Glomerular and tubular dysfunctions Tatár M.

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

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

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

Factors determining GFR filtration koefficient (K f ) surface area permeability GFR = K f x NFP NFP = P GC – P T –  GC 24 = mmHg

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

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

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

Tubular reabsorption of proteins

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

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

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)

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

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

Tubular reabsorption and secretion

Active transport

Reabsorption of glucose, amino acids, Na, K, Cl, H 2 O Proximal tubuleThick ascending limb of loop of Henle Distale tubule

Disturbances of tubular functions 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“ Transport maximum

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 NH 4 +

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

Counter-current exchange in the vasa recta

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

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

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: 1.Hypovolemia and  R-A-A activity - small glomerular abnormalities 2.Hypervolemia without R-A-A activation - more serious morphological abnormalities

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

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

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