Summary

This document discusses acid-base concepts, definitions, and calculations. It details the acid-base balance regulation in the human body and includes practice questions on the topic.

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ACID AND BASE CONCEPTS Dr NAVEEN KUMAR 1 Learning Objectives Unit-2: Acid and Base Concepts 2.1 The acid-base balance concept 2.2 Arrhenius definition 2.3 Acid–base equilibrium 2.4 Henderson-Hasselbalch equation...

ACID AND BASE CONCEPTS Dr NAVEEN KUMAR 1 Learning Objectives Unit-2: Acid and Base Concepts 2.1 The acid-base balance concept 2.2 Arrhenius definition 2.3 Acid–base equilibrium 2.4 Henderson-Hasselbalch equation 2 Arrhenius definition of Acids & Bases Acids- releases proton in water (proton donor). HA H+ + A- Acid Proton Conjugate base Base- accepts proton in water (proton acceptor) or releases hydroxyl ions (OH-) in water. BOH OH- + B+ Base Hydroxyl ion Conjugate acid Each acid has a characteristic tendency to lose its proton(H +) in an aqueous solution. The stronger the acid, the greater its tendency to lose its proton(H +) but the weak acids release their protons slowly. 3 Strong acids: A strong acid is an acid that dissociates completely into its ions in an aqueous solution or water. Eg: HCl, H2SO4, HNO3 (Inorganic acids) Weak acids: A weak acid is an acid that partially dissociates into its ions in an aqueous solution or water. Eg: Inorganic acids: Formic acid (HCOOH), Acetic acid (CH3COOH), Oxalic acid (C2H2O4), Benzoic acid (C6H5COOH) Organic acids: Lactic acid, Phosphoric acid, Carbonic acid and Citric acid. Weak acids are common in biological systems and produced during metabolic reactions. 4 Strong bases: Strong bases can be defined as basic substances that can be completely dissociate into their ions when dissolved in solutions. Eg: NaOH, KOH, Ba(OH2) Weak bases: Weak bases can be defined as basic substances that do not completely dissociate into their ions when dissolved in solutions. Eg: Amines, NH4+ , Aniline, Pyridine 5 Acids Produced In The Human Body Carbonic acid - Oxidation of carbon compounds Sulphuric acid - Oxidation of sulphur containing amino acids. Phosphoric acid- metabolism of dietary phosphoproteins , nucleoproteins, phosphatides. Organic acid- oxidation of carbohydrates, fats and proteins. e.g. pyruvic acid ,lactic acid , acetoacetic acid etc. Iatrogenic : - certain medicine like NH4Cl, mandelic acid etc. NOTE:DIET RICH IN ANIMAL PROTEIN RESULTS IN MORE ACID PRODUCTION. 6 Acidic Substances of Human body: Carbonic acid(H2CO3) Phosphoric acid( H3PO4) Sulphuric acid (H2SO4) Organic Acids: Lactate, Acetoactate, Pyruvate Alkaline Substances of Human body: Citrate Bicarbonates 7 The tendency of any acid (HA) to lose proton and form its conjugate base is defined as Dissociation constant (Ka). The dissociation constant of acid can be written as pKa = log 1 / Ka = -log Ka pKa is a quantitative measure of acid strength. 8 The Ka and Kb values are usually expressed in moles per liter (mol/L). The negative log base ten of the Ka value is called pKa, and the negative log of the Kb value is called pKb. Smaller pKa (1) refers to Weaker acid - the weaker tendency to dissociate a Proton. pKb is the criterion used to estimate the alkalinity of the bases. It is equivalent to the negative logarithm of base dissociation constant, Kb. The lesser the pKb, the more stronger the base will be, conversely the 9 higher the pKb the more weaker base or alkali. 10 pH Sorenson introduced the pH scale in 1909 using the symbol pH ranging from 0 – 14. pH refers to the H+ ion concentrations. The concentration of H+ must be expressed in Molar terms i.e. Moles/litre. The term pH is defined by the expression of pH = log 1 / [H+] = -log [H+] p - denotes the negative logarithm of H+. In pH scale 0 - 7 refers to Acidic, 7 refers to Neutral and 7 – 14 refers to Basic or Alkali. 