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Week 22 Learning Objectives
Biochemistry and Physiology of Renal Function (Part 2)
6. List and briefly explain the determinants of GFR: arterial blood pressure, pre- and postglomerular resistance, glomerular capillary pressure; colloid osmotic pressure of plasma;
properties of glomerular membrane
Arterial Blood Pressure and Glomerular Capillary Pressure
The Glomerular Filtration Rate (GFR) works by principles of pressure, namely the pressure difference
between the glomerulus (Glomerular Hydrostatic Pressure) and Bowman’s capsule (Capsular Hydrostatic
Pressure). The glomerulus contains capillaries with a porous endothelium. Filtration of the blood occurs
where the filtrate becomes excreted from the glomerular capillaries into the capsule. Essentially, the
pressure in the glomerulus is about 35mm Hg higher than in the capsule causing a filtrate to be forced
out of the golmerulous through the porous endothelium and into the capsule. Because the blood in the
glomerulous is being delivered through capillaries, changes in arterial blood pressure will affect the
pressure difference between the glomerulus and capsule. In turn, this will affect the rate of filtration:
 An increase in arterial blood pressure will result in the increase of the Glomerular Hydrostatic
Pressure, creating an increased pressure difference between the glomerulus and capsule. This
will effectively increase the filtration rate as more filtrate will be forced into the capsule.
 A decrease in arterial blood pressure will result in the decrease of the Glomerular Hydrostatic
Pressure, creating a decreased pressure difference between the glomerulus and capsule. This
will decrease the filtration rate as the impetus to force filtrate through into the capsule will be
lower. Note that if the blood pressure drops low enough to greatly diminish the Glomerular
Hydrostatic Pressure, no filtering will occur and the patient will enter renal failure.
Considering all of the above, changes to the glomerular capillary pressure will also have the same effect
in filtration.
Normal values of pressure:
Glomerular Hydrostatic Pressure (GHP) = 50mm Hg
Capsular Hydrostatic Pressure (CsHP) = 15 mm Hg
Net Hydrostatic Pressure (GHP-CsHP) = 35mm Hg
Net Hydrostatic Pressure will determine the Glomerular Filtration Rate. A higher pressure will increase
the filtration rate; a lower pressure will decrease the filtration rate.
Pre and Post Glomerular Resistance
The two terms refer to how resistance in blood flow can affect glomerular filtration. There are two
general types of resistance, one that happens anywhere before the glomerulus (pre) and one that
happens anywhere after the glomerulus (post).
 An increase of pre glomerular resistance due to a blockage or restriction of blood flow will limit
the amount of blood reaching the glomerular-capsule interchange. The result of this would be a
decrease of the glomerular hydrostatic pressure thus causing the filtration rate to decrease.

An increase of post glomerular resistance due to a blockage or restriction of blood flow after the
glomerulus will cause a sub sequential back-pressure returning back into the glomerular-capsule
interchange. This would result in an increase of the glomerular hydrostatic pressure causing the
filtration rate to increase.
Colloid Osmotic Pressure of Plasma
The colloid osmotic pressure of a solution is the osmotic pressure resulting from the presence of soluble,
in the plasma this predominantly consists of proteins. The Blood Colloid Osmotic Pressure (BCOP) tends
to draw water out of the filtrate and into the plasma; it thus opposes filtration. Over the entire length of
the glomerular capillary bed, the BCOP averages about 25mm Hg. Under normal conditions, very few
plasma proteins will pass the filter and enter the capsular space, so no opposing colloid osmotic
pressure exists within the capsule. This discrepancy of pressure will exert an osmotic force on the water
to move from the filtrate (capsule) to the plasma (glomerulus). This pressure however is normally
overrun by other forces which results in the normal process of filtration.
Net Hydrostatic Pressure = 35 mm Hg
Blood Colloid Osmotic Pressure = 25 mm Hg (opposes NHP)
Total system pressure = NHP (35) – BCOP (25) = 10 mm Hg
Properties of the Glomerular Membrane
The glomerular membrane has an important role in maintaining two separate compartments; the
glomerulus and the capsule. The membrane itself lies between the glomerular capillary lumen and the
lumen of Bowman’s capsule. The constituents of the membrane are shown below:
This membrane acts as the filter of this filtration system. It permits small soluble particles as well as
water to move from the capillary into the capsule. It prevents large particles such as proteins from
exiting the capillaries. In doing this job it maintains all the different pressures of the system and also
prevents unwanted products such as proteins and blood cells from leaving the capillaries and entering
the filtrate. Should the membrane be compromised large particles such as proteins and red blood cells
can enter the filtrate and pass through urine. The passing of proteins will cause additional pressure
changes in the system where the colloid osmotic pressure difference between the plasma and the
filtrate will drop drastically. The reduction of the blood colloid osmotic pressure will eliminate the
opposition to the net hydrostatic pressure; this will result in a much faster flow of fluid from the plasma
to the filtrate. In this scenario the GFR will increase drastically and this will lead to an increased urine
output.
