Tubular function Flashcards
What is the structure of a nephron?
Glomerulus, proximal convoluted tubule, Loop Of Henle (descending then ascending limbs), and comes up to the same glomerulus (produces the juxtaglomerular apparatus) to the distal convoluted tubule. Then passes off to bladder. NOTE, the afferent arteriole emerges from above, and the efferent leaves below. PERITUBULAR CAPILLARIES are capillaries supplied by the efferent arteriole.
What are the two parts of the collecting duct?
Cortical collecting duct and innerr-medullary collecting duct.
What is meant by ‘freely filtered’?
Meaning SOLUTE is found in the same concentration in the blood as the GF.
How is urine produced?
- Filtration of blood plasma. 2. Selective reabsorption of contents to be retained. 3. Tubular secretion of some components 4. Concentration of urine as necessary.
What is hyper-osmolarity and hypo-osmolarity?
HYPEROSMOLARITY: lots of solute. HYPOOSMOLARITY: low in solute, high in water.
What is tubular fluid?
Fluid contained within the tubules of the nephron network.
What is osmolarity?
Measure of the osmotic pressure exerted by a solution across a perfect semi-permeable membrane. it is a measure – therefore, of all the concentrations of the different solutes added together i.e. every ion. Measure das mosmol/L – 1 Osmole = 1 mole of dissolved solutes per litre. The greater the amount of dissolved particles, the greater the osmolarity.
What is the normal plasma osmolarity range?
285-295 mosmol/L.
What is the minimum and maximum urine osmolarity? Implication of range on plasma osmolarity?
50 – 1200 mosmol/L. 1200 denotes that the urine is concentrated during water suppression; 50 = the opposite. These large urine osmolarity fluctuations allow for plasma osmolarity to stay constant.
What must be the case about osmolarity in the body? What does this mean for plasma volume?
OSMOLARITY MUST BE KEPT CONSTANT: This explains why increased salt must be compensated with increased water and therefore LARGER VOLUME!
What is the most prevalent solute in the plasma and ECF?
Sodium.
What is the definition of paracellular and transcellular?
Para = across tight junctions and inter-cellular spaces. Intra = through cytosol of cell epithelium.
What are the two types of passive movement across cells?
PROTEIN-INDEPENDENT TRANSPORT: for lipophilic molecules, movement is dependent solely on concentration gradients. PROTEIN-DEPENDENT TRANSPORT: for hydrophilic molecules, movement is limited by number of protein channels available for movement.
What are the two types of active movement across cells?
DIRECTLY ATP-COUPLED: rate is dependent on availability of ATP. INDIRECTLY ATP-COUPLED: note that on baso-lateral surface, sodium movement is passive; the active process occurs at the Na+/K+ pump. Rate here depends on Na+ concentration gradient between the areas shown by green arrow.
What two ways can water move across tubular cells in the nephron?
Paracellularly through tight junctions OR intracellularly through protein channels called aquaporins.
What does transport maxima describe?
Solute concentration above which we cannot reabsorb anymore, so anything above these concentrations will appear in the urine e.g. glucose in diabetics.
How does transport maxima vary?
Applies to all substances but can vary depending on circumstances that stimulate transport and reabsorption.
What substances in the nephrons do not have specific protein transporters? How is this overcome?
Urea and water. This is overcome by water by utilising osmosis in response to build up of Na in intercellular spaces.
What is secretion?
Movement of substances from peritubular capillaries into tubular lumen. Can occur by diffusion or transcellular mediated transport.
What are the main things secreted into the urine?
H+ and K+ because of the antiporter mechanisms of reabsorption in the nephron tubules.
What is the process of reabsorption in the proximal convoluted tubule?
70% filtrate is reabsorbed – Na+ uptake by basolateral Na+ pump allows for cotransport where water and anions e.g. Cl- follow. Glucose is taken up by Na+/glucose co-transporter, and amino acids by Na+/amino acid co-transporter. Small proteins that enter the glomerular filtrate (this is normal for small proteins), are reabsorbed by endocytosis. All glucose and small proteins get reabsorbed.
What are the structural features of the proximal convoluted tubule? (x5)
□ Proximal convoluted has a dense brush border = high SA which is especially important because there’s large volumes of reabsorbed water – in APICAL MEMBRANE. □ Interdigitations in BASOLATERAL MEMBRANE. □ Cells are high in mitochondria for Na+ active transport. □ Cuboidal epithelium sealed with fairly water permeable tight junctions. □ Contains aquaporins which mediate transcellular water diffusion.
Small amounts of protein enter the filtrate: how are these reabsorbed?
There are receptor proteins on apical surface which has low specificity, but high affinity for protein. They bind to and endocytose the protein along with the receptor it is bound to. Inside the endosome containing the protein and receptor, pH drops, receptor dissociates, and returns to membrane.
