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Renal handling of substances




          Dr. Ashok Solanki
Dr. Ashok Solanki
Dr. Ashok Solanki
Dr. Ashok Solanki
Dr. Ashok Solanki
Dr. Ashok Solanki
Factors affecting G.F.R.
   Changes in renal blood flow
   Changes in glomerular capillary hydrostatic pressure
   Changes in systemic blood pressure
   Afferent or efferent arteriolar constriction

   Changes in hydrostatic pressure in Bowman's capsule
   Ureteral obstruction
   Edema of kidney inside tight renal capsule
Changes in concentration of plasma proteins: dehydration,
hypoproteinemia, etc (minor factors)
   Changes in Kf
   Changes in glomerular capillary permeability
   Changes in effective filtration surface area
                                  Dr. Ashok Solanki
Dr. Ashok Solanki
Glomerular fitration
    Substances in the blood are
filtered through capillary fenestrae
between endothelial cells (single
layer).

   filtrate then passes across the
 basement membrane and
through slit pores between the
foot processes
   (also called pedicels) and enters
the capsular space.

   From here, the filtrate is
transported to the lumen of the
proximal convoluted tubule.
                                       Dr. Ashok Solanki
Dr. Ashok Solanki
Autoregulation of GFR

• Afferent arteriolar feedback mechanism for regulating
  GFR
• Efferent arteriolar feedback mechanism for regulating
  GFR
• Myogenic mechanism regulating GFR- resist stretching
  during increase arterial pressure – stretch of vascular
  wall increase calcium ions entry from ECF into the cell –
  contract the cells – increase vascular resistance –
  decrease GFR and RBF
                         Dr. Ashok Solanki
Dr. Ashok Solanki
GFR = Kf . (PG – PB – pG + pB)

The GFR is determined by

   the sum of the hydrostatic pressure

   colloid osmotic forces across the glomerular membrane

   Bowmens capsule hydrostatic pressure

   the glomerular capillary filtration coefficient, Kf

    GFR = Kf . Net filtration pressure


                            Dr. Ashok Solanki
The 4 basic functions of the kidneys
• Ultrafiltration by glomerular capillaries




                     Dr. Ashok Solanki
glomerular filtration and tubular
                function.
• bulk flow of fluid from glomerular capillary to Bowman’s
  space
• volume = 20% of RPF (filtration fraction), ≈ 125 ml/min
• barriers to filtration
• endothelial fenestrae
• basement membrane
• Podocytes
• GFR = Kf · NFP (filtration coefficient x net filtration pressure)




                              Dr. Ashok Solanki
Dr. Ashok Solanki
Dr. Ashok Solanki
Dr. Ashok Solanki
Dr. Ashok Solanki
Dr. Ashok Solanki
Dr. Ashok Solanki
Junction- the JGA

Blood flows into the
glomerulus through
the afferent arterioles
and leaves the
glomerulus through the
efferent
arterioles.
The proximal tubule
exits Bowman’s
capsule.




                          Dr. Ashok Solanki
Tubuloglomerular feedback

o Alterations in GFR due to changes in glomerular perfusion
pressure will lead to an alteration in the composition of the fluid
delivered to the macula densa region of the nephron tubule

o The macula densa senses these changes and acts to alter
afferent arteriole tone to vary glomerular perfusion pressure to
return the GFR to normal
o




                            Dr. Ashok Solanki
Dr. Ashok Solanki
The structure of the filter
1. The glomerular capillary endothelium:
• A highly specialised capillary endothelium with fenestrations (windows)
  to minimise the filter thickness;
• This layer prevents cellular components of blood coming into contact with
  the basement membrane.

2. The glomerular basement membrane:
• Made of connective tissue, it is negatively charged;
• This is the layer that actually acts as the filter.

3. Bowman’s epithelial cells (podocytes):
• Epithelial cells with multiple projections (foot processes) which interlink
  with each other
• whilst still keeping a small gap between them creating a large surface
  area;
• Act to maintain the basement membrane, and has phagocytic functions       .




