Glomerular Filtration pdf - Dr. Abdullah

GLOMERULAR FILTRATION

Measuring GFR

•

The

glomerular filtration rate

(GFR) can be measured

in humans by measuring the

excretion and plasma

level

of a substance that is freely filtered through the

glomeruli and neither secreted nor reabsorbed by the

tubules.

• Therefore, if the substance is designated by the letter

, the GFR is equal to the

concentration of X in urine

) times the

urine flow

per unit of time

(V.)

divided

by the

arterial plasma level of X (P

), or

V./P

• This value is called the

clearance of X

•

, of course, the same in all parts of the arterial

circulation, and if X is

not metabolized

to any extent in

the tissues, the level of X in peripheral

venous plasma

can be substituted for the

arterial plasma

level

Substances Used to Measure GFR

• In addition to the requirement that it be

freely filtered

and

neither

reabsorbed nor secreted

in the tubules, a substance suitable for

measuring the GFR should be

nontoxic

and

not metabolized

by the

body.

• Inulin

, a polymer of fructose with a molecular weight of 5200,

meets these criteria

in humans and most animals and is extensively

used to measure GFR.

•

Radioisotopes such as

Cr-EDTA

are also used, but inulin remains

the standard substance.

• In practice, a loading dose of inulin is administered intravenously,

followed by a sustaining infusion to keep the arterial plasma level

constant.

• After the inulin has equilibrated with body fluids, an accurately

timed urine specimen is collected and a plasma sample obtained

halfway through the collection.

•

Substances Used to Measure GFR

• Plasma and urinary inulin concentrations are

determined and the clearance calculated:

Uin = 35 mg /ml
V = 0.9 ml /min
Pin = 0.25 mg /ml
Cin= Uin* V/Pin =35*0.9/0.25=
In C= 126ml/min

Substances Used to Measure GFR

• clearance of creatinine (C

)

can also be used to determine

the GFR, but in humans, some creatinine is

secreted

by the

tubules and some may be

reabsorbed

• In addition,

plasma creatinine

determinations are

inaccurate

at low creatinine levels because the method for

determining creatinine measures small amounts of other

plasma constituents.

•

In spite of this, the clearance of endogenous creatinine is

frequently measured in patients.

• The values agree quite well with the GFR values measured

with inulin because, although the value for U

V. is high as a

result of tubular secretion, the value for P

is also high as a

result of nonspecific chromogens, and the errors thus tend

to cancel.

Normal GFR

• The GFR in an average-sized normal man is

approximately

125 mL/min

• Its magnitude correlates fairly well with

surface

area

, but values in

women

are

10%

lower than

those in

men

even after correction for surface

area.

• A rate of

125 mL/min is 7.5 L/h

, or

180 L/d

whereas the normal urine volume is about 1 L/d.

• Thus,

99%

or more of the filtrate is normally

reabsorbed.

Control of GFR

• The factors governing filtration across the glomerular

capillaries are the same as those governing filtration across

all other capillaries , ie,

the size

of the capillary bed, the

permeability

of the capillaries, and the

hydrostatic

and

osmotic pressure

gradients across the capillary wall. For

each nephron:

GFR = Kf [(Pgc – Pt) – (π

- π

T )

]

, the

glomerular ultrafiltration coefficient

, is the product

of the glomerular capillary wall hydraulic conductivity (ie,

its

permeability

) and the effective filtration

surface area

is the

mean hydrostatic pressure

in the glomerular

capillaries, P

the mean hydrostatic pressure in the tubule,

the

osmotic pressure

of the plasma in the glomerular

capillaries, and π

the osmotic pressure of the filtrate in the

tubule.

Permeability

• The permeability of the

glomerular capillaries

is about

50 times

that of the

capillaries in skeletal muscle.

• Neutral substances with effective molecular diameters of less

than 4 nm

are freely filtered, and the filtration of neutral substances with diameters

more than 8 nm

approaches zero .

•

Between these values, filtration is

inversely

proportionate to

diameter

•

However,

sialoproteins

in the glomerular capillary wall are

negatively

charged

, and studies with anionically charged and cationically charged

dextrans indicate that the negative charges repel negatively charged

substances in blood, with the result that filtration of anionic substances 4

nm in diameter is less than half that of neutral substances of the same

size.

