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Introduction
pH Review
pH = - log [H+] H+ is really a proton Range is from 0 - 14 If [H+] is high, the solution is acidic; pH < 7 If [H+] is low, the solution is basic or alkaline ; pH > 7
Plasma ion concentrations Ion* H+ K+ Ca++ nmoles/L 40 4,000,000 2,500,000 mEq/L 40 x 105 4 5
Mg++
Na+
1,000,000
140,000,000
2
140
*K+, Potassium ion; Ca++, calcium ion; Mg++, magnesium ion; Na+, sodium ion.
7.00
7.10 7.30 Normal
100
80 50
7.4 Alkalemia
7.52 7.70 8.00
40
30 20 10
Acids: An acid is defined as any compound, which forms hydrogen ions in solution. For this reason acids are sometimes referred to as "proton donors (H+ donors)
Bases: A base is a compound that combines with hydrogen ions in solution. Therefore, bases can be referred to as "proton acceptors (H+ acceptors, or give up OH- in solution).
Acids and bases can be: Strong dissociate completely in solution HCl, NaOH Weak dissociate only partially in solution Lactic acid, carbonic acid
Strong Acids: A strong acid is a compound that ionizes completely in solution to form hydrogen ions and a base. Example 2 illustrates a strong acid in solution, where this dissociation is complete. Weak Acids and Bases: these are compounds that are only partially ionised in solution. Example 3 shows a weak acid in solution with incomplete dissociation.
Figure 3 shows how as hydrogen ions are added to a buffer solution they combine with A- (the conjugate base) and the reaction is pushed to the left. This creates more HA whilst removing the excess H+ from the solution. Similarly, as hydrogen ions are removed from solution by addition of a strong base the reaction moves to the right restoring the hydrogen ion concentration and reducing the quantity of HA.
Homeostasis of pH is tightly controlled Extracellular fluid = 7.4 Blood = 7.35 7.45 < 6.8 or > 8.0 death occurs Acidosis (acidemia) below 7.35 Alkalosis (alkalemia) above 7.45
Most enzymes function only with narrow pH ranges Acid-base balance can also affect electrolytes (Na+, K+, Cl-) Can also affect hormones
Acids take in with foods Acids produced by metabolism of lipids and proteins Cellular metabolism produces CO2. CO2 + H20 H2CO3 H+ + HCO3-
Respiratory acids
Organic only
Carbonic Acid
Acid-base balance
Body fluid pH is significant because proteins are sensitive to pH, both in terms of their conformation and optimal range of function. pH affects membrane structure, enzyme activity, & structural proteins.
H+ concentration in body fluids is the major factor contributing to pH. + Most H is result of cellular metabolism & digestive intake pH of ECF ranges between 7.35 - 7.45
Control of Acids
1. Buffer systems 2. Respiratory mechanisms 3. Kidney excretion
1. Buffer systems
Buffer systems - substances that have the ability to bind or release H+ in solution
Weak acids that donate H+ & weak bases that absorb H+ Keeps pH of a solution relatively constant despite addition of considerable quantities of H+ or OH-. Act quickly but are temporary, do not remove H+ from body.
Take up H+ or release H+ as conditions change Buffer pairs weak acid and a base Exchange a strong acid or base for a weak one Results in a much smaller pH change
A buffer solution
A buffer solution is one in which the pH changes less when an acid or base is added than would have occurred in a non-buffer solution Such a solution contains both acidic and basic groups. A mixture of a weak acid or a weak base and a salt of that acid or base in solution is a buffer solution.
Bicarbonate buffer
Sodium Bicarbonate (NaHCO3) and carbonic acid (H2CO3) Maintain a 20:1 ratio : HCO3- : H2CO3
HCl + NaHCO3 H2CO3 + NaCl NaOH + H2CO3 NaHCO3 + H2O
HendersonHasselbalch equation
The HendersonHasselbalch equation relates blood pH to the components of the bicarbonate buffer system:
where pK is the negative log of the dissociation constant of carbonic acid and has the value 6.1
Phosphate buffer
Phosphate buffer system When pH decreases, monohydrogen phosphate ion acts as H+ acceptor When pH increases, dihydrogen phosphate ion donates H+ Phosphates are major ions in intracellular fluid and in collecting tubules of kidneys where they buffer urine
Protein Buffers
2. Respiratory mechanisms
Exhalation of carbon dioxide Powerful, but only works with volatile acids Doesnt affect fixed acids like lactic acid CO2 + H20 H2CO3 H+ + HCO3Body pH can be adjusted by changing rate and depth of breathing
3. Kidney excretion
Can eliminate large amounts of acid Can also excrete base Can conserve and produce bicarb ions Most effective regulator of pH If kidneys fail, pH balance fails
Rates of correction
Buffers function almost instantaneously Respiratory mechanisms take several minutes to hours Renal mechanisms may take several hours to days
Bicarbonate and chloride ions are transported across the red blood cell membrane in opposite directions by the bicarbonate-chloride carrier protein. The chloride shift is extremely rapid, occurring within 1 second. The chloride shift results in the chloride content of venous blood being greater than that of arterial blood.
