🍔Gastro🍔 - Appetite & Thirst Flashcards
What are the common stimuli of thirst?
Body fluid osmolality increases
Blood volume reduced
Blood pressure reduced
What is the most potent stimulus for thirst?
Blood fluid osmolality strongest by far
What hormone regulates osmolality?
Antidiuretic hormone (ADH)/Vasopressin
What is the mechanism of action of ADH?
Acts on the kidneys to regulate the volume & osmolality of urine
Collecting duct - Aquaporin 2 channel
When plasma ADH is low a large volume of urine is excreted (water diuresis)
When plasma ADH is high a small volume of urine is excreted (anti diuresis)
Where is ADH stored?
Posterior pituitary gland
Which receptors are responsible for the regulation of body fluid osmolality?
Osmoreceptors
Outline osmoreceptors
Sensory receptors
Osmoregulation
Found in the hypothalamus
Which regions of the hypothalamus are osmoreceptors found?
Organum vasculosum of the lamina terminalis (OVLT)
Subfornical Organ (SFO)
How do osmoreceptors detect osmolality and affect ADH release?
Cells shrink when plasma more concentrated (water leaves via osmosis)
Proportion of cation channels increases – membrane depolarizes
Send signals to the ADH producing cells to increase ADH production
Leads to fluid retention and increased thirst
Opposite happens when plasma is less concentrated
Explain how the sensation of thirst works
Thirst is decreased by drinking even before sufficient water has been absorbed by the GI tract to correct plasma osmolality
Receptors in mouth, pharynx, oesophagus are involved
Relief of thirst sensation via these receptors is short lived
Thirst is only completely satisfied once plasma osmolality has decreased or blood volume or arterial pressure corrected
Explain how the body reacts to decreased blood pressure, in the context of fluid homeostasis
BP decreases sensed by juxtaglomerular cells - secrete renin
Activates renin-angiotensin system
Angiotensin II Stimulats thirst, vasoconstriction by increasing sympathetic activity, ADH and aldosterone secretion
Aldosterone causes H2O retention via
Na+CL- absorption and K+ excretion
What is the overarching mechanism for body weight homeostasis?
Using the “Biggest Loser” tv show as a study, what phenomenon was exhibited by the contestants that meant most returned to somewhere near their “pre-diet” weight?
Metabolic adaptation to dieting
Decreased caloric intake lead to a long-term reduction in resting metabolic rate
Which area of the brain is responsible for homeostasis of food intake and energy expenditure?
Hypothalamus
Lateral hypothalamus (feeding centre) - stimulates food intake
Ventromedial hypothalamus (satiety centre) - suppresses appetite
Paraventricular nucleus - integrates orexigenic (appetite-stimulating) and anorectic (appetite-suppressing) signals
Arcuate nucleus - key area for processing feeding signals
Which inputs influence the hypothalamus in the context of balancing food intake and energy expenditure?
Gut hormones - ghrelin, PYY, GLP-1, and others
Neural input - from peripheral systems and other brain regions
Leptin - hormone involved in signalling satiety and energy balance
Outline the arcuate nucleus in more detail
The arcuate nucleus is crucial in food intake regulation
Unique features:
-An incomplete blood-brain barrier, allowing interaction with peripheral hormones
-Integrates signals from the body (periphery) and brain (central)
Two types of neurons in the arcuate nucleus:
-NPY/AGRP neurons - stimulate appetite
-POMC neurons - suppress appetite
Which neuronal population in the arcuate nucleus will leptin stimulate?
POMC neurons to suppress appetite
Outline the effects of AGRP and POMC neurons on the melanocortin system
What other brain regions can influence food intake and energy expenditure?
Higher centres - Amygdala - emotion, memory
Other parts of the hypothalamus, e.g. lateral hypothalamus
Vagus to brain stem to hypothalamus
What hormone other than leptin is produced by fat?
Adipostat
What is the mechanism of adipostat?
Circulating hormone produced by fat
Hypothalamus senses the concentration of adipostat
Hypothalamus then alters neuropeptides to increase or decrease food intake
What is leptin?
Circulates in plasma
Acts on the hypothalamus regulating appetite (intake) and thermogenesis (expenditure)
Where is leptin secreted and what is its actions?
Secreted from white adipose tissue & gastric mucosa
Reflects energy reserves:
Low when low body fat
High when high body fat
Also increases acutely post-prandially (gastric source)
Decreases food intake and increases thermogenesis
What problems with leptin can arise?
Decreased leptin expression/secretion in adipose tissue
Leptin receptor absence
Reduced sensitivity of leptin receptor
How does leptin resistance arise?
Leptin circulates in plasma in concentrations proportional to fat mass
Overweight humans have chronically high levels of leptin - leads to resistance (just like insulin)
Obesity due to leptin resistance –
hormone is present but doesn’t signal effectively
Why is leptin ineffective as a weight control drug?
Increasing leptin levels will cause leptin receptors to become less sensitive to it
What is responsible for short term regulation of appetite (i.e. following a meal)?
Gut hormones
What are the gastrointestinal (gut) hormones?
Ghrelin - stimulates appetite
Peptide YY (PYY) and GLP-1
Secreted byenteroendocrine cellsin thestomach, pancreas & small bowel
Control various functions of digestive organs
Outline ghrelin
Blood levels of ghrelin are highest before meals - help prepare for food intake by increasing gastric motility and acid secretion
Increases appetite
Involved in regulation of reward, taste sensation, memory & circadian rhythm
How does ghrelin modulate neurons?
Directly modulates neurons in the arcuate nucleus:
-Stimulates NPY/AGRP neurons.
-Inhibits POMC neurons.
Outline PYY
Short peptide released in the terminal ileum (TI) and colon in response to feeding (36 Amino acids)
Reduces appetite – can be digested or injected IV
Food arriving to the TI and colon results in PYY release
What effect does PYY have on neurons?
Stimulates POMC neurons
Inhibits NPY release
Outline GLP-1
Short peptide released in the gut in response to feeding (30 Amino acids)
Reduces appetite
Incretin – increases insulin release in response to ingested glucose
What are the comorbidities associated with obesity?
How does genetics link to obesity?
Monogenic obesity is very rare (<0.1%)
Genetic factors can explain over 40% of the variance in obesity
Around 250 genes are associated with obesity
‘Thrifty genes’ designed to protect us from starvation by allowing us to store energy when food is abundant
Environmental factors can also affect expression of genes via ‘epigenetics’
