Endocrine HPA Axis Flashcards
Define the term hormone
Hormone is a chemical substance produced by a gland, transported by the bloodstream to distant target organs where it exerts its biological effects
Recall the 5 types of hormones. Give examples for each type.
- Amino acid derivatives - T4, T3, adrenaline, norepinephrine
- Peptides/polypeptides/proteins - insulin, glucagon, adh, oxytocin
- Steroid derivatives - aldosterone, cortisol, androgens
- Fatty acid derivatives - prostaglandins
- Glycoprotein - TSH, FSH, LH
State examples of some hormones of…
1. amino acid derivatives
2. peptides/polypeptides/proteins
AMINO ACID DERIVATIVES
- T3, T4
- adrenaline
- norepinephrine
PEPTIDES/POLYPEPTIDES/PROTEINS
- insulin
- glucagon
- adh
- oxytocin
State some examples of hormones of…
1. Steroid derivatives
2. Fatty acid derivatives
3. Glycoprotein
STEROID DERIVATIVES
- aldosterone
- cortisol
- androgens
FATTY ACID DERIVATIVES
- prostaglandins
GLYCOPROTEINS
- TSH
- FSH
- LH
State examples of free and protein-bound hormones.
Free hormones
- Free T3 (fT3), free T4 (fT4)
- Free cortisol
Protein-bound hormones
- Thyroid-binding globulin
State the hormones that act via GPCR and RTK receptors. State a difference between the two types of receptors
GPCR - glucagon
RTK-R - insulin, GH
GPCR involves cAMP and adenylyl cyclase as secondary messengers while RTK acts via cytoplasmic tyrosine kinases.
State the hormones synthesised by hypothalamus and their effects on anterior pituitary hormones.
HYPOTHALAMIC HORMONES - ANTERIOR PIT HORMONES
CRH -> increases ACTH
TRH -> increases TSH and PRL
GHRH -> increases GH
GnRH -> increases FSH and LH
Somatostatin -> decreases GH and TSH
Dopamine -> decreases PRL
State the only 2 hypothalamic hormones which result in a negative effect to anterior pituitary hormones.
Somatostatin -> decreases TSH and GH
Dopamine -> decreases PRL
State the types of link between gthe hypothalamus and the…
1. adenohypophysis
2. neurohypophysis
ADENOHYPOPHYSIS
- hypothalamus –> vascular link –> anterior pituitary
- Hormones taken via vascular link to anteiror pituitary to signal it to produce more hormones
NEUROHYPOPHYSIS
- hypothalamus –> hypothalamic neurons –> neural link –> posterior pituitary
Summarise how regulation of GH occurs. (eg: GH high)
- GHRH in hypothalamus stimulated to increase GH production and secretion in anterior pituitary
- GH produced stimulates IGF-1 secretion by liver
- IGF-1 secretion stimulates negative feedback by inhibiting GH secretion from anterior pituitary AND inhibiting GHRH secretion from hypothalamus
- IGF-1 secretion stimulates somatostatin and GHIH (GH inhibitory hormone) secretion which inhibits GH secretion
- As GH secretion decreases, TH stimulates GH to ensure homeostatic control
State some factors that affect GH secretion and their effects. (8)
- Insufficient sleep –> less GH secreted
- Old age –> less GH secreted
- Obesity –> less GH secreted
- Stress –> more GH secreted
- Exercise –> more GH secreted
- High blood glucose –> less GH secreted (somatostatin stimulated)
- High amino acid level –> more GH secreted
- TH –> more GH secreted
Describe a test used to determine diagnosis of acromegaly/gigantism.
Glucose inhibits GH release. Challege patient with glucose to observe if GH will be suppressed.
If GH is not suppressed –> postprandial sugars will be elevated as GH increases glucose levels –> after the glucose challenge, glucose remains high
Result: diagnosis as acromegaly
Explain the two tests used to determine GH deficiency.
**(1) EXERCISE GROWTH HORMONE STIMULATION TEST **
- measure GH before and after exercise
- optimal result: GH increases with exercise
(2) GLUCAGON GROWTH STIMULATION TEST
- glucagon stimulates liver to release glucose itno bloodstream –> large increase in blood glucose levels
- glucagon also induces stress response which activates hypothalamus and pituitary gland –> stimulates secretion of GHRH from the hypothalamus –> stimulates GH secretion from anterior pituitary
Recap: State some causes of increased urine output.
- Increased water intake due to POLYDIPSIA
- Osmotic diuresis
- Water diuresis
OSMOTIC DIURESIS is caused by GLYCOSURIA or POTASSIUM ELECTROLYTE IMBALANCE
- insulin deficiency in DM –> insulin normally promotes uptake of potassium into cells –> without sufficient insulin, potassium remains in extracellular space –> hyperkalaemia –> increased osmolarity of fluid in tubular
Explain how osmotic diuresis occurs and the factors that result in this phenomenon.
