Acid Base Physiology PDF

## 4.1 The Regulation of Acid-base Homeostasis **5. What are the different effects of metabolic and respiratory acidosis on the body? Why does this occur?** * **Metabolic Acidosis:** Decreases in bicarbonate levels lead to decreased pH, impacting various systems like the cardiovascular system and...

## 4.1 The Regulation of Acid-base Homeostasis **5. What are the different effects of metabolic and respiratory acidosis on the body? Why does this occur?** * **Metabolic Acidosis:** Decreases in bicarbonate levels lead to decreased pH, impacting various systems like the cardiovascular system and the nervous system, resulting in decreased cardiac contractility and CNS depression, respectively. * **Respiratory Acidosis:** Increased PaCO2 disrupts pH balance with detrimental effects on the cardiovascular system and the nervous system, leading to decreased cardiac contractility. **6. What are the effects of alkalosis upon the nervous-muscle system? What is the mechanism?** * Alkalosis leads to decreased free plasma Ca²+ and Mg2+, which increases neuromuscular excitability, manifesting as tendon hyperreflexia and convulsion. **7. What are the different causes of alkalosis responsive or unresponsive to saline? What are the clinical findings associated with these causes?** * **Saline-Responsive Alkalosis:** Caused by sodium chloride depletion and extracellular fluid volume depletion. Clinical features include hypokalemia and hypovolemia. * **Saline-Unresponsive Alkalosis:** Caused by mineralocorticoid excess. Clinical features include hypokalemia and hyperaldosteronism. **Case Study** **1. A 52-year-old man with chronic obstructive lung disease is admitted to the hospital with worsening dyspnea. He appears cyanotic and in respiratory distress. Below is available laboratory data:** | Venous Blood | Arterial Blood | | -------------- | -------------- | | Na+: 136 mmol/L | pH: 7.34 | | K+: 4.9 mmol/L | H+: 46 nmol/L | | Cl-: 96 mmol/L | PaCO2: 60 mmHg | | HCO3: 31 mmol/L | PaO2: 50 mmHg | **Questions** * **What acid base disturbance is ongoing in this patient?** This patient has respiratory acidosis, but the history and elevated plasma HCO3 suggest a chronic condition. * **This man has respiratory acidosis, but the history and elevated plasma HCO3 suggest a chronic condition. Note that, despite increased PaCO2, the arterial pH is almost normal. Are there multiple acid-base disturbances?** Yes, this patient likely has a superimposed metabolic alkalosis. * **What do you expect the urine pH to be in a patient like this? Why?** The urine pH would be expected to be alkaline because the body is trying to compensate for the respiratory acidosis by retaining bicarbonate. **2. A 36-year-old man with a history of diabetes is hospitalized with increased respiratory rate and depth. Below is available laboratory data:** | Venous Blood | Arterial Blood | Urine | | -------------- | -------------- | -------------- | | Na: 135 mmol/L | pH: 7.21 | Specific Gravity: 1.028 | | K: 2.0 mmol/L | H: 62 nmol/L | Na+: 2.0 mmol/L | | Cl: 110 mmol/L | PaCO2: 26 mmHg | | | HCO3: 12 mmol/L | PaO2: 108 mmHg | | **Questions** * **What acid base disturbance is ongoing in this patient?** The patient is experiencing metabolic acidosis. * **What are possible etiologies?** The patient's diabetes could be a contributing factor to the metabolic acidosis. * **Explain the symptoms of increased respiratory rate and depth.** Increased respiratory rate and depth are the body's attempt to compensate for the acidosis by blowing off CO2. * **What will altered respirations do for the patient?** Altered respirations will help to lower the PCO2 in the blood, which will in turn help to raise the pH. ## 4.1.1 Acid Generation * Most body acids are generated via metabolic processes. * **Volatile acid:** Carbonic acid, derived from the hydration of carbon dioxide. * **Nonvolatile acids:** Sulfuric and Phosphoric acids, produced by breakdown of amino acids, and organic acids such as acetoacetic, lactic, and beta-hydroxybutyric acid, produced by incomplete metabolism of fatty acids. ## 4.1.2 Role of the Lungs * The lungs play a vital role in regulating PCO2 and therefore, H2CO3 concentration. * Normal ventilation maintains PaCO2 at 40 mmHg. * Hypoventilation: **PaCO2 > 45 mmHg** * Hyperventilation: **PaCO2 < 35 mmHg** ## 4.1.3 Buffers * Buffers minimize variations in H⁺ concentration. * Various buffers, such as **bicarbonate, phosphate, hemoglobin, serum protein, and apatite** help to maintain stable pH. ## 4.1.4 Role of the Kidneys * The kidneys are vital in maintaining the