Regulation of Acid-Base Balance
To achieve homeostasis, there must be a balance between the intake or production of H+ and the net removal of H+ from the body.Hydrogen ion concentration is precisely regulated
The activities of almost all enzyme systems in the body are influenced by H+ concentration. The H+ concentration of the body fluids normally is low level; only 0.00004 mEq/L, and within tight limits (Normal variations are about 3 to 5 nEq/L), so any small changes in H+ concentration affect cell various functions, but under extreme conditions, the H+ concentration can vary from as low as 10 nEq/L to as high as 160 nEq/L without causing death.
Acids and basestheir definitions and meanings
A hydrogen ion is a single free proton released from a hydrogen atom.
Acid: is the molecule containing hydrogen atom that can release hydrogen ions in solutions (e.g. HCl, carbonic acid).
A base: is an ion or a molecule that accept an H+ (e.g. HCO3, HPO4= & protein due to some of its amino acids accept H+).
Acidosis : excess addition of H+ to body fluids.
Alkalosis: excess removal of H+ from the body fluids.
A strong acid is rapidly dissociate & releases large amounts of H+ in solution (HCl).
A weak acid is weakly dissociate & release H+ with less force (H2CO3).
A strong base reacts rapidly & strongly with H+ and, quickly removes it from a solution (OH reacts with H+ to form water H2O).
A weak base binds with H+ weakly (HCO3).
Mostly weak acids and weak bases (buffers) in ECF are involved in normal acid-base regulation.
pH : Due to small H+ concentration, it is better to use pH unit which is inversely related to the H+ concentration as:
pH= log[H+ ] = 7.4
A low pH refers to a high H+ concentration, and a high pH refers to a low H+ concentration.
●The normal pH of arterial blood is 7.4. Acidosis means the pH falls below 7.4 and alkalosis means the pH rises above 7.4. The lower limit of pH at which a person can live more than a few hours is about 6.8, and the upper limit is about 8.0.
The pH of venous blood and interstitial fluids is about 7.35 because of the extra amounts of carbon dioxide (CO2) released from the tissues to form H2CO3 in these fluids.
Intracellular pH usually is slightly lower than plasma pH because the metabolism of the cells produces acid, especially H2CO3. Depending on the type of cells, the pH of intracellular fluid range between 6.0 and 7.4.
The urine pH ranges from 4.5 to 8.0, depending on the acid-base status of the extracellular fluid.
Gastric HCl pH= 0.8
Defenses against changes in hydrogen ion
There are three primary systems that regulate the H+ concentration in the body fluids to prevent acidosis or alkalosis:
(1) The chemical acid-base buffer systems of the body fluids, which immediately (within a fraction of a second) combine with acid or base to prevent excessive changes in H+ concentration. Buffer systems do not eliminate H+ from or add them to the body but only keep them tied up until balance can be re-established.
(2) The respiratory center, which regulates the removal of CO2 (and, therefore, H2CO3) from the extracellular fluid (act within a few minutes).
●These first two lines of defense keep the H+ concentration from changing too much until the more slowly responding third line of defense.
(3) The kidneys, excrete either acid or alkaline urine, thereby readjusting the extracellular fluid H+ concentration toward normal during acidosis or alkalosis. Although the kidneys respond slowly over a period of hours to several days, they are the most powerful acid-base regulatory systems.
(1) The chemical acid-base buffer systems of the body fluids
a- bicarbonate buffer system
The bicarbonate buffer system consists of a water solution that contains two ingredients:
(1) a weak acid, H2CO3, and
(2) a bicarbonate salt, such as NaHCO3 (weak base).
H2CO3 is small amounts formed in the body by the slow reaction of CO2 (from metabolism) with H2O unless the enzyme carbonic anhydrase is present (in the walls of the lung alveoli, epithelial cells of the renal tubules).
H2CO3 ionizes weakly to form small amounts of H+ and HCO3.
When a strong base as sodium hydroxide (NaOH) is added to the bicarbonate buffer solution.
So, H2CO3 combines & buffer the OH from the NaOH to form NaHCO3. Thus, the weak base NaHCO3 replaces the strong base NaOH & decreases its effect. At the same time, the concentration of H2CO3 decreases (because it reacts with NaOH), causing more CO2 to combine with H2O to replace the H2CO3.
