Different kinds of biological fluids exist within the human body. These can be found in the intracellular and extracellular fluid compartments, respectively. Plasma is stored in the vascular compartment. Interstitial (including lymphatic), cerebral, pleural, pericardial, and gastrointestinal fluids are all included in the extravascular compartment. All body fluids have critical functions, such as delivering oxygen and nutrition to tissues and removing metabolic waste. They also offer a setting for biological processes to occur. In clinical practice, bodily fluids are tested to see whether there are any electrolyte or hormone imbalances.
Mechanisms that maintain normal pH values
Biochemical processes in the body create huge amounts of acid on a daily basis. In a 24-hour timeframe, these processes result in the production of 40-80 mmol of hydrogen ions. The oxidation of sulphur-containing amino acids produces these ions. Excess acid is excreted through the kidneys and excreted in the urine. The proteins in the body also act as a buffer. The acidity (i.e. hydrogen ion concentration) of an aqueous solution, such as blood and other bodily fluids, is measured by pH. A sample of blood obtained from the radial artery is used to measure it in arterial blood gas analysis. The lower the pH, the more hydrogen ions are present, and the arterial blood becomes more acidic.
A higher pH, on the other hand, denotes a basic solution. Because the most of enzymes and biochemical activities in the body function best near to pH 7, pH must be kept within limited ranges (7.35–7.45) in biological systems.
|Type of acid||Production||Rate of|
|Disposal||Rate of disposal|
|Carbon dioxide||Tissue respiration||20,000||Excretion by lungs||20,000|
|Fatty acids||Lipolysis||600||Re-esterification and|
|H+ from urea synthesis||Ureagenesis||1100||Oxidation of amino acids||1100|
|Sulphuric acid||Metabolism of|
In instances where the pH of physiological fluids is likely to vary, a buffer reduces the amount to which hydrogen ion concentration modulates the pH. The pH of blood, intracellular fluid, and extracellular fluid is balanced through buffering. There are four buffer systems in the human body. A weak acid, that is, one that only partially dissociates into hydrogen ions, and its conjugate base make up a buffer (anion). As a result, adding a strong acid or basic to such a solution has little effect on its pH.
|Bicarbonate–carbonic acid||Carbonic acid is a weak acid|
H+ combines with
bicarbonate to form carbonic
acid via carbonic anhydrase
buffer in blood
|Phosphate||Mono- and di-hydrogen|
phosphate combine with H+
to enable efficient buffering
of H+ in urine
Present in very low
concentrations in blood to
|Urine||Major buffer in urine|
|Proteins||Contain weak acidic and|
basic groups and therefore
can buffer H+
buffer in blood
Major intracellular and
|Bone||H+ is buffered by proteins|
within bone matrix
Increased H+ stimulates
bone resorption and alkaline
minerals act as buffers
in chronic acidosis (e.g.
chronic kidney disease)
There are numerous causes of acid−base imbalances. These causes can be divided into four types:
Alveolar hypoventilation causes respiratory acidosis, which is an imbalance in acid-base balance. Carbon dioxide is generated rapidly, and a lack of ventilation raises arterial carbon dioxide partial pressure (PaCO2). PaCO2 levels rise as a result of alveolar hypoventilation (hypercapnia). The bicarbonate (HCO3–)/PaCO2 ratio falls as PaCO2 rises, lowering pH. Hypercapnia and respiratory acidosis occur when ventilation is compromised and the respiratory system eliminates less carbon dioxide than is generated in the tissues.
Respiratory acidosis is most frequently caused by a lung disease or by a condition that affects normal breathing or impairs the lung’s ability to remove CO2.
Lung disorder causes include:
- Chronic bronchitis
- Severe asthma
Neuromuscular causes include:
- Diaphragm dysfunction and paralysis
- Guillain-Barré Syndrome
- Myasthenia Gravis
- Muscular dystrophy
- Motor neurone disease.
Chest wall causes include:
- Severe kyphoscoliosis
- Status post thoracoplasty
- Flail chest
Central nervous system (CNS) depression causes include:
- Drugs (e.g. narcotics, barbiturates, benzodiazepines, and other CNS depressants).
Neurologic causes include:
- Brainstem disease and trauma
- Brain tumour or abscess.
