Tubular Reabsorption Notes

Tubular Reabsorption Introduction

• Tubular reabsorption is the process by which water and other substances are transported from renal tubules back to the blood.
• When the glomerular filtrate flows through the tubular portion of the nephron, both quantitative and qualitative changes occur.
• Large quantities of water (more than 99%), electrolytes, and other substances are reabsorbed by the tubular epithelial cells.
• The reabsorbed substance move into the interstitial fluid of the renal reduce, from here, the substances move into the blood in peritubular capillaries.
• Sines the substances are taken back into the blood from the glomerular filtrate, the entire process is called tubular reabsorption.

Read And Learn More: Medical Physiology Notes

Method Of Collection Of Tubular Fluid

There are two methods to collect the tubular fluid for analysis.

Micropuncture Technique

A micropipette is inserted into the Bowman’s capsule and different parts of tubular portion in the nephrons of experimental animals, to collect the fluid.

The fluid samples are analyzed and compared with each other to assess the changes in different parts of the nephron.

Stop Flow Method

• The ureter is obstructed so that the back pressure rises and stops the glomerular filtration.
• The obstruction is continued for 8 minutes. It causes some changes in the fluid present in different parts of the tubular portion.
• Later, the obstruction is released, and about 30 samples of 0.5 mL of urine are collected separately at regular intervals of 30 seconds.
• The first sample contains the fluid from the collecting duct.
• The successive samples contain the fluid from the distal convoluted tubule, loops of Henle, and proximal convoluted tubule respectively. All the samples are analyzed.

Selective Reabsorption

• Tubular reabsorption is known as selective reabsorption because the tubular cells of the kidney selectively reabsorb the substances present in the glomerular filtrate, according to the
• needs of the body. The essential substances which are necessary for the body such as glucose, amino acids and vitamins are completely reabsorbed from the renal tubule.
• Whereas unwanted substances like metabolic waste products are not reabsorbed.

Mechanism Of Reabsorption

The basic transport mechanisms involved in tubular reabsorption are of two types:

1. Active reabsorption
2. Passive reabsorption.

1. Active Reabsorption

Active reabsorption is the movement of molecules against the electrochemical (uphill) gradient.

It needs liberation of energy which is derived from ATP.

Substances reabsorbed actively

The substances reabsorbed actively from the renal tubule are sodium, calcium, potassium, phosphates, sulfates, bicarbonates, glucose, amino acids, ascorbic- acid, uric acid, and ketone bodies.

2. Passive Reabsorption

Passive reabsorption is the movement of molecules along the electrochemical (downhill) gradient.

This process does not need energy. Substances reabsorbed passively The substances reabsorbed by passive transport are chloride, urea, and water.

Routes Of Reabsorption

There are two routes for the substances to be reabsorbed from the tubular lumen into the peritubular capillary called transcellular and paracellular routes.

Transcellular Route

In this route, the substances move through the cell. It includes:

1. Transport from the tubular lumen into the tubular cell through the apical (luminal) surface of the cell membrane
2. Transport from the tubular cell into the interstitial fluid
3. Transport from the interstitial fluid into the capillary.

Paracellular Route

In this route, the substances move through the intracellular space. It includes:

1. Transport from the tubular lumen into an interstitial fluid present in lateral intercellular space through the tight junction between the cells.
2. Transport from the interstitial fluid into the capillary

The reabsorption of the substances occurs in almost all the segments of the tubular portion of the nephron.

1. Substances Reabsorbed from Proximal Convoluted Tubule

• About 7/8 of the filtrate (about 88%) is reabsorbed in the proximal convoluted tubule.
• The proximal convoluted tubule is formed by brush-bordered epithelial cells. The brush border increases the surface area for reabsorption.
• Substances reabsorbed from the proximal convoluted tubule are glucose, amino acids, sodium, potassium, calcium, bicarbonates, chlorides, phosphates, uric acid, and water.

2. Substances Reabsorbed from Loop of Henle

The substances reabsorbed from the loop of Henle are sodium and chloride.

3. Substances Reabsorbed from Distal Convoluted Tubule

Sodium, calcium, bicarbonate, and water are reabsorbed from the distal convoluted tubule.

Regulation Of Tubular Reabsorption

Tubular reabsorption is regulated by three factors:

1. Glomerulotubular balance
2. Hormonal factors
3. Nervous factors.

1. Glomerulotubular Balance

• Glomerulotubular balance is the balance between the filtration and reabsorption of solutes and water in the kidney.
• When GFR increases, the tubular load of solutes and water in the proximal convoluted tubule is increased.
• It is followed by an increase in the reabsorption of solutes and water. This process helps in the constant reabsorption of solutes particularly sodium and water from the renal tubule.