11 For a precisely neutral solution at 250C, in which the concentration of Hydrogen ions is 1.0 x 10-7M, the pH can be calculated as follows pH = log 1 / [1.0 x 10-7] = 7.0 12 The pH scale corresponds to the concentration of hydrogen ions. For example pure water H+ ion concentration is 1 x 10^-7 M, therefore the pH would then be 7. 13 Definition of Acid Base balance Acid-base balance refers to the mechanisms, the body uses to keep its fluids close to neutral pH (that is, neither basic nor acidic) so that the body can function normally. Or Equilibrium between the acid and base elements of the blood and body fluids is called as acid base balance. 14 Regulation of Acid-Base Balance The body has three mechanisms to maintain acid-base balance Buffering The The metabolic mechanism respiratory or renal (Blood Buffer) compensation compensation mechanism mechanism 15 Buffers Buffers are aqueous systems that tend to resist or prevent the changes in pH of the solution upon addition of acid (H+) or base (OH-) ions are added. Buffers are extremely important in biological systems. Buffers are Mixtures of Weak acids (Proton donor) and their Conjugate base (Proton acceptor). Buffers are responsible for maintaining blood pH, maintaining physiological pH inside cells Example: Acetic acid (CH3COOH) and Acetate ion (CH3COO-) 16 Buffer systems and important characteristics A buffer system is a solution that resists a change in pH when acids or bases are added to it, so much so it enables a suitable environment for the chemical reactions that requires a certain pH to occur. The buffer systems functioning in the blood include bicarbonate- carbonic acid buffers, phosphate and proteins. The kidneys help control acid-base balance by excreting hydrogen ions and generating bicarbonate that helps maintain blood pH within a normal range. Protein buffer systems work predominantly inside cells. 17 Importance of Biological Buffer To maintain homeostasis. To regulate enzymatic function. To control pH in biochemical reactions of various metabolic pathways. 18 BUFFER SYSTEMS OF THE HUMAN BODY In human body two major types of Buffer systems are responsible for the maintenance of pH. 19 1). Bicarbonate Buffer System: It is the major buffer system responsible for Extracellular fluid (Blood) pH maintenance-7.4 (7.35-7.45). Composition: Sodium bicarbonate (NaHCO3) and Carbonic acid (H2CO3) in 20:1 H++ NaHCO3 ↔ H2CO3 + Na+ OH- + H2CO3 ↔ HCO3- + H2O 2). Phosphate Buffer System: It is the major buffer system responsible for Intracellular pH maintenance-7.1 - 7.2 Composition: Mono hydrogen phosphate (HPO42-) and Di hydrogen phosphate (H2PO4-) in 4:1 ratio. This ratio is kept constant with the help of the kidneys. Thus, phosphate buffer system is directly linked up with the kidneys. H+ +20 2- - - - 2- 3). Protein Buffer System : Includes hemoglobin and works in blood. Proteins are made up of amino acids and having Carboxyl group(-COOH) and Amino group(-NH2). Carboxyl group gives up H+ where as Amino Group accepts H+. Side chains that can buffer H+ are present on 20 amino acids. Among all amino acids Histidine(H) and Cysteine(C) posses buffering capacity. 21 Bicarbonate Buffer System 22 23 Hemoglobin as Buffer System 24 ACID BASE DISORDERS ACIDOSIS: PH 7.45 i) RESPIRATORY ALKALOSIS ii) METABOLIC ALKALOSIS 25 ACID- BASE BALANCE The pH of the extracellular fluid of human body maintaining in the range of 7.35 – 7.45. The changes in pH leads to Acid-Base imbalance that may leads to the dysfunction of the Cellular and metabolic activities. When the pH of blood is < 7.35, this condition referred as Acidosis. When the pH of the blood is >7.45, this condition referred as Alkalosis. Two types of conditions in Acidosis and Alkalosis, these include Respiratory & Metabolic. 