Proximal tubular cell

from Wikipedia, the free encyclopedia

Proximal tubule cells ( engl. Proximal tubular cells , PTC) are epithelial cells , in the kidney, the front part of the tubule form, the proximal tubule. These are highly differentiated cells that are single-layered isoprismatic , sometimes also cubic .

Layout and function

The schematic structure of a kidney corpuscle . In orange the proximal tubule with the proximal tubular cells.

In the glomerulum , around 20% of the inflowing blood fluid - similar to a filter - is pressed out as primary urine . For an adult, this is around 150 liters per day. Most of this fluid (almost 99%) and the nutrients and minerals it contains must be returned to the body, as such a loss cannot be compensated for by taking in new fluids. This is done by returning these substances ( resorption ) through the tubular cells in the nephrons of the kidneys. When the water is recirculated, one speaks of reabsorption ; in the vital nutrients and minerals of reabsorption . In addition to the nutrients and minerals that are valuable for the body, waste materials such as uric acid and urea are first reabsorbed and then secreted (excreted) again in a second step . In the case of urea, around 50% is reabsorbed via the proximal tubule and supplied to the vena renalis (renal vein) via the cortical blood vessels .

On the side of the proximal tubular cells facing the primary urine, there is a whole network of different receptors, coated pits and endosomes . Correspondingly, a large number of late endosomes, primary lysosomes and lysosomes are found inside the cell . Dense apical tubules are responsible for recycling receptors from the endosomes.

Receptors on the apical cell membrane of the proximal tubular cells include folate receptors , IGF2R ( insulin-like growth factor 2 receptor ) and M6PR (mannose-6-phosphate receptor) as well as especially cubilin and megalin . Aquaporin 1 , also known as CHIP-28 ( channel-forming integral proteins ), which is strongly expressed in the cell membrane , enables transcellular transport of water.

Secretion and resorption in the renal tubules change the primary urine. At the end of the tubule, the terminal urine is fed to the bladder via collecting tubes . The tubular system is divided into different sections, which have different tasks ( see main article Nephron ).

Schematic representation of a proximal tubular cell

On the luminal side, i.e. facing the primary urine, the tubular cells have microvilli . These serve to enlarge the cell surface and thus improve the exchange of substances. The basal side, on the other hand, has a fold structure. In the cytoplasm, there are relatively many mitochondria , especially on the basal side , in order to provide sufficient energy for the complex resorptive transport processes. This is particularly important for the ATP -dependent Na + / K + pumps . The reabsorption is energetically very complex: per ATP molecule only three sodium ions are transported from the primary urine through the tubular cells.

Most of the kidney's oxygen consumption occurs through the tubular cells. The transport of sodium ions alone, about 2/3 in the proximal tubule, requires about 75 percent of the total oxygen consumed .

tasks

Tubuloglomerular feedback

A tubuloglomerular feedback ( also referred to as tubuloglomerular feedback in masculine terms ) or a tubuloglomerular equilibrium is postulated in order to guarantee a more or less strict proportionality between primary urine formation and urine production. In cardiogenic shock or extreme physical exertion, a high or normal glomerular filtration rate , on the contrary, often causes oliguria or even anuria in order to compensate for relative hypovolemia when the body is dehydrated . If the tubular re- resortion rate decreases, then the secondary urine formation increases and vice versa.

The glomerular filtration rate is largely proportional to cardiac output. The tubular reabsorption is largely inversely proportional to the blood volume . So there is no direct connection between primary urination and secondary urination. Those who drink a lot produce a lot of urine with large blood volumes and little urine with small blood volumes. Those who drink little produce little urine with normal blood volumes and no urine with small blood volumes.

Mineral and water absorption

About 60% of the sodium, potassium, hydrogen carbonate and chloride ions filtered through the glomeruli are absorbed in the proximal tubules. Phosphate and sulfate ions are also included. Some of these substances are absorbed through the tubular cells ( transcellularly ). With potassium, chloride, calcium or urea, the concentration gradient enables paracellular diffusion (between the tubular cells) and thus reabsorption. With water, the osmotic pressure is sufficient for paracellular resorption. The so-called solvent drag also pulls ions dissolved in the water. In addition, the tubular cells do not have any specific potassium transporters.

