Physiology of the kidney (5/7): Tubular Reabsorption
Review literature: (Benninghoff, 1993) (Schmidt und Thews, 1995).
Tubular Reabsorption of Sodium, Chloride and Fluids
99% of the glomerular filtrate volume (primary urine, 120 ml/min), 99% of the filtrated sodium and 99% of the filtered Chloride are reabsorbed in the renal tubules of the nephron. The reabsorption is energy consuming process; the needed energy rises linearly with the NaCl-Reabsorption. The most common drive for the reabsorption is the basolateral located Na-K-ATPase (sodium-potassium pump), which transports three sodium atoms out of the cell and two potassium atoms into the cell, the energy derives from the hydrolysis of one ATP molecule.
Proximal Tubule and Descending Part of the Henle Loop
In the proximal tubule, two thirds of the primary urine volume with electrolytes are reabsorbed. Electrolyte reabsorption leads to the water reabsorption with help of the leaky intercellular spaces of the proximal tubule epithelium. The solvent drag enables the paracellular absorption of water and chloride due to electrolyte concentrations between the tubule lumen and the renal interstitium.
The drive of the sodium transport is accomplished through the basolateral sodium-potassium-pump. On the luminal side of the proximal tubule epithelium, sodium enters the cell via symporter membrane proteins (Co-transport with glucose, galactose, phosphate, sulfate or amino acids) or antiporter membrane proteins (Co-transport with protons). The reabsorption of HCO3− is linked to the sodium reabsorption and proton secretion with help of a luminal and intracellular carbonic anhydrase.
The chloride reabsorption is not so clearly identified. Beside the solvent drag, there are additional minor transcellular transport pathways for chloride in the luminal and basolateral membrane.
Ascending part of Henle Loop
The thick ascending loop (TAL) of Henle is impermeable to water and transports electrolytes into the interstitium of the kidney, producing a high osmotic pressure of the interstitium. 30% of the filtered sodium is reabsorbed using a luminal Na-K-2Cl-cotransport mechanism. The energy for the natrium reabsorption derives from the basolateral sodium-potassium pump. The effective prevention of a passive water flow with watertight tight junctions leads to a high osmotic pressure in the renal medulla. The urine at the end of the TAL is hypotonic. Furosemide inhibits the Na-K-2Cl cotransporter and leads to a massive natriuresis and loss of potassium, calcium and magnesium.
Active sodium transport via thiazide-sensitive Na-Cl-co-transporter; about 10% of the filtered sodium is reabsorbed in the distal tubule. Thiazides inhibit the sodium reabsorption in the distal tubule and lead to a mild diuresis without loss of calcium (calcium-sparing diuretic).
The permeability of the collecting ducts for water lead to a concentration of the urine up to the fivefold osmolarity of the plasma. The permeability of the collecting ducts is regulated with ADH (antidiuretic hormone, Vasopressin). ADH causes the incorporation of additional water channels (aquaporins) into the luminal membrane. The high osmotic pressure of the renal medulla is the responsible force for the urine concentration. ADH can control 10% of the primary urine volume, thus can regulate the diuresis between 1–20 l/d.
In the absence of ADH, the permeability of the collecting ducts for water is low, the urine will not be concentrated. A deficiency of ADH secretion leads to diabetes insibitus, a disorder with massive diuresis and excessive thirst.
Additional sodium reabsorption takes place in the collecting ducts via luminal sodium channels. The energy for the sodium reabsorption derives from the basolateral sodium-potassium pump. Aldosterone regulates the sodium and water reabsorption and potassium secretion via expression of the sodium channels and the basolateral sodium-potassium pump. The luminal sodium channels can be inhibited by amiloride, a potassium-sparing diuretic.
Potassium reabsorption of the kidney
60–70% of the filtered potassium (K+) is reabsorbed in the proximal tubule. There are no specific K-transporter, reabsorption is managed with the absorption of water (solvent drag). 25–35% of the filtered potassium is reabsorbed in the loop of Henle with the Na-K-2Cl-cotransport mechanism. 5–15% of the filtered potassium reaches the distal nephron. Depending on the metabolism there are now possibilities of potassium reabsorption or excretion (controlled by aldosterone).
Renal Calcium Reabsorption
60% of the filtered calcium is reabsorbed in the proximal tubule with the paracellular absorption of water (solvent drag). Additionally, there are active transport mechanisms.
Renal Phosphate Reabsorption
Phosphate is completely filtered, 80–90% of the phosphate are reabsorbed in the proximal tubule. With high phosphate concentrations in serum, a saturation of the phosphate reabsorption is reached and phosphate is excreted till the normalization of the phosphate concentration. An increased phosphate concentration is the stimulus for the parathyroid hormone release and leads to phosphate excretion, calcium phosphate deposition into the bone and lowers the serum calcium.
Proton Excretion and Acid-Base Homeostasis
The renal excretion of protons is a major factor in the acid-base homeostasis; mechanisms are the phosphate excretion, ammonia excretion and reabsorption of bicarbonate.
