Glomerular filtration

glomerular filtration and factors affecting the GFR

1. GLOMERULAR FILTRATION AND ITS REGULATION by Karishma R. Pandey Assistant professor BPKIHS, N epal

2. Objectives Introduction Mechanism of glomerular filtration Glomerular filtration Rate(GFR) Measurement of GFR Regulation of GFR Applied aspects

3. Introduction Excretory organ Extends :T 12 -L 3 Nephron=1- 2 million in each kidney

4. 3 processes involved in Urine formation Glomerular filtration Tubular reabsorption Tubular secretion

5. Glomerular Filtration Ultrafiltration of plasma in the glomerulus Governed by 2 major factors: Filtration coefficient ( K f ) Pressure gradient/ Starling forces (hydrostatic and osmotic pressure gradients)

6. Mechanism of Glomerular Filtration Filtration coefficient Capillary permeability Size of the capillary bed

7. Pressure Gradient

8. Glomerular filtration = K f [(P GC -P T ) – ( π GC - π T )]

9. Composition of the filtrate Every electrolyte Metabolic wastes Metabolites Non natural substances Lower wt proteins and peptides

10. Glomerular Filtration Rate (GFR) T he rate at which plasma is filtered by the kidney glomeruli . An important measurement in the evaluation of kidney function GFR = 125 mL plasma/min or, 180 L/day Plasma volume (70-kg young adult man) = about 3L , the kidneys filter the plasma some 60 times in a day .

11. Factors affecting GFR Change in renal blood flow Glomerular capillary hydrostatic pressure Change in capsular hydrostatic pressure Oncotic pressure Glomerular capillary permeability Effective filtration surface area Size, shape and electrical charge of the macromolecules

12. Fick principle (mass balance or conservation of mass) Where, P a x and P v x = the concentrations of substance x in the renal artery and renal vein plasma, respectively; RPF a and RPF v = the renal plasma flow rates in the artery and vein, respectively; U x = the concentration of x in the urine; and Vdot = the urine flow rate.

13. Renal Clearance The renal clearance of a substance can be defined as the volume of plasma from which that substance is completely removed (cleared) per unit time. The clearance formula is : Where, X is the substance of interest , C X is the clearance of substance X, U X is the urine concentration of substance , P X is the plasma concentration of substance X, and V is the urine flow rate.

14. Inulin Clearance Equals the Glomerular Filtration Rate Inulin clearance : highest standard highly accurate Others : iothalamate , an iodinated organic compound, EDTA, Vit B 12 Not commonly used in the clinical practice . infused intravenously, the bladder is usually catheterized; inconvenient R easons : • freely filterable • not reabsorbed or secreted • not synthesized, destroyed, or stored in the kidneys. • nontoxic. • concentration in plasma and urine can be determined by simple analysis.

15. The Endogenous Creatinine Clearance Is Used Clinically to Estimate GFR The inverse relationship between GFR and plasma [ creatinine ]allows the use of plasma [ creatinine ] as an index ofGFR

16. Renal blood flow K idneys have a very high blood flow 20% of the cardiac output (5 to 6 L/min) i.e , about 1.2 L/min.

17. Measured by electromagnetic flow-meter RBF= amount of a given substance taken up by kidney per unit time arterio -venous diff of the substance across the organ Renal blood flow (RBF) can be determined from measurements of renal plasma flow (RPF) and blood hematocrit , using the following equation: RBF = RPF/(1 - Hematocrit )

18. Renal plasma flow p - aminohippurate (PAH), infused intravenously. PAH is filtered and vigorously secreted, so it is nearly completely cleared from all of the plasma flowing through the kidneys. The renal clearance of PAH, at low plasma PAH levels, approximates the renal plasma flow. E RPF = CPAH

19. The equation for calculating the true value of the renal plasma flow is: RPF = CPAH/EPAH Where, CPAH= PAH clearance EPAH = extraction ratio for PAH = the arterial plasma [PAH] (Pa PAH) minus renal venous plasma [PAH] ( Prv PAH) divided by the arterial plasma [PAH]. The equation is derived as follows . In the steady state, the amounts of PAH per unit time entering and leaving the kidneys are equal. RPF Pa PAH= UPAH × V + RPF Prv PAH Rearranging, we get : RPF = UPAH × V ˙ /(Pa PAH – Prv PAH) If we divide the numerator and denominator of the right side of the equation by Pa PAH , the numerator becomes CPAH and the denominator becomes EPAH.

20. Measurement of GFR Modern imaging techniques Measuring renal clearance of various substances

21. Regulation of GFR Intrinsic mechanism Extrinsic mechanism Myogenic mechanism Tubuloglomerular feedback Neural mechanism Hormonal mechanism

22. Myogenic mechanism BP Stretching of blood vessels (afferent arteriole smooth muscle) Opening of cationic channels Depolarization Opening of voltage-dependent calcium channels Calcium influx Increased intracellular calcium vasoconstriction

23. Juxtaglomerular Apparatus

24. Tubuloglomerular feedback mechanism

25. Autoregulation Despite changes in mean arterial blood pressure (from 80 to 180 mm Hg), renal blood flow is kept at a relatively constant level , a process known as autoregulation

26. Neural mechanism

27. Hormonal/Autacoids mechanism Regulation Major Stimulus Mechanism Effect on GFR Angiotensin II Decreased blood volume or decreased blood pressure Constriction of both afferent and efferent arterioles Decreases GFR Atrial natriuretic peptide Stretching of the arterial walls due to increased blood volume Relaxation of the mesangial cells increasing filtration surface Increases GFR

28. Regulation Mechanism Effect on GFR Histamine Contraction of mesangial cells Dopamine Vasodilate Decrease Renin and angiotensin II production Relax mesangial cells Bradykinin Release of NO and prostaglandin Prostaglandin Decrease vasoconstrictor effect of catecholamines and angiotensin II Relax mesangial cells Nitirc oxide Vasodilate afferent and effernt arteriole Endothelin Vasoconstrict afferent and effernt arteriole Adenosine Vasoconstrict afferent arteriole

29. Clinical Applications

30. Physiological conditions that alter GFR Exercise Sympathetic stimulation Afferent arteriolar constriction GFR Pregnancy BV Hormonal changes Vascular resistance GFR Posture Sympathetic stimulation Afferent arteriolar constriction GFR Sleep Circulatory activity GFR Weather ECF GFR Gender GFR Age Loss of nephrons GFR Food intake Protein diet GFR

31. Pathological conditions that affect GFR Nephrotic syndrome Nephritic syndrome Single kidney

32. Thank you!!!