Glomerular Filtration Rate

Study guide:

Urine formation:

  • Glomerular filtration (GF).

  • Tubular Reabsorption (TR).

  • Tubular Secretion. (TS).

Urine excretion = GF – TR + TS. 

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): 

Affected factor

Changes

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.

References:

Written by:        Lama Al Luhidan

Reviewed by:     Bassam Al-Ghamdi

                         Roaa Amer

Format editor:  Adel Yasky

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