endocrine physiology

Question 1

Adrenal Hormones
Name the endogenous catecholamines and their source

Answer 1

● Adrenal medulla – adrenaline, noradrenaline, dopamine
● Intrinsic cardiac adrenergic cells – adrenaline
● Sympathetic nervous system cells – dopamine

Question 2

What are the physiological effects of adrenaline and noradrenaline?

Answer 2

● Metabolic – glycogenolysis, increased metabolic rate, mobilisation of free fatty
acids, increased lactic acid
● Cardiovascular – vasoconstriction and dilation, increased heart rate and
contractility

Question 3

Which receptors are responsible for the effects of adrenaline and noradrenaline

Answer 3

● α1 – constriction of blood vessels, smooth muscle (especially norad)
● α2- mixed smooth muscle effects and involved in negative feedback mechanisms
● B1- cardiac inotropy and chronotropy
● B2- smooth muscle relaxation, bronchodilation and dilation of blood vessels in
the liver and muscle
● B3 – lipolysis, detrusor relaxation

Question 4

How does aldosterone exert its effects in the kidney?

Answer 4

● It is a mineralocorticoid, acting on principal cells in the collecting duct
● It binds a cytoplasmic receptor and the complex travels to the nucleus where it
alters transcription of mRNA
● Aldosterone promotes resorption of Na+ and Cl from the urine in exchange for K+
and H+, via rapid insertion of preformed epithelial sodium channels (eNaC) on
the cell and increased synthesis of eNAC channels.
● The action takes 30 minutes to develop.

Question 5

Describe the serum and urine effects of hyperaldosteronism

Answer 5

● Increased sodium and chloride in plasma
● Fluid retention (follows Na)
● Hypokalaemia due to aldosterone effect in the kidney
● H+ are lost in the urine, resulting in increased urine acidity and K concentration

Question 6

What are the stimuli that increase aldosterone secretion?

Answer 6

● ACTH from pituitary
● Renin from kidney via angiotensin II
● Direct stimulatory effect of rise in plasma K+ concentration in the adrenal cortex
● Clinical causes – surgery, haemorrhage, anxiety, trauma, reduced salt intake,
secondary hyperaldosteronism i.e. CCF/cirrhosis

Question 7

Describe the feedback regulation of aldosterone secretion

Answer 7

● Fall in ECF/blood volume
● reflex increase in renal artery nerve discharge and decrease in renal artery
pressure
● increase in renin secretion → increase in angiotensin II → increase in
aldosterone secretion
● Na+ and water retention → expanded ECF volume
● decrease in stimulus that initiated renin secretion

Question 8

Glucocorticoids
What are the physiological effects of glucocorticoids?

Answer 8

● Permissive action on catecholamine effects (pressors, bronchodilation)
● Metabolic effects – increase protein catabolism, increase hepatic glycogenolysis
and gluconeogenesis, increase plasma glucose, increase lipolysis
● Increased free water excretion via decreased vasopressin activity
● Immunological - decreased inflammatory and allergy response
● Haematological – increased platelets , neutrophils, red blood cells
● CNS effects – EEG slowing, personality changes

Question 9

How is glucocorticoid secretion regulated?

Answer 9

● Glucocorticoids are secreted from the adrenal cortex, which is dependent on
ACTH secretion from the anterior pituitary
● ACTHsecretion is regulated by CRH released from the hypothalamus – in
response to low cortisol levels or stress
● Glucocorticoids provide a negative feedback loop on the hypothalamus and the
anterior pituitary to reduce ACTH secretion

Question 10

What are the vascular effects of stopping long term glucocorticoid therapy?

Answer 10

● Vascular smooth muscle becomes unresponsive to noradrenaline and adrenaline
● Capillaries dilate and increase in their permeability
● Failure to respond to noradrenaline impairs vascular compensation for
hypovolaemia and promotes vascular collapse

Question 11

What is the benefit of elevated glucocorticoid levels in stress?

