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Urophysiology 2


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# Glomerular filtration Rate and it's Autoregulation.
# Glomerular filtration barrier.

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Urophysiology 2

  1. 1. Glomerular Filtration, Renal Blood Flow, and Their Control
  2. 2. GLOMERULAR FILTRATION—THE FIRST STEP IN URINE FORMATION: • The first step in urine formation is the filtration of large amounts of fluid through the glomerular capillaries into Bowman’s capsule - almost 180 liters each day. • Most of this filtrate is reabsorbed, leaving only about 1 liter of fluid to be excreted each day. • Renal fluid excretion rate may be highly variable depending on fluid intake. • The high rate of glomerular filtration depends on: 1- A high rate of kidney blood flow, 2- As well as the special properties of the glomerular capillary membranes.
  3. 3. COMPOSITION OF THE GLOMERULAR FILTRATE: • Glomerular capillaries are relatively impermeable to proteins. • Filtered fluid (called the glomerular filtrate) is essentially protein free and devoid of cellular elements, including red blood cells. • The concentrations of other constituents of the glomerular filtrate, including most salts and organic molecules, are similar to the concentrations in the plasma. • A few low molecular weight substances such as calcium and fatty acids that are not freely filtered because they are partially bound to the plasma proteins.
  4. 4. GFR IS ABOUT 20 PERCENT OF RENAL PLASMA FLOW: • The GFR is determined by: (1) The balance of hydrostatic and colloid osmotic forces acting across the capillary membrane and (2) The capillary filtration coefficient (Kf), the product of the permeability and filtering surface area of the capillaries. • Normal GFR is 125 mL/minute or about 180 L/day. • Filtration fraction is the fraction (portion) of the renal plasma, which becomes the filtrate. • Filtration fraction = GFR (125ml)/Renal plasma flow (650ml) or Filtration fraction = 0.2 or 15 % – 20%
  5. 5. GLOMERULAR CAPILLARY MEMBRANE: (1) The endothelium of the capillary. (2) A basement membrane. (3) A layer of epithelial cells (podocytes) surrounding the outer surface of the capillary basement membrane. • Together, these layers make up the filtration barrier. • Surrounding the endothelium is the basement membrane, which consists of a meshwork of collagen and proteoglycan (negatively charge) fibrillae that have large spaces through which large amounts of water and small solutes can filter. • The epithelial cells of podocytes, also have negative charges, provide additional restriction to filtration of plasma proteins.
  6. 6. Filterability of Solutes Is Inversely Related to Their Size. Negatively Charged Large Molecules Are Filtered Less Easily Than Positively Charged Molecules of Equal Molecular Size. Keep in mind that positively charged molecules are filtered much more readily than are negatively charged molecules. In certain kidney diseases, the negative charges on the basement membrane are lost such as minimal change nephropathy.
  7. 7. DETERMINANTS OF THE GFR: • The GFR is determined by: (1) The sum of the hydrostatic and colloid osmotic forces across the glomerular membrane, which gives the net filtration pressure. (2) The glomerular filtration coefficient Kf = GFR/ net filtration GFR = Kf × Net filtration pressure. • Although increased Kf raises GFR and decreased Kf reduces GFR. • Disease that decrease the Kf are (chronic hypertention, diabetic mellitus). increasing the thickness of the glomerular capillary basement membrane + damaging the capillaries so severely that there is loss of capillary function.
  8. 8. FACTORS REGULATING (AFFECTING) GFR: 1- Renal Blood Flow: • GFR is directly proportional to renal blood flow. 2- Tubuloglomerular Feedback. 3- Glomerular Capillary Pressure: • GFR is directly proportional to glomerular capillary pressure. 4- Colloidal Osmotic Pressure: • GFR is inversely proportional to colloidal osmotic pressure 5- Hydrostatic Pressure in Bowman Capsule: • GFR is inversely proportional to this. 6- Constriction of Afferent Arteriole: • Constriction of afferent arteriole reduces the blood flow to the glomerular capillaries, which in turn reduces GFR 2- Tubuloglomerular Feedback.
