(25.5.6) S2: Tubular Reabsorption & S3: Tubular Secretion

Describe the Location and Function of Tubular Reabsorption

• Begins as soon as filtrate enters the proximal tubules

  1. Quickly reclaims most of tubular contents and returns them to blood

  2. Selective process

     • Almost all organic nutrients are reabsorbed

     • Water and ion reabsorption is hormonally regulated and adjusted

Name the mechanisms underlying water and solute reabsorption from the renal tubules into the peritubular capillaries

Includes active and passive tubular reabsorption

1. Transcellular Route

2. Paracellular Route

Describe Steps of Transcellular Route

1. Transport across the apical membrane

2. Diffusion through the cytosol

3. Transport across the basolateral membrane

   • Often involves the lateral intercellular spaces because membrane transporters transport ions into these spaces

4. Movement through the interstitial fluid into the capillary

Describe Steps of Paracellular Route

1. Movement through leaky tight junctions, particularly in the proximal convoluted tubule

2. Movement through the interstitial fluid and into the capillary

Through which pathway are most water and solutes reabsorbed in the kidney tubule?

→ Transcellular

• This means that transport must take place across the apical membrane and across the basolateral membrane for the substance to move from the lumen of the kidney tubule into the blood.

T/F: Tubular Reabsorption includes only active tubular reabsorption

→ FALSE

Tubular Reabsorption includes active AND passive tubular reabsorption

Describe Sodium Transport Across the Basolateral Membrane

Primary Active Transport

• Na+ is most abundant cation in filtrate

• Transport of Na+ across basolateral membrane of tubule cell is via primary active transport

• Na+-K+ ATPase pumps Na+ into interstitial space

Steps of Tubular Reabsorption of water and nutrients Using Active & Passive Transport

1. At basolateral membrane, Na+ is pumped into the intestinal space by the Na+-K+ ATPase → Active Na+ transport creates concentration gradients that drive:

   • “Downhill” Na+ entry at the apical membrane

   • Reabsorption of organic nutrients and certain ions by co-transport at the apical membrane

2. Reabsorption of water by osmosis through aquaporins → Water reabsorption increases the concentration of the solutes that are left behind. These solutes can then be reabsorbed as they move down their gradients:

   • Lipid-soluble substances diffuse by the transcellular route

   • Various ions (C^l-, Ca²⁺, K⁺) and urea diffuse by the paracellular route

Describe Sodium Transport Across the Apical Membrane

Secondary Active Transport

• Electrochemical gradient created by pumps at basolateral surface give “push” needed for transport of other solutes

• Organic nutrients reabsorbed by secondary active transport are co-transported with Na+

  • Glucose, amino acids, some ions, vitamins

Distinguish between Passive Tubular Reabsorption of Water vs Solutes

Passive Tubular Reabsorption of Water

• Obligatory water reabsorption

  • Aquaporins are ALWAYS present in PCT

• Facultative water reabsorption

  • Aquaporins are inserted in collecting dusts ONLY if ADH is present

Passive Tubular Reabsorption of Solutes

• Solute concentration in filtrate increases as water is reabsorbed

  • Creates concentration gradients for solutes, which drive their entry into tubule cell and peritubular capillaries

• Fat-soluble substances, some ions, and urea will follow water into peritubular capillaries down their concentration gradients

  • For this reason, liquid-soluble drugs and environmental pollutants are reabsorbed even through it is not desirable

SUMMARY List and Describe Sodium Transport Across the Basolateral Membrane

1. Primary Active Transport

   • Na+ is most abundant cation in filtrate

   • Transport of Na+ across basolateral membrane of tubule cell is via primary active transport

   • Na+-K+ ATPase pumps Na+ into interstitial space

2. Secondary Active Transport

   • Electrochemical gradient created by pumps at basolateral surface give “push” needed for transport of other solutes

   • Organic nutrients reabsorbed by secondary active transport are co-transported with Na+

     • Glucose, amino acids, some ions, vitamins

3. Passive Tubular Reabsorption of Water

   • Obligatory water reabsorption

     • Aquaporins are ALWAYS present in PCT

   • Facultative water reabsorption

     • Aquaporins are inserted in collecting dusts ONLY if ADH is present

4. Passive Tubular Reabsorption of Solutes

   • Solute concentration in filtrate increases as water is reabsorbed

     • Creates concentration gradients for solutes, which drive their entry into tubule cell and peritubular capillaries

   • Fat-soluble substances, some ions, and urea will follow water into peritubular capillaries down their concentration gradients

     • For this reason, liquid-soluble drugs and environmental pollutants are reabsorbed even through it is not desirable

Define Transport Maximum

Transcellular transport systems are specific and limited

• Transport maximum (T_m) exists for almost every reabsorbed substance

• Reflects number of carriers in renal tubules that are available

• When carriers for a solute are saturated, excess is excreted in urine

• EX: hyperglycemia leads to high BG levels that exceed T_m, and glucose spills over into urine

Patients with uncontrolled diabetes mellitus often have glucose in their urine. This is because the concentration of glucose in the filtrate exceeds the ____________ of the carrier proteins in the proximal tubule.

→ Transport maximum

• Normally, all of the glucose in the filtrate gets reabsorbed by transport proteins in the proximal tubule.  When an individual has extremely high levels of blood glucose that enter the filtrate (as in uncontrolled diabetes mellitus), there are not enough transport proteins to reabsorb all of the glucose.  The glucose that doesn't get reabsorbed remains in the filtrate and is excreted.

