ACID-BASE REVIEW
Acid-base balance is mainly concerned with two ions: Hydrogen (H+) and Bicarbonate (HCO3−). Derangements of hydrogen and bicarbonate concentrations in body fluids are common in disease processes. Proton (H+) ion has special significance because of the narrow ranges that it must be maintained in order to be compatible with living systems.
Acid-base regulation is primarily controlled by regulation of H+ ions in the body fluids, especially extracellular fluids. Enzymes, hormones and ion distribution are all affected by hydrogen ion concentrations. Maintenance of an acceptable pH range in the extracellular fluids is accomplished by three mechanisms:
- Chemical buffers: react very rapidly (less than a second)
- Respiratory regulation: reacts rapidly (seconds to minutes)
- Renal regulation: reacts slowly (minutes to hours).
Acid: It can be defined as proton (H+) donor molecules, which dissociate in solution to release H+. Physiologically important acids include: carbonic acid (H2CO3), phosphoric acid (H3PO4), pyruvic acid, and lactic acid. These acids are dissolved in body fluids.2
Base: It can be defined as a proton (H+) acceptor molecule capable of accepting proton. Physiologically important bases include: bicarbonate (HCO3−), and biphosphate (HPO4−2).
pH scale: Expresses hydrogen ion concentration in water solutions. Water ionizes to a limited extent to form equal amounts of H+ ions and OH− ions.
Pure water is neutral, H+ ion is an acid, and OH− ion is a base.
If concentration of H+ = concentration of OH−, pH = 7.
In acid, concentration of H+ is more than OH− concentration. i.e. pH is less than 7.
In base, concentration of H+ is less than OH− concentration. i.e. pH is more than 7.
Normal blood pH is 7.35 – 7.45
pH range compatible with life is 6.7 – 7.9
ACIDOSIS/ALKALOSIS Refers to physiological conditions in which:
- A relative increase in hydrogen ions results in acidosis
- A relative increase in bicarbonate results in alkalosis.
Carbonic acid (H2CO3) is the source of H+ ions in the body. Normal ratio of HCO3− to H2CO3 is 20:1. Deviations from this ratio are used to identify acid-base imbalances (acidosis and alkalosis).
Acid Production (volatile and fixed)
Volatile acid is CO2, which is the end product of complete oxidation of carbohydrate, fats and protein (13,000 mmol of CO2 is produced daily in normal humans) is excreted by the lung.
Fixed or metabolic acid must ultimately be excreted by kidney. Daily production is between 1 to 1.5 mEq/kg. Fixed acids are:
H2SO4 (sulfuric acid) from catabolism of sulfur containing proteins and amino acids (Cystine, and methionine).3
Organic acids are formed from catabolism of neutral foodstuffs such as carbohydrates, which yield lactic, pyruvic, and citric acid. Catabolism of fats yields beta-hydroxybutyrate).
H3PO4 (Phosphoric acid) is formed during hydrolysis of phosphoesters.
Bicarbonate Production
Cells of the gastric mucosa secrete hydrogen ions (H+) into the lumen of the stomach in exchange for bicarbonate ions (HCO3−) that diffuse into the blood stream to maintain electrical neutrality in the parietal cell.
The direction of the diffusion of these ions is reversed in pancreatic epithelial cells, where H+ ions are secreted into the blood and bicarbonate ions diffuse into pancreatic juice.
If the two processes are balanced, there is no net change in the amount of bicarbonate in blood.
Loss of gastric or pancreatic juice can change the above balance.
Buffers in Body Fluids (Table 1.1)
Acidosis
A pH of 7.4 corresponds to a 20:1 ratio of HCO3− and H2CO3 (concentration of HCO3− is 24 mEq/liter and H2CO3 is 1.2 mEq/liter).
Acidosis is a decrease in pH below 7.35, which means a relative increase of H+ ions. Fall in pH may be as low as 7.0 without irreversible damage but any fall less than 7.0 is usually fatal.4
Acidosis may be caused by an increase in H2CO3, or a decrease in HCO3−. Both lead to a decrease in the ratio of 20:1.
