3.3 Acid- Base Balance and Pathophysiology and Review1 (1) copy.ppt

Acid-Base Balance Lecture Outline Chemistry of Acids, Bases, and Buffers Buffer Systems of the Human Body Acidosis and Alkalosis and Compensation Causes of Hypoxia 1 Acid-Base Balance Objectives 1. Explain the difference in acids, bases, and buffers 2. Describe main buffer systems available in the b...

Acid-Base Balance Lecture Outline Chemistry of Acids, Bases, and Buffers Buffer Systems of the Human Body Acidosis and Alkalosis and Compensation Causes of Hypoxia 1 Acid-Base Balance Objectives 1. Explain the difference in acids, bases, and buffers 2. Describe main buffer systems available in the body 3. Describe the interrelationship of pH, PCO2 of blood, and plasma bicarbonate concentration 4.Define acidosis and alkalosis 5.List potential causes of respiratory acidosis and alkalosis and metabolic acidosis and alkosis 6.Discuss the respiratory and renal mechanisms that help compensate for alkalosis and acidosis 7.Classify and explain the causes of tissue hypoxia 2 References Assigned reading from your text: Levitzky Chapter 8 Apex Anesthesia Review (selected content) for Acid- Base Balance 3 I. Chemistry of Acids, Bases, and Buffers 4 Acid-Base Regulation The respiratory system is intimately involved in acid-base regulation for homeostasis Chemistry of acids, bases, and buffers pH regulation important since most biochemical reactions are pH dependent An acid is a molecule that releases a hydrogen ion (proton) in solution A base is a molecule that can accept a hydrogen ion in solution; a strong base A strong acid completely dissociates ; a weak acid has a strong conjugate base Sources of acids in the body are from cellular metabolism CO2 formed by metabolism is hydrated to H2CO3, resulting in large total H+ load – Most CO2 excreted by lungs – Small remaining quantities of H+ excreted by kidneys Hydrogen Ions  Regulation of acid-base balance is equivalent to regulation of [H+] in body fluids pH is a measure of the [H+] in a solution, and is expressed by the following formula pH = - log [H+] A negative log yields an inverse relationship Increase [H+] decreases pH & Decrease [H+] increases pH In the body, pH of gastric acid is ~ 1; pH of alkaline pancreatic secretion is ~ 8 Body attempts to regulate blood pH to 7.40 Normal pH = 7.35-7.45 pH limits under pathologic conditions = 6.9- 7.8 Acidosis/acidemia occurs at a pH < 7.35 Alkalosis/alkalemia occurs at a pH > 7.45 II. Buffer Systems of the Body 7 pH Homeostasis Three mechanisms that resist pH changes are: 1. Lungs remove volatile acids- ~20,000 mmol CO2/day 2. Kidneys remove fixed acids- ~ 100 mEq/day – sulfuric, phosphoric, hydrochloric, lactic acid (*lactic acid is not always fixed) 3. Buffers reversibly bind hydrogen ions to minimize changes in H+ concentration/ pH Three major acid-base buffer systems in the blood include: – Carbonic acid- Bicarbonate System- Most important – Proteins (mainly hemoglobin)- Second most important – Phosphate (glucose-1-phosphate and ATP) Additional buffers: – Bicarbonate buffer system is the major buffer of interstitial fluid – Bone salts of hydroxyapatite can buffer H+ ions in chronic acidosis Respiratory Control of Acid-Base Balance Respiratory system controls: CO2 directly by altering ventilation to change PaCO2 (volatile acid) [H+1] indirectly by controlling CO2/H2CO3 via the carbonic acid reaction Respiratory correction of imbalance occurs within minutes- Does not completely correct eg Ketoacidosis must produce a large increase in arterial [H +1] to stimulate carotid bodies Stimulated peripheral chemoreceptors cause an increase in ventilation rate This results in a shift of the carbonic acid reaction to the left pH increases with less acidity in the blood Incomplete since the original source of H+ hasn’t been eliminated 9 Renal Regulation of Acid-Base Balance Renal regulation occurs by altering the excretion of fixed acids and HCO3 retention Renal compensation for acidosis occurs by: 1. Secretion of H+ ions into the tubular fluid (Carbonic acid dissociation in the cell) H+ secreted HCO3- reabsorbed in the peritubular capillary 2. Removal of titratable acids (fixed acids) Ketoacids (acetoacetic acid and -hydroxybutyric acid) Acidic compounds ingested from diet or medications 3. Following glutamine metabolism, ammonia formed and secreted in exchange for HCO3 Renal compensation for alkalosis occurs by: Decreased H+ secretion and Decreased HCO3- reabsorption Compensation for acid-base imbalances takes hours to days