The sodium ions are absorbed in the antiport with protons and in the symport with glucose , galactose , amino acids , phosphate and sulfate ions, as well as mono- and dicarboxylic acids . On the basolateral side of the tubular cells, the sodium-potassium pump (3 Na + / 2 K + -ATPase) ensures that the concentration gradient across the cell membrane is maintained. Hydrogen carbonate ions are broken down into water and carbon dioxide through the reaction with protons and can thus passively diffuse back.

Glucose absorption

In the healthy kidney, 100% of the glucose is reabsorbed by the tubular cells. This is mainly done with the help of the glucose transporter SGLT-2 . In contrast, the glucose transporter SGLT-1 in particular is expressed on the cell membrane in the distal tubule . The glucose transporters GLUT-2 and GLUT-5 play a subordinate role. The so-called kidney threshold of glucose is approx. 180 mg / dl (10 mmol / l) in the serum, since the saturation of the systems involved in reabsorption is reached from this concentration of glucose. From a concentration of 22 mmol / l onwards there is complete saturation and the glucose excretion in the urine increases proportionally to the concentration in the plasma.

Absorption of amino acids, peptides and small proteins

Peptides or proteins that are small enough to get through the glomerulum into the primary urine are also taken up by the tubular cells and completely catabolized. An example is composed of 120 amino acids constructed Cystatin C .

The membrane proteins megalin and cubilin of the proximal tubular cells play an important role in the endocytosis of peptides and proteins. Both are expressed on the apical side facing the primary urine. After endocytotic uptake, the proteins are transported to the lysosomes for proteolysis (breakdown) and the two receptors are transported back to the apical side of the cell membrane (receptor recycling). In contrast, there is hardly any transcellular protein transport. The resorption of proteins in the proximal tubule is very efficient in a healthy kidney, so that the terminal urine of humans is free of proteins.

The Megalin-Cubilin complex can not only absorb amino acids, peptides and proteins, but also a large number of other essential compounds, such as vitamins or trace elements bound to plasma proteins .

Diseases

The proximal tubular cells play a central role in a number of kidney diseases and dysfunction, such as glomerular proteinuria and chronic transplant nephropathy . Damage or stimulation of the proximal tubular cells triggers a series of signal cascades via messenger substances . This can lead, for example, to the production of proteins of the complement system , chemokines , cytokines and components of the extracellular matrix in the proximal tubular cells. The locally generated messenger substances can further damage the proximal tubular cells through increased diapedesis (leukocyte migration) , especially of macrophages , granulocytes and T cells , and lead to a downward spiral . The production of chemokines and cytokines in particular can irreversibly impair kidney function through proinflammatory processes, which can lead to renal insufficiency . The targeted immunosuppression of the proximal tubular cells is a potential therapeutic starting point for the treatment of the diseases mentioned.

Mutations in the LRP2 gene, which codes for the membrane protein megalin , can limit the functionality of this receptor, which can lead to proteinuria and the very rare Donnai-Barrow syndrome .

further reading

  • D. Brown et al .: Regulation of the V-ATPase in kidney epithelial cells: dual role in acid-base homeostasis and vesicle trafficking. In: J Exp Biol 212, 2009, pp. 1762-1772. PMID 19448085 (Review)
  • U. Panchapakesan et al .: Review article: importance of the kidney proximal tubular cells in thiazolidinedione-mediated sodium and water uptake. In: Nephrology 14, 2009, pp. 298-301. PMID 19444964 (Review)
  • Y. Motoyoshi et al .: Megalin contributes to the early injury of proximal tubule cells during nonselective proteinuria. In: Kidney Int . 74, 2008, pp. 1262-1269. PMID 18769366
  • AA El-Sheikh et al: Mechanisms of renal anionic drug transport. In: Eur J Pharmacol 585, 2008, pp. 245-255. PMID 18417112 (Review)
  • YJ Lee et al .: Regulatory mechanisms of Na (+) / glucose cotransporters in renal proximal tubule cells. In: Kidney Int Suppl 106, 2007, pp. 27-35. PMID 17653207 (Review)
  • EE Robertson and GO Rankin: Human renal organic anion transporters: characteristics and contributions to drug and drug metabolite excretion. In: Pharmacol Ther 109, 2006, pp. 399-412. PMID 16169085 (Review)
  • BC Burckhardt and G. Burckhardt: Transport of organic anions across the basolateral membrane of proximal tubule cells. In: Rev Physiol Biochem Pharmacol 146, 2003, pp. 95-158. PMID 12605306 (Review)

