Mechanism of urine concentration: osmotic pressure changes in different segments of the renal tubule
The decrease in concentration due to less urea is reabsorbed into the interstitial marrow from the manifold when ADH levels are low and the kidneys form a large volume of diluted urine.
The changes in the osmolality and volume of tubular fluid as it passes through the different parts of the nephron are shown in the figure.
Tube glide close
About 65% of the filtered electrolytes is reabsorbed in the proximal tubule. However, the proximal tubule membranes are highly permeable to water, so whenever the solutes are reabsorbed, the water diffuses through the tubular membrane by osmosis. The diffusion of water from side to side of the proximal tubule epithelium is supported by water channels aquaporin 1 (AQP-1). Therefore, the osmolality of the remaining fluid is still about the same as the glomerular dialysis solution-300 mOsm / L.
Branch down the handle Henle
As the fluid drains down the branches to the loops of Henle, the water is reabsorbed into the kidney marrow. The lower end of the branch also contains AQP-1 and is highly permeable to water, but more or less permeable to sodium chloride and urea. Therefore, the permeability of the fluid flowing through the descending branch gradually increases until it is approximately equal to the surrounding interstitial fluid, which is about 1200 mOsm / L when the ADH concentration in the blood is high.
Figure. Changes in the osmotic pressure of the tubular fluid as it passes through different tubular segments in the presence of high concentrations of antidiuretic hormone (ADH) and in the absence of ADH (numerical values indicate approximate volume in millilitres per minute or by osmolality in milliosmoles per litre of fluid that flows along with different tubular segments).
When diluted urine has been formed, as a result of low concentrations of ADH, the interstitial osmolality is less than 1200 mOsm / L; therefore, the osmosis of the tubular fluid in the descending branch also becomes less concentrated. This reduction in concentration is due in part to the fact that less urea is reabsorbed into the interstitial marrow from the manifold when ADH levels are low and the kidneys form a large volume of diluted urine.
The thin part branches up Henle's straps
The ascending thin lower end is essentially impervious but does reabsorb some of the sodium chlorides. Due to the high concentration of sodium chloride in the tubular fluid as a result of the removal of water from the branch down to the loop of Henle, there is some passive diffusion of sodium chloride from the lower end of the thin branch to the interstitial canal. Thus, the tubular fluid becomes thinner because sodium chloride diffuses out of the tubule and water remains in the tubule.
Some of the urea reabsorbed into the interstitial marrow from the manifold diffuses into the lower end of the ascending branch, thereby bringing the urea back into the tubular system and helping to prevent its leaching from the renal marrow. This recycling of urea is an additional mechanism that contributes to the creation of the hypertonic medullary region.
The thick part branches up the cap Henle
The thickened portion of the ascending loop of Henle is also nearly impervious, but large amounts of sodium, chloride, potassium and other ions are actively transported from the renal tubule into the interstitial medulla. As a result, the fluid in the head under the thickened loops of Henle becomes very thin, decreasing to a concentration of about 100 mOsm / L.
The tip of the tube is far away
The distal tubule end has the same properties as the branched thickening of the Henle loop, so further dilution of the tubular fluid to about 50 mOsm / L occurs as the solutes are reabsorbed while the water remains clear. renal tubules.
The distal tubule end and the shell manifold
In the distal tubule end and the envelope manifold, the osmotic pressure of the fluid depends on the concentration of ADH. With high concentrations of ADH, these tubules are highly permeable to water and a considerable amount of water is reabsorbed. Urea, though, does not permeate this part of the nephron, leading to an increase in urea concentrations as water is reabsorbed. This process allows most of the urea delivered to the distal tubule and the manifold to enter the inner medullary collecting duct, from which it is eventually reabsorbed or excreted in the urine. In the absence of ADH, little water is reabsorbed at the end of the distal tubule and the envelope manifold; therefore, the permeability will be further reduced as the active reabsorption of ions from these fractions continues.
Collectors in the medullary region
The concentration of the fluid in the inner medullary manifold also depends on (1) ADH and (2) the permeability around the interstitial medulla by the upstream mechanism. In the presence of a large amount of ADH, these manifolds are highly permeable to water, and water diffuses from the tubular fluid into the interstitial fluid until osmotic equilibrium is reached, with tubular fluid to the same concentration. as the interstitial region of the kidneys (1200-1400 mOsm / L).
Thus, a small volume of concentrated urine is produced when the ADH concentration is high. Because water reabsorption increases the concentration of urea in the tubular fluid and because the inner marrow manifold has its own urea transporter, it greatly facilitates diffusion, high concentrations of urea in the manifold diffuses out of the lumen of the renal tubule into the interstitial medulla. This reabsorption of urea into the renal marrow contributes to the hypertonic concentration of the interstitial region and the high concentration of the kidneys.
Some of the key points considered may not be obvious from this discussion. First, although sodium chloride is one of the major solutes contributing to the hypertonic interstitial region, the kidneys can when necessary, excrete highly concentrated urine with little sodium chloride. Hypertonic concentrations of urine in these cases are due to high concentrations of other solutes, especially waste products such as urea. One condition for this is dehydration coupled with low sodium intake. Low sodium intake stimulates the formation of the hormone’s angiotensin II and aldosterone, which together cause eager sodium reabsorption from the renal tubules while leaving urea and other solutes to maintain urine concentration. high. Second, large amounts of diluted urine can be excreted without increasing sodium excretion.