How are low intracellular concentrations of reabsorbed substances maintained in PCT? Importance?
Blood flow. Important as a lot of reabsorption happens here.
What is the role of Na+ in the early proximal tubule, and what mechanisms does Na+ use to do this? (x4)
- CO-TRANSPORT glucose and amino acids on apical surface. Glucose and amino acids move out passively from basolateral surface because of low concentration in blood.
- COUNTER-TRANSPORT of H+ ions to regulate pH.
- Exchange with potassium ions in direct ATP-dependent active-transport to maintain concentration gradients for passive diffusion of Na+ into cell at the apical surface.
- Indirect movement of HCO3- out and into blood – explained in net flashcard.
How is Na+ indirectly responsible for reabsorption of HCO3- in PCT?
- Na+/H+ exchange mechanism means that H2CO3 is formed in the tubular fluid, where HCO3- is present.
- Presence of carbonic anhydrase means H2CO3 can be converted to H2O and CO2.
- H2O and CO2 can cross the membrane and continue to associate (and dissociate) to form H2CO3 in the tubule cell.
- H2CO3 in the tubule cell can dissociate to form H+ to replenish supply in cell, AND CRUCIALLY, form HCO3- again for movement out and into the blood.
What is the purpose of carbonic anhydrase activity in the PCT? (x2)
Na+ reabsorption and increased urinary acidity.
What happens in terms of secretion in the PCT?
There is net secretion.
Why is secretion in PCT important? (x2)
Route of excretion for some substances AND some drugs enter the tubular fluid here and act further down the nephron.
What is the major function of the loop of Henle? Name of mechanism?
Purpose is to concentrate the urine – creation of hyper-osmotic extracellular fluid. Done using the COUNTERCURRENT MECHANISM.
What happens in the countercurrent mechanism?
DESCENDING THIN TUBULE: passive osmotic equilibrium (aquaporins present). Ions and water move out down concentration gradient freely.
ASCENDING THICK LIMB: Cl- actively pumped out of tubular fluid into ECF, and Na+ passively moves out because tubular fluid initially very watery. Impermeable to water. Results in hypo-osmotic (lots of water) tubular fluid and hyper-osmotic (lots of solute) extracellular fluid. This produces the environment for the large movement of water out and back into the blood in the descending limb – so lots of water can be retained in the body.
What happens to osmolarity at different depths of the medulla? What mechanism makes this happen?
Higher osmolarity (more salty) as you go further down the medulla. LOOK AT PHOTO AS THIS EXPLAINS WHY.
What is the nature of osmolarity of tubular fluid when it leaves ascending limb? Why?
Hypo-osmolar (more watery) than plasma because more sodium has been reabsorbed (90%) than water (85%) across the PCT and LOH by this point.
What is the mechanism of movement in ascending limb?
Na/K/CL co-transporter, where Cl-, Na+ and K+ are moved out of tubular fluid. Concentration gradients maintained by anti- and co-transporters in basolateral membrane. There is also SOME paracellular movement.
What do loop of Henle diuretics target?
Na/K/Cl co-transporter in ascending loop of Henle on apical surface.
What is the structure and physical characteristics of the descending and ascending limbs of the loop of Henle?
DESCENDING LIMB: thin, simple SQUAMOUS EPITHELIUM, quite passive so not many mitochondria, loose tight junctions because it concerns water reabsorption. ASCEDNDING LIMB: less thin, CUBOIDAL EPITHELIUM and many mitochondria because it concerns Na+ movement, few microvilli.
How is ascending limb impermeable to water? (x2)
Very tight, tight junctions. Unlike descending limb where there are loose tight junctions, so water can move paracellularly. ALSO lack aquaporins.
The counter-current multiplier system is not enough to concentrate the urine: what other mechanism enhances the reabsorption of water in the loop of Henle and collecting duct?
MOVEMENT OF UREA! The circled areas are both permeable to urea. At these points, fluid inside the tubules are hyperosmolar (not much water), so concentration of urea is high! The process is:
- At the distal end of collecting duct, urea moves out down concentration gradient into interstitium. Movement continues until equilibrium.
- When this happens, concentration of urea in intersititum will be higher than concentration of urea in loop of Henle, so urea diffuses into descending limb of loop of Henle (and lower region of ascending limb).
- Urea cycles back round to same region of the collecting duct where urea moves out again. This cycle continues and each time, urea concentration in interstitium continues to rise, so urine can be concentrated even more!
What are the four types of urea transporter? Where are each found? Don’t emphasise these in revision!
UT-A2 (descending limb), UT-A1 and UT-A3 (inner medullary collecting duct – A1 in apical, and A3 in basolateral membrane) found in the nephron. UT-B1 found in the descending vasa recta.