CO2 + H2O (H2CO3((HCO3 + H+
+NaOH +Na
So blood CO2((inhibits respiration and decreases the rate of CO2 expiration. The rise in blood HCO3 that occurs is compensated for by increased renal excretion of HCO3.
The second component is bicarbonate salt, as sodium bicarbonate (NaHCO3) in the extracellular fluid. NaHCO3 dissociate to form HCO3 and Na+.
When a strong acid such as HCl is added to the bicarbonate buffer solution, the increased H+ released from the acid
(HCl ( H+ + Cl) is buffered by HCO3.
(H+ + HCO3 ( H2CO3 ( CO2 + H2O
So H+ from the strong acid HCl reacts with HCO3 to form the very weak acid H2CO3, which in turn forms CO2 and H2O.The excess CO2 greatly stimulates respiration, which eliminates the CO2 from the extracellular fluid.
Henderson-Hasselbalch Equation
For any acid, the concentration of the acid relative to its dissociated ions is defined by the dissociation constant K which can be expressed in a similar manner to pH.
pK = log K
PH=Pk + log HCO3/ (0.03*PCO2)
Note: (PCO2 in this pH equation come instead of CO2 which in turn come instead of H2CO3 which cannot be measured in solution because it rapidly dissociates into CO2 and H2O.)
The Henderson-Hasselbalch equation advantage:
1- Calculation the pH of a solution.
2- An increase in HCO3 indicates alkalosis. An increase in PCO2 indicates acidosis.
3-Provides insight about which system control acid and base of the ECF as by lung or by kidney relative to PCO2 increases or HCO3– increases respectively.
●“Buffer Power” The buffer system is most effective where the pH is near the pK of the system (e.g. when each of the components bicarbonate buffer system (HCO3 – and CO2) constitutes 50 % of the total concentration of the buffer system. But it is still effective for 1.0 pH unit on either side of the pK.
●For the bicarbonate buffer system, the pK is 6.1. & its effective extends from a pH of about 5.1 to 7.1 units. Beyond these limits, the buffering power rapidly diminishes. And when all the CO2 convert to HCO3 or vice versa, the system has no more buffering power. Also a low concentration of a buffer decreases its power.
●Bicarbonate buffer system is the most important and powerful extracellular buffer despite these characteristics:
(1- the gap between the ECF pH (7.4) & its pK (6.1).
2-the concentrations of both CO2 and HCO3 –, are not great.
This due to the fact that HCO3 and CO2, are regulated, respectively, by the kidneys and the lungs, as discussed later.
b- Phosphate Buffer System
The main elements of the phosphate buffer system are H2PO4 and HPO4= (both are weak).
The phosphate buffer system has a pK of 6.8, it is important in the tubular fluids of the kidneys & intracellular fluid because the concentration of phosphate in these fluids is many times that in the ECF & the pH of these fluids is lower than that of ECF, bringing the operating range of the buffer closer to the pK (6.8) of the system. Its concentration in the ECF is low and less than that of the bicarbonate buffering system.
C-Proteins buffer system
It is important intracellular buffers because:
1- Proteins have high concentrations in the body especially within the cells. Approximately 60 to 70 % of the total chemical buffering of the body fluids is inside the cells, and most of this results from the intracellular proteins.
2- Its power due to the fact that the pKs of many of these protein systems are close to 7.4.
The pH in intracellular fluid changes, when there are changes in extracellular pH due to the diffusion of H+, HCO3 & CO2. The slowness diffusion of H+ and HCO3 through the cell membranes delays the maximum ability of the intracellular proteins to buffer extracellular acid-base abnormalities for several hours. CO2, however, can rapidly diffuse through all the cell membranes.
●Hemoglobin (Hb) is an important buffer in the red blood cell, as follows:
H+ + Hb HHb
In the red blood cells there is rapid equilibrium occur.
●So the blood buffers are plasma protein and Hb.
Isohydric Principle:
All buffers in the body fluids work together. They are in equilibrium with the same hydrogen ion concentration because H+ is common to the reactions of all the systems. Therefore, whenever there is a change in H+ concentration in the ECF, the balance of all buffer systems changes at the same time by shifting H+ back and forth between them.