GLOMERULAR FILTERATION

بسم الله الرحمن الرحيم

Dr.Mohammed Sharique Ahmed QuadriAssistant prof. Physiology

Al Maarefa College

OBJECTIVES • Identify three basic processes involved in urine formation;

glomerular filtration, tubular reabsorption and tubular secretion• Define GFR and quote normal value in men and women• Describe the composition of the glomerular filtrate• Detect the structural & functional peculiarities of the glomerular

filtration membrane• Outline the factors controlling GFR• Given capillary and Bowman’s capsule hydrostatic and oncotic

pressures calculate the net filtration pressure.• Correlate between net filtration pressure along glomerulus and

plasma flow• List the characteristics that a compound must have before it can

be used for measuring GFR e.g. Inulin, creatinine etc.• Given the data, calculate GFR .

Basic Renal Processes

• Glomerular filtration• Tubular reabsorption• Tubular secretion

Urine results from these three processes.

Glomerular filtration

• Is the first step in urine formation.

• Definition: Glomerular filtration is the transfer of fluid and solutes from the glomerular capillaries along a pressure gradient into Bowman's capsule.

Composition of the Glomerular Filtrate

• It is the fluid within the Bowman’s capsule that is essentially cell-free and protein-free and contains crystalloids in virtually the same concentrations as in the plasma.

• It is free from:– Blood cells– Protein– Protein-bound molecules(calcium, fatty aids, amino acids)

Glomerular Filtration• Fluid filtered pass through three layers of the

glomerular membrane– Glomerular capillary wall• Single layer of endothelial cells• More permeable to water and solutes than capillaries

elsewhere in the body– Basement membrane• Acellular gelatinous layer• Composed of collagen and glycoproteins

– Inner layer of Bowman’s capsule• Consists of podocytes that encircle the glomerulus tuft

Glomerular Capillary Filtration Barrier Endothelium (fenestrated) Basement Membrane negatively

charged, restriction site for proteins Epithelial Cells, restriction site for

proteins. Characterized by foot-like processes (podocytes).

Filtration• Despite the three layers of the barrier, the glomerulus filters

several hundred times as much water and solutes as the usual capillary membrane.

• Even with this high rate of filtration, the glomerular capillary membrane normally prevents filtration of plasma proteins.

Glomerular Capillary MembraneFilterability depends on: Size of the molecule– the pores of the glomerular membrane are about 8

nanometers (80 angstroms)Electrical Charge of the molecule– positively charged molecules are filtered much more easily

than negatively charged molecules of equal molecular size.– the negative charges of the basement membrane and the

podocytes provide an important means for restricting negatively charged molecules, including the plasma proteins.

– Diameter of albumin is only about 6 nanometers, but negatively charged.

Clinical Significance of Proteinuria

• Early detection of renal disease in at-risk patients- Hypertension: Hypertensive renal disease

- Diabetes: Diabetic nephropathy

- Pregnancy: gestational proteinuric hypertension (pre-eclampsia)

- annual “check-up”: renal disease can be silent

• Assessment and monitoring of known renal disease

Microalbuminuria• Definition: urine excretion of > 25-30 but

< 150mg albumin per day

• Causes: early diabetes, hypertension

• Prognostic Value: diabetic patients withmicroalbuminuria are 10-20 fold morelikely to develop persistent proteinuria

Glomerular Filtration Rate (GFR)

GFR: The volume of plasma filtered from both kidneys per minute.

GFR = 125 ml/min = 180 liters/dayPlasma volume is filtered 60 times per day

GFR= Filtration Coefficient (Kf) x Net Filtration Pressure(NFP)

Factors Affecting GFR

Filtration Coefficient (Kf)

Net Filtration Pressure(NFP)

Filtration coefficient

• Filtration coefficient (Kf): A measure of the

product of the hydraulic conductivity (water

permeability) and filtering surface area of the capillaries.

• glomerular capillary filtration coefficient = 12.5 ml/min per mmHg, or 4.2 ml/min per mmHg/ 100gm• (400 x greater than in tissues such a muscle)

Increased Glomerular Capillary Filtration Coefficient (Kf) Increases GFR• Normally not highly variable• Kf reduces by reducing the number of functional

glomerulus (decrease surface area) or by increasing the thickness BM (reducing its hydraulic conductivity).

• Diseases that can reduce Kf and eventually GFR- Chronic hypertension- Diabetes mellitus- Glomerulonephritis

Forces determining Net Filtration Pressure (NFP)

• Three physical forces involved– Glomerular capillary blood

hydrostatic pressure– Plasma-colloid osmotic

osmotic pressure– Bowman’s capsule hydrostatic

hydrostatic pressure

NET FILTRATION PRESSURE (NFP)=GBHP – CHP – BCOP= 55 mmHg 15 mmHg 30 mmHg= 10 mmHg

GLOMERULAR BLOODHYDROSTATIC PRESSURE(GBHP) = 55 mmHg

Capsularspace

Glomerular(Bowman's)capsule

Efferent arteriole

Afferent arteriole

1

Proximal convoluted tubule

NET FILTRATION PRESSURE (NFP)=GBHP – CHP – BCOP= 55 mmHg 15 mmHg 30 mmHg= 10 mmHg