Phosphate dissociates in the blood to 80% in HPO42-. In the renal tubulus, this secondary phosphate binds a proton and the result is H2PO4−. The newly formed primary phosphate cannot be reabsorbed and with the help of phosphate excretion, a proton is eliminated.
Glomerular filtered bicarbonate is reabsorbed in the proximal tubule via the following mechanism: the filtered HCO3− and secreted H+ from the tubular cell (Na-H exchanger) forms with the help of luminal carbonic anhydrase H2CO3, which dissociates to CO2 ad H2O. The CO2 enters easily into the tubule cell and binds with OH− (remnants of the H+ secretion) to bicarbonate (HCO3−). With the help of the Na+/HCO3−-cotransporter in the basal membrane, bicarbonate is returned into the blood. In the case of alkalosis, bicarbonate can be secreted to balance the acid-base homeostasis.
The ammonium excretion can be 10-fold increased in case of acidosis. NH3 is formed in the kidney by deamination of glutamine by the tubular cells and can diffuse into the tubular lumen. In the renal tubules, NH3 forms together with a proton NH4+, which cannot be reabsorbed.
Glucose Reabsorption in the Kidney
Glucose reabsorption happens to 100% in the proximal tubule using the sodium-glucose-cotransporter. In the case of too high glucose concentration in the serum, this mechanism is subject to saturation and glucosuria results. The threshold concentration for this saturation is 10 mmol/l (180 mg/dl) of glucose in the serum.
Amino Acid Reabsorption in the Kidney
Different sodium-amino acid cotransporter are responsible for the reabsorption of amino acids in the proximal tubule. So far, seven different transporters have been described: for acidic amino acids (Glu, Asp), basic amino acids (Arg, Lys, Orn) and five other systems for neutral amino acids. There are similar principles for the saturation of the amino acid transport as for glucose reabsorption (see above). The failure of amino acid cotransporter, usually for genetic reasons or side effects of medication, causes selective aminoaciduria (Cystinuria, Hartnup's disease, Fanconi syndrome).
Urea Transport of the Kidney
About 50 g of urea are filtered per day, of which approximately 25–40 g are excreted in the urine. The reabsorption of urea (proximal tubule, collecting ducts) and active secretion of urea (Henle loop) leads to a urea circulation between the lumen of the nephron and renal medulla, which is an important element of the renal urine concentration.
Urea is freely filtered, 50% are reabsorbed in the proximal tubule with the reabsorption of water (solvent drag). Urea is secreted in the thin ascending limb of Henle loop, so significant amounts of urea reach the distal nephron. In the collecting ducts, urea is reabsorbed together with water. These mechanisms enable the formation of a high-osmolar urea gradient in the renal medulla, which is important for the renal urine concentration. If the absorption of urea (and water) is stopped in the collecting duct, the osmolarity of the medulla decreases and the concentration mechanisms collapse.
Uric acid transport of the kidney
Uric acid is filtered completely and is partially absorbed in the proximal tubule. In addition, uric acid is secreted in the proximal tubule. Uric acid is has a good solubility in form of sodium urate. To prevent calcium urate crystals in the course of the urine concentration, various complexing agents such as calcium citrate, calcium-binding proteins and mucopolysaccharides are necessary.
Mechanism of the Urine Concentration
In the case of water deficiency, the human kidney can concentrate the urine up to 4 times of the plasma osmolarity of 290 mosmol/l. With antidiuresis, the daily urine volume is 0.5–1 l. A complex countercurrent system, which includes the Henle loops, Vasa recta and collecting ducts, generates a hypertonic renal medulla of 1200 mosmol/l. The high osmolarity of the renal medulla enables a urine concentration with a urine osmolarity up to these values.
Renal Countercurrent System
The motor of the renal countercurrent system and the urine concentration is the NaCl reabsorption of the thick ascending loop (TAL) of Henle. The active Na+ and Cl− transport in the watertight ascending Henle loops leads to an increase in osmolarity of the renal interstitium. Another mechanism of the high osmolarity of renal medulla is the reabsorption of urea (proximal tubule, collecting ducts) and active secretion of urea (Henle loop). The urea circulation between proximal and distal nephron helps to establish the gradual increase in osmolarity in the direction of the renal papillae.
The blood supply of the renal medulla is scarce and also designed on the principle of countercurrent; the high osmolarity is not washed out. The osmolarity increases in the vasa recta in direction to the renal papillae and decreases in the outflow towards the cortex. In principle, the osmotically active substances of the renal interstitium circulate continuously. In the case of an increased renal blood flow, the renal interstitium loses osmotically active substances. The result is a so-called pressure diuresis, a mechanism to correct arterial hypertension.
Index: 1–9 A B C D E F G H I J K L M N O P Q R S T U V W X Y Z
Benninghoff 1993 BENNINGHOFF, A.:
- Makroskopische Anatomie, Embryologie und Histologie des
München; Wien; Baltimore : Urban und Schwarzenberg, 1993
Schmidt, R. F. & Thews, G. T. (ed.)
- Physiologie des Menschen
Berlin; Heidelberg; New York: Springer, 1995