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Physiology Block 3 > 4 - Renal Tubular Transport > Flashcards

4 - Renal Tubular Transport Flashcards

1
Q

What are processes in the kidney that determine the final composition of urine?

A

RPF, GFR, and reabsorption.

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2
Q

For many substances, what percentage of of the filtered load (from the glomerulus) is reabsorbed? Give a few examples of substances for which this is true.

A

Over 99%.

Glucose, bicarb, sodium, chloride.

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3
Q

What is the structure of renal tubules?

A

They are a collection of epithelial cells organized analogously to a 6-pack of cans held together with plastic rings.

Top of can = apical or luminal side of cells

Sides and bottoms of cans = basolateral or interstitial side of the cells.

Plastic rings = tight junctions

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4
Q

What are the basic pathways that fluid can be reabsorbed from the lumen? Is energy used?

A

By paracellular (across the tight junctions) or transcellular (across the cells) pathways.

This can be active (coupled to ATP) or passive diffusion.

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5
Q

How does water move across the renal epithelial cells?

A

Via osmosis, therefore it will follow solute reabsorption in the segments that are permeable to water.

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6
Q

Why is the mechanism for sodium handling so important?

A

It’s the most common cation in the ECF.

The reabsorption of other substances is dependent (directly or indirectly) on the tubular handling of sodium and potassium by the Na/K ATPase on the basolateral membranes of epithlial cells. .

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7
Q

What is the function of the Na/K ATPase? Why is this important?

A

Maintain a low intracellular Na and a high intracellular K to maintain a charge of ~70mV inside the cell.

This gradient is used in many co/counter transport systems in which other solutes are reabsorbed or secreted in mechanisms coupled to sodiums movement into the cell.

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8
Q

What does the proximal tubule (PT) reabsorb?

A

67% filtered water, Na+, and K+ (water follows Na passively-isosmotic reabsorption)

50% filtered urea

85% filtered HCO3-

~100% filtered load of glucose, amino acids, and protein.

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9
Q

Where is the energy for PT reabsorption obtained from?

A

Na/K ATPase pump.

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10
Q

What does the reabsorption of NaHCO3 and water generate?

A

A Cl- gradient which is the force for the passive reabsorption of sodium.

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11
Q

What is one mechanism by which sodium is reabsorbed in the PT?

A

1/3 occurs by the Na/H counter-transporter.

Uses electrochemical gradient for sodium reabsorption in PT cells and couples it to the secretion of H ion.

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12
Q

Where is bicarbonate permeable to the PT cells?

A

It is impermeable to the apical membrane, but the brush borders of the membrane and the cytoplasm contain carbonic anhydrase (ca).

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13
Q

What is the role of carbonic anhydrase?

A

In the tubular lumen, filtered bicarb combines with H+ ions to form carbonic acid (H2CO3); this dissociates into CO2 and H2O (catalyzed by CA).

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14
Q

What happens to the CO2 and H2O created by carbonic anhydrase.

A

CO2 diffuses into the cytoplasm to combine with water and participate in the reverse rxn to reform HCO3- and H+.

HCO3- can then move across the basolateral membrane by a transporter while H+ is secreted by the Na/H exchanger.

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15
Q

What are the three things that the Na/H exchanger and CA accomplish together?

A

Sodium reabsorption, bicarbonate reabsorption, and acid secretion.

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16
Q

What is a second major mechanism for sodium reabsorption in the PT?

A

Co-transport with glucose or amino acids. Takes advantage of the gradient favoring reabsorption of sodium.

This accounts for the reabsorption of 100% of the filtered load of glucose and aas and ~1/3 of the sodium reabsorption.

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17
Q

What is a third mechanism for sodium reabsorption in the PT?

A

An Na/H exchanger that’s coupled to an anion/Cl exchanger in which the anion is going into the lumen and the Cl- is reabsorbed.

Anions include formate, hydroxide, oxalate, or sulfate

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18
Q

The reabsorption of Na early in the PT leads to what?

A

An increase in Cl- concentration and lumen negative potential.

This provides a driving force for passive Cl- movement across the tight junction.

Na+ is reabsorbed along with Cl- through this mechanism.

19
Q

How are sodium and chloride reabsorbed in the late PT?

A

Passive diffusion.

The reabsorption of Na+ (with water) in the early segments, leads to increased Cl and negative luminal potential, and increased urea concentration.

This leads to passive reabsorption of urea and Cl- in the late PT.

20
Q

How does the proximal tubular fluid/plasma (TF/P) concentration ratio of creatine change from the beginning to the end of the PT?

A

Creatine is not absorbed, so the concentration increases as fluid progresses through the PT.

21
Q

How does the proximal tubular fluid/plasma (TF/P) concentration ratio of Cl-, Urea, Na+, and osmolarity change throughout the PT?

A

Cl- and urea (like creatine) increase, which provides the driving force for their passive diffusion in the late PT.

Na+ and osmolarity are fairly constant due to isosmotic reabsorption in this segment.

22
Q

How does the proximal tubular fluid/plasma (TF/P) concentration ratio of HCO3-, glucose, and amino acids change throughout the PT?