CAPSULAR HYDROSTATICPRESSURE (CHP) = 15 mmHg

GLOMERULAR BLOODHYDROSTATIC PRESSURE(GBHP) = 55 mmHg

Capsularspace

Glomerular(Bowman's)capsule

Efferent arteriole

Afferent arteriole

1 2

Proximal convoluted tubule

NET FILTRATION PRESSURE (NFP)=GBHP – CHP – BCOP= 55 mmHg 15 mmHg 30 mmHg= 10 mmHg

BLOOD COLLOIDOSMOTIC PRESSURE(BCOP) = 30 mmHg

CAPSULAR HYDROSTATICPRESSURE (CHP) = 15 mmHg

GLOMERULAR BLOODHYDROSTATIC PRESSURE(GBHP) = 55 mmHg

Capsularspace

Glomerular(Bowman's)capsule

Efferent arteriole

Afferent arteriole

1 2

3

Proximal convoluted tubule

Net (effective) Filtration Pressure (NFP)

• Definition: = NFP is an algebraic sum of opposing hydrostatic and osmotic forces acting across the capillary

• NFP = forces inducing filtration - forces opposing filtration

• NFP = ( PGC + BC ) - ( PBC + GC )

– PGC Glomerular hydrostatic pressure– GC Glomerular oncotic pressure– PBC Bowman’s capsule hydrostatic pressure– BC Bowman’s capsule oncotic pressure

• NB: as there is virtually no protein, BC ~ 0, • therefore NFP = PGC - (PBC + GC)

PGC

PBC

BC

GC

Glomerular Filtration Rate

• Net filtration pressure = glomerular capillary blood pressure – (plasma-colloid osmotic pressure + Bowman’s capsule hydrostatic pressure)

For example: 55 mm Hg – (30 mm Hg + 15 mm Hg) = 10 mm Hg • Glomerular filtration rate (GFR)

– Depends on• Net filtration pressure• How much glomerular surface area is available for penetration• How permeable the glomerular membrane is

Unregulated influences on the GFR

Increased Bowman’s Capsule Hydrostatic Pressure (PBc) Decreases GFR

• Do not serve as physiological regulator of GFR

• Increase of PBc can be caused by• Tubular Obstruction• kidney stones• tubular necrosis

• Urinary tract obstruction• Prostatic enlargement

Unregulated influences on the GFR

plasma colloid osmotic pressure

• Do not serve as physiological regulator of GFR

• Plasma-colloid osmotic pressure• Severely burned patient ↑ GFR

• Dehydrating diarrhea ↓ GFR

Glomerular Filtration Rate• Controlled adjustments in GFR– Glomerular capillary hdrostatic pressure can be

controlled to adjust GFR to suit the body’s needs– Two major control mechanisms• Extrinsic sympathetic control -by adjusting the

constriction of afferent/efferent arterioles– Mediated by sympathetic nervous system input to afferent

arterioles– Baroreceptor reflex

• Autoregulation (aimed at preventing spontaneous changes in GFR)– Myogenic mechanism– Tubuloglomerular feedback (TGF)

Adjustments of AfferentArteriole Caliber to AlterThe GFR

Baroreceptor Reflex Influence on the GFR

•GFR = Filtration Coefficient (Kf ) x Net Filtration Pressure (NFP)

• GFR = 12.5 x 10 = 125 ml/min = 180 liters/day• GFR in females is less (110 ml/min)• Plasma volume is filtered 60 times per day

Calculation of Glomerular Filtration Rate (GFR)

Autoregulation

• Myogenic autoregulation• Tubuloglomerular feedback

The major function of autoregulation in the kidneys is to maintain a relatively constant GFR and renal blood flow despite considerable arterial pressure fluctuations that can occur.

Autoregulation:

Myogenic Mechanism

Stretch ofBlood Vessel

Cell Ca++

PermeabilityArterial Pressure

Intracell. Ca++Blood Flow VascularResistance

Vascular smooth muscle contraction in response to increased stretch

Macula Densa Feedback (Tubuloglomerular feedback)

GFR

Distal NaCl Delivery

Macula Densa NaCl Reabsorption

Afferent Arteriolar Resistance

GFR (return toward normal)

(macula densa feedback)

Macula Densa feedback mechanism for GFR autoregulation

What is a Glomerular Filtration Fraction?

• The Filtration Fraction (FF) is the ratio of the GFR to the renal plasma flow (GFR/TRPF).

• Renal blood flow = 1.1 L/min• 20-25% of total cardiac output (5 L/min).• Of the 625 ml of plasma enters the glomeruli via the

afferent, 125 (the GFR) filters in the Bowman’s capsule, the remaining passing via efferent arterioles into the peritubular capillaries

• Filtration fraction = (GFR/TRPF) = 0.2• So, GFR is About 20% of the Renal Plasma Flow

The filtration fractionThe Filtration Fraction (FF)

is the ratio of the GFR to the renal plasma flow = (GFR/TRPF).

References

• Human physiology by Lauralee Sherwood, seventh edition

• Text book physiology by Guyton &Hall,11th edition

• Text book of physiology by Linda .s contanzo,third edition