An important aspect of clinical chemistry consciousness- death. is information on a patient's acid-base balance and blood gas homeostasis. Acid-Base balance These data often are used to assess • Because pH is the negative log of patients in life-threatening situations. the cH+ This lecture discusses: • Decrease in H+ ion Increase pH • Increase H + ions Decrease pH the body's mechanisms to maintain • Arterial blood pH is controlled by: acid-base balance and 1. Buffers exchange of gases, carbon dioxide and 2. Respiratory System oxygen, 3. and Kidneys
Definitions: Acid, Base, Buffer Buffer System: Regulation of H+
a substance that yields H+ ions in H2O. • First line of defense to changes in
H+ consist of: Base: - weak acid (H2CO3) & its salt a substance that yields a hydroxyl ion (HCO3-) (OH-). • Add acid to H2CO3 & HCO3- system: Buffer: - the HCO3- combines with H from the combination of a weak acid and its the acid to form H2CO3. salt, is a system that resists changes in • Add a base to the system: pH. - H2CO3 combines with OH to form H2O and HCO3 Strong acids vs. Strong Base • Keeps the body at the correct pH ( ) have pK value of less than 3.0 Buffer System: Regulation of H+ Strong base: Bicarbonate – carbonic acid system has have a pK value greater than 9.0 low buffering capacity but still an important buffer system for 3 reasons: Acid-Base balance 1. H2CO3 dissociates into CO2 & Maintenance of hydrogen ions: H2O allowing H+ to be eliminated as CO2 by lungs • Body produces mmol of H/day, 2. Changes in CO2 modify the • normal concentration of H in ECF ventilation rate ranges from nmol (pH, ) 3. HCO3- conc. can be altered by • Any deviation from the values the the kidneys body will try to compensate. • >44 nmol/L: altered consciousness, coma- death Other systems - To maintain electroneutrality chloride diffuses into the cell • HPO4–2 H2PO4– system (chloride shift) • Proteins are capable of binding H+ • Hemoglobin Regulation of Acid-Base Balance by Lungs Regulation of Acid-Base Balance: Lungs and Kidneys In the lungs:
• The lungs and kidneys play • The process is reversed.
important roles in regulating blood • Inspired O2 diffuses from the alveoli pH. into the blood and is bound to • The lungs regulate pH through hemoglobin, forming oxyhemoglobin retention or elimination of CO2 (O2Hb). - by changing the rate and volume • The H+ that was carried on the of ventilation. (reduced) hemoglobin in the venous • The kidneys regulate pH by: blood is released to recombine with - excreting acid, primarily in the HCO3- to form H2CO3, ammonium ion, - which dissociates into H2O and - and by reclaiming HCO3- from CO2. the glomerular filtrate. • The CO2 diffuses into the alveoli and is eliminated through ventilation. Regulation of Acid-Base Balance by • The net effect of the interaction of Lungs these two buffering systems is a • End product of aerobic metabolic minimal change in H+ concentration process is CO2 between the venous and arterial - diffuses out the tissue into circulation. plasma and RBC • When the lungs do not remove CO2 at the rate of its production In Plasma & RBCs: (hypoventilation) it accumulates in - a small amount of CO2 is the blood, dissolved - causing an increase in H+ - or combined with proteins to form concentration. carbamino compounds. • If, however, CO2 removal is faster - Most of the CO2 combines with than production (hyperventilation) H2O to form H2CO3, which - the H+ concentration will be quickly dissociates into H+ and decreased. HCO3- • Consequently, ventilation affects the - The dissociation of H2CO3 pH of the blood. causes the HCO3- concentration • A change in the H+ concentration of to increase in the RBCs and blood that results from non- diffuse into the plasma. respiratory disturbances causes the respiratory center to respond - altering the rate of ventilation in • A disorder caused by ventilatory an effort to restore the blood pH dysfunction is termed primary to normal. respiratory acidosis or alkalosis. • The