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1.6: Disorders of Acid-Base Balance - Biology

1.6: Disorders of Acid-Base Balance - Biology



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Learning Objectives

By the end of this section, you will be able to:

  • Identify the three blood variables considered when making a diagnosis of acidosis or alkalosis
  • Identify the source of compensation for blood pH problems of a respiratory origin
  • Identify the source of compensation for blood pH problems of a metabolic/renal origin

Normal arterial blood pH is restricted to a very narrow range of 7.35 to 7.45. A person who has a blood pH below 7.35 is considered to be in acidosis (actually, “physiological acidosis,” because blood is not truly acidic until its pH drops below 7), and a continuous blood pH below 7.0 can be fatal. Acidosis has several symptoms, including headache and confusion, and the individual can become lethargic and easily fatigued. A person who has a blood pH above 7.45 is considered to be in alkalosis, and a pH above 7.8 is fatal. Some symptoms of alkalosis include cognitive impairment (which can progress to unconsciousness), tingling or numbness in the extremities, muscle twitching and spasm, and nausea and vomiting. Both acidosis and alkalosis can be caused by either metabolic or respiratory disorders.

As discussed earlier in this chapter, the concentration of carbonic acid in the blood is dependent on the level of CO2 in the body and the amount of CO2 gas exhaled through the lungs. Thus, the respiratory contribution to acid-base balance is usually discussed in terms of CO2 (rather than of carbonic acid). Remember that a molecule of carbonic acid is lost for every molecule of CO2 exhaled, and a molecule of carbonic acid is formed for every molecule of CO2 retained.

Metabolic Acidosis: Primary Bicarbonate Deficiency

Metabolic acidosis occurs when the blood is too acidic (pH below 7.35) due to too little bicarbonate, a condition called primary bicarbonate deficiency. At the normal pH of 7.40, the ratio of bicarbonate to carbonic acid buffer is 20:1. If a person’s blood pH drops below 7.35, then he or she is in metabolic acidosis. The most common cause of metabolic acidosis is the presence of organic acids or excessive ketones in the blood. Table 1 lists some other causes of metabolic acidosis.

Table 1. Common Causes of Metabolic Acidosis and Blood Metabolites
CauseMetabolite
DiarrheaBicarbonate
UremiaPhosphoric, sulfuric, and lactic acids
Diabetic ketoacidosisIncreased ketones
Strenuous exerciseLactic acid
MethanolFormic acid*
Paraldehydeβ-Hydroxybutyric acid*
IsopropanolPropionic acid*
Ethylene glycolGlycolic acid, and some oxalic and formic acids*
Salicylate/aspirinSulfasalicylic acid (SSA)*
*Acid metabolites from ingested chemical.

The first three of the eight causes of metabolic acidosis listed are medical (or unusual physiological) conditions. Strenuous exercise can cause temporary metabolic acidosis due to the production of lactic acid. The last five causes result from the ingestion of specific substances. The active form of aspirin is its metabolite, sulfasalicylic acid. An overdose of aspirin causes acidosis due to the acidity of this metabolite. Metabolic acidosis can also result from uremia, which is the retention of urea and uric acid. Metabolic acidosis can also arise from diabetic ketoacidosis, wherein an excess of ketones is present in the blood. Other causes of metabolic acidosis are a decrease in the excretion of hydrogen ions, which inhibits the conservation of bicarbonate ions, and excessive loss of bicarbonate ions through the gastrointestinal tract due to diarrhea.

Metabolic Alkalosis: Primary Bicarbonate Excess

Metabolic alkalosis is the opposite of metabolic acidosis. It occurs when the blood is too alkaline (pH above 7.45) due to too much bicarbonate (called primary bicarbonate excess).

A transient excess of bicarbonate in the blood can follow ingestion of excessive amounts of bicarbonate, citrate, or antacids for conditions such as stomach acid reflux—known as heartburn. Cushing’s disease, which is the chronic hypersecretion of adrenocorticotrophic hormone (ACTH) by the anterior pituitary gland, can cause chronic metabolic alkalosis. The oversecretion of ACTH results in elevated aldosterone levels and an increased loss of potassium by urinary excretion. Other causes of metabolic alkalosis include the loss of hydrochloric acid from the stomach through vomiting, potassium depletion due to the use of diuretics for hypertension, and the excessive use of laxatives.

Respiratory Acidosis: Primary Carbonic Acid/CO2 Excess

Respiratory acidosis occurs when the blood is overly acidic due to an excess of carbonic acid, resulting from too much CO2 in the blood. Respiratory acidosis can result from anything that interferes with respiration, such as pneumonia, emphysema, or congestive heart failure.

Respiratory Alkalosis: Primary Carbonic Acid/CO2 Deficiency

Respiratory alkalosis occurs when the blood is overly alkaline due to a deficiency in carbonic acid and CO2 levels in the blood. This condition usually occurs when too much CO2 is exhaled from the lungs, as occurs in hyperventilation, which is breathing that is deeper or more frequent than normal. An elevated respiratory rate leading to hyperventilation can be due to extreme emotional upset or fear, fever, infections, hypoxia, or abnormally high levels of catecholamines, such as epinephrine and norepinephrine. Surprisingly, aspirin overdose—salicylate toxicity—can result in respiratory alkalosis as the body tries to compensate for initial acidosis.

Practice Question

Watch this video to see a demonstration of the effect altitude has on blood pH. What effect does high altitude have on blood pH, and why?

[reveal-answer q=”62067″]Show Answer[/reveal-answer]
[hidden-answer a=”62067″]Because oxygen is reduced, the respiratory rate increases to accommodate, and hyperventilation removes CO2 faster than normal, resulting in alkalosis.[/hidden-answer]

Compensation Mechanisms

Various compensatory mechanisms exist to maintain blood pH within a narrow range, including buffers, respiration, and renal mechanisms. Although compensatory mechanisms usually work very well, when one of these mechanisms is not working properly (like kidney failure or respiratory disease), they have their limits. If the pH and bicarbonate to carbonic acid ratio are changed too drastically, the body may not be able to compensate. Moreover, extreme changes in pH can denature proteins. Extensive damage to proteins in this way can result in disruption of normal metabolic processes, serious tissue damage, and ultimately death.

