Acidosis




(1)
Professor of Medicine, Department of Medicine, Chief, Division of Nephrology and Hypertension, Rutgers New Jersey Medical School, Newark, NJ, USA

 



Keywords

CO2 ChemoreceptorsMedulla and ponsRespiratory musclesRespiratory acidosisAlveolar ventilationAcute respiratory acidosisChronic respiratory acidosis


Physiology


As stated in Chap. 4, respiratory acid–base disorders are due to changes in pCO2. In normal individuals, the arterial partial pressure of carbon dioxide (pCO2) is maintained at approximately 40 mmHg. This consistency of pCO2 is maintained by the alveolar ventilation. Lungs are the only organs that eliminate (excrete) CO2. Several physiologic mechanisms participate in the maintenance of CO2 balance (given later). Disturbance in any one of these mechanisms leads either to retention (hypercapnia or an increase in pCO2) or excessive elimination (hypocapnia or a decrease in pCO2) of CO2. The respiratory acid–base disorder that is associated with hypercapnia is called respiratory acidosis, whereas that associated with hypocapnia is known as respiratory alkalosis.


In a normal individual, CO2 balance is maintained by the following mechanisms:


  1. 1.

    CO2 production


     

  2. 2.

    CO2 transport


     

  3. 3.

    CO2 elimination


     

  4. 4.

    Control of ventilation by central nervous system (CNS)


     

CO2 Production






  • CO2 is produced by metabolism of carbohydrates and fats.



  • Approximately 15000 mmol of CO2 are produced daily.



  • Heavy exercise generates severalfold higher quantity of CO2 than when the body is in resting state.



  • Lungs are the only organs that excrete all the CO2 that is produced.



  • Thus, the arterial pCO2 tension represents the balance between its production and elimination. The inspired CO2 is negligible.


CO2 Transport






  • The CO2 that is produced during metabolism is transported by the blood (plasma and red blood cells) to the lungs via pulmonary arteries.



  • The pCO2 difference (gradient) between the tissues and alveoli is only 6 mmHg.



  • In red blood cells, CO2 is converted to carbonic acid (H2CO3) in the presence of carbonic anhydrase.



  • H2CO3 then dissociates into H+ and HCO3 −. It is this HCO3 − that diffuses into the plasma via Cl/HCO3 exchanger and is carried to the lungs, where it is converted back to CO2.


CO2 Elimination






  • Alveolar ventilation is the major determinant of CO2 elimination.



  • A decrease in alveolar ventilation causes retention of CO2, resulting in an increase in total body CO2 balance.



  • Other determinants include blood flow through the aerated lung, diffusion of CO2 from the capillary to the alveolar space, and physiologic dead space.


CNS Control of Ventilation


In a normal individual, variations in pCO2, partial pressure of oxygen (pO2), and pH are minimized and kept within normal limits by the respiratory control system, which includes the following:


  1. 1.

    Sensors (chemoreceptors)


     

  2. 2.

    Central controller (medulla and pons)


     

  3. 3.

    Effectors (respiratory muscles)


     

Sensors


Two types of chemoreceptors are involved in ventilation:


  1. 1.

    Central chemoreceptors , located in the medulla, are surrounded by the interstitial and cerebrospinal fluid and respond to changes in [H+] or pCO2. For example, an increase in [H+], i.e., a decrease in pH, stimulates respiration and decreases pCO2. These responses, in turn, raise pH. On the other hand, a decrease in [H+] or an increase in pH depresses alveolar ventilation and causes retention of pCO2, so that the pH is returned to near normal. An increase in pCO2 stimulates ventilation, whereas a decrease depresses ventilation. Central chemoreceptors are not sensitive to changes in pO2


     

  2. 2.

    Peripheral chemoreceptors are located in the carotid body and aortic arch. They respond to decreases in pO2 and pH and increases in pCO2. The sensitivity to changes in pO2 begins at around 500 mmHg, but little response occurs until pO2 is <60 mmHg. The receptors of carotid body are more sensitive to decrease in pO2 (hypoxemia) than the receptors located in the aortic arch


     

Medullary Center





  1. 1.

    Central controller includes neurons located in the medulla and pons, which are referred to as respiratory centers


     

  2. 2.

    Medullary respiratory center has two identifiable areas of neurons. One group of neurons is located in the dorsal region of the medulla (nucleus tractus solitarius). It is called the dorsal respiratory group, which is involved in inspiration (firing on inspiration). In addition, these neurons receive afferent stimuli from peripheral and central chemoreceptors and from receptors in the lung. The other group of neurons, the ventral respiratory group, controls both expiration (firing on expiration) and inspiration


     

Effectors





  1. 1.

    Once changes are sensed in the medullary respiratory center, they are transmitted through nerves to the muscles of respiration (diaphragm, intercostal muscles, abdominal muscles, and sternocleidomastoid muscles). It is the coordinated effort of these muscles that is responsible for ventilation


     

Any disturbance in sensing and signaling results in either hypercapnia or hypocapnia, leading to either respiratory acidosis or respiratory alkalosis, respectively. Let us discuss respiratory acidosis.