26 27 28 Acid–Base Balance Disturbances Interactions among the Carbonic Acid–Bicarbonate Buffer System and Compensatory Mechanisms in the Regulation of Plasma pH. 29 ACIDOSIS ( pH 45mmHg – Hypercapnea. Chronic conditions: Depression of respiratory center in brain that controls breathing rate – drugs or head trauma Paralysis of respiratory or chest muscles Emphysema Asthma Pneumonia Pulmonary edema Obstruction of respiratory tract Congestive Cardiac Failure 30 RESPIRATORY ACIDOSIS Obstruction of air passages due to: Vomit, Anaphylaxis, Tracheal Cancer 31 Metabolic Acidosis Bicarbonate (HCO3-) levels decreases (< 22 mEq/Litre) due to loss through Diarrhea and Renal dysfunction. The main reason for this condition is untreated diabetes that leads to the production of excess amount of ketone boides in body; these include β-Hydroxybutyric acid and Aceto acetic acid. These ketone bodies are acidic in nature and reduces the pH of the blood called Ketoacidosis which eventually leads to coma and finally death. Lacto acidosis – it due to excess of Lactic acid in blood due to strenuous exercise. 32 Treatment of Metabolic Acidosis In ketoacidosis, give intravenous fluids, insulin and potassium replacement. Oxygen is given to the patient diagnosed with lactic acidosis. In all cases, potassium abnormalities should be carefully treated. Bicarbonate Requirement mEq of base needed = body wt in Kg x 0.2 – base excess in mEq/L. 33 ALKALOSIS ( pH - >7.45 ) Respiratory Alkalosis: Carbonic acid (H2CO3) levels decreases; CO2 levels decreases < 35mmHg – Hypocapnea. It is due to hyperventilation and excess removal of CO2. Metabolic Alkalosis: Bicarbonate (HCO3-) levels increases (> 26 mEq/Litre). It is due to excessive loss of acids due to prolonged vomiting. 34 35 Organ dysfunction And Acid Base Imbalance CNS – respiratory acidosis (suppression) and alkalosis (stimulation) Pulmonary – respiratory acidosis (COPD) and alkalosis (hypoxia, pulmonary embolism) Cardiac – respiratory alkalosis, respiratory acidosis, metabolic acidosis (pulmonary edema) GIT – metabolic alkalosis (vomiting) and acidosis (diarrhea) Liver – respiratory alkalosis, metabolic acidosis (liver failure) Kidney – metabolic acidosis (RTA) and alkalosis (1st Aldosterone) 36 ACIDOSIS decreased failure of metabolic production absorption of prolonged removal of kidneys to acid of keto acids metabolic acids diarrhea CO2 from excrete from GI tract lungs acids accumulation accumulation excessive loss of CO2 in blood of acid in blood of NaHCO3 from blood deep vomiting from respiratory metabolic GI tract increase in acidosis plasma H+ acidosis concentratio kidney n disease (uremia) depression of nervous system 37 ALKALOSIS anxiety overdose high prolonged ingestion of excess of certain altitudes vomiting excessive aldosterone drugs alkaline drugs hyperventilatio loss of acid accumulation n of base loss of CO2 and H2CO2 from blood respiratory metabolic alkalosis alkalosis decrease in plasma H+ concentratio n overexcitability of nervous system 38 Acidosis and Alkalosis Respiratory Acidosis Respiratory Alkalosis A. Pneumonia A. High altitude B. Bronchitis, Asthma , COPD B. Hyperventilation C. Pneumothorax C. Hysteria D. Narcotics, Sedatives D. Febrile conditions E. Paralysis of respiratory E. Septicemia muscles F. Meningitis F. CNS trauma G. Congestive Cardiac Failure G. Ascites, Peritonitis Metabolic Acidosis Metabolic Alkalosis i. High anion gap A. Severe vomiting A. Diabetic ketosis B. Cushing Syndrome B. Lactic acidosis C. Milk alkali syndrome C. Renal failure D. Diuretic therapy (K loss) ii. Normal anion gap A. Renal tubular acidosis B. CA Inhibitors C. Diarrhea 39 Respiratory Acidosis Respiratory Alkalosis A. Pneumonia A. High altitude B. Bronchitis, Asthma , COPD B. Hyperventilation C. Pneumothorax C. Hysteria D. Narcotics, Sedatives D. Febrile conditions E. Paralysis of respiratory E. Septicemia muscles F. Meningitis F. CNS trauma G. Congestive