Appetite Flashcards
What are the 3 main triggers of the control of thirst?
- body fluid osmolality
- reduced blood volume
- reduced blood pressure
What is the most potent stimulus for thirst control?
Plasma osmolality
What change in plasma osmolality is required to induce thirst?
2-3%
What change in blood volume/arterial pressure is required to induce thirst?
10-15%
How does the body regulate osmolality?
Anti-diuretic hormone (ADH)/vasopressin
Where does ADH act?
- on the kidneys to regulate the volume and osmolality of urine
- collecting duct, aquaporin 2 channel
What happens when ADH is low?
large volumes of urine is excreted (water diuresis)
What happens when ADH is high?
small volumes of urine are excreted (anti-diuresis)
Where is ADH stored?
in the posterior pituitary gland
How does the body measure osmolality?
via osmoreceptors in the hypothalamus
What are osmoreceptors?
- sensory receptors
- involved in osmoregulation
- found in the hypothalamus
Where are osmoreceptors in the hypothalamus?
- Organum vasculosum of the lamina terminalis (OVLT)
- Subfornical Organ (SFO)
How is ADH release regulated in a dehydrated condition?
- cells shrink when plasma is more concentrated
- the proportion of cation channels increases, and the membrane depolarizes
- sends signals to ADH producing cells to increase ADH
- fluid retention, invokes drinking
How is ADH release regulated in a hydrated condition?
- cells expand when plasma is less concentrated
- cation channels are inhibited, the membrane is hyperpolarised
- inhibits signals
- excretion of fluid
What causes a decrease in thirst?
drinking
What detects that drinking has occured in order to stop thirst?
receptors in the mouth, pharynx and oesophagus
When is thirst completely satisfied?
when plasma osmolality is decreased or blood volume/arterial pressure is corrected
What type of relief is provided by mouth/pharynx/oesophagus receptors?
temporary
What else can prompt thirst?
- habit
- cravings
- desire
What are the negatives of excessive fluid consumption?
- energy wastage
- ## interference with nutrient absorption (dependent/driven by sodium)
What system responds to changes in blood pressure/volume?
the renin-angiotensin-aldosterone system
What happens when blood pressure drops?
juxtaglomerular apparatus secretes renin
Where is the juxtaglomerular apparatus?
the renal afferent arterioles
What happens when renin is released?
- activates the renin-angiotensin system by cleaving angiotensinogen into angiotensin I
What secretes angiotensinogen?
the liver
What happens to angiotensin I?
it is converted into angiotensin II by (angiotensin converting enzyme) in the lung
What is the effects of angiotensin II?
- induces thirst
- release of aldosterone
- ADH secretion
- vasoconstriction (sympathetic activation)
How does angiotensin II trigger the release of aldosterone?
- binds onto receptors on the intraglomerular messenger cells
- cell contraction
- release of aldosterone in the zona glomerulosa of the adrenal cortex
What does aldosterone do?
Influences: - sodium reabsorption - potassium excretion and therefore, - water retention
What happens when there is a reduction in fat mass?
- increase in food intake
- reduction in energy expenditure
- reduces the effect of the thyroid gland
- sympathetic inhibition
What happens when there is adipose tissue expansion?
- reduces food intake
- increases energy expenditure
- sympathetic activation
What is the impact of changes in adipose tissue?
activates responses that favour the return to the previous/original weight
Which part of the brain regulates hunger?
hypothalamus
What are the 2 main gut hormones involved in appetite regulation (peripheral signalling)?
- Ghrelin
- PYY
What is the long term hormonal appetite regulation?
leptin system
What are the 3 main factors involved in appetite regulation?
- Ghrelin/PYY
- neural input from periphery/other brain regions
- Leptin
What does orexigenic mean?
appetite stimulant
What does anorectic mean?
appetite supressive
What is the role of the arcuate nucleus?
- regulation of food intake
- both orexigenic and anorectic
What is the role of the paraventricular nucleus?
- neurones to the posterior pituitary (oxytocin)
- regulates appetite
What is the role of the lateral hypothalamus?
produces orexigenic peptides
What is the role of the ventromedial hypothalamus?
- satiety
What is the effect of lesions in the ventromedial hypothalamus?
severe obesity
What is the effect of arcuate nucleus pro-opiomelanocortin (POMC) neurones activate?
reduced food intake
What is also thought to be implicated in appetite regulation?
- endocannabinoids
- AMP (activated protein kinase)
- protein tyrosine phosphokinase
What is so advantageous about the arcuate nucleus?
- incomplete blood-brain barrier
- allows access to the peripheral hormones in the plasma
- able to integrate peripheral and central feeding signals
What are the 2 different types of neurones in the arcuate nucleous?
