LECTURE: Acid-base disorders CLINICAL Dr Bakri Saeed Aims and Objectives AIMS To illustrate and explain normal acid-base

se balance To illustrate and explain the pathology of disturbances in acid-base balance BIOCHEMISTRY

OBJECTIVES After this lecture you should: Understand the need to maintain a pH in the physiological range Understand the basic physiology of acid-base balance Be able to classify the types of acid-base disturbance Know the causes, pathogenesis and effects of metabolic acidosis and alkalosis Know and be able to apply the tests used in metabolic acidosis and alkalosis Know the causes, pathogenesis and effects of respiratory acidosis and alkalosis Know and be able to apply the tests used in respiratory acidosis and alkalosis Be able to interpret an arterial blood gas report Lecture Content Clinical significance: A lot of acids are produced by normal metabolic activity, like phosphoric acid, sulphuric acid, lactic acid and hydrochloric acid. These acids release hydrogen ions (H+). Despite this, the pH of the blood remains constant at about 7.4 in health. This is due to the buffering capacity of the body and the ability to dispose of acids. The ability of the body to maintain normal acidbase balance is affected by disease and assessment of acid-base balance constitutes some of the commonly performed tests. Often they are performed as a point-of-care investigation, by junior doctors and other staff. A working knowledge of the acid-base system is essential for any medical practitioner. What is the need to maintain pH within physiological range? pH is a measure of hydrogen ion (H+) concentration. A decrease in pH value indicates increased H+ while a rise in pH indicates a drop in H+ concentration. A change in pH of one unit is equivalent to a 10 fold change in H+ concentration. An acid is a substance that donates H+ and a base is a substance that accepts H+.

H+ needs to be kept within a tight range. The H+ is small, highly mobile and very reactive, and it tends to bind to negatively charged (anionic) substances. When the concentration of H+ rises, they occupy many anionic sites and make them lose their charge. On the other hand, when blood pH rises (when concentration of H+ drops), additional anionic sites e.g. albumin are exposed. Some of these can bind physiologically active substances (e.g. calcium) and reduce their concentration. Proteins are especially vulnerable to changes in pH, which influence the charge on their constituent amino acids and influence their function. In that way, the activity of enzymes, transmembrane channels and pumps may be affected. Buffers Buffers are substances that limit the change in hydrogen ion concentration to the physiological range to ensure survival. They are capable of mopping up H+, and are also able to contribute H+. The buffer consists of a strong base and a weak conjugate acid. The equation of dissociation and formation of an acid is: HB H+ + BWhere HB is the conjugate acid and B- is the conjugate base. The bicarbonate buffer is the most important plasma buffer, both because of buffering capacity and also because of the ease of elimination of carbonic acid, as CO2. Buffering is illustrated in this equation: H+ + HCO3- H2CO3 The carbonic acid produced is removed by its diffusion as CO2 into the alveolar air of the lungs. Other plasma buffers are phosphate and plasma proteins. Intracellular buffers are haemoglobin, the most important buffer intracellularly, and other proteins. The buffer systems of the body are like gears of a machine. They all turn together and influence each other. Basic physiology of acid-base balance: Regulation of arterial CO2: In health the concentration of arterial CO2 is held constant. The body maintains this constant level by matching rates of CO2 production and excretion. This is done by varying the ventilatory rate. The only other route whereby H+ can be excreted from the body is in urine. The renal tubular cells secret H+, which are buffered in the glomerular filtrate by phosphate or by ammonia. Kidney handling of Bicarbonate: Bicarbonate ions are filtered from the blood by the glomerulus and enter the lumen of the tubule. They are returned to the blood by reabsorption across the tubule wall. The kidney is also capable of regeneration of bicarbonate from CO2 .