Finally, the required volume of urine is determined by the maximum concentration of the kidneys and the amount of solute that must be expelled. Therefore, if large amounts of solute are released, they should be accompanied by the minimum amount of water required to dispose of them. For example, if 600 milliosmoles of solute are eliminated per day, this would require at least 0.5 litters of urine if the maximum concentration of urine is 1200 mOsm / L.
Quantification of renal urine concentration and dilution of free water and clearance
The process of concentrating or diluting urine requires the kidneys to excrete water and dissolved substances independently. When urine is diluted, excess water is excreted compared to dissolved substances. In contrast, when urine is concentrated, dissolved substances are excreted in excess of water.
The total clearance of dissolved substances in the blood can be expressed as the clearance concentration (Cosm); here is the volume of plasma cleared by solutes per minute, in the same way, that the clearance of a single substance is calculated:
Cosm = (Uosm x V)/Posm
Uosm is the urine osmolality, V is the urine flow rate, and Posm is the plasma osmolality.
For example, if the plasma osmolality is 300 mOsm / L, the urine osmolality is 600 mOsm / L, and the urine outflow rate is 1 ml / min (0.001 L / min), the excretion rate. osmolar is 0.6mOsm / min (600mOsm / L x 0.001 L / min) and the osmolar clearance is 0.6 mOsm / min divided by 300mOsm / L, or 0.002 L / min (2.0 ml / min). This means that 2 ml of plasma is dissolved by solute per minute.
Relevance between solutes and wastewater can be assessed using the term "free water clearance".
The free water clearance (CH2O) is calculated as the difference between the water excretion (urine flow rate) and the osmotic clearance:
CH2O = V - Cosm = V - (Uosm x V) / Posm
Thus, the level of free water clearance represents the level of the free water-solutes excreted by the kidneys. When the free water clearance is positive, the excess water is excreted by the kidneys; when free water clearance is negative, excess solutes are removed from the blood by the kidneys and water is preserved.
Using the example discussed earlier, if the urine flow rate is 1 ml/min and the osmotic clearance is 2 ml/min, the free water clearance will be -1 ml/min.
This means that instead of water continuing to be flushed out of the kidney in excess of dissolved substances, the kidneys are actually bringing water back into the circulatory system, as happens in dehydration. Therefore, whenever urine osmolality is greater than plasma osmolality, the free water clearance is negative, indicating water conservation.
When the kidneys are forming dilute urine (for example, urine osmolality is lower than plasma osmolality), the free water clearance will be a positive value, indicating that the water is being discarded. from the plasma through the kidney’s excess solutes. Thus, the released water of solutes, called "free water", is being lost from the body and the plasma is being concentrated when the free water clearance is positive.
Disorders of urine concentration
A decrease in the kidney's ability to concentrate or dilute urine appropriately may occur with one or more of the following abnormalities:
1. Inappropriate excretion of ADH. Either too much or too little ADH excretion leads to abnormal water excretion by the kidneys.
2. Degradation of the upstream mechanism. A hypertonic interstitial region is required for maximum urine concentration. Regardless of how much ADH is present, maximum urine concentration is limited by the degree of interstitial hypertonia.
3. The inability of distal tubules, papillae, and manifolds in response to ADH.
Decreased production of ADH: "central" diabetes mellitus
An inability to produce or release ADH from the posterior pituitary gland can be caused by head injuries or infections or it may be congenital.
Because distal tubular segments cannot reabsorb water in the absence of ADH, this condition, known as "central" diabetes mellitus, results in the formation of a large volume of phase urine. dilute with urine volume may exceed 15 L / day. The thirst mechanisms, discussed later in this chapter, are triggered when too much water is lost from the body; therefore, as long as the person drinks enough fluids, a major depletion of body fluids does not occur. The main clinical abnormality observed in people with this condition is a large volume of diluted urine. However, if water intake is limited, as can occur in a hospital setting when fluid intake is restricted or patient is abnormal (for example, due to a head injury), severe dehydration can occur. out quickly.
Treatment for central diabetes is the administration of an ADH-like synthase, desmopressin, which selectively acts on the V2 receptors to increase water permeability at the distal tubule end and the manifold. Desmopressin can be given by injection, as a nasal spray, or by mouth, and it quickly restores urine output to normal.
The inability of the kidney to respond to ADH: diabetes insipidus "at nephron". In some cases, normal or high concentrations of ADH are present but the tubular segments cannot respond appropriately. This condition is called “nephron” diabetes insipidus because the abnormality resides in the kidneys. This abnormality may be due to either a failure of the retrograde mechanism to form a hypertonic interstitial region or the failure of the distal tubules and the papillary and tubules in response to ADH. In both cases, a large volume of dilute urine is formed, which tends to cause dehydration unless fluid intake is increased with an increased amount of urine volume.
Many types of kidney diseases can impair the concentrating mechanism, especially those with damage to the kidney marrow. Also, the impaired function of the Henle loop, as occurs with diuretics that inhibit the reabsorption of electrolytes in this segment, such as furosemide, can impair the ability to concentrate. urine. Furthermore, some drugs such as lithium (used to treat manic-depressive disorders) and tetracyclines (used as antibiotics) may decrease the ability of distal nephron segments in response to ADH.
Diabetes insipidus at the nephron can be differentiated from central diabetes by administration of desmopressin, a synthetic analogue of ADH. The lack of rapid urinary loss and increase in urine osmolality within 2 hours of desmopressin administration is strongly suggestive of diabetes insipidus at nephron. Treatment for diabetes insipidus at nephron is to correct, if possible, the underlying kidney disorders. Hypernatremia can also be diluted by a low-sodium diet and administration of a diuretic increases renal sodium excretion, such as a thiazide diuretic.