Acid Base Balance (L5+6)

Question 1

Why do we need to regulate pH?

Answer 1

A small change in pH can lead to a large change in bodily function. The pH scale is logarithmic, so a small change in pH is actually a big change in proton concentration. pH can fluctuate due to acids/alkalis entering the body e.g. due to metabolism (CO2 from lings, breakdown of proteins e.g. western diets consist of a large amount of meat and there are many acids in fruit) - overall you get a net excess if 70mmol per day of protons that needs to be dealt with

Question 2

What are the normal pH and proton conc. range?

Answer 2

The normal physiological range is between 7.35 and 7.45. Plasma proton conc. is between 35-45 nM per litre. Venous blood is more acidic due to a higher concentration of CO2.
Some fluids differ in their pH but this is not pathophysiological like acidosis is.
Gastric secretions are about 7.3
Pancreatic secretions are about 8.1
Final urine is about 5.4 however this can vary depending on the composition

Question 3

What systems are involved in the regulation of pH?

Answer 3

Blood and tissue buffers - very quick, start working in seconds, for inside and out of cells and a localised change
Respiration - starts working in minutes
Renal - works in hours/days - for a more body-wide response - the only system that actually extrudes excess acid/alkalis, the rest just buffer it to reduce damage. - this is also why renal failure causes acidosis

Question 4

Where are buffers present in the body?

Answer 4

Blood plasma and red blood cells, extracellular fluid, intracellular fluid, urine

Question 5

What are some examples of buffers

Answer 5

Haemoglobin, HCo3-, inorganic phosphates, weak acids and bases on proteins (they can accept or donate protons)

Question 6

What is the primary extracellular fluid buffer? Explain how it works

Answer 6

Carbonic acid/bicarbonate us the primary extracellular fluid buffer. Carbon dioxide plus water goes to carbonic acid, which can then dissociate to form protons and bicarb. At equilibrium, you have all 5 parts present, but it can all shift around. If you increase the carbon dioxide, more carbonic acid will be made and therefore more dissociates to try and balance this out - this is why carbon dioxide makes the blood slightly more acidic. The bicarb can buffer this slightly but the plasma will end up slightly more acidic because a buffer can minimise the change, but not actually stop it .

Question 7

What is the Henderson-Hasselbach equation

Answer 7

pH = pK + log [HCo3]/[H2co3]
pK is a constant at 37 degrees (6.1)
Normally, the ratio of bicarb to carbdon dioxide is 20:1, so 6.1 + log20 = 7.4 which is the normal pH.

Question 8

Explain the Davenport diagram

Answer 8

A graph which shows the bicarb/carbon dioxide system well - The middle dot represents the normal physiological pH. The top right corner shows a high pH due to an increase in bicarb (the protons have been used up)- which shows metabolic acidosis. Bottom right shows a high pH but a low bicarb level, meaning carbon dioxide level levels have gone down (so not much carbonic acid and therefore protons produced), this respiratory alkalosis
The top left shows a decreased pH (acidic) but an increase in bicarb, so there too much dissociation of carbonic acid meaning there’s too much carbon dioxide, so this is respiratory acidosis. Bottom left shows a decrease in pH and bicarb, which shows its metabolic acidosis because bicarb can’t be used to buffer

Question 9

What cells make up carotid bodies?

Answer 9

The main cells of carotid bodies are glomus cells - which act like a nerve. The other cells (type II) are supporting cells

Question 10

What are sinusoids?

Answer 10

The vessels that run through the carotid body, they are swollen to allow for increased blood flow.

Question 11

What is the mechanism cells in the carotid body use to affect respiration?

Answer 11

A decrease in oxygen (hypoxia), increase in CO2 (hypercapnia) or a decrease in pH causes inhibition of BK potassium channels. This causes the membrane potential to increase (depolarise) because the potassium ions can’t get out of the membrane. This depolarization leads to an action potential being generated. This causes voltage-gated calcium channels to open, which increases extracellular calcium. This causes vesicle fusion and NT release (including ACh, dopamine, NA, 5HT, substance P and ANP). The release of these NTs causes afferent nerve fibre stimulation and tells the medulla and respiratory centre to increase breathing.

Question 12

What is thought to possibly be causing death in SIDS babies?

Answer 12

Some Sudden infant death syndrome babies have been found to have higher concentrations of carotid body dopamine and NA, this may be causing a disruption to their breathing pattern, which may be causing their death. some SIDS babies also lack serotonergic neurones, which may show a defect in their central chemoreceptors - so they have no neurones that are activated by high acid levels, so they can’t hyperventilate to correct this.

Question 13

How do central chemoreceptors help control blood pH

Answer 13

When blood gas parameters are normal, central chemoreceptors are the primary source for the tonic drive for breathing. Their main activator is hypercapnia. When the partial pressure of carbon dioxide is between 40-45 mmHg, ventialtion is doubled (this is only seen with a 50% fall in the partial pressure of oxygen, as they are so much more sensitive to hypercapnia than hypoxia). However, the pH is the actual parameter (partial pressures effect the pH)

Question 14

How were central chemoreceptors found and how are they stimulated?

Answer 14

identified in the 1950s by isidore Leusen. He perfused cerebral ventricles with acidic solution and observed the hyperventilation.
Central chemoreceptors are found within the brain parenchyma. They’re bathed in ECF and are separated from arterial blood by the BBB. The BBB has poor ion permeability. If arterial CO2 increases, the brain ECF increases and therefore the pH falls. This stimulates the receptors

Question 15

Why are glomus cell less sensitive with a higher pH?

