Acid-base Balance:- Part 2 – Metabolic acidosis, Metabolic Alkalosis, and Anion Gap
Metabolic Acidosis, Metabolic Alkalosis
What sample is needed for acid-base balance?
- The better choice is the Radial artery.
- The sample may be taken from the femoral artery or brachial.
 - Blood can be drawn from the indwelling arterial line.
 
 - The tests are done immediately because oxygen and carbon dioxide are unstable.
- Place the sample on ice and immediately transfer it to the lab.
 
 - Arterial blood is better than venous blood.
 - For a venous blood syringe or tube, be filled, and apply a tourniquet for a few seconds.
 - Arterial blood is risky, and a trained person should do it.
- Never apply a tourniquet.
 - Don’t apply the pull to the plunger of the syringe.
 
 
What are the indications for Acid-base Balance?
It is advised in:
- Diabetes mellitus.
 - Starvation.
 - Lactic acidosis.
 - Ingestion of NH4CL, ethylene glycol, methanol, salicylates, and paraldehyde.
 - In the case of diarrhea.
 - In the case of renal failure.
 - In the case of proximal tubular acidosis.
 
What are the precautions for the collection of blood?
- Avoid pain and anxiety in the patient, which will lead to hyperventilation.
- Hyperventilation due to any cause leads to decreased CO2 and increased pH.
 
 - Keep blood cool during transit.
 - Don’t clench your finger or fist. This will lead to lower CO2 and increased acid metabolites.
 - pCO2 values are lower in the sitting or standing position than in the supine position.
 - Don’t delay the performance of the test.
 - Avoid air bubbles in the syringe.
 - Excess of heparin decreases the pCO2 by maybe 40% less.
 - Not mixing the blood properly before the test may give a false result.
 - A prolonged tourniquet or muscular activity decreases venous pO2 and pH.
 - The best way to collect arterial or venous blood is anaerobic.
 - Arterial blood precautions:
- Only syringe and needle, no tourniquet, no pull on the plunger.
 
 - Venous blood precautions:
- The needle and syringe of the heparinized evacuated tube were filled and drawn a few seconds after the tourniquet.
 - Liquid heparin is the only suitable anticoagulant with the proper amount.
- Less amount will lead to clot formation.
 - The increased amount will lead to increased CO2 and a decrease in pH.
 - This will lead to a dilutional error.
 
 
 - Glass collection devices are better than plastic.
 
How will you define acid-base balance?
- This regulation of the extracellular fluid environment involves the ratio of acid to base, measured clinically as pH.
- Physiologically, all positively charged ions are called acids, and all negatively charged ions are bases.
 
 - Physiological changes in the concentration of H+ ions in the blood lead to acid-base balance.
 - A systemic increase in the concentration of H+ ions is called acidosis.
 - A systemic decrease in the H+ ions is called alkalosis.
 - The acid-base must be regulated within a narrow range for the body to function normally.
- A very slight change in the pH will affect the body.
 - A slight change in the H+ ions can change the cell and tissue.
 
 
Why H+ ions are needed?
- To maintain the integrity of the membrane.
 - Speed of the metabolic reactions.
 - Any change in the pH will lead to more harmful effects than other diseases.
 - The symbol pH represents the power of H+.
 - When pH changes, one unit, like 7.0 to 6.0 = [H+] [H+] = H+ ions, the concentration changes 10-fold.
 
What is the mechanism of body acid formation?
- Metabolism of proteins.
 - Metabolism of Carbohydrates.
 - Metabolism of fats.
 - This must be balanced by the number of basic substances in the body to maintain the normal pH.
- Lungs, kidneys, and bones are the major organs involved in regulating acid-base balance.
 
 
What are the various Buffer Systems?
| Buffer system (pairs) | Buffer system | Buffer reaction | Mechanism | 
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 (Carbonic acid/bicarbonate buffer system)  | 
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- Acid-base control by the various organs of the body.
 
What is the pH of different body fluids?
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What is the significance of pH in our life?
- For normal body functions, the pH range is very narrow and needs to be maintained within these limits.
 
| pH value | Effects on the body | 
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What are the types of Acid-base balance?
- H+ ions and electrolytes disturbances may be:
- Acute.
 - Chronic.
 - Modest or severe.
 - Simple or mixed.
 
 - When there is an accumulation of H+ ions, it is called acidosis.
- When blood pH declines below 7.3, this process is called acidemia.
 
 - Alkalemia. When there is a deficiency of H+ ions, it is called alkalosis.
- Blood pH rises above 7.45.
 