Answer 11

Effect on vascular activity to catecholamines, plus mobilisation of FFA for emergency
energy source

Question 12

Calcium Homeostasis
Where in the body is calcium stored?

Answer 12

Bone 99%
Plasma – both bound to protein and unbound, where it is an important secondary
messenger and is required for coagulation, nerve function and muscle contraction

Question 13

How is the plasma calcium level regulated?

Answer 13

● Parathyroid hormone – increases plasma calcium by mobilising calcium from the
bone. Increases calcium resorption in the kidney and increases formation of 1,25
DHCC in the kidney
● 1,25 DHCC (from Vit D) increases calcium absorption from intestines and
kidneys
● Calcitonin (from thyroid) – lowers circulating calcium levels by inhibiting bone
resorption. It also increases calcium loss in the urine.
● Glucocorticoids – decrease plasma calcium by inhibiting osteoclast formation and
activity
● Oestrogen – inhibit the stimulatory effect of cytokines on osteoclasts
● Calcium can also be raised by pathological processes like paraneoplastic
syndrome or bone erosion.

Question 14

How does bone resorption occur?

Answer 14

● Osteoclasts – monocytes that develop from stromal cells under the influence of
RANK-L
● They attach to the bone via integrins
● Hydrogen dependent proton pumps acidify the area The acid dissolves the
hydroxyapatite and the acid proteases break down collagen
● Products move across the osteoclast to the interstitial fluid.

Question 15

What factors determine the plasma glucose level?

Answer 15

● Dietary intake
● Absorption from the intestine
● Rate of entry into cells
● Gluconeogenesis in the liver
● Reabsorption in the kidney
● Fasting status

Question 16

Explain how blood glucose is maintained during fasting

Answer 16

● Short fasting - Liver glycogen is broken down and glucose is released into the
bloodstream
● Extended fasting time – Glycogen depletion leads to gluconeogenesis from
glycerol and amino acids in the liver

Question 17

What happens to glucose homeostasis in the absence of insulin?

Answer 17

● Hyperglycaemia due to
● Decreased peripheral uptake of glucose into muscle and fat
● Reduced glucose uptake by the liver
● Increased glucose output by the liver and lack of glycogen synthesis
● GIT, renal brain and red cells can continue uptake in the absence of insulin

Question 18

how does exercise affect glucose levels?

Answer 18

● Increased entry of glucose into skeletal muscle via an insulin independent
mechanism
● This increases GLUT 4 transporters in muscle cell membranes
● Effects persist for several hours and regular exercise can lead to prolonged
increases in insulin sensitivity
● Exercise in T1DM can precipitate hypo because the absorption of injected insulin
is more rapid during exercise.

Question 19

What are the physiological actions of glucagon?

Answer 19

● Raises BGL via
● Glycogenolysis in the liver
● Gluconeogenesis from amino acids
● Lipolysis
● Ketogenesis
● Positive inotropic effect on the heart
● Increases blood flow to kidneys
● Stimulates secretion of growth hormone, insulin and somatostatin

Question 20

What factors affect glucagon secretion?

Answer 20

Stimulation
● Beta adrenergic stimulants
● Cortisol
● Protein meal
● Vagal stimulation
● Starvation, stress, exercise
● CCk
● Gastrin

Inhibitors
● Glucose and insulin
● Somatostatin
● FFA
● Ketones
● Alpha adrenergic stimulators
● GABA

Question 21

What happens when insulin binds to an insulin receptor?

