Basic Transport Mechanisma and Renal Handling of Organic Solutes

Question 1

What does the basolateral face?

Apical membrane?

Answer 1

Basolateral membrane face the Body. Blood- peritubular capillaries

Apical membrane- faces the tubular membrane– it may have increased folding for increase in SA and the membrane is sometimes called the brush border

Question 2

Two means of trasnport between lumen and circulation

The transcellular route takes the substance through the epithelial cells

Answer 2

Paracellular- transport pathway where the substance travels between cells through

Question 3

What happens in transcellular? What determines paracellular?

Answer 3

**Transcellular-** This route
requires the substance to cross **both the apical and basolateral** membranes. Substances cross these membranes using a variety of different **transport mechanisms (channels, carriers, pumps, etc)**. Thus, transcellular transport depends on parameters like concentration gradients (across the membranes), membrane potential, membrane permeability and (of course) the presence of
particular transporters (channels, carriers, pumps, etc). Transcellular transport can be eitherpassive or active transport.

Paracellular- crosses the so-called tight junctions as well as the intercellular spaces between neighboring cells. Transport via the paracellular route is determined by the permeability (or
“tightness” of tight junctions), the concentration gradients across the tight junction and in some cases (i.e. for ions) the transepithelial potential. Paracellular transport is passive and is generally non-selective

Question 4

Common explains of transcelluar solutes?

paracellular?

Answer 4

Trancellular- H2O, Na+, Ca2+ and glucose.

Paracellular- H2O, Cl- and urea.

Question 5

What is a unique requirement of transcellular transport?

Answer 5

Cells must be functionally polzrized. i.e.
transport mechanisms in apical & basolateral membranes are different). For example, the mechanism of Na+ transport at the apical membrane may be different than the mechanism of Na+
transport at the basolateral membrane.

Question 6

Explain the 4 major steps in renal transport of NaCl and Water

Answer 6

Step 1 is the active transport (directly ATPdependent)
of Na+ across the basolateral membrane by the Na-K-ATPase. This moves Na+ up its electrochemical gradient into the interstitium near the peritubular capillaries. The active Na+pumping lowers the Na+ concentration inside the epithelial cell.

Step 2- is Na+ transport across the apical membrane. This may occur via a variety of symporters, antiporters and channels. The
driving force for this apical transport is the Na+ gradient that was established by the active Na+ pumping on the basolateral membrane.

Step 3- Water moves across cell layer because the Na+ accumulation made a local osmotic gradient.

Step 4- Bulk flow of water from interstium into peritubular capillary.

1. Active of Na+ across basolateral
2. Seconday of Na acorss apical
3. Water follows b/c of local osmotic gradient
4. Bulk flow from interstiutum to capillary

Question 7

Characteristics of passive flow

Answer 7

1. No energy
2. Diffusion (sometimes bulk flow) down a chemical or electrical gradient

Call facilated when it involved transport proteins. (like GLUT)

Question 8

Characterisitcs of active transport

Answer 8

1. Requires energy
2. Can be primary or seconday

A. Primary direct use of metabolic eneryg

B. transport that does not directly utilize metabolic energy in the transport process, but instead utilizes the electrochemical
gradient of some solute (frequently Na+) that was established by a primary active transport mechanism.

Question 9

Special transport proteins?

Other methods of trasnport

Answer 9

Uniporters, symporters, antiporters

Endocytosis, exocytosis

Question 10

Explain Transport Max

What’s another possible limiting factor?

Answer 10

Remember however- that anything that uses a transport protein can saturate. The reason is that there can be only so many transporters in a membrane and each of these can only work so fast. Thus, the rate of transport will saturate once all transporters are working at 100% capacity

Pump leak- substance is “pumped” in one direction but can “leak” back in the other. Thus, transport (or pumping) will be limited by the size of the leak. In renal tubules, a pump may move a solute transcellularly and it may then leak back via the paracellular route. So the tight junctions can greatly effect efficiency

Question 11

What is the primary site of reabsorption of nutrients

Answer 11

Proximal tubule (liek glucose, AA, Kreb cycle intermediates, vitamins)

Question 12

What are some standarizations about nutrient reabsorption

Answer 12

1. Nutrients are usually actively transported (usually by symport with Na+)
2. Most nutrient transport mechanisms have a TM.
3. Nutrient transport mechanisms have specificity. Meaning that the transport mechanism will only recognize one (or a few) substances and ignore others. but this doesn’t mean every nutrient has it’s own transporter. Like may recgonize several closely related AA— which can lead to competition and the loser being excreted.