7. Explain why plasma creatinine concentration changes inversely with the GFR in the steady
state, and therefore why plasma creatinine is useful as an index of renal function
Creatinine is an end product of muscle metabolism and is almost exclusively excreted out of the body as
a result of glomerular filtration. Though there is a very small amount of creatinine which is involved with
tubular secretion, this amount is almost clinically negligible. Because creatinine excretion is dictated by
glomerular filtration, the GFR has a linear inverse relationship with levels of creatinine in the blood:
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An increase in GFR will reduce creatinine concentrations in the blood
A decrease in GFR will increase creatinine concentrations in the blood
Since creatinine is the end product of muscle metabolism, normal levels of creatinine in the blood will
vary from person to person. Typically, the more muscle mass a person possesses, the higher their
normal creatinine levels will be.

Normal Ranges present in the blood: 0.08 to 0.13 mg/L (70 to 114 mmol/L) in men and 0.06 to
0.10 mg/L in women
Creatinine clearance is one of the most effective tests for assessing the GFR. To assess the GFR, a
comparison between the concentration of creatinine excreted in the urine, the volume of urine excreted
and the concentration of creatinine in the blood.
Normal GFR ranges can vary greatly because of the variability of muscle mass between individuals.
Normal GFRs can range from 146-55 mL/min in males and 134-52 mL/min in females.
Creatinine clearance however, is not 100% accurate since a small amount of creatinine is secreted out
through the proximal tubules. As a result, the urine concentration of creatinine and the GFR would be
slightly overestimated. This error can be reduced by using cimetidine to minimize tubular secretion of
creatinine bit will not eliminate it completely. Regardless, measuring the GFR through creatinine levels is
still highly effective due to the highly-dependant relationship between creatinine clearance from the
body and glomerular filtration.
8. Explain why the normal diet results in the net production of acid, and outline the
mechanisms in the kidney that allow the conservation of the base bicarbonate and the net
excretion of acid.
There are three types of acids in the body:
Volatile Acids – These are acids that can leave solution and enter the atmosphere. Carbonic acid is one
of the most important volatile acids and forms spontaneously as a result of the interaction between
carbon dioxide and water.
Organic Acids – These are acids that participate in or are by products of aerobic metabolism. Examples
include lactic acid and ketone bodies.
Fixed Acids – These acids cannot leave solution and do not leave the body until they are excreted out
through the kidneys. Fixed acids are formed from the catabolism of amino acids, phospholipids and
nucleic acids. Consuming food will ultimately lead to the creation of these fixed acids.
While diet has a direct impact on the formation of fixed acids, it also has an indirect impact on the
formation of organic acids and volatile acids through metabolism. Consumed food eventually becomes
involved in a metabolic process to produce energy either aerobically or anerobically. The result of this
metabolism is the creation of products like lactic acid (organic acid) or carbon dioxide (part of the
volatile acid reaction).
Acidity is often described as the amount of hydrogen ions present within a solution. In order to balance
the acidity of the blood, the body acts through the kidneys and the lungs in order to expel acidic
contents.
The lungs act as a quick changing system by expelling carbon dioxide in a very rapid manner if necessary.
The expulsion of carbon dioxide will impede the formation of H2CO3 and hydrogen ions, thus reducing
the acidity of the blood. This can be observed in the following equation:

CO2 + H2O → H2CO3 → H+ + HCO3-
The kidneys however, work to excrete hydrogen ions and also to retain bicarbonate (a base) in order to
maintain a stable pH. This primarily works in three ways:
Method 1 – Bicarbonate Retention (Proximal Tubule)
The one way the kidneys attempt to maintain a pH balance is to retain bicarbonate (HCO3-) which is a
base that is constantly being filtered by the glomeruli.
1. In a reaction to a drop of pH, hydrogen ions (H+) are secreted from the plasma into the tubular
fluid in the proximal convoluted tubule.
2. The hydrogen ions combine with bicarbonate (HCO3-) in the tubular fluid and form carbonic acid
(H2CO3). Carbonic acid is then dissociated by the carbonic anhydrase (CA) enzyme into water
(H2O) and carbon dioxide (CO2).
3. The water will remain in the tubular fluid but the carbon dioxide will passively diffuse into the
tubule epithelial cell. In the cell, the carbon dioxide (CO2) will combine with water (H2O) from
the cell to re-form carbonic acid (H2CO3).
4. This carbonic acid (H2CO3) will now dissociate into hydrogen ions (H+) and bicarbonate (HCO3-)
inside the tubule epithelial cell.
5. The hydrogen ions (H+) will be swapped with sodium ions (Na+) from the tubules and re-secreted
back into the tubular fluid in a process called counter-transport.
