Filtration coefficient (Kf ): Kf = GFR / net filtration pressure -GFR for both kidneys is about 125 ml/ min,the -- -net filtration pressure is 10 mm Hg, -normal Kf about 12.5 ml/min/mm Hg of filtration pressure.

. Chronic uncontrolled hypertension and diabetes mellitus gradually reduce Kf by increasing the thickness of the glomerular capillary basement membrane and, by damaging the capillaries.

Two factors influence the glomerular capillary colloid osmotic pressure : (1) the arterial plasma colloid osmotic pressure. (2) the fraction of plasma filtered by the glomerular capillaries (filtration fraction).

- A greater rate of blood flow into the glomerulus tends to increase GFR, and a lower rate of blood flow into the glomerulus tends to decrease GFR. - Increased glomerular capillary hydrostatic pressure increases GFR.

Glomerular hydrostatic pressure is determined (1) arterial pressure, (2) afferent arteriolar resistance, (3) efferent arteriolar resistance.

Increased arterial pressure ↑↑ glomerular hydrostatic pressure and, therefore, ↑↑ GFR. Increased resistance of afferent arterioles ↓↓glomerular hydrostatic pressure and ↓↓ GFR. Conversely, dilation of the afferent arterioles increases both glomerular hydrostatic pressure and GFR. Constriction of the efferent arterioles increases the resistance to outflow from the glomerular capillaries. This raises the glomerular hydrostatic pressure,

Factors That Can Decrease the Glomerular Filtration Rate (GFR)

Renal Blood Flow

- In an average 70-kg man, the combined blood flow through both kidneys is about1100 ml/min, ( about 22 % of the cardiac output). -The two kidneys constitute only about 0.4% of the total body weight, (high blood flow compared with other organs). -This is necessary for precise regulation of body fluid volumes and solute concentration.

-The kidneys normally consume oxygen at twice the rate of the brain -The kidneys have almost seven times the blood flow of the brain. -Renal oxygen consumption varies in proportion to renal tubular sodium reabsorption, which is closely related to GFR and the rate of sodium filtered.

Blood flow in the renal medulla accounts for only % of the total renal blood flow. Flow to the renal medulla is supplied by a specialized portion of the peritubular capillary system( vasa recta).

Physiologic control of glomerular filtration and renal blood flow 1-Sympathetic Activation Strong activation of the renal sympathetic nerves can constrict the renal arterioles and decrease renal blood flow and GFR. The renal sympathetic nerves important in reducing GFR during severe, acute disturbances lasting for a few minutes to a few hours, in (defense reaction, brain ischemia, or severe hemorrhage). In the healthy resting person, sympathetic tone appears to have little influence on renal blood flow.

2-Hormonal and Autacoid Control *norepinephrine and epinephrine released from the adrenal medulla (constrict afferent and efferent arterioles, causing reductions in GFR and renal blood flow). *endothelin, is a peptide released by damaged vascular endothelial cells of the kidneys as well as by other tissues. (vasoconstrictor). Plasma endothelin levels also are increased in certain disease states associated with vascular injury, such as toxemia of pregnancy, acute renal failure, and chronic uremia, and may contribute to renal vasoconstriction and decreased GFR in some of these pathophysiologic conditions.

3- Angiotensin II A circulating hormone is formed in the kidneys& in the systemic circulation. angiotensin II constricts efferent arterioles. * increased angiotensin II levels raise glomerular hydrostatic pressure while reducing renal blood flow. *increased angiotensin II levels that occur with a low-sodium diet or volume depletion help preserve GFR and maintain normal excretion of metabolic waste products such as urea and creatinine. *angiotensin II–induced constriction of efferent arterioles increases tubular reabsorption of sodium and water, which helps restore blood volume and blood pressure.

4-Endothelial-derived nitric oxide :An autacoid that decreases renal vascular resistance and is released by the vascular endothelium. A basal level of nitric oxide production important for maintaining vasodilatation of the kidneys.

