What is the relationship between net filtration pressure and glomerular filtration rate?

Glomerular Filtration Rate

Study guide:

Urine formation:

• Glomerular filtration (GF).

• Tubular Reabsorption (TR).

• Tubular Secretion. (TS).

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Urine excretion = GF – TR + TS. 

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Definition of GFR:

• The speed of which blood is filtered.

• GFR = Net filtration pressure (NFP)x filtration coefficient (Kf).

  • Kf = GFR / NFP = 120 / 10 = 12 ml/mmHg/minute/total glomeruli of total renal substance in both kidneys (300 g).

• Depends on (net filtration pressure and filtration coefficient):

  • Net filtration pressure (↑pressure →↑GFR).

    • Net filtration pressure = Forces favoring filtration – forces apposing filtration.

      • Favoring filtration:

        • Hydrostatic pressure (PGC) = 50 mmHg (depends on systemic BP, afferent arteriolar resistance, efferent arteriolar resistance).

        • Colloid osmotic pressure in Bowman capsule (PBS)= 0 mmHg.

      • Apposing filtration:

        • Colloid osmotic pressure in glomerular capillaries (π GC) = 30 mmHg (depends on plasma protein and filtration fraction).

        • Hydrostatic pressure in Bowman space (π BC)= 10 mmHg.

    • Net filtration pressure = 50 – 40 = 10 mmHg.

  • Filtration coefficient (Kf):

    • Depends on the permeability of the filtering membrane:

      • Hydraulic conductivity (permeability).

      • Total surface area of filtering membrane (directly proportional to the filtration rate).

• Every minute both kidneys receive 1 L of blood (20 – 25% of the cardiac output), out of which 600 ml is plasma, and out of this plasma 120 ml will be filtered.

• Filtration fraction (fraction of the plasma fluid which has been filtered).

  • FF = GFR/ Renal plasma flow (RPF) = 120/600 = 0.2 

Pathologies affecting GFR (decrease GFR leading to renal failure): 

Pathologies affecting the filtration coefficient (Kf):

1. Reduce hydraulic conductivity (permeability):

• Thickening of the membrane:

  • Diabetes.

  • Hypertension.

2. Reduced total surface area of filtering membrane:

• Fibrosis of the membrane:

  • Chronic pyelonephritis.

  • Chronic glomerulonephritis. 

Pathologies affecting the net filtration pressure:

1. Decrease pressure favoring filtration:

• Hydrostatic pressure (PGC) = 50 mmHg.

  • Systemic BP

  • Afferent arteriolar resistance

• Constriction → ↓ Glomerular blood flow →↓ PGC.

  • Epinephrine and Norepephrine.

  • Endothelin (acute and chronic renal failure, preeclampsia).

• Efferent arteriolar resistance.

  • Dilation:

    • Angiotensin II →↓ PGC.

  • Constriction:

    • Mild → ↑ PGC→↑ GFR.

    • Severe →↑↑ FF → ↑↑ π GC → ↓ GFR.

• Colloid osmotic pressure in Bowman capsule (π BC)= 0 mmHg.

2. Increase pressure apposing filtration:

• Colloid osmotic pressure in glomerular capillaries (π GC) = 30 mmHg.

  • High plasma protein → increase π GC.

    • Multiple myeloma.

  • Conditions increasing the FF → increase π GC

• ​Hydrostatic pressure in Bowman space (PBS)= 10 mmHg

  • ​Obstructions in the urinary system → increase PBS.

Alteration of some parameters and their affect on RPF, GFR, and FF: 

Filtration (of the plasma, 600 ml/min):

• Substances not filtered:

  • Plasma proteins.

  • Plasma protein-bound substances:

    1. Bilirubin

    2. Calcium (~50%).

    3. Fatty acids.

    4. Drugs.

    5. T3, T4.

• Substances filtered:

  • H2O.