Individual evidence

  1. ↑ Manuscript: The Kidney. ( Memento from July 18, 2003 in the Internet Archive ) University Hospital Giessen, accessed on January 7, 2010.
  2. ^ S. Kawamura, JP Kokko: Urea secretion by the straight segment of the proximal tubule. In: The Journal of clinical investigation. Volume 58, Number 3, September 1976, pp. 604-612, doi : 10.1172 / JCI108507 , PMID 956389 , PMC 333219 (free full text).
  3. ^ T. Armsen and HW Reinhardt: Transtubular movement of urea at different degrees of water diuresis. In: Pflügers Arch 326, 1971, pp. 270-280. PMID 5106093 .
  4. ↑ B. Yang and L. Bankir: Urea and urine concentrating ability: new insights from studies in mice. In: Am J Physiol Renal Physiol 288, 2005, pp. F881-896. PMID 15821253 (Review).
  5. ↑ a b E. I. Christensen u. a .: Membrane receptors for endocytosis in the renal proximal tubule. In: Int Rev Cytol 180, 1998, pp. 237-284. PMID 9496636 (Review).
  6. ↑ S. Nielsen and P. Agre: The aquaporin family of water channels in kidney. In: Kidney Int 48, 1995, pp. 1057-1068. PMID 8569067 (Review).
  7. ↑ I. Sabolić and D. Brown: Water transport in renal tubules is mediated by aquaporins. In: Clin Investig 72, 1994, pp. 698-700. PMID 7531521 (Review).
  8. ^ EM Wintour: Water channels and urea transporters. In: Clin Exp Pharmacol Physiol 24, 1997, pp. 1-9. PMID 9043798 (Review).
  9. ↑ AS Verkman: Mechanisms and regulation of water permeability in renal epithelia. In: Am J Physiol 257, 1989, pp. C837-850. PMID 2688434 (Review).
  10. ↑ Anatomy of the kidneys: Tubular system of the nephron. after A. Benninghoff: Macroscopic anatomy, embryology and histology of humans. 15th edition, Verlag Urban and Schwarzenberg, 1993.
  11. ↑ a b Anatomy of the Kidneys: Physiology (tubular reabsorption). after A. Benninghoff: Macroscopic anatomy, embryology and histology of humans. 15th edition, Verlag Urban and Schwarzenberg, 1993.
  12. ↑ A. Wehner: Cystatin C as a clinical parameter for determining kidney function in dogs. Dissertation, LMU Munich, 2008.
  13. ↑ a b c E. Dayal: Characterization of the chemokine receptor CXCR3 in human proximal tubular cells of the kidney. Dissertation, Albert-Ludwigs-Universität Freiburg im Breisgau, 2005.
  14. ↑ Gekle et al., Pocket Textbook Physiology, 2nd, revised edition, Stuttgart 2015, p. 368.
  15. ↑ H. Lofberg and AO Grubb: Quantitation of gamma-trace in human biological fluids: indications for production in the central nervous system. In: Scand J Clin Lab Invest 39, 1979, pp. 619-626. PMID 119302 .
  16. ^ A. Grubb et al .: Serum concentration of cystatin C, factor D and beta 2-microglobulin as a measure of glomerular filtration rate. In: Acta Med Scand 218, 1985, pp. 499-503. PMID 3911736 .
  17. ↑ A. Saito et al.: Role of megalin, a proximal tubular endocytic receptor, in calcium and phosphate homeostasis. In: Ther Apher Dial 11, 2007, pp. 23-26. PMID 17976080 (Review).
  18. ↑ a b E. I. Christensen et al: Receptor-mediated endocytosis in renal proximal tubule. In: Pflugers Arch 458, 2009, pp. 1039-1048. PMID 19499243 (Review).
  19. ^ MR Daha and C. van Kooten: Is the proximal tubular cell a proinflammatory cell? In: Nephrol Dial Transplant . 15, 2000, pp. 41-43. PMID 11143986 (Review)
  20. ↑ S. Kantarci et al. a .: Mutations in LRP2, which encodes the multiligand receptor megalin, cause Donnai-Barrow and facio-oculo-acoustico-renal syndromes. In: Nat Genet 39, 2007, pp. 957-959. PMID 17632512 .

Web links