GLOMERULAR FILTRATION RATE AND RENAL CONTROL ACID-BASE BALANCE

1. Glomerular Filtration Rate

a. Composition of the Glomerular Filtrate
The filtered fluid (called the glomerular filtrate) is essentially protein free
and devoid of cellular elements, including red blood cells.
most salts and organic molecules, are similar to the concentrations in the
plasma.
Exceptions to this generalization include a few low-molecular-weight
substances, such as calcium and fatty acids, that are not freely filtered
because they are partially bound to the plasma proteins.
b. GFR Is About 20 Percent of the Renal Plasma Flow
the GFR is determined by:
1. the balance of hydrostatic and colloid osmotic forces acting across the
capillary membrane
2. the capillary filtration coefficient (Kf), the product of the permeability
and filtering surface area of the capillaries.
The fraction of the renal plasma flow that is filtered (the filtration fraction)
averages about 0.2; this means that about 20 percent of the plasma
flowing through the kidney is filtered through the glomerular capillaries
The filtration fraction is calculated as follows:
Glomerular Capillary Membrane
- The high filtration rate across the glomerular capillary membrane is
due partly to its special characteristics:
*The capillary endothelium is perforated by thousands of small holes
called fenestrae. Although the fenestrations are relatively large,
endothelial cells are richly endowed with fixed negative charges that
hinder the passage of plasma proteins.
*the basement membrane, which consists of a meshwork of collagen
and proteoglycan fibrillae that have large spaces through which
large amounts of water and small solutes can filter. The basement
membrane effectively prevents filtration of plasma proteins, in part
because of strong negative electrical charges associated with the
proteoglycans.
*The epithelial cells, which also have negative charges, provide
additional restriction to filtration of plasma proteins. Thus, all layers
of the glomerular capillary wall provide a barrier to filtration of
plasma proteins.
Filterability of Solutes Is Inversely Related to Their Size
 -
- Negatively Charged Large Molecules Are Filtered Less Easily Than
Positively Charged Molecules of Equal Molecular Size
c. Determinants of the GFR
- GFR=Kf x Net Filtration Pressure
- The GFR is determined by:
o the sum of the hydrostatic and colloid osmotic forces
across the glomerular membrane, which gives the net
filtration pressure
o the glomerular capillary filtration coefficient, Kf.
- The net filtration pressure represents the sum of the hydrostatic and colloid
osmotic forces that either favor or oppose filtration across the glomerular
capillaries:
- These forces include (1) hydrostatic pressure inside the glomerular
capillaries (glomerular hydrostatic pressure, PG), which promotes filtration;
(2) the hydrostatic pressure in Bowman's capsule (P B) outside the
capillaries, which opposes filtration; (3) the colloid osmotic pressure of the
glomerular capillary plasma proteins (G), which opposes filtration; and (4)
the colloid osmotic pressure of the proteins in Bowman's capsule ( B), which
promotes filtration. (Under normal conditions, the concentration of protein
in the glomerular filtrate is so low that the colloid osmotic pressure of the
Bowman's capsule fluid is considered to be zero.)

- Increased Glomerular Capillary Filtration Coefficient Increases GFR

- Increased Bowman's Capsule Hydrostatic Pressure Decreases GFR
- Increased Glomerular Capillary Colloid Osmotic Pressure Decreases GFR
- Increased Glomerular Capillary Hydrostatic Pressure Increases GFR
Glomerular hydrostatic pressure is determined by three variables, each of
which is under physiologic control: (1) arterial pressure, (2) afferent
arteriolar resistance, and (3) efferent arteriolar resistance
 d. Physiologic Control of Glomerular Filtration and Renal Blood Flow
1. Sympathetic Nervous System Activation Decreases GFR
Strong activation of the renal sympathetic nerves can constrict the renal
arterioles and decrease renal blood flow and GFR. Moderate or mild
sympathetic stimulation has little influence on renal blood flow and GFR.
2. Hormonal and Autacoid Control of Renal Circulation

3. Endothelial-Derived Nitric Oxide Decreases Renal Vascular Resistance

and Increases GFR
4. Prostaglandins and Bradykinin Tend to Increase GFR

2. Renal Control Acid-Base Balance

The kidneys control acid-base balance by excreting either acidic or basic
urine
The overall mechanism by which the kidneys excrete acidic or basic urine
is as follows: Large numbers of HCO3- are filtered continuously into the
tubules, and if they are excreted into the urine this removes base from the
blood. Large numbers of H+ are also secreted into the tubular lumen by the
tubular epithelial cells, thus removing acid from the blood. If more H + is
secreted than HCO3- is filtered, there will be a net loss of acid from the
 extracellular fluid. Conversely, if more HCO 3- is filtered than H+ is secreted,
there will be a net loss of base
When there is a reduction in the extracellular fluid H + concentration
(alkalosis), the kidneys fail to reabsorb all the filtered HCO 3- thereby
increasing the excretion of HCO3-. Because HCO3- normally buffers H+ in
the extracellular fluid, this loss of HCO3- is the same as adding an H+ to the
extracellular fluid. Therefore, in alkalosis, the removal of HCO 3- raises the
extracellular fluid H+ concentration back toward normal.
In acidosis, the kidneys do not excrete HCO 3- into the urine but reabsorb all
the filtered
HCO3- and produce new HCO3- , which is added back to the extracellular
fluid. This reduces the extracellular fluid H + concentration back toward
normal.
Thus, the kidneys regulate extracellular fluid H + concentration through
three fundamental mechanisms: (1) secretion of H +, (2) reabsorption of
filtered HCO3- , and (3) production of new
HCO3- .