Appetite Flashcards
How many people die everywhere as a result of being overweight or obese?
2.8 million people
What are the three triggers for regulation of thirst?
Body fluid osmolality
Blood volume is reduced
Blood pressure is reduced
Which of the three thirst triggers is the most potent?
Plasma osmolality increase is the more potent stimulus – change of 2-3% induces strong desire to drink
Decrease of 10-15% in blood volume or arterial pressure is required to produce the same response
How does ADH regulate osmolality?
Antidiuretic hormone (ADH) or vasopressin
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
What are the features of osmoreceptors?
Sensory receptors
Osmoregulation
Found in the hypothalamus
In which region of the hypothalamus are osmoreceptors found?
Organum vasculosum of the lamina terminalis (OVLT)
Subfornical Organ (SFO)
How do Osmoreceptors cause ADH release?
Cells shrink when plasma more concentrated
Proportion of cation channels increases – membrane depolarizes
Send signals to the ADH producing cells to increase ADH
Fluid retention
Invokes drinking
What is thirst decreased by?
Thirst is decreased by drinking even before sufficient water has been absorbed by the GI tract to correct plasma osmolality
What receptors are involved in thirst?
Receptors in mouth, pharynx, oesophagus are involved
Relief of thirst sensation via these receptors is short lived
When is thirst completely satisfied?
Thirst is only completely satisfied once plasma osmolality is decreased or blood volume or arterial pressure corrected.
How does changes is pressure regulate thirst?
Renin-angiotensin-aldosterone system
How does Aldosterone achieve water retention?
H2O retention via
Na+CL- absorption and K+ excretion
What does Angiontensin II do to increase water retention?
Vasoconstriction, increase sympathetic activity
ADH secretion
What occurs in a weight reduced - underfed state?
Decreased sympathetic nervous activity Decreased energy expenditure Increased hunger and food intake Decreased thyroid activity Weight gain
What occurs in a weight augmented - overfed state?
Increased sympathetic nervous activity
Increased energy expenditure
Decreased hunger and food intake
Weight loss
What is involved in appetite regulation?
Hypothalamus
Ghrelin
Leptin
What does hypothalamus do to regulate appetite?
Arcuate nucleus is an aggregation of neurons in the medial basal path
Produces appetite increasing (Orexigenic) and appetite decreasing (anorectic) peptides
Lateral hypothalamus - orexigenic
Ventrolmedial hypothalamus - associated with satiety
What do lesions in the ventromedial hypothalamus lead to?
Decreased satiety
Obesity
What are other hyporthalmic factors implicated in appetite regulation?
Endocannabinoids
AMP activated protein kinase
Protein thyrosine phosphatase
What are the main features of the arcuate nucleus?
Brain area involved in the regulation of food intake
Incomplete blood brain barrier, allows access to peripheral hormones.
Integrates peripheral and central feeding signals
What are the two neuronal populations in the arcuate nucleus?
Two neuronal populations:
Stimulatory (NPY/Agrp neuron)
Inhibitory (POMC neuron)
What can the arcuate nucleus neurons be affected by?
Leptin
Insulin
What do POMC neuron activation do?
Decreases feeding
What do NPY/Agrp neurone activation do?
Increases feeding
How does the melanocortin system work?
Melanocortins are products of the POMC gene
Regulates energy balance in feeding behviours and energy expenditures
MC4R receptors are stimulated by serotonin
Leads to reduction in appetitis
What does POMC deficiency and MC4-R mutations cause?
Obesity
What higher brain regions also play a role in appetite?
Higher centres.
Amygdala- emotion, memory.
Other parts of the hypothalamus, e.g. lateral hypothalamus
Vagus to brain stem to hypothalamus.
What is the adipostat mechanism?
Circulating hormone produced by fat
More fat, more hormones
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 ?
What is the ob/ob mouse?
Obese mouse
Unable to produce leptin leading to obesity
Identification of the gene in the mouse led to discovery of leptin significance
What are the features of leptin?
Meaning - thin
Discovered in 1994.
Missing in the ob/ob mouse.
Made by adipocytes in white adipose tissue.
Circulates in plasma.
Acts upon the hypothalamus regulating appetite (intake) and thermogenesis (expenditure).
Plays a role in atherosclerosis
What is congenital leptin deficiency?
Very rare
Causes severe obesity early in life
Constant hunger
What is the systemic effects of leptin?
Low when low body fat
High when high body fat
Replacement in the ob/ob mouse decreases weight
Hormone that decreases food intake and increases thermogenesis
What are the three mechanisms of action of leptin?
Insufficient production
Defective receptor signalling
Decreased sensitivity of leptin
What are the features of leptin resistance?
Leptin circulates in plasma in concentrations proportional to fat mass
Fat humans have high leptin
Obesity due to leptin resistance- hormone is present but doesn’t signal effectively
Leptin is ineffective as a weight control drug.