Osmotic diuresis = Increased urine production due to the presence of non-reabsorbable solutes in the renal tubules, which draw water into the urine by osmosis
(1) Glycosuria (DM) –> elevated blood glucose exceeds kidney’s ability to reabsorb it –> water follows glucose down the osmotic gradient –> polyuria
(2) Insulin deficiency –> DKA (DM) –> insulin which normally promotes uptake of potassium into cells now insufficient –> potassium remains in extracellular space –> hyperkalaemia –> hydrogen ions move into cells in exchange for K+ ions –> further increase in K+ –> increased osmolarity of tubular fluid –> water follows K+ to balance osmotic gradient –> polyuria
Explain how water diuresis occurs and the factors that result in this phenomenon.
Water diuresis = Increased urine production due to the excretion of dilute urine with a low concentration of solutes.
(1) Psychogenic polydipsia
(2) Diabetes insipidus –> ADH deficiency –> inability to form AQP-2 channels to increase water reabsoprtion –> polyuria
Explain how ADH levels are regulated via 2 mechanisms.
1. Increase in ECF osmolality
2. Decrease in ECF volume
(1) INCREASE IN ECF OSMOLALITY
- Detected by osmoreceptors –> signal transfuced to supraoptic nucleus (SON) and paraventricular nucleus (PVN) in hypothalamus –> neurons (neural link) –> posterior pituitary stiumulated to release ADH
(2) DECREASE IN ECF VOLUME
- Decreased BP detected by baroreceptors –> signal transduced to supraoptic nucleus (SON) and paraventricular nucleus (PVN) in hypothalamus –> neurons (neural link) –> posterior pituitary stimulated to release ADH
RECAP:
State which part of the adrenal medulla primarily absorbs water and Na+ ions.
Water - proximal tubule (descending limb)
Na+ ions - distal tubule (ascending limb)
State the end result of decreased ADH (central diabetes insipidus) and how that result occurs.
result = polyuria
ADH (vasopressin) stimulates the increased production of aquaporin-2 channels at the collecting ducts –> increases permeability of collecting ducts to promote water reabsorption
Hence, ADH deficiency prevents water reabsorption –> water remains in tubular fluid –> polyuria
State a test which can differentiate between CENTRAL DIABETES INSIPIDUS and OTHER PATHOLOGIES RELATED TO WATER OSMOSIS.
Test = Administer ADH aimed at increasing osmolality
If pathology is central DI –> osmolality will increase as ADH deficiency is countered by the administration of ADH allowing for aquaporin-2 channels to be embedded in membranes of collecting duct to promote water reabsorption
If pathology is (nephrogenic) central DI –> osmolality remains low as ADH is not deficient and pathology is likely linked to receptors (eg: ADH receptor deficiency, receptor-ligand malformations) –> water reabsoption remains low
Explain the difference in serum sodium content in patients with
1. Diabetes insipidus
2. Psychogenic polydipsia
(1) DIABETES INSIPIDUS = [Na+] is high or normal
- insufficient ADH –> water excreted without adequate replacement –> hypernatremia
(2) PSYCHOGENIC POLYDIPSIA = [Na+] is low
- increased thirst –> increased drinking –> dilution effect in tubular fluid + intracellular fluid
Recall: State a hallmark feature of SIADH and DI.
SIADH - hyponatraemia
DI - polyuria
State the 3 factors that allow for effective defence against hyponatremia.
- Adequate fluid delivery to diluting segment (thick ascending limb) - insufficient fluid can result in insufficient Na+ reabsorbed causing [Na+] to be diluted
- Normal functioning diluting segment - allows Na+ reabsorption
- Suppression of ADH - prevents too much water from being reabsorbed to prevent dilution of [Na+] in blood
State some causes of hyponatremia. (link to adrenal system)
- Excessive fluid intake –> dilution of sodium in blood due to intake > excretion
- Low GFR –> insufficient water filtered out –> dilution effect
- Low solute intake –> low intrinsic [Na+]
- Diuretics –> prevents Na+ reabsorption
- Low volume states
Recall: What hormones do adrenal glands secrete? What are their functions?
adrenal cortex:
1. zona glomerulosa –> aldosterone
2. zona fasciculata + zona reticularis –> cortisol, androgens
adrenal medulla - adrenaline, noradrenaline
Aldosterone - maintains electrolyte balance by promoting Na+ retention and K+ excretion
Cortisol - regulate BMR
Androgens - regulation of sexual characteristics