Maintenance of the blood pH: pH= pka + log [Base]

[acid]

Pka is the negative logarithm of the dissociation constant of the acid. The equation for the carbonic acid system could be written as follows: pH= 6.1 + log [HCO3- ] [0.03PCO2] PCO2 is the partial pressure of CO2, which determines the concentration of carbonic acid. If the pH is to be maintained at 7.4, the ratio: [Bicarbonate] [Carbonic acid] has to remain at 20. The changes in pH are minimised by three homeostatic mechanisms: 1. Buffering in ECF, ICF and bone. 2. Compensation, which prevents further pH change. 3. Correction Acid-base disturbance: The pH can be altered by a primary change of either PCO2 or plasma bicarbonate (HCO3-) concentration. Primary respiratory disorders change blood pH by causing changes in PCO2, and primary metabolic disturbances are caused by changes in bicarbonate concentration. The primary disturbances are usually accompanied by compensatory changes. The change in pH depends on the speed of onset of the condition and the extent of compensation. Metabolic acidosis: Excess acid is neutralized by bicarbonates. There is therefore a fall in the pH of the blood and the bicarbonate level in plasma. It is compensated by a fall in CO2 level. Causes: 1. Increased endogenous acid production due to abnormal metabolism e.g. lactic acidosis or ketoacidosis. 2. Increased acid production due to ingestion of exogenous chemicals such as methanol, ethylene glycol or salicylates. 3. Loss of bicarbonates due to sub-pyloric GI disease/pathology e.g. diarrhoea, lower GI drainage. 4. Decreased renal net acid excretion due to renal failure or renal tubular acidosis.

Other useful tests in metabolic acidosis: Osmolar gap: The difference between measured osmolality and calculated osmolality. Calculated osmolality = 2(Na+ + K+) + urea + glucose The presence of an osmolar gap in metabolic acidosis indicates the presence of unmeasured osmoles (e.g. methanol, ethanol, ethylene glycol, etc). Anion gap: The number of positive charges or cations must equal the number of negative charges or anions in every solution. Plasma anion gap is calculated as follows: [Na+ + K+] [Cl- + HCO3] = 12 16 mmol/L, due to presence of unmeasured anions like lactate, formate or oxalate. Addition of acids will lower the bicarbonate level and increase the anion gap. The anion gap will indicate the amount of acid added. It is useful in monitoring the patients response to therapy. High anion gap metabolic acidosis: Lactic acidosis Ketoacidosis Renal failure Ingestion of methanol, ethanol, ethylene glycol Normal anion gap metabolic acidosis: In this condition, the low bicarbonate of metabolic acidosis is associated with hyperchloraemia, so that the anion gap remains normal. Two main categories of normal anion gap metabolic acidosis: GI loss of bicarbonate: Loss of small bowel secretions in diarrhoea or pancreatic drainage. Renal Tubular Acidosis: Type I Distal renal tubular acidosis: Is caused by deficiency in H+ secretion in the distal tubule. It is a hypokalaemic, hyperchloraemic metabolic acidosis. Urinary pH is always above 5.5 and renal stones are frequent complications. Type II Proximal renal tubular acidosis: Is due to a defect in the ability of the proximal tubule to re-absorb bicarbonates. It is a hypokalaemic, hyperchloraemic metabolic acidosis. It occurs as an isolated disorder or part of Fanconi syndrome. Clinical effects of metabolic acidosis: Air hunger is a classical symptom. Severe metabolic acidosis may cause neurological symptoms culminating in coma. It impairs cardiac function and a state of shock may result. Severe acidosis can cause cardiac dysrhythmias, cardiac arrest and sudden death.