correct HCO3 concentration in extracellular fluids. * They must reclaim bicarbonate filtered through the glomerulus and replenish lost bicarbonate. ## 4.2 Simple Acid-base Disorders ### 4.2.1 Metabolic Acidosis * **Metabolic acidosis** is a condition characterized by a decrease in plasma bicarbonate concentration ([HCO3¯]). * **Elevated Anion Gap Metabolic Acidosis:** A decrease in HCO3¯ is compensated by an increase in an unmeasured anion (e.g. ketoacids in diabetic ketoacidosis), resulting in an increased anion gap. * **Normal Anion Gap Metabolic Acidosis:** A decrease in HCO3¯ is compensated by an increase in Cl, resulting in a normal anion gap. #### **Causes of Metabolic Acidosis:** * **Overdose of Fixed Acids:** Ingestion of large quantities of fixed acids can lead to metabolic acidosis (e.g., aspirin poisoning). * **Overproduction of Fixed Acids:** Conditions like hypoxia, tissue hypoxia, severe liver dysfunction, starvation, and diabetes mellitus increase lactic acid and ketoacid production, leading to metabolic acidosis. * **Impaired Renal Bicarbonate Generation:** Occurs in conditions like renal failure and distal renal tubular acidosis (RTA) as the kidneys are unable to reclaim and generate bicarbonate. * **Gastrointestinal Losses:** Losses of bicarbonate through diarrhea, fistulas, or ureterosigmoid anastomosis can lead to metabolic acidosis. * **Renal Tubular Acidosis (RTA):** A specific type of metabolic acidosis caused by impaired renal bicarbonate reclamation or generation. * **Chronic Renal Failure:** Leads to decreased glomerular filtration rate and impaired excretion of weak acid anions, reducing bicarbonate regeneration and resulting in metabolic acidosis. #### **Compensation for Metabolic Acidosis:** * **Buffering System:** The buffering system in the blood helps to compensate for metabolic acidosis by consuming HCO3¯ and generating H2CO3, which is excreted through the lungs. * **Respiratory System:** The respiratory system compensates by increasing alveolar ventilation, leading to decreased PaCO2. * **Renal System:** The kidneys compensate by reclaiming all HCO3¯ through the glomerulus and further generating bicarbonate by enhancing ammonium or hydrogen excretion. ### 4.2.2 Respiratory Acidosis * **Respiratory acidosis:** is caused by an increase in PaCO2 due to impaired alveolar ventilation, leading to increased H2CO3 concentration and lowered blood pH. * **Causes:** Conditions that impair ventilation, such as CNS depression, respiratory muscle paralysis, airway obstruction, chest pathology, pulmonary diseases, and improper breathing machine settings. #### **Compensation for Respiratory Acidosis:** * **Buffering System:** The buffering system compensates by consuming H+ and generating HCO3¯. * **Intra/extracellular Exchange of ions:** Red blood cells compensate by buffering H+ with Hb-, and HCO3¯ exchanges with Cl- in the plasma, increasing plasma HCO3¯ while decreasing Cl levels. * **Renal System:** The kidneys compensate by reclaiming HCO3¯ and generating new HCO3¯, which is excreted through the urine. ### 4.2.3 Metabolic Alkalosis * **Metabolic alkalosis:** is characterized by a primary increase in plasma bicarbonate concentration ([HCO3¯]) due to either excessive loss of acid or inappropriate addition of bicarbonate. #### **Causes:** * **Gastrointestinal H+ Ion Loss:** Vomiting or nasogastric suction can lead to loss of gastric fluid rich in HCl, resulting in metabolic alkalosis. * **Diuretics:** Diuretics can lead to increased sodium and fluid loss, causing enhanced hydrogen excretion and increased bicarbonate reabsorption, resulting in metabolic alkalosis. * **Excess Aldosterone Secretion:** Aldosterone stimulates sodium reabsorption and hydrogen ion secretion, leading to metabolic alkalosis. * **Ingestion of Alkaline Solutions:** Ingestion of alkaline solutions, such as sodium bicarbonate, can cause metabolic alkalosis. #### **Compensation for Metabolic Alkalosis:** * **Respiratory System:** The respiratory system compensates by decreasing alveolar ventilation (increasing PaCO2) to decrease blood pH. * **Intra/extracellular Exchange of Ions:** The body compensates by moving H+ ions extracellularly and K+ ions intracellularly, leading to hypokalemia. #### **Renal Compensation for Metabolic Alkalosis:** * The kidney compensates by decreasing HCO3 reabsorption, decreasing H+ and NH4+ secretion to decrease blood pH. ### 4.2.4 Respiratory Alkalosis * **Respiratory alkalosis:** is caused by hyperventilation (increased alveolar ventilation) leading to decreased PaCO2 and a rise in blood pH. #### **Causes:** * **Physical