 - Conditions related to the respiratory system lead to respiratory acidosis or alkalosis.
 - There are metabolic conditions related to the kidneys, and abnormal intake/output leads to metabolic acidosis/alkalosis.
 
What is the importance of blood pH?
- It is normally maintained at 7.38 to 7.42. Any deviation from this range indicates a change in the concentration of H+ ions.
 - Blood pH is a negative logarithm of [H+], as shown in the following equation:
- pH = log10 [H+]
 - This equation shows that an increase in the H+ ions leads to a fall in the blood pH, which is called acidemia.
 - So, a decrease in the H+ ions will lead to an increase in the blood’s pH, which is called alkalemia.
 - The conditions that cause the pH change are called acidosis and alkalosis.
 
 - H+ ion changes in the blood lead to acid-base imbalance.
- A systemic increase in the H+ ions is called acidosis.
 - In the case of acidemia, the pH of the arterial blood is <7.4.
 
 - In alkalemia, the pH of the arterial blood is >7.4.
- Alkalosis is a systemic decrease in the H+ ions in the systemic blood.
 
 - The following diagram explains how pH is maintained by the arterial carbon dioxide tension (pCO2) and plasma bicarbonate (HCO3–).
 
- Plasma HCO3– decreases in the plasma caused by gastrointestinal or renal losses will increase H+ ions and lower the pH.
 
What is the Anion gap?
How will you define the anion gap?
- Anion gap refers to anions usually not measured in the laboratory, like sulfate, phosphate, and lactate.
 - The anions usually measured are Chloride (Cl–) and bicarbonate (HCO3–).
 - The sum of the anions is subtracted from the sum of cations (Na+ ); there is a gap of around 10 to 12 meq/L called an anion gap. An elevated anion gap gives clues for acidosis.
 - The anion gap is measured in meq/L.
 - This is the difference between the plasma concentration of the major cation sodium (Na+) and that of the other anions, HCO3—and Cl–.
- Anion gap = [Na+] – ([HCO3–] + [Cl–])
 
 - The normal anion gap is 3 to 13 meq/L, and the mean is 10 meq/L.
 - This is dependent mainly on the plasma protein, primarily albumin.
 - 2.5 meq/L falls for every 1 gram/dl of albumin concentration in the blood.
 - The anion gap is important in identifying the etiology of metabolic acidosis.
 
What causes a high anion gap (>12 meq/L)?
- Methanol toxicity.
 - Uremia due to renal failure.
 - Starvation.
 - Diabetes mellitus (ketoacidosis).
 - Lactic acidosis.
 - Salicylates toxicity.
 - Ethyl alcohol toxicity.
 - Isoniazid toxicity.
 - Iron toxicity.
 
What causes a decreased anion gap (<6 meq/L)?
- Hypoalbuminemia.
 - Plasma cell disorders.
 - Bromide intoxication.
 
What causes the normal anion gap (6 to 12 meq/L)?
- Intestinal fistula.
 - Pancreatitis.
 - Renal tubular acidossis.
 - Acid and chloride administration:
- NH4Cl and HCL for the treatment of severe metabolic acidosis.
 - Hyperalimentataion.
 
 - Bicarbonate or other alkali losses:
- Diarrhea.
 - Recovery from ketoacidosis.
 
 
Metabolic acidosis
How will you define metabolic acidosis?
- Metabolic acidosis occurs whenever there is a primary decrease in the HCO3¯ in the blood.
 - This may occur due to:
- Exogenous acid administration.
 - Endogenous acid production.
 - Impaired renal H+ secretion.
 - HCO3– losses from the kidney or in the gastrointestinal secretions.
 
 
What are the causes of metabolic acidosis?
- In metabolic acidosis, noncarbonic acid increases, or HCO3¯ is lost from the extracellular space.
- The buffering system becomes active and maintains the pH.
 - In case of the buffering system’s failure, the anion gap HCO3¯: H2CO3 = 20:1 changes.
 
 - Increased noncarbonic acid with an elevated anion gap and Increased H+ load:
- Diabetes mellitus with ketoacidosis. There is a production of acetoacetic acid and β-hydroxybutyric acid in diabetic acidosis.
 - In the case of starvation.
 - Lactic acidosis in shock and hypoxemia. There is the production of lactic acid.
 - Ingestion of drugs like NH4CL, salicylates, methanol, ethylene glycol, and paraldehyde.
 