lungs, by responding within • A disorder resulting from a change in seconds, together with the buffer the bicarbonate level is termed a systems, provide the first line of non-respiratory disorder. defense to changes in acid-base • Technically, the suffix -osis refers to status. a process in the body; the suffix - emia refers to the corresponding Kidney system state in blood • Main role is reabsorption of • Body's cellular and metabolic bicarbonate activities are pH dependent • Kidneys respond to increase or • The body tries to restore acid-base decrease in hydrogen ions by homeostasis whenever an imbalance selectively excreting or reabsorbing: occurs. 1. Hydrogen ions • This action is termed compensation 2. Sodium • Done by altering the factor not 3. Chloride primarily affected by the pathologic 4. Phosphate process. 5. Ammonia - eg., if the imbalance is of 6. Bicarbonate nonrespiratory origin, the body Reabsorption of Bicarbonate compensates by altering ventilation. • Reabsorption of bicarbonate (HCO3 - For disturbances of the –) takes place in the renal tubule respiratory component, the cells. kidneys compensate by • Na + is exchanged for H+ ion. selectively excreting or • H+ ion combines with the HCO3 – reabsorbing anions and cations. and carbonic acid dissociates into • Lungs can compensate immediately H2O and CO2. but: • CO2 diffuses into the tubule cells - the response is short term combining with H2O forming H2CO3. - and often incomplete. • Reabsorption of bicarbonate in the • The kidneys compensate are slower blood system. to respond (2- 4 days) but: • Urinary H+ combines with HPO4– - the response is long term and NH3. - and potentially complete
• Alkalosis (increased pH)→alkalemia • Bicarbonate decreased (<24 mmol/L) • metabolic or respiratory • Caused by: - acid producing substance or Metabolic Acidosis process Caused by either - or reduce excretion of acids i) INCREASED acid production or Compensation: ii) IMPAIRED acid excretion. Can occur 1o - Respiratory compensation: in response to; - Hyperventilation, decrease CO2 1) High protein diet - protein catabolism in circulation. produces 2o - Renal compensation: phosphoric acid and sulphuric acid. - increase H ion loss by increasing 2) High fat diet - fat catabolism H2PO4 and NH4 excretion and produces fatty acids. retain HCO3- - acid-producing substance, such 3) Heavy exercise – stimulates as ammonium chloride or calcium anaerobic metabolism, producing lactic chloride, or by excessive acid. formation of organic acids as seen with diabetic ketoacidosis 4) Addition of fixed acids and starvation (e.g. diabetic ketoacidosis). Respiratory Acidosis Caused by 5) Severe diarrhoea - loss of hypoventilation bicarbonate from intestines. • decrease the elimination of CO2 in 6) Alterations in renal function (inability the lungs, it builds up in the blood to excrete H+). • decrease in pH, increase in H and 7) Tissue hypoxia (produces lactic acid) HCO3 8) Ingested substances such as • Diseases: emphysema, drugs , methanol, aspirin (acetylsalicylic acid), congestive heart failure, ethylene glycol. bronchopneumonia. Metabolic (non-respiratory) alkalosis Compensation • HCO3- increased, H+ decreased, pH • Renal compensation increased - increase H+ excretion & increase • Causes of non-respiratory alkalosis: reabsorption of HCO3- - excess administration of - Emphysema gradually damages NaHCO3 the air sacs (alveoli) in the lungs, - ingestion of HCO3– producing making progressively shorter of salts such as Na- lactate, citrate breath or acetate - excessive loss of acid through vomiting Compensation • Respiratory compensation - hypoxemia; - Hypoventilation with CO2 - chemical stimulation of the retention respiratory center by drugs, such • Renal compensation as salicylates (stimulate the - excrete HCO3- and retain H+ respiratory center to cause ions. hyperventilation); - pulmonary fibrosis. Metabolic Alkalosis Compensation Relatively rare phenomenon that can occur in response to; Renal compensation