Respiratory Acidosis
It is caused by hyperkapnia due to hypoventilation, characterized by a pH decrease and an increase in PaCO2 (partial pressure of carbon dioxide in arterial blood). Hyperkapnia is defined as an accumulation of carbon dioxide in extra-cellular fluids that is the underlying cause of respiratory acidosis.
Respiratory acidosis is usually the result of decreased carbon dioxide removal from the lungs, which could be the result of:
- Obstruction of air passages as in bronchial asthma and bronchospasm
- Decreased respiration (shallow, slow breathing)
- Decreased gas exchange between pulmonary capillaries and air sacs of lungs as in emphysema, bronchitis, pulmonary edema
- Collapse of lung.
Metabolic Acidosis
Any acid-base imbalance not attributable to CO2 is classified as metabolic. Metabolic production of acids or loss of bases is the result of:
- Diabetes mellitus (metabolic production of acids). Unregulated diabetes mellitus causes ketoacidosis, in this condition body metabolizes fat rather than glucose that leads to excessive production of ketones (Acetone, acetoacetic acid, and β-hydroxybutyric acid), which in turn contribute excessive numbers of hydrogen ions to body fluids.
- Chronic renal failure (retention of H+ and loss of bicarbonate)
- Strenuous exercise (anaerobic conversion of pyruvic acid to lactic acid
- Vomiting loss of excessive bicarbonate
- Diarrhea loss of excessive bicarbonate
- Malnutrition or starvation increased fat metabolism.
Alkalosis
A pH of 7.4 corresponds to a 20:1 ratio of HCO3− and H2CO3 (concentration of HCO3− is 24 mEq/liter and H2CO3 is 1.2 mEq/liter).
Alkalosis is an elevation in pH above 7.45, due to an increased 20:1 ratio HCO3− and H2CO3, which means a relative decrease of H+ ions.
Respiratory Alkalosis
It is the result of hyperventilation that eliminates excessive amounts of carbon dioxide (increased loss of CO2 from the lungs) at a rate faster than it is produced, that decreases hydrogen ions.
Hyperventilation could result from anxiety, emotional disturbances, fever, salicylate poisoning (overdose), assisted respiration, and high altitude (low PO2).
In all these situations, kidneys compensate by retaining hydrogen ions and increasing bicarbonate excretion.
Decreased CO2 in the lungs will eventually slow the rate of breathing that will permit a normal amount of CO2 to be retained in the lung.
Metabolic Alkalosis
Elevation of pH has a nonrespiratory origin, i.e. imbalance is not attributable to carbon dioxide (PaCO2). Elevation of pH is due to an increase of bicarbonate or a decrease in hydrogen ions that could result from:
- Excessive use of antacids such as sodium bicarbonate (NaHCO3)
- Vomiting that result in loss of HCl and excessive loss of H+
- Diarrhea that result in excessive loss of H+.
Body reacts to alkalosis by lowering pH through:
- Retaining CO2 by decreasing breathing rate
- Increasing the retention of hydrogen ions from kidneys.
Body's Response to Acidosis and Alkalosis
The mechanisms that protect the body against life-threatening changes in hydrogen ion concentration are:
- Buffering systems in body fluids
- Respiratory responses
- Renal control
- Intracellular shifts of ions.
BUFFERS (Table 1.1)
These are weak acids, weak bases and their associated ions that resist any significant change in pH.
Buffering systems provide an immediate response to fluctuations in pH. They ameliorate changes in H+ by accepting H+ ions. This property enables buffers to transport H+ to and from the excretory organs (kidneys and lungs). Predominant buffer system in extracellular fluid is the bicarbonate system.
Phosphate Buffering System
Phosphate buffering system is the most important in the intracellular system (Fig. 1.1). It regulates pH within the cells and the urine, because phosphate concentrations are higher intracellularly and within the kidney tubules.
Protein Buffer System
Proteins behave as a buffer in both plasma and within the cells. They can act as a buffer for both acids and bases. Protein buffer system works instantaneously making it the most powerful in the body since bicarbonate and phosphate buffer systems require several hours to be effective.
