Acid-base Balance Lecture Notes PDF

## CASE STUDY - Mrs. Hira, a 75 year old diabetic, has a long history of non-compliance with her insulin. - She was recently admitted to the hospital with the following ABG results: - pH = 7.26 - PCO2 = 42 mmHg - HCO3- = 17 mg/dl ## Lecture Objectives At the end of the lecture student...

## CASE STUDY - Mrs. Hira, a 75 year old diabetic, has a long history of non-compliance with her insulin. - She was recently admitted to the hospital with the following ABG results: - pH = 7.26 - PCO2 = 42 mmHg - HCO3- = 17 mg/dl ## Lecture Objectives At the end of the lecture students will be able to: - List the volatile and Non-volatile acids - Describe the Henderson's Hasselbalch Equation - Explain the mechanism of buffer in human body - Discuss the normal regulation of pH by buffers, respiratory and renal systems - Explain the anion gap and its biochemical significance - Interpret the values of Arterial Blood Gases (ABGs) ## The Body and pH - Homeostasis of pH is tightly controlled - Extracellular fluid = 7.4 - Blood = 7.35 - 7.45 - < 6.8 or > 8.0 death occurs - Acidosis (acidemia) below 7.35 - Alkalosis (alkalemia) above 7.45 A diagram showing the pH scale and the normal, acidosis and alkalosis ranges is included. ## Acids and Bases - **Bronsted-Lowry theory** - Acids are H+ donors. - Bases are H+ acceptors. - **Strong Acids** - dissociate completely in solution - HCl, NaOH - **Weak Acids** - dissociate only partially in solution - Lactic acid, carbonic acid ## Acids & Bases - **Strong acid:** HCl + H2O → H+ + Cl- - **Weak acid:** CH3COOH + H2O ↔ CH3COO- + H+ - **Strong base:** NaOH + H2O → Na+ + OH- - **Weak base:** NH3 + H2O ↔ NH4+ + OH- ## Buffers - **FUNCTION:** Resists change in pH, following the addition of strong acid/base. - **COMPOSITION:** Buffer always exists as a PAIR - Weak acid + salt of its conjugate base - Weak base + salt of its conjugate acid ## Henderson-Hasselbalch Equation - To determine pH of blood or any other buffer solution. - $pH = pK_a + log \frac{[conjugate \ base]}{[acid]}$ ## How buffer resist the change in pH - Buffer pH=pKa when [HA]=[A-] - A diagram showing how a weak acid reacts with HCl and NaOH is included. ## Efficiency of a Buffer - A buffer is most effective when: [Salt] = [Acid] - i.e pH=pKa ## Titration Curve For Weak Acids A graph is included showing the Titration Curve for Weak Acids. ## Acids Produced in 24 Hours is Sufficient to Drop the Blood pH From 7.4 to 1 - During metabolic reactions - Lactic acid and Pyruvic acid (Glucose oxidation). - Acetoacetic acid, Beta hydroxyl butyrate (oxidation of Fats). - A huge amount of carbon dioxide is produced during cellular respiration is converted to Carbonic acid. - Uric acid, Oxaloacetic acid and Succinic acid are liberated during normal biological activities. ## Even a slight change in pH may be life threatening - Most enzymes function only with narrow pH ranges - Acid-base balance can also affect electrolytes (Na+, K+, Cl-) - Can also affect hormones ## Mechanisms of Regulation of pH - **First line of defense against pH shift** - Chemical buffer systems: - Bicarbonate buffer system - Phosphate buffer system - Protein buffer system - **Second line of defense against pH shift** - Physiological buffers: - Respiratory mechanism (CO2 excretion) - Renal mechanism (H+ excretion) ## Buffers of Body Fluids - **Bicarbonate buffer System**: H2CO3/ NaHCO3 - Carbonic acid / Bicarbonates - Major extracellular buffer - **Phosphate buffers**: NaH2PO4 / Na2HPO4 - Major intracellular buffer - **Proteins buffers (Includes Hb)** - Intracellular and extraxellular Buffers ## Bicarbonate Buffer System - Major extracellular buffering system - When a strong acid enters the blood it is fixed up by Bicarbonate ion (HCO3) which is converted to carbonic acid (H2CO3). - H+ + HCO3 ↔ H2CO3 - OH + H2CO3 ↔ HCO3 + H2O - Accounts for 65% of the buffering capacity in plasma. ## Normal ratio in blood - The ratio of HCO3 (salt) to H2CO3 (acid) is normally 20:1 - Allows blood pH of 7.40 - The pH falls (acidosis) as bicarbonate decreases in relation to carbonic acid - The pH rises (alkalosis) as bicarbonate increases in relation to carbonic acid ## Phosphate Buffer System - Important intracellular buffer system - When a strong acid enters it is fixed up by alkaline PO4 (Na2HPO4) which is converted to acid PO4 (NaH2PO4). - HCI + Na2HPO4 ↔ NaH2PO4 + NaCl - NaOH + NaH2PO4 ↔ Na2HPO4 + H2O ## Protein buffer system - Most abundant buffer in Intracellular fluid and blood plasma - Albumin in blood plasma - A chemical diagram showing the chemical reactions of