S5) Corticopapillary Gradient and Countercurrent Exchange Flashcards
Outline the effect of water balance of plasma osmolarity
- Water intake < water excretion = plasma osmolarity ↑
- Water intake > than water excretion = plasma osmolarity ↓
What is the value for normal plasma osmolarity?
280-310 mOsm/Kg (280-310 mmol/L)
Outline the 2 different mechanisms of regulating plasma osmolarity in the body
Which sensors in the body detect changes in plasma osmolarity?
Osmoreceptors – located in the Hypothalamus (OVLT)
How do hypothalamic osmoreceptors act?
Signal secondary responses leading to two different complimentary outcomes:
- Concentration of urine
- Thirst
Where is ADH produced?
Produced by neurosecretory cells in the hypothalamus
What does ADH do?
ADH acts on the kidney to increase the permeability of the collecting duct to water and urea
Describe the actions of ADH in terms of diuresis
- Low plasma ADH = diuresis
- High plasma ADH = anti-diuresis
Describe the events occurring in the efferent pathway: ADH
- Released from posterior pituitary
- Released in conditions of predominant H2O loss
- Renal H2O excretion decreases
- Inhibited by decreased plasma osmolarity
Identify and describe 2 clinical conditions which result from problems with ADH secretion
- Central diabetes insipidus: low plasma ADH levels
- Nephrogenic diabetes insipidus: acquired insensitivity of the kidney to ADH
Identify 2 forms of clinical management for low plasma ADH
- ADH injections
- ADH nasal spray treatments
Identify 5 different causes of low plasma ADH
- Damage to hypothalamus / pituitary gland
- A tumour
- An aneurysm
- Sarcoidosis
- Tuberculosis
What is Syndrome of Inappropriate ADH secretion?
- SIADH is the excessive release of ADH from the posterior pituitary gland or another source e.g. small cell lung tumour
- Dilutional hyponatremia results
Identify the different aquaporin channels and their location in the nephron
In terms of aquaporins, explain how a lack of ADH secretion leads to diuresis
- No Aquaporin 2 in apical membrane
- No AQP 3 and 4 on basolateral membrane
- Limited water reuptake in DCT2 and collecting duct
- Hyposmotic urine produced
Describe the relationship between haemodynamic and osmotic changes
Large deficits in water are only partially compensated for in the kidney.
Describe the events occuring in the efferent pathway: thirst
- Induced by increases in plasma osmolarity or by decreases in ECF volume
- Thirst increases intake of free water
- Stops when sufficient fluid has been consumed
How does the osmolarity of the nephron increase down the LoH?
- Descending limb of LoH is highly permeable to H2O (AQP 1)
- Descending limb is not permeable to Na+
- Na+ remains in the lumen and filtrate concentration (osmolarity) increases
Where is the maximum osmolality reached in the nephron?
Maximum osmolality is at apex of LoH = 1200 mOsm/Kg
Explain how the thick ascending limb of the Loop of Henle generates the medullary gradient
- Ascending limb actively transports NaCl out of tubular lumen into interstitial fluid
- Ascending limb is impermeable to H2O
- Filtrate is diluted and osmolarity of interstitium increases
What is the osmolality of the filtrate at DCT1?
Fluid entering the DCT has low osmolality = 100 mOsm/Kg
What is the juxtamedullary nephron what does it do?
- Juxtamedullary nephron is a long-looped nephron of 20% abundance
- It has importance in establishing the medullary vertical osmotic gradient
What is the vertical osmotic gradient?
The vertical osmotic gradient is a gradient of increasing osmolarity established in the interstitial fluid of the medulla
Describe 2 features of the vertical osmotic gradient
- Isotonic (300mOsm/Kg) at corticomedullary border
- Hyperosmotic in medullary interstitium up to 1200 mOsm/Kg at papilla
Why is the vertical osmotic gradient an essential mechanism?
- Active NaCl transport in thick ascending limb
- Recycling of urea (effective osmole)
What is an ineffective osmole?
If the membrane allows a solute to freely cross it, then the solute is totally ‘ineffective’ at exerting an osmotic force across this membrane
Why is urea an effective osmole in the kidney?
Urea is hydrophilic and does not readily permeate artificial lipid bilayers
In which circumstance would urea be an ineffective osmole?
In the presence of urea transporters which facilitate urea diffusion across most cell membranes
Describe the recycling of urea in the kidney under the influence of ADH
- Urea is reabsorbed from the medullary CD
- Cortical CD cells are impermeable to urea
- Urea moves into interstitium and diffuses back in LoH to increase concentration gradient for H2O reabsorption
What is the Counter Current Multiplication?
Counter Current Multiplication is the increased osmolarity of the interstitial fluid surrounding the LoH due active transport of Na+
What does the vasa recta do?
The vasa recta maintains the concentration gradient by acting as a counter-current exchanger
How does the vasa recta act as a counter current exchanger?
Flow in vasa recta is in opposite direction to fluid flow in the tubule so the osmotic gradient is maintained
Compare and contrast blood flow in the renal cortex and medulla
- Renal cortex: blood flow is one of the highest per gram of any tissue in the body
- Renal medulla: low blood flow (5-10% of total RPF)
Explain why the renal medulla and cortex have contrasting blood flow
- Need to deliver nutrients to renal cortex (high blood flow)
- Need to maintain medullary hyper-tonicity (low blood flow)
What happens in the descending limb of the vasa recta?
- Isosmotic blood in vasa recta enters hyperosmotic milieu of the medulla
- Na+, Cl- and urea diffuse into the lumen of vasa recta
- Osmolarity in vasa recta increases as it reaches tip of hairpin loop
What happens in the ascending limb of the vasa recta?
- Blood ascending towards cortex has a higher solute content than surrounding interstitium
- Water moves into vasa recta from the descending limb of the LoH