Metabolic alkalosis: This is encountered when there is a rise in pH and bicarbonate level in plasma. It is compensated by a rise in PCO2 Causes 1. Loss of gastric fluid vomiting or upper GI drainage 2. Diuretics thiazide or loop diuretics 3. Posthypercapnic metabolic alkalosis 4. Hyperaldosteronism or Cushings syndrome 5. Alkali administration with decreased GFR Clinical effects: No characteristic symptoms and signs. Orthostatic hypotension may occur. Weakness and hyporeflexia may be due to hypokalaemia. Tetany and neuromuscular excitability may occur. Respiratory acidosis Respiratory acidosis results from hypoventilation and a subsequent rise in arterial PCO2. The retained PCO2 forms carbonic acid, which is the source of H+. Respiratory acidosis is acute or chronic. In chronic respiratory acidosis, bicarbonate levels rise as a compensatory change but to a lesser extent than PCO2. The ratio of bicarbonate:carbonic acid falls, as does the pH. Causes: 1. Airway obstruction: generalized bronchospasm or laryngospasm tend to cause acute respiratory acidosis, while chronic obstructive lung disease (bronchitis, emphysema) cause chronic respiratory acidosis. 2. Respiratory centre depression: sedative overdose, brain tumour 3. Neuromuscular defects: respiratory muscle disease, multiple sclerosis. 4. Restriction defects: respiratory muscle disease, pneumothorax, interstitial fibrosis, kyphoscoliosis. Clinical effects: There is peripheral vasodilation, which may raise the intracranial pressure. Also confusion, myoclonus and coma. Respiratory alkalosis: This occurs when hyperventilation reduces PCO2, which leads to an increase in pH. Plasma bicarbonate levels fall as compensation. Causes: 1. Psychogenic hyperventilation fear, anxiety, pain 2. Acute asthma 3. Hypoxia congestive cardiac failure, congenital heart disease 4. Salicylates 5. Sub-arachnoid haemorrhage Clinical effects:

In acute cases there could be lightheadedness, parasthesia, numbness around the mouth and a tingling sensation in the hands and feet. Tetany may occur.

How to interpret an arterial blood gas report? If pathological changes occur in bicarbonate, the body responds by changing PCO2. Thus during metabolic acidosis the body responds by increasing alveolar ventilation and hence lowering PCO2. Similarly in respiratory acidosis, the kidney acts to raise the plasma bicarbonate. The original pathological change is called primary and the change that occurs in response to the primary change is termed compensatory. Disturbance Metabolic acidosis Metabolic alkalosis Respiratory acidosis Respiratory alkalosis Primary change HCO3 down HCO3 up PCO2 up PCO2 down Compensatory change PCO 2 down PCO2 up HCO3 up HCO3 down

Note in each case up yields up, down yields down compensation follows the same-direction rule. Compensatory (secondary) changes in PCO2 are called respiratory, while compensatory changes in HCO3 are called metabolic or renal because the kidney orchestrates them. Measuring acid-base parameters: In order to assess acid-base status, you need the values of pH, PCO2 and plasma bicarbonate measured in arterial blood. The venous total CO2 is a determination of bicarbonate level. Total CO2 is equivalent to bicarbonate level (+ 3 meq/L). The syringe used for taking arterial blood gas determination is coated with heparin. Reading a blood gas report: 1. Is there acid-base disturbance? Is it acidosis or alkalosis? Assess pH: If pH <7.38, it is acidosis If pH >7.42, it is alkalosis 2. Is the acid-base disturbance respiratory or metabolic? Assess PCO2: If the pH is moving in the opposite direction to PCO 2, this is a respiratory problem. In respiratory acid-base disorders, bicarbonate will be moving in the same direction as PCO2. In metabolic acid base disorders, pH, PCO2 and bicarbonates will all be moving in the same direction. 3. Reference ranges: PCO2 reference range: 4.5 6 Kpa

Bicarbonate reference range: 24 30 mmol/L.

Case Exercise: Evaluate the following blood gases: Example 1 2 3 4 PH 7.3 7.57 7.57 7.6 HCO3 mmol/L 14 42 18 32 P CO kpa 2.5 8 2 4

Reading a blood gas report

pH

<7.4 pH Acidosis pH

>7.4

Alkalosis

PCO 2 HCO3-

PCO 2 HCO3-

PCO 2 HCO3-

PCO 2 HCO3-

Metabolic acidosis

Mixed

Respiratory acidosis

Metabolic alkalosis

Mixed

Respiratory alkalosis