5.15 Acid Base Balance

Question 1

What is an acid

Answer 1

A proton donor that releases H+ ions in a solution

Question 2

What is a base

Answer 2

A proton acceptor that accepts H+ ions from a solution

Question 3

What is the difference between a strong base/acid and a weak base/acid

Answer 3

A strong base/acid will completely dissociate into ions in the solution but a weak base/acid will only partly ionise in the solution

Question 4

What is a conjugate base and a conjugate acid

Answer 4

A conjugate base is what remains after the acid has donated its proton. A conjugate acid is what remains after the base has accepted its proton.

Question 5

Describe how pH is calculated and what its scale indicates

Answer 5

pH = -log10 [H+]
[H+] being the concentration of hydrogen ions in mol/L

As the pH scale is logarithmic, a 1 unit change corresponds to a 10 fold change in the hydrogen concentration. Hence even a small change in blood pH would have a big impact on the biological function

Question 6

Describe blood pH in humans

Answer 6

Blood pH is in a scale from 7.35 at the venous end to 7.45 in the arterial end. An average set point is 7.4.

Question 7

What is acidosis and when is it classified as severe

Answer 7

Acidosis can be a variety of processes that make plasma pH more accidic. Severe acidosis is when blood [H⁺] > 160 nmol/L (aka pH<6.8).

Question 8

What is alkalosis and when is it classified as severe

Answer 8

Alkalosis can be a variety of processes that make plasma pH more basic. Severe acidosis is when blood [H⁺] < 16 nmol/L (aka pH>7.8).

Question 9

Describe how volatile acid is produced by the body

Answer 9

From metabolism, the body produces 12-15 moles of CO2 a day. CO2 itself is not an acid but it reacts with water to form carbonic acid (H₂CO₃). Carbonic acid is considered volatile because it can reverse back into CO2 and water. This reaction is catalysed by carbonic anhydrase. This carbonic acid can dissociate into bicarbonate (HCO3-) and hydrogen ions.

Question 10

Describe how fixed acid is produced by the body.

Answer 10

The body produces 0.1 moles of fixed acid from metabollic processes such as the breakdown of sulfur containing amino acids to produce suphuric acid, gastric secretions producing hydrochloric acid, anaerobic metabolism producing lactic acid. Fixed acids can not be exhaled and must be excreted from the kidneys.

Question 11

What is the purpose of acid/base homeostasis

Answer 11

To maintain blood pH between 7.35 and 7.45

Question 12

What are the 3 regulatory mechanisms of acid/base homeostasis

Answer 12

-buffers (as the immediate response)
-respiratory regulation (response taking minutes)
-renal regulation (response taking hours to days)

Question 13

What is a pH buffer

Answer 13

It is something that resists change in pH when an extra acid or base is added. They can absorb or release H+ in response to this pH change. They can not prevent the pH change but they can help to minimise it.

Question 14

In what environment does a buffer work best and what dictates this

Answer 14

The buffer works best at its optimal pH, where acid and base levels are near equal. This allows the buffer to resist pH changes by absorbing or releasing H+ when small amounts of acid or base are added.

The actual pH of the buffer is determined by the ratio of conjugate base to weak acid. However the capacity of the buffer is determined by the absolute concentrations of the conjugate base and weak acid

Question 15

How is the pH of a buffer solution determined

Answer 15

The Henderson-Hasselbalch equation

pH = pKa + log10 ([B-]/[H-B])

pKa = dissociation constant of the weak acid, indicating its strength.
[B-] = Concentration of Conjugate Base
[H-B] = Concentration of Weak Acid

Question 16

What is the proportion of carbonic acid directly proportional to

Answer 16

The partial pressure of CO2

Question 17

What is the key balance in determining the pH of blood

Answer 17

The balance of bicarbonate and carbonic acid. An increase in bicarbonate will increase the pH of the blood, an increase in carbonic acid will decrease the pH of the blood. Hence the pH is directly proportional to the bicarbonate concentration and inversely proportional to the partial pressure of carbon dioxide

Question 18

What are the 3 major buffer systems in the body

Answer 18

Intracellular buffers
Extracellular buffers
Bone buffering

Question 19

What are intracellular buffers

Answer 19

The principal intracellular buffer is haemoglobin. Other intracellular buffers include other intracellular proteins and the phosphate buffer system

Question 20

What are extracellular buffers

Answer 20

The principal extracellular buffer is the bicarbonate buffer. Other extracellular buffers include inorganic phosphates and plasma proteins such as

Question 21

In what situation is bone buffering used

Answer 21

Bone buffering is a long term mechanism that is only used in cases of prolonged acidosis once the over compensatory buffering systems are already overwhelmed. However if bone buffering is used for too long in times of prolonged acidosis, there is continuous calcium and phosphate loss which can result in osteopenia and osteoporosis.

Question 22

Describe the mechanism of bone buffering

Answer 22

Calcium phosphate in the bone is mobilised to release phosphate ions and carbonate, this will help buffer excess hydrogen ions.
-H+ is absorbed onto the surface of the bone and is exchanged with Na, K and Ca that are released
-hyrdoxyapatite crystals on the bone are dissolved to release carbonate and calcium which will help to buffer any excess H+
-osteoclast activity is increased, this causes further bone resoprtion and release of ions used for buffering

Question 23

What is the disadvantage of buffering systems as a tool for acid/base homeostasis

Answer 23

They can only provide a short term solution and have limited capacity for longterm pH disturbances. Once the buffer capacity is exceeded, dynamic regulatory systems such as respiration and renal regulatory systems are required.

