Renal Physiology: Guyton Chapter 28

Question 1

[33-minute video]: Guyton and Hall Medical Physiology (Chapter 28) - Renal Tubular Reabsorption and Secretion

Answer 1

💧

Question 2

What are the two main steps for a substance to be reabsorbed in the kidneys?

Answer 2

(1) Transport across the tubular epithelial membranes into the renal interstitial fluid.
(2) Transport through the peritubular capillary membrane back into the blood.

Question 3

What mechanisms are involved in the reabsorption of water and solutes in the kidneys?

Answer 3

(1) Active or passive transport across the tubular epithelium into the interstitial fluid.
(2) Transcellular route: through cell membranes.
(3) Paracellular route: through spaces between cell junctions.
(4) Transport through peritubular capillary walls into blood by ultrafiltration (bulk flow) mediated by hydrostatic and colloid osmotic forces.

Question 4

How does the Na+-K+ ATPase system function in sodium reabsorption?

Answer 4

It hydrolyzes ATP to transport sodium ions out of the cell into the interstitium and potassium into the cell, maintaining low intracellular sodium and high intracellular potassium concentrations.

Question 5

What creates the electrochemical gradient favoring sodium diffusion into the cell?

Answer 5

The low intracellular sodium concentration (12 mEq/L) and high tubular fluid sodium concentration (140 mEq/L), along with the negative intracellular potential of about -70 millivolts.

Question 6

What role does the brush border on the luminal side of the proximal tubule play in sodium reabsorption?

Answer 6

It multiplies the surface area by about 20-fold and contains carrier proteins that facilitate the diffusion of sodium into the cell.

Question 7

What are the three steps involved in the net reabsorption of sodium ions from the tubular lumen back into the blood?

Answer 7

(1) Sodium diffuses across the luminal membrane into the cell.

(2) Sodium is transported across the basolateral membrane by the Na+-K+ ATPase pump.

(3) Sodium, water, and other substances are reabsorbed from the interstitial fluid into the peritubular capillaries by ultrafiltration.

Question 8

What is secondary active transport and how does it work?

Answer 8

In secondary active transport, two or more substances interact with a specific membrane protein (a carrier molecule) and are transported together across the membrane. As one substance (e.g., sodium) diffuses down its electrochemical gradient, the energy released is used to drive another substance (e.g., glucose) against its electrochemical gradient. This process does not require energy directly from ATP but uses the energy from the simultaneous facilitated diffusion of another substance down its own electrochemical gradient.

Question 9

How does the reabsorption of glucose depend on the Na+-K+ ATPase pump?

Answer 9

The reabsorption of glucose depends on the energy expended by the primary active Na+-K+ ATPase pump in the basolateral membrane. This pump maintains an electrochemical gradient for the facilitated diffusion of sodium across the luminal membrane. The downhill diffusion of sodium provides the energy for the simultaneous uphill transport of glucose across the luminal membrane, making this process secondary active transport.

Question 10

What is the transport maximum in the context of renal reabsorption?

Answer 10

The transport maximum is the limit to the rate at which a solute can be actively reabsorbed or secreted, due to the saturation of specific transport systems when the tubular load exceeds the capacity of carrier proteins and enzymes.

Question 11

What happens when the filtered load of glucose exceeds the transport maximum in the proximal tubule?

Answer 11

When the filtered load of glucose exceeds the transport maximum, the excess glucose is not reabsorbed and passes into the urine, leading to urinary excretion of glucose.

Question 12

What is the average transport maximum for glucose in adult humans, and what is the normal filtered load of glucose?

Answer 12

The average transport maximum for glucose in adult humans is about 375 mg/min, while the normal filtered load of glucose is about 125 mg/min. When the filtered load exceeds 375 mg/min, glucose begins to appear in the urine.

Question 13

What is gradient-time transport?

Answer 13

Gradient-time transport refers to the type of active transport where the rate of transport depends on the electrochemical gradient and the time the substance remains in the tubule, rather than reaching a transport maximum.

Question 14

What factors determine the rate of gradient-time transport?

Answer 14

The rate of gradient-time transport is determined by:
(1) the electrochemical gradient for diffusion of the substance across the membrane
(2) the permeability of the membrane for the substance, and
(3) the time that the fluid containing the substance remains within the tubule.

Question 15

How does sodium reabsorption in the proximal tubule demonstrate gradient-time transport?