Red blood cells
Hemoglobin buffering system is of prime importance in respiratory acid-base disorders and transport of carbon dioxide (CO2) (Fig. 1.2).
H2CO3 + HBG → H/HGB + HCO3− (participates in Cl: HCO3 exchange/chloride shift)
Bicarbonate Buffer System
It is the predominant system in extracellular fluid as well the most important because the concentration of both components (carbonic acid and bicarbonate) can be regulated (Fig. 1.3).
Carbonic acid component is regulated by the respiratory system.
Bicarbonate component is regulated by the renal system.
Hydrogen ions generated by metabolism or by ingestion react with bicarbonate base to form more carbonic acid that shifts equilibrium toward the formation of acid.
Hydrogen ions that are lost (vomiting) causes carbonic acid to dissociate yielding replacement H+ and bicarbonate that shifts equilibrium to formation of base and concentration of H+ ion remain the same.
Special Role of H2CO3/HCO3 (Carbonic acid/bicarbonate) system
Since CO2 gas diffuses rapidly it is an open buffer system.
Physiological regulation is by lungs and kidneys, through buffers, and cellular exchanges of H+ and potassium (K+) (Fig. 1.4).
Respiratory Response
Neurons in the medulla oblongata and pons constitute the respiratory center.
Stimulation and limitation of respiratory rates are controlled by the respiratory center and is accomplished by responding to CO2 and H+ concentrations in the blood.
Chemosensitive areas of the respiratory center are able to detect blood concentration levels of CO2 and H+. Increases in CO2 and H+ stimulate the respiratory center, the effect is to raise respiration rates but diminish in 1–2 minutes.
Chemoreceptors are also present which respond to changes in partial pressures of O2 (PO2) and CO2 (PCO2). Increased levels of CO2 or decreased levels of O2 stimulate respiration rates to increase the overall compensatory response by:
- — Hyperventilation in response to increased CO2 or H+
- — Hypoventilation in response to decreased CO2 or H+.
Renal Response
The kidney compensates for acid-base imbalance within 24 hours and is responsible for long-term control.
The kidney in response to:
Acidosis retains bicarbonate ions and eliminates hydrogen ions.
Alkalosis eliminates bicarbonate ions and retains hydrogen ions.
Primary role of the kidney is to regulate bicarbonate [HCO3−] in extracellular fluid via 2 processes:
- Reclamation (conservation) of filtered HCO3−
- Regeneration of consumed HCO3−
Reclamation of Filtered HCO3−
About 5100 mEq of bicarbonate (HCO3−) is filtered by renal glomeruli per day. Normally, more than 95% of the filtered load is reabsorbed (conserved) by the renal tubules to prevent acidosis. Of this amount, more than 90% is reabsorbed in the proximal tubule. General characteristics of HCO3− reclamation are:
Normal plasma [HCO3−] = 25–28 mEq/L
At plasma [HCO3−] < 25 mEq/L, renal reabsorption is complete, i.e., no HCO3− is excreted.
At plasma [HCO3−] = 25–28 mEq/L bicarbonaturia ensues.
At this point, renal bicarbonate threshold is exceeded.
Regeneration of Lost HCO3− (or generation of new HCO3−)
Daily fixed acid excretion is achieved via urinary buffers. Without buffers, acid load cannot be excreted because; minimal achievable urine pH is 4. Thus, 1 L of urine would contain only 0.1 mEq H+, but more than 50 mEq H+ must be excreted to equal H+ production. Therefore, sans buffers only 0.2% of H+ load can be excreted.
Tissue Cells Response
In acidosis, H+ enters cells in exchange for K+ that regenerate HCO3− in extracellular fluid.
In alkalosis, H+ leaves cells in exchange for K+ that consume HCO3− in extracellular fluid.
Acute acidosis tends to cause hyperkalemia and acute alkalosis tends to cause hypokalemia.
But there is no good quantitative relationship between changes in K+ and changes in pH.
Plasma K+ changes are most common in metabolic disorders.
K+ changes are less predictable in respiratory disorders.
K+ changes are least likely to occur in organic acidosis (e.g. lactic acidosis).
In metabolic acidosis up to 50% of an acid load may enter intracellular fluid.