Reabsorption + Secretion Flashcards
What substances are reabsorbed by carrier mediated transport systems?
e.g. glucose, amino acids, organic acids, sulfate and phosphate ions
What is Tm? How does it relate to carriers?
Maximum transport capacity
Carrers have a Tm which is due to saturation of carriers; if it is exceeded, then excess substrate enters the urine
Capacity is limited by number of carriers; what is ‘renal threshold’?
Plasma threshold (mg/mL) at which saturation occurs
Tm (mg/min), is transport rate at saturation
How much of glucose is filtered?
All - it is freely filtered
Up to what value will glucose be reabsorbed?
10mmoles/l
What happens if concentration of glucose exceeds 10mmoles/l? So what is the distribution of 15mmoles/l plasma {glucose]?
Beyond this level of plasma {glucose}, it appears in the urine = renal plasma threshold for glucose
So 15mmoles/l - 15 filtered, 10 reabsorbed and 5 excreted
Does the kidney regulate [glucose]?
NO; insulin and the counter-regulatory hormones are responsible for its regulation
What is the normal [glucose]?
5mmoles/l
So Tm is set way above any possible level of (non-diabetic) [glucose], ensuring all this valuable nutrient is normally reabsorbed
What does the appearance of glucose in the urine of diabetic patients indicate?
Glycosuria - due to failure of insulin NOT the kidney
Any patient w glucose in urine should be followed up
For amino acids, is Tm set high?
YES, set so high that urinary excretion does not occur, as with glucose
(AAs regulated by insulin and counter-regulatory hormones same as glucose)
Does the kidney regulate sulfate and phosphate ions?
YES, by means of the Tm mechanism
How does the kidney regulate sulfate and phosphate ions by the Tm mechanism?
Tm is set at a level whereby the normal [plasma] causes saturation; so any increase above normal level will be excreted, therefore achieving its plasma regulation
(also subject to PTH regulation for phosphate, PTH decreases reabsorption)
Which ions are the most abundant in ECF?
Na+
What does this abundance of Na+ ions in ECF mean in terms fo filtration?
A large amount is filtered every day
How much Na+ is reabsorbed
180 l/day x 142 mmoles/l = 25560 mmoles/day so 99.5% is reabsorbed
How much of Na+ reabsorption occurs in the proximal tubule?
65-75%
How are Na+ ions reabsorbed? (NOT by Tm mechanism)
Active transport (establishes a gradient for Na+ across tubule wall)
What drives the whole process of Na+ transport?
Na+ pumps
Where are active Na+ pumps located? Why?
On the basolateral surface - side which is exposed to the interstitial fluid, not side which is exposed to the tubule lumen, because there is a high density of mitochondria
Active Na+ pumps decrease [Na+] in epithelial cells, meaning waht for the gradient of Na+ ions?
Increases the gradient for Na+ ions to move into cells passively across the luminal membrane
Na+ is NOT permeable at cell membranes tho, so what about the brush border of the proximal tubule cells has a higher permeability to Na+ ions than most other membranes of the body?
Enormous surface area offered by microvilli and large number of Na+ ion channels, which faciliate this passive diffusion of Na+
Reabsorption of Na+ ions is key to what?
Reabsorption of other components of the filtrate
How do Cl- ions diffuse across the proximal tubular membrane?
Cl- diffuse across passively down the electrical gradient established and maintained by the active transport of Na+
What force does the active transport of Na+ out of the tubule followed by Cl- create? What happens as a result?
Osmotic force
H2O is drawn out of tubules by osmosis meaning the substances left in the tubule are concentrated creating outgoing concentration gradients
What 2 factors does rate of reabsorption of these non-actively reabsorbed solutes depend on?
- Amount of H2O removed, which will determine the extent of the concentration gradient
- The permeability of the membrane to any particular solute
How much urea is reabsorbed? Why?
50%
Because the tubule membrane is only moderately permeable to urea and so remainder stays in the tubule
For some substances the tubular membrane is impermeable, name 2; so what happens to them?
Inulin
Mannitol
Despite conc gradient favouring their reabsorption, they cant gain access through tubule membrane so all that is filtered stays in the tubule and passes out in urine
It is the active transport of Na+ that establishes the gradients down which other ions, H2O and solutes pass passively, so anything that decreases active transport e.g. decreased BF, leads to what?
Disruption of renal function
How is transport of sodium related to transport of substances such as glucose, amino acids etc?
They share the same carrier molecule as Na+ (symport)
High [Na+] in the tubule facilitates and low [Na+] inhibits glucose transport
(Na+ reabsorption also linked to HCO3- ion reabsorption)
What is the function of the SGLT (sodium-dependent glucose transporter)?
Allows Na+ to move into the proximal tubule cell down its electrochemical gradient and pulls glucose into the cell against its concentration gradient
How are glucose and Na+ diffused out of the proximal tubule cell?
Glucose diffuses out the basolateral side of the cell using the GLUT protein
Na+ is pumped out by Na+-K+-ATPase
What is tubular secretion?
Secretory mechanisms transport substances from the peritubular capillaries into the tubule lumen and provide a second route into the tubule
What substances is tubular secretion important for? Why?
Substances that are protein-bound, since filtration at glomerulus is very restricted
Also for potentially harmful substances, means they can be eliminated more rapidly
Tm -limited carrier-mediated secretory mechanisms are known for a large number of endogenous as well as exogenous substances such as…
drugs
What is the benefit to carrier-mediated secretory mechanisms not beinf very specific?
So that e.g. organic acid mechanism (which secretes lactic and uric acid) can also be used for substances such as penicillin, aspirin and PAH (para-amino-hippuric acid)
Similary, organic base mechanism for choline, creatinine etc can be used for what?
Morphine and atropine
Where are all of these substances secreted?
Proximal tubule
What is the major cation in the cells of the body? (making its balance essential for life)
K+
What is normal ECF[K+]
~4mmoles/l
What happens in hyperkalaemia ([K+] up to 5.5mmoles/l)?
Decreased resting membrane potential of excitable cells and eventually ventricular fibrillation and death
(Nernst equation)
What happens in hypokalaemia ([K+] <3.5mmoles/l)?
Increased resting membrane potential i.e. hyperpolarises muscle, cardiac cells -> cardiac arrythmias and eventally death
Where is K+ filtered at the glomerulus primarily reabsorbed?
Proximal tubule
What are changes in K+ excretion due to?
Changes in its secretion in the distal parts of the tubule
Any increase in renal tubule cell [K+] due to increased ingestion will result in…
Increased K+ secretion
Any decrease in intracellular [K+] will result in…
reduced secretion
In addition, K+ secretion is regulatd by what hormone?
Aldosterone
How is aldosterone production stimulated by potassium?
An increase in [K+] in ECF bathing the aldosterone secreting cells stimulates aldosterone release which circulates to the kidneys to stimulate increase in renal tubule cell K+ secretion
In addition to regulating potassium, what else does aldosterone act on?
Also stimulates Na+ reabsorption at the distal tubule (but by a diff reflex pathway)
How are H+ ions secreted?
Actively secreted from the tubule cells (not the peritubular capillaries) into the lumen - A/B balance
Summarise Biomed Sessions vid on function of nephron
