Chapter 4: Acid-Base Homeostasis and Regulation in the Body

1 Acid-Base Homeostasis CH 4 Acid-Base Homeostasis  Blood hydrogen ion concentration maintained within tight Limits in health.  Normal levels lie between 35-45 nmol/l (pH 7.35-7.46) in extracellular fluid.  In intracellular fluid is slightly higher but also tightly controlled • Normal pH of body fluids – Arterial blood is 7.4 – Venous blood and interstitial fluid is 7.35 – Intracellular fluid is 7.0 2 Acid-Base Homeostasis CH 4 • Alkalosis or alkalemia – arterial blood pH rises above 7.45 • Acidosis or acidemia – arterial pH drops below 7.35 (physiological acidosis) 3 Acid-Base Homeostasis CH 4 Acid-Base Homeostasis CH 4  Sources of Hydrogen Ions Most hydrogen ions originate from cellular metabolism • Breakdown of Sulfur-containing proteins releases H into the ECF • Incomplete oxidation of energy substrates generates acids like: • Anaerobic respiration of glucose produces lactic acid • Fat metabolism yields organic acids and ketone bodies, these intermediates will be further metabolized and consumed (e.g., lactate in gluconeogenesis, oxidation of ketones). • Temporary imbalances between the rates of production and consumption may occur in health (e.g., the accumulation of lactic acid during anaerobic exercise),  Transporting carbon dioxide as bicarbonate releases hydrogen ions  In disease states increased hydrogen ion production is an important cause of acidosis.  The total amount of hydrogen ion produced each day is 100,000 times more acid than normal !  This just does not happen because excess hydrogen ions are efficiently excreted 4 in urine. 5 Acid-Base Homeostasis CH 4 Acid/Base Homeostasis: Overview 6 Acid-Base Homeostasis CH 4 • Hydrogen Ion Regulation Concentration of hydrogen ions is regulated sequentially by: – Chemical buffer systems – act within seconds – The respiratory center in the brain stem – acts within 1-3 minutes – Renal mechanisms – require hours to days to effect pH changes Chemical Buffer Systems • Three major chemical buffer systems – Bicarbonate buffer system – Phosphate buffer system – Protein buffer system • Any drift in pH is opposed by the entire chemical buffering system 7 Acid-Base Homeostasis CH 4 Buffering of hydrogen ions Acid-Base Homeostasis CH 4 As hydrogen ions are generated they are buffered, thus limiting the rise in hydrogen ion concentration which would otherwise occur. A buffer is: a solution of the salt or a weak acid which is able to bind hydrogen ions. If hydrogen ions are added to a buffer,  some will combine with the conjugate base and convert it to the undissociated acid. Buffering does not remove hydrogen ions from the body. Buffers temporarily wash up any excess hydrogen ions which are produced. …. In the same way that a sponge soaks up water.  Buffering is only a short term solution to the problem of excess hydrogen ion. Eventually, the body must get rid of the hydrogen ions by renal excretion. The efficacy of any buffer is limited by …..its concentration and by the position of the equilibrium 8 The body contains Three major chemical buffer systems to resist sudden changes in hydrogen ion production Phosphate buffer system: Phosphate is a minor buffer in the ECF but is of fundamental importance in the urine. Protein buffer system: hemoglobin in the erythrocytes has a high capacity for binding hydrogen ion Bicarbonate buffer system: it is the most important in the ECF Bicarbonate (HCO3-) combines with hydrogen ion to form carbonic acid (H2CO3) The addition of hydrogen ions  increasing the amount of carbonic acid and consuming bicarbonate ions.  Conversely, if the hydrogen ion concentration falls, carbonic acid dissociates, thereby generating hydrogen ions. This buffer system is unique in that  the H2CO3, can dissociate to water and carbon dioxide. 