1) Excessive vomiting - loss of HCI from - decrease renal excretion of H+
stomach (:: retention of (duodenal) ions, HCO3- excreted. bicarbonate in circulation). - Hypoxemia: an abnormally low concentration of oxygen in the 2) Alterations in renal function (f blood. excretion of titratable acid - pulmonary fibrosis causes faster e.g., thiazide and loop diuretics 1 Nat breathing and more excretion of reabsorption ↑ excretion of H+). CO2 - Salicylates directly stimulate the 3) Excessive ingestion of bicarbonate respiratory center to cause antacids paired with renal failure. hyperventilation 4) Volume contraction (e.g via diuretic ABG ANALYSIS therapy 1 plasma [HCO,1). ABG-Arterial blood gas 5) Excess aldosterone (stimulates collecting duct H+-ATPases to excrete –Measurement of the acidity and H+). alkalinity of the arterial circulation
• Loss of acid ↑ dissociation of H2CO3 –Measure gases and carbon dioxide
= ↑HCO3→ Increase in pH 4 Important components of ABG REDUCES ventilation rate, elevating, pH • Pco2 levels. → Reduction in renal • Measurement of the acidity and absorption and ↑ excretion of HCO, alkalinity of in the nephron. • Characterized by ELEVATED blood plasma [HCO3-] and pH • NV-7.35-7.45 Respiratory alkalosis CO2/PaCO2 • Decreased CO2, decreased H+, • Measurement of carbon dioxide increased pH • Causes of respiratory alkalosis • NV-35-35 include: • Controlled by lungs 7.45. Your body is constantly striving to keep pH in balance. • Acid • pH level below 7.35 is Acidosis – The amount of CO2 is directly proportional to the • pH level above 7.45 is Alkalosis number of hydrogen ions-related to acid 3. Determine If the Acid Base is Respiratory or Metabolic – The more CO2 in the blood the more acidic • Next thing you need to determine is whether the acid base is HCO3 Respiratory or Metabolic. • Bicrbonate • paCO2 = Respiratory • Nv-22-26 • HCO3 = Metabolic • Controlled by kidenys 4. Remember ROME • Lungs and kidenys work-maintain - Still, it all boils down to mnemonics. blood ph The mnemonic RO-ME. • Basic- the more bicarbonate in the • Respiratory Opposite blood, the more basic the blood is – When pH is up, PaCO2 is down = PaO2 Alkalosis • Oxygen – When pH is down, PaCO2 is up = • Regulated by the lungs Acidosis • NV 80-100 • Metabolic Equal ABG ANALYSIS/INTERPRETATION – When pH is up, HCO3 is up = Alkalosis 8-STEP GUIDE TO ABG ANALYSIS: – When pH is down, HCO3 is down = Tic-Tac-Toe Method Acidosis 1. Know the Normal Values 5. Tic-Tac-Toe Know the normal and abnormal ABG And yes, ABG problems work using the values when you review the lab reports. Tic-Tac-Toe method. All you have to do 2. Check for Acidosis or Alkalosis is make a blank chart a bit like a tic-tac- toe chart. The first thing you need to determine when checking ABG results is the acidity of the blood which is determined by the value of the pH. The pH level in a healthy human should be between 7.35 to 6. Mark the Chart = Uncompensated • Using the lab result values, mark them – Therefore this ABG is METABOLIC on your Tic-Tac-Toe chart. Now begin ACIDOSIS, PARTIALLY with this given COMPENSATED example. • pH 7.1, PaCO2 40, HCO3 18 • pH 7.26, paCO2 32, HCO3 18 • pH is LOW = ACID so place pH under Acid – pH is LOW = ACID so place pH under Acid • PaCO2 is NORMAL = NORMAL so place – paCO2 is LOW = BASE so place paCO2 under PaCO2 under Normal Base • HCO3 is LOW = ACID so place HCO3 – HCO3 is LOW = ACID so place HCO3 under Acid under Acid 7. Match It up – In this step, look at which column matches up with the pH. In this case HCO3 goes with pH. - HCO3 is considered Metabolic (shown in step 3), and both are under Acid, so this example implies Metabolic Acidosis. 8. Determine Compensation – The last step is to determine if the ABG is Compensated, Partially Compensated, or Uncompensated. – If pH is NORMAL, PaCO2 and HCO3 are both ABNORMAL = Compensated – If pH is ABNORMAL, PaCO2 and HCO3 are both ABNORMAL = Partially Compensated – If pH is ABNORMAL, PaCO2 or HCO3 is ABNORMAL