protein buffers with H+ is included. ## Hemoglobin Buffer System (Dig) - **Intracellular Buffer System** - Deoxygenated hemoglobin (Hb) is a better proton acceptor than the oxygenated hemoglobin (HbO2). - In red blood cells, the enzyme carbonic anhydrase catalyzes the conversion of dissolved carbon dioxide to carbonic acid, which rapidly dissociates to bicarbonate and a free proton: CO2 + H2O → H2CO3 → H+ + HCO3-. - Bicarbonate diffuses out of red cells. Deoxygenated hemoglobin accept the proton. H+ + Hb ↔ H+Hb ## Carbon Dioxide Transport in the Blood & Haemoglobin Buffering A diagram is included showing the transport of carbon dioxide in the blood with the Haemoglobin buffering system. ## Hemoglobin Buffer System - As carbonic acid dissociates Bicarbonate ions diffuse into plasma, in exchange for chloride ions (chloride shift). - Hydrogen ions are buffered by hemoglobin molecules. - Helps prevent major changes in pH when plasma PCO2 is rising or falling. - Most of the buffering action of Hb is due to the imidazole group of amino acid histidine. ## BUFFER SYSTEMS A diagram illustrating the various buffers of the body is included. ## Maintenance of blood pH 1. **Blood Buffers** - Uses bicarbonate, phosphate, and protein 2. **Respiratory Mechanism** - Uses bicarbonate 3. **Renal Mechanism** - Uses bicarbonate, phosphate, and ammonia ## Rates of correction - Buffers function almost instantaneously - Respiratory mechanisms take several minutes to hours - Renal mechanisms may take several hours to days ## When chemical buffers alone cannot prevent changes in blood pH, the respiratory and renal system is the second line of defense against changes ## 2. Respiratory mechanisms - Lungs (For volatile acids) - Example: Carbonic acid A diagram of the lungs is included. ## 3. Renal Mechanisms - Kidneys (For non-volatile acids) - Example: lactic acids, Keto acids A diagram of a kidney is included. ## What is the ABG? - Arterial blood gas analysis is an essential part for diagnosing and managing the patient's oxygenation status, ventilation status and acid base balance. - Drawn from arteries(radial, brachial and femoral) - A diagram of the components of an ABG is included, which show: Oxygenation, Ventilation, and Acid-Base. ## ABGs - An arterial blood gas (ABG) is a sample of arterial blood that reports: - pH: 7.35-7.45 (H ion concentration) - PaCO2: 35-45 mm Hg. (dissolved CO2 in blood) - HCO3: 22 to 26 mEq/L (metabolic effectiveness) - PaO2: 80-100 mm Hg (02 content of blood) - SaO2 = 95% - 100% (% of hemoglobin saturated) ## The acid-base disorders are mainly classified as - **Acidosis** - Metabolic acidosis (due to ↓ in bicarbonate) - Respiratory acidosis (due to ↑ in carbonic acid) - **Alkalosis** - Metabolic alkalosis (due to ↑ in bicarbonate) - Respiratory alkalosis (due to ↓ in carbonic acid) A diagram showing the four types of acid-base disorders is included. ## Anion Gap - **Clinical Significance of Anion Gap** - The anion gap is a biochemical tool which sometimes helps in assessing acid-base problems. It is used for the diagnosis of different causes of metabolic acidosis. ## Anion Gap - The total concentration of cations and anions (expressed as mEq/l) is equal in the body fluids. - This is required to maintain electrical neutrality. - The commonly measured electrolytes in the plasma are Na+, K+, CI and HCO3-. - Sodium and potassium together account for 95% of the cations whereas chloride and bicarbonate account for only 86% of the anions. - Hence there is always a difference between the measured cations and the anions. - This is due to the presence of protein anions, sulphate, phosphate and organic acids. ## Anion Gap - Anion gap is defined as the difference between the total concentration of measured cations (Na+ and K+) and that of measured anion (CI and HCO3). - The anion gap (A) in fact represents the unmeasured anions in the plasma which may be calculated as follows... - Na+ + K+ = Cl- + HCO3- + A- - 136 + 4 = 100 + 25 + A- - A- = 15 mEq/l - The anion gap in a healthy individual is around 15 mEq/l (range 8-18 mEq/l) ## Anion gap and Metabolic Acidosis - Increased production and accumulation of organic acids causes an elevation in the anion gap. - This type of picture is seen in metabolic acidosis associated with diabetes (ketoacidosis) A diagram showing the electrolyte concentrations in normal, acidosis and hyperchloremic acidosis is included. ## High anion gap acidosis - Renal failure - Diabetic ketoacidosis - Lactic acidosis ## Normal anion gap acidosis - Diarrhoea - Hyperchloremic acidosis ## Low anion gap - Multiple myeloma