Describe the Reabsorptive Capabilities of Renal Tubules and Collecting Ducts @ Proximal Convoluted Tubule

• Site of MOST reabsorption

  1. All nutrients, such as glucose and amino acids are reabsored

  2. 65% of Na+ and water reabsorbed

  3. Ions

  4. Almost all uric acid

  5. About half of urea (later secreted back into filtrate

Describe the Reabsorptive Capabilities of Renal Tubules and Collecting Ducts @ Nephron Loop

• Descending limb

  1. H₂O can leave and Solutes cannot

     • Thin segment is passive to Na+ movement

• Ascending limb

  1. H₂O cannot leave and Solutes can

     • Thick segment has Na⁺-K⁺-2Cl^- symporters and Na⁺-H⁺ antiporters that transport Na+ into cell

     • Some Na+ can pass into cell by paracellular route in this area of limb

Describe the Reabsorptive Capabilities of Renal Tubules and Collecting Ducts @ Distal Convoluted Tubule & Collecting Duct

• Reabsorption is hormonally regulated in these areas

  1. Antidiuretic hormone (ADH)

  2. Aldosterone

  3. Atrial natriuretic peptide

  4. Parathyroid hormone

Reabsorption of which of the following drives the reabsorption of water and many other solutes in the proximal tubule?

→ Sodium

• Sodium ions are reabsorbed down their concentration gradient into the tubular cells. Na⁺K⁺pumps in the tubular cell membranes are responsible for maintaining the concentration gradient. The energy provided by the Na⁺ gradient is used to fuel secondary active transport of many other substances

SUMMARY of Reabsorptive Capabilities of Renal Tubules and Collecting Ducts

Proximal Convoluted Tubule

• Site of MOST reabsorption

  1. All nutrients, such as glucose and amino acids are reabsored

  2. 65% of Na+ and water reabsorbed

  3. Ions

  4. Almost all uric acid

  5. About half of urea (later secreted back into filtrate

Nephron Loop

• Descending limb

  1. H₂O can leave and Solutes cannot

     • Thin segment is passive to Na+ movement

• Ascending limb

  1. H₂O cannot leave and Solutes can

     • Thick segment has Na⁺-K⁺-2Cl^- symporters and Na⁺-H⁺ antiporters that transport Na+ into cell

     • Some Na+ can pass into cell by paracellular route in this area of limb

Distal Convoluted Tubule & Collecting Duct

• Reabsorption is hormonally regulated in these areas

  1. Antidiuretic hormone (ADH)

  2. Aldosterone

  3. Atrial natriuretic peptide

  4. Parathyroid hormone

List how sodium and water reabsorption are regulated in the distal tubule and collecting duct

1. Antidiuretic hormone (ADH)

2. Aldosterone

3. Atrial natriuretic peptide

4. Parathyroid hormone

Role of Antidiuretic Hormone (ADH)

• Released by posterior pituitary gland

• Causes principal cells of collecting ducts to insert aquaporins in apical membranes, increasing water reabsorption

• INCREASED ADH levels cause an increase in water reabsorption

Role of Aldosterone

• Targets collecting ducts (principal cells) and distal DCT

• Promotes Na+ reabsorption (water follows)

• As a result, little Na+ leaves body

• Function: INCREASES BP and DECREASE K+ levels

Role of Atrial Natriuretic Peptide

• Released by cardiac atrial cells if blood volume or pressure elevated

• Reduces blood Na+ → resulting in decreased blood volume and BP

Role of Parathyroid hormone

• Acts on DCT to increase Ca2+ reabsorption

When given to a patient, which of the following substances would increase his or her urinary output?

A.) intravenous saline

B.) albumin

C.) aldosterone

D.) antidiuretic hormone

→ A.) intravenous saline

SUMMARY of Tubular Reabsorption and Secretion

1. Antidiuretic hormone (ADH)

   • Released by posterior pituitary gland

   • Causes principal cells of collecting ducts to insert aquaporins in apical membranes, increasing water reabsorption

   • INCREASED ADH levels cause an increase in water reabsorption

2. Aldosterone

   • Targets collecting ducts (principal cells) and distal DCT

   • Promotes Na+ reabsorption (water follows)

   • As a result, little Na+ leaves body

   • Function: INCREASES BP and DECREASE K+ levels

3. Atrial natriuretic peptide

   • Released by cardiac atrial cells if blood volume or pressure elevated

   • Reduces blood Na+ → resulting in decreased blood volume and BP

4. Parathyroid hormone

   • Acts on DCT to increase Ca2+ reabsorption

Describe the Location and Function of Tubular Secretion

• Occurs almost completely in PCT

  1. Tubular secretion is reabsorption in reverse

  2. Selected substances are moved from peritubular capillaries through tubule cells out into filtrate

List several substances that are secreted from Tubular secretion

1. K⁺

2. H⁺

3. NH₄⁺

4. Creatinine

5. Organic acids and bases

6. Substances synthesized in tubule cells also are secreted (EX: HCO₃^-)

Describe the importance of Tubular secretion

1. Disposing of substances, such as drugs or metabolites

2. Eliminating undesirable substances that were passively reabsorbed

   • EX: urea and uric acid

3. Ridding body of excess K⁺ (aldosterone effect)

4. Controlling blood pH by altering amounts of H+ or HCO₃^- in urine

SUMMARY of Tubular Reabsorption and Secretion

Predict the Effect of HIGH and LOW GFR on Tubular Reabsorption & Explain Tubuloglomerular Feedback would respond to HIGH and LOW GFR