Acid Base Balance

Question 1

How do Acids and Bases behave?

Answer 1

Acids donate H+

• Strong acids readily give up H+

Bases accept H+

• Strong bases readily accept H+

Question 2

What are conjugate acids and bases

Answer 2

• Conjugate acid - Formed by the addition of a proton to a base e.g. Ammonium ion, NH4+ (ammonia is the base)
• Conjugate base - Formed by the removal of a proton from an acid e.g. Hydrogen carbonate ion, HCO3- (carbonic acid is the acid

Question 3

What is the definition of pH?

Answer 3

pH of a solution is defined as the negative logarithm of the hydrogen ion activity

pH = -log10[H+]

Question 4

What is the pH of blood?

Answer 4

pH of blood is 7.35 – 7.45 (35 – 45 nmol/L)

• Blood [H+] > 45 nmol/L acidaemic
• Blood [H+] < 35 nmol/L alkalaemic

Question 5

Describe the hydrogen ion production within the body?

Answer 5

• Normal metabolic processes cause the net formation of 40 – 80 mmol of H+ ions in 24hrs
• Temporary imbalances can be absorbed by buffering
• Disease states where there is an imbalance leads to acidosis or alkalosis

Question 6

How does the buffer system work within the body?

Answer 6

• Consists of a weak acid i.e. not completely dissociated and conjugate base
• If H+ are added to a buffer some will combine with the conjugate base and convert it to the undissociated acid
• Buffer works most efficiently at H+ concentrations which result in approximately equal concentrations of undissociated acid and conjugate base

Question 7

What is the pKa?

Answer 7

pKa represents the negative logarithm of the ionisation constant of an acid (Ka)

pKa is the pH at which a buffer exists in equal proportions with its acid and conjugate base

• Acids have pKa values < 7.0
• Bases have pKa values > 7.0

Question 8

How is pH derived from the pKa?

Answer 8

Henderson-Hesselbach

Question 9

What are the Buffering systems in the body?

Answer 9

Blood

• Bicarbonate
• Haemoglobin
• Plasma proteins

Bone

Urine

• Phosphate
• Ammonium

Question 10

How does haemoglobin provide a buffering system?

Answer 10

• Anaerobic metabolism therefore little CO2 in red blood calls
• Hb is a more powerful buffer when in deoxygenated state and the proportion in this state increases during the passage of blood through capillary beds because oxygen is lost to tissues
• Hb combines with the Hydrogen ions

Question 11

How do Plasma proteins provide a buffering system?

Answer 11

• Proteins contain weakly acidic and basic groups due to their amino acid composition
• Account for 95% of the non-bicarbonate buffering capacity of plasma. Also act as buffers intracellularly
• Albumin is the predominant plasma protein and is the main protein buffer in this compartment
• Albumin behaves as a weak acid due to high concentration of negatively charged amino acids

Question 12

How does Bone protein buffering occur?

Answer 12

• Bone proteins play a major role in acid-base balance
• Protein buffering within bone matrix
• Increased H+ stimulates bone resorption (alkaline minerals act as buffers)

Question 13

What are the renal processes to buffer plasma/serum?

Answer 13

• Excess H+ are excreted in the urine and, because the body is a net producer of acid, the urine is usually acidic. To achieve this, the body must reabsorb bicarbonate filtered at the glomerulus and excrete H+, usually against a steep concentration gradient
• The reactions linking these are mediated by carbonic anhydrase and occur in the renal tubular cell
• Glomerular filtrate contains bicarbonate at the same concentration as the plasma (18-24mmol/L)
• Urine is virtually bicarbonate-free (the kidney is not 100% efficient at reabsorption)
• The excreted H + is then buffered in urine by, e.g. phosphate and ammonia

Question 14

What are the ways in which hydrogen ions are produced?

Answer 14

Turnover of H+ ions from normal metabolic processes

• Incomplete oxidation of energy substrates generates acid e.g. lactic acid by glycolysis
• Further metabolism of these intermediates consumes it e.g. gluconeogenesis from lactate

Temporary imbalances between rates of production and consumption may occur in health

• Accumulation of lactic acid during anaerobic exercise

Metabolism also produces CO2

• Greater than 15000 mmol of CO2 is produced every 24 hr and in water this converts to a weak acid (H2CO3, carbonic acid)
• H+ can be generated stoichiometrically therefore potentially equivalent to 15000 mmol H+ ions
• In health pulmonary ventilation is controlled so excretion matches rate of formation

Question 15

How is Bicrabonate filtered and reabsorbed?

Answer 15

• Glomerular filtrate contains same concentration of bicarbonate ions as the plasma
• Virtually all filtered bicarbonate is reabsorbed
• Luminal surface of renal tubules is impermeable to bicarbonate therefore reabsorption must occur indirectly

Question 16

How does Bicarbonate work as a buffering compound?

