5. Control of plasma osmolality

Question 1

does regulation of plasma osmolality involve isotonic, hypertonic or hypotonic secretion/reabsorption?

Answer 1

hypotonic - as only secreting/reabsorbing water to/from tubules in order to change plasma [Na]

Question 2

how are changes in plasma osmolality detected?

Answer 2

osmoRs in hypothalamic OVLT (supraoptic nucleus)

Question 3

what are the 2 main mechanisms to regulate plasma osmolality and how much change is needed to activate each

Answer 3

1. ADH release - activated with 1% change in osmolality

2. thirst behaviour - activated with 10% change in osmolality

Question 4

describe the effector response stimulated by osmoRs detecting an increased plasma osmolality

Answer 4

1. ADH release from posterior pituitary… ADH stimulates:
   a) translocation of AQP2 on apical membrane of CD principal cells… increased H2O reabsorption from tubules
   b) increased permeability of CD to urea… increased urea reabsorption… increased corticopapillary gradient
   c) increased activity of basolateral Na/K ATPase of thick ascending limb of loop of Henle… enhances activity of apical NCCK2… increased Na reabsorption… increased corticopapillary gradient
2. Stimulation of thirst… increased water intake

Question 5

what is the corticopapillary osmotic gradient?

Answer 5

large osmolarity gradient existing in renal interstitium between the renal cortex (300mOsm/L - isosmotic) and medulla (1200mOsm/L - hyperosmotic)

Question 6

which 2 nephron structures are required to generate and maintain the coricopapillary gradient

Answer 6

• produced by juxtamedullary nephrons: possess long loops of Henle that extend far into renal medulla
• maitained by vasa recta: acts as counter current exchanger - hairpin loop with opposite flow to loop of Henle

Question 7

what is the role of the loop of Henle in generating the corticopapillary gradient

Answer 7

• Na reabsorption via NKCC2 transporters in thick ascending limb allows…
• water reabsorption in thin descending limb - driven by high interstitial osmolarity generated by TAL and high permeability of epithelial barrier here

Question 8

what is the role of urea recycling in generating the corticopapillary gradient

Answer 8

Urea conc. increases throughout nephron tubule (due to water reabsorption), and because permeability is greatest at medullary portion of CDs, urea is reabsorbed here. Acts as effective osmole, stimulating water reabsorption at CD.
Urea reabsorbed into vasa recta is secreted into thin loop of Henle allowing it to be recycled.

Question 9

how is the corticopapillary gradient modulated by ADH

Answer 9

increased ADH increases gradient size (causing greater water absorption) by:

• stimulating basolateral Na/K ATPase of thick ascending loop of Henle… enhances activity of apical NKCC2… increased Na reabsorption… wider osmotic gradient
• increases no. of specific urea transporters in medullary CDs… increases urea permeability… increases driving force for water reabsorption

Question 10

Which condition can cause: high plasma [Na] and osmolality, and low urine [Na] and osmolality

Answer 10

diabetes insipidus

Question 11

Which condition can cause: low plasma [Na] and osmolality, and high urine [Na] and osmolality

Answer 11

syndrome of inappropriate ADH (SIADH)

Question 12

what is the difference between SIADH and DI

Answer 12

SIADH = excess ADH secretion… increased water retention… dilutes serum Na and increases plasma volume. increased plasma volume inhibits aldosterone release… increased Na excretion into urine followed by water… plasma volume normalised but significant decrease plasma[Na] and osmolality.

DI = hyposecretion of or insensitivity to effects of ADH… inability to concentrate urine in distal renal tubules… polyuria

Question 13

what are the 2 main types of DI and what are the main causes of each

Answer 13

1. cranial DI: decreased ADH secretion, generally caused by hypothalamus damage, e.g. tumours, intracranial surgery, trauma, infections, vascular disorders (haemorrhage/thrombosis, sickle cell disease, Sheehan’s syndrome)
2. nephrogenic DI: kidney insensitivity to ADH. Can be caused by hypokalaemia, hypercalcaemia, CKD, renal tubular acidosis…

Question 14

what are the symptoms of DI

Answer 14

polyuria and polydypsia

Question 15

how can DI be diagnosed

Answer 15

1. fluid deprivation test: continued polyuria

2. desmopression stimulation test: if resolves polyuria = central DI, if doesn’t = nephrogenic polyuria

Question 16

name possible causes of SIADH

Answer 16

• strokes, cerebral haemorrhage, cerebral trauma
• drugs, e.g. anti-depressants, anti-epileptics
• surgery, esp. to pituitary
• ectopic ADH release from small cell lung carcinoma

Question 17

what are the symptoms of SIADH

Answer 17

early symptoms: headaches, nausea and vomiting, muscle cramps and trmors

later symptoms: cerebral oedema - confusion, mood swings and hallucinations

end: seizures, coma and death