 - Decreased H+ ions excretion was seen in:
- Uremia.
 - Distal renal tubular acidosis (decreased renal H+ secretion).
- There is an accumulation of the acid that consumes the bicarbonate (HCO3¯).
 
 
 - Bicarbonate (HCO3¯) loss from the extracellular space and normal anion gap:
- Renal failure.
 - Diarrhea.
 - Proximal tubular acidosis (there is renal HCO3¯ loss).
- Plasma HCO3¯ falls, associated with a rise in the concentration of the inorganic anions, mostly CL¯ or a fall in Na+ concentration.
 
 
 
What are the biochemical changes in metabolic acidosis?
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How is there compensation for metabolic acidosis?
- Hyperventilation by rapid breathing from the lungs will blow off CO2.
 - Kidneys will conserve HCO3¯ and eliminate H+ ions in the urine, where urine will be acidic.
 
What are the signs and symptoms of metabolic acidosis?
- Kussmaul respiration suggests metabolic acidosis.
 - The early symptoms are headache and lethargy.
 - There is anorexia, nausea, vomiting, diarrhea, and abdominal discomfort.
 - If acidosis progresses, then ultimately, the end is death.
 - The patient can have neurological, respiratory, gastrointestinal, and cardiovascular signs and symptoms.
 - Deep rapid respiration indicates respiratory compensation.
- There is increased tidal volume rather than respiratory rate, which characterizes these ventilatory changes resulting from the low pH stimulating the brain stem respiratory center.
 
 - Decreased blood pH leads to:
- Decreased myocardial contraction, causing decreased blood pressure.
 - Arterial vasodilatation.
 - pH below 7.15 to 7.20, the effect of acidemia is prominent.
 
 - Ketoacidosis is associated with increased thirst and polyuria.
 - There is secondary hypotension in severe acidotic patients.
 - Severe acidosis produces life-threatening dysrhythmias, like ventricular fibrillation.
 - Ultimately, the patient will go into a coma.
 
How will you diagnose metabolic acidosis?
- Take the history of the patient.
 - There are clinical signs and symptoms.
 - Lab. findings are:
- pH = <7.35. (low pH).
 - HCO3¯ = <24 meq/L (low plasma bicarbonate).
 - Anion gap = >14 meq/L  seen in:
- High-anion metabolic acidosis.
 - Lactic acidosis.
 - Ketoacidosis.
 - Asprin over-dose.
 - Renal failure.
 - Overuse of alcohol.
 
 - Anion gap = 12 meq/L or less is seen in:
- Increased acid load.
 - Rapid I/V saline administration.
 - Other diseases are characterized by HCO3– loss.
 
 
 - Urine pH = <4.5 in the absence of renal disease.
 - Lactic acid = Increased (in lactic acidosis).
 - There may be concomitant hypokalemia or hyperkalemia, which helps in the diagnosis.
 
How will you treat metabolic acidosis?
- Until arterial pH falls below 7.15 to 7.20, acidemia’s adverse effect is usually compensated for by elevated plasma catecholamines.
 - In case of severe acidosis, give NaHCO3 to elevate the pH.
 - Correct the sodium and water deficiency.
 - Give lactate ringer solution.
 - Correct the electrolyte imbalance.
 - Try to treat the underlying cause of the acidosis.
 - In case mechanical ventilation may be needed.
 - May need dialysis for patients with renal failure.
 - Needs antibiotics to treat the infection.
 
Metabolic Alkalosis
How will you define metabolic alkalosis?
- There is excessive loss of metabolic acids.
 - An increase in the plasma HCO3‾.
 - An arterial pH >7.4 leads to metabolic alkalosis.
 
What are the causes of metabolic alkalosis?
- This common condition is often induced by diuretic therapy or loss of gastric secretions (in vomiting or nasogastric suction).
 - This condition is caused by:
- There must be an initial increase in the HCO3— level caused by the loss of H+ ions in the gastrointestinal secretions or the urine.
 - H+ ions move into the cell.
 - Akali administration.
- Volume contraction around a relatively constant amount of extracellular HCO3-.
 
 
 - One of the following factors in case of absence of renal failure to maintain high HCO3–:
- Chloride (Cl–) depletion.
 - Hypochloremia or hypokalemia.
 - Effective circulating volume depletion.
 
 - This occurs in the acid loss by vomiting or nasogastric suction.
- Pyloric or upper duodenal obstruction.
 - In the case of villous adenoma.
 
