Endocrine and Neuro-physiology

  • Created by: pheegrace
  • Created on: 01-02-20 17:31
3 ways cells communicate over short distances
gap junctions, membrane proteins communicating with adjacent cells and membrane proteins communicating with the extracellular matrix
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autocrine soluble messengers
simplest, shortest range, binds back to cell that released it
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paracrine soluble messengers
cell releases a soluble factor that diffuses locally to influence behaviour of small numbers if neighbouring cells, e.g. blood clotting cascade
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endocrine soluble messengers
hit a lot of target cells over a long distance, access to circulation meaning all tissue are then accessible
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neural soluble messengers
can be very long range, limited by ability to influence relatively small numbers of target cells but has the advantage of speed, e.g. neural reflexes can save your life
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problems with endocrine factors being released into the circulation and solutions
rapidly diluted but work at low concentrations, metabolised and inactivated but bind to circulating proteins or endocrine cells clump to form glands
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how is hormone activity controlled?
negative feedback loop
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3 classes of hormone
peptides and proteins, amino acid derivatives and steroids
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can steroids be stored?
lipophilic so can't be stored
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how do steroids act?
1. Steroid bound to circulatory binding proteins 2. Approaches target cell and dissociates from binding proteins to diffuse across plasma membrane 3. Binds the cytosolic receptor causing heat shock proteins to dissociate 4. Receptors moves through th
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what are the regions of cytosolic-nuclear receptors and what do they do?
o Amino to carboxy terminus o Variable region – recruit transcription factors in the nucleus o DNA binding region – bind DNA o Hinge region – nuclear localisation sequence exposed by conformational change when heat shock proteins fall off o Hormone b
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can peptide/protein hormones be stored?
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how do peptide/protein hormones act?
Ca2+ dependent release into the circulation where they don’t require binding proteins. The target cell has specific membrane receptors. Binding to the receptors causes cell signalling pathways which change the levels of second messengers e.g. Ca2+ an
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what do hydrophilic messengers act via?
gpcr, receptor tyrosine kinases,
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what is a gpcr?
when no stimulation, GDP is bound to alpha subunit. when stimulation, hormone binds receptor, alpha subunit dissociates, gap replaced with gap, adenylate cyclase activated, camp activated, aka activated (?)
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what is a receptor tyrosine kinase?
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what is the hypothalamus?
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what functions can hormones have?
• Stimulate growth e.g. growth hormone and insulin • Control reproduction e.g. FSH, LH, oestrogen and testosterone • Regulate lactation e.g. prolactin and oxytocin • Determine internal environment e.g. ADH, aldosterone and insulin • Influence other h
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how can hormones cause disease?
• Excess e.g. Gigantism • Deficiency e.g. type 1 diabetes mellitus • Resistance e.g. type 2 diabetes mellitus • Hormones as drugs e.g. fertility treatment and contraception • Hormone blockers as drugs e.g. tamoxifen (cancer treatment) • Hormones as d
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where is the pancreas?
behind the stomach
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what are the islets of langerhans?
contain beta cells(insulin) and alpha cells(glucagon)
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what is the incretin effect?
glucose releases insulin but oral glucose is more effective than intravenous glucose
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what is gip?
released by k cells in mucosa of SI, can be injected to cause secretion of more insulin for diabetes treatment
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what happens at the beta cells?
Carbohydrates are ingested and enter the GI tract where glucose is absorbed. The pancreas detects the increase in plasma glucose concentration. The glucose travels into the beta cells which are full of mitochondria via GLUT2(passive glucose transport
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what are Sulphonylurea compounds?
increase insulin release by blocking ATP sensitive K+ channels; they are useful for treatment of type 2 diabetes (metformin)
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what causes insulin release?
increase glucose, increase AA, increase FA, increase GIP
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what causes glucagon release?
decrease glucose, increase AA, decrease FA
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what are the actions of insulin?
uptake of glucose, glycogenesis, lipogenesis, utilisation, stimulate proteogenesis, inhibit proteogenesis, inhibit gluconeogenesis
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are the effects of insulin anabolic or catabolic?
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what is the signalling mechanism of insulin?
(?) Insulin binds to the receptor and the two chains phosphorylate each other to activate the receptor. This phosphorylates the IRS and activates cell signalling for anabolic processes. 1. Insulin binding and receptor activation 2. Activate of the IR