5- Prostaglandins and Bradykinin cause vasodilatation and increased renal blood flow and GFR. Under stressful conditions, such as volume depletion or after surgery, the administration of nonsteroidal anti- inflammatory agents, such as aspirin, that inhibit prostaglandin synthesis may cause significant reductions in GFR.

Adaptive mechanisms in the kidneys * Autoregulation * Glomerulotubular balance

Autoregulation of GFR and Renal Blood Flow Autoregulation: Feedback mechanisms intrinsic to the kidneys normally keep the renal blood flow and GFR relatively constant, despite marked changes in arterial blood pressure. (These mechanisms still function in blood perfused kidneys that have been removed from the body, independent of systemic influences).

Myogenic mechanism of the autoregulation

The GFR normally remains autoregulated (that is, remains relatively constant), despite arterial pressure fluctuations that occur during a person’s usual activities. A decrease in arterial pressure to as low as 75 mm Hg or an increase to as high as 160 mm Hg changes GFR only a few percentage points.

Normally, GFR is about 180 L/day and tubular reabsorption is L/day, leaving 1.5 L/day of fluid to be excreted in the urine. In the absence of autoregulation, a relatively small increase in blood pressure (from 100 to 125 mm Hg) would cause a similar 25 % increase in GFR (from about 180 to 225 L/day). If tubular reabsorption remained constant at L/day, this would increase the urine flow to 46.5 L/day (the difference between GFR and tubular reabsorption)— a total increase in urine of more than 30-fold. Because the total plasma volume is only about 3 liters, such a change would quickly deplete the blood volume.

Glomerulotubular balance: Additional adaptive mechanisms in the renal tubules that allow them to increase their reabsorption rate when GFR rises.

GFR measurement Inulin, a polysaccharide used to measure GFR, Inulin not reabsorbed or secreted by the renal tubules so it can be used to measure the GFR.

Q. Is the GFR constant or variable? And how to be regulated? A. GFR depend on the three forces mentioned above, but, the two forces (plasma colloid pressure and the bowman’s capsule hydrostatic pressure) are constant in normal conditions, so, only the Glomerular capillary pressure will affect the GFR, if increased it will increase the GFR and vise versa * Glomerular capillary pressure depends on amount of blood flow to glomerulus, which depend on the diameter of the afferent arteriole (caliber), when the diameter of the afferent arteriole increase (dilation), the blood flow will increase, and by this increasing the Glomerular capillary pressure, so that filtration will increase (GFR)

Q. What are the factors that regulate GFR? A/ 1.sympathetic system: sympathetic stimulation to afferent arteriole make vasoconstriction (narrowing of blood vessel) and by this reducing blood flow to glomerular capillary which lead to decrease GFR, this is in addition to effect of sympathetic system on systemic blood vessels to make vasoconstriction and elevate blood pressureblood pressure

2. Auto regulation of afferent arteriole: when systemic blood pressure increase it will dilate afferent arteriole, this dilation will stimulate the smooth muscles of afferent arteriole to contract, as to say when they contract they will narrow, and by this they are opposing the effect of dilation to keep the diameter of afferent arteriole constant i.e. to keep blood flow to glomerulus constant, this is called auto regulation and vise versa when blood pressure decrease, smooth muscle of afferent arteriole will relax

A) Autoregulation of the renal blood flow RBF is kept relatively constant between ABP; mmHg, It is present in denervated, isolated kidney, This proving that this property is intrinsic property - Beyond blood pressure range 80 – 180 mmHg, there is no autoregulation. mechanism; by changing the renal vascular resistance.

a. Myogenic mechanism - Increased ABP,stretch of afferent arteriole, increased Ca influx from extracellular fluid into muscle fibre,direct vasoconstriction prevent increase in RBF.- Smooth muscles in the wall of afferent arteriole relax when blood pressure decreases leading to vasodilatation causing increase in blood flow and increase in GFR back to normal. decrease in RBF & GFR or vasodilator substance leading to afferent arteriolar vasodilatation (in case of decrease in bloodpressure) →

b. Tubuloglomerular feedback Macula densa in the juxtaglomerular apparatus release of vasoactive chemicals (in case of increase in blood pressure) afferent arteriolar vasoconstriction → increase in RBF & GFR