What is the mechanism of ion movement in the DCT?
Na+ and Cl- cotransporter is linked to Ca2+ reabsorption.
- Na+/K+ pump on basolateral membrane pumping sodium out of cell.
- This creates low concentration of sodium inside cell.
- Therefore, sodium moves in passively by Cl- cotransport in apical surface AND Ca2+ COUNTER-transporter in basolateral surface.
- Ca2+ moves in passively from tubular fluid to replace Ca2+ that has moved into blood.
What happens to DCT mechanism when Thiazides are used? Result and mechanism?
Blocks Na+/Cl- cotransporter.
- Na+/K+ pump continues pumping as normal.
- Low intracellular Na+ concentration must be compensated by Na+/Ca2+ counter-transporter.
- So, more Na+ is pumped in and more Ca2+ out than normal from the counter-transporter.
- This means that more Ca2+ must be moved in from the apical side from the tubular fluid.
- RESULT: rise in plasma Ca2+!
What is the function of the principal cell of the collecting duct?
Contains aldosterone-sensitive Na+ system, important in Na+, K+ and water balance. Mediated by Na/K ATP pump (linked to K+ channel).
What is the function of the intercalated cell in the collecting duct?
Important in acid-base balance using H+-ATP pump.
How does the collecting duct concentrate the urine? Aquaporins in luminal and basolateral membrane?
Remember, medulla has hyper-osmotic extracellular fluid, so water can move out of the collecting duct as urine passes down it. As it goes down the collecting duct, more and more water is removed, as the medulla gets more hyper-osmotic.
Rate of water movement depends on aquaporin-2 in apical membrane, controlled by ADH.
Basolateral membrane has aquaporin-3, not controlled by ADH. Allows for rapid movement of water into the blood once it has moved into the collecting duct walls.
What is the negative feedback loop of ADH release and urine flow rate when plasma osmolarity falls? Limit?
Solute reabsorption without water reabsorption can lower urine osmolarity to a minimum of 50 mosmol/L = as dilute as the urine can get (already mentioned earlier, but this is contextual application).
What is the negative feedback loop of ADH release and urine flow rate when plasma osmolarity rises?
Plasma osmolarity increases in dehydration.
There are two effects when this is recognised by osmoreceptors – thirst AND ADH release – aim is the increase water intake and decrease fluid loss respectively, to lower plasma osmolarity. ADH release means aquaporins inserted, so osmotic equilibration in cortex and medulla occurs = high urine osmolarity.
What proportion of sodium is reabsorbed at each region of the nephron? Note about sodium regulation?
Overall in the nephron, what proportion of Na+ should be reabsorbed into the blood?
Remember, none happens in the descending limb, because it is impermeable - look at photo.
> 99%.
How does percentage of water remaining in filtrate change as filtrate moves through nephron?
Absorbed in PCT at the same rate as sodium, and reabsorbed in the descending limb. Ascending limb is impermeable to water, but DCT reabsorbs water further. The CD fine-tunes water reabsorption via ADH from central osmolarity receptors.
How does percentage of INULIN remaining in filtrate change as filtrate moves through nephron? What is inulin?
It is an exogenous (but small) substance and FREELY FILTERED and not reabsorbed and not secreted.
How does percentage of SODIUM remaining in filtrate change as filtrate moves through nephron?
Two thirds reabsorbed in PCT, the descending limb is impermeable to sodium, and the ascending limb absorbs another 20% or so. Last 20% reabsorbed equally across DCT and collecting duct.
How does percentage of GLUCOSE remaining in filtrate change as filtrate moves through nephron?
100% reabsorbed in PCT.
SUMMARY: How do epithelial cells of the nephron differ?
What is the mechanism underlying renal tubule acidosis? (x2)
(1) Failure to excrete potassium, so urine does not remove acidity from blood. (2) Problem with carbonic anhydrase, so protons are not produced for excretion.
What is the mechanism of Bartter syndrome? Where does the mutation effect?
ASCENDING LOOP OF HENLE. Mutations in the following mechanism – photo.
What is the mechanism of Dent’s disease?
Mutation affects acidification of endosome carrying protein into proximal convoluted tubule cell, so receptor that carries the protein cannot dissociate:
- NORMALLY: H+ gets pumped into the endosome containing the protein-receptor complex, and pH goes down. At the same time, positive charge goes up, so electrochemical gradient means that it becomes harder to pump further H+ ions into the endosome.
- More H+ ions need to be moved into the endosome to lower the pH enough for the protein-receptor complex to dissociate. SO, there is a counter-transporter that takes one H+ out (meaning some acidity is lost), and 2Cl- are pumped in – so more protons can be pumped in to lower pH further.
- MUTATION: affects counter transport, so you cannot not get to low enough pH to dissociate the protein.
