# Glomerular filtration Rate and it's Autoregulation. # Glomerular filtration barrier.

1. Glomerular Filtration, Renal Blood
Flow, and Their Control

2. GLOMERULAR FILTRATION—THE FIRST
STEP IN URINE FORMATION:
• The first step in urine formation is the filtration of
large amounts of fluid through the glomerular
capillaries into Bowman’s capsule - almost 180
liters each day.
• Most of this filtrate is reabsorbed, leaving only
about 1 liter of fluid to be excreted each day.
• Renal fluid excretion rate may be highly variable
depending on fluid intake.
• The high rate of glomerular filtration depends on:
1- A high rate of kidney blood flow,
2- As well as the special properties of the glomerular
capillary membranes.

4. COMPOSITION OF THE
GLOMERULAR FILTRATE:
• Glomerular capillaries are relatively impermeable to
proteins.
• Filtered fluid (called the glomerular filtrate) is essentially
protein free and devoid of cellular elements, including red
blood cells.
• The concentrations of other constituents of the glomerular
filtrate, including most salts and organic molecules, are
similar to the concentrations in the plasma.
• A few low molecular weight substances such as calcium and
fatty acids that are not freely filtered because they are
partially bound to the plasma proteins.

5. GFR IS ABOUT 20 PERCENT
OF RENAL PLASMA FLOW:
• The GFR is determined by:
(1) The balance of hydrostatic and colloid osmotic forces
acting across the capillary membrane and
(2) The capillary filtration coefficient (Kf), the product of the
permeability and filtering surface area of the capillaries.
• Normal GFR is 125 mL/minute or about 180 L/day.
• Filtration fraction is the fraction (portion) of the renal
plasma, which becomes the filtrate.
• Filtration fraction = GFR (125ml)/Renal plasma flow
(650ml)
or
Filtration fraction = 0.2
or
15 % – 20%

7. GLOMERULAR CAPILLARY
MEMBRANE:
(1) The endothelium of the capillary.
(2) A basement membrane.
(3) A layer of epithelial cells (podocytes) surrounding the
outer surface of the capillary basement membrane.
• Together, these layers make up the filtration barrier.
• Surrounding the endothelium is the basement membrane,
which consists of a meshwork of collagen and
proteoglycan (negatively charge) fibrillae that have large
spaces through which large amounts of water and small
solutes can filter.
• The epithelial cells of podocytes, also have negative
charges, provide additional restriction to filtration of
plasma proteins.

9. Filterability of Solutes Is Inversely Related to Their Size.
Negatively Charged Large Molecules Are Filtered Less Easily Than
Positively Charged Molecules of Equal Molecular Size.
Keep in mind that positively charged molecules are filtered much
more readily than are negatively charged molecules.
In certain kidney diseases, the negative charges on the basement
membrane are lost such as minimal change nephropathy.

10. DETERMINANTS OF THE GFR:
• The GFR is determined by:
(1) The sum of the hydrostatic and colloid osmotic forces across
the glomerular membrane, which gives the net filtration
pressure.
(2) The glomerular filtration coefficient Kf = GFR/ net filtration
GFR = Kf × Net filtration pressure.
• Although increased Kf raises GFR and decreased Kf reduces
GFR.
• Disease that decrease the Kf are (chronic hypertention, diabetic
mellitus).
increasing the thickness of the glomerular capillary basement
membrane + damaging the capillaries so severely that there is
loss of capillary function.

13. FACTORS REGULATING (AFFECTING)
GFR:
1- Renal Blood Flow:
• GFR is directly proportional to renal
blood flow.
2- Tubuloglomerular Feedback.
3- Glomerular Capillary Pressure:
• GFR is directly proportional to glomerular
capillary pressure.
4- Colloidal Osmotic Pressure:
• GFR is inversely proportional to colloidal
osmotic pressure
5- Hydrostatic Pressure in Bowman Capsule:
• GFR is inversely proportional to this.
6- Constriction of Afferent Arteriole:
• Constriction of afferent arteriole reduces
the blood flow to the glomerular
capillaries, which in turn reduces GFR 2- Tubuloglomerular Feedback.

14. 7. Constriction of Efferent Arteriole:
• initially the GFR increases, Later when all the substances are
filtered from this blood, further filtration does not occur.
8. Systemic Arterial Pressure:
• Variation in pressure above 180 mm Hg or below 60 mm Hg
affects the renal blood flow and GFR accordingly, because the
autoregulatory mechanism fails beyond this range.
9. Sympathetic Stimulation:
• Afferent and efferent arterioles are supplied by sympathetic
nerves.
• The mild or moderate stimulation of sympathetic nerves does
not cause any significant change either in renal blood flow or
GFR.
• Strong sympathetic stimulation causes severe constriction of the
blood vessels by releasing the neurotransmitter substance,
noradrenaline.
• The effect is more severe on the efferent arterioles than on the
afferent arterioles.