Respiratory Compensation

Respiratory compensation for metabolic acidosis increases the respiratory rate to drive off CO2 and readjust the bicarbonate to carbonic acid ratio to the 20:1 level. This adjustment can occur within minutes. Respiratory compensation for metabolic alkalosis is not as adept as its compensation for acidosis. The normal response of the respiratory system to elevated pH is to increase the amount of CO2 in the blood by decreasing the respiratory rate to conserve CO2. There is a limit to the decrease in respiration, however, that the body can tolerate. Hence, the respiratory route is less efficient at compensating for metabolic alkalosis than for acidosis.

Metabolic Compensation

Metabolic and renal compensation for respiratory diseases that can create acidosis revolves around the conservation of bicarbonate ions. In cases of respiratory acidosis, the kidney increases the conservation of bicarbonate and secretion of H+ through the exchange mechanism discussed earlier. These processes increase the concentration of bicarbonate in the blood, reestablishing the proper relative concentrations of bicarbonate and carbonic acid. In cases of respiratory alkalosis, the kidneys decrease the production of bicarbonate and reabsorb H+ from the tubular fluid. These processes can be limited by the exchange of potassium by the renal cells, which use a K+-H+ exchange mechanism (antiporter).

Diagnosing Acidosis and Alkalosis

Lab tests for pH, CO2 partial pressure (pCO2),and HCO3can identify acidosis and alkalosis, indicating whether the imbalance is respiratory or metabolic, and the extent to which compensatory mechanisms are working. The blood pH value, as shown in Table 2, indicates whether the blood is in acidosis, the normal range, or alkalosis. The pCO2 and total HCO3 values aid in determining whether the condition is metabolic or respiratory, and whether the patient has been able to compensate for the problem. Table 2 lists the conditions and laboratory results that can be used to classify these conditions. Metabolic acid-base imbalances typically result from kidney disease, and the respiratory system usually responds to compensate.

Table 2. Types of Acidosis and Alkalosis
pHpCO2Total HCO3
Metabolic acidosisN, then ↓
Respiratory acidosisN, then ↑
Metabolic alkalosisN, then↑
Respiratory alkalosisN, then ↓
Reference values (arterial): pH: 7.35–7.45; pCO2: male: 35–48 mm Hg, female: 32–45 mm Hg; total venous bicarbonate: 22–29 mM. N denotes normal; ↑ denotes a rising or increased value; and ↓ denotes a falling or decreased value.

Metabolic acidosis is problematic, as lower-than-normal amounts of bicarbonate are present in the blood. The pCO2 would be normal at first, but if compensation has occurred, it would decrease as the body reestablishes the proper ratio of bicarbonate and carbonic acid/CO2.

Respiratory acidosis is problematic, as excess CO2 is present in the blood. Bicarbonate levels would be normal at first, but if compensation has occurred, they would increase in an attempt to reestablish the proper ratio of bicarbonate and carbonic acid/CO2.

Alkalosis is characterized by a higher-than-normal pH. Metabolic alkalosis is problematic, as elevated pH and excess bicarbonate are present. The pCO2 would again be normal at first, but if compensation has occurred, it would increase as the body attempts to reestablish the proper ratios of bicarbonate and carbonic acid/CO2.

Respiratory alkalosis is problematic, as CO2 deficiency is present in the bloodstream. The bicarbonate concentration would be normal at first. When renal compensation occurs, however, the bicarbonate concentration in blood decreases as the kidneys attempt to reestablish the proper ratios of bicarbonate and carbonic acid/CO2 by eliminating more bicarbonate to bring the pH into the physiological range.

Chapter Review

Acidosis and alkalosis describe conditions in which a person’s blood is, respectively, too acidic (pH below 7.35) and too alkaline (pH above 7.45). Each of these conditions can be caused either by metabolic problems related to bicarbonate levels or by respiratory problems related to carbonic acid and CO2 levels. Several compensatory mechanisms allow the body to maintain a normal pH.

Self Check

Answer the question(s) below to see how well you understand the topics covered in the previous section.

Critical Thinking Questions

  1. Case Study: Bob is a 64-year-old male admitted to the emergency room for asthma. His laboratory results are as follows: pH 7.31, pCO2 higher than normal, and total HCO3 also higher than normal. Classify his acid-base balance as acidosis or alkalosis, and as metabolic or respiratory. Is there evidence of compensation? Propose the mechanism by which asthma contributed to the lab results seen.
  2. Case Study: Kim is a 38-year-old women admitted to the hospital for bulimia. Her laboratory results are as follows: pH 7.48, pCO2 in the normal range, and total HCO3 higher than normal. Classify her acid-base balance as acidosis or alkalosis, and as metabolic or respiratory. Is there evidence of compensation? Propose the mechanism by which bulimia contributed to the lab results seen.

[reveal-answer q=”653699″]Show Answers[/reveal-answer]
[hidden-answer a=”653699″]

  1. Respiratory acidosis is present as evidenced by the decreased pH and increased pCO2, with some compensation as shown by the increased total HCO3. His asthma has compromised his respiratory functions, and excess CO2 is being retained in his blood.
  2. Metabolic alkalosis is present as evidenced by the increased pH and increased HCO3, without compensation as seen in the normal pCO2. The bulimia has caused excessive loss of hydrochloric acid from the stomach and a loss of hydrogen ions from the body, resulting in an excess of bicarbonate ions in the blood.

[/hidden-answer]

Glossary

metabolic acidosis: condition wherein a deficiency of bicarbonate causes the blood to be overly acidic

metabolic alkalosis: condition wherein an excess of bicarbonate causes the blood to be overly alkaline

respiratory acidosis: condition wherein an excess of carbonic acid or CO2 causes the blood to be overly acidic

respiratory alkalosis: condition wherein a deficiency of carbonic acid/CO2 levels causes the blood to be overly alkaline


Contents

Welcome. This text is being slowly edited and expanded and references and other links are being added. If you notice any errors, or have a query, or would like to provide feedback, please click here. I hope you find this free resource useful in your studies.

This Acid-base online text was independently reviewed in 2006 by the American Thoracic Society for their "Best of the Web" series. (The link has now been taken down). This text was rated 4 and a half stars (out of 5) and shared equal top ranking

This material is available under a Creative Commons licence which permits copying and reuse under certain terms. In particular you are required to give appropriate credit (or attribution) to the author (me) for any material from this text that you use. Some published texts do this (e.g. Hasan: Handbook of Blood Gas/Acid Base Interpretation) including a thanks in the preface. Other books use selected parts without such attribution (e.g. Respiratory Care Plans: Principles and Practice (2015) in acid-base chapter - see example at bottom of this page). Anyway writers of various published texts use this on-line text as a source of material for their books so that is some recognition.