6. The bicarbonate (HCO3-) however will engage in co-transport with the sodium ions (Na+) and will
move back into the peritubular fluid and eventually the blood.
In this way, bicarbonate which would have been lost into the urine would be retained, increasing the
base concentration in the blood which will counteract acidity.
Method 2 – Hydrogen secretion from Potassium counter-transport (Distal Tubule)
In this system, carbon dioxide (CO2) and water (H2O) is processed and in the intercalated cell of the distal
tubule the result is the excretion of hydrogen ions (H+) into the tubular fluid and the retention of
bicarbonate (HCO3-).
1. Carbon dioxide (CO2) and water (H2O) are catalyzed by carbonic anhydrase (CA) to form carbonic
acid (H2CO3).
2. Carbonic acid (H2CO3) will freely dissociate into hydrogen ions (H+) and bicarbonate (HCO3-).
3. The hydrogen ions (H+) will be excreted via the potassium (K+) counter-transport pump. At the
same time bicarbonate (HCO3-) will be moved into the peritubular fluid and eventually into the
bloodstream using the same potassium (K+) pump as a co-transport system.
The result of this is the retention of the base bicarbonate (HCO3-) and the secretion of hydrogen ions (H+)
into the filtrate. The net effect of this process will work to increase pH and reduce the acidity of the
blood.
Method 3 – Catabolization of Glutamine (Tubules in general)
The third way the kidneys can buffer acidity is by catabolizing glutamine to form a counter-acting base
as well as a product which can “carry” hydrogen ions out of the body.
1. Glutamine is catabolized in the epithelial cells of the tubules to form bicarbonate (HCO3-) and
ammonium (NH3).
2. Bicarbonate (HCO3-) will pass into the peritubular fluid via co-transport with sodium (Na+) and
counter-transport with chloride (Cl-) ions.
3. Ammonia (NH3) in the epithelial cell will then combine with free hydrogen ions (H+) to form
ammonium (NH4+).
4. Ammonium (NH4+) will then be secreted into the tubular fluid via the sodium (Na+) countertransport system.
The end result of this reaction is the net secretion of hydrogen ions (H+) into the urine and the
conservation of bicarbonate (HCO3-).
9. Interpret laboratory results on acid-base status
Interpretation of the acid-base status of arterial blood gasses involves understanding:
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pH, which measures the acidity or alkalinity of the blood
Hydrogen ion (H+) concentration
Bicarbonate (HCO3-) concentration
Pressure of carbon dioxide in blood (PaCO2)
The normal blood pH is approximately 7.4. As concentrations of hydrogen ions increase, the blood
becomes more acidic and hence pH will decrease. A decrease of concentration of hydrogen ions will
increase the pH making the blood more alkaline. The presence of bases like bicarbonate will increase the
pH, though you must keep in mind that acids and bases are always present within the body and
counteracting each other. It is only when there is a disproportion of these two that you will have
abnormal readings of the acid-base status. Any situation where the arterial pH increases above 7.45
would be called alkalosis of the blood whereas any situation where the arterial pH is below 7.35 is
considered acidosis.
Additionally, there are two types of each:
 Metabolic – which is the result of the body’s inability to produce either hydrogen ions or
bicarbonate. Or because of the body’s overproduction of hydrogen ions or bicarbonate.
 Respiratory – where the body is incapable of releasing carbon dioxide, which ultimately leads to
the accumulation of hydrogen ions within the body.
Metabolic acidosis is the direct result of an increased production of hydrogen ions within the body
and/or the inability of the body to form bicarbonate. As a result, metabolic acidosis is possible if you
would find high hydrogen ion concentration and/or low bicarbonate concentration.
Metabolic alkalosis is the result of an increased production of bicarbonate and/or a decrease of
hydrogen ion concentration. When looking at the results, a high bicarbonate concentration along with a
low hydrogen ion concentration would indicate metabolic alkalosis.
Respiratory acidosis is the result of the body not sufficiently releasing carbon dioxide. Carbon dioxide
and water act to form carbonic acid – which hydrogen ions are derived from. Retaining large amounts of
carbon dioxide will encourage the formation of carbonic acid, resulting in the accumulation of hydrogen
ions. Bicarbonate however, is also derived from carbonic acid, though it’s affect on pH will not be
equivalent to that of hydrogen ions as bicarbonate will be processed further by the body. The net result
of this situation will be an acidic state. On test results, respiratory acidosis will show elevated hydrogen
ion and bicarbonate levels.
These results can be better interpreted on the image below.
Changes in blood [H+], PaCO2 and plasma [HCO3-] in acid-base disorders. The rectangle indicates limits
of normal reference ranges for [H+] and PaCO2. The bands represent 95% confidence limits of single
disturbances in human blood in vivo. When the point obtained by plotting [H+] against PaCO2 does not
fall within one of the labelled bands, compensation is incomplete or a mixed disorder is present.