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

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.

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

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

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.

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.

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.

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-15-30 ; GBPH=45 However, NFP is increased very little when MAP rises. GFR is nearly constant if MAP is 80-180 mmHg

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

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.

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

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

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.

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)

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

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