Chapter 1 : Introduction

Chapter 2 : Control of Acid-Base Balance

Chapter 3 : Acid-Base Disorders

Chapter 4 : Respiratory Acidosis

Chapter 5 : Metabolic Acidosis

Chapter 6 : Respiratory Alkalosis

Chapter 7 : Metabolic Alkalosis

Chapter 8 : Major Types of Metabolic Acidosis

Chapter 9 : Assessment of Acid-Base Disorders

Chapter 10 : Quantitative Acid-Base Analysis

Chapter 11 : Special Aspects of Acid-Base Physiology

'Acid-base pHysiology' by Kerry Brandis -from http://www.anaesthesiaMCQ.com



This work is licensed under a Creative Commons License. NB: Non-commercial use only.


Acid-base balance in alcohol users seen in an emergency room

Over 10% of emergency room patients are diagnosed as having alcohol (6.0%) or drug intoxication. In the present study 196 alcohol intoxications treated in a hospital were studied retrospectively 49.2% of the patients had abnormal acid-base values, alcoholics more often than non-alcoholics (p = 0.04). Mean blood ethanol concentration (BAC) was 310 mg/dl (SD 120) alcoholics had higher concentrations of alcohol. BAC was the higher the lower the serum pH was (p less than 0.002, r = -0.45). The deeper the coma the lower the serum pH (p less than 0.05) and the higher the BAC (p less than 0.0001). Respiratory acidosis (31.7%) was an important finding in those intoxicated. Metabolic acidosis (7.9%) could be explained by the presence metabolites of ethanol in the serum and by decreased extra-cellular fluid volume. Metabolic alkalosis related to vomiting and an extra-cellular fluid volume decrease was found in 7.9% of the patients. Respiratory alkalosis was a rare finding (1.6%). Hypokalemia (22.5%) and hypernatremia (15.3%) were the most important electrolyte changes. Chronic alcoholics had lower serum potassium than had non-alcoholics 3.6% (n = 7) of the patients had to be intubated. Acid-base disturbances were frequent in adults with alcohol intoxication. Serum pH correlated well with the state of consciousness and the BAC.


Conclusion: A change in [SID] alone is the major mechanism by which acid-base differences occur across a membrane as the other two independent variables cannot be responsible.

Important processes involved include Na + -H + exchange and K + -H + exchange across the cell membrane.

The kidney is usually said to excrete acid from the body (ie if urine has a lower pH than plasma, some net amount of H + is being excreted). This is not correct. The kidney certainly has a role in decreasing the [H + ] of plasma but the real mechanism is different from the conventional explanation. As proteins cannot cross membranes, this decrease in plasma [H + ] must be due to the kidney causing changes in SID across the renal tubules. The change in [H + ] is due to differential movement of strong electrolytes (eg Na + , Cl - , K + ) across the tubules causing a change in the SID on each side of the membrane: it cannot be due directly to the secretion or absorption of H + or HCO3 - (or adjustment in any of the other dependent variables). For example in the distal tubule. it is not the secretion of H + that causes the pH of the distal tubular fluid to fall but the movement of the strong ion (eg Na + ) associated with the process.

A further example of acid-base interactions across a membrane is that occurring in the stomach. Gastric juice is acidic not because of the transport of H+ into the stomach but because of the movement of Cl - that occurs. Alternatively, if the H + was exchanged for a positive ion like Na + or K + then the SID would be altered by the same amount and again gastric secretions would be acidic. The factor which determines the [H + ] is the change in SID due to movement of Cl - into the gastric juice.

The intracellular pH is altered mostly by control of intracellular SID. The ion pumps regulate concentrations of the various ions and thereby indirectly control the intracellular SID and pH.

The control of [H + ] in all body fluids is due to changes in the 3 independent variables.

Proteins don't normally contribute much to acid-base interactions because they cannot cross membranes. Most plasma proteins are synthetised in the liver. If protein levels fall (eg due to hepatic dysfunction or excretion as in the nephrotic syndrome) this will have predictable effects on acid-base balance. Strong ions are normally absorbed in the gut and excreted by the kidney. What is important is not the absolute concentrations of the individual strong ions, but the total amount of charge which is present on them which is not balanced by other strong ions (ie SID). The pCO2 is under respiratory control. Changes in pCO2 can cause rapid changes in the [H + ] of all body fluids.

Changes in SID are very important in controlling transmembrane exchanges which affect the acid-base situation in adjacent fluid compartments.


Acid-base disturbances in children, Acidosis, Alkalosis

The pH of the blood is controlled via three systems: chemical buffering, respiratory function, and renal function.

Acidosis means a clinical disturbance in which there is an increase in plasma acidity, whether due to increased production by the tissues, loss of buffering ability or decreased clearance by the kidneys. A multitude of problems, congenital and acquired, can result in metabolic acidosis. The hallmark of a metabolic acidosis is a low serum HCO3 level.

Metabolic alkalosis means the patient has an elevated HCO3, most typically seen with administration of loop diuretics.

A respiratory acidosis means an increase in the partial pressure of carbon dioxide in the blood (PaCO2) due to inadequate respiration.

Respiratory alkalosis typically occurs in response to a metabolic stimulus, such as hyperammonemia (seen in urea cycle defects) or diabetic ketoacidosis (DKA).

Metabolic and respiratory mechanisms affect the acid-base state. The relationship between the pH and PaCO2 is dependent upon the plasma bicarbonate-plasma carbonic acid pool. To estimate the effect of pH change, for every 10 mmHg PaCO2, the pH will change by approximately 0.08 for example, if the PaCO2 rises to 50 from a normal 40 mmHg, then the expected pH will be approximately 7.32, or decreased by 0.08.

Comparison of the base excess with the reference range assists in determining whether an acid-base disturbance is caused by a respiratory, metabolic or mixed metabolic/respiratory problem. While CO2 defines the respiratory component of acid-base balance, base excess defines the metabolic component. To generalize, a metabolic acidosis will have a low serum HCO3 and a respiratory acidosis will have an elevated PaCO2, and in compensating states, as HCO3 decreases, the physiologic response is for minute ventilation to increase and PaCO2 to decrease, and vice versa.

