Metabolic Rate Growth and Disease Flashcards
what does a deficiency of GH or excess lead to in children
defi - dwarfism
excess - gigantism
what does an excess or deficiency of GH lead to in adults
excess - acromegaly
deficiency - no obvious disease but replacement increases lean body mass, decreases fat
what centre in the brain regulates growth hormone
hypothalamus
where is Gh secreted from
anterior pituitary
what stimulates and inhibits GH
GRH increases and somatostatin inhibits
what are target organs of GH
fat cartilage bone liver muscle
describe the rate of secretion of GH
pulsatile (lots of rapid pulses) more at night
describe the synthesis of GH
20 and 22 k Da
22 predominates
secreted as prepro from nucleus and cleaved to pro from RER to golgi where it is packaged into granules
what is the half life of GH
about 25 mins
what do GH bind to and what does it cause
acts vi tyrosine kinase associated receptor leading to protein phosphorylation
what are the physiological effects of gH
liver increases gluconeogenesis
fat increases lipolysis
muscle decreases glucose uptake
insulin resistance
what are the long term effects of GH mediated by
insulin like growth factor 1 (somatomedin) - IGF
what are IGFs and what do they do/cause
somatomedins which enhance protein synthesis and growth but can cause hypoglycaemia
IGF1 is the main one as IGF 2 not controlled by GH
how do sex steroids and glucocorticoids affect growth
SS - accelerate growth but hasten maturity
gluco - slow growth
what are the two forms of thyroid hormone
t3 (triiodothyronine) and T4 (thyroxine)
what proteins in the blood bind to thyroxine
globulin and transthyretin
what are the half live of the two types of thyroxine when bound to proteins
t4 - 8 days
t3 1 day
what is production and release stimulated by
TSH
what does thyroxine release do to the body
increases metabolic rate and heat generation also essential for normal growth and development
what are the steps of TSH inducing release of T3 and T4
trapping iodination conjugation endocytosis proteolysis secretion
what happens to T4 once it is released
deiodinated to T3 by two enzymes
what two enzymes break down T4
type 1 - found in liver, kidney and thyroid which is inhibited by stress and caloric restriction
type 2 in pituitary, CNS and placenta
what does T3 bind to in a cell
nuclear receptor in nucleus which unities gene transcription
what are the specific processes that thyroid hormone affect
increase gluconeo and glycolysis in the liver
causes lipolysis and lipogenesis
increased proteolysis for aa and gluconeo but also protein synthesis
increases NaKATPase
increased B receptor expression
what are the chronic effects of thyroid hormone
crucial for normal brain development and growth
TSH drives thyroid hypertrophy, so low TH (and lack of feedback) leads to a goitre: common in areas with low environmental iodine (e.g. “Derbyshire neck”)
what can cause hyper/hypothyroidismm
autoimmunity
what causes graves disease
antibodies against the TSH receptor may activate it driving excess TH production and hyperthyroidism
what are the the symptoms of graves (hyper)
weight loss, tremor sweating tachycardia
double vision
exophthalmus (in GD)
what causes hashimotos disease (hypo)
antibodies that destroy TSH receipts or other thyroid targets
what are the symptoms of hashimotos (hypo)
weigh gain, hypothermia, tired, constipation, brady cardia - secondary an ovulation
what symptom is found in both hyper and hypothyroidism
myxoedema (lesions in the skin)
what is the main natural glucocorticoid
cortisol
what causes release of CRH (cortisol releasing hormone)
hypothalamus integrates stress factors and diurnal rhythm
what affect does release of CRH have
induces ACTH from the anterior pituitary
what does ACTH stimulate
adrenal cortex (zona fasiculata and reticularis) induing hyperthopy and cortisol production
what are the acute effects of glucocorticoids
Inhibit insulin responses, and enhance SNS responses
Targets glucose to brain: other organs use fats
In liver, promotes gluconeogenesis and glucose release
In fat, lipolysis (glycerol for gluconeogenesis, FFA for energy)
In muscle, protein breakdown for gluconeogenesis
what are the chronic effects of glucocorticoids
Immunosuppression
Reduction in inflammation and cytokine production
Stimulate haematopoiesis and GI tract mucosa
Fat redistribution – peripheral to central
Skin thinning, muscle wasting, osteoporosis
Complex CNS effects: euphoria to psychosis!
what disease is caused bye excess glucocorticoids
cushings
what disease is characterised by adrenocortical insufficiency
addisons diseases (high ACTH gives pigmentation)