9 Acid-Base Homeostasis CH 4 Bicarbonate Buffer System • A mixture of carbonic acid (H2CO3) and its salt, sodium bicarbonate (NaHCO3) (potassium or magnesium bicarbonates work as well) • If strong acid is added: – Hydrogen ions released combine with the bicarbonate ions and form carbonic acid (a weak acid) – The pH of the solution decreases only slightly • If strong base is added: – It reacts with the carbonic acid to form sodium bicarbonate (a weak base) – The pH of the solution rises only slightly • This system is the most important ECF buffer 10 Acid-Base Homeostasis CH 4  Simple buffers rapidly become ineffective as the association of the hydrogen ion and the anion of the weak acid reaches equilibrium.  The bicarbonate system keeps working because the carbonic acid is removed as CO2. CO2 + H2O  * H2CO3  H+ + HCO3The limit to the effectiveness of the bicarbonate system is the initial concentration of bicarbonate. Only when all the bicarbonate is used up does the system have no further buffering capacity. The capacity of the bicarbonate system in the body is greatly enhanced by the fact that carbonic acid can readily be formed from carbon dioxide or disposed of by conversion into carbon dioxide and water.  Buffering by the bicarbonate system effectively removes hydrogen ion from the ECF at the expense of bicarbonate. The extracellular fluid contains a large amount of bicarbonate but it falls as H+ is increased To maintain the capacity of the buffer system,  the bicarbonate must be regenerated. 11 Acid-Base Homeostasis CH 4 Bicarbonate reabsorption and hydrogen ion excretion  The glomerular filtrate contains the same concentration of bicarbonate ions as the plasma  If not reabsorbed  large amounts would be excreted in the urine  depleting the body’s buffering capacity  causing an acidosis  Virtually all the filtered bicarbonate is reabsorbed. The luminal surface of renal tubular cells is  impermeable to bicarbonate and therefore direct reabsorption can not occur.  Bicarbonate is reabsorbed indirectly: within the renal tubular cells, ….carbonic acid is formed from carbon dioxide and water  This reaction is catalyzed in the kidney by the enzyme carbonic anhydrase.  The carbonic acid thus formed dissociates to give hydrogen and bicarbonate ions. The bicarbonate ions pass across the basal border of the cells into the interstitial fluid. The hydrogen ions are secreted across the luminal membrane in exchange for sodium ions, which accompany bicarbonate into the interstitial fluid. 12 Acid-Base Homeostasis CH 4 Acid-Base Homeostasis CH 4 Bicarbonate reabsorption 13 Acid-Base Homeostasis CH 4 Bicarbonate reabsorption 14 Hydrogen ion excretion  Although hydrogen ions are secreted into the tubular fluid, there is no net hydrogen ion excretion, as the formation of hydrogen ions provides the means for the reabsorption of bicarbonate. Hydrogen ion excretion depends upon the same reactions occurring in the renal tubular cells but, in addition, requires the presence of a suitable buffer system in the urine. The excreted hydrogen ions must be buffered in urine OR the [H+] would rise to very high levels. Phosphate acts as one such buffer, while ammonia is another. 15 Acid-Base Homeostasis CH 4 Bicarbonate reabsorption and hydrogen ion excretion  The principal urinary buffer is phosphate. This is present in the glomerular filtrate (HPO42-). This combines with hydrogen ions and is converted to H2PO4-. HPO4 2- + H +  H2PO4 Ammnia, produced by the deamination of glutamine by glutaminase enzyme in renal tubular cells,  Ammonia can readily diffuse across cell membranes and ammonium ions are formed and excreted. NH3  H   NH4  16 Acid-Base Homeostasis CH 4 Acid-Base Homeostasis CH 4 Bicarbonate reabsorption and hydrogen ion excretion  17 18 Acid-Base Homeostasis CH 4 Transport of Carbon dioxide Acid-Base Homeostasis CH 4  Carbon dioxide, produced by aerobic metabolism, diffuses out of cells and dissolves in the ECF.  A small amount combines with water to form carbonic acid, thereby increasing the hydrogen ion concentration of the ECF.  