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Glomerular filtration
- 1. GLOMERULAR FILTRATION AND ITS REGULATION by Karishma R. Pandey Assistant professor BPKIHS, Nepal
- 2. Objectives 1. Introduction 2. Mechanism of glomerular filtration 3. Glomerular filtration Rate(GFR) 4. Measurement of GFR 5. Regulation of GFR 6. Applied aspects
- 3. Introduction • Excretory organ • Extends :T12-L3 • Nephron=1- 2 million in each kidney
- 4. 3 processes involved in Urine formation 1.Glomerular filtration 2.Tubular reabsorption 3.Tubular secretion
- 5. Glomerular Filtration • Ultrafiltration of plasma in the glomerulus Governed by 2 major factors: 1. Filtration coefficient (Kf) 2. Pressure gradient/ Starling forces (hydrostatic and osmotic pressure gradients)
- 6. Mechanism of Glomerular Filtration Filtration coefficient 1. Capillary permeability 2. Size of the capillary bed
- 10. Glomerular filtration = Kf [(PGC-PT) – (πGC- πT)]
- 12. Composition of the filtrate 1. Every electrolyte 2. Metabolic wastes 3. Metabolites 4. Non natural substances 5. Lower wt proteins and peptides
- 13. Glomerular Filtration Rate (GFR) • The 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.
- 14. Factors affecting GFR 1. Change in renal blood flow 2. Glomerular capillary hydrostatic pressure 3. Change in capsular hydrostatic pressure 4. Oncotic pressure 5. Glomerular capillary permeability 6. Effective filtration surface area 7. Size, shape and electrical charge of the macromolecules
- 17. Fick principle (mass balance or conservation of mass) Where, • Pa x and Pv x = the concentrations of substance x in the renal artery and renal vein plasma, respectively; • • RPFa and RPFv = the renal plasma flow rates in the artery and vein, respectively; • Ux = the concentration of x in the urine; and • Vdot = the urine flow rate.
- 18. 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, CX is the clearance of substance X, UX is the urine concentration of substance, PX is the plasma concentration of substance X, and V is the urine flow rate.
- 19. Inulin Clearance Equals the Glomerular Filtration Rate Inulin clearance : highest standard highly accurate Others : iothalamate, an iodinated organic compound, EDTA, Vit B12 Not commonly used in the clinical practice. 1. infused intravenously, 2. the bladder is usually catheterized; 3. inconvenient Reasons: • 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.
- 20. 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
- 21. Renal blood flow • Kidneys have a very high blood flow • 20% of the cardiac output (5 to 6 L/min) i.e, about 1.2 L/min.
- 22. • 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)
- 23. 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. ERPF = CPAH
- 24. • 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] (PaPAH) 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.
- 25. Measurement of GFR • Modern imaging techniques • Measuring renal clearance of various substances
- 27. 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
- 32. 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
- 33. Neural mechanism
- 34. 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
- 35. 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
- 37. 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
- 38. Pathological conditions that affect GFR 1. Nephrotic syndrome 2. Nephritic syndrome 3. Single kidney
- 40. Thank you!!!
Editor's Notes
- Filtrate collects in urinary space of Bowman’s capsule then flows downstream through the tubule lumen, where its composition and volume are altered by tubular activity
- An important measurement in the evaluation of kidney function is the glomerular filtration rate (GFR), the rate at which plasma is filtered by the kidney glomeruli. If GFR is 125 mL plasma/min, then the volume of plasma filtered in a day is 180 L (125 mL/min 1,440 min/day). Plasma volume in a 70-kg young adult man is only about 3L, so the kidneys filter the plasma some 60 times in a day. The glomerular filtrate contains essential constituents (salts, water, metabolites), most of which are reabsorbed by the kidney tubules.
- The following equation defines the mass balance relationship: This relationship permits the quantification of the amount of x excreted in the urine versus the amount returned to the systemic circulation in the renal venous blood. Thus, for any substance that is neither synthesized nor metabolized, the amount that enters the kidneys is equal to the amount that leaves the kidneys in the urine plus the amount that leaves the kidneys in the renal venous blood.
- A useful way of looking at kidney function is to think of the kidneys as clearing substances from the blood plasma. When a substance is excreted in the urine, a certain volume of plasma is, in effect, freed (or cleared) of that substance. The product UX V ˙ equals the excretion rate per minute and has dimensions of amount per unit time (e.g., mg/min or mEq/day). The clearance of a substance can easily be determined by measuring the concentrations of a substance in urine and plasma and the urine flow rate (urine volume/time of collection) and substituting these values into the clearance formula.
- The ideal substance to measure GFR is inulin, a fructose polymer with a molecular weight of about 5,000. The principle behind the use of inulin is illustrated in Figure 23.6. The amount of inulin (IN) filtered per unit time, the filtered load, is equal to the product of the plasma [inulin] (PIN) GFR. The rate of inulin excretion is equal to UIN V ˙ . Since inulin is not reabsorbed, secreted, synthesized, destroyed, or stored by the kidney tubules, the filtered inulin load equals the rate of inulin excretion. The equation can be rearranged by dividing by the plasma [inulin]. The expression UINV ˙ /PIN is defined as the inulin clearance. Therefore, inulin clearance equals GFR.
- This allows them to filter the blood plasma at a high rate. This is about Both kidneys together weigh about
- Estimated by measuring the clearance of the organic anion p-aminohippurate (PAH), infused intravenously
- The PAH is supplied to the kidneys in the arterial plasma and leaves the kidneys in urine and renal venous plasma, or PAH entering kidneys is equal to PAH leaving kidneys: entering kidneys is equal to PAH leaving kidneys:
- Grf and rpf are held within narrow range by the phenomenon called autoregulation Intrinsic mechanisms of autoregulation Two major mechanisms are believed to contribute to autoregulation: • Myogenic mechanism – detects changes in blood pressure • Tubuloglomerular feedback mechanism – detects changes in the flow of tubular fluid.
- vascular resistance and counteracts the increased driving pressure, thereby acting to maintain the glomerular capillary hydrostatic pressure within its normal range of 50–60 mmHg.