Answer 15

Sodium reabsorption in the proximal tubule demonstrates gradient-time transport because the maximum transport capacity of the basolateral Na+-K+ ATPase pump is usually far greater than the actual rate of net sodium reabsorption.

Question 16

What happens to solute concentrations and water movement when solutes are transported out of the tubule and into the renal interstitium?

Answer 16

When solutes are transported out of the tubule by primary or secondary active transport, their concentrations decrease inside the tubule and increase in the renal interstitium, creating a concentration difference that causes osmosis of water from the tubular lumen to the renal interstitium.

Question 17

How does water move in the proximal tubules and what is solvent drag?

Answer 17

In the proximal tubules, water moves rapidly through channels known as aquaporins in the cell membranes and through the tight junctions between epithelial cells. Water moving across the tight junctions by osmosis also carries some solutes with it, a process referred to as solvent drag.

Question 18

How does water permeability vary in different parts of the nephron?

Answer 18

💧 In the proximal tubule and descending loop of Henle, water permeability is always high due to the abundant expression of aquaporin-1 (AQP-1).
💧 In the ascending loop of Henle, water permeability is always low.
💧 In the distal tubules, collecting tubules, and collecting ducts, water permeability can be high or low depending on the presence or absence of antidiuretic hormone (ADH).

Question 19

How are chloride ions transported along with sodium during reabsorption in the renal tubules?

Answer 19

💧 When sodium is reabsorbed through the tubular epithelial cell, negative ions such as chloride are transported along with sodium due to electrical potentials. The transport of positively charged sodium ions out of the lumen leaves the inside of the lumen negatively charged, causing chloride ions to diffuse passively through the paracellular pathway.
💧 Additionally, chloride ions are reabsorbed due to a chloride concentration gradient that develops when water is reabsorbed from the tubule by osmosis.
💧 Chloride ions can also be reabsorbed by secondary active transport, primarily through the co-transport of chloride with sodium across the luminal membrane. [The sodium-chloride symporter is found in the DCT.]

Question 20

How is urea reabsorbed in the renal tubules?

Answer 20

Urea is passively reabsorbed from the tubule. As water is reabsorbed from the tubules by osmosis coupled to sodium reabsorption, the urea concentration in the tubular lumen increases, creating a concentration gradient favoring urea reabsorption. However, urea does not permeate the tubule as readily as water, and only about half of the filtered urea is reabsorbed.

Question 21

What facilitates passive urea reabsorption in some parts of the nephron?

Answer 21

In some parts of the nephron, especially the inner medullary collecting duct, passive urea reabsorption is facilitated by specific urea transporters.

Question 22

How is creatinine handled by the renal tubules?

Answer 22

Creatinine is essentially impermeant to the tubular membrane. Therefore, almost none of the creatinine that is filtered is reabsorbed, so virtually all the creatinine filtered by the glomerulus is excreted in the urine.

Question 23

What cellular characteristics of proximal tubule epithelial cells support their high capacity for active and passive reabsorption?

Answer 23

Proximal tubule epithelial cells are highly metabolic with large numbers of mitochondria for active transport. They have an extensive brush border on the luminal side and a labyrinth of intercellular and basal channels, providing a large membrane surface area for rapid transport of sodium ions and other substances.

Question 24

How do protein carrier molecules in the proximal tubule epithelial cells contribute to sodium reabsorption?

Answer 24

💧 Protein carrier molecules in the epithelial brush border transport a large fraction of sodium ions across the luminal membrane via co-transport with organic nutrients like amino acids and glucose.
💧 Sodium is also transported by counter-transport mechanisms that reabsorb sodium while secreting other substances, such as hydrogen ions, into the tubular lumen.

Question 25

What is the difference in sodium reabsorption mechanisms between the early and late portions of the proximal tubule?

Answer 25

💧 In the first half of the proximal tubule, sodium is reabsorbed by co-transport with glucose, amino acids, and other solutes.
💧 In the second half, with little glucose and few amino acids remaining, sodium is mainly reabsorbed with chloride ions. The higher chloride concentration in the second half favors chloride diffusion from the tubule lumen into the renal interstitial fluid.

