Tubular Transport of Other Molecules (B2: W4) Flashcards
What is the transport maximum (TM)?
The highest rate (e.g. mg/min) at which the renal tubules can transfer a substance either from the tubular luminal fluid to the interstitial fluid or from the interstital fluid to the tubular luminal fluid.
How is glucose tranported out of the proximal tubule lumen?
Transporter move glucose from the lumen using the concentration gradient of sodium
What is the equation for calculateing the reabsorption rate (TX)?
TX = Filtered load - Excretion rate
= (GFR x PX) - (UX x V)
What happens when the plasma concentration of a substance is below the transport maximum?
The substance is freely filtered into the nephron, and then reabsorbed into he peritubular capillaries by transporters
Nothing is excreted in the urine
What happens when the plasma concentration of a substance increases beyond the transport maximum?
At low plasma concentration (PX), the reabsorption rate (TX) continues to rise
Once the TM has been exceeded, the reabsorption rate remains constant, and the excess is lost in the urine
What happens to the filtration rate as plasma concentration of a subtance increases?
Filtered load goes up
What happens to excretion rate as plasma concentration of glucose increases?
- At low PX, no excretion
- As PX increases, it spills into urine
- Transporters give us splay
- First detection of glucose in urine is not the TM
- Excretion after that is the portion that cannot be reabsorbed
What happens to the reabsorption rate as the plasma concentration of glucose increases?
- There is greater reabsorption as PX increases
- THere is a maxium rate for reabsorption (TM) where it remains constant
How do Sodium-glucose linked transporter-2 (SGLT2) inhibitors work?
Block the reabsorption of glucose so that it can eb excreted in the urine
Antidiabetic drugs
What will happen to the shap of the glucose excretion relationship wif we belock all reabsorption with phlorizin (antidiabetic)?
The curve will shift left
All glucose in the tubule will be excreted
Why is urine flow increased with diabetes mellitus?
- Extra glucose gets into PCT
- More Na goes back into body to transport glucose
- Lowering the NaCl in the PCT, so less NaCl is deliverd to the macula densa
- Sets off TGF → increases GFR → tubular flow and urine flow increase
What happens when a substance is cleared less than inulin?
This substance is reabsorbed and not cleared
E.g. glucose
What happens when a substance has a clearance that is greater than that of inulin?
That substance is being secreted in extra amounts
Compare glucose clearance to that of inulin
- Excretion at low plasma concentration of glucose is 0
- As glucose increases, it is cleared more and more
- Approaches the clearance of inulin, or GFR
- All of inulin in the plasma gets into the tubule, gets trapped, and gets cleared
- Equal to GFR
How is para aminohippurate (PAH) secreted into the tubular lumen?
Picked up by two anion transporters in the late proximal tubule
What is the equation for calculating secretion rate (TX)?
Secretion rate = Excretion Rate - Filtered Load
= (UX x V) - (GFR x PX)
What happens as we increase the plasma concentration of PAH?
- Small amout of PAH in plasma immediately appears in urine
- With increased loads, there is more secretion
- Past a certain load, the transport mechanism can’t work - it has reached TM (80 mg/min)
- Filtration and excretion continue to increase
What happens when the concentration of PAH is below TM?
- 20% is filtered into PCT
- All PAH is secreted in urine
- All plasma is cleared
What happens when the concentration of PAH exceeds the TM?
- Maximal amount of PAH is secreted
- Not all can be secreted
- More is excreted
- Excess PAH stays in capillaries
- Not cleared
- Goes back to body
Compare inulin clearance to that of PAH
- As concentation of PAH increases, clearance of PAH decreases
- Excretion goes up
- Clearance goes down
- TM = 600 ml/min (plateau)
- Inulin clearance remains constant = GFR
How does probenecid work to treat gout?
Probenecid reduces reabsorption of uric acid
- Dumps out uric acid
- Still has side effects
How does allopurinol work to treat gout?
Allopurinol stops the formation of uric acid
- Used more often
What factors affect passive reabsorption of urea?
Reabsorption rate is dependent upon
- Tubular area
- Urea permeability
- Concentration gradient
Although urea must be eliminated every day, ~60% is reabsorbed
Urea goes back into the body because it has been concentrated
Compare the clearance of urea to that of inulin
- Clearance of urea is dependent upon tubular flow
- Increases with increased flow rate
- Inulin concentration does not change based on flow
- GFR must be constant over all of these flow rates
How does urea handling correspond with drinking (water) behavior?
- When drinking - flow is faster
- Lower concentration of urea
- Cleared more
- Reabsorbed less
- When thirsty - flow is low
- Higher concentration of urea
- Cleared less
- Reabsorbed more
How do non-ionic diffusion and diffusion trapping work?
Charged molecules are not likely to move across membranes - get trapped
- If pH in tubule is low
- HA is high
- A- gets trapped in tubule
- If pH in tubule is high
- A- increases
- HA moves in
A patient is brought into the ER after ingesting large quantities of phenobarbital. How might you use the kidneys to help eliminate phenobarbital from his body?
- Give base (e.g. bicarbonate)
- Alkalization of the tubular lumen enhances phenobarbitol secretion
- Give an osmotic diuretic (e.g. manitol) to hold water in the tubule
