Glomerular and tubular dysfunctions

1. Glomerular and tubular dysfunctions Tatár M.

2. Basic kidney functions • Water and electrolyte homeostasis • Acid – base balance • Elimination of waste products and ingested chemicals • Hormone production

4. Mechanisms of renal excretion • 180 l glomerular filtrate per day (2 ml/s) • 99% - back reabsoption • Renal perfusion at rest = 20% of cardiac output (this is higher than in heart, brain and liver

7. Glomerular filtration rate • Balance of hydrostatic and osmotic pressures acting across diffusion barrier (endotelium fenestrae, basement nenbrane, slit diaphragms betweens the podocytes) • Factors determining GFR: • Surface area (1 milion nephrons within each kidney) • Permeability • Net filtration pressure (NFP) across diffusion barrier

8. Factors determining GFR • surface area • permeability filtration koefficient (Kf) GFR =Kf x NFP NFP = PGC – PT – GC 24 = 60 - 15 - 21 mmHg

10. Disturbances of glomerular function (1) • Decrease of glomerular filtration •  renal blood flow stenosis of renal artery •  glomerular capillary hydrostatic pressure (PGC) hypovolemia, circulatory shock •  hydrostatic pressure in Bowman´s capsule (PT) block of fluid flow ( intra- and extrarenal) •  concentration of plasma proteins (GC) •  Kf  effective filtration surface area

11. Disturbances of glomerular function (2) B. Increase of glomerular permeability Proteinuria • Glomerular proteinuria • Size-selective properties of the glomerulus • Charge-selective propeties of the glomerulus • Hamodynamic forces operating across the glomerulus

14. Glomerular proteinuria • Selective proteinuria • Albumin • Small amount of low-molecular globulins • Non-selective proteinuria • Albumin • Globulins of various molecular weight

15. Tubular reabsorption of proteins

16. Tubular proteinuria • excretion of low molecular proteins • 1-microglobulin, 2-microglobulin

17. Overload (prerenal) proteinuria • Small molecular weight proteins can rise when are synthetised in excess • Tissue degradedproducts • Proteins of acute phase (pyretic proteinuria) • Myoglobin (rhabdomyolysis) • Ligfht immunoglobulin chains (myeloma)

18. Proteinuria • Healthy adult subject • No more than 150 mg/day • Small proteinuria • 1 g/day • Haevy proteinuria • 3,5 g/day and more • Nephrotic syndrome (10 – 30 g/day)

19. Renal hematuria • Glomerular • Abnormally increased permeability • Non-glomerular • Rupture of tumor or cyst vessels • Bleading from urinary tract

20. Relation between the reduction of GFR and excretion function of kidneys  GF   retention of substrates 1. urea, creatinín 2. phosphates, K+, H+ 3. NaCl

22. Tubular reabsorption and secretion

23. Active transport

24. Reabsorption of glucose, amino acids, Na, K, Cl, H2O Proximal tubule Thick ascending limb of loop of Henle Distale tubule

25. Disturbances of tubular functions Transport maximum • Tubular proteinuria • Glucosuria • Aminoaciduria • Diabetes insipidus • Neurogenic ( ADH) • Nephrogenic (insensitivity of the renal tubule to ADH) • Osmotic diuresis • Pressure of large quantities of unreabsorbed solutes in the renal tubules  increase in urine volume • Unreabsorbed solutes in the proximal tubules „hold water in the next tubules“

26. Hydrogen ion secretion and bicarbonate reabsorption Renal tubular acidosis - impairment of the ability to make the urine acidic - chronic renal disease – reduction of secreted hydrogen ion because of impaired renal tubular production of NH4+

27. Loop of Henle and production of concentrated urine - Permeability for water and NaCl - ADH

28. Counter-current exchange in the vasa recta

29. Disturbances of kidney ability to concentrate urine • Disturbances of water reabsorption - diabetes insipidus • Disturbances of the production of medullar hyperosmolarity - osmotic diuresis -  blood flow in vasa recta - morphologic deformations of medulla

30. Nephrotic syndrome • Proteinuria: 3.5 g or more of protein in the urine per day • Minimal changes of glomerular membrane: 90% albumin (selective proteinuria) • Hypoproteinemia (hypoalbuminemia) • Mechanisms: proteinuria + • Protein loss by stool • Plasma proteins are shifted to extravascular space • Increased albumin katabolism • Inadequately increase albumin synthesis in liver • Hyperlipidemia • Incresed lipoprotein synthesis in liver • Generalised edema

31. Mechanisms of edema in nephrotic syndrome (NS) • Classis theory • Hypoalbuminemia   plasma oncotic pressure  hypovolemia  R-A-A + ADH  Na + water retention • !!! But hypovolemia is present only in 30% of patients suffering from NS; plasma renin activity and aldosteron are decreased • Two groups of patients with NS: • Hypovolemia and  R-A-A activity - small glomerular abnormalities • Hypervolemia without R-A-A activation - more serious morphological abnormalities

32. Pathophysiology of edema formation • Extracellular fluid volume is determined by the balance between Na intake and its renal excretion • Common feature: renal salt retention despite progressive expaansion of ECF volume • Primary abnormality of the kidney • Secondary response to some disturbances in the circulation

33. Primary edema (overfill) • Primary defect in renal sodium excretion • Hyperevolemia leads to high cardiac output •  R-A-A,  ADH,  sympathetic activity Examples: blomerulonephritis, renal failure

34. Secondary edema (underfill) • Response of normal kidnay to actual or sensed underfilling of the circulation • Primary disturbances within the circulation secondary triggers renal sodium retention •  R-A-A,  ADH,  sympathetic activity • Effective arterial blood volume