Question 13

Normal plasma glucose level in mg/ml and mM

Answer 13

.9mg/ml

5mM

Question 14

Steps of reabsorbing glucose

Answer 14

Glucose is freely filtered and all should be reabsrobed in the proximal tubule entirely through transcellular since the tight junctions in the proximal tubule are nearly impermeable to glucose

1. primary active transport of Na+ by the Na-K-ATPase on the basolateral membrane– making lwo intracellular Na+

2. The chemical energy in the Na+ gradient is used by the Na-
Glucose symporter (on the apical membrane) to move glucose up its concentration gradient into the cell from the tubular lumen-- **Seconday active trasnport!!!** -- This is the rate limiting step

3. Facilitated movement of glucose out of the cell through GLUT passively on baslateral membrane
4. Water and solute from interstitum into the peritubular capillary.
5. Active Na+ making intracelluar Na+ low
6. Seconday (RLS) of symport on apical of Glucose nA
7. Glut so glcuose passively facilated at basolateral
8. Bulk flow from interstitum to pertibullary

Question 15

At what value does glucose usually reach Tm- what happens

Answer 15

plasema glucose of 3mg/mL or 300mg/dL

At this point the Pglucose x GFR is a little under 400 mg/min and then the maximal rate of glucose transport will be insufficient to reabsorb the entire filtered load of glucose. In this case, the glucose that is not transported (reabsorbed) will be excreted

At this point we have very hyperosmotic product in the tubes so water is drawn in and we would urinate omre– diresis in diabetics!

Question 16

Explain what proteins are in filtrate

How are they reabsorbed (2)

Answer 16

the 1% of small proteins- insulin and angioII are freely filtered
and reaborbed in the proximal tubule one of two ways

1. Some through endocytosis. Protein binds to receptor of apical membrane– this can reach Tm. Endocytosis takes the protein through a membrane vesicle to the cytoplasm and it merges iwth lysosomes that degrade the proteins into small fragments that can cross the basolateral membrane
2. Others can be tethered to the apical membrane and degraded by peptidases and the resulting AA are trasnported across apical membrane by Na-dependent Aa symported thatnormally reabosrb filter AA

Question 17

Explain seceteion of organic anions

Answer 17

1. Some are filtered and secttrion adds to excretio, but others are bound to plasma proteins to large to be filtered so the only means is secetion

Tight junctions are no permeable to organic anions so they are trhoguhs transcellular transport.

there are active transporters for these anions on the basolateral membrane that pump these substances into the cell. Then, their
transport across the apical membrane is accomplished by facilitated diffusion using uniporters or
occasionally by Na-dependent antiporters.

Question 18

Explain the process of urate filtration

Answer 18

Urate is filtered (as it’s not protein bound) and then the proximal tubule successively reabsorbed, secretes and then again reabsorbs urate. The rate of the secretory process can be
controlled/adjusted by the body. In the end, typically 10% of filtered urate is excreted. Why urate handing is so complex is not yet clear.

Question 19

Two main functions of urea

Answer 19

1. It is both a waste product
2. key to controlling the body’s water balance.

Question 20

Explain urea prodcution and excrettion

Answer 20

1. Urea is produced continuously by the liver as an end product of protein metabolism.
2. Its rate of production may vary with diet but it never stops.
3. Toxic plasma levels of urea result in a condition called uremia. 4. Over days and weeks, renal urea excretion normally
   matches hepatic production. This may not be the case over hours and days because urea excretion is regulated for other purposes

Question 21

Explain what it happening to urea at each step of the nephon

Answer 21

1. BC- freely filtered because it’s small and water soluble
2. Proximal tubule about half is reabsrobed
3. Loop of Henle- about half is secreted back to filtrate
4. urea is reabasorbed again from the medullary collecting
   duct.

Steps 3 and 4 are in the medulla- and part of medulla urea cycling

The net result is that about half of the filtered urea ends up in the urine. The numbers here can (and do) vary with body hydration status

Question 22

The ratio around the nephron regarding urea is what?

What are the figures at each point and why

Answer 22

Top number equals percent of filtered urea in tube over the lumenal concentraiton relative to plasma

1. BC- 100%/1- everything filtered is there and the urea concentratio is identical to the plasma.
2. Proximal- 50%/1.2- half is reaborded (PARACEULLARLY PASSIVELY) and but it’s still 25x more concentration because more water is reabsorbed than urea
3. loop of Henle- (100/5.5) tight junctions are not permeable to urea so they must go through transcellar. Although its higher than plasma (110/5.5) it’s still lower than the medulla, so more is driven into the lumen by uniportes facilatation.
4. CD- (50/25) more water is reabosrbed so the urea concentration is even higher. So high that when it reaches the medulla again urea leaves the tubule goig down it’s gradient facilitated by uniporters.

3 and 4 can vary greatly ebcause the medulla concentration of urea varies with hydration status. Long term urea excretion matches heptic urea production and the body should stay in urea balance.