In red blood cells, metabolism is anaerobic and little carbon dioxide is produced. Carbon dioxide thus diffuses into red cells down a gradient and carbonic acid is formed, facilitated by carbonate dehydatase (Carbonic unhydrase)  The overall effect of this process is that  carbon dioxide is converted to bicarbonate in red blood cells. This bicarbonate diffuses out of the red cells with…. exchange with…. chloride ions (the chloride shift). 19 In the lungs, the reverse process occurs because of  the low partial pressure of carbon dioxide in the alveolar capillaries.  Carbon dioxide is produced from bicarbonate and diffuses into the alveoli to be excreted in the expired air. How is CO2 Exported? Most of the carbon dioxide in the blood is present in the form of bicarbonate. Dissolved carbon dioxide, carbonic acid and carbamino compounds (compounds of carbon dioxide and protein) account for less than 2.0 mmol/L in a total carbon dioxide conc. Of appro. 26 mmol/L. The term ‘bicarbonate’ and ‘total carbon dioxide’ are frequently used synonymously. Acid-Base Homeostasis CH 4 20 21 Acid-Base Homeostasis CH 4 Assessing Acid-base Status Acid-Base Homeostasis CH 4  An indication of the acid-base status of the patient can be obtained by measuring the components of the bicarbonate buffer system. H + + HCO3 -  H H22CO CO33  H2O  CO2 H + is proportinal to PCO2 HCO3- Excess hydrogen ions are buffered by bicarbonate  the formed carbonic acid dissociates  carbon dioxide is lost in the expired air  limits the potential rise in hydrogen ion concentration at the expense of a reduction in bicarbonate The hydrogen ion concentration in blood varies as  the bicarbonate concentration and PCO2 If everything else remains constant: change. Adding hydrogen ion, removing bicarbonate or increasing the PCO2…….. will all have the same effect an increase in [H+]. Removing hydrogen ions, adding bicarbonate will all cause the [H+] to fail.  Blood [H+] is 40 nmol/l and is controlled by the functioning of our kidneys. 22 or lowering PCO2 …………. our normal pattern of respiration and Acid Base Balance Disorders of hydrogen ion homeostasis 1. “Metabolic” acid-base disorders are those that directly cause a change in the bicarbonate concentration, like diabetes mellitus because of the absence of insulin  building up of [H+], of ketone bodies or loss of bicarbonate from the extracellular fluid. 2. “Respiratory” acid-base disorders affect PCO2  Impaired respiratory function causes a build up of CO2 in blood or in the case of hyperventilation causes a decreased PCO2 Compensation The body has physiological mechanisms which try to restore [H+] to normal these processes are called 'compensation', The observed [H+] in any acid-base disorder reflects the balance between the primary disturbance and the amount of compensation. Renal Compensation: where lung function is compromised (primary respiratory disorder). The body attempts to increase the excretion of hydrogen ion via the renal route. Renal compensation is slow to take place. Respiratory compensation: where there are metabolic disorder some compensation is possible by lung Acid-Base Homeostasis  CH 4 24 Remember 25 When you see “respiratory”, think PCO2 When you see “metabolic”, think [HCO3] Acid-Base Homeostasis CH 4 26 Acid-Base Homeostasis CH 4 Respiratory compensation: where there are metabolic disorder Acid-Base Homeostasis CH 4  some compensation is possible by lung 27 Disorders of hydrogen ion homeostasis ‘Acidemia' and 'alkalemia' refer simply to whether the [H+] in blood is higher or lower than normal 28 PCO2 H  HCO3+ Acid-Base Homeostasis CH 4 Disorders of hydrogen ion homeostasis Acidosis and alkalosis are clinical terms which define the primary acid-base disturbance. They can be used even when the [H+] is within the normal range. i.e. when the disorders are fully compensated. The definitions are: H+  PCO2 HCO3 - 1. Non-respiratory (Metabolic) acidosis: The primary disorder is a decrease in bicarbonate concentration. 2. Non-respiratory (Metabolic) alkalosis: The primary disorder is an increased bicarbonate. 