GFR

1. GFR

3. GFR
- 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.
- In the average adult human, the GFR is about 125 ml/min, or
180 L/day.
- The fraction of the renal plasma flow that is filtered (the
filtration fraction) averages about 0.2;
- this means that about 20 per cent of the plasma flowing
through the kidney is filtered
- Filtration fraction = GFR/Renal plasma flow

4. Glomerular Capillary
Membrane

5. Glomerular Capillary
Membrane- The capillary endothelium is perforated by thousands of
small holes called fenestrae
- Although the fenestrations are relatively large, endothelial
cells are richly endowed with fixed negative charges that
obstruct the passage of plasma proteins.
- The basement membrane consists of a meshwork of
collagen and proteoglycan fibrillae that have large spaces
through which large amounts of water and small solutes can
filter.
- The basement membrane effectively prevents filtration of
plasma proteins because of strong negative electrical
charges associated with the proteoglycans.

6. Glomerular Capillary
Membrane- The final part of the glomerular membrane is a layer of
epithelial cells that line the outer surface of the
glomerulus.
- These cells are not continuous but have long foot like
processes (podocytes) that encircle the outer surface
of the capillaries.
- The foot processes are separated by gaps called slit
pores through which the glomerular filtrate moves.
- The epithelial cells also have negative charges, provide
additional restriction to filtration of plasma proteins.

8. 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 capillary filtration coefficient,
Kf.
- GFR = Kf X Net filtration pressure
- The net filtration pressure represents the sum of
the hydrostatic and colloid osmotic forces that
either favor or oppose filtration across the
glomerular capillaries

9. Determinants of the GFR
- (1) hydrostatic pressure inside the glomerular
capillaries (glomerular hydrostatic pressure, PG),
which promotes filtration;
- (2) the hydrostatic pressure in Bowman’s capsule
(PB) outside the capillaries, which opposes filtration;
- (3) the colloid osmotic pressure of the glomerular
capillary plasma proteins (µG), which opposes
filtration; and
- (4) the colloid osmotic pressure of the proteins in
Bowman’s capsule (µB), which promotes filtration.

10. Determinants of the GFR
- (Under normal conditions, the concentration
of protein in the glomerular filtrate is so
low that the colloid osmotic pressure of
the Bowman’s capsule fluid is considered to
be zero.)
- The GFR can therefore be expressed as
- GFR = Kf X (PG – PB – µG + µB)

13. Determinants of the GFR
- Increased Bowman’s Capsule Hydrostatic
Pressure Decreases GFR
- In certain pathological states associated with
obstruction of the urinary tract, Bowman’s
capsule pressure can increase markedly - serious
reduction of GFR.
- Precipitation of calcium or uric acid may lead to
“stones” that lodge in the urinary tract, often in
the ureter, thereby obstructing outflow of the
urinary tract and raising Bowman’s capsule
pressure.

14. Determinants of the GFR
- Increased Glomerular Capillary Colloid Osmotic Pressure
Decreases GFR
- As blood passes from the afferent arteriole through the
glomerular capillaries to the efferent arterioles,
- the plasma protein concentration increases about 20 %
- (1) the arterial plasma colloid osmotic pressure and
- (2) the fraction of plasma filtered by the glomerular
capillaries (filtration fraction).
- Increasing the arterial plasma colloid osmotic pressure
raises the glomerular capillary colloid osmotic pressure -
decreases GFR.

15. Determinants of the GFR
- Increased Glomerular Capillary Colloid
Osmotic Pressure Decreases GFR
- Increasing the filtration fraction also
concentrates the plasma proteins and raises
the glomerular colloid osmotic pressure
- a greater rate of blood flow into the
glomerulus tends to increase GFR, and a
lower rate of blood flow into the glomerulus
tends to decrease GFR.