Answer 15

Sensitivity to the change in the partial pressure of oxygen changes with a change in acid/base status (what the pH is). So, if the pH is lower (i.e. the partial pressure of CO2 is higher), the chemoreceptors become more sensitive to a lower partial pressure of oxygen, and if the pH is quite high, they’re less sensitive to oxygen. Sensitivity to changes in the partial pressure of CO2 is also altered with a change in pH. As carbon dioxide levels rise, more APs are fired, so the glomus cells are less sensitive with a higher pH.

Question 16

Why do metabollic disorders effect brain pH more than respiratoy?

Answer 16

In the brain ECF, there is less non-bicarb buffering power due to fewer proteins, so there is a larger fall in t pH when the partial pressure of CO2 increases. Some long term compensation for this includes the transport of bicarb from the blood. The poor ion permeability of the BB means metabolic disorders can change the pH of the brain ECF by 10-35% of that observed with respiratory disorders with the same change in blood oH

Question 17

Where are some central chemoreceptors found and what are the different neuronal populations?

Answer 17

Some central chemoreceptors are found in the ventrolateral medulla and other brainstem nuclei. There are 2 neuronal populations: Acid activated (serotonin) and acid inhibited (GABA)

Question 18

How to peripheral and chemoreceptors respond to respiratory acidosis in a staggered way?

Answer 18

Physiologically, they all change at the same time, however, they have integrated responses.
Both central and peripheral receptors are stimulated due to a fall in the partial pressure of oxygen (peripheral receptors) and an increase in the partial pressure of carbon dioxide (central). 65=80% of normoxic central receptors (ones that sense oxygen tensions between 10-21%) are activated. Peripheral receptors act faster. As the partial pressure of oxygen falls, the response to carbon dioxide is enhanced.

Question 19

How does breathing pattern change during acidosis?

Answer 19

During metabolic acidosis, hyperventilation occurs to decrease carbon dioxide levels. Kassmaul breathing - deep laboured breathing pattern which is often associated with a severe metabolic acidosis - particularly diabetic acidosis and kidney failure (acute renal acidosis). This is a peripheral acute response, and a central long term role (so quick from peripheral receptors and longer for central)

Question 20

What are the 3 renal mechanisms used in controlling blood pH?

Answer 20

Bicarb handling, urine acidification, ammonia synthesis. They used for the long term regulation of pH. Bicarb handling happens 90% in the proximal tubule and 10% in the distal tubule

Question 21

Explain what a proximal cell does

Answer 21

Filtered bicarb from out of the blood combines with the hydrogen transported out of the proximal tubule cell (via NHE3) to make carbonic acid. The carbonic acid is split into carbon dioxide and water by carbonic anhydrase. The water and carbon dioxide then enters the cell and recombine via carbonic anhydrase again. The carbonic acid now in the cell splits into bicarb and protons. The protons are recycled across the apical membrane by the NHE3 again. The bicarb is transported back across the basolateral membrane into the blood via a sodium-bicarb transporter. This is how bicarb is absorbed back into the blood (bicarb handling)

Question 22

What contributes to base conservation?

Answer 22

25% urine acidification

75% ammonia synthesis

Question 23

How does urine acidification occur?

Answer 23

Where an alkaline salt is converted into an acid salt. an Alkali phosphate is acidified and NaHPO4 turns into NaH2PO4. Uric acid and creatinine are made. Filtered disodium hydrogen phosphate loses a sodium which is used for the NHE3 (goes into the cell), it then combines with the hydrogen coming out of the cell via NHE3 to make sodium dihydrogen phosphate - this all happens in the filtrate, not in the cell- so is not reabsorbed. The sodium dihydrogen phosphate is an acid and goes into the collecting duct, so makes the urine more acidic. Inside the cell, carbonic anydrase combines water and carbon dioxide to make carbonic acid. It then splits into a proton and bicarb. the proton is recycled and the bicarb is recycled like in the proximal tubule.

Question 24

How does ammonia production take place?

Answer 24

Stimulated by acidosis.
Ammonia (NH3) combines with protons to make ammonium (NH4+) - which is a reversible reaction.
Ammonia is permeable and ammonium is impermeable, so the ammonia can be moved into the urine but ammonium can’t. Ammonia is formed from glutamine. Glutamine gives off ammonia and protons as it is converted into alpha keto-glutarate. The ammonia and proton leaves (proton leaves via NHE3 and ammonia can just leave by itself), they combine outside the cell into ammonium which stops it from re-entering and is lost in the urine (ammonium is acidic). the alpha-kg contributes too the bicarb added back into the blood.

Question 25

What is the renal response to acid-base disorders?

Answer 25

During acidosis, proton excretion increases and bicarb excretion is 0 because it’s being used to buffer the extra protons. The urine becomes more acidic and as a result, the pH plasma should be increasing because protons are being excreted. During alkalosis, proton excretion decreases and bicarb excretion increases. So the urine becomes more alkali and the pH or the plasma decreases because the bicarb is being excreted.

Question 26

What is meant by the term mixed disorders and how does it affect the patient?

Answer 26

When someone has more than 1 primary disorder.
E.g. respiratory acidosis due to a high carbon dioxide partial pressure and metabolic acidosis due to low bicarb level. Both elicit the same type of pH change which causes a big pH change - can be life-threatening
If you get one type of acidosis and one type of alkalosis its not as serious because they cancel out so its much milder.
E.g. alcoholic patients experience metabolic acidosis due to breakdown of ketones and metabolic alkalosis due to vomiting
Asthma patients experience respiratory acidosis and lactic acidosis due to lack of oxygen
COPD patients are treated with diuretics due to having metabolic alkalosis and respiratory acidosis.
Salicylate poisoning causes respiratory alkalosis (due to an increase in the respiratory centre) and metabolic acidosis due to an increase in acid.