Acid Base Balance 1
HYDROGEN ION CONCENTRATION and CONCEPT OF ph Blood hydrogen ion concentration (abbreviated [H + ]) is maintained within tight limits in health, with the normal concentration being between 35-45 nmol/l. Concentrations below 20 nmol/l or above 120 nmol/l are generally incompatible with life. Blood hydrogen ion concentration is often expressed as ph. The [H+] when expressed in mol/l is 3.5-4.5 x 10-8 mol/l, and such negative exponential numbers are difficult to work with, therefore SORENSON formulated a term, ph, which describes the free H + concentration. The definition of ph is : 2
3
SOURCES OF HYDROGEN IONS 1- The oxidation of proteins, nucleic acids and phospholipids that produces phosphoric and sulphuric acids, while the incomplete (anaerobic) metabolism of fat and carbohydrates produces organic acids such as lactic, acetoacetic and β-hydroxybutyric acids. This produces of 50-100 mmoles of hydrogen ions per day. [H+] would be about 5 mmol/l which is 125,000 times more acid than normal! (excreted by the kidneys ) 4
2- Complete (aerobic) metabolism of fat and carbohydrates produces CO 2. In solution, CO 2 forms a weak acid (carbonic acid) which therefore has the potential to affect [H + ] and ph. This process produces 15,000-20,000 mmoles of CO 2 per day. CO 2 is however volatile, and under normal circumstances is transported to the lungs in the blood and is rapidly excreted by the lungs. Only if respiratory function is impaired do problems occur. 5
BACKGROUND TO BUFFERS Before we can define a buffer, or describe what a buffer does and how it does it, there are certain concepts that must be understood. 6
7
8
DEFINITION OF A BUFFER A buffer is a solution containing a conjugate acid-base pair, made up of a weak acid and its salt, which minimises changes in ph. Buffers bind or release hydrogen ions depending on the surrounding hydrogen ion concentration, by shifting the equilibrium of the reaction. 9
10
Physiological Buffers 11
This buffer system also manages by lungs 12
HENDERSON-HASSELBALCH Equation 13
14
15
Role of the Kidney in Handling Bicarbonate and Hydrogen 16
17
ASSESSING ACID-BASE BALANCE An indication of the acid-base status of a patient can be obtained by measuring the components of the bicarbonate buffer system. Because of the sites of excretion and regulation, the pco 2 is called the respiratory component, and the HCO 3- the metabolic component of the bicarbonate buffer system. NORMAL VALUES ph 7.35-7.45 pco 2 4.5-6.1 kpa [HCO 3- ] 22-26 mmol/l size of buffer pools bicarbonate 24 mmol/l Haemoglobin 10 mmol/l plasma protein 10 mmol/l size of free [H + ] pool 40 nmol/l (40 x 10-6 mmol/l) i.e., a million fold smaller 18
CONCEPTS AND TERMINOLOGY OF ACID-BASE IMBALANCE ACIDOSIS A condition characterised by a decrease in blood ph. The condition can be of metabolic or respiratory origin. [HCO 3- ] Since ph = 6.1 + log ---------------- 0.225 x pco 2 Therefore a decrease in ph can be due to: a decrease in [HCO 3- ] (metabolic acidosis) an increase in pco 2 (respiratory acidosis) 19
ALKALOSIS A condition characterised by an increase in blood ph. The condition can be of metabolic or respiratory origin. [HCO 3- ] Since ph = 6.1 + log ---------------- 0.225 x pco 2 Therefore an increase in ph can be due to an increase in [HCO3-] (metabolic alkalosis) a decrease in pco2 (respiratory alkalosis) 20
COMPENSATION Primary Respiratory Disorders (metabolic compensation) In a respiratory acidosis (decreased ph due to increased pco 2 ), more H+ is excreted and more HCO 3- is generated by the kidneys, increasing blood HCO 3- In a respiratory alkalosis (increased ph due to decreased pco 2 ), less H+ is excreted and less HCO 3- is generated by the kidneys, decreasing blood HCO 3- These called metabolic compensation that is slow to take effect, coming into effect over 2-4 days. 21
Primary Metabolic Disorders (Respiratory compensation) In a metabolic acidosis (decreased ph due to decreased HCO 3- ), the rate and depth of respiration are increased (hyperventilation), decreasing blood pco 2 In a metabolic alkalosis (increased ph due to increased HCO 3- ) the rate and depth of respiration are decreased (hypoventilation), increasing blood pco 2 These called respiratory compensation that is quick to take effect, coming into effect within 15-30 minutes. 22
ANION GAP The anion gap is a concept which is useful in establishing the cause of a metabolic acidosis. Blood is always electroneutral, even if there is an acid-base disturbance, i.e., it always contains an equal number of positive cations and negative anions. Normally: the millimolar sum of all cations = the millimolar sum of all anions 140 mm Na + 105 mm Cl - 4 mm K + 25 mm HCO 3-2 mm Ca 2+ 2 mm PO 3-4 1 mm Mg 2+ 15 mm proteins - < 1 mm organic anions - 23