16. Determinants of the GFR
- Increased Glomerular Capillary Hydrostatic
Pressure Increases GFR
- Increased arterial pressure tends to raise
glomerular hydrostatic pressure and so increases
GFR.
- Increased resistance of afferent arterioles
reduces glomerular hydrostatic pressure and
decreases GFR.
- dilation of the afferent arterioles increases
both glomerular hydrostatic pressure and GFR

18. Determinants of the GFR
- Increased Glomerular Capillary Hydrostatic
Pressure Increases GFR
- Constriction of the efferent arterioles increases
the resistance to outflow from the glomerular
capillaries.
- This raises the glomerular hydrostatic pressure,
and as long as the increase in efferent
resistance does not reduce renal blood flow too
much, GFR increases slightly

19. Determinants of the GFR
- Increased Glomerular Capillary Hydrostatic Pressure
Increases GFR
- Efferent arteriolar constriction reduces renal blood flow
- the filtration fraction and glomerular colloid osmotic
pressure increase
- So, if the constriction of efferent arterioles is severe, the
rise in colloid osmotic pressure exceeds the increase in
glomerular capillary hydrostatic pressure caused by
efferent arteriolar constriction.
- When this occurs, the net force for filtration actually
decreases, causing a reduction in GFR.

21. Determinants of the GFR
- Increased Glomerular Capillary Hydrostatic
Pressure Increases GFR
- constriction of afferent arterioles reduces GFR.
- the effect of efferent arteriolar constriction
depends on the severity of the constriction;
- moderate efferent constriction raises GFR,
- severe efferent constriction reduces GFR.

23. Physiologic Control of GFR and
RBF- Sympathetic Nervous System Activation
Decreases GFR
- Strong activation of the renal
sympathetic nerves can constrict the renal
arterioles and decrease renal blood flow and
GFR
- Norepinephrine, Epinephrine and
Endothelin Constrict Renal Blood Vessels
and Decrease GFR

24. Physiologic Control of GFR and
RBF- Angiotensin II Constricts Efferent Arterioles
- raise glomerular hydrostatic pressure while
reducing renal blood flow - helps prevent
decreases in glomerular hydrostatic pressure and
GFR
- Endothelial-Derived Nitric Oxide Decreases
Renal Vascular Resistance and Increases GFR
- Prostaglandins and Bradykinin Tend to Increase
GFR

26. Autoregulation of GFR and
RBF- Feedback mechanisms intrinsic to the
kidneys normally keep the renal blood flow
and GFR relatively constant, despite marked
changes in arterial blood pressure.
- Role of Tubuloglomerular Feedback in
Autoregulation of GFR
- Decreased Macula Densa Sodium Chloride
Causes Dilation of Afferent Arterioles and
Increased Renin Release

29. Myogenic Autoregulation
- the ability of individual blood vessels to resist
stretching during increased arterial pressure.
- Arterioles respond to increased wall tension or wall
stretch by contraction of the vascular smooth muscle.
- Stretch of the vascular wall allows increased movement
of calcium ions from the ECF into the cells, causing
them to contract
- This contraction prevents overdistension of the vessel
and raises vascular resistance - prevent excessive
increases in RBF and GFR when arterial pressure
increases.

30. Clearance Methods
- The rates at which different substances are “cleared”
from the plasma provide a useful way of quantitating the
effectiveness with which the kidneys excrete various
substances.
- The renal clearance of a substance is the volume of
plasma that is completely cleared of the substance by
the kidneys per unit time
- renal clearance of a substance is calculated from the
urinary excretion rate (U X V) of that substance divided
by its plasma concentration (P).
C = U X V / P

31. Inulin Clearance
- If a substance is freely filtered and is not
reabsorbed or secreted by the renal tubules,
- then the rate at which that substance is excreted in
the urine is equal to the filtration rate of the
substance by the kidneys
- Inulin, a polysaccharide molecule with a molecular
weight of about 5200.
- Inulin is not produced in the body, is found in the
roots of certain plants and must be administered
intravenously to a patient to measure GFR.