                                  Dr. Ashok Solanki
Dr. Ashok Solanki
Dr. Ashok Solanki
Dr. Ashok Solanki
Dr. Ashok Solanki
Dr. Ashok Solanki
Dr. Ashok Solanki
Tubuloglomerular feedback




        Dr. Ashok Solanki
Dr. Ashok Solanki
Dr. Ashok Solanki
Dr. Ashok Solanki
Dr. Ashok Solanki
Factors affecting GFR
1. Glomerular capillary hydrostetic pressure –

   - arterial pressure

   - afferent arterial resistance

    - efferent arterial resistance

2. Colloidal osmotic pressure of glomerulus –

3. bowmen’s capsular hydrostetic pressure – ureteric stone,
  obstruction of urinary tract

4. RBF – GFR directly related to RBF

5. Sympathetic stimulation
                                 Dr. Ashok Solanki
Factors affecting GFR
• Decrease Kf decrease GFR
• Increase Kf increase GFR
• In some diss. Lower Kf by reducing the
  number of functional glo. Capillaries
• Increase thickness of the glo. Capillaries
• Chronic uncontrolled hypertension and
  diabetes mellitus


                      Dr. Ashok Solanki
Autoregulation of GFR
Afferent arteriolar feedback mechanism for regulating
GFR
Efferent arteriolar feedback mechanism for regulating
GFR
Myogenic mechanism regulating GFR- resist stretching
during increase arterial pressure – stretch of vascular
wall increase calcium ions entry from ECF into the cell –
contract the cells – increase vascular resistance –
decrease GFR and RBF


                       Dr. Ashok Solanki
Glomerular capillary filtration coefficient - Kf
The Kf is a measure of the product of the hydraulic conductivity and surface

area of the glomerular capillaries

Kf = GFR / Net filtration pressure

GFR – 125 ml / min

Net filtration pressure – 10 mm of Hg

Kf – 12.5 ml / min /mm of Hg

4.2 ml/min/mm of Hg/100g of kidney wt.


                               Dr. Ashok Solanki
Dr. Ashok Solanki
Net filtration pressure
• Forces favoring filtration (mm Hg)
  glomerular hydrostatic pressure - Pg       60
  bowmen’s capsule colloid
              osmotic pressure –     πb       0
• Forces opposing filtration (mm Hg )
  bowmen’s capsule hdrostatic
                       pressure - Pg       18
  glomerular capillary colloid
                osmotic pressure – πg       32
Net filtration pressure = 60 – 18 – 32 = +10 mmof Hg

                       Dr. Ashok Solanki
Forces promoting & opposesing filtration

• Net filtration force is +ve causing filtration




                      Dr. Ashok Solanki
GFR is sum of Kf x Net filtration pressure

The amount of the glomerular filtrate by all the nephrons of both the kidneys

in a one minute is called GFR

GFR = filtration fraction x RBF

In the average human adult, the GFR is about 125 ml / min. or 180 L / day

Filtration fraction – the fraction of the renal plasma which becomes the filtrate

Filtration fraction = GFR / RBF


                                  Dr. Ashok Solanki
Dr. Ashok Solanki
Dr. Ashok Solanki
Dr. Ashok Solanki

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Gfr factors. 17.02.13.