• This probably explains why

albumin

, with an effective molecular diameter

of approximately

7 nm

, normally has a glomerular concentration only

0.2%

of its plasma concentration rather than the higher concentration that

would be expected on the basis of diameter alone;

circulating albumin is

negatively charged.

•

Filtration of

cationic substances

is greater than that of

neutral substances

Effect of electrical charge on the fractional clearance of dextran molecules of various

sizes in rats. The negative charges in the glomerular membrane retard the passage of

negatively charged molecules (anionic dextran) and facilitate the passage of positively

charged molecules (cationic dextran).

Permeability

• The amount of protein in the urine is normally

less than

100 mg/d

, and most of this is not

filtered but comes from

shed tubular cells

• The presence of significant amounts of albumin

in the urine is called

albuminuria

• In nephritis, the

negative charges

in the

glomerular wall are dissipated, and albuminuria
can occur for this reason

without an increase in

the size of the "pores"

in the membrane.

Size of the Capillary Bed

• K

can be

altered

by the

mesangial cells

contraction

these cells producing a

decrease

in K

that is largely due

to a reduction in the area available for filtration.

• Contraction of

points

where the capillary loops

bifurcate

probably shifts flow away from some of the

loops, and elsewhere, contracted mesangial cells
distort and encroach on the capillary lumen.

• Angiotensin II

is an important regulator of

mesangial

contraction

, and there are angiotensin II receptors in

the

glomeruli

• In addition, there is some evidence that

mesangial

cells

make renin

Agents causing contraction or

relaxation of mesangial cells.

Hydrostatic & Osmotic Pressure

• The

pressure in the glomerular capillaries

is higher

than that in other capillary beds because the afferent

arterioles are short, straight branches of the

interlobular arteries.

• Furthermore, the vessels "downstream" from the

glomeruli, the

efferent

arterioles, have a

relatively high

resistance.

• The

capillary

hydrostatic pressure is opposed by the

hydrostatic pressure in

Bowman's capsule

• It is also opposed by the

osmotic pressure

gradient

across the glomerular capillaries (π

- π

• π

is normally negligible, and the gradient is equal to

the

oncotic pressure

of the plasma proteins.

Hydrostatic & Osmotic Pressure

• The

net filtration pressure

) is

15 mm Hg

at the

afferent end of the glomerular capillaries, but it falls to

zero—ie,

filtration equilibrium

is reached—proximal to

the efferent end of the glomerular capillaries.

• This is because fluid leaves the plasma and the oncotic

pressure rises as blood passes through the glomerular

capillaries.

• It is apparent that portions of the glomerular

capillaries do not normally contribute to the formation

of the glomerular ultrafiltrate; ie, exchange across the

glomerular capillaries

is flow-limited rather than

diffusion-limited

Changes in GFR

• Changes in renal vascular resistance as a result of

autoregulation

tend to stabilize filtration

pressure, but when the

mean systemic arterial

pressure

drops below

90 mm Hg

, there is a sharp

drop in GFR.

• The GFR tends to be maintained when

efferent

arteriolar constriction is greater than afferent
constriction

, but either type of constriction

decreases blood flow to the tubules.

Factors affecting the GFR

1. Changes in

renal blood flow .

2. Changes in glomerular capillary

hydrostatic pressure .

3. Changes in

systemic blood pressure

4. Afferent

efferent

arteriolar

constriction

5. Changes in

hydrostatic pressure in Bowman's

capsule

6. Ureteral obstruction

Edema of kidney inside tight renal capsule

8. Changes in concentration of

plasma proteins

dehydration, hypoproteinemia, etc (minor factors)

9. Changes in

10. Changes in glomerular capillary

permeability

11. Changes in effective filtration

surface area

Filtration Fraction

• The ratio of the

GFR

to the

renal plasma flow

(RPF), the

filtration fraction

, is normally 0.16-

0.20.

• The GFR varies less than the RPF.
• When there is a fall in systemic blood

pressure, the GFR falls less than the RPF
because of efferent arteriolar constriction, and
consequently the filtration fraction rises.