Cardiac Failure G. Ascites, Peritonitis Metabolic Acidosis Metabolic Alkalosis i. High anion gap A. Severe vomiting A. Diabetic ketosis B. Cushing Syndrome B. Lactic acidosis C. Milk alkali syndrome C. Renal failure D. Diuretic therapy (K loss) ii. Normal anion gap A. Renal tubular acidosis B. CA Inhibitors C. Diarrhea 40 Acidosis and Alkalosis Respiratory Acidosis Respiratory Alkalosis A. Pneumonia A. High altitude B. Bronchitis, Asthma , COPD B. Hyperventilation C. Pneumothorax C. Hysteria D. Narcotics, Sedatives D. Febrile conditions E. Paralysis of respiratory E. Septicemia muscles F. Meningitis F. CNS trauma G. Congestive Cardiac Failure G. Ascites, Peritonitis Metabolic Acidosis Metabolic Alkalosis i. High anion gap A. Severe vomiting A. Diabetic ketosis B. Cushing Syndrome B. Lactic acidosis C. Milk alkali syndrome C. Renal failure D. Diuretic therapy (K loss) ii. Normal anion gap A. Renal tubular acidosis B. CA Inhibitors C. Diarrhea 41 Respiratory Acidosis Respiratory Alkalosis A. Pneumonia A. High altitude B. Bronchitis, Asthma , COPD B. Hyperventilation C. Pneumothorax C. Hysteria D. Narcotics, Sedatives D. Febrile conditions E. Paralysis of respiratory E. Septicemia muscles F. Meningitis F. CNS trauma G. Congestive Cardiac Failure G. Ascites, Peritonitis Metabolic Acidosis Metabolic Alkalosis i. High anion gap A. Severe vomiting A. Diabetic ketosis B. Cushing Syndrome B. Lactic acidosis C. Milk alkali syndrome C. Renal failure D. Diuretic therapy (K+ loss) ii. Normal anion gap A. Renal tubular acidosis B. CA Inhibitors C. Diarrhea 42 ANION GAP The sum of cations and anions in ECF is always equal , so as to maintain the electrical neutrality. Commonly measured electrolytes in plasma are Na+, K+, Cl-, HCO3-. Sodium and Potassium accounts for 95% of cations. Chloride and bicarbonate accounts for 85% of anions. There is difference between measured anion and cation. The unmeasured anion in the plasma constitutes the ANION GAP The unmeasured anions, i.e. PO4-, SO4-, proteins and organic acids average - 24 mmol/L. 43 This is due to presence of protein anions, sulphate, phosphate and organic acids. Serum Anion Gap (A-): (Na+ + K+) - (Cl- + HCO3-) = Anion gap Normally anion gap is about 15 mEq/l Normal A- range is typically 12 ± 4 mEq/L 44 Calculation of Anion Gap Na + + K+ = Cl- + HCO3- 140 + 5 = 105 + 25 A- = 15 mEq/L 45 Significance of Anion Gap Calculation Calculation of Anion gap and its values help in diagnosing conditions of Acid Base Balance and Imbalance. 46 47 This is mainly a measure for patients with kidney or gastrointestinal problems. This test does not definitely point toward any one condition. Anion gap reveals the presence of metabolic acidosis, where the pH levels in your body are off-kilter. It differentiates the causes of metabolic acidosis and helps confirm other findings. Let’s take for instance that a patient has lactic acidosis (where there's also a buildup of lactate. In this case, the serum bicarbonate levels will automatically reduce (because of the buildup) so that when you calculate for the anion gap, you’ll see that the anion gap increases. 48 High anion gap acidosis (>25) I. Renal failure II. Diabetic Metabolic Ketoacidosis III. Lactic acidosis IV. Aspirin, Ethylene, Glycol, Methanol, Paraldehyde Normal anion gap acidosis I. Diarrhoea II. Hyperchloremic acidosis Low anion gap I. Multiple myeloma 49 Stepwise Approaches History & physical examination Arterial blood gas for pH, pCO2, (HCO3-) Use the HCO3- from ABG to determine compensation Serum Na+, K+, Cl-, CO2 content Use CO2 content to calculate anion gap Calculate anion gap Determine appropriate compensation Determine the primary cause 50 DIAGNOSTIC LAB VALUES & INTERPRETATION 51 Arterial Blood Gas(ABG )Analyzer determines Acid Base Balance and Imbalance Portable ABG Analyzer 52 Diagnosis of Acid-Base Imbalances 1. Note whether the pH is low (acidosis) or high (alkalosis) 2. Decide which value, pCO2 or HCO3- , is outside the normal range 3. If the cause is a change in pCO2 /H2CO3 the problem is respiratory. 