Powerful - can completely compensate for acid-base imbalances Returns ECF pH to normal 10 Buffer Systems Buffer systems: Neutralize excessive amounts of acid or base to maintain a relatively constant blood pH Onset of buffer activity is immediate The availability of buffer system determines its value; HCO3- most valuable Isohydric principle states that all buffer pairs will be in equilibrium since the change in pH causes a change in ratios (base/ undissociated acid) of all buffer pairs 11 Bicarbonate Buffer System 1. Bicarbonate buffer system is the most important buffer system Weak yet important since components are easily regulated: Two parts: -H2CO3 functions as the weak acid -HCO3 functions as the conjugate base Components can be easily regulated: HCO3-1 in the kidney and H2CO3 as CO2 in the lungs Henderson-Hasselbalch equation for the bicarbonate buffer system: -pK is the point where equal amounts of acid or base can be buffered -pK for the bicarbonate system is 6.1 -pH is a function of the ratio of dissociated anion [A-] to non-dissociated acid [HA} Changes in either component [HCO3-1] or PaCO2 will alter pH Alkalosis can result from an increase in [HCO 3-1] or a decrease of PaCO2 Acidosis can result from a decrease in [HCO3-1] or a increase of PaCO2 12 Protein Buffer System 2.Protein buffer systems are the second most abundant and powerful chemical buffer since large quantities of protein in the body – 75% of all chemical buffering occurs within cells – relatively high protein content – Hemoglobin in RBCs has 6 x the buffering capacity of plasma proteins – At the systemic capillary, CO2 continuously diffuses from tissues into the blood CO2 enters erythrocytes and undergoes the carbonic anhydrase reaction  H+1 and HCO3-1 Some HbO2 unloads O2 to the tissues with the formation of Hhb (deoxyhemoglobin) – Hb has a greater affinity for H+1 than does HbO2. (See image next slide) – Some CO2 not buffered in the plasma produces small amounts of H +1 ions in the venous blood Reason venous blood is slightly more acidic pH 7.35 vs 7.4 13 Phosphate Buffer System 3. Phosphate buffer system- 2 components – H2PO4-1 (dihydrogen phosphate- acid) and HPO4-2 (monophosphate- conjugate base) – This buffer system is weaker than the bicarbonate system- smaller amounts components – Phosphates high intracellularly 14 Hb is a better buffer than HbO2 15 III. Acidosis and Alkalosis and Compensation 16 Respiratory Regulation Of Acid-base Balance Respiratory system assists in regulation of pH in terms of [H+1] by controlling PaCO2 Tissues are constantly producing CO2 Equivalent to an acid since CO2 + H2O = H2CO3 Hyperventilation causes respiratory alkalosis- a loss of a loss of CO2 [H+1] Resulting in an increase in blood pH Hypoventilation causes respiratory acidosis- an increase of [H+1] because of reduced exhalation of CO2 Results in a decrease in blood pH There will be an increase in blood [HCO3-1] because of an increased H2CO3 dissociation into H+1 and HCO3-1 in RBCs Decreased exhalation will promote a shift of the carbonic acid reaction to the right; With an increased production of [H+] and [HCO3-] Followed by the chloride shift into erythrocytes with [HCO 3-] added to the blood plasma The increase in blood [HCO3-1] is independent of the kidneys The ratio of the bicarbonate ions to carbonic acid decreases but does not fully compensate 17 Acid-Base Abnormalities Acid-base abnormalities produce changes in pH, PCO2, and plasma bicarbonate – Most often result in acidosis Normal values: – pH 7.35-7.45 – PaCO2 35-45 mmHg – HCO3- 22-26 mEq/L Compensation – Full compensation restores pH to normal value – Partial compensation moves pH towards normal, but the pH is still abnormal – Mixed disorders are possible (pt with DKA receives opiates- mixed resp/metab acidosis) Primary Problem Respiratory acidosis Respiratory alkalosis Metabolic acidosis Metabolic alkalosis How pH Changes Compensation Respiratory Acidosis  Impaired alveolar ventilation – Causes: Increased CO2 production Decreased CO2 elimination Rebreathing – Consequences See table – Metabolic compensation Kidneys excrete H+ ions/conserve HCO3 Takes hours to days Acute respiratory acidosis pH lower Chronic respiratory acidosis pH partially compensated by kidneys Correcting PaCO2 in chronic COPD (retains HCO3-) may cause alkalosis Respiratory Alkalosis  Alveolar ventilation exceeds CO2 production – Causes: Mechanical ventilation Hypoxia (high altitude, low FiO2, profound anemia) Pain Anxiety Most asthma (not severe) Drugs Pulmonary embolism Reducing