 - Prolonged diuretic therapy.
 - Cystic fibrosis.
 - Primary Hyperaldosteronism leads to retention of the NaHCO3 and loss of H+ and K+.
 - Secondary hyperaldosteronism.
 - Bilateral adrenal hyperplasia.
 - Congenital adrenal hyperplasia.
 - Cushing’s syndrome.
 - Pituitary adenoma secreting ACTH (Cushing’s syndrome).
 - Exogenous cortical therapy.
 - Excessive licorice ingestion.
 - Diuretics also produce mild alkalosis because they produce more Na+, K+, and CL¯ excretion than HCO3¯.
 - Milk-alkali syndrome.
 - Massive blood transfusion.
 - High doses of carbenicillin or penicillin.
 
What are the changes in metabolic alkalosis?
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How will you summarize metabolic alkalosis?
- Before alkalosis, the HCO3: H2CO3 ratio was 20:1.
 - Then pH increases, PCO2 no change, and HCO3¯ also increases.
- HCO3: H2CO3 = 40 :1
 
 - HCO3¯ increases because of the loss of CL¯ ions or excess ingestion of NaHCO3.
 
What is the compensatory mechanism of metabolic alkalosis?
- Breathing will be suppressed to hold the CO2.
- The increase in the pH depresses the respiratory center, causing CO2 to be retained, which will increase H2CO3 and CO2.
 
 - The kidney will conserve H+ ions and excrete more HCO3¯ in the urine, which will be alkaline.
 
What are the signs and symptoms of metabolic alkalosis?
- The patients are irritated, twitching, and confused.
 - There are nausea, vomiting, and diarrhea.
 - Some patients may have severe cramping, paresthesia, or even tetany, but in others with similar electrolytes, data have no such S/S; the reason is unknown.
 - Ask about the history of vomiting or diuretic therapy.
 - There is a weakness.
 - There are muscle cramps.
 - There are hyperactive reflexes.
 - There is shallow and slow respiration. There are cyanosis and apnoea.
 - There will be tetany.
 - The patient will have confusion and convulsions.
 - There are cardiovascular abnormalities due to hypokalemia.
- Ultimately, the patient will have atrial tachycardia.
 
 
How will you diagnose metabolic alkalosis?
- The arterial blood shows increased pH and HCO3¯.
 - pH = >7.45.
 - HCO3– = >29 meq/L.
 - K+ = <3.5 meq/L (low).
 - Calcium (Ca++)= <8.9 mg/dl.
 - Chloride (Cl–) = <98 meq/L.
 - There may be an increased anion gap.
 - Measurement of the Na+ in a random urine sample differentiates urinary volume depletion Na+ <20 meq/L and euvolemic Na+ >40 meq/L.
- Metabolic alkalosis is the condition in which volume depletion may not lead to a low urinary Na+.
 - The capacity to retain the Na+ in this situation may be antagonized by the need to excrete HCO3– (as Na+ salt) to correct the alkalosis.
 - In such cases, a random urinary Cl– determination is more useful.
 
 
How will you summarize metabolic alkalosis?
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How will you treat metabolic alkalosis?
- In the case of mild alkalosis, the patient can tolerate it.
 - In the case of severe cases of pH >7.6, urgent treatment is needed.
 - Can give KCl and normal saline.
 - Discontinue diuretics and supplementary KCl.
 
How will you summarize the characteristic features of acidosis and alkalosis?
| Clinical condition | Etiology of the condition | pH (7.37 to 7.43) | HCO3– (19 to 25 meq/L) | pCO2 (38 to 42 mmHg) | 
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What are the Panic values?
| Clinical parameter | Panic value | 
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What are the parameters needed for the acid-base balance?
| Lab test | Importance | 
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How will you summarize metabolic and respiratory acidosis/alkalosis?
| Clinical condition | pH | HCO3– | pCO2 | 
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| Acute metabolic acidosis | Decreased | Decreased | Normal | 
| Compensated metabolic acidosis | Normal | Decreased | Decreased | 
| Acute respiratory acidosiss | Decreased | Normal | Increased | 
| Acute compensated respiratory acidosis | Normal | Increased | Increased | 
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| Acute metabolic alkalosis | Increased | Increased | Normal | 
| Chronic metabolic alkalosis | Increased | Increased | Increased | 
| Acute respiratory alkalosis | Increased | Normal | Decreased | 
| Compensated respiratory alkalosis | Normal | Decreased | Decreased | 
Questions and answers:
Question 1:  What is the panic value in acid-base balance?
Question 2:  What are decreased anion gap causes.
                        






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