S4: osmolality

Question 1

Explain 3 ways in which renin release by granular cells is stimulated

Answer 1

Fall in Na+ leads to a fall in ECF -> release of renin by:

1) Increased sympathetic innervation – increased renin release from granular cells
2) Wall tension in afferent arterioles falls – decrease wall tension at granular cells, stimulating renin release
3) Decreased Na+ to the macula densa – less NaCl reaches the macula densa -> secretes prostaglandins -> act on granular cells -> renin release

Question 2

Explain the importance of prostaglandins in response to low BP

Answer 2

Decrease in effective circulating volume stimulates cortical prostaglandin synthesis
In the kidney it occurs in the: cortex, medullary interstitial cells & collecting duct epithelial cells
Result in: vasodilators & renin release

Question 3

Describe the action of ANP is response to high BP

Answer 3

Atrial natriuretic peptide (ANP) is produced by cardiac atrial cells in response to an increase in ECF volume

1) Inhibits sodium-potassium pump & closes Na+ channels of the collecting ducts & DCT, reducing Na+ reabsorption -> Na+ and water excretion is increased
2) Vasodilate afferent arterioles
3) Inhibits aldosterone secretion
4) Inhibits ADH release
5) Decrease renin release

Question 4

Describe the effect of Starling’s forces in response to increased BP

Answer 4

Changes in body fluid volume alter plasma hydrostatic & oncotic pressure
Increased hydrostatic pressure & decreased oncotic pressure, so NaCl and water reabsorption by the PCT decreases

Question 5

What happens when the blood pressure in the renal artery increases?

Answer 5

Reduced number of Na/H antiporter & reduced Na/K/ATPase activity in proximal tubule
Causes reduction in sodium resorption in proximal tubule
Reduction in water resorption
-increased sodium excretion = pressure natriuresis
-increased water excretion = pressure diuresis

Question 6

Describe hypervolaemia

Answer 6

Excess of total body sodium and water
Leads to expansion of ECF compartment – ascites, pulmonary oedema, swelling in ankles & legs
Typically due to: kidney retention of sodium and water, reduced effective arterial volume, excess sodium/fluid intake, cirrhosis and hyperaldosteronism

Question 7

Describe hypovolemia and shock

Answer 7

Shock = medical emergency in which the vital organs are inadequately perfused
Inadequate compensation, tissue hypoxia & necrosis can occur in vulnerable organs
Severe decrease in circulating volume stimulates sympathetic activity to maintain the BP by: tachycardia, peripheral vasoconstriction & increase in myocardial contractility

Question 8

What is hypovolemic shock?

Answer 8

Acute reduction in effective circulating blood volume from blood loss, loss of plasma or loss of water and electrolytes
To counteract excessive vasoconstriction, more prostaglandins are secreted -> maintains adequate blood flow through kidney
2 major consequences: volume depletion & electrolyte and acid-base disturbances

Question 9

What is the treatment for hypovolemic shock?

Answer 9

Fluid replacement to restore extracellular volume

NB: if blood flow to the kidneys is not restored, acute kidney injury results from tissue anoxia and necrosis

Question 10

Describe hypertensive renal disease

Answer 10

Increase in BP transferred to kidney/glomerulus
Hypertensive changes seen in the kidney include:
-arteriosclerosis of the major renal arteries
-hyalinization of small vessels with intimal thickening
Can lead to chronic renal damage & a reduction in the size of the kidneys

Question 11

Describe the osmoreceptors

Answer 11

Located in the OVLT in hypothalamus
Fenestrated leaky endothelium exposed directly to systemic circulation
Sense changes in plasma osmolarity – signal 2 different responses: concentration of urine & thirst

Question 12

Describe central diabetes insipidus

Answer 12

Impaired ADH synthesis/secretion by the hypothalamus
Damage to hypothalamus/pituitary gland due to: brain injury, tumour, aneurysm etc
Treated by giving ADH (desmopressin)

Question 13

Describe nephrogenic diabetes insipidus

Answer 13

Acquired insensitivity of the kidney to ADH
Difficult to manage clinically but a low-salt, low-protein diet reduces urine output
Causes: mutations in gene coding for V2 receptors, polycystic kidneys, chronic pyelonephritis or drugs (lithium)
Plasma ADH levels are normal

Question 14

Describe syndrome of inappropriate antidiuretic hormone secretion

Answer 14

SIADH – characterised by excessive release of ADH from the posterior pituitary gland or another gland
Dilutional hyponatremia, in which the plasma sodium concentration is lowered – total body fluid is increased
Occasionally ADH is secreted inappropriately, causes include CNS disorders, malignancy, lung disease, drugs & metabolic disease

Question 15

Describe how to produce hypoosmotic urine

Answer 15

Decreased ADH results in decreased aquaporins in apical membrane
Tubular fluid rich in water passes through the hyperosmotic renal pyramid with no change in water content
Loss of large amount of hypoosmotic (dilute) urine

Question 16

Describe how to produce hyperosmotic urine

Answer 16

Kidney must reabsorb as much water as possible from the kidney tubule
Water will move out of the collecting duct into hyperosmotic environment if there are AQP’s in both the apical and basolateral epithelium of the tubule cells
Release of ADH causes increased insertion of AQP2 channels into apical membrane

Question 17

Describe hypernatremia

Answer 17

Plasma [Na+] > 146mmol/L & there is an increased solute:water ratio in body fluids & increased serum osmolality
Causes: osmotic diuresis, fluid loss without replacement, diabetes insipidus, incorrect IV replacement, primary aldosteronism

Question 18

Describe hyponatremia

Answer 18

Serum [Na+] < 130/135mmol/L
Low sodium very common in hospital patients
Symptoms: agitation, nausea, focal neurology, coma (correlates to severity & rate of onset)
Causes: diuretics, water overload/retention, increased ADH secretion, increased plasma osmolality
-true Na+ loss: D&V, diuretics/renal failure, peritonitis, burns/CF

Question 19

What is the equation for calculated osmolarity?

Answer 19

2Na+ + glucose + urea

Question 20

Describe hypovolemic hyponatremia

Answer 20

Nonrenal loss – GI losses, excessive sweating, third spacing of fluids & cerebral salt-wasting syndrome
Treatment: depends on the cause but fluid restriction nearly always works, infusion of hypertonic saline & furosemide can be used in symptomatic patients

Question 21

List the actions of ADH

Answer 21

1) Reduced water excretion (V2 mediated) - creates a channel for which water can pass through passively
2) Activation of V1 receptor on VSM causes vasoconstriction, triggering thirst response in hypothalamus

Question 22

Explain how renal artery stenosis can lead to hypertension

Answer 22

Decreased renal perfusion
Activates RAAS
Angiotensin II causes systemic vasoconstriction
Angiotensin II causes synthesis of aldosterone
Aldosterone causes increased sodium reabsorption in the DCT & hence water