dead space with same alveolar ventilation – Consequences See table – Metabolic compensation Kidneys excrete HCO3- Metabolic Acidosis Metabolic acidosis is due to the ingestion, infusion, overproduction, or decreased renal excretion of H+ ions- or a loss of bicarbonate ions. – Causes: – Accumulation of nonvolatile acids Loss of bicarbonate Large volume resuscitation with a NaCl solution Acidosis with a large anion gap indicates an increased plasma concentration of anions other than chloride and bicarbonate or a decreased plasma concentration of K+, Ca++, and Mg++ Respiratory compensation is increased alveolar ventilation Increased minute ventilation Decreases PaCO2 PaCO2 decreases ~1 mmHg for every decrease 1 mEq/L HCO3- Treat underlying cause Gap acidosis- treat Non-gap acidosis- usually will give HCO3- Anion Gap Acidosis with a large anion gap indicates an increased plasma concentration of anions other than chloride and bicarbonate or a decreased plasma concentration of K+, Ca++, and Mg++ –Anion gap = Major cations – Major anions = 8-12 mEq/L –Anion gap >14 mEq/L= Anion gap acidosis » eg uremia, lactate, ethanol » Accumulation of acid –Anion gap < 14 mEq/L = Non-anion gap acidosis » eg diarrhea, large volume resuscitation with NaCl » Loss of bicarbonate or dilution Treat underlying cause –Gap acidosis- treat –Non-gap acidosis- usually will give HCO3- Metabolic Alkalosis Metabolic alkalosis is due to the ingestion, infusion, or excessive renal reabsorption of bases, or loss of hydrogen ions. – Causes: Increased HCO3Loss of nonvolatile acid Increased mineralcorticoid – Respiratory compensation is decreased alveolar ventilation Decreased minute ventilation Increases PaCO2 PaCO2 Increases ~1 mmHg for every increase 1 mEq/L HCO3Treatment Treat underlying cause Acetazolamide increases renal excretion of HCO3 Spironolactone is a mineralcorticoid antagonist Dialysis – Identify the consequence of each: (Increased or Decreased) Acidosis Alkalosis P50 (Increased = right shift, Decreased= left shift) Risk of dysrhythmias Cerebral blood flow and ICP Pulmonary vascular resistance Plasma K+ 24 IV. Causes of Hypoxia 25 Causes of Hypoxia 4 main causes of hypoxia- Brain and heart cells are most susceptible to hypoxia Hypoxemic hypoxia - reduced PO2 of arterial blood Lack of oxygen in air or factors affecting the alveolar-capillary unit Low PAO2- eg high altitude Diffusion impairment – pulmonary edema Shunts V/Q mismatch- low V/Q ratios contribute to arterial hypoxia Anemic hypoxia: reduced functioning hemoglobin available for oxygen transport Inadequate number of erythrocytes Inadequate amount of Hb in erythrocytes (iron deficiency) Presence of abnormal hemoglobin (sickle cell disease) Ischemic or Hypoperfusion hypoxia – low blood flow prevents adequate O2 delivery aka Stagnant hypoxia or circulatory hypoxia Histotoxic hypoxia: toxic agents prevent cellular utilization of O2 Cyanide- prevents mitochondria from utilizing oxygen in cellular respiration Combines with hemoglobin preferentially over oxygen Cyanosis occurs when more than 5 g Hb/dL blood is in the deoxy state Overutilization hypoxia can occur- metabolic demands exceed tissue supply 26 1. In comparing uncompensated respiratory acidosis (URA) and uncompensated metabolic acidosis (UMA) which one of the following is true? A. Plasma pH change is always greater in uncompensated respiratory acidosis compared to uncompensated metabolic acidosis B. There are no compensation mechanisms for metabolic acidosis C. Uncompensated respiratory acidosis involves changes in plasma [HCO3-], whereas plasma [HCO3-] is unchanged in uncompensated metabolic acidosis D. Uncompensated respiratory acidosis is associated with a change in PCO2, whereas in uncompensated metabolic acidosis PCO2 is constant 2. A 48 yo man arrives at the ED with decreased LOC. An arterial blood gas shows pH 7.25, PaCO2 25, PaO2 62, and HCO3- 15. Which of the following likely explains the observed abnormalities? A. Chronic obstructive pulmonary disease B. Diabetic ketoacidosis C. Gastroenteritis with vomiting D. Morbid obesity 3. A 65 yo female presents with hemorrhagic shock with an active GI bleed. After intubation to prevent aspiration of blood, vent settings are volume control ventilation with TV 450 mL, FiO2 0.5, breath sounds are equal, trachea is midline, and BP drops from 110/70 to 85/50. What is the most likely cause of her hypotension? A. B. C. D. Hypercarbia Atelectasis due to high FiO2 (absorption atelectasis) Right main stem intubation Decrease in venous return 27