GLOMERULAR FILTRATION /TUBULAR REABSORPTION AND SECRETION

GLOMERULAR FILTRATION /TUBULAR REABSORPTION AND SECRETION

1. GLOMERULAR FILTERATION BY: Mrs.Keerthi Kalabathula Asst.Professor , Vijay Marie CON

2. GLOMERULAR FILTRATE The fluid that enters the capsular space that has been filtered by capillaries of glomerulus is called Glomerular Filtrate. The fraction of blood plasma in afferent arterioles of the kidneys that become glomerular filtrate is the FILTRATION FRACTION. On an average daily GF in females is 150lit and in males is 180lit

3. FILTRATION MEMBRANE Together the glomerular capillaries and podocytes forms a leaky barrier called FILTRATION MEMBRANE. It is semi-permeable- permits filtration of water and small solutes but prevents filtration of plasma proteins, blood cells, platelets.

4. FILTRATION MEMBRANE Substances filtered from blood crosses 3 barriers: GLOMERULAR ENDOTHELIAL CELLS BASAL LAMINA] FLITRATION SLIT FORMED BY A PODOCYTE.

5. I.GLOMERULAR ENDOTHELIAL CELLS Quiet leaky because they have large FENESTRATIONS that measure 0.07-0.1 micrometers in diameter. This size permits all solutes in blood plasma to exit glomerular capillaries but prevents filtration of blood cells and platelets. In the cleft between afferent and efferent arterioles and among glomerular capillaries – there are Mesangial cells- the contractile cells and helps regulate GFR.

6. II.BASAL LAMINA Layer of Acellular material between the endothelium and podocytes- made of collagen and proteoglycans in a glycoprotein matrix. Negative charges in matrix – prevents filtration of larger negatively charged plasma proteins (< 0.07 –albumin)

7. III.FILTRATION SLIT Extending from each podocytes are thousands of foot like processes termed as PEDICELS that wrap around glomerular capillaries. The space between these pedicels –FILTRATION SLIT. A thin membrane called SLIT MEMBRANE extends across each filtration slit. This permits passage of molecules of diameter <0.006-0.007um incuding water, glucose,vitamins,aminoacids,ammonia , urea and ions. <1% of albumin passes slit membrane because with diameter of 0.007um it is too big to get through.

8. PRINCIPLES OF FILTRATION The use of pressure to force fluids and solutes through a membrane is same in glomerular capillaries as in capillaries elsewhere in body. However the volume of fluid filtered by renal corpuscle is much larger than in other capillaries of body for 3 reasons:

9. PRINCIPLES OF FILTRATION Glomerular capillaries a larger surface area for filtration because they are long and extensive . The mesangial cell regulate surface area available for filtration. Mesangial cells are relaxed : surface area is maximal –GFR increases . Contraction of mesangial cells – reduces available surface area- GFR decreases.

10. PRINCIPLES OF FILTRATION 2 . THIN AND POROUS FILTRATION MEMBRANE: Despite having many layers , the thickness of filtration membrane is only 0.1mm. Glomerular capillaries also are about 50times leakier than capillaries in most other tissues , mainly because of their large fenestrations.

11. PRINCIPLES OF FILTRATION 3. HIGH GLOMERULAR B.P: Because efferent arteriole is smaller in diameter than afferent arteriole – resistance to outflow of blood from glomerulus is high. As a result BP in glomerular capillaries is considerably high than in capillaries anywhere.

12. NET FILTRATION PRESSURE

13. NET FILTRATION PRESSURE NFP= TOTAL PRESSURE THAT PROMOTES FILTRATION NFP= GBHP-CHP-BCOP =55 mm Hg-15mm Hg-30mmHg NFP=10mmHg Thus a pressure of only 10mm Hg causes normal amount of blood plasma to filter from glomerulus into capsular space.