3. Respiratory acidosis: The primary disorder is an increased PCO2. 4. Respiratory alkalosis: The primary disorder is a decreased PCO2. 5. Primary mixed acid-base disorders, that is, disorders of combined respiratory and non-respiratory origin, ‘Acidemia' and 'alkalemia' refer simply to whether the [H+] in blood is higher or lower than normal 29 Acid-Base Homeostasis CH 4 30 Acid-Base Homeostasis CH 4 1. Non-respiratory (metabolic) acidosis  The primary abnormality in non-respiratory acidosis is either: increased production or decreased excretion of hydrogen ions. In some cases, both of these may contribute. Loss of bicarbonate and retention of hydrogen ions may result in acidosis in patients losing alkaline secretions from the small intestine. Causes of non-respiratory acidosis * Increased H+ formation ketoacidosis (usually diabetic, also alcoholic) lactic acidosis poisoning: e.g., ethanol, methanol, ethylene glycol and salicylate * Acid ingestion acid poisoning * Decreased H+ excretion renal tubular acidosis generalised renal failure carbonate dehydratase inhibitors * Loss of bicarbonate diarrhea pancreatic, intestinal and biliary fistulae or drainage 31 Acid-Base Homeostasis CH 4 The characteristic biochemical changes seen in the blood in nonrespiratory acidosis can be summarized as follows: Non-respiratory acidosis (metabolic) high [H+], Low pH, low PCO2 and Low [HCO3-] Compensation is effected by hyperventilation, which increases the removal of carbon dioxide and lowers the PCO2. Hyperventilation is a direct result of the increased [H+] stimulating the respiratory centre. Respiratory compensation cannot completely normalize the [H+] since it is  * the high concentration itself [H+] that stimulates the compensatory hyperventilation. * Also the increased work of the respiratory muscle produces carbon dioxide, so…… limiting the extent to which the pCO2 can be lowered. In a healthy person, hyperventilation would produce a respiratory alkalosis. If renal function is normal in a patient with non-respiratory acidosis, excess hydrogen ions can be excreted by the kidneys. 32 Acid-Base Homeostasis CH 4 The complete correction of a non-respiratory acidosis requires reversal of the underlying cause, for example, rehydration and insulin for diabetic ketoacidosis. Hyperkalaemia is common in acidotic patients. H+ K+ K+ K+ K+ K+ 33 H+ H+ K+ H+ H+ H+ ACIDOSIS H+ HYPERKALEMIA H+ H+ Acid-Base Homeostasis CH 4 Clinical effects of acidosis The compensatory response to metabolic acidosis is hyperventilation, since the increased [H+] acts as  a powerful stimulant of the respiratory centre. The deep, rapid and gasping (wheezing) respiratory pattern  is known as Kussmaul breathing. Hyperventilation is the appropriate physiological response to acidosis and it occurs rapidly. A raised [H+] leads to increased neuromuscular irritability. There is a hazard of …..arrhythmias progressing to cardiac arrest, this will be more likely in the presence of hyperkalaemia which will accompany the acidosis Depression of consciousness can progress to 34 Acid-Base Homeostasis CH 4 coma and death. 35 Acid-Base Homeostasis CH 4 2- Metabolic Alkalosis (Non-respiratory alkalosis): is characterized by a * primary increase in the ECF bicarbonate concentration, with * a consequent reduction in [H+] (increase pH).  Normally, an increase in plasma bicarbonate concentration leads to incomplete renal tubular bicarbonate reabsorption and excretion of bicarbonate in the urine.  BUT in non-respiratory (metabolic) alkalosis, high renal bicarbonate reabsorption occurs. Factors which may be responsible for this include a decrease in ECF volume, mineralocorticoid excess increased Sod along with carbonate reabsorption and potassium depletion.  Massive quantities of bicarbonate must be ingested to produce a sustained alkalosis. 36 Acid-Base Homeostasis CH 4 Metabolic Alkalosis (Non-respiratory alkalosis): The causes of a metabolic alkalosis are:  Loss of Hydrogen ion in gastric fluid during vomiting especially when there is no parallel loss of bicarbonate.  