15. 10. Surface Area of Capillary Membrane:
• GFR is directly proportional to the surface area of the
capillary membrane.
11. Permeability of Capillary Membrane:
• GFR is directly proportional to the permeability of
glomerular capillary membrane.
• In many abnormal conditions like hypoxia, presence of toxic
agents, etc. the permeability of the capillary membrane
increases.
• In such conditions, even plasma proteins are filtered and
excreted in urine.
12. Contraction of Glomerular Mesangial Cells:
• Glomerular mesangial cells are situated in between the
glomerular capillaries. Contraction of these cells decreases
surface area of capillaries resulting in reduction in GFR

16. 13. Hormonal and Other Factors:
• Many hormones and other secretory factors alter GFR by
affecting the blood flow through glomerulus.
Factors increasing GFR by
vasodilatation
i. Atrial natriuretic peptide
ii. Brain natriuretic peptide
iii. cAMP
iv. Dopamine
v. Endothelial - derived nitric oxide
vi. Prostaglandin (PGE2).
Factors decreasing GFR by
vasoconstriction
i. Angiotensin II
ii. Endothelins
iii. Noradrenaline
iv. Platelet - activating factor
v. Platelet - derived growth factor

17. AUTOREGULATION
OF GFR AND RENAL
BLOOD FLOW

18. • Autoregulation is the intrinsic ability of an organ to
regulate its own blood flow.
• Autoregulation is present in some vital organs in the
body such as brain, heart and kidneys.
• It is highly significant and more efficient in kidneys.
• Renal Autoregulation:
• is important to maintain the glomerular filtration
rate (GFR).
• Two mechanisms are involved in renal
autoregulation:
1. Myogenic response.
2. Tubuloglomerular feedback.

19. MYOGENIC AUTOREGULATION OF
RENAL BLOOD FLOW AND GFR:
• Is the ability of individual blood vessels to resist stretching during
increased arterial pressure.
• Mechanism of action:
1. Whenever the blood flow to kidneys increases.
2. Stretch of the vascular wall allows increased movement of calcium
ions from the extracellular fluid into the cells.
3. causing them to contract.
4. So, the blood flow is decreased.
• Importance of this mechanism is:
A. Prevents excessive stretch of the vessel and at the same time, by
raising vascular resistance.
B. helps prevent excessive increases in renal blood flow and GFR when
arterial pressure increases.
• Keep in mind this mechanism may be more important in protecting the
kidney from hypertension-induced injury.

21. TUBULOGLOMERULAR FEEDBACK
AND AUTOREGULATION OF GFR:
• Macula densa plays an important role in tubuloglomerular
feedback, which controls the renal blood flow and GFR.
• Macula densa with the control of renal arteriolar resistance and
autoregulation of GFR.
• This feedback helps ensure a relatively constant delivery of
sodium chloride to the distal tubule and helps prevent spurious
fluctuations in renal excretion that would otherwise occur.
• The tubuloglomerular feedback mechanism has two
components that act together to control GFR:
(1) an afferent arteriolar feedback mechanism
(2) an efferent arteriolar feedback mechanism.
• These feedback mechanisms depend on special anatomical
arrangements of the juxtaglomerular complex (apparatus).

22. The juxtaglomerular complex
consists:
1- macula densa cells in the initial portion of the distal
tubule.
2- juxtaglomerular cells in the walls of the afferent and
efferent arterioles.
• The macula densa is a specialized group of epithelial cells
in the distal tubules that comes in close contact with the
afferent and efferent arterioles.
• The macula densa cells contain Golgi apparatus, which
are intracellular secretory organelles directed toward the
arterioles, suggesting that these cells may be secreting a
substance toward the arterioles.
• Decreased Macula Densa Sodium Chloride Causes
Dilation of Afferent Arterioles and Increased Renin
Release.

24. Vasoconstriction Vasodilatation

25. Other Factors That Increase Renal
Blood Flow and GFR:
• A high protein intake is
known to increase both renal
blood flow and GFR.
• Increases in renal blood flow
and GFR that occur with
large increases in blood
glucose levels in persons with
uncontrolled diabetes
mellitus.
 Remember that absorption
of amino acid and glucose
depend with co transport of
Na as discussed in digestive
system