When faced with a metabolic acidosis, the calculation of an anion gap will aid determining the etiology:

Anion gap (AG) = [Na + ] – ([Cl – ]+ [HCO3 – ]) Normal range: 3-11 mEq/L

Of note, the older calorimetric method of measurement had a normal range of 8-16 mEq/L. One should verify the normal range for your respective laboratory.

In an elevated anion gap endogenous or exogenous acids are present, whereas a normal gap means a loss of bicarbonate from the gastrointestinal tract or the kidneys either losing bicarbonate or failing to excrete H + . The normal gap reflects the presence of unmeasured anions such as albumin and sulphates.

Clinical features

The respiratory and renal systems will try to compensate for acidosis. This is manifested by an increase in respiratory rate and depth of breathing, facilitating a respiratory alkalosis to partially offset the metabolic acidosis. In extreme states of acidosis, there may be lethargy, altered mental status and cardiovascular instability.

Symptoms associated with lactic acidosis:

Diabetic ketoacidosis (DKA) has as its clinical features:

Tachypnea, hyperventilation, Kussmaul breathing

Nausea/vomiting – due to increased β-hydroxybutyrate

Altered mental status in severe cases, coma

Inborn errors of metabolism – organic acidurias:

Often present as neonates

Renal tubular acidosis, distal (RTA type 1):

Elevated urine pH, greater than 5.5

Severe hyperchloremic acidosis, serum bicarbonate may be less than 10 mEq/L

Renal tubular acidosis, proximal (RTA type 2):

Respiratory acidosis is due to alveolar hypoventilation, which results in an increased PaCO2. Acute respiratory insufficiency and failure may result from lung disease, neuromuscular disease, airway obstruction or CNS dysfunction causing impaired respiratory drive.

As the PaCO2 rises, the pH of the blood decreases estimated as a 0.08 pH decrease for each 10 mmHg increase in PaCO2. When the respiratory insufficiency is chronic, the kidneys compensate by holding on to plasma bicarbonate. For each 10 mmHg increase in PaCO2 chronically, the plasma bicarbonate level will increase by approximately 3.5 mEq/L.

As PCO2 rises, symptoms may include somnolence from hypercarbia. The acidosis may result in cardiac arrhythmias and decreased responsiveness to inotropes.

Metabolic alkalosis

Metabolic alkalosis appears in the setting of increased H + losses or when exogenous buffer is administered. When assessing a patient with metabolic alkalosis, one should use the urine chloride in the evaluation.

The most common type of metabolic alkalosis encountered in the ICU is the chloride-responsive type. Patients with chloride-responsive metabolic alkalosis have a urine chloride less than 10 mEq/L. Typically this form of acid-base disturbance results from therapy with loop diuretics or thiazides. The loss of fluid secondary from Na + excretion and HCO3 – reabsorption results in a contraction alkalosis. Vomiting and prolonged NG drainage also may result in a metabolic alkalosis due to loss of HCl in gastric fluid.

Chloride-resistent metabolic alkalosis, when the urine chloride is greater than 20 mEq/L, is most commonly seen with overuse of antacids or the incorporation of excessive acetate in hyperalimentation fluids. Most commonly this is seen with overuse of antacids or the incorporation of excessive acetate in hyperalimentation fluids.

Respiratory alkalosis

Primary respiratory alkalosis is most frequently encountered in the ICU setting due to over-ambitious mechanical ventilation. Outside of that situation, the causes of respiratory alkalosis include:

CNS: disturbances of the respiratory regulation – apneustic respirations (or agonal respirations – deep, gasping breaths with pause at full inspiration), central neurogenic hyperventilation (deep, rapid), Cheyne-Stokes respirations (oscillatory pattern of breathing of deep breathing then apnea followed again by deep breaths) due to tumor, meningitis, encephalitis, psychosis or pain.

Anxiety and panic attacks.

Brief loss of consciousness due to the combination of hypocarbia-induced cerebral vascular vasoconstriction and decreased off-loading of oxygen from hemoglobin due to the Bohr effect.

Chronic respiratory alkalosis can be diagnosed if the serum HCO3 is below the normal range.

2. Emergency Management

Metabolic acidosis

Acidosis, whether metabolic or respiratory, warrants immediate attention. Alkalosis will allow a more measured evaluation and response.

Metabolic acidosis is generally well tolerated, but extremes can be life-threatening. Myocardial depression, arrhythmias and diminished response to inotropic agents can occur and can then result in a ever-deepening cycle of worsening acidosis. Hyperventilation, sometimes profound, is an appropriate physiologic response to acidosis.

IV fluid resuscitation. Initial resuscitation is aimed at providing adequate intravascular volume. After an initial normal saline bolus, 20 cc/kg x 1-2, fluid deficit replacement is begun with 0.9% saline.

Insulin replacement. No bolus of insulin is given. An insulin infusion is begun at 0.1 unit/kg/hr with the goal of a gradual correction of the serum glucose by 50-100 mg/dL/hr. Once the blood glucose level falls below 300 mg/dL, then dextrose should be added to the IV fluids rather than decreasing the insulin infusion.

Observation for changes in mental status indicating potential cerebral edema. If coma is present, then treatment with hypertonic saline (3% NaCl) 5 cc/kg or mannitol (0.5-1 g/kg) and monitoring of intracranial pressure (ICP) is warranted.

A recent study used MRI to determine the degree of cerebral edema in children with DKA and found that the degree of edema during DKA episodes correlated with the degree of dehydration and hyperventilation and thus cerebral hypoperfusion, and not the hyperosmolarity or osmotic changes incurred with therapy.

Management of potassium repletion. Serum potassium levels may decrease rapidly once insulin is started. Once urine flow is adequate, special attention needs to be paid to the child’s potassium. Children with hypokalemia on presentation are severely total body potassium depleted. Potassium may be given at 30-40 mEq/L as potassium chloride or phosphate.

Serum sodium. In patients with DKA, the measured serum sodium will be reduced by 1.6 mEq/L for each 100-mg/dL rise in glucose >100 mg/dL.

Monitor sodium, potassium, glucose, and pH every 2 hours until factors stabilize.