Respiratory Acidosis


Respiratory acidosis, also called primary hypercapnia , is initiated by an increase in arterial pCO2. This increase is related to decreased excretion relative to the production of CO2. Whenever pCO2 increases, the pH falls. The excess H+ is immediately (within minutes) buffered by nonbicarbonate buffers, such as hemoglobin, phosphates, and plasma proteins, so that HCO3 − is not used up. During this buffering, some HCO3 − is also formed from dissociation of H2CO3. The acute nonbicarbonate buffer response is completed within 10–15 min, and a steady state condition persists for 1 h. If hypercapnia continues for >12 h, the kidneys generate additional HCO3 − by excretion of H+, and the maximum level of HCO3 − generation is completed within 3–5 days. Thus, respiratory acidosis can be classified into acute (<12 h) or chronic (>5 days) types. Both acute and chronic hypercapnias are associated with hypoxemia.


Pathophysiology


From the above discussion, respiratory acidosis can develop from any or combination of the following ventilation abnormalities: (1) overproduction of CO2; (2) decreased alveolar ventilation; (3) impaired gas exchange; (4) decreased respiratory center response; and (5) abnormalities of the chest wall and respiratory muscles.



Overproduction of CO 2


Either an increase or decrease in CO2 production can occur in several clinical settings, as shown in Table 12.1. This excess CO2 production is eliminated by proportionate increase in alveolar ventilation. Thus, positive CO2 balance does not usually develop with intact respiratory system. Therefore, overproduction of CO2 does not cause significant hypercapnia. However, CO2 retention does occur whenever there is an abnormality in alveolar ventilation.


Table 12.1

Clinical settings associated with CO2 production














Increase

Decrease

Fever


High glucose loads


Exercise


Hyperthermia


Hyperthyroidism


Multiorgan failure


Increased work of breathing (severe dyspnea)

Hypothermia


High fat loads


Inactivity (sleep)


Hypothyroidism


Weight loss


Decreased work of breathing (mechanical ventilation, sedatives)



Decreased Alveolar Ventilation (Hypoventilation)


Alveolar ventilation (V A) is defined as the amount of gas that reaches the alveoli per minute. Decreased alveolar ventilation may be related to low minute ventilation (V E, which is equal to the tidal volume and respiratory rate) or an increase in dead space (V D, which is an airway volume that does not participate in gas exchange) or both. Tidal volume (V T) is the amount of gas inspired or expired per breath. V E (minute ventilation) refers to total ventilation, which is expressed as L/min; however, all this volume does not participate in gas exchange. V A (alveolar ventilation) refers to that volume of air in the alveoli participating in gas exchange. Therefore, V A is equal to:



$$ {\displaystyle \begin{array}{l}{V}_{\mathrm{A}}=\left({V}_{\mathrm{T}}-{V}_{\mathrm{D}}\right)\times \mathrm{Respiratory}\kern0.5em \mathrm{rate}\\ {}\mathrm{or}\\ {}{V}_{\mathrm{A}}=\left({V}_{\mathrm{E}}-{V}_{\mathrm{D}}\right)\end{array}} $$

Alveolar hypoventilation causes not only CO2 retention but also inadequate (poor) oxygenation. Impaired response of medullary CO2 receptors (due to narcotics) or carotid pO2 receptors (due to trauma or surgical removal) may cause alveolar hypoventilation.


Increase in V D (dead space) alone rarely causes alveolar hypoventilation unless the ratio of V D/V T (dead space to tidal volume) exceeds 0.6. Normal V D/V T ratio is 0.3. Conditions such as pulmonary embolism and shock lung may increase V D and result in high ratio. Also, relative decrease in V T can be seen in patients with increased respiratory rate (rapid but shallow breathing) due to neuromuscular disease and pulmonary edema or fibrosis. Increased V D/V T ratio is thought be the mechanism for acute exacerbation of COPD due to rapid shallow breathing. Thus, V D is an important contributor of alveolar hypoventilation.



Impaired Gas Exchange


Impaired alveolar gas exchange (ventilation–perfusion mismatch) can lead to hypoxemia and hypercapnia. Patients with lung disease and superimposed acute conditions such as pulmonary edema and pneumonia can cause impaired gas exchange with resultant hypoxemia and hypercapnia.



Decreased Respiratory Center Response


Drugs such as sedatives and narcotics, CNS diseases such as medullary infarcts and tumors, and diseases like hypothyroidism cause hypercapnia by inhibiting the central respiratory drive. Sedatives and narcotics should be used with caution in patients with severe asthma or COPD who retain CO2. However, some individuals with anxiety or pain who develop hypocapnia because of hyperventilation may benefit from the use of these drugs by lowering pH.



Abnormalities of the Chest Wall and Respiratory Muscles


Hypercapnia develops despite normal central drive and lung structure. Disorders of respiratory muscles and motor neurons are examples of this pathophysiologic mechanism of hypercapnia. Fatigue and weakness of diaphragm is an important contributor for hypercapnia. Electrolyte abnormalities such as severe hypokalemia and hypophosphatemia and malnutrition may cause respiratory muscle weakness and cause CO2 retention. Chest wall stiffness such as kyphoscoliosis is another cause for hypercapnia.


