Download Physiology د. نصير جواد المختار Lecture X: Acid – Base Balance The

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Physiology
Lecture X: Acid – Base Balance
The H ion concentration has always to be kept with normal range,
otherwise enzymatic activities might be affected as increasing or
decreasing the level and this might either stimulate or depress the
activity. In general the H+ concentration of extracellular fluid represented
by blood is usually considered. However in the intracellular
compartment and some other cells in the renal tubules might have higher
concentration or lower pH.
The pH is usually considered of extracellular which is about 7.357.4, however, it might be as low as 6.8 and high as 7.8. these two limits
are compatible with life.
Decreasing of pH below the normal range is known as acidosis and
increase of pH above the normal range is known as alkalosis.
Normally the body has certain mechanisms in order to bring the pH
value with normal limits, these are:
1. Buffer system.
2. Respiratory system.
3. Kidneys.
The most effective system present in the body is the buffer system,
which act within 15 sec., however if buffer system is not enough to
overcome the pH value, then the respiratory system starts to be involved
in such a case, so either the respiratory rate increase or decrease. This is
usually responding within 10 minutes and if these two mechanisms fail to
adjust the pH of the body fluid, then the kidneys will be involved to
excrete either an alkaline or an acidic urine.
Buffer System:
1. HCO3- buffer system:
The most important buffer in the body fluids, however it is not a
very powerful because it PK value is much below the pH that the body
fluids have to be adjusted.
As PK for HCO3- = 6.1 and pH is about 7.4, so if pK level was
higher we could reach the 7.4 in a less amount of alkaline substance, as
we see in the HCO3-.
2. PO4-2 buffer system:
The most powerful one, because it has a PK value which is 6.8
which is just near 7.4, however the PO4-2 buffer system is not present in
large quantities.
+
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Physiology
3. Protein buffer system:
Very powerful buffer system located in the blood.
The respiratory system usually involve when there is an increase in
+
H or decrease in pH, then respiration rate will increase and vice versa.
The kidneys usually respond after a week or more to adjust the pH,
this occurs by bicarbonate buffer system which exchanges the H + with
Na+ or vice versa, or by phosphate method, in which inside the lumen
there is a component of NaNaHPO4, so the H+ in the cells comes from
H2CO3 and Na+ in the lumen comes from NaNaHPO4, so exchange
occurs.
Na+
HCO3
-
CO2
Cell
Lumen
Na
NaNaHPO4
HCO3- + H+

H2CO3

CO2 + H2O
NaH2PO4
Or by ammonia buffer, from which ammonia comes from Glycine
which is found in the cells and H+ comes from the H2CO3 in the cells, as
NH3 combines with Cl in NaCl to form NH4Cl, the H+ is exchanged with
Na+ and this is mentioned as below:
Na
Na+
HCO3
CO2
-
HCO3- + H+

H2CO3

CO2 + H2O
NH3

Glycine
2
NaCl (Na + Cl)
H+
NH3
NH4Cl
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Physiology
In acidosis subjects die from coma, while alkalosis patient might
die in tetany because alkalosis cause hyperexitation of nervous system.
Hyperventilation usually causes alkalosis due to the wash out of
CO2, while hypoventilation causes acidosis due to the accumulation of
CO2.
Acidosis and alkalosis can be classified as:
1. Metabolic acidosis or alkalosis.
2. Respiratory acidosis or alkalosis.
Metabolic acidosis occurs due to increase in acids other than CO2,
such as sulfuric acid and acetoacetic acid.
Metabolic alkalosis and acidosis usually compensated by
respiratory system, so a metabolic acidosis is usually associated with an
increase in the rate of respiration in order to assist wash out excess CO 2
and the same for metabolic alkalosis which is causes the decrease of the
rate of respiration to accumulate CO2.
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Physiology
Autoregulation of renal blood flow:
Below a mean hydrostatic pressure of 80 mmHg, filtration is
directly proportional to the pressure and the flow is also proportional to
the pressure. However, when the mean arterial pressure is increased, there
is only slight increase in the blood flow in order to adjust the rate of
filtration. This is because there is especial system that can regulate renal
blood flow. There are two hypothesis for adjusting renal blood flow:
1. Myogenic hypothesis.
2. The contribution of the juxtaglomerular apparatus.
1. Myogenic hypothesis:
When the hydrostatic pressure increase, blood flow in the afferent
arterioles also increase and this causes an increase in the rate of filtration.
However, this usually doesn’t occur except for a fraction of a second, as
in the wall of the afferent arterioles there are a certain receptors that are
very sensitive for any increase in the flow and so when there is an
increase in flow, these receptors cause a constriction in the walls of the
afferent arterioles in an attempt to decrease flow.
According to this myogenic hypothesis there are 3 phases involved
in this process:
A: → A sharp increase in flow.
B: → A sharp decrease in flow.
C: Gradual adjust to normal flow.
The sharp increase in flow is due to change of hydrostatic pressure.
The sharp decrease on the other hand, is due to strong concentration in
the walls of the afferent arterioles caused by their receptor, but this makes
the rate of filtration below normal, so there is gradual relaxation flows to
reach the adjusted normal flow. These three phases takes about 10-15
seconds.
The Juxtaglomerular Apparatus:
When renal blood flow increase, filtration also increase and so the
rate of the flow of filtration inside the tubules increase. At the end of the
distal tubules there is an area known as the macula densa which is very
sensitive to the increase in the flow and together with certain cells on the
walls of the afferent arterioles they form what known as the
Juxtaglomerular apparatus.
When the cells of the apparatus are stimulated they cause the
release of rennin, this rennin will then combine with plasma fraction
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Physiology
protein forming potent vasoconstrictor that affect on the afferent
arterioles adjust renal blood flow to the normal level.
In addition to that there are many substances that may be cause
vasoconstriction such as epinephrine, norepinephrin, prostaglandine and
so on, but the degree of contribution is not clear.
Glomerular Filtration Rate (GFR):
The rate at which blood is filtered in the glomerulus per min. is
known as glomerular filtration rate (GFR) which is about 125 ml/min.
Measurement of GFR:
The clearance of a substrate A is the volume of plasma that can be
cleared of A in one minute.
C = Clearance, UA = Concentration of A in urine
V = Volume of urine, PA = Concentration of A in plasma
In order to measure the GFR we chose a substance that should be
completely filtered and not absorbed at all. The substance which satisfy
this, the Inulin.
Inulin is a substance that completely filtered, but not reabsorb, so
its clearance will equal to GFR.
Every substances has its own clearance depending on the degree of
reabsorption and excretion. For example urea has clearance of ????
because urea is completely filtered but is reabsorbed and secreted. The
glucose on the other hand has a clearance of zero because it is usually
filtered, but is completely reabsorbed.
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