Bicarbonate is not recommended as this can lead to a paradoxical worsening of CNS acidosis.

In patients with DKA, the measured serum sodium will be reduced by 1.6 mEq/L for each 100-mg/dL rise in glucose greater than 100mg/dL. A normal or high serum sodium in a patient in DKA indicates severe free water losses. Sodium levels that fail to rise with appropriate treatment may reflect excessive free water accumulation.

Total body potassium and phosphate stores are typically depleted due to urinary losses and need to be repleted. Use of a two-bag system, one bag of 10% dextrose and another bag without dextrose, can be employed to more easily titrate the amount of glucose being infused without having to order and then wait for a new bag with a differing concentration.

Inborn error of metabolism

Extracorporeal removal of toxic metabolite via hemofiltration or hemodialysis.

Specific emergency treatment depends upon the diesease entity. A few are below:

Methylmalonic aciduria – hydroxycobalamin

Organic acidurias, fatty acid oxidation disorders: L-carnitine

Respiratory acidosis

Positive pressure ventilation, whether invasive or non-invasive.

Naloxone (Narcan), if history of narcotic exposure.

Metabolic alkalosis:

Generally emergent care is not warranted and correction may be facilitated slowly.

Intravascular volume expansion with normal saline.

If a neonate, consider pyloric stenosis.

Consider anti-emetics, H + blockers, or proton pump inhibitors (PPI) if H + losses are from GI tract.

Discontinue or decrease diuretic therapy.

Respiratory alkalosis

Generally, emergent care is not warranted.

Seek diagnosis of underlying cause.

If patient is mechanically ventilated, decrease minute ventilation by:

Decreasing respiratory rate

Decreasing peak inspiratory pressure

Sedation or anxiolysis, if patient is agitated and hyperventilating.

3. Diagnosis

Diagnostic testing

The diagnosis of metabolic or respiratory acidosis and alkalosis may be made from a basic electrolyte profile and an arterial, or arteriolized, capillary blood gas. Once acidosis or alkalosis have been identified, additional testing will be needed to determine the etiology.

Glucose – elevated in DKA and hyperosmolar hyperglycemia syndrome (HHS), though pH is usually greater than 7.3 in HHS.

Toxic substances screen – salicylates, ethylene glycol, methanol.

Complete blood count – to evaulate for sepsis or severe anemia.

Liver function tests – hepatic failure may result in hypocarbia.

Cultures, as indicated, from blood, urine, sputum, CSF.

Figure 1 shows a decision tree to determine the type of acid-base disturbance.

Decision tree to determine type of acid-base disturbance.

How do I know this is what the patient has?

Any disturbance of the acid-base status of a patient requires a comprehensive review of the acute and chronic medical conditions, medications (many have electrolyte effects, especially diuretics), and laboratory findings. The basic analysis requires a serum chemistry and blood gas. The remainder of the laboratory investigation will depend upon the intial findings.

DKA is typically diagnosed by the following:

Presence of serum ketones greater than 5 mEq/L.

Serum glucose greater than 250 mg/dL.

Low serum bacarbonate, less than 18 mEq/L.

In severe cases there may be altered mental status or coma.

Renal tubular acidosis, proximal (RTA 2):

Serum bicarbonate greater than 15 mEq/L.

Fractional excretion of bicarbonate greater than 15% in RTA 2, when serum bicarbonate is greater than 20 mEq/L.

Urine pH less than 5.5 when HCO3 low.

Fractional excretion of HCO3greater than 15-20% during alkali therapy.

Renal tubular acidosis, distal (RTA 1):

Non-gap hyperchloremic acidosis.

Serum HCO3 may be less than 10 mEq/L.

Fractional excretion of HCO3less than 10%.

Extrarenal etilogy of acidosis:

Elevated urine ammonium. Urine electrolytes will typically reveal [urine chloride] greater than ([urine sodium] + [urine potassium]) by approximately 50mEq/L.

Other possible diagnoses

Presence of lactic acidosis may be seen in inborn errors of metabolism, including disorders of carbohydrate metabolism, electron transport and some organic acidurias. If multiple organ systems are affected, a mitochondrial oxidative phosphorylation disorder should be suspected.

DKA may clinically appear very similarly to sepsis, toxic ingestion, acute gastroenteritis, pneumonia or urinary tract infection.

RTA, either acquired or congenital, affects the kidney’s ability to absorb bicarbonate or excrete ammonia or an acid. In general, the anion gap is normal in these patients. RTA 1 (distal RTA) and RTA 2 (proximal RTA) are the two most common types in children.

Thiamine deficiency, especially if child is dependent upon total parenteral nutrition without sufficient multivitamins.

Deoxycorticosterone (DOC) excess syndrome.

Congenital chloride diarrhea.

Bronchopulmonary dysplasia – usually well compensated.

Restrictive lung disease, such as severe scoliosis, asphyxiating thoracic dystrophy.

Cystic adenoid malformation.

Confirmatory tests

If an inborn error of metabolism is suspected, then the following should be obtained:

Plasma acylcarnitine profile

Lactate/pyruvate ratio – Normal approximately 20 mMol/L:

Ratio less than 10 suggests pyruvate dehydrogenase deficiency.

Ratio greater than 25 suggests tissue hypoxia, pyruvate decarboxylase deficiency, mitochondrial oxidative phosphorylation disorders.

Fractional excretion of bicarbonate greater than 15% in RTA 2, when serum bicarbonate is less than 20 mEq/L

Muscle biopsy – Useful in cases of suspected mitochondrial phosphorylation defects, looking for ragged red fibers.

4. Specific Treatment

Metabolic acidosis

Treat the underlying disorder.

In cases of extreme acidosis (pH less than 7.0), sodium bicarbonate may be given, but it must be acknowledged that this may improve or correct the acidotic state but not alter the cause of the acidosis, which may be ongoing and clinically significant.

Rapid infusions of bicarbonate are not needed and may be deleterious in certain situations. Hypernatremia may result from overzealous bicarbonate administration. Tromethamine (THAM) may also be given to buffer, especially in situations where additional HCO3 (CO2) load is undesirable. To achieve equivalent dosing to NaHCO3, about three-fold more volume of THAM must be given.

