Urinary 6 - Plasma osmolarity (disorders + diuretics) Flashcards
What are the main receptors in the body that detect changes in plasma osmolarity, and where are they located?
Hypothalamic osmoreceptors
Organum Vasculosum of Lamina Terminalis (OVLT)
How do the hypothalamic osmoreceptors respond if they detect increased osmolarity?
- Increase thirst stimulus
- Increase ADH secretion
For the hypothalamic osmoreceptors to increase the thirst response, what change in osmolarity must be detected?
Increased osmolarity by 10%
For the hypothalamic osmoreceptors to change ADH secretion rate, what change in osmolarity must be detected?
Increased or decreased osmolarity by 1%
How does an increase in ADH secretion cause reduction of plasma osmolarity?
ADH increases the insertion of AQP2 into the apical membrane of principal cells of collecting ducts = increased water reabsorption
Which aquaporin channels are controlled by ADH?
AQP2 in the principle cells of the collecting duct
ADH mediates aquaporin insertion in what part of the kidney tubule?
Collecting ducts (principle cells)
Which aquaporin channels are present in the apical membrane of the PCT?
AQP1
AQP7
Which aquaporin channels are present in the apical membrane of the descending LoH?
AQP1
Which aquaporin channels are present in the basolateral membranes of the PCT and descending LoH?
AQP1
Which aquaporin channels are present in the basolateral membrane of the collecting ducts?
AQP3
AQP4
List some causes of Central Diabetes Insipidus:
Damage to hypothalamus and/or pituitary gland:
- Brain injury (particularly fracture of base of skull)
- Meningitis
- Brain tumour
- Sarcoidosis
- TB
- Encephalitis
- Aneurysm
- Langerhans cells histiocytosis
What is the pathophysiology of central diabetes insipidus?
Damage to hypothalamus and/or pituitary gland
= lack of circulating ADH
= inadequate reabsorption of H2O from collecting ducts
What are the symptoms of central diabetes insipidus?
Polyuria
Polydipsia
What is the treatment of central diabetes insipidus?
ADH nasal spray
ADH injections
List some causes of Nephrogenic Diabetes Insipidus:
- Hereditary
- Acquired (Lithium, hypercalcaemia, hypokalaemia, polycystic kidney disease, sickle cell anaemia, severe pyelonephritis)
What is the inheritance pattern of hereditary nephrogenic diabetes insipidus?
X-Linked Recessive
What is the pathophysiology of nephrogenic diabetes insipidus?
Kidney is less sensitive to ADH
= Inadequate reabsorption of H2O from collecting ducts
What are the symptoms of Nephrogenic Diabetes Insipidus?
Polydipsia
Polyuria
What are the treatments for Nephrogenic Diabetes Insipidus?
Mild: - Reduced intake of salt and protein - Adequate water intake More severe: - NSAIDs - Thiazide diuretics
What does SIADH stand for?
Syndrome of Inappropriate ADH secretion
List some causes of SIADH:
- Nervous system disorders (MS, encephalitis, infection, epilepsy)
- Brain injury
- Drug induced (Lithium, antidepressants, opiates)
- Pulmonary disorders (Infection, asthma, CF)
Describe the pathophysiology of SIADH:
Excessive release of ADH
= Massive volume expansion
= Hyponatraemia
List some symptoms of SIADH:
Nausea/Vomiting
Cramps/Tremors/Seizures
Depressed mood/Irritability/Confusion
What is the treatment for SIADH?
- Treat underlying cause
- Fluid restriction
- Na+ replacement (IV hypertonic saline)
- ADH receptor antagonists
Define diuretic:
Substance which promotes diuresis by increasing renal excretion of H2O and Na+, to decrease ECF volume
List the 5 classes of diuretic:
1) Loop
2) Thiazide
3) K+ Sparing
4) Carbonic Anhydrase inhibitors
5) Osmotic
What is the mechanism of action of Loop diuretics?
Block NKCC2 in TAL (Thick ascending limb of LoH)
What class of diuretic does Furesomide belong in?
Loop diuretic
What type of diuretic is the most powerful?
Loop diuretics
What conditions are Loop diuretics used to treat?
- Heart failure
- Fluid retention and oedema in Nephrotic syndrome, Liver cirrhosis and renal failure
- Hypercalcaemia
What are the main complications of Loop diuretics?
- Hypokalaemia
- Dehydration
- Hyperuricaemia = Gout attack
- Hyponatraemia (less common)
Give an example of a diuretic that acts on the TAL (Thick ascending limb of LoH):
Furosemide