R leading to a reduction of appetite and decreased food intake
How can CNS mutations affect appetite?
• No NPY or Agrp mutations associated with appetite discovered in humans
• POMC deficiency and MC4-R mutations cause morbid obesity
• Mutations not responsible for the prevalence of obesity - but useful to explain signalling
What is the adipostat mechanism?
mechanismby which the brain detects and maintains constant levels of energy stored in adipocytes in the form of lipids
• Circulating hormones produced by fat - LEPTIN
how does the adipostat mechanism work?
• Circulating hormones produced by fat - LEPTIN
• Hypothalamus senses the concentration of hormone
• Hypothalamus then alters neuropeptides to increase or decrease food intake.
• Perhaps a problem with the regulation of the adipostat mechanism leads to obesity?
Where is leptin produced?
Adipose tissue and enterocytes
Where does leptin act on? What affect?
Receptors in arcuate and ventromedial nuclei of hypothalamus.
Decreases appetite and increases thermogenesis
What are the effects of a congenital leptin deficiency?
can lead to severe obesity in early life
• subjects carrying mutation are born with normal weight but are constantly hungry
• gain weight quickly
• only a few people are known to have this effect
How does leptin vary with body fat?
Low when low body fat
High when high body fat
How does high leptin lead to obesity?
High leptin due to high body fat therefore become leptin resistant so leptin becomes ineffective as a weight control drug
What is the affect of Ghrelin?
Stimulates appetite, increases gastric emptying
What is the affect of peptide YY (PYY)?
Inhibits food intake
When are blood levels of Ghrelin highest? why
Before meals, help prepare for food intake by increasing gastric motility and acid secretion
What affect does Ghrelin have on neurones in the arcuate nucleus?
Stimulates NPY/Agrp neurones
Inhibits POMC neurones
Ghrelin is a regulator of_______
Reward, taste sensation, memory and circadian rhythm
Where is peptide YY released and why?
Released in the terminal ileum and colon in response to feeding
Food arriving to the terminal ilium and colon results in what?
PYY release, inhibition of NPY release, stimulations of POMC neurons
What are the comorbodities associated with obesity?
Depression, sleep apnoea, bowl cancer, osteoarthritis, diabetes, stroke, hypertension, gout, peripheral vascular disease, MI
What is the major CNS region regulating thirst and hunger?
The hypothalamus