Estimated bicarbonate replacement (about half should be replaced in the first few hours) = (desired HCO3 – measured HCO3) x Weight (in kg) x 0.6

In DKA, the use of bicarbonate administration is not recommended except in cases of extreme acidosis as use may exacerbate CSF acidosis and contribute to the development of cerebral edema.

RTA 2 (proximal) will respond to exogenous alkali administration. Sodium bicarbonate or citrate can be given, 5-15 mEq/kg/day. Potassium supplementation is generally needed once alkali administration is begun due to enhanced urine potassium losses. Treatment with thiazide diuretics can enhance proximal reabsorption of bicarbonate but may have the secondary effect of potassium loss.

In cases of GI losses of HCO3, agents to slow motility may be helpful. The etiology of diarrhea should be investigated.

In cases of salicylate intoxication, use of bicarbonate can facilitate toxin elimination.

Metabolic alkalosis

Treat the underlying disorder.

Reduce or eliminate diuretic use, if clinically possible.

If vomiting or gastric loses are present, the use of anti-emetics, H2 blockers, or proton pump inhibitors (PPI) may be beneficial.

Respiratory acidosis

Treat the underlying disorder.

If patient is mechanically ventilated, decrease effective minute ventilation by:

Increasing respiratory rate

Increasing peak inspiratory pressure

Administer naloxone if receiving or potentially has received narcotics.

Respiratory alkalosis

Treat the underlying disorder.

If patient is mechanically ventilated, decrease effective minute ventilation by:

Decreasing respiratory rate

Decreasing peak inspiratory pressure

5. Disease Monitoring, Follow-up and Disposition

Expected response

DKA – Factors associated with an increased risk of developing cerebral edema include: younger age, longer duration of symptoms, lower pCO2, severe acidosis, elevated BUN, failure of serum sodium to rise with therapy, treatment with bicarbonate and a higher volume of fluid resuscitation. See chapter on diabetes mellitus for specifics.

Acidosis and alkalosis are secondary findings of underlying diseases or medical conditions. Monitoring and follow up of the disease state are etiology specific. For example, children with RTA 2 can have growth retardation, rickets, osteomalacia and abnormal vitamin D metabolism but that is beyond the scope of this text ICU text.

Patient follow-up

Acidosis in general is more alarming than alkalosis and warrants close monitoring of the patient’s response to therapy. If bicarbonate has been administered, a follow-up blood gas is recommended. If a ventilator adjustment has been made, then follow up monitoring by a blood gas or measurement of end-tidal CO2 should be done.

Pathophysiology

Acid-base balance is maintained by buffering of the acid load via intracellular and extracellular mechanisms, excretion of hydrogen ions in the urine, reabsorption of bicarbonate from the urine and alveolar ventilation. Metabolism of dietary carbohydrates, fats, and proteins results in the addition of acids to the blood.

Alveolar ventilation is a major contributor to extracellular buffering. CO2, a product of fat and carbohydrate metabolism, is excreted by the lungs. Other non-volatile acids are buffered by the HCO3 – /H2CO3system and CO2 is expired.

The kidneys contribute by resorbing any filtered HCO3 (approximately 90% in the proximal tubule via carbonic anhydrase and approximately 10% via the thick ascending limb and the medullary collecting duct) and excreting H+ via the collecting duct. Of note, urine cannot achieve a pH much less than 5.0. Phosphate and ammonia also act as buffers in the urine.

Additionally, as plasma pH decreases, the respiratory system attempts to compensate by increasing minute ventilation, which decreases PaCO2. Therefore the respiratory system is a buffering system with limited gain as it cannot completely compensate for changes in pH due to metabolic disorders. The respiratory system is an efficient mechanism to buffer in the short term until the kidneys can manifest chronic buffering.

The kidneys have the capacity to control acid-base balance by excreting acidic or basic pH urine. Large volumes of bicarbonate and H + are filtered by the kidneys and the regulation of how much is excreted versus how much is resorbed determines the net flux of the pH.

The kidneys excrete H + and resorb excreted HCO3 – from the renal tubule. The filtered HCO3 – reacts with secreted H + via conversion by carbonic anhydrase in order to be resorbed as H2CO3. During periods of alkalosis, excess HCO3 – is not bound by H + and gets excreted, effectively increasing H + in the plasma, correcting the alkalosis.

Over time, the kidneys can completely correct for pH abnormalities. H + secretion and HCO3 – reabsorption take place in all segments of the kidney, with varying efficiency, except in the thin loop of Henle.

The classification of the acid-base disorder depends upon determination of the presence of a base excess or base deficit, then eliciting the metabolic and respiratory impacts.

Metabolic acidosis has many etiologies. In general it can be divided into gap acidoses and non-gap acidoses. Gap acidoses result from the accumulation of organic acids (lactate, ketoacids, renal dysfunction) or the effect of toxins (methanol, ethylene glycol, salicylates, paraldehyde).

Lactic acidosis be seen in:

Low cardiac output syndrome, shock.

Hypoxemia, with anaerobic metabolism.

Inborn errors of metabolism, such as electron transport chain disorders, carbohydrate metabolism errors and some types of organic acidurias (proprionic acidemia, methylmalonic acidemia).

Hyperchloremic acidosis is associated with:

Excessive bicarbonate losses, typically from profuse diarrhea.

RTA 2 (proximal) – bicarbonate wasting or Fanconi’s syndrome.

Excessive administration of NaCl-containing IV fluids.

DKA – A state of relative or absolute deficiency of insulin observed in new or known diabetics. Increases in counter-regulatory hormones including glucagon, cortisol, growth hormone and epinephrine occur, resulting in hepatic gluconeogenesis, glycogenolysis and lipolysis. Lipolysis yields an increase in free fatty acids, which are used as an alternative energy source and result in an increase of ketoacid metabolites, such as beta-hydroxybutyrate, acetoacetate and acetone. Initially these ketoacids are buffered by various mechanisms, but once those mechanisms are overloaded, they spill into the urine, causing ketonuria.

Proximal – RTA 2 results from defects in the proximal renal tubule’s ability to resorb bicarbonate. In the first year of life, an immature proximal tubule may result in symptoms and poor growth, which resolves with alkali administration for several years. A more common cause of RTA 2 in children is Fanconi’s syndrome, a generalized dysfunction of the proximal tubule, which may be associated with various genetic disorders or may be acquired as a result of exposure to heavy metals or certain drugs, such as aminoglycosides, ifosfamide and cisplatin.