  • Electrolytes

      1. Cations (Na+, K+, Ca+2, Mg+2)
      2. Anions (Cl-,HCO3-)
  • Metabolic waste products: Urea, and Creatinine
  • Metabolites:
      1. Glucose.
      2. Amino acids.
      3. Organic acids (ketone bodies).
  • Low molecular weight protein:
      1. Insulin (reabsorbed by the PCT → catabolic affect).
      2. Hemoglobin (reabsorbed by the PCT → necrosis).
  • Non natural substances:
      1. Inulin → marker of GFR.
      2. Para aminohippuric acid (PAH) → marker of RPF.
  • Some drugs.

Measurement of GFR:

• Inulin: 

  • Properties:

    1. Freely filters.

    2. Small.

    3. Non-toxic.

    4. Non-plasma protein binding.

    5. Not charged.

    6. Not absorbed and not secreted.

  • Filtered load of inulin = urine load of inulin.

    • Filtered load depends on inulin concentration in plasma and GFR ([p] inulin x GFR).

    • Urine load depends on inulin concentration of urine and urine flow rate ([U] inulin x V).

• Creatinine (ideal GFR marker):

  • Properties:

    1. Freely filters.

    2. Small.

    3. Normally present in the body

    4. Non-toxic.

    5. Non-plasma protein binding.

    6. Not charged.

    7. Absorbed but not secreted.

Auto regulation of GFR and renal blood flow:

• Systemic blood pressure does not affect GFR between 70- 170 mmHg.

1. ​Hypertension

   • ​Tubuloglomerular balance:

     • Renal flow increase → increase renal artery pressure → increase hydrostatic pressure in glomerular capillaries (PGC)→ GFR will increase for a short time → tubular flow becomes fast → Na+ reabsorption will be less → total NaCl load delivered to the distal convoluted tubule is increased → macula densa senses the increase → macula densa secrete vasoconstrictors (ATP and adenosine) → afferent arteriole constriction → GFR back to normal.

     • Decreased renin → decreased conversion of Angiotensinogen to AGT I (AGT II) → efferent arteriole dilation.

   • Myogenic mechanism:

     • Afferent arteriole smooth muscle stretch → stretch sensitive Ca channels sensitized àcontraction of the afferent arteriole muscle → constriction → GFR back to normal.

2. Hypotension:

   • Tubuloglomerular balance:

     • Renal flow decrease →decrease renal artery pressure → decrease hydrostatic pressure in glomerular capillaries (PGC)→ GFR will decrease for a short time → tubular flow becomes sow → Na reabsorption will be more → total NaCl delivered to the distal convoluted tubule is decreased àmacula densa sense the decrease → macula densa secrete vasodilator substance and increase the production of renin → afferent arteriole vasodilation → GFR back to normal.

     • Increased renin → increased conversion of Angiotensinogen to AGT I (→ AGT II)→ efferent arteriole constriction → GFR back to normal.

3. ​​Increased amino acids:

   • Proximal convoluted tubule absorption (coupled with Na+) → less NaCl sensed by macula densa → macula densa sense the decrease → macula densa secrete vasodilator substance and increase the production of renin → afferent arteriole vasodilation and efferent arteriole vasoconstriction → GFR back to normal.

4. ​​​Increased glucose:

   • Proximal convoluted tubule absorption (coupled with Na+) → less NaCl sensed by macula densa → macula densa sense the decrease → macula densa secrete vasodilator substance and increase the production of renin → afferent arteriole constriction → GFR back to normal.

General points:

• Plasma protein:

  • ​Less than normal:

    • Protein losing anteropathies.

    • Liver cirrhosis.

    • Protein energy malnutrition.

    • Protein losing nephropathies.

  • ​Higher than normal:

    • Multiple myeloma.

• ​​Afferent arteriolar resistance:

  • Constriction → ↑ glomerular blood flow →↑ PGC.

    • Epinephrine and Norepephrine.

    • Endothelin (acute and chronic renal failure, preeclampsia).

  • Dilatation → ↑ glomerular blood flow → ↑PGC

    • Nitric oxide (NO)

    • Bradykinin.

    • Prostaglandin (reduced by NSAIDs).

• Efferent arteriolar resistance:

  • Dilation:

    • ↓ PGC.

  • Constriction

    • Mild constriction → ↑PGC →↑ GFR.

    • Severe constriction → ↑↑↑ FF → ↑↑↑ π GC → ↑GFR.

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