Other causes include:
- Obesity-hypoventilation syndrome
- Obstructive sleep apnoea
- Lung-protective mechanical ventilation with permissive hypercapnia in the treatment of acute
- respiratory distress syndrome (ARDS).
Respiratory alkalosis occurs when the acid-base balance is disrupted by alveolar hyperventilation, resulting in a reduction in arterial carbon dioxide partial pressure (PaCO2). Reduced PaCO2 raises the blood pH by increasing the bicarbonate concentration ratio. When the respiratory system removes more carbon dioxide than generated metabolically in the tissues, hypocapnia occurs.
PaCO2 has a typical range of 4.5–6 kPa (33.7–45mmHg). When hydrogen concentrations in the brain and carotid bodies are detected, chemoreceptors in the brain and carotid bodies affect breathing to alter PaCO2 and pH. When these receptors detect a rise in hydrogen ions, they accelerate respiration to ‘blow out’ the carbon dioxide and decrease hydrogen ions. Disease processes, on the other hand, might enhance ventilation, leading to hypocapnia as hyperventilation increases.
The PaCO2 level goes below the minimal threshold of normal in acute respiratory alkalosis, and the blood pH becomes alkaline. The PaCO2 level goes below the minimal limit of normal in chronic respiratory alkalosis, while the pH remains around normal or normal.
Central nervous system causes include:
- Head injury
- Cardiovascular accident (CVA)
- Anxiety (hyperventilation syndrome)
- Supra-tentorial (e.g. pain, fear, stress)
- Chronic liver failure
- Drug induced (e.g. salicylate intoxication, aminophyllines)
- Endogenous compounds (e.g. progesterone during pregnancy, cytokines during sepsis)
Hypoxemia or tissue hypoxia causes include:
- High altitude
- Respiratory stimulation via peripheral chemoreceptors
Pulmonary causes include:
- Pulmonary embolism
- Pulmonary oedema
- Chronic obstructive pulmonary disease (COPD)
Cardiac causes include:
- Myocardial infarction
Iatrogenic causes include:
- Excessive controlled ventilation
A rise in the synthesis of fixed or organic acids, which results in a drop in blood pH, is the most prevalent cause of metabolic acidosis. The bicarbonate buffer system is affected by three primary factors:
Lactic acidosis is a condition that occurs when the body produces too much acid. This is most commonly induced by either intense activity or tissue hypoxia, which is produced by anaerobic respiration within the cells.
Ketoacidosis can develop as a result of malnutrition or poorly managed diabetes. A less common reason is impaired hydrogen (H+) secretion by the kidneys (owing to renal injury). Metabolic acidosis can also be caused by diuretics that block the sodium–hydrogen transport pathway in the renal tubules. This happens because the production of H+ is related to sodium (Na+) reabsorption. The release of H+ stops when sodium reabsorption ends.
Severe loss of Bicarbonate: Bicarbonate ions are utilized to maintain the pH equilibrium within the body by balancing hydrogen ions in the carbonic acid–bicarbonate buffering system. Carbonate ions are carried into the intestine by pancreatic, hepatic, and mucosal secretions. Before the feces are evacuated, these ions are reabsorbed. When a patient has chronic diarrhoea, this reabsorption is disrupted, resulting in carbonate loss and a consequent decrease in HCO3.
Metabolic alkalosis has been linked to 50 percent of acid-base problems treated in hospitals. The incidence of vomiting, suction, and the use of diuretics in the clinical hospital environment is consistent with these findings. Patients with an arterial pH of 7.55 have a 45 percent related mortality rate, which climbs to 80 percent when the pH is over 7.65. When a severe metabolic alkalosis appears, it should be taken seriously and treated according to the underlying reasons.
- Gastric losses (vomiting, mechanical drainage, bulimia)
- Chloruretic diuretics (bumetanide, chlorothiazide, metolazone, etc.)
