GFR ,factors affecting it & its Regulation Learning Objectives :

At the end of lecture student must be able to know,      

Describe glomerular filtration membrane and how it excludes blood cells and proteins from the filtrate Explain the forces that promote and oppose glomerular filtration How you will calculate net filtration pressure if given the magnitude of these forces The glomerular filtration rate (GFR) Factors affecting GFR Regulation of GFR (describe how the nervous system, hormones, kidney itself regulate glomerular filtration).

Functional anatomy of the kidney

Urine formation              

Nephrons remove wastes from the blood and regulate water and electrolyte concentrations Urine is the final product of the processes of: Glomerular filtration Tubular reabsorption Tubular secretion Glomerular Filtration Substances move from blood to glomerular capsule Tubular Reabsorption Substances move from renal tubules into blood of peritubular capillaries Glucose, water, urea, proteins, creatine Amino, lactic, citric, and uric acids Phosphate, sulfate, calcium, potassium, and sodium ions Tubular Secretion Substances move from blood of peritubular capillaries into renal tubules

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Drugs and ions

Glomerular Filtration  The first step in urine formation is filtration of substances out of the glomerular capillaries into the glomerular capsule. 

Glomerular filtrate passes through the fenestrae of the capillary endothelium.

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The kidneys converts blood plasma to urine in three stages: Glomerular filtration Tubular reabsorption and secretion Water conservation

Key functions

Filtration Reabsorption Secretion Excretion :Glomerular filtration    

As we trace the fluid through the nephron, we will refer it by different names that reflect its changing composition. The fluid in the capsular space, called glomerular filtrate, is similar to blood plasma except it has almost no protein. The fluid from PCT through the DCT is called tubular fluid. It differ from glomerular filtrate b/c of the substances added and removed by the tubule cells The fluid will be called urine once it enters the collecting duct.

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lomerular Filtrate and Urine Composition

Glomerular membrane  

The first layer is the wall or endothelium of the capillary. In the glomerulus this single layer of cells has thousands of gaps (pores). The basement membrane between the two cell layers is composed of glycoprotein and collagen fibres. Its mesh-like structure acts as a filter during ultrafiltration.

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Filtration Membrane

 Glomerular membrane

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The second cell layer is the wall of the Bowman’s capsule The epithelial cells in this wall are called podocytes They have foot-like processes and do not fit tightly together so have gaps between them (filtration slits). Glomerular membrane The glomerulus consists of a network of parallel capillaries. It is a filter made up from different layers: Endothelium cells containing pores in their cytoplasm of radius 25-50nm The basal membrane Lamina rara interna Lamina densa Lamina rara externa Epithelium cells

Glomerular Filteration Rate (GFR)         

Urine is formed as a result of filtration of plasma through filteration membrane in the glomeruli (= glomerular filtration) then reabsorption & secretion process in renal tubules. Normally,GCP receives about 650 ml plasma/min. from Which only one 1/5(125) is filtered into bowman’s capsule, while the remaining 4/5 pass to the peritubular capill.(PTC). GFR: is the fraction of renal arteriolar plasma from aff. arteriol. W’ is filterd /min. in renal glomeruli =125 ml/min. =7.5L/hour =180 L/day. As plasma vol. is 3L, So it is filtered 60 times /day. Filtration Fraction: This is the fraction in % of renal arterial plasma that is filtered in the glomeruli. It is equal the GFR/RPF x 100=125/650x100=19% (16-20%)

Filtration Pressure   

The glomerular filtration is almost protein free and has no significant COP (this can change markedly in kidney diseases that allows protein to filter into the capsular space). On balance, we have high outward pressure of 60mmHg, opposed by two inward pressures of 18 and 32mmHg giving a net filtration pressure (NFP) OF: NFP = 60out – 18in – 32in = 10mmHg

The glomerular filtration rate (GFR)

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The glomerular filtration rate (GFR) is the volume of filtrate formed each minute by all the glomeruli (~2 million) of the kidneys combined Normal GFR in adults is 120-125 mL /min Maintenance of a relatively constant GFR is important because reabsorption of water and solutes depends on how quickly filtrate flows through the tubules.

