K4; Loop of Henle Flashcards
What is osmotic pressure?
The pressure applied by a solution to prevent the flow of water (osmosis) across a semi-permeable membrane; directly related to the concentration of osmotically-active particles in that solution.
In a high osmotic pressure/hyperosmotic environment, what is the ratio of solute to water?
- High [solute]
- Low [water]
»> Concentrated
In a low osmotic pressure/hyposmotic environment, what is the ratio of solute to water?
- Low [solute]
- High [water]
»> Dilute
What is an osmoe?
1 mole solute particles (6.02 x 10^23; Avogadro’s)
What is the difference between osmolality and osmolarity?
- Osmoles per kg solution
- Osmoles per L solution
What is the normal serum osmolality and how does it differ to the corresponding osmolarity?
- Normal serum = 290 mOsm/kg
- Very similar osmolarity
- As the body fluid is a dilute solution; difference between osmolarity and osmolality is negligible as 1L water = 1kg water and weight of solute is minor
What 2 things ensure that the kidney conserves water and concentrates urine?
- ) High osmolality in the renal medullary interstitium; provides osmotic gradient for water reabsorption, passing out the tubule. LoH responsible. (PCT = isosmotic fluid, DCT = hyposmotic fluid)
- ) Action of ADH/AVP; increase water (& urea) permeability
What is the general structure of the Loop of Henle?
- U-shape (hairpin) that dips into the medulla
- Thin descending limb: from PCT, ends in hairpin turn, plunges from cortex to medulla
- Thin ascending limb (only present in nephrons with long LoH)
- Thick ascending limb: carries fluid up and out of the medulla into the DCT in the cortex
What is the cellular make-up/structure like for the thin descending and ascending limb?
What does this tell you about these sections?
- Descending: cells interlock sparsely (leaky)
- Poorly differentiated surfaces, few mitochondria
- Thus suggests not much reabsorption/less active transport
How does the thick ascending limb differ from the thin descending/ascending limbs in structure and thus function?
- Abundant mitochondria; lots of active transport
- Apical membrane is invaginated to form many projections (microvilli); increasing SA for reabsorption
Is the thin descending limb permeable to H2O/Na+/Cl-?
- Permeable to H2O (leaky cells)
- Impermeable to Na+/Cl- (little reabsorption)
Is the thin ascending limb permeable to H2O/Na+/Cl-?
- Impermeable to H2O (cells interlock better)
- Permeable to Na+/Cl- (differential expression)
What is the thick ascending limb permeable and impermeable to?
- Permeable to Na+/Cl-/HCO3-/Ca2+/K+
- Impermeable to H2O
What transporters/carriers etc feature on the thick ascending limb?
- Na+/K+ ATPase in basolateral membrane maintains low Na+ in tubular cell
(Allows for Na+ to flow into the cell down its concentration gradient) - Via Na+/K+/2Cl- symporter in the apical; an electroneutral transporter where Na+/2Cl- are moving down its concentration gradient allow K+ to be taken into the cell against its concentration gradient
- K+ channel in apical membrane enables K+ cycling back into the lumen from Na+/K+/2Cl- function
- Na+/H+ antiporter enables Na+ reabsorption and H+ secretion so it can be cycled for HCO3- reabsorption (via H2CO3 formation etc)
- K+/Cl-/HCO3- leave cell through respective pathways
What occurs to the tubular lumen as a result of ion movements into the tubular cell?
What are the consequences of this?
- Becomes slightly positive at +10mV relative to interstitial fluid
- Allows for paracellular diffusion of K+/Na+/Ca2+/Mg2+/NH4+ moving down their electrochemical gradient
(in particular the divalent Ca2+/Mg2+)
What happens to the tubular fluid after passing the thick ascending limb of the LoH?
- Impermeable to H2O
- Losing solutes not losing H2O (no reabsorption)
- Thus hyposmotic
Which nephron has the long LoH?
- Juxtamedullary nephron (not cortical); plays key role in concentrating urine
What does countercurrent multiplication achieve?
Maintains flow of solutes and H2O in and out of the medulla to produce high medullary osmolality
What are the steps in the renal medulla becoming hyperosmotic?