Secondary Physiologic Response to Hypercapnia


As stated earlier, the renal and extrarenal mechanisms respond to an increase in pCO2 by preventing loss of HCO3 − so that dangerous decreases in pH are avoided. Although acute respiratory acidosis causes low pH, chronic respiratory acidosis maintains pH at slightly low but near-normal levels because of renal regeneration of HCO3 −. The secondary responses to both acute and chronic respiratory acidosis are given below:



  • Acute respiratory acidosis: For each mmHg increase in pCO2, HCO3 − increases by 0.1 mEq/L.



  • Chronic respiratory acidosis: For each mmHg increase in pCO2, HCO3 − increases by 0.4 mEq/L.


Table 12.2 shows the relationship between rise in pCO2, secondary response (compensation), and arterial pH in acute and chronic respiratory acidosis.


Table 12.2

Relationship between hypercapnia, secondary response, and pH



































Type

pCO2 (mmHg)

Expected secondary response (compensation)

Expected serum [HCO3 −]

pH (calculated from Henderson equation) after compensation

Normal

40

–

24

7.40


Acute

70a


For each mmHg increase in pCO2, HCO3 − increases by 0.1 mEq/L, ΔpCO2 = 30 (70–40 = 30 × 0.1 = 3)

27 (24 + 3 = 27)

7.18


Chronic

70a


For each mmHg increase in pCO2, HCO3 − increases by 0.4 mEq/L, ΔpCO2 = 30 (70–40 = 30 × 0.4 = 12)

36 (24 + 12 = 36)

7.34



aArbitrary value


Mechanism of Secondary Physiologic Response



Acute Respiratory Acidosis


An increase in pCO2 increases the production of carbonic acid (H2CO3) and H+ production. As a result of increased H+, the blood pH decreases (as shown in Table 12.2). The secondary physiologic response for this low pH or hypercapnia is an increase in plasma HCO3 − concentration, which is due to buffering of H+ by nonbicarbonate buffers such as red blood cells, hemoglobin, and tissue buffers. The increase in HCO3 − concentration is 0.1 mEq/L for each 1 mmHg increase in pCO2 above 40 mmHg (as shown in Table 12.2). The adaptive increase in HCO3 − concentration is complete in 10–15 min. Following this period of time, no further changes in HCO3– occur for hours, and this period is called acute steady state.



Chronic Respiratory Acidosis


As stated above, the kidney responds to chronic hypercapnia by increasing serum HCO3 − concentration. This occurs by increasing excretion of H+ mostly in the form of NH4 + (see Chap. 2). These changes start to happen 12–24 h after hypercapnia. Excretion of H+ results in formation and reabsorption of HCO3 −. This increase in HCO3 − is complete in 3–5 days. As shown in Table 12.2, for each mmHg increase in pCO2, HCO3 − increases by 0.4 mEq/L. Secretion of H+ and reabsorption of HCO3 − seem to occur in the proximal and distal tubules. Studies have shown an increased activity of luminal Na/H exchanger and basolateral Na/HCO3 cotransporter in the proximal tubule. Also, chronic hypercapnia has been shown to induce luminal insertion of H-ATPase in the proximal tubule and in type A intercalated cells of the cortical and medullary collecting ducts as well as abundance of basolateral Cl/HCO3 exchanger in the latter type of cells. These studies provide evidence for increased luminal H+ secretion and increased basolateral HCO3 − reabsorption in chronic hypercapnia. With the increase in serum HCO3 − concentration, a new steady develops, but the blood pH will not return to normal. Therefore, the patient will have persistent acidic pH despite high concentration of HCO3 −.


The increased HCO3 − reabsorption is associated with inhibition of Cl− reabsorption. As a result, Cl− is excreted in the urine with depletion of body stores. Cl− is also excreted with Na+ and K+. Thus, persistent hypochloremia exists in chronic respiratory acidosis.


Acute Respiratory Acidosis


Causes


There are several causes of acute respiratory acidosis, as shown in Table 12.3.


Table 12.3

Causes of acute respiratory acidosis


































































Depression of medullary respiratory center


Drugs, anesthetics, sedatives, opiates


Cerebral trauma or infarct


Central sleep apnea


Cardiac arrest


Failure of motor functions of respiratory muscles and chest wall


Drugs: succinylcholine, curare, aminoglycosides, fluoroquinolones


High cervical cordotomy


Myasthenia gravis crisis


Guillain–Barrè syndrome


Status epilepticus


Tetanus


Acute botulism poisoning


Familial hypokalemic periodic paralysis


Severe hypophosphatemia


Airway obstruction


Aspiration


Laryngospasm


Severe bronchospasm


Obstructive sleep apnea


Ventilatory defects


Flail chest


Pneumothorax


Hydrothorax


Adult respiratory distress syndrome


Acute pulmonary embolism


Acute pulmonary edema


Severe asthma


Severe pneumonia


Mechanical ventilation, increased production of CO2 due to high carbohydrate feedings and fixed minute ventilation

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Oct 20, 2020 | Posted by in NEPHROLOGY | Comments Off on Acidosis

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