14. GLOMERULAR FILTRATION RATE The amount of filtrate formed in all renal corpuscle of both kidneys each minute is GFR. In adults GFR averages 125/min in males, 105ml/min in females. Homeostasis requires that kidneys maintain constant GFR. If GFR is too high- needed substances pass quickly---not reabsorbed properly----- are lost in urine. GFR is directly proportional to pressure that determine NFP. Ex: Severe blood loss----- decreases MAP----- decreased GBHP-----if GBHP decreases below 45mmHg-----filtration ceases. GFR is constant when MAP is anywhere between 80-180mmHg

15. GLOMERULAR FILTRATION RATE-MECHANISMS

16. GLOMERULAR FILTRATION- RENAL AUTOREGUALTION The capability of kidneys to maintain constant blood flow and GFR by themselves , despite everyday changes in BP is called RENAL AUTOREGULATION. It consists of 2 mechanisms: Myogenic mechanism Tubuloglomerular feedback

17. GLOMERULAR FILTRATION- RENAL AUOREGUALTION

18. 1.RENAL AUOREGUALTION-Myogenic Mechanism

19. 1.RENAL AUOREGUALTION-Tubulo-Glomerular Feedback

20. 2. NEURAL AUOREGUALTION

21. 3. HORMONAL REGULATION-ANGIOTENSIN-II

22. 3. HORMONAL REGULATION-Atrial Natriuretic Peptide

23. TUBULAR REABSORPTION AND TUBULAR SECRETION

24. PRINCIPLES OF TUBULAR REABSORPTION AND SECRETION The volume of fluid entering the PCT in just half an hour is greater that total blood plasma volume- because the normal rate of GF is so high. Obviously some of this fluid should return somehow to blood stream.

25. PRINCIPLES OF TUBULAR REABSORPTION AND SECRETION Re-absorption – return of most filtered water and many of the filtered solutes to blood stream is the 2 nd basic function of nephron and collecting duct. Normally about 99% of filtered water is reabsorbed. Epithelial cells of entire renal tubule especially PCT carry out reabsorption. Solutes reabsorbed are- glucose, aminoacids , urea and ions such as Na+,K+,Ca+,Cl-,Hco3-,Hpo4-

26. PRINCIPLES OF TUBULAR REABSORPTION AND SECRETION Mos t small proteins are reabsorbed through PINOCYTOSIS. The other function of nephron is tubular secretion- transfer of materials from blood and tubule cells into tubular fluid. Secreted substances include-H+,K+,NH4+, creatinine, drugs such as penicillin. Tubular secretion has 2 outcomes H+ ion secretion- helps in PH control Secretion of other substances- eliminate them from body.

27. ROUTES OF REABSORPTION A substance being reabsorbed from fluid in tubule lumen has to take any one route. It can move between adjacent cells It can move through an individual tubule cell. Among renal tubule, tight junctions surround and connect neighboring cells to one another , much like plastic rings that holds a six pack of soda cans together.

28. MEMBRANES OF REABSORPTION Tight junction do not completely seal off the interstitial fluid in tubule lumen

29. ROUTES OF REABSORPTION

30. TRANSPORT MECHANISMS When renal cells transport solutes in and out into tubular fluid- they move specific substances in one direction only. Different types of transport proteins are present apical and basolateral membranes. The tight junction forma a barrier which prevents mixing of proteins in 2 compartments. Cells lining the renal tubules, like other cells throughout the body- has low conc. Of sodium in cytosol due to the activity of sodium-potassium pumps (Na+/K+ ATPases) These pumps are located in basolateral membranes and eject Na+ from renal tubule cells.

31. TRANSPORT MECHANISMS

32. TRANSPORT PROTEINS Each type of transporter has an upper limit on how fast it can work , just as an escalator has a limit to how many people it can carry – this limit is called TRANSPORT MAXIMUM (Tm), measured in mg/min.

33. SOLUTE REABSORPTION The composition of tubular fluid changes as it flows along nephron tubule and through collecting duct due to reabsorption and secretion. Fluid that drains from papillary ducts into renal pelvis is URINE.

34. Largest amount of solute and water reabsorption from filtered fluid occurs in PCT which reabsorbs 65% of filtered water, Na+, K+, water. Most soluble reabsorption in PCT involves Na+ Sodium transport occurs via symport and antiport REABSORPTION AND SECRETION IN PCT

35. I. Normally filtered glucose, amino acids and lactic acid, water soluble vitamins are not lost in urine, rather they are completely reabsorbed in first half of PCT by several types of Na+ symporters in PCT. Ex: Na+-Glucose symporters in apical membrane in PCT. 2 Na+ and 1 molecule of glucose attach to the symporter protein which carries them from tubular fluid into tubule cell. Then glucose molecule molecules exit the basolateral membrane via facilitated diffusion and they diffuse into peritubular capillaries Ex 2: Na+,Hpo4- symporter and Na+ and So4-2 symporter. REABSORPTION AND SECRETION IN PCT

