GLOMERULAR FILTRATION

AND ITS REGULATION

by Karishma R. PandeyAssistant professor

BPKIHS, Nepal

Objectives

1. Introduction

2. Mechanism of glomerular filtration

3. Glomerular filtration Rate(GFR)

4. Measurement of GFR

5. Regulation of GFR

6. Applied aspects

Introduction

• Excretory organ

• Extends :T12-L3

• Nephron=1- 2 million in each kidney

3 processes involved in Urine formation

1.Glomerular filtration

2.Tubular reabsorption

3.Tubular secretion

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)

Mechanism of Glomerular Filtration

Filtration coefficient1. Capillary permeability2. Size of the capillary bed

Pressure Gradient

Glomerular filtration= Kf [(PGC-PT) – (πGC- πT)]

Composition of the filtrate

1. Every electrolyte2. Metabolic wastes3. Metabolites4. Non natural substances5. Lower wt proteins and peptides

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.

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

Fick principle (mass balance or conservation of mass)

Where,• Pa

x and Pvx = 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.

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.

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 determinedby simple analysis.

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

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.

• 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)

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

• 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 renalvenous 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.

Measurement of GFR

• Modern imaging techniques

• Measuring renal clearance of various substances

Regulation of GFR

Intrinsic mechanism

Extrinsic mechanism

Myogenic mechanism

Tubuloglomerularfeedback

Neuralmechanism

Hormonal mechanism

Myogenic mechanism

BP

Stretching of blood vessels (afferent arteriole smooth muscle)

Opening of cationic channelsDepolarization

Opening of voltage-dependent calcium channelsCalcium influx

Increased intracellular calcium

vasoconstriction

Juxtaglomerular Apparatus

Tubuloglomerular feedback mechanism

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

Neural mechanism

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

Regulation Mechanism Effect on GFRHistamine Contraction of mesangial cells

Dopamine • Vasodilate• Decrease Renin and

angiotensin II production• Relax mesangial cells

Bradykinin Release of NO and prostaglandin

Prostaglandin • Decrease vasoconstrictoreffect of catecholamines and angiotensin II

• Relax mesangial cells

Nitirc oxide Vasodilate afferent and efferntarteriole

Endothelin Vasoconstrict afferent and effernt arteriole

Adenosine Vasoconstrict afferent arteriole

Clinical Applications

Physiological conditions that alter GFR

Exercise Sympathetic stimulation

Afferent arteriolarconstriction

GFR

Pregnancy BV Hormonal changes

Vascular resistance GFR

Posture Sympathetic stimulation

Afferent arteriolarconstriction

GFR

Sleep Circulatory activity GFR

Weather ECF GFR

Gender GFR

Age Loss of nephrons GFR

Food intake Protein diet GFR

Pathological conditions that affect GFR

1. Nephrotic syndrome

2. Nephritic syndrome

3. Single kidney

Thank you!!!