33. Inulin Clearance
- (1) if the clearance rate of the substance
equals that of inulin, the substance is only
filtered and not reabsorbed or secreted;
- (2) if the clearance rate of a substance is less
than inulin clearance, the substance must have
been reabsorbed by the nephron tubules; and
- (3) if the clearance rate of a substance is
greater than that of inulin, the substance
must be secreted by the nephron tubules.

35. Creatinine Clearance
- Creatinine is a by-product of muscle metabolism
and is cleared from the body fluids almost entirely
by glomerular filtration.
- Because measurement of creatinine clearance does
not require intravenous infusion into the patient,
this method is much more widely used than inulin
clearance for estimating GFR clinically.
- creatinine clearance is not a perfect marker of
GFR because a small amount of it is secreted by the
tubules, so that the amount of creatinine excreted
slightly exceeds the amount filtered

36. Creatinine Clearance
GFR = CCreatinine = Ucreatinine X V / Pcreatinine
- If GFR suddenly decreases by 50%, the
kidneys will transiently filter and excrete only
half as much creatinine,
- causing accumulation of creatinine in the
body fluids and raising plasma concentration
- plasma creatinine concentration is inversely
proportional to GFR

40. GLOMERULAR DISEASES
- Glomerular diseases include a large and clinically
significant group of renal diseases.
- Glomerulonephritis (GN) is the term used for
diseases that primarily involve the renal glomeruli.
- I. Primary glomerulonephritis in which the
glomeruli are the predominant site of involvement.
- II. Secondary glomerular diseases include certain
systemic and hereditary diseases which secondarily
affect the glomeruli.

41. GLOMERULAR DISEASES
- The clinical presentation of glomerular
disease is quite variable but in general
four features—proteinuria, hematuria,
hypertension and disturbed excretory
function
- nephritic and nephrotic syndromes;
- acute and chronic renal failure;
- asymptomatic proteinuria and
haematuria

42. ACUTE NEPHRITIC
SYNDROME- This is the acute onset of haematuria, proteinuria,
hypertension, oedema and oliguria following an infective
illness about 10 to 20 days earlier.
- 1. The haematuria is generally slight giving the urine
smoky appearance and erythrocytes are detectable by
microscopy
- 2. The proteinuria is mild (less than 3 gm per 24 hrs)
and is usually non-selective (nephritic range
proteinuria).
- 3. Hypertension is generally mild.
- 4. Oedema in nephritic syndrome is usually mild and
results from sodium and water retention.
- 5. Oliguria is variable

43. NEPHROTIC SYNDROME
- it is characterised by findings of massive proteinuria,
hypoalbuminaemia, oedema, hyperlipidaemia, lipiduria,
and hypercoagulability.
- 1. Heavy proteinuria (protein loss of more than 3 gm
per 24 hrs) is the chief characteristic of nephrotic
syndrome (nephrotic range proteinuria).
- A highly-selective proteinuria consists mostly of loss
of low molecular weight proteins, while a poorly-
selective proteinuria is loss of high molecular weight
proteins in the urine.
- In nephrotic syndrome, proteinuria mostly consists of
loss of albumin (molecular weight 66,000) in the urine.

44. NEPHROTIC SYNDROME
- 2. Hypoalbuminaemia is produced primarily
consequent to urinary loss of albumin, and partly
due to increased renal catabolism and inadequate
hepatic synthesis of albumin.
- 3. Oedema in nephrotic syndrome appears due to
fall in colloid osmotic pressure resulting from
hypoalbuminaemia.
- 4. Hyperlipidaemia - the liver faced with the
stress of massive protein synthesis in response to
heavy urinary protein loss, also causes increased
synthesis of lipoproteins

45. NEPHROTIC SYNDROME
- 5. Lipiduria occurs following hyperlipidaemia
due to excessive leakiness of glomerular
filtration barrier.
- 6. Hypercoagulability –
- increased urinary loss of antithrombin III,
- hyperfibrinogenaemia from increased
synthesis in the liver,
- decreased fibrinolysis,
- increased platelet aggregation and
- altered levels of protein C and S.

47. Thank You…