Why do we feel less hungry after a meal?
Hormonal signals from gastrointestinal hormones
What secretes the gastrointestinal hormones?
Enteroendocrine cells of stomach
What are the two main gastrointestinal hormones?
Ghrelin
Stimulates appetite, increases gastric emptying
Peptid YY
Inhibits food intake
When are the blood levels of ghrelin highest?
Blood levels of ghrelin are highest before meals
help prepare for food intake by increasing gastric motility and acid secretion
What does ghrelin do?
Directly modulates neurons in the arcuate nucleus
Stimulates NPY/Agrp neurons.
Inhibits POMC neurons
What are the affects of ghrelin?
Increases appetite
Regulation of reward, taste sensation, memory, circadian rhythm
What is PPY?
Short peptide released in the terminal ileum (TI) and colon in response to feeding (36 Amino acids)
What are the affects of PPY?
Reduces appetite – can be digested or injected IV
Food arriving to the TI and colon results in PYY release
Inhibits NPY release
Stimulates POMC neurons
What is the affect of PPY when taken?
Experience less hunger
Early fullness
Nausea
What are co-morbidities associated with obesity?
Depression Stroke MI Hypertension Diabetes Peripheral vascular disease Gout Osteoarthritis Bowel cancer Sleep apnoea
What is adipisia?
Inappropriate lack of thirst
with consequent failure in order to correct hyperosmolarity
What are the types of polydipsia?
Primary
Secondary
What are the main features of secondary polydipsia?
More common
Medical issues that disrupt any step in osmoregulation or alter ADH can cause secondary polydipsia
What are the causes of secondary polydipsia?
Chronic medical conditions
Medications
Dehydration
What chronic medical conditions cause secondary polydipsia?
Diabetes insipidus & mellitus Kidney failure Conn’s syndrome (primary aldosteronism) Addison's disease (hypoadrenocorticsm) Sickle cell anaemia
What medications cause secondary polydipsia?
Diuretics
Laxatives
Both result in dehydration
Antidepressants
What causes dehydration?
Acute illness Sweating Fevers Vomiting Diarrhoea Underhydration
What does insipid mean?
Tasteless
What does Mellitus mean?
Sweet tasting
What are the main features of diabetes mellitus?
General population - common
Related to high blood sugar
Treatment of high blood sugar
What are the main features of diabetes insipidus?
General population - uncommon
Related to pituitary problems
Impaired ADH production
Treatment with desmopressin
What causes primary polydipsia?
Mental illness - psychogenic polydipsia (or acquired) Schizophrenia Mood disorders - depressionandanxiety Anorexia Drug use
Braininjuries
Organic brain damage
Why is polydipsia a problem?
Kidney and bone damage Headache Nausea Cramps Slow reflexes Slurred speech Low energy Confusion Seizures
What are the 4 types of polydipsia?
Type A
Type B
Type C
Type D
Give examples of eating disorders
Binge eating disorder Anorexia nervosa Bulimia nervosa Pica Rumination syndrome Avoidant/restrictive food intake disorder
Describe global prevalence of eating disorders
Global eating disorderprevalence ↑ed from 3.4% to 7.8% between 2000 and 2018.
70 million people live with eating disorder
What is Pica?
Eating inappropriate things
e.g. hair, soil, dust
What is rumination syndrome?
Regurgitate and swallow
repeat
What are the signs of anorexia?
Low BMI, continuous weight loss, amenorrhea, halitosis, mood swings, dry hair, skin & hair thinn
What are the different BMI categories for anorexia?
Mild: BMI > 17
Moderate: BMI of 16–16.99
Severe: BMI of 15–15.99
Extreme: BMI < 15
What are the causes of anorexia?
Genetic, environmental, psychological, sociological
What is halitosis?
Bad breath
What is the mechanism of anorexia?
Via serotonin release
Increase in CSF
What percentage of the worlds population will be obese by 2030?
51%
Why is obesity increasing?
Cheap, calorie rich, readily available food
What are the screening tools used for obesity?
Height, weight and abdominal girth
Medical history:
Dietary and physical activity patterns, psychosocial factors, weight-gaining medications, familial traits
BMI = kg/m2
BMI of ≥30 or ≥25 + comorbidity or risk factor
What surgical treatments are available for obesity?
People with a > BMI 40 or 35+ comorbidities
Various procedures
Most common Roux-en-Y gastric bypass & sleeve gastrectomy
WL 5 yrs after BS: 30% - 35%
Remission of comorbidities
Diabetes (80%)
OSA (80%-85%)
What are the hormones related to obesity?
GLP1 and GLP2:
Stimulate insulin release
Inhibit glucagon release
Ghrelin:
Hunger hormone
NPY activation – initiate appetite
PYY:
Satiety
anorexogenic
What hormonal changes are seen after bariatric surgery?
Ghrelin reduces
GLP1, GLP2 and PYY elevated