Stimulatory - Neuropeptide Y (NPY) - Agouti-related peptide (Agrp neuron) Inhibitory - pro-opiomelanocortin sensitising (POMC neuron)
Where are NPY/Agrp neurones found?
only in the arcuate nucleus
How do NPY/Agrp neurones stimulate food intake?
make peptides that:
- increasing neuropeptide Y signaling
- reducing melanocortin signaling
by AGRP release
What is ARGP?
an endogenous melanocortin receptor antagonist
What can activate NPY/Agrp neurones?
decrease in:
- leptin
- insulin
What conditions cause an increase in food intake by impacting the NPY/Agrp neurones?
- fasting
- uncontrolled diabetes
- genetic leptin deficiency
What is the arcuate nucleus involved in?
- feeding
- fertility
- cardiovascular regulation
What is the central melanocortin system?
collection of:
- NPY
- AGRP neurones
- POMC
What are melanocortins?
products of the POMC
What is an example of melanocortin
alpha-MSH
What is the role of the central melanocortin system?
central regulator of energy balance
including:
- feeding behaviours
- energy expenditure
Where are melanocortin-4 receptors expressed?
paraventricular nucleus
What stimulates melanocortin-4 receptors?
serotonin
What is the effect of the stimulation of melanocortin-4 receptors?
- reduction of appetite
- weight loss
- reduced food intake
What has a encouraging/stimulating effect on melanocortin-4 receptor?
alpha-MSH
What has a inhibiting effect on melanocortin-4 receptor?
Agrp
What is the effect of Agrp and NPY mutations?
No associated effects to appetite
What is the effect of POMC deficiency and MC4-R mutations?
causes morbid obesity
What role does the amygdala play?
controls reward related motivation pathways, affects appetite
How is neural information from the digestive tract passed on to the hypothalamus?
carried by the vagus to the brain stem and eventually the hypothalamus
What is the adipostat mechanism?
- circulating hormones are produced by adipose tissue (more=more hormone)
- sensed by the hypothalamus
- hypothalamus alters neuropeptides to change food intake
What produces leptin?
made by:
- adipocytes in white adipose tissue
- enterocytes
What does leptin impact?
acts on the hypothalamus to regulate:
- decreases appetite (intake)
- increases thermogenesis (expenditure)
Where in the hypothalamus does leptin act?
cell receptors in:
- arcuate nuclei
- ventromedial nuclei
What is the role of leptin?
- regulation of adipose tissue mass
- development of atherosclerosis (innate system)
What conditions have been associated with low levels of leptin?
- Alzheimer’s disease
- Depression
What happens in congenital leptin deficiency?
RARE
morbid/severe obesity
low serum leptin levels
How can congenital leptin deficiency be managed?
leptin to reduce body weight
What happens to serum leptin in obesity?
serum leptin concentration is correlated to the body fat %
- obesity, leptin resistance
What is the mechanism of leptin in obesity?
- absent leptin
- leptin resistance
- regulatory defect in leptin (signalling issue)
Would leptin be an effective weight control drug?
No, due to leptin resistance
What reduces hunger after a meal?
hormonal signalling from the gut
What secretes gut hormones?
enteroendocrine cells in:
- stomach
- pancreas
- small intestine
- colon
What are the roles of the gut hormones?
- motility regulation
- appetite regulation
- satiety
- salvation
What gut hormones regulate appetite?
- Ghrelin
- Peptide YY (PYY)
What is the effect of Ghrelin?
- stimualtes appetite
- increases gastric emptying
What is the effect of Peptide YY?
- inhibits food intake
When is Ghrelin highest?
- before meals
- increases gastric motility and acid secretion
- prepares for food
What impact does Ghrelin have in the hypothalamus?
- stimulates NPY/Agrp neurones
- inhibits POMC neurones
What does Ghrelin regulate?
- reward
- taste sensation
- memory
- circadian rhythm
What rhythm is seen by Ghrelin levels?
diurnal rhythm
What does circulating Ghrelin correlate with?
- time of day
- positive with age
What is the physiological role of Ghrelin?
meal initiation
Where is Peptide tyrosine tyrosine (PYY) released?
- terminal ileum and colon
- response to feeding
What is the effect of PYY in the hypothalamus?
- stimulates: POMC neurones
- inhibits: NPY release
What types of food trigger PYY release?
- dietary fibres
- wholegrains
- enzymatic breakdown of crude fish proteins
What does PPY do?
induces satiety
What is the degree of PPY release proportional to?
calorie intake
What is the impact of PPY on food/calorie intake?
reduces it
What are the side effects of PYY?
- nausea
- fullness
- less hunger
- early fullness
What co-morbidities are associated with obesity?