Question 26

How do the concentrations of various solutes change along the proximal tubule? [Hints: sodium, organic solutes, creatinine]

Answer 26

💧 Although the amount of sodium in the tubular fluid decreases markedly along the proximal tubule, sodium concentration (and total osmolarity) remains relatively constant due to the high water permeability of the proximal tubules.
💧 Organic solutes like glucose, amino acids, and bicarbonate are reabsorbed more avidly [at a faster rate] than water, leading to a marked decrease in their concentrations.
💧 Less permeant solutes like creatinine increase in concentration along the proximal tubule. The total solute concentration remains essentially the same due to the high water permeability of the nephron.
💧 [Diagram]

Question 27

What are some organic acid and base metabolic waste products secreted at the PCT?

Answer 27

bile salts, oxalate, urate, catecholamines [adrenaline, noradrenaline]

Question 28

List the three functionally distinct segments of the Loop of Henle.

Answer 28

the thin descending segment, thin ascending segment, and thick ascending segment

Question 29

What are the epithelial characteristics of the thin descending and ascending segments of the Loop of Henle?

Answer 29

💧 epithelial cells are squamous
💧 few mitochondria
💧 absence of brush border

Question 30

Compare the descending and ascending loops in terms of permeability to water.

Answer 30

💧 The descending part of the thin segment is highly permeable to water [and moderately permeable to most solutes, including urea and sodium]. Its main function is to allow simple diffusion of substances through its walls. About 20% of the filtered water is reabsorbed in the loop of Henle, mostly in the thin descending limb.
💧 The ascending limb is virtually impermeable to water, which is important for concentrating the urine.

Question 31

Compare the thick and thin portions of the ascending loop in terms of permeability to solutes.

Answer 31

💧 The thick segment of the loop of Henle, which begins about halfway up the ascending limb, has thick epithelial cells that have high metabolic activity and are capable of active reabsorption of sodium, chloride, and potassium. [About 25% of the filtered loads of sodium, chloride, and potassium are reabsorbed in the loop of Henle, mostly in the thick ascending limb.] Considerable amounts of other ions, such as calcium, bicarbonate, and magnesium, are also reabsorbed in the thick ascending loop of Henle.
💧 The thin segment of the ascending limb has a much lower reabsorptive capacity than the thick segment, and the thin descending limb does not reabsorb significant amounts of any of these solutes.

Question 32

What is the role of the Na+-K+ ATPase pump in the epithelial cell basolateral membranes of the thick ascending limb of the loop of Henle?

Answer 32

The Na+-K+ ATPase pump in the epithelial cell basolateral membranes maintains a low intracellular sodium concentration, which provides a favorable gradient for the movement of sodium from the tubular fluid into the cell. This pump is crucial for the reabsorption of other solutes in the thick ascending limb. [The potential energy released by the downhill diffusion of sodium into the cell is used to drive the cotransport of other ions.]

Question 33

Briefly discuss the NKCC2 transporter.

Answer 33

💧 The NKCC2 transporter, also known as the sodium-potassium-chloride cotransporter 2, is a crucial transporter in the thick ascending limb of the loop of Henle.
💧 It mediates the reabsorption of sodium, potassium and chloride ions from the tubular fluid into the epithelial cells of the thick ascending limb.
💧 It uses energy released by the downhill diffusion of sodium into the cell to drive the reabsorption of potassium and chloride against their concentration gradients.

Question 34

Discuss the regulation and clinical relevance of the NKCC2 transporter.

Answer 34

💧 Regulation: NKCC2 is regulated by hormones such as vasopressin and aldosterone which can increase its activity to enhance sodium reabsorption.

💧 Clinical relevance: Inhibitors of the NKCC2 transporter, such as loop diuretics e.g. furosemide, ethacrynic acid, and bumetanide are used to treat hypertension and edema. This is because they promote increased excretion of these ions and water, thereby reducing blood volume and pressure.

[Diagram]

Question 35

What mechanism in the thick ascending limb mediates sodium reabsorption and hydrogen secretion?

Answer 35

The sodium-hydrogen counter-transport mechanism in the luminal cell membrane mediates sodium reabsorption and hydrogen secretion.
[Diagram]

Question 36

How does the slight positive charge in the tubular lumen of the thick ascending limb affect cation reabsorption?

Answer 36

The slight positive charge of about +8 millivolts in the tubular lumen, created by the backleak of potassium ions, forces cations such as Mg²⁺, Ca²⁺, Na⁺, and K⁺ to diffuse from the tubular lumen through the paracellular space into the interstitial fluid.