Answer 16

When dissolved in blood, CO2 becomes an acid

• The more carbon dioxide added to blood, the more carbonic acid (H2CO3) is produced, which readily dissociates to release H+

Blood pH depends, not on absolute amounts of CO2 or HCO3-, but the ratio of the two. (20:1 HCO3:CO2)

Question 17

How does the Acidification of Urine take place?

Answer 17

Achieved by active secretion of H+ by the intercalated cells of the distal tubular cells and proximal collecting duct cells

• Minimal urine pH that can be achieved (4.5 or ~38 µmol/L) which Insufficient to remove daily H+ production, which is measured in mmol
• Significant acid excretion is achieved by H+ being buffered by phosphate, titrating HPO42- and H2PO4-

Question 18

How is H+ buffered in the Urine?

Answer 18

Monohydrogen (HPO42-) and dihydrogen phosphate (H2PO4-) form a buffer pair with a pKa of 6.8

• In renal filtrate, these molecules are in higher concentrations and are an important buffer.
• 30 – 40 mmol hydrogen is excreted in this way daily

Ammonium allows for urea syntheis to allow excretion fo hydrogen ions without generating H+

• pKa of ammonium (NH4+) is ~100 x lower than the physiological [H+], so almost all of ammonia in the body is already in the ammonium form

Question 19

What regulates respiratory rate?

Answer 19

Carbon dioxide is excreted by the lungs

• Respiratory control mechanisms are extremely sensitive to plasma CO2 concentrations.
• In health (excluding a conscious effort to hypo- or hyper-ventilate), the rate of CO2 elimination is equal to the rate of production
• Blood CO2 remains constant and is what regulates respiratory rate

Question 20

How are Blood Gases measured?

Answer 20

• Heparin blood sample from radial artery and measured in blood gas analyser
• Capillary blood maybe used for pH and PCO2 in neonates

Question 21

What are some measurements that can be made on Blood gases?

Answer 21

• pH: Measure of the level of hydrogen ion (H+)
• PO2: The partial pressure of O2 (the amount of oxygen gas dissolved in blood).
• PCO2: The partial pressure of CO2 (the amount of carbon dioxide gas dissolved in the blood)
• O2 saturation: A calculation of how much oxygen is bound to haemoglobin in the red blood cells and available to be carried through the arteries to nourish the body’s cells
• HCO3- (bicarbonate): Directly related to the pH level
• Base Excess: the amount of acid/base to titrate 1 litre of blood to a pH of 7.4

Question 22

What are causes of acid base disorders?

Answer 22

Respiratory

• Primarily due to breathing
• Impaired respiratory function causes a build-up of CO2 in blood
• Hyperventilation can cause a decreased PCO2

Metabolic

• Primarily due to bicarbonate concentration e.g.diabetic ketoacidosis

Question 23

How does H2CO3 relate to pCO2?

Answer 23

• H2CO3 is proportional to the dissolved carbon dioxide, which is in turn proportional to the partial pressure of CO2
• [H2CO3] can, therefore, be replaced in the equation by PCO2

Question 24

Describe the process of compensation of acid base disorders?

Answer 24

• Body tries to compensate for derangements in acid–base balance by means of physiological mechanisms that try to return [H +] to normal.
• Metabolic compensation for respiratory disorders takes a longer time and happens through H+ excretion and simultaneous bicarbonate regeneration
• Respiratory compensation for primary metabolic disorders occurs quickly – it takes the form of increased ‘blowing off’ of CO2 by the lungs.
• If compensation is complete, [H +] returns to normal and the acid–base disorder is described as fully compensated . A good example is stable chronic obstructive pulmonary disease.
• Body will never overcompensate

Question 25

What is the Anion Gap?

Answer 25

• Concentration of all the unmeasured anions in the plasma
• Negatively charged proteins account for ~10% of plasma anions and make up the majority of the unmeasured anion represented by the anion gap

([Na+] + [K+]) – ([Cl-] + [HCO3-])

Normal range: 6-16

Question 26

What is the purpose of Anion Gap?

Answer 26

• Identifies the presence of a metabolic acidosis
• Assists in assessing the biochemical severity of the acidosis and follow the response to treatment
• Help differentiate between causes of a metabolic acidosis: high vs. normal anion gap

Question 27

What causes changes in the anion gap?

Answer 27

• In an inorganic metabolic acidosis (e.g. due HCl infusion), the infused Cl- replaces HCO3-, the Anion Gap is normal
• In an organic acidosis, the lost HCO3- is replaced by the acid anion which is not normally measured then Anion Gap is increased
• Hypoalbuminaemia causes a low anion gap