4. If the change is in HCO3- the problem is metabolic. 53 Normal Serum Electrolyte and Arterial Blood Gas Values  Arterial blood pH = 7.35 -7.45  Bicarbonate = 22–26 mEq/L  Chloride = 96–106 mEq/L  Potassium = 3.5–5 mEq/L  Sodium = 136–145 mEq/L  pO2 = 95 (85–100) mm Hg  pCO2 = 40 (35–45) mm Hg  Base Excess = -2 to +2 54 Case Study A patient is in intensive care because he suffered a severe myocardial infarction 3 days ago. The lab reports the following values from an arterial blood sample: pH 7.30 HCO3- = 19 mEq / L ( 22 - 26) pCO2 = 32 mm Hg (35 - 45) 55 Acid-base Parameters are to be Checked in the patients with Any serious illness Multi-organ failure Respiratory failure Cardiac failure Uncontrolled diabetes mellitus Poisoning (barbiturates, ethylene glycol) 56 Henderson-Hasselbalch Equation The Henderson-Hasselbalch equation provides a mathematical relationship between the pH, pKa, and the concentrations of the acid and its conjugate base. The quantitative relationship among pH, buffering action of a mixture of weak acid with its conjugate base, and the pKa of the weak acid is given by a simple expression called Henderson-Hasselbalch Equation. It allows us to calculate pKa, given pH and the molar ratio of proton donor and acceptor. 57 Henderson Hasselbalch Equation-Bicaronate Buffer pH= pka +log [HCO3-] / [H2CO3] At pH 7.4 the ratio of HCO3-/H2CO3 is 20:1. A buffer is most effective when pH=pKa When concentration of salt and acid are equal. 58 Significance of Henderson Hasselbalch Equation The equation helps in calculating pH of Buffers based on known concentrations. The equation helps in assessing status of Acid Base balance. 59 Practice Questions What is the normal pH range of human blood? A) 7.0 - 7.2 B) 7.35 - 7.45 C) 7.5 - 7.7 D) 6.8 - 7.2 Which of the following is the primary buffer system in the human body? A) Phosphate buffer system B) Protein buffer system C) Bicarbonate buffer system D) Hemoglobin buffer system A patient presents with a pH of 7.30, pCO2 of 50 mmHg, and HCO3- of 24 mEq/L. What type of acid-base disturbance is present? A) Metabolic acidosis B) Respiratory acidosis C) Metabolic alkalosis D) Respiratory alkalosis Which of the following acids is produced during strenuous exercise due to excess lactic acid in the blood? A) Ketoacidosis B) Lactic acidosis C) Sulphuric acidosis D) Pyruvic acidosis 60 What is the primary organ responsible for regulating bicarbonate levels in the blood? A) Lungs B) Liver C) Kidneys D) Heart In respiratory alkalosis, what would you expect the bicarbonate (HCO3-) levels to be? A) Decreased B) Increased C) Normal D) Variable Which of the following statements is true regarding respiratory acidosis? A) It is caused by excessive loss of carbon dioxide. B) It can result from conditions like COPD. C) It is characterized by a high pH. D) It is primarily a metabolic disorder. Which of the following substances is responsible for the regulation of intracellular pH? A) Phosphate buffer system B) Bicarbonate buffer system C) Ammonia buffer system D) Citrate buffer system 61 What happens to pH in metabolic alkalosis? A) Decreases B) Increases C) Remains the same D) Fluctuates Which of the following can be a cause of respiratory alkalosis? A) Severe diarrhea B) Anxiety or panic attacks C) Kidney failure D) Renal tubular acidosis Answer: B) Anxiety or panic attacks Which of the following conditions can lead to metabolic acidosis? A) Vomiting B) Hyperventilation C) Diabetic ketoacidosis D) Excessive antacid intake Which of the following is a conjugate base of carbonic acid? A) HCO3- B) H2CO3 C) OH- 62 D) NaHCO3 Thank You 63

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