Question 37

With regards to the distal tubules, discuss:
(a) parts
(b) sodium and chloride
(c) water and urea

Answer 37

(a) parts:
◾ early distal tubule: continuous with the thick ascending limb of Henle
◾ late distal tubule: continuous with the early distal tubule and leads into the collecting duct

(b) sodium and chloride: The distal tubule reabsorbs a significant amount of sodium, chloride and other ions. The early distal tubule contains the sodium-chloride co-transporter (NCC), which moves sodium and chloride from the tubular lumen into the epithelial cells. The Na⁺-K⁺ ATPase pump then transports sodium out of the cells into the interstitial fluid, while chloride diffuses out through chloride channels.

(c) water and urea: the early distal tubule is virtually impermeable to water and urea, which helps in diluting tubular fluid. [It is for this reason that it is often referred to as the “diluting segment”.] The late distal tubule has variable permeability to water depending on the presence or absence of ADH.

Question 38

Name two cell types that make up the second half of the distal tubule and subsequent cortical collecting tubule.

Answer 38

(a) principal cells
(b) intercalated cells

Question 39

What do principal cells of the late distal convoluted tubule reabsorb and secrete?

Answer 39

principal cells reabsorb sodium and secrete potassium

Question 40

What is the role of the Na+-K+ ATPase pump in principal cells?

Answer 40

The Na+-K+ ATPase pump, located in the basolateral membrane, maintains a low sodium concentration inside the cell, favoring sodium diffusion into the cell and facilitating potassium secretion into the tubular lumen.

Question 41

What are the two steps involved in potassium secretion by principal cells?

Answer 41

💧 Potassium enters the cell due to the Na+-K+ ATPase pump.
💧 Potassium diffuses down its concentration gradient across the luminal membrane into the tubular fluid.

Question 42

What are the primary sites of action for potassium-sparing diuretics?

Answer 42

principal cells

Question 43

(a) Name two mineralocorticoid receptor antagonists that act as potassium-sparing diuretics.
(b) Briefly discuss how they cause their effects.

Answer 43

(a) spironolactone, eplerenone

(b) They compete with adolsterone for receptor sites in principal cells, inhibiting the stimulatory effects of aldosterone on sodium reabsorption and potassium secretion.

Question 44

(a) Name two sodium channel blockers that act as potassium-sparing diuretics.
(b) Briefly discuss how they cause their effects.

Answer 44

(a) amiloride, triamterene

(b) They directly inhibit the entry of sodium into the sodium channels of the luminal membranes, reducing sodium transport across the basolateral membranes by the Na+-K+ ATPase pump, and decreasing potassium secretion into the tubular fluid.

Question 45

(a) What is the role of intercalated cells found in the late distal convoluted tubule?
(b) What are the two types of intercalated cells?

Answer 45

(a) acid-base regulation
(b) type A, type B

Question 46

How do type A intercalated cells function?

Answer 46

💧 Type A intercalated cells secrete hydrogen ions by a hydrogen-ATPase transporter and a hydrogen-potassium-ATPase transporter, and they reabsorb bicarbonate ions.
💧 Hydrogen is formed by the action of carbonic anhydrase on water and carbon dioxide to form carbonic acid, which then dissociates into hydrogen ions and bicarbonate ions.
💧 The hydrogen ions are then secreted into the tubular lumen and, for each hydrogen ion secreted, a bicarbonate ion becomes available for reabsorption across the basolateral membrane.

[Type A intercalated cells are especially important in eliminating hydrogen ions while reabsorbing bicarbonate in acidosis.]

Question 47

How do type B intercalated cells function?

Answer 47

💧 Type B intercalated cells secrete bicarbonate into the tubular lumen while reabsorbing hydrogen ions in alkalosis.
💧 These cells have a chloride-bicarbonate counter-transporter on the apical membrane of type B cells called pendrin [it is different from the chloride-bicarbonate transporter of type A cells].
💧 Hydrogen ions are actively transported out of the type B intercalated cell on the basolateral side of the cell membrane by hydrogen-ATPase, and bicarbonate is secreted in the lumen, thus eliminating excess plasma bicarbonate in alkalosis.

Question 48

Medullary collecting ducts are the final site of processing of urine and therefore play a role in determining the final urine output of water and solutes. How is the permeability of the medullary collecting duct to water controlled?