- Diarrheal states (villous adenoma, congenital chloridorrhea)
- Posthypercapneic state
- Dietary chloride deprivation with base loading (chloride-deficient infant formulas)
- Cystic fibrosis (high sweat chloride)
Potassium depletion/mineralocorticoid excess:
- Primary aldosteronism (adenoma, idiopathic, hyperplasia, renin-responsive, glucocorticoidsuppressible, carcinoma)
- Apparent mineralocorticoid excess
- Primary deoxycorticosterone excess (11b- and 17α-hydroxylase deficiencies)
- Drugs: licorice (glycyrrhizic acid) as a confection or flavouring, carbenoxolone
- Liddle syndrome
- Secondary aldosteronism
- Adrenal corticosteroid excess (primary, secondary, exogenous)
- Severe hypertension (malignant, accelerated, renovascular)
- Hemangiopericytoma, nephroblastoma, renal cell carcinoma
- Bartter and Gitelman syndromes and their variants
- Laxative abuse, clay ingestion.
- Hypercalcemia of malignancy
- Acute or chronic milk-alkali syndrome
- Carbenicillin, ampicillin, penicillin
- Bicarbonate ingestion (massive or with renal insufficiency)
- Recovery from starvation
When a respiratory or metabolic acid-base imbalance persists over time, the body will seek to compensate. Compensation is done by the use of an organ that is not the primary source of the impairment, and is dependent on the functioning of the lungs, kidneys, and the degree of the disturbance. If the problem is metabolic, the lungs will adjust by blowing out or holding CO2. The goal of compensation is to get the pH level back to normal. Neither the respiratory nor the metabolic systems, on the other hand, have the potential to overcompensate (cause the pH to go above its normal range).
Uncompensated, partially compensated, or completely compensated acid-base imbalances are all possible. The pH, as well as metabolic and respiratory indicators, are out of range in partially compensated gases, indicating that the body is attempting to compensate by employing the opposite organ.
Causes and compensatory effects of acid-base disturbances
|Disturbance||pH||Primary cause||Compensatory effect|
|Respiratory acidosis||Low||CO2 high||HCO3 high|
|Respiratory alkalosis||High||CO2 low||HCO3 low|
|Metabolic acidosis||Low||HCO3 low||pCO2 low|
|Metabolic alkalosis||High||HCO3 high||pCO2 high|
Interpreting arterial blood gas results
The metabolic and respiratory components that impact this balance must be evaluated when investigating acid-base disorders. The findings of arterial blood gas analysis can be interpreted using these algorithms.
Blood gas analyzers
Blood gas analyzers are used to determine the pH, partial pressure of carbon dioxide (pCO2), and partial pressure of oxygen (pO2) of bodily fluids. These indicators must be measured in order to identify the acid–base balance in the body. A rapid drop in pH and pCO2 can cause cardiac arrhythmias, ventricular hypotension, breathing issues, and even death. This emphasizes the necessity of maintaining physiological neutrality in blood and, as a result, the critical function of blood gas analyzers in clinical practice.
Blood pH measurement
It consists of three parts: a glass electrode, a reference electrode, and the liquid junction that forms between the two electrodes. By exchanging H+ ions with glass-electrode membrane metallic ions, an electrical potential difference is created. When the glass electrode measures the potential difference between the sample and the reference electrode, the difference is compared to the reference electrode’s value, which is directly proportional to the sample’s H+ level. Ag/AgCl or Hg/HgCl can be used as the reference electrode.
Measurement of Blood pCO2
The partial pressure of CO2 in blood collected anaerobically is called blood pCO2. It is measured in millimeters of mercury (mmHg) and is proportional to CO2 concentration:
pCO2 = Barometric pressure – Water vapour pressure × % CO2 /100
The water vapour pressure at 37°C is 47 mmHg, therefore 5.7 percent CO2 equates to a pCO2 of 40 mm at 750 mm barometric pressure.
Blood pO2 Measurement
The partial pressure of oxygen in blood or plasma shows the degree of oxygen exchange between the lungs and the blood, as well as the blood’s capacity to effectively perfuse the bodily tissues with oxygen in normal circumstances. A polarographic electrode is commonly used to determine oxygen partial pressure. Any element in solution has a distinctive polarizing voltage, which for oxygen is 0.6–0.9 V. The current flowing through the electrochemical cell is proportional to the oxygen content in the solution at this voltage range.
- Biochemistry et Metabolism
- Textbook of clinical chemistry
- Arterial blood gas interpretation – a case study approach
- Compendium of biomedical instrumentation