Ingestion of an absorbable alkali as sod bicarbonate: very large quantities are required except there is renal impairment  In sever potassium depletion (consequences of diuretic therapy) hydrogen ions are retained inside cells to replace missing potassium ions. In renal tubules more hydrogen are exchanged for reabsorption of sod. So, despite there being an alkalosis, the patient passes acidic urine. This often referred to as a ‘paradoxical’ acid urine, because in other causes of metabolic alkalosis urinary [H+] usually falls. 37 Acid-Base Homeostasis CH 4 Acid-Base Homeostasis CH 4 38 Clinical effects of metabolic alkalosis The clinical effects of alkalosis include: hypoventilation, confusion and eventually coma. Muscle cramps, tetany and paraesthesia (any abnormality in sensation) may be a consequence of a decrease in the unbound plasma calcium concentration which is a consequence of the alkalosis. 39 Acid-Base Homeostasis CH 4 Metabolic Alkalosis (Non-respiratory alkalosis. Increase in HCO3 with less H): The correction of non-respiratory alkalosis primary cause and  requires reversal both of the for the mechanism for its maintenance. The expected compensatory would be an increased in PCO2 which would increase the ratio PCO2/[HCO3] and thus [H+]. A low arterial [H+] inhibits the respiratory centre, causing hypoventilation, and thus an increase in PCO2. However, since an increase in PCO2 is itself a powerful stimulus to respiration, this compensation, particularly in acute non-respiratory alkalosis, may be self-limiting. In more chronic disorders, significant compensation may occur, presumably because the respiratory centre becomes less sensitive to carbon dioxide. Should hypoventilation lead to significant hypoxaemia, provide a powerful stimulus to respiration 40 however, this will and prevent further compensation. Acid-Base Homeostasis CH 4 Management: The management of a non-respiratory alkalosis depends upon: the severity of the condition and upon the cause. When hypovolaemia are present, they can be simultaneously corrected by an infusion of isotonic sodium chloride solution (normal saline) which will also improve renal perfusion and allow excretion of the bicarbonate load. It is very rarely necessary to  attempt rapid correction of non-respiratory alkalosis, for example, by administration of ammonium chloride. The mild alkalosis commonly associated with potassium depletion may require correction 41 Acid-Base Homeostasis CH 4 “Respiratory” acid-base disorders 42 Acid-Base Homeostasis CH 4 3- Respiratory acidosis: The primary disorder is an increased PCO2 Respiratory acidosis is characterized by an increase in PCO2, (CO2 retention)  For every hydrogen ion produced a bicarbonate ion is generated BUT the effect of adding one H+ to a concentration of 40 nmol/l is much greater than adding one bicarbonate molecule to a concentration of 26 mmol/l. The majority of hydrogen ions are buffered by intracellular buffers, particularly hemoglobin. 43 Acid-Base Homeostasis CH 4 Respiratory acidosis: The primary disorder is an increased PCO2 Respiratory acidosis: Respiratory acidosis may be acute or chronic. Acute conditions occur within minutes or hours, they are uncompensated. Renal compensation has no time to develop as the mechanisms that adjust bicarbonate reabsorption take 48-72 hours to become fully effective.  The primary problem in acute respiratory acidosis is alveolar hypoventilation  If airflow is completely or partially reduced, the PCO2 in the blood will rise immediately and the [H+] will rise quickly. A resulting low PO2 and high PCO2 causes coma. If this is not relieved rapidly, death results. Examples of acute respiratory acidosis are:  Acute airway obstruction: * choking (obstruction of the flow of air from the environment into the lungs) * bronchopneumonia, * acute exacerbation of asthma. Depression of respiratory centre: * Anaesthetics, *Sedatives Acid-Base Homeostasis CH 4 44 Chronic respiratory acidosis: