Metabolic Rate Growth and Disease

Question 1

what does a deficiency of GH or excess lead to in children

Answer 1

defi - dwarfism

excess - gigantism

Question 2

what does an excess or deficiency of GH lead to in adults

Answer 2

excess - acromegaly

deficiency - no obvious disease but replacement increases lean body mass, decreases fat

Question 3

what centre in the brain regulates growth hormone

Answer 3

hypothalamus

Question 4

where is Gh secreted from

Answer 4

anterior pituitary

Question 5

what stimulates and inhibits GH

Answer 5

GRH increases and somatostatin inhibits

Question 6

what are target organs of GH

Answer 6

fat 
cartilage 
bone 
liver 
muscle

Question 7

describe the rate of secretion of GH

Answer 7

pulsatile (lots of rapid pulses) more at night

Question 8

describe the synthesis of GH

Answer 8

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

Question 9

what is the half life of GH

Answer 9

about 25 mins

Question 10

what do GH bind to and what does it cause

Answer 10

acts vi tyrosine kinase associated receptor leading to protein phosphorylation

Question 11

what are the physiological effects of gH

Answer 11

liver increases gluconeogenesis
fat increases lipolysis
muscle decreases glucose uptake
insulin resistance

Question 12

what are the long term effects of GH mediated by

Answer 12

insulin like growth factor 1 (somatomedin) - IGF

Question 13

what are IGFs and what do they do/cause

Answer 13

somatomedins which enhance protein synthesis and growth but can cause hypoglycaemia
IGF1 is the main one as IGF 2 not controlled by GH

Question 14

how do sex steroids and glucocorticoids affect growth

Answer 14

SS - accelerate growth but hasten maturity

gluco - slow growth

Question 15

what are the two forms of thyroid hormone

Answer 15

t3 (triiodothyronine) and T4 (thyroxine)

Question 16

what proteins in the blood bind to thyroxine

Answer 16

globulin and transthyretin

Question 17

what are the half live of the two types of thyroxine when bound to proteins

Answer 17

t4 - 8 days

t3 1 day

Question 18

what is production and release stimulated by

Answer 18

TSH

Question 19

what does thyroxine release do to the body

Answer 19

increases metabolic rate and heat generation also essential for normal growth and development

Question 20

what are the steps of TSH inducing release of T3 and T4

Answer 20

trapping 
iodination
conjugation 
endocytosis 
proteolysis 
secretion

Question 21

what happens to T4 once it is released

Answer 21

deiodinated to T3 by two enzymes

Question 22

what two enzymes break down T4

Answer 22

type 1 - found in liver, kidney and thyroid which is inhibited by stress and caloric restriction
type 2 in pituitary, CNS and placenta

Question 23

what does T3 bind to in a cell

Answer 23

nuclear receptor in nucleus which unities gene transcription

Question 24

what are the specific processes that thyroid hormone affect

Answer 24

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

Question 25

what are the chronic effects of thyroid hormone

Answer 25

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”)

Question 26

what can cause hyper/hypothyroidismm

Answer 26

autoimmunity

Question 27

what causes graves disease

Answer 27

antibodies against the TSH receptor may activate it driving excess TH production and hyperthyroidism

Question 28

what are the the symptoms of graves (hyper)

Answer 28

weight loss, tremor sweating tachycardia
double vision
exophthalmus (in GD)

Question 29

what causes hashimotos disease (hypo)

Answer 29

antibodies that destroy TSH receipts or other thyroid targets

Question 30

what are the symptoms of hashimotos (hypo)

Answer 30

weigh gain, hypothermia, tired, constipation, brady cardia - secondary an ovulation

Question 31

what symptom is found in both hyper and hypothyroidism

Answer 31

myxoedema (lesions in the skin)

Question 32

what is the main natural glucocorticoid

Answer 32

cortisol

Question 33

what causes release of CRH (cortisol releasing hormone)

Answer 33

hypothalamus integrates stress factors and diurnal rhythm

Question 34

what affect does release of CRH have

Answer 34

induces ACTH from the anterior pituitary

Question 35

what does ACTH stimulate

Answer 35

adrenal cortex (zona fasiculata and reticularis) induing hyperthopy and cortisol production

Question 36

what are the acute effects of glucocorticoids

Answer 36

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

Question 37

what are the chronic effects of glucocorticoids

Answer 37

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!

Question 38

what disease is caused bye excess glucocorticoids

Answer 38

cushings

Question 39

what disease is characterised by adrenocortical insufficiency

Answer 39

addisons diseases (high ACTH gives pigmentation)