Although almost all these electrolytes can be measured, we commonly only measure Na+, K+, Cl- and HCO3-. When we subtract the commonly measured anions from the commonly measured cations, we find an anion gap of about 10-20 mmol/l. (Na + + K + ) - (Cl - + HCO 3- ) = "anion gap" = 10-20 mmol/l increased anion gap indicates excess unmeasured anions- i.e., an increased anion gap acidosis 24
COMMON CAUSES OF METABOLIC ACIDOSIS 1. DIARRHOEA in both acute and chronic diarrhoea bicarbonate is lost. Since no additional anion has accumulated, the kidney reabsorbs more chloride and the increased chloride maintains electroneutrality. Diarrhoea is therefore a cause of a normal anion gap acidosis. 2. DIABETIC KETOACIDOSIS (DKA) 25
3. LACTIC ACIDOSIS 26
4. CHRONIC RENAL FAILURE Chronic renal failure causes retention of many metabolites which are normally filtered and excreted by the kidneys, including H + and phosphate- ions. The excess hydrogen ions are buffered by the bicarbonate system, leading to consumption of the available bicarbonate and a metabolic acidosis. Since additional phosphate - anions have accumulated in the blood, chronic renal failure is therefore a cause of an increased anion gap acidosis. 27
LESS COMMON CAUSES OF METABOLIC ACIDOSIS 1. RENAL TUBULAR ACIDOSIS i) PROXIMAL RENAL TUBULAR ACIDOSIS (RTA type II) ii) DISTAL RENAL TUBULAR ACIDOSIS (RTA TYPE I) 28
SYSTEMATIC LIST OF CAUSES OF METABOLIC ACIDOSIS 1. GAIN OF HYDROGEN Anion gap i) Increased production of fixed acid a) Ketoacidosis increased b) Lactic acidosis increased ii) Ingestion of acids or potential acids (extremely rare) sometimes increased iii) Decreased excretion of hydrogen by kidneys a) Chronic renal failure increased b) Distal Renal Tubular Acidosis (RTA type I) normal 2. LOSS OF BICARBONATE i) GIT loss a) Diarrhoea normal b) Transplantation of ureters into colon (extremely rare) normal ii) Renal loss a) Proximal Renal Tubular Acidosis (RTA type II) normal b) Some diuretics 29
CLINICAL EFFECTS OF ACIDOSIS Increased [H+] stimulates the respiratory centre and causes hyperventilation. This causes deep, rapid and gasping respiration known as Kussmaul breathing. This is a physiological compensatory response which decreases the pco2 and therefore returns the ph towards normal. Increased [H+] commonly causes hyperkalaemia. Intracellular polyanions such as proteins- and glycogen- normally bind hydrogen and potassium ions. In an acidosis, excess hydrogen ions move into cells, displacing potassium ions Increased [H+] causes increased neuromuscular irritability. There is thus a risk of cardiac arrhythmias, especially in the presence of hyperkalaemia. Increased [H+] depresses consciousness, which can progress to coma and death. 30
TREATMENT OF METABOLIC ACIDOSIS 1. Treat the primary cause. 2. Treat any dehydration and hyperkalaemia which are commonly present. 3. Treat the acidosis if severe (ph < 7.0) by administering NaHCO3 31
METABOLIC ALKALOSIS In a metabolic alkalosis there is an increase in the blood ph caused by an increase in the bicarbonate concentration. The increase in the bicarbonate concentration can be caused by one of two mechanisms - the gain of bicarbonate, or the loss of hydrogen ions. 32
COMMON CAUSES OF METABOLIC ALKALOSIS 1. VOMITING Gastric fluid is rich in hydrochloric acid. However, loss of gastric fluid is followed by the production of new hydrochloric acid. The hydrogen ions are secreted into the stomach by the proton pump, while the bicarbonate ions diffuse into the circulation, causing alkalosis with a loss of chloride, water and some potassium from the stomach. A good biochemical sign to identifying vomiting as the cause of a metabolic alkalosis, is that the urine chloride concentration is < 5 mmol/l. 33
2. INCREASED RENAL HYDROGEN ION LOSS Any mechanism that increases distal renal tubular sodium reabsorption, causes a simultaneous increase in hydrogen ion and potassium secretion. The increased hydrogen ion secretion causes increased bicarbonate regeneration and metabolic alkalosis, while the increased potassium secretion causes hypokalaemia. These mechanisms include : Diuretics that inhibit proximal renal reabsorption of NaCl, leading to an increased load of sodium to the distal tubule. Excess mineralocorticoid secretion or action. 34
SYSTEMATIC LIST OF CAUSES OF METABOLIC ALKALOSIS 1. GAIN OF BICARBONATE i) Ingestion or infusion of alkali a) antacids b) citrate, acetate or lactate c) bicarbonate ii) Too-rapid reversal of chronic respiratory acidosis 2. LOSS OF HYDROGEN i) GIT loss (could be considered a gain of bicarbonate instead of a loss of hydrogen) a) vomiting b) nasogastric suction ii) Renal loss a) diuretics b) excess mineralocorticoid action c) potassium depletion due to many causes, including purgatives 35
CLINICAL EFFECTS OF ALKALOSIS Hypokalaemia, due to decreased distal tubular hydrogen ion secretion. In turn hypokalaemia worsens and prolongs the alkalosis. Tetany. TREATMENT OF METABOLIC ALKALOSIS 1. Treat the primary cause. 2. Treat any dehydration and hypochloraemia which are present with normal saline (NaCl). 3. Treat any hypokalaemia present with KCl. 36