Mechanism of glomerulotubular balance

• Glomerulotubular balance occurs because of osmotic pressure in the peritubular capillaries.
• When GFR increases, more amount of plasma proteins accumulate in the glomerulus.
• Consequently, the osmotic pressure increases in the blood by the time it reaches efferent arteriole and peritubular capillaries.
• The elevated osmotic pressure in the peritubular capillaries increases the reabsorption of sodium and water from the tubule into the capillary blood.

2. Hormonal Factors

The hormones which regulate GFR

3. Nervous Factor

• Activation of the sympathetic nervous system increases the tubular reabsorption (particularly of sodium) from renal tubules.
• It also increases tubular reabsorption indirectly by stimulation of renin from juxtaglomerular cells.
• Renin causes the formation of angiotensin II which increases sodium reabsorption

Threshold Substances

Depending upon the degree of reabsorption, the various substances are classified into three categories:

1. High threshold substances
2. Low threshold substances
3. Nonthreshold substances.

1. High Threshold Substances

• High-threshold substances are those substances that do not appear in urine under normal conditions.
• The food substances like glucose, amino acids, acetoacetate ions, and vitamins are completely reabsorbed from renal tubules and do not appear in urine under normal conditions.
• These substances can appear in urine, only if their concentration in plasma is abnormally high or in renal diseases when reabsorption is affected.
• So, these substances are called high-threshold substances.

2. Low Threshold Substances

• Low-threshold substances are substances that appear in urine even under normal conditions.
• The substances such as urea, uric acid, and phosphate are reabsorbed to a little extent.
• These substances appear in urine even under normal conditions.

3. Nonthreshold Substances

Nonthreshold substances are those substances that are not at all reabsorbed and are excreted in urine irrespective of their plasma level.

The metabolic end products such as creatinine are the non-threshold substances.

Transport Maximum – Tm Value

• Tubular transport maximum or Tm is the rate at which a substance is reabsorbed from the renal tubule.
• The substances reabsorbed actively from the renal tubules require some specific transport system.
• The rate of reabsorption of any substance depends upon the rate at which this specific transport system operates.
• The transport system, in turn, depends upon the carrier substances or enzymes.
• So. for every actively reabsorbed substance, there is a maximum rate at which it could be reabsorbed.
• For example, the transport maximum for glucose. (TmG) is 375 mg/minute in adult males and about 300 mg/minute in adult females.
• Threshold Level in Plasma for Substances having Tm Value
• The renal threshold is the plasma concentration at which a substance appears first in urine.
• Every substance having a Tm value has also a threshold level in plasma or blood.
• Below that threshold level, the substance is completely reabsorbed and does not appear in the urine.
• When the concentration of that substance reaches the threshold. the excess amount is not reabsorbed and so it appears in urine.
• This level is called the renal threshold of a substance.
• For example, the renal threshold for glucose is 180 mg/dL. That is, glucose is completely reabsorbed from tubular fluid if its concentration in the blood is below 180 mg/dL.
• So. the glucose does not appear in the urine. When the blood level of glucose reaches 180 mg/dL it is not reabsorbed completely; hence it appears in urine.

Reabsorption Of Important Substances

Reabsorption of Sodium

From the glomerular filtrate, 99% of sodium is reabsorbed. Two-thirds of sodium is reabsorbed in the proximal convoluted tubule and the remaining one-third in other segments (except descending limb) and collecting duct.

Sodium reabsorption occurs in three steps:

Transport from the lumen of renal tubules into the tubular epithelial cells Transport from tubular cells into the interstitial fluid

3. Transport from Interstitial Fluid to the Blood

From the interstitial fluid, sodium ions enter the peritubular capillaries by a concentration gradient.

In the distal convoluted tubule, sodium reabsorption is stimulated by the hormone aldosterone secreted by the adrenal cortex.

