2. Glomerular Filtration Rate (GFR) (GFR) DR. Khaled Khalil

3. At the end of the session the students should be able to:  Define GFR (glomerular filtration rate)  Discuss the mechanism  Discuss the regulatory factors At the end of the session the students should be able to:  Define GFR (glomerular filtration rate)  Discuss the mechanism  Discuss the regulatory factors

7. It is the passive flow of water through the glomerular filter, carrying with it all solutes that are small enough to pass through the filter. Glomerular filtration Definition:

9. - The blood in the glomerular capillaries is separated from Bowman's space by a membrane called “glomerular or filtering membrane”. Filtering Membrane (Glomerular Filter) Filtering Membrane (Glomerular Filter) - It is composed of three layers:

13. 1- Capillary endothelium2- Basement membrane 3- Bowman's capsular epithelium It is a single layer of fenestrated endothelium. * width of the holes is 50-100 nm. * Function: acts as a screen to prevent blood cells and platelets from coming into contact with basement membrane. * It is a meshwork of loose fibrils in a jel-like matrix. * Its thickness is about 0.2-0.3 µm. * Function: acts as a sieve allowing retention of plasma proteins. It represents the major barrier for filtration of large molecules. * It is a single layer of podocytes, each has a finger- like processes. * In between the processes, there are spaces called “slit pores” (5-20 nm wide). * Function: a) lay down and maintain the basement membrane. B) it may also phagocytose macromolecules which has escaped from capillaries.

14. Factors affecting the permeability (filterability) of the glomerular membrane (=The factors determining the composition of the glomerular fluid): i.e., * Particles of molecular radius smaller than 18 A 0 are readily filtered. * Particles with a molecular radius greater than 36 A 0 are not filtered. * particles between 18-36 A 0 are filtered at rates depending on the size and the charge, cationic (positive charged) substances are more readily filtered than anionic (negatively charged) ones because the filtering membrane has negative charges repelling the negatively charged Particles and attracting the positive ones. i.e., * Particles of molecular radius smaller than 18 A 0 are readily filtered. * Particles with a molecular radius greater than 36 A 0 are not filtered. * particles between 18-36 A 0 are filtered at rates depending on the size and the charge, cationic (positive charged) substances are more readily filtered than anionic (negatively charged) ones because the filtering membrane has negative charges repelling the negatively charged Particles and attracting the positive ones. 1)Molecular size and Weight. 2)Shape and Configuration. 3)Electrical charge of the substance. N. B.: nm = 10 Angestrom

15. Pathological conditions that result in loss of the membrane -ve charges are accompanied by proteinuria even before detection of any microscopic change in the membrane.

17. is an ultrafiltrate i.e., has the same composition of the plasma except the plasma protein (only 1% of albumin is filtered + small fraction of globulin). the glomerular filtrate: SO, Glomerular Filtrate = Blood – [(cells) + Plasma Proteins] = Plasma – Plasma Proteins Glomerular Filtrate = Blood – [(cells) + Plasma Proteins] = Plasma – Plasma Proteins

18. Glomerular Filtration Rate GFR GFR - It is the volume of plasma filtered through the glomerular filter per unit time. Definition: Normal values:  125 ml/min (human adult male). = 180 L/day. = 60 nl./min for single nephron (SNGFR).

19. The forces of filtration in the glomeruli (Dynamics of glomerular filtration) The forces of filtration in the glomeruli (Dynamics of glomerular filtration) As any capillary elsewhere in the body, glomerular filtration is determined according to Starling principle which states that "the rate and direction of fluid movement is proportional to the algebric sum of hydrostatic and oncotic pressures".

21. So, GFR α {(Gp - Bp) - (Gπ - Bπ)} GFR = KF {(Gp - Bp) - (Gπ - Bπ)} Where; KF = Filtration coeffecient. Gp = Hydrostatic pressure of glomerular capillaries. (60 mmHg) Bp = Hydrostatic pressure of Bowman’s space. (18 mmHg) Gπ = Oncotic pressure of plasma proteins. (32 mmHg) Bπ= Oncotic pressure of proteins in Bowman’s space. (can be neglected) GFR = KF x Net filtering force Net filtering force = 60 - (18 + 32) = 10mm Hg KF = GFR / Net filtering force = 125 / 10 = 12.5 ml /1 mm Hg/min.

22. So, * Pressure favouring glomerular filtration is: - Hydrostatic pressure of glomerular capillaries. * Pressures opposing glomerular filtration are: 1- Hydrostatic pressure in Bowman's capsule. 2- Oncotic pressure of plasma protein.

23. 1- Hydrostatic pressure of glomerular capillaries: * It is estimated to be 45-60 mm Hg. * This pressure is considered higher than that of capillaries elsewhere in the body due to: a- Afferent arteriole is a straight branch of the interlobular artery. b- The efferent arteriole has a relatively high resistance, its diameter is less than the afferent arteriole. c- The glomerular capillaries is present between the afferent & efferent arteriole, a peculiar position for the glomeruli. d- The renal artery is a direct, wide, straight & at a right angle. * This pressure can be altered by: changes in arterial blood pressure:

24. 2- Hydrostatic pressure in Bowman’s capsules: * It is estimated to be 18 mm Hg. * This pressure is altered by: back pressure transmitted from urinary tract. Obstruction that increases Bowman’s pressure result in decrease of GFR. 3-Oncotic pressure of plasma proteins: * It is estimated to be 32 mm Hg. * This pressure is altered by: alteration in plasma protein concentration.

25. It is the volume of plasma filtered through the glomerular filter for a net filtering force of 1 mmHg per minute. Filtration coefficient Definition: Surface area of the filtering membrane: which is affected by: 1)Total number of the functioning glomeruli. (direct relation) 2)State of intraglomerular mesangium:  Relaxed: increased surface area.  Contracted: Decreased surface area. Factors affecting:

27. ContractedRelaxed  the filtration surface area. By: AII, ADH, Norepinephrine, PGF 2 , thromboxane A 2, Leucotirens C & D, Platelet-derived growth factor, histamine.  the filtration surface area. By: ANP, Dopamine, PGE 2 & cAMP.