Week 5 - Plasma Osmolarity Regulation Flashcards
1
Q
What is the process that maintains plasma fluid osmolarity?
A
Osmoregulation
- Even small changes in plasma osmolarity result in hormonal changes that alter water uptake by the kidney and stimulate thirst
- If water intake excretion → plasma osmolarity decreases
- Body must match ingestion to excretion
2
Q
What senses changes in plasma osmolarity?
A
Hypothalamic osmoreceptors
- Found in the organum vasculuom of the laminae terminalis (OVLT)
- – This is anterior and ventral to the 3rd ventricle
- – Fenestrated leaky endothelium exposed directly to systemic circulation
- They signal secondary responses which are mediated via 2 pathways leading to 2 different complimentary outcomes
- – Concentration of urine
- – Thirst
3
Q
Describe ADH
A
- Small peptide
- Acts on the kidney to regulate the volume and osmolarity of urine
- If plasma ADH is low → lots of urine produced (water diuresis)
- If plasma ADH is high → small volume of urine excreted (anti-diuresis)
- Increases the permeability of the collecting duct to water and urea
- – Causes the addition of aquaporin 2 channels to the apical membrane of the collecting duct
- – This allows for reabsorption of water to decrease plasma osmolarity
4
Q
Where are aquaporin channels found in the collecting duct?
A
- If ADH is present, AQP2 is inserted into the apical membrane
- If ADH is removed then the AQP2 channel is retrieved from the apical membrane by endocytosis
- The basolateral membrane always contains AQP3 and AQP4
- – So it is always permeable to water
- – Any water which enters across the apical membrane is thus able to pass into the peritubular blood
- – Resulting in a net absorption of water
5
Q
Describe urea recycling
A
- ADH increases the permeability of the medullary part of the collecting duct to urea, causing its reabsorption
- This in turn, causes water to follow
- The rise in urea concentration in the tissues causes it to passively move down its concentration gradient into the ascending limb
- – This is permeable to urea but impermeable to water
- Urea then passes back into the collecting duct, where it is reabsorbed in the medullary portion and more water follows
- Urea is therefore recycled
6
Q
Describe how the corticopapillary osmotic gradient is set up
A
- At the cortico-medullary border, there is no osmotic gradient
- However the medullary interstitium is hyper osmotic
- There is a gradient of increasing osmolarity as you descend
— The active transport of NaCl out of the thick AL and the recycling of urea sets up the osmotic gradient
— Action of the TAL Is crucial, removing solute without water, diluting the filtrate and increasing interstitium osmolarity
— If you block the NKCC2 transporters in the TAL with a loop diuretic, the medullary interstitium becomes isosmotic and large amounts of dilute urine is produced - Counter-current multiplication
— Loop of henle acts as a counter-current multiplier, to set up the osmotic gradient
— The tubule is filled initially with isotonic fluid
— Water moves out of the descending limb through aquaporin channels
• It is instantly removed by the vasa recta
— Large amounts of passive reabsorption of sodium ions initially occurs in the thin ascending limb
• The Na+ ions sit in the medulla as there is no water to wash them away
— Na+ ions are pumped out of the ascending loop (using NKCC2 channels)
• This raises the osmotic pressure outside the tubule and lowers it inside
— Fresh fluid enters from the glomerulus and enters the descending limb
• As the descending limb is permeable to water, it leaves via osmosis to raise the osmotic pressure inside the descending tubule
• Further Na+ ions leaves the ascending limb, adding to the Na+ in the medulla, further increasing the concentration gradient
— Further along the nephron, water will move out of the collecting duct, in order to decrease the plasma osmolarity of the surrounding interstitium
• Dependent on the amount of ADH and hence aquaporin channels present
7
Q
Describe the role of the vasa recta in maintaining the corticopapillary gradient
A
Blood vessels that run alongside the loops, but with opposite flow direction
- This counter-current flow allows for the maintenance of the concentration gradient
- Isosmotic blood in the descending limb of the vasa recta enters the hyperosmotic milieu of the medulla, where there is a high concentration of ions
- – These ions diffuse into the vasa recta and water diffuses out
- The osmolarity of the blood in the vasa recta increases as it reaches the tip of the hairpin loop, where it is isosmotic with the medullary interstitium
- Blood ascending towards the cortex will have a higher solute concentration than the surrounding interstitium
- – So solutes move back out and water moves back in
- The vasa recta prevent the medullary hyperosmolarity from being dissipated
8
Q
Describe SIADH
A
Syndrome of inappropriate antidiuretic secretion
- Excessive release of ADH from the posterior pituitary gland or another source
- Dilutional hyponatremia in which the plasma sodium levels are lowered and total body fluid is increased
- Symptoms of hyponatremia:
- – Nausea and vomiting
- – Headache
- – Confusion
- – Lethargy
- – Fatigue
- – Appetite loss
- – Restlessness and irritability
- – Muscle weakness
- – Spasms
- – Cramps
- – Seizures
- – Decreased consciousness or coma
9
Q
What are the factors involved in renal stone formation?
A
- Low urine volume
- Hypercalcuria
- Low urine pH
10
Q
What are most renal tract stones made of?
A
Calcium
11
Q
How do renal stones manifest?
A
- Increasing fluid intake
- Restricting dietary oxalate and sodium
- Considering dietary restriction of calcium and animal protein
12
Q
How can you conservatively manage renal stones?
A
- Haematuria
- Pain and associated complications of an obstruction in the renal tract
- Need not produce symptoms
13
Q
What are some causes of hypercalcaemia?
A
- Primary hyperparathyroidism
- Haematological malignancies
- – Comes about due to the production of parathyroid hormone-related peptide
- Non-haematological malignancies
14
Q
What are some symptoms for hypercalcaemia?
A
- GI:
- – Anorexia
- – Nausea/vomiting
- – Constipation
- – Acute pancreatitis
- CVS:
- – Hypertension
- – Shortened QT interval on ECG
- – Enhanced sensitivity to digoxin
- Renal
- – Polyuria and polydipsia
- – Occasional nephrocalcinosis
- CNS:
- – Cognitive difficulties and apathy
- – Depression
- – Drowsiness, coma
15
Q
How can you manage hypercalcamia?
A
- General:
- – Hydration (increase Ca2+ excretion)
- – Loop diuretics (increase Ca2+ excretion)
- Specific:
- – Bisphosphonates (inhibits breakdown of bone)
- – Calcitonin (opposes action of PTH)
- Treat underlying condition