- ) Tubular fluid enters LoH from PCT at isotonic osmolality to medullary interstitial fluid concentration (300)
- ) Na+/K+ ATPase & Na+/K+/2Cl- symporter (Cl- channel) in (thick) ascending limb actively transport Na+ and Cl- out of lumen into interstitial fluid (tubular fluid osmolality drops); gradient of 200 mOsm/kg develops between tubular and interstitial fluid (200/400)
- Net diffusion of H2O occurs from descending limb into interstitial fluid by osmosis (aquaporins)
- Tubular fluid in descending limb increases in osmolality and water leaves until equilibration with interstitial fluid (400) - ) Flow of tubular fluid pushes 200 mOsm/kg out into the DCT
- Isotonic 300 mOsm/kg fluid enters from the PCT
- Prior equilibrated 400 mOsm/kg fluid is pushed into the ascending limb - ) Process continues and concentration gradient of 200 mOsm/kg is created across the tubular fluid and interstitial (300/500) via Na+/K+/2Cl- symporter pumping NaCl out of tubular fluid
- Thus net diffusion of water from descending limb occurs leaving descending limb and passing into interstitial fluid
- 200 mOsm/kg gradient is present between ascending limb and both the interstitial fluid and descending limb (after equilibration)
- Gradual increase [solute] in descending limb
- Gradual decrease in [solute] in ascending limb - ) 200 mOsm/kg gradient is further disrupted as movement of fluid continues (into the DCT)
- ) Gradient is re-established following simultaneous active movement of NaCl from ascending limb and passive movement of H2O from the descending limb (as it equilibrates with the renal medulla)
- ) Creates a progressive hyperosmotic solution in descending limb (1200 mOsm/kg)
- And a progressive decrease in solute concentration in the ascending limb from NaCl extrusion; progressively hyposmotic
How is the 200 mOsm/kg gradient maintained at the ascending limb in countercurrent multiplication?
- When too much NaCl is in the renal interstitial medulla it passively diffuses back into the tubular fluid
- This maintains the 200 mOsm/kg gradient
What are the key features to countercurrent multiplication/the renal medulla becoming hyperosmotic?
- Tubular fluid progressively concentrated as it flows down the descending limb
- Medullary interstitial fluid is progressively concentrated to the same degree
- 200 mOsm/kg gradient maintained across ascending limb tubular membrane
- Large osmotic gradient from top to bottom of LoH (300 vs. 1200)
- Active reabsorption of NaCl (via Na+/K+/2Cl- symporters) from tubular fluid to interstitial fluid with passive movement of H2O is essential
What are the contributing factors to the hyperosmotic renal medullary interstitium in the outer and inner renal medulla?
Outer: 100% NaCl
Inner: 50/50 NaCl/Urea
How is urea reabsorbed?
- 50% of urea is reabsorbed at the PCT
- LoH (thick asc.) & DCT are impermeable
- [Urea] increases as it passes along the tubule; water and other solutes are reabsorbed
- Collecting duct is permeable; and high [urea] thus urea diffuses down concentration gradient, moving into the interstitial fluid and increasing hyperosmolality
How is urea recycled?
Some urea passes from the interstitium into the thin LoH, cycling around and contributing to hyperosmolality.
How does ADH affect urea reabsorption?
- ADH increases permeability of CD to urea, further increasing osmolality and thus water reabsorption
- Following aquaporin 2 expression for water reabsorption, urea transporters are also expressed creating greater osmotic gradient for water to be reabsorbed into the vasa recta of the peritubular capillaries
What is countercurrent exchange?
- Medullary capillaries (particularly the hairpin arranged vasa recta) are highly permeable to solutes and water
- The parallel configuration of the long vascular loops of the vasa recta minimizes washout of built up solute gradient from the medullary interstitium (if there were a one way blood supply; solutes would diffuse from interstitium into blood), preserving hyperosmolality of renal medulla
What is the path of solutes/water in the descending vasa recta?
- Solutes enter
- Water leaves
- Hyperosmotic
What is the path of solutes/water in the ascending vasa recta?
- Solutes leave
- Water enters
- Isosmotic once again
What is the function of the peritubular capillaries?
- Delivers O2, takes away CO2
- Without disturbing hyperosmolality
