1. RENAL SYSTEM PHYSIOLOGY
Dr Shahab Shaikh PhD, MD
Lecture – 2: Glomerular Filtration
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College of Medicine
Al Maarefa Colleges of Science & Technology

2. OBJECTIVES Identify three basic processes involved in urine formation.
Define GFR and quote normal value
Describe the composition of the glomerular filtrate
Detect the structural & functional peculiarities of the glomerular filtration membrane
Outline the factors controlling GFR
Understand the concept of Net filtration pressure.
Correlate between net filtration pressure along glomerulus and plasma flow
List the characteristics that a compound must have before it can be used for measuring GFR e.g. Inulin, creatinine etc.

3. Urine Formation
Three Basic Mechanisms (Renal Processes) of Urine Formation include:
Glomerular filtration - GF
Tubular reabsorption - TR
Tubular secretion - TS

4. Urine Formation
Renal Handling of different substances during Urine Formation:
Urine
Substance X
Substance Y
Substance Z
Substance W
W: filtered & secreted, but not reabsorbed (e.g. H+ ions)
X : filtered & partially reabsorbed ( e.g. Urea, Na+ etc.)
Y : filtered & completely reabsorbed (e.g. Glucose)
Z :filtered but neither reabsorbed nor secreted (e.g. Creatinine)

5. Glomerular Filtration
The first step in urine formation is the Glomerular filtration during which, large quantity of water and solutes pass through the filtration membrane from the blood into the Bowman’s Capsule due to pressure gradient.
The glomerular capillaries are relatively impermeable to plasma proteins, so the filtered fluid (glomerular filtrate) is free from :
Blood cells
Protein
Protein-bound molecules (calcium, fatty aids, amino acids)
The glomerular filtrate contains crystalloids in virtually the same concentrations as in the plasma.

6. Glomerular Filtration
Thus essentially the composition of Glomerular filtrate is similar to plasma (except Plasma Proteins) and consists of:
Water
Electrolytes
Glucose, Amino Acids
Urea
Creatinine
Uric Acid
Urobilinogen etc.

7. Glomerular Filtration
Proteinuria:
means the presence of an excess of serum proteins in the urine.
An increase in the level of urine albumin between 30–300 mg/24 hours is called as Microalbuminuria
Value higher than 300mg/24 hours is called as Macroalbuminuria.
Clinical Significance of Proteinuria:
Early detection of renal disease in at-risk patients
Hypertension: Hypertensive Renal Disease
Diabetes: Diabetic Nephropathy
Pregnancy: Pre-eclampsia
Assessment and monitoring of known renal disease

8. Glomerular Filtration
Glomerular Filtration Rate (GFR):
Definition:
It is the Volume of plasma filtered by all nephrons of both kidneys per unit time.
Normal GFR = 125ml/min or 180L/day.
Determined By:
Sum of the hydrostatic and colloid osmotic pressures across the glomerular membrane, called the NET FILTRATION PRESSURE.
The Capillary Filtration Coefficient (Kf)
Thus GFR = Kf x Net Filtration Pressure

9. Glomerular Filtration
Filtration coefficient (Kf):
“Surface Area” available for filtration and “Membrane Permeability” determine Filtration Coefficient (Kf).
The normal Membrane Permeability of glomerular capillaries is very high as compared to other capillaries in body.
Normally it is not highly variable.
Disease that can reduce Kf and thus GFR are:
chronic hypertension
obesity / diabetes mellitus
glomerulonephritis

10. Glomerular Filtration
Net filtration Pressure:
The net filtration pressure is the sum of the hydrostatic and colloid osmotic pressures that either favor or oppose filtration across the filtration membrane.
These pressures are:
Glomerular hydrostatic pressure (PG)
Glomerular colloid osmotic pressure (πG)
Bowman’s capsular hydrostatic pressure (PB)
Bowman’s capsular colloid osmotic pressure (π B).
It is approximately 10 mmHg

11. Glomerular Filtration
Net filtration Pressure: 10mmHg
Forces Favoring filtration
Glomerular hydrostatic pressure PG = 60 mmHg
Due to high renal blood supply and high efferent arteriolar resistance
Bowman’s capsular colloid osmotic pressure πB = 0 mmHg
Due to absence of proteins in the Bowman’s capsular space
Forces Opposing filtration
Bowman’s capsular hydrostatic pressure PB = 18 mmHg
Due to filtered fluid in the Bowman’s capsule
Glomerular colloid osmotic pressure πG = 32mmHg
Due to the osmotic pressure exerted by the plasma proteins.
Note: the values here are from Guytons Textbook. Different books may mention slightly different values.