Answer 21

● The insulin receptor is a tyrosine kinase receptor with intra and extracellular
components
● Insulin binding to the extracellular alpha subunits triggers tyrosine kinase activity
of the beta subunits in the cell
● This leads to autophosphorylattion of the beta subunits and triggers secondary
messengers
● Once bound, then insulin receptors aggregate in patches and are endocytosed
● They enter lysosomes where they are broken down or recycled

Question 22

What are the principle actions of insulin

Answer 22

● Net effect is the storage of CHO, protein and fat
● Rapid(seconds): increase the transport of glucose, amino acids and K+ into
insulin sensitive cells
● Intermediate (minutes): stimulation of protein synthesis and inhibition of protein
degradation; activation of glycolytic enzymes and glycogen synthase, inhibition of
phosphorylase and gluconeogenic enzymes
● Delayed (hours) increased mRNA production for lipogenic and other enzymes

Question 23

What are the effects of insulin deficiency?

Answer 23

● Decreased peripheral utilisation of glucose
● Hyperglycaemia with low intracellular glucose
● Derangement of glucostatic function of the liver
● Hyperglycaemia with no associated decrease in gluconeogenesis
● Secondary osmotic diuresis with dehydration
● Electrolyte and calorie loss
● Catabolism of protein and fat due to low intracellular glucose
● Ketosis, leading to ketoacidosis
● Breakdown of amino acids for energy
● Increased free fatty acids from breakdown of triglycerides

Question 24

What factors determine the rate of ACTH secretion?

Answer 24

Increased by stress - pain, emotional distress
Driven by circadian rhythms through the hypothalamus via release of CRH
Inhibited by circulating glucocorticoids and afferent signals from baroreceptors

Question 25

What happens to ACTH levels after prolonged treatment with glucocorticoids is
stopped abruptly?

Answer 25

ACTH slowly increases over weeks
The pituitary might not be able to secrete normal amounts of ACTH for a month
Presumed to be secondary to diminished ACTH synthesis

Question 26

What hormones are secreted by the anterior pituitary?

Answer 26

TSH, ACTH, GH, LH, FSH

Question 27

What are the clinical effects of anterior pituitary insufficiency?

Answer 27

● Adrenal cortical atrophy → glucocorticoid and sex hormone levels fall.
Mineralocorticoid secretion is maintained so salt loss and hypovolaemia does not
occur, but unable to mount a stress response
● Hypothyroidism
● Growth inhibition
● Gonadal atrophy, loss of some secondary sexual characteristics
● Tendency towards hypoglycaemia due to increased insulin sensitivity

Question 28

What hormones are secreted by the posterior pituitary?

Answer 28

Vasopressin and oxytocin

Question 29

What are the physiological effects of vasopressin?

Answer 29

Renal retention of water

Question 30

How are thyroid hormones regulated?

Answer 30

● Thyrotropin releasing hormone from the hypothalamus
● Acts on the anterior pituitary to promote release of TSH
● Causes thyroid to release T4 and some T3
● T4 is converted to T3 in periphery
● Negative feedback loop on TSH by free T3 and T4
● Secretion and synthesis of TSH is also increased by cold exposure, decreased
by stress and glucocorticoids/dopamine.

Question 31

What are the physiological effects of thyroid hormones?

Answer 31

● Cardiovascular - chronotropic and inotropic effects on the heart via increasing the
number of beta receptors, increasing the response to catecholamines. Increase
circulating volume, HR and cardiac output
● Calorigenic - raises metabolic rate, increases O2 consumption
● Adipose tissue- stimulates lipolysis
● Muscle - catabolism
● Bone - promotes normal bone development
● Nervous system - promotes normal brain development

Question 32

Describe the steps in synthesis of thyroid hormone

Answer 32

● Thyroid epithelial cells secrete thyroglobulin and iodine into colloid
● Iodide transport is via a symport with sodium (NIS)
● Thyroid peroxidase makes iodotyrosines (MIT and DIT) then combines them to
make T3 and T4
● Endocytosis and lysis of colloid releases the free hormone
● T4 is converted to T3 in the periphery
● All of these steps are controlled by TSH

Question 33

How do thyroid hormones alter metabolism?

Answer 33

Binds to intracellular receptors in the cell nuclei
Alters gene expression to increase metabolism and catabolism of most cells