Kidneys: Basic Renal Processes- Tubular Reabsorption

Dr. Huising, Fall 2024, Lecture 19-20

Tubular Reabsorption

• Selective movement of filtered substances from the tubular lumen into the peritubular capillaries (H₂O, Na+, Cl-)

Tubular Epithelium

• Throughout its entire length, the tubule is one cell layer thick

• It has a luminal and basolateral membrane

• Adjacent tubular cells form tight junctions (barriers so nothing can get through, therefore pores are needed)

Capillary Endothelium

• Throughout its entire length, the capillary is one very thin cell layer thick

• No tight junctions between endothelial cells (little barrier for H₂O and solutes)

• Fenestrated capillaries are even more permeable

What five barriers does transepithelial transport cross?

1. The luminal membrane of tubular cell- allows reabsorption to be selective

2. The cytosol of tubular cell

3. The basolateral membrane of tubular cell- allows reabsorption to be selective

4. The interstitial fluid

5. The capillary wall

• Permeability of tubular cell membrane varies along the length of the tubular system and in some areas is subject to hormonal control

What are the two types of tubular reabsorption?

• Passive: movement down an osmotic or electrochemical gradient (H₂O)

• Active: requires ATP (Na+, glucose, amino acids, other electrolytes)

How much of Na+ is reabsorbed and where?

• 99.5% of Na+ is reabsorbed

  • 67% in proximal tubule

  • 25% in loop of Henle

  • 8% in distal and collecting tubules (subject to hormonal control)

What is the role of Na+ reabsorption in different regions?

• Proximal Tubule: Plays role in reabsorption of glucose, amino acids, H₂O, Cl-, and urea

• Loop of Henle: Plays role in kidneys ability to produce urine of varying concentrations and volumes

• Distal Tubule: Subject to hormonal control, important in the regulation of ECF volume

Na+ Reabsorption

• The active step in Na+ reabsorption (tubular cells → interstitial fluid) involves the energy dependent Na/K ATPase pump loated in the tubular cells basolateral membrane

• Intracellular concentration of Na+ is low, Na+ diffuses into the tubular cell down tis concentration gradient

• Interstitial concentration of Na+ is high, Na+ diffuses into the peritubular capillary down its concentration gradient

Control Over Na+ Reabsorption

• In the proximal tubule and loop of Henle, a constant percent of filtered Na+ is reabsorbed regardless of the amount of Na+ in the body

• In distal and collecting tubules, the reabsorption of a small percent of Na+ is subject to hormonal control, the extent of this reabsorption is inversely related to the magnitude of the Na+ load in the body

  • The hormones are aldosterone and atrial natriuretic peptide

Aldosterone

• Hormone that stimulates Na+ reabsorption in the distal and collecting tubules

Atrial Natriuretic Peptide

• Hormone that inhibits Na+ reabsorption in the distal and collecting tubules

Active Na+ reabsorption drives…

• Passive reabsorption of H₂O, Cl-, and urea

• H 2 O (osmotic gradient),
  facilitated by aquaporins (AQP).

  • Proximal tubules express AQP1 (always open). Distal and collecting tubules express AQP2 (regulated by vasopressin)

• Cl- (electrochemical gradient)

• Urea (only partial, concentration
  gradient that increases towards
  the end of the proximal tubules
  as more H₂O has left the filtrate)

How does aldosterone stimulate Na+ reabsorption in the distal and collecting tubules?

• Insertion of additional leak channels in the luminal membrane

• Inserting additional Na/K ATPase in the basolatereal membrane

What controls aldosterone release?

• The renin-agiotensin-aldosterone system (RAAS)

What triggers RAAS?

• Low NaCl concentration

• Low ECF volume

• Low systemic arterial blood pressure

What are the steps in RAAS?

1. Triggers are sensed in the kidneys which release the hormone renin

2. Renin will act on angiotensinogen from the liver (that is always in the blood) and convert it to angiotensin I

3. Angiotensin I is converted into angiotensin II by angiotensin-converting enzyme from the lungs (always produced)

4. Angiotensin II does four things

   1. Causes the release of vasopressin from the hypothalamus which sends a signal to the kidneys to reabsorb H₂O

   2. Works on thirst center of the brain to make you thirsty

   3. Causes general arterial vasoconstriction

   4. Acts on adrenal cortex to release hormone aldosterone

What does aldosterone do when it is released?

• Travels to the kidneys and drive the insertion of additional Na+ leak channels in the luminal membrane and Na/K ATPase in the basolateral membrane

• This causes the reabsorption of the final 8% of Na+, allowing the body to retain it and more H₂O

• This restores the low blood pressure and low volume, which deactivates RAAS

Angiotensinogen

• Hormone and enzyme

• Synthesized in the liver

• Always present in the plasma

Renin

• Released from the kidneys (granular cells) into plasma

• Converts angiotensinogen into angiotensin I

Angiotensin-Converting Enzyme (ACE)

• Enzyme present in the lungs

• Converts angiotensin I into angiotensin II

Angiotensin II

• Has many effects

• Stimulates adrenal cortex to release aldosterone

Aldosterone

• Increases Na+ reabsorption in the distal and collecting tubules by promoting the insertion of Na+ channels and Na/K ATPase carriers

What triggers natriuretic peptides to inhibit Na+ reabsorption?

• High NaCl concentration

• High ECF volume

• High arterial blood pressure

What do natriuretic peptides inhibit?

• Na+ reabsorption

• RAAS

• Smooth muscle of arterioles (increased GFR)

• Sympathetic nervous system to reduce cardiac output and peripheral resistance

• Natriuretic peptides are the opposite of RAAS, they reduce blood pressure

Reabsorption of glucose and amino acids

• Reabsorbed in the proximal tubule by Na+ dependent specific symport carriers across the tubular membrane into the cell (secondary active transport)

• Glucose then diffuses across the basolateral tubular membrane via glucose transporters (facilitated diffusion)

• Glucose reabsorption is efficient and complete but the number of sodium-glucose symporters are finite, there is a tubular maximum

  • Excess glucose is lost in urine- uncontrolled diabetes