  9. 9. 7. Constriction of Efferent Arteriole: • initially the GFR increases, Later when all the substances are filtered from this blood, further filtration does not occur. 8. Systemic Arterial Pressure: • Variation in pressure above 180 mm Hg or below 60 mm Hg affects the renal blood flow and GFR accordingly, because the autoregulatory mechanism fails beyond this range. 9. Sympathetic Stimulation: • Afferent and efferent arterioles are supplied by sympathetic nerves. • The mild or moderate stimulation of sympathetic nerves does not cause any significant change either in renal blood flow or GFR. • Strong sympathetic stimulation causes severe constriction of the blood vessels by releasing the neurotransmitter substance, noradrenaline. • The effect is more severe on the efferent arterioles than on the afferent arterioles.
  10. 10. 10. Surface Area of Capillary Membrane: • GFR is directly proportional to the surface area of the capillary membrane. 11. Permeability of Capillary Membrane: • GFR is directly proportional to the permeability of glomerular capillary membrane. • In many abnormal conditions like hypoxia, presence of toxic agents, etc. the permeability of the capillary membrane increases. • In such conditions, even plasma proteins are filtered and excreted in urine. 12. Contraction of Glomerular Mesangial Cells: • Glomerular mesangial cells are situated in between the glomerular capillaries. Contraction of these cells decreases surface area of capillaries resulting in reduction in GFR
  11. 11. 13. Hormonal and Other Factors: • Many hormones and other secretory factors alter GFR by affecting the blood flow through glomerulus. Factors increasing GFR by vasodilatation i. Atrial natriuretic peptide ii. Brain natriuretic peptide iii. cAMP iv. Dopamine v. Endothelial - derived nitric oxide vi. Prostaglandin (PGE2). Factors decreasing GFR by vasoconstriction i. Angiotensin II ii. Endothelins iii. Noradrenaline iv. Platelet - activating factor v. Platelet - derived growth factor
  13. 13. • Autoregulation is the intrinsic ability of an organ to regulate its own blood flow. • Autoregulation is present in some vital organs in the body such as brain, heart and kidneys. • It is highly significant and more efficient in kidneys. • Renal Autoregulation: • is important to maintain the glomerular filtration rate (GFR). • Two mechanisms are involved in renal autoregulation: 1. Myogenic response. 2. Tubuloglomerular feedback.
  14. 14. MYOGENIC AUTOREGULATION OF RENAL BLOOD FLOW AND GFR: • Is the ability of individual blood vessels to resist stretching during increased arterial pressure. • Mechanism of action: 1. Whenever the blood flow to kidneys increases. 2. Stretch of the vascular wall allows increased movement of calcium ions from the extracellular fluid into the cells. 3. causing them to contract. 4. So, the blood flow is decreased. • Importance of this mechanism is: A. Prevents excessive stretch of the vessel and at the same time, by raising vascular resistance. B. helps prevent excessive increases in renal blood flow and GFR when arterial pressure increases. • Keep in mind this mechanism may be more important in protecting the kidney from hypertension-induced injury.
  15. 15. TUBULOGLOMERULAR FEEDBACK AND AUTOREGULATION OF GFR: • Macula densa plays an important role in tubuloglomerular feedback, which controls the renal blood flow and GFR. • Macula densa with the control of renal arteriolar resistance and autoregulation of GFR. • This feedback helps ensure a relatively constant delivery of sodium chloride to the distal tubule and helps prevent spurious fluctuations in renal excretion that would otherwise occur. • The tubuloglomerular feedback mechanism has two components that act together to control GFR: (1) an afferent arteriolar feedback mechanism (2) an efferent arteriolar feedback mechanism. • These feedback mechanisms depend on special anatomical arrangements of the juxtaglomerular complex (apparatus).
  16. 16. The juxtaglomerular complex consists: 1- macula densa cells in the initial portion of the distal tubule. 2- juxtaglomerular cells in the walls of the afferent and efferent arterioles. • The macula densa is a specialized group of epithelial cells in the distal tubules that comes in close contact with the afferent and efferent arterioles. • The macula densa cells contain Golgi apparatus, which are intracellular secretory organelles directed toward the arterioles, suggesting that these cells may be secreting a substance toward the arterioles. • Decreased Macula Densa Sodium Chloride Causes Dilation of Afferent Arterioles and Increased Renin Release.
  17. 17. Vasoconstriction Vasodilatation
  18. 18. Other Factors That Increase Renal Blood Flow and GFR: • A high protein intake is known to increase both renal blood flow and GFR. • Increases in renal blood flow and GFR that occur with large increases in blood glucose levels in persons with uncontrolled diabetes mellitus.  Remember that absorption of amino acid and glucose depend with co transport of Na as discussed in digestive system