36. It is an active process. Na/H+ antiporters. They carry filtered sodium across its concentration gradient. PCT cell as H+ is moving from cytosol into the lumen. Causes Na+ to be reabsorbed into blood and H+ to be secreted into tubular fluid . PCT cells produce H+ needed to keep antiporters running in the following way. CO2 diffuses from peritubular blood or tubular fluid or by metabolic reaction with in the cells. The enzyme carbonic anhydrase catalyzes reaction REABSORPTION AND SECRETION IN PCT

37. Most of Hco3- in filtered fluid is reabsorbed in PCT – safeguarding body's buffer. As Hco3- levels rise in the cytosol, it exits via facilitated diffusion transporters in the basolateral membranes. Diffuses into blood with Na+ Solute reabsorption in PCT promotes osmosis. REABSORPTION AND SECRETION IN PCT

38. Each reabsorbed solute increases osmolarity first inside and then in interstitial fluid and finally in blood. Water thus moves rapidly from tubular fluid via paracellular and transcellular routes into peritubular capillaries and restores osmotic balance. Cells lining PCT, DCT and LOH are permeable to water as they have many molecules of AQUAPORIN-I which is an integral protein that increases the rate of water movement across apical and basolateral membranes REABSORPTION AND SECRETION IN PCT

39. Because all of PCT absorb about 65% of filtered water (80ml/min) Fluid enters next part of nephron –LOH at 40-45ml/min. The chemical composition is little different cause glucose, amino acids and other nutrients are no longer present. LOH absorbs-15% filtered water, 20-30% of filtered Na+ and K+, 35% of cl-, 10-20% of HCO3- The apical membrane of cells in thick ALOH has Na+-K+-2cl-. Symporters that simultaneously reclaim Na+-K+-2cl- from fluid in tubular lumen. REABSORPTION AND SECRETION IN LOH

40. Na+ is actively transported into interstitial fluid and then into vaso recta Cl- moves through leakage channels into basolateral membrane into interstitial fluid and into vasa recta. K+ leakage channels are present in apical membrane, most K+ brought in by symporter moves down its concentration back into tubular fluid. Thus, the main effects of Na+-K+-2Cl- symporters is reabsorption of Na+ and cl-. As a result the interstitial fluid and blood is more of negative charges relative to fluid in ascending limb of LOH REABSORPTION AND SECRETION IN LOH

41. Although about 15% of filtered water is reabsorbed in the descending limb of LOH,little or no water is reabsorbed in ascending limb. In this segment of tubule, the apical membrane are virtually permeable to water. REABSORPTION AND SECRETION IN LOH

42. Fluid enters DCT at a rete of about 25ml/min because 80% of filtered water has now been reabsorbed. Early DCT reabsorbs about -10-15% of filtered water , 5% of filtered Na+, 5% of filtered Cl-. Reabsorption of Na+ and Cl- occurs by means of Na+-cl- symporters in apical membrane. Na+-K+ pumps and Cl- leakage channels in basolateral membranes- then permit reabsorption of Na+ and Cl- into peritubular capillaries. The early DCT also is a major site where PTH stimulates reabsorption of Ca+2 REABSORPTION AND SECRETION IN EARLY DCT

43. By the time fluid reaches the end of DCT. 90-95% of filtered solutes and water have returned to the blood stream. PRINCIPAL CELLS: reabsorbs sodium INTERCALATED DISCS : reabsorb K+ and Hco3- and secrete H+ In late DCT and collecting ducts, the amount of water and the amount of solute secretion vary depending on body’s needs. In contrast to earlier segments of nephron, Na+ passes through apical membrane of principal cells via Na+ leakage channels rather than by means of symporters or antiporters. REABSORPTION AND SECRETION IN LATE DCT &COLLECTING DUCT

44. Concentration of sodium in cytosol remains low, as usual because Na+-K+ pumps actively transport Na+ across basolateral membrane. Normally transcellular and paracellular reabsorption in PCT and LOH return most filtered K+ to blood stream. To adjust for varying dietary intake of potassium and to maintain a stable level of K+ in body fluids. REABSORPTION AND SECRETION IN LATE DCT &COLLECTING DUCT

45. HORMONAL REGULATION OF TUBULAR REABSORPTION AND SECRETION-RAA SYSTEM

46. HORMONAL REGULATION OF TUBULAR REABSORPTION AND SECRETION-ADH

47. HORMONAL REGULATION OF TUBULAR REABSORPTION AND SECRETION-ANP

48. HORMONAL REGULATION OF TUBULAR REABSORPTION AND SECRETION-PTH