12. Glomerular Filtration
Net filtration Pressure:

13. Being Curious …
Can you think of some situations where there may occur Increase/Decrease in following Pressures and what might be the effect?
Glomerular hydrostatic pressure (PG)
Bowman’s capsular colloid osmotic pressure (πB)
Bowman’s capsular hydrostatic pres sure (PB)
Glomerular colloid osmotic pressure (πG)

14. Glomerular Filtration
Factors affecting GFR:
Changes in renal blood flow
Changes in glomerular capillary hydrostatic pressure
Changes in systemic blood pressure
Afferent or efferent arteriolar resistance
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.
Changes in Kf
Changes in glomerular capillary permeability
Changes in effective filtration surface area

15. Glomerular Filtration
Glomerular Capillary Hydrostatic Pressure (PG):
It is the primary means for physiologic regulation of GFR.
Increase PG  raises GFR, and vice versa.
It is determined by three variables:
Arterial Pressure
Afferent Arteriolar Resistance
Efferent Arteriolar Resistance.

16. Glomerular Filtration
Regulation of GFR:
Glomerular capillary hydrostatic pressure can be controlled to adjust GFR to suit body’s needs
Two major control mechanisms
Extrinsic control by adjusting the constriction of afferent/efferent arterioles
Mediated by sympathetic nervous system input to arterioles
Baroreceptor reflex
Autoregulation
Myogenic mechanism
Tubuloglomerular feedback (TGF)

17. Glomerular Filtration
Effect of Afferent and Efferent Arteriolar Constriction on Glomerular Pressure: Re PG
GFR Ra
Ra GFR Renal
Blood Flow
Blood Flow
Re GFR Renal

18. Glomerular Filtration
Autoregulation of GFR:
Feedback mechanisms intrinsic to the kidneys normally keep the renal blood flow and GFR relatively constant, despite marked changes in arterial blood pressure.
Autoregulation involves two mechanisms:
Tubuloglomerular Feedback Mechanism
Myogenic Mechanism

19. Glomerular Filtration
TubuloGlomerular Feedback:
GFR
Distal NaCl
Delivery
Macula Densa NaCl Reabsorption
Afferent Arteriolar Resistance
GFR (return toward normal)

20. Glomerular Filtration
Myogenic Mechanism:
Stretch of
Blood Vessel
Cell Ca++
Permeability
Arterial
Pressure
Intracell. Ca++
Blood Flow
Vascular
Resistance

21. Glomerular Filtration
Filtration Fraction (FF) :
Filtration Fraction is the ratio of the GFR to the renal plasma flow (GFR/TRPF).
Renal blood flow is 20-25% of total cardiac output. Thus it is approximately = 1.1 L/min
Thus of the 625 ml of plasma which enters the glomeruli via the afferent every minute, 125 (the GFR) filters in the Bowman’s capsule, the remaining passing via efferent arterioles into the peritubular capillaries
Filtration fraction = (GFR/TRPF) = 0.2
So, GFR is About 20% of the Renal Plasma Flow

22. Glomerular Filtration
Measurement of GFR:
Characteristic of substance used for measurement:
Freely filtered (not reabsorbed and not secreted)
Not metabolized by the kidney
Not toxic and stable
Not bound to plasma protein
Does not change renal plasma flow
The substance used to measure GFR is Inulin, a polysaccharide.

23. References Human physiology by Lauralee Sherwood, 8th edition
Text Book Of Physiology by Guyton & Hall, 11th edition
Review of Medical Physiology by Ganong. 24th edition

24. THANK YOU