Fundamentals Of The Endocrine System And AVP

Question 1

What is the difference between the intrinsic and extrinsic classes?

Answer 1

Intrinsic - built into the organ, increased O2 consumption by skeletal muscles during exercise.
Extrinsic - regulatory mechanism initiated outside an organ to change the organ’s activity

Question 2

What are amine/amino acid hormones derived from?

Answer 2

Tryptophan or tytosine

Question 3

How are peptide/protein hormones formed?

Answer 3

Prehormone: Initial peptide hormones that comes off the ribosome is a large inactive protein. Enters lumen with a signal sequence within the (endoplasmic recticulum). Signal sequence is removed creating a smaller inactive molecule (prohormone). Golgi apparatus, prohormone is packaged into secretory vesicles along a proteolytic enzyme that lyse the prohormone into an active hormone and other fragments.

Question 4

How are steroid hormones made?

Answer 4

They are synthesized in the smooth endoplasmic reticulum. They diffuse easily through cell membranes and synthesis of hormones is on demand. Insoluble in plasma and bound to protein carrier molecules.

Question 5

What are tropic hormones?

Answer 5

They are hormones that regulate the production and secretion of other hormones.

Question 6

Define paracrine, autocrine and local hormones.

Answer 6

Paracrine - local hormones that act on neighbouring cells
Autocrine - act on the same cell that secreted

Question 7

What is the role of hormone receptors?

Answer 7

If a hormone is present in excess, target cell receptors are down-regulated. If the hormone is deficient, target cell receptors are up-regulated.

Question 8

Define permissive, synergistic and antagonistic effect

Answer 8

Permissive - actions of some hormones on target cells requires recent exposure to a second hormone. E.g. action of adrenaline on lipolysis increases action in the presence of thyroid hormone
Synergistic effect - when 2 hormones acting together elicit a greater effect E.g. FSH and estrogens
Antagonistic effect - when one hormone opposes the action of another. Insulin and glucagon

Question 9

Define hormone deficiency, resistance and excess

Answer 9

Deficiency - caused by gladular destruction
Resistance - inherited defects in membrane/nuclear receptors. Characterised by defective hormone action, despite normal levels of hormone.
Excess - hormone is produced in excess because of tumours of endocrine glands

Question 10

Name the hormones the posterior pituitary gland secretes

Answer 10

Oxytocin - contraction of uterine smooth muscles, milk ejection during lactation
Vasopressin, ADH - Act on smooth muscles, leading to contraction, acts on the kidneys, decreases H2O excretion in the urine.

Question 11

What are some of the actions of vasopressin?

Answer 11

Decreases urine production and H2O loss through sweating, increases H2O resoprtion by the kidneys, decreases urine volume, increases BP by constricting aterioles.

Question 12

Name and list the functions of AVP receptors

Answer 12

V1- found in vascular smooth muscles, AVP binding in vascular contraction thus increases BP.
V2 - Found in the renal tubules of the kidneys.

Question 13

How do V1 receptors get activated?

Answer 13

AVP binds to V1 receptors stimulates phospholipase B via stimulation of a G-coupled protein which in turn results in inositol triphosphate formation and mobilization of Ca. A separate phosphorylation cascade occurs via DAG and PKC, which has downstream effects, including vasoconstriction,cell growth, ACTH release and platelet aggregation

Question 14

How do V2 receptors get activated?

Answer 14

V2 activates Gs type G protein leading to the activation id adenylate cylase resulting in increased cAMP levels and activation of protein kinase A. This leads to insertion of aquaporin 2 channels into luminal membrane of the collecting duct.

Question 15

What is usually the cause of SIADH?

Answer 15

Ectopic vasopressin produced by tumors causes SIADH. The cause of SIADH is a failure to maximally dilute the urine.

Question 16

What are essentials for diagnosis for SIADH?

Answer 16

Euvolemic hypotonic hyponatraemia. Serum sodium [] <135mmol/L. Plasma osmolality < 280 mOsmo/kg.

Question 17

What are some clinical manifestations of SIADH?

Answer 17

Hyponatraemia, weakness, nausea, confusion, depressed mental status, seizures.

Question 18

How do we manage hyponatraemia?

Answer 18

Admin 100ml 3% NaCl bolus IV over 10 min bd prn to raise serum Na by 1-2 mmol/L.

Question 19

What the MoA and indication of tolvaptan?

Answer 19

Selective V2 receptor anatgonist, results in net fluid loss and increased urine output and decreased urine osmolality. It restores normal sodium levels. Its metabolised by CYP3A4

Question 20

What is a serious adverse effect of tolvaptan?

Answer 20

It can cause serious and potentially fatal liver injury. Other adverse effects include, nausea, polyuria, increased thirst, fatigue and dizziness.

Question 21

What is Diabetes Insipidus and what are the mainstay symptoms?

Answer 21

A decrease in the secretion/action of AVP. Symptoms include urinary frequency, enuresis and nocturia.

Question 22

What are the 3 types of DI?

Answer 22

Diseases of the CNS (affecting the synthesis or secretion of vasopressin. Diseases of the kidney (loss of the kidney to respond to circulating DI)
Pregnancy, increased metabolic clearance of vasopressin.

Question 23

What is the MoA of Desmopressin?

Answer 23

Its the DOC of V2-receptor mediated action. Long-acting synthetic analogue of vasopressin. It increases cAMP in renal tubular cells. Increases water permeability resulting in decreased urine volume. Increased urine osmolality.