Pathology:** Conditions like pulmonary embolism, pneumonia, or pneumothorax can induce hyperventilation, leading to respiratory alkalosis. * **Psychoneurosis:** Anxiety or panic attacks can sometimes cause hyperventilation, leading to respiratory alkalosis. * **High Altitude:** The low oxygen pressure at high altitudes can trigger hyperventilation, resulting in respiratory alkalosis. #### **Compensation for Respiratory Alkalosis:** * **Buffer System:** The buffering system compensates by consuming H+ and generating HCO3¯, which will lower the pH. * **Renal System:** The kidney compensates by increasing renal bicarbonate excretion, leading to a reduction in blood pH. ## 4.4 Clinical Measurements and Analysis of Acid-base Disorders * By analyzing the pH, PCO2, and bicarbonate concentration in arterial blood, we can categorize simple acid-base disorders into metabolic acidosis, respiratory acidosis, metabolic alkalosis, and respiratory alkalosis. * **Anion Gap:** Anion gap is used to differentiate causes of metabolic acidosis. A high anion gap suggests that the cause is due to an increase in unmeasured anions like those seen in lactic acidosis or ketoacidosis. A normal anion gap suggests the cause is due to an increase in Cl-. ## 4.4.1 The Judgment of the Simple Acid-base Disorders * **Step 1:** Determine whether the primary disorder is acidosis or alkalosis. **pH <7.4** indicates acidosis, while **pH >7.4** indicates alkalosis. * **Step 2:** For acidosis, if **PCO2 is increased**, look at plasma bicarbonate. If the plasma bicarbonate is also increased, the disorder is respiratory acidosis. * **Step 3:** For acidosis, if **PCO2 is decreased**, look at plasma bicarbonate. If the plasma bicarbonate is decreased, the disorder is metabolic acidosis. * **Step 4:** For alkalosis, if **PCO2 is decreased**, look at the plasma bicarbonate. If the plasma bicarbonate is increased, the disorder is metabolic alkalosis. * **Step 5:** For alkalosis, if **PCO2 is increased**, look at the plasma bicarbonate. If the plasma bicarbonate is decreased, the disorder is respiratory alkalosis. ## 4.4.2 Use of Anion Gap to Diagnose Acid-base Disorders * **Anion gap:** A difference between the concentrations of unmeasured anions and unmeasured cations. * **Calculated as:** Anion gap = [Na+] - [HCO3-] - [Cl-] * **Normal range:** 6-8 mmol/L * A **high anion gap** suggests an increase in unmeasured anions, which is often seen in lactic acidosis, ketoacidosis, and renal failure. * A **normal anion gap** suggests an increase in Cl- due to metabolic acidosis caused by conditions like diarrhea or renal tubular acidosis. ## 4.5 Complex Acid-base Disorders * **Mixed acid-base disorders:** Two or more underlying causes for the acid-base disturbance. * For example, a patient with a low pH, low bicarbonate, and high PCO2 may have both respiratory acidosis and metabolic acidosis. ## Summary The blood pH needs to be carefully maintained to ensure the proper functioning of the body's systems. This is a challenging task because metabolic processes generate acids and bases, and food also contributes to the body's acid-base balance. Several regulatory mechanisms keep the blood pH within a narrow range. **These mechanisms include:** * **Buffers:** Chemical pairs found in the blood, such as bicarbonate, phosphates, hemoglobin, and serum protein, help to minimize fluctuations in H⁺ concentration. * **Lungs:** By regulating ventilation, the lungs control blood PaCO2. * **Kidneys:** The kidneys reclaim all bicarbonate through the glomelulus and replenish any lost bicarbonate, which allows for the removal of H+ ions. **Disturbances of these mechanisms can lead to acid-base disorders, which can be classified into four main types:** * **Metabolic acidosis:** A decrease in serum bicarbonate concentration. * **Respiratory acidosis:** An increase in PaCO2, usually due to hypoventilation.. * **Metabolic alkalosis:** An increase in serum bicarbonate concentration. * **Respiratory alkalosis:** A decrease in PaCO2, usually due to hyperventilation.. **By analyzing the pH, PCO2, and bicarbonate concentration, we can diagnose and treat these disorders.** **Mixed acid-base disorders:** Two or more underlying causes for the acid-base disturbance. **Important factors to consider**: * If the acidosis is severe or prolonged, it can have a negative impact on the cardiovascular system, nervous system, and other organs. * If the alkalosis is severe or prolonged, it can lead to hypokalemia and CNS disorders. * Accurate clinical diagnosis is essential for proper treatment of acid-base disorders.