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what are the main energy storage forms?
fat, protein, glycogen
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which storage form is most readily used out of fat and protein?
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how is fat used for energy?
lipolysis to make FA and then ketogensis to make ketone bodies
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how is protein used for energy?
proteolysis to get AA and then gluconeogenesis to get glucose
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is glucagon catabolic or anabolic?
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at what glucose conc is glucagon released?
below 5mM
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what does the growth hormone do?
stimulates protein synthesis, stimulates lipolysis, stimulates gluconeogenesis, inhibits glucose uptake
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what does cortisol do?
promotes lipolysis, promotes gluconeogenesis, inhibits protein synthesis, inhibits glucose uptake
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what does Catecholamines do?
stimulate gluconeogenesis, simulate glycogenolysis, stimulate lipolysis
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what is the oral glucose tolerance test?
reveals how a glucose load is removed from the blood, periodic blood samples are taken to measure plasma glucose concentration
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what is the renal threshold?
10mM, when the kidneys are saturated and cannot recapture glucose anymore hence there is glucose present in the urine
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what is type 1 diabetes?
insulin deficiency, often from childhood, autoimmune, loss of beta cells, insulin injections required for life
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what is type 2 diabetes?
maturity onset, often with elevated plasma insulin due to insulin resistance, associated with obesity and hypertension, incidence increasing with the obesity epidemic.
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what is the thrifty genotype hypothesis?
evolutionary pressure favours genes promoting weight gain, i.e. when access to food is unreliable there is efficient storage of ingested calories
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what would be an example of a good thrifty gene?
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what is body weight determined by?
interactions between diff genes and interactions between genes & environment
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what is body weight regulated by?
balance between energy expenditure and energy intake, maintained to within 10-20kcal/day (<1% of daily energy needed) in order for minimal variation in body weight over long periods of time
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what is energy expenditure?
exercise and basal metabolic rate
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what is energy intake?
food availability and appetite/satiety
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what is satiety?
when you start to feel hungry after eating
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how is food intake controlled?
hypothalamus, glucostat&lipostat, gut
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how does the hypothalamus control intake?
hunger and satiety centres
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how does glucostat and lipostat control intake?
dietary carbs and fats can influence appetite
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how does the gut control intake?
inhibit food intake through gastric distension & CCK or stimulate through ghrelin
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what happened in the Ob/Ob mice experiment?
Ob/Ob mice resemble morbid human obesity, used parabiosis to link circulatory system of obese and healthy mice, obese mouse became healthier due to transfer of endocrine factors from healthy mouse
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what does leptin do?
secreted by fat/adipose tissue and circulates in proportion to amount of fat in body to the hypothalamus where it indicates energy status of body, lower=food restriction, higher=obesity
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how do endocrine factors get across blood brain barrier?
absent or leaky in places such as by the hypothalamus and brain stem
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which neutrons are controlled by hormones?
POMC, NPY, Agrp (?)
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what does POMC do?
shuts down feeding behaviour and promotes satiety
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what does NPY and Agrp do?
makes you feel hungry
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what are the two routes of signalling from the gut to the brain?
o Cells in the gut release endocrine factors which travel in circulation to the hypothalamus o Gut is innovated by nerves which have receptors for hormones that then fire information to the brain stem which relays it to the hypothalamus
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what is ghrelin?
makes you want to eat, levels peak just before meal, stimulates adipocyte proliferation and lipid retention, could antagonise to stop obesity/hunger
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hypothalamic circuits???
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problems with gastric bypass
affects gut hormone levels such as PYY and ghrelin
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autocrine soluble messengers


simplest, shortest range, binds back to cell that released it

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paracrine soluble messengers


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endocrine soluble messengers


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neural soluble messengers


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