Glomerular Filtration Rate
Study guide:
Urine formation:
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Glomerular filtration (GF).
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Tubular Reabsorption (TR).
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Tubular Secretion. (TS).
Urine excretion = GF – TR + TS.
Definition of GFR:
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The speed of which blood is filtered.
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GFR = Net filtration pressure (NFP)x filtration coefficient (Kf).
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Kf = GFR / NFP = 120 / 10 = 12 ml/mmHg/minute/total glomeruli of total renal substance in both kidneys (300 g).
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Depends on (net filtration pressure and filtration coefficient):
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Net filtration pressure (↑pressure →↑GFR).
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Net filtration pressure = Forces favoring filtration – forces apposing filtration.
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Favoring filtration:
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Hydrostatic pressure (PGC) = 50 mmHg (depends on systemic BP, afferent arteriolar resistance, efferent arteriolar resistance).
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Colloid osmotic pressure in Bowman capsule (PBS)= 0 mmHg.
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Apposing filtration:
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Colloid osmotic pressure in glomerular capillaries (π GC) = 30 mmHg (depends on plasma protein and filtration fraction).
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Hydrostatic pressure in Bowman space (π BC)= 10 mmHg.
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Net filtration pressure = 50 – 40 = 10 mmHg.
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Filtration coefficient (Kf):
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Depends on the permeability of the filtering membrane:
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Hydraulic conductivity (permeability).
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Total surface area of filtering membrane (directly proportional to the filtration rate).
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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.
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Filtration fraction (fraction of the plasma fluid which has been filtered).
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FF = GFR/ Renal plasma flow (RPF) = 120/600 = 0.2
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Pathologies affecting GFR (decrease GFR leading to renal failure):
Affected factor
Changes
Pathologies affecting the filtration coefficient (Kf):
1. Reduce hydraulic conductivity (permeability):
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Thickening of the membrane:
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Diabetes.
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Hypertension.
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2. Reduced total surface area of filtering membrane:
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Fibrosis of the membrane:
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Chronic pyelonephritis.
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Chronic glomerulonephritis.
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Pathologies affecting the net filtration pressure:
1. Decrease pressure favoring filtration:
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Hydrostatic pressure (PGC) = 50 mmHg.
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Systemic BP
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Afferent arteriolar resistance
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Constriction → ↓ Glomerular blood flow → ↓ PGC.
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Epinephrine and Norepephrine.
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Endothelin (acute and chronic renal failure, preeclampsia).
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Efferent arteriolar resistance.
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Dilation:
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Angiotensin II → ↓ PGC.
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Constriction:
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Mild → ↑ PGC → ↑ GFR.
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Severe → ↑↑ FF → ↑↑ π GC → ↓ GFR.
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Colloid osmotic pressure in Bowman capsule (π BC)= 0 mmHg.
2. Increase pressure apposing filtration:
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Colloid osmotic pressure in glomerular capillaries (π GC) = 30 mmHg.
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High plasma protein → increase π GC.
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Multiple myeloma.
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Conditions increasing the FF → increase π GC
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Hydrostatic pressure in Bowman space (PBS)= 10 mmHg
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Obstructions in the urinary system → increase PBS.
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Alteration of some parameters and their affect on RPF, GFR, and FF:
Filtration (of the plasma, 600 ml/min):
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Substances not filtered:
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Plasma proteins.
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Plasma protein-bound substances:
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Bilirubin
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Calcium (~50%).
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Fatty acids.
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Drugs.
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T3, T4.
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Substances filtered:
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H2O.
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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.
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Measurement of GFR:
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Inulin:
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Properties:
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Freely filters.
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Small.
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Non-toxic.
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Non-plasma protein binding.
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Not charged.
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Not absorbed and not secreted.
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Filtered load of inulin = urine load of inulin.
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Filtered load depends on inulin concentration in plasma and GFR ([p] inulin x GFR).
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Urine load depends on inulin concentration of urine and urine flow rate ([U] inulin x V).
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Creatinine (ideal GFR marker):
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Properties:
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Freely filters.
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Small.
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Normally present in the body
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Non-toxic.
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Non-plasma protein binding.
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Not charged.
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Absorbed but not secreted.
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Auto regulation of GFR and renal blood flow:
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Systemic blood pressure does not affect GFR between 70- 170 mmHg.
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Hypertension
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Tubuloglomerular balance:
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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.
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Decreased renin → decreased conversion of Angiotensinogen to AGT I (AGT II) → efferent arteriole dilation.
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Myogenic mechanism:
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Afferent arteriole smooth muscle stretch → stretch sensitive Ca channels sensitized àcontraction of the afferent arteriole muscle → constriction → GFR back to normal.
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Hypotension:
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Tubuloglomerular balance:
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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.
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Increased renin → increased conversion of Angiotensinogen to AGT I (→ AGT II)→ efferent arteriole constriction → GFR back to normal.
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Increased amino acids:
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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.
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Increased glucose:
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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.
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References:
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Dr. Najeeb Lectures. Dr. Najeeb Lectures - World's Most Popular Medical Lectures [Internet]. 2016 [cited 16 February 2016]. Available from: http://www.drnajeeblectures.com
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Hall J, Guyton A. Guyton and Hall textbook of medical physiology.
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Kumar P, Clark M. Kumar & Clark's clinical medicine.
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Le T, Krause K. First aid for the basic sciences. New York: McGraw-Hill Medical; 2012.
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Slideshare.net. creatinine clearance test [Internet]. 2016 [cited 16 February 2016]. Available from: http://www.slideshare.net/mprasadnaidu/rft-creatinine-clearance-test (Figure 1).
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300. Apsubiology.org. CH25 Physiology of Glomerular Filtration [Internet]. 2016 [cited 16 February 2016]. Available from: http://www.apsubiology.org/anatomy/2020/2020_Exam_Reviews/Exam_4/CH25_Physiology_of_Glomerular_Filtration.htm (Figure 2).
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301. Solanki A. Lect4. gfr.22.02.13 [Internet]. Slideshare.net. 2013 [cited 16 February 2016]. Available from: http://www.slideshare.net/ashoksolanki161214/lect4-gfr220213 (Figure 3).
Written by: Lama Al Luhidan
Reviewed by: Bassam Al-Ghamdi
Roaa Amer
Format editor: Adel Yasky