A

Ratio of HCO3- decreases, reflecting the reabsorption of the majority of filtered HCO3- in the PT.

Glucose and amino acids is decreases the greatest because they are almost 100% reabsorbed.

23
Q

Describe the carrier mediated reabsorption of solutes in the PT? Describe this in terms of the Na/glucose co-transporter.

A

It is saturable.

The Na/glucose transporter will remove all of the filtered glucose up until it reaches its maximum capacity (375 mg/min). At that point, the filtered load exceeds the reabsorptive rate for glucose.

24
Q

What is the difference between filtered load and reabsorption of glucose equal to?

A

The glucose spilled into the urine (urine glucose excretion rate).

25
Q

How does filtered load relate to GFR? What does this tell us about an increase in plasma glucose concentration?

A

Filtered load = GFR x plasma concentration of substance

This means that filtered load will increase as plasma glucose concentration increases if GFR remains constant.

26
Q

Describe the balance of hydrostatic and oncotic forces in the peritubular capillaries?

A

It favors reabsorption back into the blood (as opposed to net filtration like the glomerulus).

This makes sense because about 99% of filtered water and solute is reabsorbed, which must occur in the post-glomerular capillary beds.

27
Q

Which osmotic pressure is higher in the peritubular capillaries?

A

They have a relatively low hydrostatic pressure (compared to glomerular capillaries) and a high oncotic pressure (due to the presence of proteins that were not filtered by the glomerulus).

There is also low interstitial pressure and interstitial oncotic pressure.

Net: favors reabsorption

28
Q

What is an additional property of PT epithelial cells?

A

Secretion, the movement of solute from interstitium into the tubular lumen.

Complex process in which organic anions are secreted. These mechanisms are saturable.

29
Q

Describe the secretion of PAH?

A

It is equal to the sum of the filtered load and secreted PAH.

When plasma PAH exceeds .1 mg/ml, the transport maximum of the organic anion secretory mechanism is exceeded.

Thus the clearance of PAH at plasma concentrations greater than 0.1 mg/ml is not an accurate measure of RPF. (must be corrected for PAH extraction)

30
Q

What are the endogenous organic anions secreted in the proximal tubule?

A

cAMP, bile salts, hippurates, oxalate, prostaglandins, and urate.

31
Q

What are the exogenous organic anions secreted in the PT?

A

PAH, acetazolamide, chlorothiazide, furosemide, penecillin, and salicylates.

32
Q

Filtered load of PAH + secreted PAH = _________?

A

Excreted PAH

33
Q

What are the endogenous organic cations secreted in the PT?

A

Creatinine, dopamine, epi, and norepi.

34
Q

What are the exogenous organic cations secreted in the PT?

A

Atropine, isoproterenol, cimetidine, morphine, quinine, and amiloride.

35
Q

What occurs in the thin descending loop of henle?

A

Permeable to water but limitedly permeable to solutes.

Water is reabsorbed following an osmotic gradient.

36
Q

What occurs in the thin ascending loop of henle?

A

It is impermeable to water, but permeable to sodium and urea.

Passive reabsorption of sodium by passive diffusion.

Urea is excreted.

37
Q

What occurs in the thick ascending limb of the loop of Henle?

A

Impermeable to water.

Differs from other segments b/c there is active transport of Na+ by the Na/K/2Cl transport mechanism, driven by the electrochem gradient for Na reabsorption.

Here ~25% of the filtered load of Na is reabsorbed.

38
Q

What is another important mechanism for reabsorption in the thick ascending limb of the loop of henle?

A

The Na/H exchanger in the apical membrane, which allows H secretion and HCO3- reabsorption.

There is also paracellular reabsorption of divalent cations and magnesium.

39
Q

What happens to the K+ reabsorbed by the Na/K/2Cl transporter in the thick ascending loop?

A

It diffuses back across the apical membrane.

This leads to a slightly positive luminal membrane charge that favors diffusion of cations across the tight junctions in this segment.

40
Q

What occurs in the early distal tubule? What is it permeable to and what is reabsorbed?

A

Impermeable to water.

The primary reabsorption in this segment is by a Na/Cl co-transporter that’s sensitive to thiazide diuretic agents.

Calcium and magnesium are also reabsorbed here.

41
Q

What is the function of the principal cells of the late distal tubule and cortical collecting duct?

A

Primary site for water reabsorption, permeability regulated by ADH.

They also reabsorb sodium and secrete potassium, which is dependent on aldosterone.

42
Q

How is sodium reabsorbed in the late distal tubule and cortical collecting duct?

A

A sodium channel in the apical membrane, known as the epithelial sodium channel (ENaC).

Coupled to secretion of K through a separate channel.

43
Q

What is a second type of cell in the collecting duct?

Where are these located specifically?

A

The intercalated cell: important for reabsorption of bicarb and potassium.

These are found in the collecting duct segment in the outer medulla.

44
Q

How do the inner medullary collecting duct cells differ from the principal cells?

A

They reabsorb water in the presence of ADH.

Reabsorb Na in a process similar to principal cells, but this process is not coupled to K secretion.

In the distal portion, urea is reabsorbed, which is mediated by ADH.

Physiology Block 3 (17 decks)

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