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
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
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
15.
16.
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
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
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
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.