Acid-Base Imbalances
pH< 7.35 acidosis pH > 7.45 alkalosis The body response to acid-base imbalance is called compensation May be complete if brought back within normal limits Partial compensation if range is still outside norms.
Compensation
If underlying problem is metabolic, hyperventilation or hypoventilation can help : respiratory compensation. If problem is respiratory, renal mechanisms can bring about metabolic compensation.
Acidosis
Principal effect of acidosis is depression of the CNS through in synaptic transmission. Generalized weakness Deranged CNS function the greatest threat Severe acidosis causes Disorientation coma death
Alkalosis
Alkalosis causes over excitability of the central and peripheral nervous systems. Numbness Lightheadedness It can cause : Nervousness muscle spasms or tetany Convulsions Loss of consciousness Death
Clinical states of pH disturbance (acid-base imbalance) can conveniently be divided into two groups, i.e.
(a) respiratory and (b) metabolic or non-respiratory.
The reasons for this division into respiratory and non-respiratory are that: i) the compensatory mechanisms and treatments of the two types are different.; ii) the recognition of non-respiratory disturbances is masked by compensatory alterations in PCO2 and the recognition of changes in pH caused by PCO2 changes are masked by renal compensation.
Respiratory Acidosis
Any condition that increases blood pCO2 (above 45 mmHg, pH <7.35). ex. emphysema, pneumonia, pulmonary edema This is synonymous with CO2 retention and is usually a sign of hypoventilation. Compensation is renal. There is renal loss HCl in the form of buffer or as NH4Cl. During recovery chloride has to be supplied and retained.
Causes:
Hypoventilation:
Central nervous system Peripheral nervous system Neuromuscular transmission Muscle disorders Chest wall abnormalities Lung and airway disorders.
Carbonic acid excess caused by blood levels of CO2 above 45 mm Hg. Hypercapnia high levels of CO2 in blood
Chronic conditions: Depression of respiratory center in brain that controls breathing rate drugs or head trauma Paralysis of respiratory or chest muscles Emphysema
Breathlessness Restlessness Lethargy and disorientation Tremors, convulsions, coma Respiratory rate rapid, then gradually depressed Skin warm and flushed due to vasodilation caused by excess CO2
Respiratory Alkalosis
Respiratory alkalosis - any condition that decreases blood pCO2 (below 35 mmHg, pH >7.45). This is associated with hyperventilation. Usually these are acute so there is no time for renal compensation, but if prolonged, such as in acclimatization to high altitudes, there would probably be renal compensation.
Carbonic acid deficit pCO2 less than 35 mm Hg (hypocapnea) Most common acid-base imbalance Primary cause is hyperventilation
Deliberate induced hyperventilation during anaesthesia Some causes of hypoxia associated with hyperventilation Fever Some types of C.N.S. damage Hysterical hyperventilation
Treat underlying cause Breathe into a paper bag IV Chloride containing solution Cl- ions replace lost bicarbonate ions
This (non-respiratory acidosis) is due to increase in acids (i.e. H+ donating substances) other than H2CO2 or decrease in base (i.e. H+ acceptors) in the blood. Compensation is by hyperventilation. This lowers the PaCO2 thus deducing the any pH change
Increased ventilation Renal excretion of hydrogen ions if possible K+ exchanges with excess H+ in ECF ( H+ into cells, K+ out of cells)
IV lactate solution
Metabolic Alkalosis
Alkalosis most commonly occurs with renal dysfunction, so cant count on kidneys Respiratory compensation difficult hypoventilation limited by hypoxia
Electrolytes to replace those lost IV chloride containing solution Treat underlying disorder
2.
Note whether the pH is low (acidosis) or high (alkalosis) Decide which value, pCO2 or HCO3- , is outside the normal range and could be the cause of the problem. If the cause is a change in pCO2, the problem is respiratory. If the cause is HCO3- the problem is metabolic.
3. Look at the value that doesnt correspond to the observed pH change. If it is inside the normal range, there is no compensation occurring. If it is outside the normal range, the body is partially compensating for the problem.
Example
A patient is in intensive care because he suffered a severe myocardial infarction 3 days ago. The lab reports the following values from an arterial blood sample:
pH 7.3 HCO3- = 20 mEq / L ( 22 - 26) pCO2 = 32 mm Hg (35 - 45)
Diagnosis
Metabolic acidosis With compensation