Glomerular filtration  

Glomerular filtration is a passive process in which hydrostatic pressure forces fluids through the glomerular membrane. Water, glucose, amino acids, & nitrogenous wastes pass freely from blood into glomerular capsule

Glomerular Filtration    

Glomerular filtration The net filtration pressure (NFP) responsible for filtrate formation; may also be considered the glomerular blood pressure. Moves water and solutes out of blood & across filtration membrane The fact that no proteins are able to cross the membrane and enter the glomerular capsule prevents all water from being pulled out of the blood and into filtrate (and ultimately into the urine).

Glomerular filtration rate       

The total amount of filtrate formed per minute by both kidneys. Factors governing filtration rate at the capillary bed are: Total surface area available for filtration Filtration membrane permeability Net filtration pressure GFR is directly proportional to the NFP. Changes in GFR normally result from changes in glomerular blood pressure.

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Filtration Pressure and Rate

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Net Filtration Pressure = force favoring filtration – forces opposing filtration glomerular capillary hydrostatic pressure capsular hydrostatic pressure glomerular capillary osmotic pressure

Glomerular Filtration Rate      

directly proportional to the net filtration pressure The glomerular filtration rate (GFR) The glomerular filtration rate (GFR): is influenced by two factors 1 – Net filtration pressure 2 – Filtration coefficient The net filtration pressure is determined by:

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Blood flow Blood pressure The filtration coefficient has 2 component: Surface area of glomerular capillaries Permeability of capillary-bowman's space

Factors that influence the Glomerular filtration rate (GFR) 1- Renal blood flow (RBF); GFR is directly proportionate with RBF. 2- The glomerular capillary pressure; this pressure increases by dilatation of afferent arterioles or constriction of efferent arterioles. 3- The pressure in Bowman's capsules (intra-capsular pressure); Glomerular filtration decreases with any increase in the intra-capsular pressure (re-absorption force). 4- The plasma proteins concentration; an increase in the plasma proteins concentration (e.g. in dehydration), decease GFR & vice versa. 5- The glomerular capillary permeability; this may be changed either by damage of capillary wall or abolishing the negative charges around there pores.

Control of Filtration Rate o Whole body BP requires constant blood volume; the kidneys need a constant GFR to do their job Recall: BP maintained by neural and endocrine actions o GFR is held relatively constant through intrinsic autoregulatory mechanisms, and extrinsic neural & hormonal mechanisms Regulation of Glomerular Filtration     

The GFR must be precisely controlled. The only way to adjust GFR from moment to moment is to change Glomerular blood pressure and this is achieved by 3 homeostatic mechanisms: Renal autoregulation Sympathetic control Hormonal control

3 Levels of GFR Control   

Autoregulation (local level) Hormonal regulation (initiated by kidneys) Autonomic regulation (by sympathetic division of ANS)

Renal Autoregulation

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Autoregulation entails two types of control Myogenic – responds to changes in pressure in the renal blood vessels Tubuloglomerular feedback – senses changes in the juxtaglomerular apparatus

Regulation of Filtration Pressure

Tubuloglomerular Feedback  Tubuloglomerular Feedback : in this mechanism, the juxtaglomerular apparatus (JGA) monitors the fluid entering the distal convoluted tubule and adjust the GFR to maintain homeostasis.  The components of the JGA:  The juxtaglomerular (JG) cells  The macula densa  The mesangial cells

Juxtaglomerular apparatus

Sympathetic Control 

Sympathetic nerves fibers richly innervate the renal blood vessels.

Sympathetic Nervous System (SNS) Controls       

When the SNS is at rest: Renal blood vessels are maximally dilated Autoregulation mechanisms prevail Under stress: Norepinephrine is released by the SNS Epinephrine is released by the adrenal medulla Afferent arterioles constrict and filtration is inhibited

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The SNS also stimulates the renin - angiotensin mechanism

Hormonal Regulation of GFR  By hormones of the:  Renin –angiotensin system  Natriuretic peptides (ANP) Renin -Angiotensin Mechanism       

Is triggered when the JG cells release renin Renin acts on angiotensinogen to release angiotensin I Angiotensin I 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

Aldosterone  

Accelerates sodium reabsorption: in DCT and cortical portion of collecting system

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Renin-Angiotensin system

Atrial Natriuretic Peptide (ANP)    

Is produced by atria due to stretching of walls Acts opposite to aldosterone Stimulates salt & H20 excretion Acts as an endogenous diuretic

Regulation of Glomerular Filtration  

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.

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