- depression
- stroke
- sleep apnoea
- MI
- hypertension
- diabetes
- bowel cancer
- osteoarthritis
- peripheral vascular disease
- gout
Which factors are most dominant in terms of increasing risk of obesity?
environmental factors and genetic predisposition
What is polydipsia?
excessive thirst or drinking
What is adipsia?
inappropriate lack of thirst
- consequent failure to drink
What is anorexia?
loss/lack of appetite for food
What is obesity?
abnormal or excessive fat accumulation that presents health risks
What can cause secondary polydipsia?
- chronic medical issues that disrupt any step in osmoregulation or alter ADH
- medications
- dehydration
What does ADH do?
regulates the volume and osmolality of urine
Where does ADH act?
Aquaporin 2 channel of the collecting duct in the kidneys
What happens when ADH is low?
large volume of urine excretion (water diuresis)
What happens when ADH is high?
small volume of urine excreted (anti-diuresis)
Where is ADH stored?
in the posterior pituitary
What chronic medical conditions can cause secondary polydipsia?
- Diabetes Insipidus and Mellitus
- Kidney failure
- Conn’s syndrome
- Addison’s disease
- Sickle cell anaemia
What medications can cause secondary polydipsia?
- diuretics
- laxatives
- antidepressants
What chronic medical conditions can cause dehydration?
- acute illness
- sweating
- fevers
- vomiting
- diarrhoea
- underhydration
What is the difference between diabetes insipidis and mellitus?
DM: blood sugar
DI: impaired ADH production
What are the symptoms of diabetes?
- always tired
- frequent urination
- sudden weight loss
- wounds that don’t heal
- sexual dysfunction
- constant hunger
- blurry vision
- numb of tingling peripherals
- constant thirst
- vaginal infections
What is Conn’s syndrome?
primary aldosteronism
What is Addison’s syndrome?
hypoadrenocorticism
What are the causes of primary polydipsia?
- mental illness
- brain injuries
- organic brain damage
What mental illnesses can cause primary polydipsia?
- psychogenic polydipsia
- schizophrenia
- mood disorders (depression and anxiety)
- anorexia
- drug use
What can polydipsia cause?
- kidney and bone damage
- headache
- nausea
- cramps
- slow reflexes
- slurred speech
- low energy
- confusion
- seizures
What can cause adipsia?
- increased osmolality of urine
- stimulates the secretion of ADH
- water retention
- decreased thirst sensation
How many different types of adipsia are there?
4
What receptors are used to detect ADH levels?
osmoreceptors
What triggers the release of ADH?
- cells shrink when plasma is more concentrated
- proportion of cation channels increases - depolarizing the membrane
- sends signals to the ADH producing cells to increase ADH
- fluid retention that invokes drinking
What is an eating disorder?
a mental disorder defined by abnormal eating habits
What are some examples of eating disorders?
- binge eating disorder
- anorexia nervosa
- bulimia nervosa
- PICA
- rumination syndrome
- avoidant/restrictive food intake disorder
What are the signs of anorexia?
- Low BMI
- continuous weight loss
- amenorrhea
- halitosis
- mood swings
- dry hair
- skin and hair thinning
What are the causes of anorexia?
- genetic
- environmental
- psychological
- sociological
What is the mechanism of anorexia?
serotonin
What BMI would classify anorexia as mild?
> 17
What BMI would classify anorexia as moderate?
16-16.99
What BMI would classify anorexia as severe?
15-15.99
What BMI would classify anorexia as extreme?
<15
What co-morbidities are associated with anorexia?
- depression
- sleep apnoea
- bowel cancer
- osteoarthritis
- gout
- peripheral vascular disease
- diabetes
- hypertension
- MI
- stroke
What is included in a screening for obesity?
- height
- weight
- abdominal girth
- BMI
Medical history - dietary and physical activity
- psychosocial factors
- weight-gaining medications
- familial traits
What is necessary for a classification of obesity?
BMI >/= 30
or
BMI >/= 25 + co-morbidity/risk factor
What is involved in the treatment of obesity?
Lifestyle modification - diet - exercise Surgical treatment - gastric bypass - gastric sleeve
What is needed to qualify for bariatric surgery for obesity treatment?
BMI >40
or
BMI >35 + co-morbiditiesx
What is the effect of GLP1 and GLP2?
- stimulate insulin release
- inhibit glucagon release
What is the effect of ghrelin?
NPY activation to initiate appetite
What is the effect of PYY?
- satiety
- anorexgenic
What is the impact of bariatric surgery on Ghrelin?
- decreases
stomach fills easier/quicker therefore, when full ghrelin inhibition
What is the impact of bariatric surgery on GLP1/2 and PYY?
- increases
