Glomerular Filtration Rate

Introduction

The glomerular filtration rate or GFR is the amount of fluid filtered from the capillaries into the Bowmans capsule of the kidneys per unit time. The GFR can be expressed as the following formula:

GFR = K_f x net filtration pressure

K_f = the filtration coefficent

K_f can furthermore be expressed by the following formula

K_f = membrane permeability x filtration area

The GFR is practically proportional to metabolic body mass. Therefore the bigger the animal the greater the GFR.

Regulation of the GFR

The following formula helps us to understand GFR and how various factors affect it. Whilst reading this article you may find it useful to refer back to it:

Q = (PA - PE) ÷ R

Q = Flow, PA = Pressure in afferent arteriole, PE = Pressure in efferent arteriole, R = Resistance

There are two major forces opposing GFR. These are the hydrostatic pressure in the Bowmans space and the plasma protein osmotic pressure. These are not under physiological control. The filtration coefficient is also beyond the realms of physiological control. On the other hand the hydrostatic pressure in the capillaries and the renal blood flow are under physiological regulation and adjust filtration according to the bodies needs.

Regulation of Renal Blood Flow and Capillary Hydrostatic Pressure

These two factors are determined by the arterial blood pressure coupled with the contraction of both the afferent and efferent arterioles. The total resistance of the afferent and efferent arterioles, which is determined by the contraction of them, determines the renal blood flow and any particular arterial pressure. Therefore it is important that they change with arterial pressure in order to maintain a steady renal blood flow.

Constriction of the Afferent and Efferent Arterioles

Normally the afferent arteriole is of larger diameter than the efferent. This means there is high resistance as the blood is forced from a wider vessel to a narrower one and this promotes filtration. If the arterial blood pressure remains constant then contracting either vessel reduces blood flow as it increases resistance. However contracting either has opposite effects on the filtration pressure. If you contract the afferent arteriole there will be less of a pressure difference between the afferent and efferent arteriole so there will be reduced filtration pressure. However if you constrict the efferent arteriole you are increasing the pressure difference between the two and filtration pressure increase.

Overall the constriction of the afferent arteriole decreases both blood flow and filtration pressure where as constricting the efferent arteriole decreases blood flow but increases filtration pressure. (Both of these statements are assuming a constant blood pressure). The fact that both can be altered allows independent regulation of both GFR and blood flow.

Physiological Regulators of GFR

The main systems which regulate renal blood flow and GFR are:

Autoregulation

Q = (PA - PE) ÷ R

Q = Flow, PA = Pressure in afferant arteriole, PE = Pressure in efferant arteriole, R = Resistance

If renal resistance to blood flow was constant then any change to mean arterial blood pressure would alter blood flow, glomerular hydrostatic pressure and therefore filtration. However if blood pressure is changed by a small amount over a short period of time blood flow and filtration to the kidneys is not really affected. This is due to autoregulatory feedback mechanisms which allow the kidney to vary the resistance in the afferent arteriole. If it wasn't for these autoregulatory mechanisms then a small increase in arterial blood pressure would drastically increase the excretion of salt and water leading to a drastic reduction in the concentration of NaCl in the ECF.

Pressure Autoregulation

If arterial blood pressure increases then resistance in the afferent arteriole increases also and the opposite occurs if blood pressure falls. The role of pressure autoregulation is to ensure that during transient changes in blood pressure there is little effect on renal blood flow and therefore filtration providing the bodies need for the excretion of water and solutes remains the same. This is essential as only a small change in renal blood flow and thus filtration rate can have a massive change on urine output. The mechanisms for this response are found within the kidneys:

Myogenic Response

• Stretching of blood vessels due to increased blood pressure results in the blood vessel decreasing it's diameter.
  • This results in an increased resistance to blood flow
  • Thus keeping the GFR constant

Tubuloglomerular Feedback (TGF)

• When blood pressure increases for a short amount of time more blood flows through the glomerulus and therefore more filtrate is produced.
• This results in a decrease in proximal tubule reabsorption
• This increases the concentration of NaCl in the distal tubule which is detected by the Macula Densa
• This structure releases local factors resulting in the vasoconstriction of the afferent arteriole
• If blood pressure decreases the opposite occurs

The Limitations of Autoregulation

Despite the efforts of the autoregulatory system an increase in blood pressure still leads to an increased secretion of salt and water. This is because even a small percentage change in GFR leads to large percentage change in the excretion of salt and water. This excretion is however far less drastic than would be the case without autoregulation and actually helps to restore pressure to normal. This increase in urinary output as a result of an increase in arterial blood pressure is termed pressure diuresis.

Sympathetic Nervous System

When the animal is in a situation of crisis or stress blood flow to the kidneys is reduced for the sake of other organs such as the brain, heart and skeletal muscles. The sympathetic nervous system and a heightened level of adrenalin in the plasma cause the contraction of both the afferant and efferant arterioles. As the efferant arteriole is contracted alongside the afferant one there is still a pressure differance allowing for filtration to still occur and reducing the impact on filtration compared to the impact on blood flow. At times when sympathetic tone is very high the renal blood flow could be reduced to 10-30% of normal. This practically stops filtration occuring and thus stops urine production.

Resting Sympathetic Activity

Unlike many other organs the kidneys have a low resting sympathetic tone. Therefore the sympathetic nervous system cannot effectively decrease the resistance by decreasing itself. This suggests that its main aim is to compensate for a fall in blood pressure or to prepare the body for the fight or flight response.

Effect on Reabsorption

As GFR is less affected than blood flow the filtration of what blood does pass through the glomerulus is more efficent. This means that the blood entering the pertitubular capillaries will have a higher protein osmotic pressure and a lower hydrostatic pressure as more of the plasma will have been filtered. This causes greater reabsorption of water and salt from the tubules. This causes urine volume to fall. It also stimulates renin, The Renin Angiotensin Aldosterone System (RAAS) and aldosterone which all in turn have their effect on reabsorption.

Net Effect of Increased Sympathetic Nervous Activity on the Kidneys

• Reduced renal blood flow
• Small decrease in excreted waste
• Increased conservation of water and sodium

Nitrous Oxide and Prostaglandins

Nitrous Oxide and Prostaglandins have an impact on arteriolar resistance. Their role in the regulation of renal blood flow and filtration is however uncertain.

Nitrous Oxide

• Mediates dilation in the cortical circulation

Prostaglandins

• Mediates dilation in medullary circulation (cortical in extremes)
• PGE2 is involved in the regulation of the reabsorption of sodium
• Prostacyclin increases the secretion of potasium by stimulating renin secretion thus activating the Renin-Angiotensin-Aldosterone System and as a result increasing the amount of Aldosterone secreted.
• Prostacyclin increases renal blood flow and gfr when circulating volume is decreased. This results in increased tubular flow and increased potasium secretion
• In healthy/hydrated individuals these compounds do not play a significant role in sodium/water homeostasis

Effects of Blocking Nitric Oxide or Prostaglandins

• Loss of medullary circulation - reduced ability to concentrate water
• Loss of medullary flow - reduces the ability to preserve sodium balance and maintain normal blood pressure
• Loss of either may result in ischaemic damage

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