Ethylene glycol (antifreeze).

Metabolic alkalosis occurs due to gastrointestinal loss of HCl or as a result of renal issues.

Chloride-responsive alkalosis is seen in:

Loss of gastric fluid, typically from emesis or NG drainage.

Diuretic-induced contraction alkalosis. Generally this is seen with use of loop diuretics and thiazides.

Resolution of compensated hypercarbia.

Chloride-resistant metabolic alkalosis can seen in other syndromes and situations, including:

Exogenous buffer administration, such as acetate in hyperalimentation fluids.

Hyperaldosteronism (Conn’s syndrome).

Bartter’s syndrome – inherited defect in the thick ascending loop of Henle associated with low potassium, hypercalcuria, polyuria, polydipsia.

Liddle’s syndrome – rare disorder characterized by dysregulation of the epithelial sodium channel (ENaC) due to a genetic mutation causing excessive loss of potassium with sodium reabsorption in the renal tubule resulting in hypertension, hypokalemia, hypoaldosteronism

17-α-hydroxylase deficiency – uncommon form of congenital adrenal hyperplasia characterized by high levels of ACTH and manifested as hypertension, hypokalemia, low renin.

Licorice ingestion – inhibition of 11-β-hydroxysteroid dehydrogenase results in hypokalemia and hypertension.

Acute respiratory acidosis may be due to airway obstruction, central nervous system depression, neuromuscular disease and acute pulmonary disease. No matter what the etiology of respiratory acidosis is, there is primary hypoventilation, which results in retention of carbon dioxide and acidosis.

Buffering of the acidotic state occurs acutely via various cellular mechanisms, including renal retention of bicarbonate. Within a few days, renal mechanisms will maximally compensate for respiratory acidosis.

Chronic respiratory acidosis is usually compensated via renal mechanisms. Causes of chronic respiratory acidosis include chronic obstructive and restrictive lung disease, neuromuscular disease, and obesity-related hypoventilation.

Respiratory alkalosis results from hyperventilation, which increases exhalation of CO2. The increased alveolar ventilation pulls CO2 from the circulation. In an effort to maintain chemical equilibrium, circulating H + and bicarbonate via carbonic anhydrase generates more CO2, consuming H + and resulting in an increased pH or alkalotic state.

Epidemiology

In general, metabolic acidosis can occur in any age group and has no sex or race predilection.

Accounts for 50% of diabetes-related hospital admissions in children.

Admission for DKA is much more common in children than adults.

Inborn errors of metabolism do have more defined ages of presentation, and race and gender predilection. Specifics are beyond the scope of this ICU text.

In general, metabolic alkalosis can occur in any age group and has no sex or race predilection. It is common after cardiac surgery in children

In general, respiratory acidosis can occur in any age group and has no sex or race predilection.

In general, respiratory alkalosis can occur in any age group and has no sex or race predilection.

Prognosis

The prognosis of any disturbance in acid-base equilibrium in a child is dependent upon the etiology. Physiologic alterations in neurologic, cardiovascular, pulmonary, gastrointestinal, renal and musculoskeletal systems can cause acid-base disequilibrium.

Complications of acidosis

Respiratory muscle fatigue

Increased pulmonary vascular resistance

Reduced splanchnic blood flow

Decreased arrhythmia threshold

Decreased responsiveness to catecholamines

Increased metabolic demands

Inhibition of anaerobic glycolysis

Reduction in synthesis of ATP

Increased protein degradation

DKA: For children under 10, DKA causes 70% of all diabetes-related deaths.

Certain inborn errors of metabolism result in cerebral edema due to accumulation of toxic metabolites. In urea cycle defects, ammonia is not metabolized to urea and it accumulates, crossing the blood-brain barrier. In the brain ammonia is buffered by production of glutamine, but this process is rapidly overwhelmed. As brain ammonia levels rise, astrocytes swell, cerebral blood flow increases and brain ATP is depleted. Cerebral cytotoxic edema and stroke may result.

Children with RTA 2 require exogenous alkali in order to reduce the effects of acidosis on growth.

Special considerations for nursing and allied health professionals.

What's the Evidence?

Glaser, N, Barnett, P, McCaslin, I. “Risk factors for cerebral edema inchildren with diabetic ketoacidosis. The pediatric Emergency medicineCollaborative Research Committee of the American Academy of Pediatrics”. NEJM. vol. 344. 2001. pp. 264-9.

Chua, HR, Schneider, A, Bellomo, R. “Bicarbonate in diabetic ketoacidosis – a systematic review”. Ann Intensive Care. vol. 1. 2011. pp. 23 (This is a systematic analysis of the data presented in 44 studies. The authors find that there were no benefits of bicarbonate administration and it may lead to paradoxical ketosis and cerebral edema.)

Davenport, Horace W. “The ABC of Acid-Base Chemistry: The Elements of Physiological Blood-Gas Chemistry for Medical Students and Physicians”. 1974.

Glaser, N, Barnett, P, McCaslin, I. “Risk factors for cerebral edema in children with diabetic ketoacidosis. The pediatric Emergency medicine Collaborative Research Committee of the American Academy of Pediatrics”. NEJM. vol. 344. 2001. pp. 264-9. (The authors found the only significant risk factor for the development of cerebral edema in children with DKA is the use of bicarbonate.)

van Thiel, RJ, Koopman, SR, Takkenberg, JJ. “Metabolic alkalosis after pediatric cardiac surgery”. Eur J Cardiothorac Surg. vol. 28. 2005. pp. 229-33.

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Control of Acid-Base Balance

The body's balance between acidity and alkalinity is referred to as acid-base balance.

The blood's acid-base balance is precisely controlled because even a minor deviation from the normal range can severely affect many organs. The body uses different mechanisms to control the blood's acid-base balance. These mechanisms involve the

Role of the lungs

One mechanism the body uses to control blood pH involves the release of carbon dioxide from the lungs. Carbon dioxide, which is mildly acidic, is a waste product of the processing (metabolism) of oxygen and nutrients (which all cells need) and, as such, is constantly produced by cells. It then passes from the cells into the blood. The blood carries carbon dioxide to the lungs, where it is exhaled. As carbon dioxide accumulates in the blood, the pH of the blood decreases (acidity increases).