  • 1. Renal handling of substances Dr. Ashok Solanki
  • 7. Factors affecting G.F.R.  Changes in renal blood flow  Changes in glomerular capillary hydrostatic pressure  Changes in systemic blood pressure  Afferent or efferent arteriolar constriction  Changes in hydrostatic pressure in Bowman's capsule  Ureteral obstruction  Edema of kidney inside tight renal capsule Changes in concentration of plasma proteins: dehydration, hypoproteinemia, etc (minor factors)  Changes in Kf  Changes in glomerular capillary permeability  Changes in effective filtration surface area Dr. Ashok Solanki
  • 9. Glomerular fitration Substances in the blood are filtered through capillary fenestrae between endothelial cells (single layer). filtrate then passes across the basement membrane and through slit pores between the foot processes (also called pedicels) and enters the capsular space. From here, the filtrate is transported to the lumen of the proximal convoluted tubule. Dr. Ashok Solanki
  • 11. Autoregulation of GFR • Afferent arteriolar feedback mechanism for regulating GFR • Efferent arteriolar feedback mechanism for regulating GFR • Myogenic mechanism regulating GFR- resist stretching during increase arterial pressure – stretch of vascular wall increase calcium ions entry from ECF into the cell – contract the cells – increase vascular resistance – decrease GFR and RBF Dr. Ashok Solanki
  • 13. GFR = Kf . (PG – PB – pG + pB) The GFR is determined by the sum of the hydrostatic pressure colloid osmotic forces across the glomerular membrane Bowmens capsule hydrostatic pressure the glomerular capillary filtration coefficient, Kf GFR = Kf . Net filtration pressure Dr. Ashok Solanki
  • 14. The 4 basic functions of the kidneys • Ultrafiltration by glomerular capillaries Dr. Ashok Solanki
  • 15. glomerular filtration and tubular function. • bulk flow of fluid from glomerular capillary to Bowman’s space • volume = 20% of RPF (filtration fraction), ≈ 125 ml/min • barriers to filtration • endothelial fenestrae • basement membrane • Podocytes • GFR = Kf · NFP (filtration coefficient x net filtration pressure) Dr. Ashok Solanki
  • 22. Junction- the JGA Blood flows into the glomerulus through the afferent arterioles and leaves the glomerulus through the efferent arterioles. The proximal tubule exits Bowman’s capsule. Dr. Ashok Solanki
  • 23. Tubuloglomerular feedback o Alterations in GFR due to changes in glomerular perfusion pressure will lead to an alteration in the composition of the fluid delivered to the macula densa region of the nephron tubule o The macula densa senses these changes and acts to alter afferent arteriole tone to vary glomerular perfusion pressure to return the GFR to normal o Dr. Ashok Solanki
  • 25. The structure of the filter 1. The glomerular capillary endothelium: • A highly specialised capillary endothelium with fenestrations (windows) to minimise the filter thickness; • This layer prevents cellular components of blood coming into contact with the basement membrane. 2. The glomerular basement membrane: • Made of connective tissue, it is negatively charged; • This is the layer that actually acts as the filter. 3. Bowman’s epithelial cells (podocytes): • Epithelial cells with multiple projections (foot processes) which interlink with each other • whilst still keeping a small gap between them creating a large surface area; • Act to maintain the basement membrane, and has phagocytic functions . Dr. Ashok Solanki
  • 32. Tubuloglomerular feedback Dr. Ashok Solanki
  • 37. Factors affecting GFR 1. Glomerular capillary hydrostetic pressure – - arterial pressure - afferent arterial resistance - efferent arterial resistance 2. Colloidal osmotic pressure of glomerulus – 3. bowmen’s capsular hydrostetic pressure – ureteric stone, obstruction of urinary tract 4. RBF – GFR directly related to RBF 5. Sympathetic stimulation Dr. Ashok Solanki
  • 38. Factors affecting GFR • Decrease Kf decrease GFR • Increase Kf increase GFR • In some diss. Lower Kf by reducing the number of functional glo. Capillaries • Increase thickness of the glo. Capillaries • Chronic uncontrolled hypertension and diabetes mellitus Dr. Ashok Solanki
  • 39. Autoregulation of GFR Afferent arteriolar feedback mechanism for regulating GFR Efferent arteriolar feedback mechanism for regulating GFR Myogenic mechanism regulating GFR- resist stretching during increase arterial pressure – stretch of vascular wall increase calcium ions entry from ECF into the cell – contract the cells – increase vascular resistance – decrease GFR and RBF Dr. Ashok Solanki
  • 40. Glomerular capillary filtration coefficient - Kf The Kf is a measure of the product of the hydraulic conductivity and surface area of the glomerular capillaries Kf = GFR / Net filtration pressure GFR – 125 ml / min Net filtration pressure – 10 mm of Hg Kf – 12.5 ml / min /mm of Hg 4.2 ml/min/mm of Hg/100g of kidney wt. Dr. Ashok Solanki
  • 42. Net filtration pressure • Forces favoring filtration (mm Hg) glomerular hydrostatic pressure - Pg 60 bowmen’s capsule colloid osmotic pressure – πb 0 • Forces opposing filtration (mm Hg ) bowmen’s capsule hdrostatic pressure - Pg 18 glomerular capillary colloid osmotic pressure – πg 32 Net filtration pressure = 60 – 18 – 32 = +10 mmof Hg Dr. Ashok Solanki
  • 43. Forces promoting & opposesing filtration • Net filtration force is +ve causing filtration Dr. Ashok Solanki
  • 44. GFR is sum of Kf x Net filtration pressure The amount of the glomerular filtrate by all the nephrons of both the kidneys in a one minute is called GFR GFR = filtration fraction x RBF In the average human adult, the GFR is about 125 ml / min. or 180 L / day Filtration fraction – the fraction of the renal plasma which becomes the filtrate Filtration fraction = GFR / RBF Dr. Ashok Solanki