Reabsorption of Water

• Reabsorption of water occurs from proximal and distal convoluted tubules and in the collecting ducts.
• Reabsorption of water from proximal convoluted tubule – obligatory water reabsorption
• Obligatory reabsorption is the type of reabsorption of water in the proximal convoluted tubule, which is secondary to sodium reabsorption.
• The proximal convoluted tubule is highly permeable to water.
• However, water reabsorption is secondary (obligatory) to sodium reabsorption.
• When sodium is reabsorbed from the tubule, the osmotic pressure decreases.
• It causes osmosis of water from the renal tubule.
• Reabsorption of water from distal convoluted tubule and coll-acting duct – facultative water reabsorption.
• Facultative reabsorption is the type of water reabsorption in distal convoluted tubule and collecting duct that occurs by the activity of antidiuretic hormone (ADH).
• Normally, the distal convoluted tubule
• and the collecting duct are not permeable to water. But in the presence of antidiuretic hormone (ADH), these segments become permeable to water.
• So, water is reabsorbed from the distal convoluted tubule and collecting duct.
• Mechanism of action of antidiuretic hormone
• ADH combines with V2 receptors in the tubular epithelial membrane and activates adenyl cyclase, to form cyclic AMP.
• This cyclic-AMP increases the permeability of the tubules for water.
• Earlier it was thought that ADH facilitates water reabsorption by acting on the simple water channels.
• Now it is found that the water channels are formed by snecTc proteins called aquaporins.

Aquaporins

• Aquaporins (AQP) are membrane proteins that function as water channels.
• Though about 10 aquaporins are identified in mammals only 5 are found in humans.
• Aquaporin-1, 2, and 3 are present in renal tubules. Aquaporin-4 is present in the brain and aquaporin-5 is found in salivary glands.
• Aquaporin 2 forms the water channels in renal tubules. It is found that ADH increases water reabsorption in distal convoluted tubules and collecting ducts by regulating the aquaporin.

Reabsorption of Glucose

• Glucose is completely reabsorbed in the proximal convoluted tubule. It is transported by secondary active transport (sodium co-transport) mechanism.
• Glucose and sodium bind to a common carrier protein in the luminal membrane of the tubular epithelium and enter the cell.
• The carrier protein is called sodium-dependant glucose transporter 2 (SGLT 2).
• From tubular cells, glucose is transported into the medullary interstitium by another carrier protein called glucose transporter 2 (GLUT 2).

Tubular maximum for glucose (TmG)

In adult males TmG is 375 mg/minute and in adult females it is about 300 mg/minute.

The renal threshold for glucose

The renal threshold for glucose is 180 mg/dL in venous blood. When the blood level reaches 180 mg/dL glucose is not reabsorbed completely and appears in the urine.

Splay

Splay means deviation. With a normal GFR of 125 mL/ minute and TmG of 375 mg/minute in an adult male, the predicted (expected) renal threshold for glucose should be 300 mg/dL. But actually, it is only 180 mg/dL.

When the renal threshold curves are drawn by using these values, the actual curve deviates from the ‘should be’ or predicted or ideal curve.

This type of deviation is called splay. The splay is because of the fact that all the nephrons do not have the same filtering and reabsorbing capacities.

Reabsorption of Amino Acids

Amino acids are also reabsorbed completely in the proximal convoluted tubule. Amino acids are reabsorbed actively by the secondary active transport mechanism along with sodium.

Reabsorption of Bicarbonates

• Tvrboneie is absorbed actively, mostly in proximal It is reabsorbed in the form of carbon dioxide
• Bicarbonate is mostly present as sodium bicarbonate in the filtrate. Sodium bicarbonate dissociates into sodium and bicarbonate ions in the tubular lumen.
• Sodium diffuses into tubular cells in exchange for hydrogen. Bicarbonate combines with hydrogen to form carbonic acid.
• Carbonic acid dissociates into carbon dioxide and water in the presence of carbonic anhydrase. Carbon dioxide and water enter the tubular cell.
• In tubular cells, carbon dioxide combines with water to form carbonic acid.
• It immediately dissociates into hydrogen and bicarbonate. Bicarbonate from the tubular cell enters the interstitium.

There it combines with sodium to form sodium bicarbonate.

Tubular Secretion

Introduction

• Tubular secretion is the process by which substances are transported from blood into renal tubules.
• It is also called tubular excretion. In addition to reabsorption from renal tubules, some substances are also secreted into the lumen from the peritubular capillaries through the tubular epithelial cells.
• In experimental conditions, the dye phenol red was the first substance found to be secreted in renal tubules.

Later many other substances were found to be secreted such as:

1. Para-aminohippuric acid (PAH)
2. Diodrast
3. Hydroxyindole acetic acid
4. Amino derivatives
5. Penicillin.

Substances Secreted In Different Segments Of Renal Tubules

1. Potassium is secreted actively by sodium-potassium pump in proximal and distal convoluted tubules and collecting ducts.
2. Ammonia is secreted in the proximal convoluted tubule.
3. Hydrogen ions are secreted in the proximal and distal convoluted tubules. Maximum hydrogen ion secretion occurs in the proximal tubule. Thus, urine is formed in the nephron by the processes of glomerular filtration, selective reabsorption, and tubular secretion.