1. Glomerular Filtration and Regulation of Glomerular Filtration Rate
Reference: Principles of Anatomy and Physiology; Tortora & Derrickson
Chapter 26
Dr. Ebaa M. Alzayadneh, DDS, PhD.

2. Learning Objectives
Define Forces in the renal corpuscle that contribute to net filtration Pressure (equation).
Understand the consequences of alterations in these forces on the net filtration pressure.
Define glomerular filtration rate(GFR), filtration fraction, renal blood flow and renal plasma flow and understand how they relate to GFR.
Describe renal Autoregulation of GFR.
Describe neural and hormonal regulation of GFR.

3. Glomerular Filtration Forces
Forces Involved in Glomerular Filtration
Net Filtration Pressure (NFP):  This is the pressure responsible for filtrate formation.
NFP equals the glomerular hydrostatic pressure (GBHP) minus the oncotic pressure of glomerular blood (BCOP) and capsular hydrostatic pressure (CHP)
NFP = GBHP – BCOP – CHP
NFP = 55 – 30 – 15 = 10

4. Colloid Osmotic Pressure
Large molecules or Proteins
Colloid osmotic pressure is formed by large   molecular weight materials such as proteins
Water moves from areas of low osmolality to areas of high osmolality

5. Glomerular Filtration Rate (GFR)
Filtration Fraction (FF)= Fraction of blood plasma in the afferent arterioles that becomes filtrate= 16-20%.
GFR =The volume (ml) of fluid filtered through all the corpuscles of both kidneys per minute.
The volume of fluid filtered daily through all the corpuscles of both kidneys per day = 180 L
Hence, GFR= 180 L/24hours * (1000 ml/ L)*(1hour/60 min)= 125 ml/min (Males)
For 125ml/min;  renal plasma flow = 625ml/min
FF * PF=GFR, PF= 125/(20%)=625 ml/min
55% of blood is plasma, so blood flow = 1140ml/min
55% * BF= PF; BF= 625ml/min/ (55%)=1140 ml/min
Renal Blood Flow of 1140 ml/min = (22.8 % of 5 liters) is required to have GFR of 125ml/min.

6. Clinical Application Edema
Some kidney diseases result in a damage of the glomerular Capillaries leading to an increase in their permeability to large proteins .
Hence, Bowman’s capsule colloid pressure will increase significantly leading to drawing more water from plasma to the capsule (i.e more filtered fluid).
Proteins will be lost in the urine causing deficiency in the blood colloid pressure which worsens the situation, blood volume decreases and interstitial fluids increases causing edema.

7. Regulation of Glomerular Filtration
Homeostasis of body fluids requires constant GFR by kidneys.
If the GFR is too high, needed substances cannot be reabsorbed quickly enough and are lost in the urine.
If the GFR is too low -everything is reabsorbed, including wastes that are normally disposed of.

8. Regulation of Glomerular Filtration
GFR is directly related to the pressures that determine NFP.
Filtration ceases (become zero) if glomerular hydrostatic pressure drops to 45 mmHg
NFP = GBHP – BCOP – CHP
0= GBPH ; GBPH=45
However, NFP is increased very little when MAP rises. GFR is nearly constant if MAP is mmHg

9. Regulation of Glomerular Filtration
Control of GFR normally result from adjusting glomerular capillary blood pressure
3 mechanisms control the GFR 
Renal autoregulation (intrinsic system)
Neural controls
Hormonal mechanism

10. Regulation of Glomerular Filtration
Renal Autoregulation of GFR
Under normal conditions (MAP =80-180mmHg) renal autoregulation maintains a nearly constant glomerular filtration rate
2 mechanisms are in operation for autoregulation to adjust Renal blood flow and Glomerular surface area:
Myogenic mechanism:
Arterial pressure rises, afferent arteriole stretches
Vascular smooth muscles contract
Increased arteriole resistance offsets pressure increase; RBF (& hence GFR) remain constant. 
Opposite is true, when Arterial pressure drops, afferent arterioles stretch less and smooth muscles relax.

11. Renal Autoregulation of GFR
Tubuloglomerular feed back mechanism:
Feedback loop consists of a flow rate (increased NaCl in filtrate) sensing mechanism in macula densa of juxtaglomerular apparatus (JGA)
Increased GFR (& RBF) inhibits release of the vasodilator ; Nitric Oxide (NO)
Afferent arterioles constrict leading to a decreased GFR (& RBF).
When NaCl delivery decreasese, Renin-Ang II and NO will increase GFR

12. Effect of afferent and efferent arteriolar
constriction on glomerular pressure Ra Re PG PG
Blood
Flow
Blood
Flow
GFR
GFR
Ra GFR + Renal
Blood Flow
Re GFR + Renal
Blood Flow

13. Neural Regulation
When the sympathetic nervous system is at rest; very low:
Renal blood vessels are maximally dilated
Autoregulation mechanisms prevail
Under stress:
Norepinephrine is released by the sympathetic nervous system
Epinephrine is released by the adrenal medulla
Afferent arterioles(Mainly) constrict (more than efferent) and filtration is inhibited (GFR drops) 
The sympathetic nervous system also stimulates the renin-angiotensin mechanism.
Sympathetic stimulation causes reduction in urine out put and permits greater blood flow to other vital organs.
Under moderate sympathetic stimulation both afferent and efferent arterioles constricts to same degree so GFR would not be affected.

14. Hormonal Regulation Renin-Angiotensin Mechanism
A drop in filtration pressure stimulates the Juxtaglomerular apparatus (JGA) to release renin.
Renin-Angiotensin Mechanism
Renin acts on angiotensinogen to release angiotensin I  which is converted to angiotensin II
Angiotensin II
Causes mean arterial pressure to rise.
Stimulates the adrenal cortex to release aldosterone.
As a result, both systemic and glomerular hydrostatic pressure rise (because eferent arterioles constricts more than afferent arterioles)

15. Renin secretion regulation
Juxtaglomerular apparatus
1- Perfusion Pressure
low perfusion in afferent arterioles stimulates renin secretion while high perfusion inhibits renin secretion.
2-Sympathetic nerve activity
Activation of the sympathetic nerve fibers in the afferent arterioles increases renin secretion.
3- NaCl delivery to macula densa: When NaCl is decreased, Renin secretion is stimulated and vice versa. (Tubuloglomerular Feedback)
Glomeruli
JG cells: Secretes renin
JG cells= Juxtaglomerular cells
Macula Densa: sensor cells
Tubuloglomerular Feedback

16. Hormonal Regulation Atrial Natriuritic Peptide ANP
(ANP) release is stimulated from the atrium under increased pressure/volume.
ANP causes:
Vasodilation of the afferent arterioles
Inhibition of Renin secretion
Inhibition of aldosterone and ADH secretion