usually results from chronic obstructive airways disease (COAD) and is usually a long-standing condition, accompanied by maximal renal compensation. In a chronic respiratory acidosis the primary problem is also usually impaired alveolar ventilation, but renal compensation contributes markedly to the acid-base picture. Compensation may be The kidney and partial or complete. increases hydrogen ion excretion ECF bicarbonate levels rise. Blood [H+] tends back towards normal 45 Acid-Base Homeostasis CH 4 Acid-Base Homeostasis CH 4 46 Management of Acidosis  The aim when treating respiratory acidosis is to improve alveolar ventilation and lower the PCO2.  In acute alveolar hypoventilation:  hypoxia causes the main threat to life  If ventilation is stopped abruptly, death from hypoxia will occur In chronic respiratory acidosis, it is rarely possible to correct the underlying cause and treatment is directed at  maximizing alveolar ventilation by, for example, utilizing physiotherapy, bronchodilators and antibiotics. 47 Acid-Base Homeostasis CH 4 4- Respiratory alkalosis  Respiratory alkalosis is much less common than acidosis but can occur when respiration is stimulated or is no longer subject to feedback control. Usually these are acute conditions, and there is no renal compensation. Renal compensation in a respiratory alkalosis develops slowly, as it does in respiratory acidosis.  The treatment is to inhibit or remove the cause of the hyperventilation, and the acid-base balance should return to normal.  Causes are: 1. hysterical over-breathing, 2. mechanical over-ventilation in an intensive care patient, 3. raised intracranial pressure, or hypoxia, both of which may 48 stimulate the respiratory centre. Acid-Base Homeostasis CH 4 49 Acid-Base Homeostasis CH 4 Acid-Base Homeostasis CH 4 50 5- Mixed acid-base disorders Patients can have more than one acid-base disorder.  A patient may have both a metabolic and respiratory acidosis, such as  the chronic bronchitic patient who develops renal impairment  the PCO2 will be increased and the bicarbonate concentration will be low,  Hyperventilation causing a respiratory alkalosis, with prolonged nasogastric suction that causes a metabolic alkalosis Sometimes the two acid-base conditions are antagonistic in the way they affect the [H+], a metabolic acidosis and a co-existent respiratory alkalosis, Some examples of mixed acidbase disorders commonly encountered are:  A patient with chronic obstructive airways disease, causing a respiratory acidosis, with thiazide-induced potassium depletion and consequent metabolic alkalosis  Salicylate poisoning in which respiratory alkalosis occurs due to stimulation of the respiratory centre, together with metabolic acidosis due to the effects of the drug on metabolism. 51 Acid-Base Homeostasis CH 4 Interpretation of Acid-Base Data  A comprehensive understanding of the pathophysiology of acid-base homoeostasis is essential for the correct interpretation of laboratory data, but these data should always be considered in the clinical background.  The starting point in any evaluation should be the hydrogen ion concentration or pH. This will indicate whether the predominant disturbance is an acidosis or an alkalosis. However, a normal value does not exclude an acid-base disorder.  There may be either a fully compensated disturbance or  Two primary disturbances where effects on hydrogen ion concentration cancel each other out.  If the PCO2 is abnormal, there must be a respiratory component to the disturbance; if the PCO2 is raised in an acidosis, the acidosis is respiratory and the value of the hydrogen ion concentration will indicate whether there is an additional metabolic component.  If the PCO2 is low in an acidosis, the acidosis is non-respiratory and there is an additional respiratory component, which will often reflect compensation.  A similar rationale applies to alkalotic states. 