Answer 48

The permeability of the medullary collecting duct to water is controlled by the level of ADH. High levels of ADH increase water reabsorption into the medullary interstitium, reducing urine volume and concentrating solutes in the urine.

Question 49

What is one key difference between the cortical collecting tubule and the medullary collecting duct?

Answer 49

The medullary collecting duct is permeable to urea, and there are special urea transporters that facilitate urea diffusion across the luminal and basolateral membranes.

Question 50

Explain the principle behind the use of inulin to assess water reabsorption by renal tubules.

Answer 50

💧 Inulin is not reabsorbed or secreted, thus its concentration in tubular fluid only changes due to water reabsorption. As water is reabsorbed along the nephron, the concentration of inulin in the remaining tubular fluid increases.
💧 By measuring the inulin concentration in the tubular fluid and comparing it to the inulin concentration in the plasma, we can determine the extent of water reabsorption.

Question 51

Regulation of tubular reabsorption

What is glomerulotubular balance?

Answer 51

Glomerulotubular balance is the intrinsic ability of the tubules to increase their reabsorption rate in response to increased tubular load (increased tubular inflow), ensuring that the total rate of reabsorption increases as the filtered load increases.

Question 52

Regulation of tubular reabsorption

(a) What is the normal rate of peritubular capillary reabsorption?
(b) How is reabsorption across the peritubular capillaries calculated?

Answer 52

(a) approximately 124 mL/min
(b) Reabsorption = K_f × Net reabsorptive force

Question 53

Regulation of tubular reabsorption

The net reabsorptive force is used in the calculation of the rate of peritubular capillary reabsorption. It represents the sum of the hydrostatic and colloid osmotic forces that favor or oppose reabsorption across the peritubular capillaries. List these forces and indicate whether they favor or oppose reabsorption.

Answer 53

(1) peritubular hydrostatic pressure (P_c), which opposes reabsorption
(2) hydrostatic pressure in the renal interstitium (P_if) which favors reabsorption
(3) colloid osmotic pressure of the peritubular capillary plasma proteins (π_c), which favors reabsorption
(4) colloid osmotic pressure of the proteins in the renal interstitium (π_if), which opposes reabsorption

Question 54

Regulation of tubular reabsorption

What are two determinants of peritubular capillary reabsorption that are directly influenced by renal hemodynamic changes?

Answer 54

hydrostatic and colloid osmotic pressures of the peritubular capillaries

Question 55

Regulation of tubular reabsorption

Briefly discuss how peritubular capillary hydrostatic pressure is influenced by the arterial pressure and resistances of the afferent and efferent arterioles.

Answer 55

(1) Increases in arterial pressure tend to raise peritubular capillary hydrostatic pressure and decrease the absorption rate. This effect is however buffered to some extent by autoregulatory mechanisms that maintain relatively constant hydrostatic pressures in the renal blood vessels.
(2) An increase in resistance of the afferent or efferent arterioles reduces peritubular capillary hydrostatic pressure and tends to increase reabsorption rate.
Although constriction of the efferent arterioles increases glomerular capillary hydrostatic pressure, it lowers peritubular capillary hydrostatic pressure.

Question 56

Regulation of tubular reabsorption

What determines the colloid osmotic pressure of peritubular capillaries?

Answer 56

(1) the systemic plasma colloid osmotic pressure, which increases with higher plasma protein concentration, and

(2) the filtration fraction, where a higher filtration fraction increases the concentration of proteins in the remaining plasma, thus enhancing reabsorption.

Further notes:
Renal vasoconstrictors like angiotensin II can increase peritubular capillary reabsorption by decreasing renal plasma flow (RPF) and increasing the filtration fraction.

Question 57

Regulation of tubular reabsorption

What are pressure natriuresis and pressure diuresis?

Answer 57

Pressure natriuresis and pressure diuresis are phenomena where small increases in arterial pressure cause marked increases in urinary excretion of sodium and water.

Question 58

Regulation of tubular reabsorption

How does increased arterial pressure affect peritubular capillary hydrostatic pressure and renal interstitial fluid hydrostatic pressure?

Answer 58

Increased arterial pressure causes a slight increase in peritubular capillary hydrostatic pressure and renal interstitial fluid hydrostatic pressure, enhancing the backleak of sodium into the tubular lumen and reducing net reabsorption of sodium and water.