L17*-Physiology of the renal system III-Tubular reabsorption Flashcards
(17 cards)
What are the 2 parts that the Proximal tubule is divided into and where are they found ?
-early 60% of the part is proximal convoluted tubule; the rest is the proximal straight tubule.
-Is present in the renal cortex
What is the surface area of the P.T is enhanced by ?
The surface area of the proximal tubules is greatly enhanced by the presence of microvilli
forming a brush border.
What are the different transport mechanisms found in the PT ?
- selective distribution of ion channels, exchanges and co transporters (secondary A.T) and pumps (Primary A.T) on the apical and basolateral membrane.
- movement of ions through cells( transcellular) and between the cells (paracellular)
- movement of Na+ creates an osmotic gradient for the movement of water transcellularly.
- Proximal tubule is water 💦 permeable, making the filtrate is isotonic with the interstitial space so in cortex it is isotonic with plasma.
*By the end of the tubule, about 70% of the water is reabsorbed.
How is the movement of Na+ important in PT and how is the Na+ removes after ?
- Uses the movement of Na+ down its
electrochemical gradient into the epithelial cells to drive the movement of other substances (e.g. glucose, and amino acids). - Uses the Na+/K+ ATPase (and other mechanisms) to move Na+ out of the cell on the basolateral membrane.
Explain the water movement in the proximal tubule.
-Water flows through paracellular route bc of the net outward hydrostatic and osmotic forces.
-Water flows through transcellular route bc of aquaporins. AQP1, from the filtrate into the cortical interstitial space.
Explain the glucose transport in the proximal tubule.
and
explain tubular maximum
- 90% of glucose is transported by the low affinity/high-capacity sodium glucose cotransporter 2 (SGLT2). The rest is carried by SGLT2 ( high affinity/low-capacity) transporter 1.
-Basolateral transport is by GLUT2 or GLUT1.
-Tubular maximum(Tm) is the maximum tubular load for glucose .about 380 mg.min-1; 2.1 mmol.min-1)
Examples of SGLT2 inhibitors
SGLT2 inhibitors > treatment of diabetes.
- canagliflozin, dapagliflozin.
* The concept is that by inhibiting the
transporters, you cause glucosuria(glucose in urine), and hence drop blood glucose.
Explain amino acids transport in the proximal tubule.
Sodium-dependent transporters( Na+ amino acid cotransporters) actively move amino acids from the tubular lumen into epithelial cells = reabsorb
after entering tubular cells, a.a are transported into the blood stream via facilitated diffusion or A.T, ensuring they return to circulation = transport across the basolateral membrane.
Explain Cl- movement in the proximal tubule.
-Both active and passive movement of Cl-
-main active movement of Cl-through an antiporter for other anions like HCO3- /HCOO- > methanoatel.
- Given the absorption of HCO3-, with the charge difference balanced by Na+ absorption, less Cl- is moved than Na+ in the early proximal tubule. Given that water is
reabsorbed with the Na+ and HCO3-, this means that the Cl- concentration modestly increases along the proximal tubule.
* As this Cl- concentration increases (towards the end of the proximal tubule), it drives (passive) paracellular Cl- movement down its concentration gradient.
Explain active secretion in the proximal tubule.
-many organic anions are actively secreted in the proximal tubule (e.g. penicillin, p-aminohippuric acid [PAH], furosemide); the negative charge often comes from carboxylates of sulfonates.
* Organic anions compete with one another for
excretion
* Basolateral membranes: organic anion
transporters (OAT)
* Luminal membrane: multidrug resistance-
associated protein (MRP)
What are the 2 distinct components of loop of Henle ?
Descending limb
Thick ascending limb
Function of the thick ascending limb
- To create a hyperosmolar interstitial space(area with a high concentration of solutes like Na and urea) in the medulla ,AND…..,
-to drive water loss from the descending limb and cortical collecting duct.
-Uses the Na+/K+/2Cl- cotransporter to move ions out of the filtrate.
Common abbreviation: NKCC2; Systematic name of the gene: SLC12A1. This is a member of the SLC12 family of ‘cation coupled chloride transporters’.
* K+ recycling through the apical membrane is
necessary in order to ensure that the transporter can maintain its role of transporting large quantities of Na+ and Cl-
Function of descending limb.
D.limb is highly permeable to water so water leaves the filtrate in the nephron due to high osmolarity outside(or due to osmotic force).
What is Furosemide
- Acts in the ascending limb of Loop of Henle (a “loop” diuretic)
- Blocks Na+/K+/2Cl- co-transporter, stops the osmotic gradient building up in the medulla hence stopping water reabsorption > 👆se in urine output.
- Allows up to 20% of filter Na+ to be excreted, causing enormous natriuresis and diuresis.
- Uses: cardiac failure, renal failure
Side effects: K+ loss (and subsequent hypokalaemia), leading to cardiac dysrhythmias (particularly when administered with digoxin)
Other side effects:
Hypovolaemia (assessed by acute weight changes)
Mild metabolic alkalosis (distal Na+/H+ exchange)
Loss of Mg2+ and Ca2+ (loss of filtrate +ve charge)
What stimulates the synthesis of Na+,K+ transport sand water transport in C.D and explain briefly about CD.
- Na+,K+ transport - Aldosterone
- water transport -ADH
-C.D is the last place where the body can regulate composition of urine. - place with most regulation
Give an example of a diuretic in the CD and what it inhibits and what it causes ?
- Spironolactone
Acts in the Collecting tubules and ducts - Blocks the effect of aldosterone
- Moderately effective diuretics
- Uses: heart failure (K+ sparing diuretic)
Other side effects:
Gynaecomastia, menstual disorders, testicular atrophy hyperkalaemia
Explain the urea countercurrent multiplication mechanism in the collecting duct.
-Urea is not just a waste product, urea is used by the kidney to help reabsorb water via cycling around few times before being eliminated.
- Urea is transported from the UT-A1 in CD into the UT-A2 in D.L(recycling) which allows the reabsorption of urea. Urea 👆ses the osmolality of the medulla.