The brain regulates the amount of carbon dioxide that is exhaled by controlling the speed and depth of breathing (ventilation). The amount of carbon dioxide exhaled, and consequently the pH of the blood, increases as breathing becomes faster and deeper. By adjusting the speed and depth of breathing, the brain and lungs are able to regulate the blood pH minute by minute.

Role of the kidneys

The kidneys are able to affect blood pH by excreting excess acids or bases. The kidneys have some ability to alter the amount of acid or base that is excreted, but because the kidneys make these adjustments more slowly than the lungs do, this compensation generally takes several days.

Buffer systems

Yet another mechanism for controlling blood pH involves the use of chemical buffer systems, which guard against sudden shifts in acidity and alkalinity. The pH buffer systems are combinations of the body's own naturally occurring weak acids and weak bases. These weak acids and bases exist in pairs that are in balance under normal pH conditions. The pH buffer systems work chemically to minimize changes in the pH of a solution by adjusting the proportion of acid and base.

The most important pH buffer system in the blood involves carbonic acid (a weak acid formed from the carbon dioxide dissolved in blood) and bicarbonate ions (the corresponding weak base).


A worldwide yearly survey of new data in adverse drug reactions and interactions

Metformin

Endocrine In a 28 year old man with hypothyroidism secondary to thyroxine resistance metformin appeared to potentiate the action of thyroid hormones [ 27 A ]. While taking levothyroxine 500 micrograms/day his thyroid function was stable, but within 3 months of the addition of metformin 2.55 g/day he developed symptoms of thyrotoxicosis and there appeared to be increased sensitivity to thyroid hormones. The thyrotropin concentration had fallen, as had the free thyroxine and free triiodothyronine concentrations. The dose of levothyroxine was reduced to 300 micrograms/day and metformin was withdrawn. His hypothyroidism returned and the thyrotropin concentration increased.

Nutrition Six girls without diabetes, aged under 10 years, who had had a low birth weight, took metformin 850 mg with their evening meal for 8 months [ 28 c ]. Vitamin B12 concentrations were reduced compared with patients taking placebo, whose concentrations increased (–57 versus + 173 ng/l). Other adverse reactions included gastrointestinal problems and fatigue (37% versus 15%).

Acid base balance Lactic acidosis continues to be reported in patients taking metformin [ 29 c , 30 A , 31 A ].

A 62 year old woman with type 2 diabetes took metformin 850 mg tds with insulin aspart and insulin glargine [ 32 A ]. After diarrhea, nausea, and vomiting for 1 week she developed lactic acidosis (pH 6.86, bicarbonate 2.0 mmol/l, serum lactate 22 mmol/l), with renal failure. Metformin was withdrawn and her lactate concentration gradually fell.

Patients should be warned to stop taking metformin during intercurrent illnesses of this sort.

A 34 year old man without diabetes deliberately took metformin 144 g [ 33 A ]. He was treated 2 hours later with charcoal gastric washout, intravenous bicarbonate, and dextrose. His blood glucose was 7.8 mmol/l, creatinine 240 μmol/l, pH 7.1, bicarbonate 3.6 mmol/l, and lactate 17 mmol/l. He was treated with bicarbonate hemodialysis and needed dialysis with a high-flux membrane over 10 hours with continuous bicarbonate in order to cope with a rising lactate.

Other cases of metformin-associated lactic acidosis have been successfully treated with hemodialysis or continuous venovenous hemodiafiltration [ 34 A , 35 A ].

The dose of metformin required to induce lactic acidosis in healthy subjects is unknown. In a review of cases of metformin exposure, 132 were due to metformin alone and 280 to metformin combined with other drugs [ 36 C ]. Of the former, 12 developed lactic acidosis, and the median estimated dose of metformin was 15 (range 9–35) g.

A 67-year-old woman with type 2 diabetes took metformin (dose not documented), lisinopril, aspirin, metoprolol, clopidogrel, and paracetamol + hydrocodone [ 37 A ]. She developed bilateral loss of vision over 1 hour. Her creatinine, previously normal, was 620 μmol/l, lactate 20 mmol/l, and pH 6.65. The visual loss resolved on treatment of the lactic acidosis.

A 54-year-old man with type 1 diabetes developed acute loss of vision, severe hypoglycemia, hyperventilation, a metabolic acidosis, and acute renal failure after a bout of diarrhea and vomiting [ 38 A ]. He was taking insulin lantus, valsartan 160 mg/day, amlodipine 5 mg/day, and metformin 850 mg bd. His lactate concentration was 15 mmol/l and creatinine 807 μmol/l.

Loss of vision secondary to metabolic acidosis has been described [ 39–41 A ], but it is rare.

Tumorigenicity Studies are underway to investigate whether metformin could be used as a treatment for breast cancer. The theoretical mechanisms of action are activation of AMP-activated protein kinase, inhibition of mTOR, and up-regulation of p53. Insulin concentrations and IGF signalling may also be reduced. Longer term use of metformin has suggested a reduction in the development of breast cancer [ 42 R , 43 c ].

Pregnancy In 100 women with gestational diabetes, mean age 32 years, who were randomized to metformin retard or insulin, the drugs were combined if blood glucose targets were not reached with maximal doses of metformin, 32% who started with metformin alone required additional insulin [ 44 C , 45 r ]. One who began with metformin was changed to insulin because of abnormal liver function tests after 3 weeks. One woman had her dose reduced because of diarrhea. The mean gestational age at delivery did not differ between the two groups (both at 39 weeks). Outcomes between the two groups were similar, although metformin was associated with more vacuum extractions (15% versus 8%) and cesarean sections (38% versus 20%).


Nutrition for the equine athlete

Dietary cation-anion balance (DCAB)

Rations with a DCAB <100 mEq/kg DM can be acidogenic and, in theory, will promote the demineralization of bone as well as increased renal Ca loss. 66,67 Cereal grains have a low DCAB (<100 mEq/kg DM), which may be a concern for young, growing and exercising animals. However, there is evidence of adaptation to low-DCAB diets. 68 In addition, the roughage to concentrate ratio and type of roughage strongly influences the effect of diet on acid–base balance. 69 Feeding even currently recommended levels of salt to exercising horses may cause a mild metabolic acidosis unless there is an adequate intake of roughage. 70


Watch the video: ABG Interpretation: Mixed Acid-Base Disorders with Normal pH Lesson 7 (August 2022).