Question 24

Describe respiratory regulation of acid/base homeostasis

Answer 24

The respiratory system regulates the CO2 levels which influences the carbonic acid levels. Increased ventilation removes more CO2 which reduces H+ and raises pH. Decreased ventilation retains more CO2 which increases H+ an lowers pH.

Question 25

What are the benefits of respiratory regulation of acid/base homeostasis

Answer 25

Via chemoreceptors, any pH change directly influences ventilation rate. These changes respond in minutes which is faster than renal regulation

Question 26

What are the detriments of respiratory regulation of acid/base homeostasis

Answer 26

In times of severe hypoxia, the body will shift its priority to increasing ventilation, this can limit the effectiveness of respiratory regulation (e.g In early acclimatisation to altitude, there is a respiratory alkalosis due to the low pCO2 caused by increased ventilation)

Question 27

What is renal regulation of acid/base homeostasis

Answer 27

Renal regulation give long term control over acid/base balance by modifying bicarbonate levels and excreting fixed acids. This process takes hours/days to fully compensate for the disturbances in pH.

Question 28

What are the two mechanisms of renal regulation

Answer 28

reabsorption of filtered bicarbonate and excretion of fixed acids

Question 29

Describe the reabsorption of filtered bicarbonate

Answer 29

The bicarbonate that has been filtered into the renal tubules is mostly reabsorbed in the PCT via active transport (there is no net loss or gain of total bicarbonate or H+). In the lumen of the PCT, the bicarbonate combines with H+ to form carbonic acid. The carbonic acid is then converted to CO2 and water, this is catalysed by carbonic anhydrase in the luminal membrane of the PCT. The CO2 and water then diffuse into the epithelial cells of the PCT where carbonic anhydrase then converts them back into carbonic acid. The carbonic acid can then dissociate into bicarbonate and H+. The bicarbonate is transported into the peritubular capillaries where it can increase pH. The H+ is transported back into the lumen via Na+/H+ transporters.

Question 30

What are the 3 ways in which fixed acids are excreted in renal regulation

Answer 30

-secretion of free H+ into the urine
-excretion of ammonium into the urine
-titration of phosphate buffers in urine

Question 31

Describe the secretion of free H+ into the urine

Answer 31

In alpha intercalated cells in the collecting duct, CO2 combines with water to form carbonic acid which then dissociates into bicarbonate and H+. The bicarbonate is absorbed into the peritubular capillaries and the H+ is secreted into the collecting duct lumen via bothe K+/H+ exchangers and an H+-ATPase pump. The kidneys can lower the urine pH to a minimum of 4.5 which corresponds to an H+ conc of approximately 25 µmol/L

Question 32

Describe the titration of phosphate buffers in urine

Answer 32

Some H+ is buffered by filtered inorganic phosphate in the urine. The hydrogen phosphate combines with H+ to form dihydrogen phosphate which is then excreted in the urine. The rate of this depends on the serum phosphate concentration and the glomerular filtration rate, but typically it accounts for 30-40 mmol of acid excreted a day.

Question 33

Describe the excretion of ammonium into urine

Answer 33

Renal glutamine metabolism produces ammonium for acid secretion and generates bicarbonate, this glutamine is synthesised in the liver and enters the renal cells via peritubular capillaries (80%) and the filtrate (20%). In the PCT, glutamine is converted into glutamate via the glutaminase enzyme, this produces one ammonium ion. This glutamate is then converted into a-ketoglutarate via the glutamate dehydrogenase enzyme, this produces another ammonium ion. Hence 2 ammonium ions are produced for each glutamate metabolised in the kidneys. 2 bicarbonate ions are generated from the carbon skeleton of glutamine and are returned to the blood stream. This response is slower as the up/down regulation of the enzymes and production of glutamine in the liver takes time.

Question 34

How can ammonium excretion levels be adjusted

Answer 34

In times of acidosis glutaminase and glutamate dehydrogenase are upregulated to excrete more ammonium and eliminate excess H+ to restore pH.

Question 35

Define acidaemia and alkalaemia

Answer 35

Acidaemia = where arterial blood pH <7 .35

Alkalaemia = where arterial blood pH > 7.45

Question 36

In normal arterial blood, what is the pH, pCO2 and bicarbonate levels

Answer 36

pH = 7.35 – 7.45

pCO2 = 35-45 mmHg

bicarbonate = 22-26 mmol/l

Question 37

What are the 2 categories of acid/base balance disorders

Answer 37

Metabolic disorders which alter the bicarbonate levels and respiratory disorders which alter the pCO2 levels

Question 38

Describe metabolic acidosis and alkalosis

Answer 38

Metabolic acidosis: serum HCO3− < 22 mmol/L

Metabolic alkalosis serum HCO3− >26 mmol/L

Question 39

Describe respiratory acidosis and alkalosis

Answer 39

Respiratory acidosis is Pco2 > 6 kPa (45 mm Hg)

Respiratory alkalosis is Pco2< 4.5 kPa (35 mm Hg)

Question 40

What are some conditions that will cause metabolic acidosis

Answer 40

-diabetic ketoacidosis
-renal failure
-methanol poisoning
-diarrhoea

Question 41

What are some conditions that will cause metabolic alkalosis

Answer 41

-vomiting
-diuretics

Question 42

What are some conditions that will cause respiratory acidosis

Answer 42

-asthma attack
-chronic obstructive airway disease
-opiate overdose

Question 43

What is a condition that will cause respiratory alkalosis

Answer 43

Hyperventilation (e.g due to hypoxia at high altitudes)