52 Acid-Base Homeostasis CH 4 Interpretation of Acid-Base Data 53 Acid-Base Homeostasis CH 4 Case 1 A 70-year-old man was admitted to hospital as an emergency. He gave a history of dyspepsia and epigastric pain extending over many years. He had never sought medical attention for this. One week prior to admission, he had started to vomit, and had since vomited frequently, being unable to keep any food. He was clinically dehydrated, and had marked epigastric tenderness, but no signs of abdominal rigidity. Analysis of an arterial blood specimen gave the following results. Plasma Analysis Urea Sodium Potassium Creatinine 17.3 mmol/L 117 mmol/L 2.2 mmol/L 250 mol/L (2.5-6.6) (132-144) (3.3-4.7) (55-120) Blood Gas Analysis Hydrogen PCO2 Bicarbonate PO2 26 nmol/L 6.2 kPa 44 mmol/L 9.5 kPa (36-44) (4.4-6.1) (21.0-27.5) (12-15) How would you describe this patient’s acid-base status? What might have caused the various abnormalities revealed by these results? Why is the plasma potassium so low? ======================================================================================= The patient had a metabolic alkalosis. This was caused by his persistent vomiting, the vomit being likely to consist almost entirely of gastric contents. In this age group, the cause could be carcinoma of the stomach or chronic peptic ulceration with associated fibrosis, leading to obstruction of gastric outflow. Gastric juice potassium is about 10 mmol/L. Also, in the presence of an alkalosis, potassium shifts from the ECF into cells. Furthermore, dehydration causes secondary hyperaldosteronism, in order to maintain ECF volume, and sodium avidly retained by the kidneys in exchange for hydrogen and potassium. Patients such as this man, despite having an alkalosis and despite hyperkalemic, often excrete acidic urine containing large amounts of potassium. 54 Acid-Base Homeostasis CH 4 Case 2 A young woman was admitted in a confused and restless condition. History taking was not easy, but it seemed that she had been becoming progressively unwell over the preceding week or two. Acid-base analysis was preformed, and results were as follows: Blood Gas Analysis Hydrogen 78 nmol/L (36-44) PCO2 3.2 kPa (4.4-6.1) Bicarbonate 6 mmol/L (21-27.5) PO2 11.8 kPa (12-15) What is her acid-base disorder? What are the most likely causes, and what investigations could narrow this down? ========================================================== •She has a metabolic acidosis. Despite the long list of possible causes of metabolic acidosis, the commonest causes are diabetic ketoacidosis, renal failure, salicylate overdose and lactic acidosis. These can usually be differentiated on the basis of history; by measuring U & Es, glucose, and salicylates if indicated; and performing urinanalysis (using dipstick, and looking especially for ketones). Lactate can also be measured if required, but is not often necessary. This woman was a newly presenting Type I diabetic. 55 Acid-Base Homeostasis CH 4 Case 2 An elderly man was brought into the ER after collapsing in the street. He was deeply comatose and cyanosed, with unrecordable blood pressure. The results of acid-base analysis were as follows: Blood Gas Analysis Hydrogen 124 nmol/L (36-44) PCO2 10.4 kPa (4.4-6.1) Bicarbonate 15.4 mmol/L (21-27.5) PO2 4.8 kPa (12-15) What is the acid-base status? What are possible causes? ============================================================ •He has a combined metabolic and respiratory acidosis. The combination of the elevated hydrogen and PCO2 may initially suggest that he has a respiratory acidosis, but the bicarbonate would not be reduced in a simple respiratory acidosis. This means that there is an additional component of a metabolic acidosis present. Results of this sort are seen in patients with markedly impaired circulatory and respiratory function, such as occurs after a cardiac arrest. This man had a large abdominal aortic aneurysm that had ruptured. 56 Acid-Base Homeostasis CH 4 57 Acid-Base Homeostasis CH 4 58 Acid-Base Homeostasis CH 4 59 Acid-Base Homeostasis CH 4 60 Acid-Base Homeostasis CH 4