INTEGRATED PHYSIOLOGY
Systems 2
Table of Contents
Integrated Physiology 2
Lectures 1 & 2: Acid Base 1 & 2 2
Lecture 3: Temperature Regulation 9
Lecture 4: Physiological Adaptations to High Altitude 11
Lecture 5: Stress Response to Traumatic Injury, Surgery and Critical Illness 14
Lecture 6: Aging and Changes in Homeostatic Mechanisms 17
, Integrated Physiology
Lectures 1 & 2: Acid Base 1 & 2
• Why does hyperventilation lead to light headedness? When you hyperventilate you drive off CO2.
Remember PACO2 α Rate of CO2 production / Alveolar ventilation rate, so if you increase alveolar
ventilation rate you decrease PACO2. Since CO2 is a natural vasodilator, when you drive off lots of CO2
the arterioles tend to vasoconstrict. When this happens to the cerebral arterioles you feel light
headed.
• Why does hyperventilation lead to alkalosis? Because CO2 when dissolved in water forms carbonic
acid, CO2 + H2O à H2CO3. This is a weak acid that dissociates into H+ + HCO3-. Hence, when you
remove CO2 from the equilibrium CO2 + H2O ⇔ H2CO3 ⇔ H+ + HCO3-, the whole thing shifts left. This
reduced the amount of H+ in the blood, raising pH.
• What is the equation relating pH to [H+]? pH = -log[H+], and rearranging [H+] = 10-pH
• What are the following things?
Term Description
Acid A proton donor.
+ -
For example HCl is an acid because it dissociates into H + Cl
Base A proton acceptor
+
For example NH3 is a base because it accepts a proton to become NH4
Strong Acid An acid that completely dissociates.
+ -
For example HCl à H + Cl happens almost entirely, leaving practically
+ -
no HCl left in the solution. All of it becomes H + Cl
Weak Acid An acid that partially dissociates.
+ -
For example H2CO3 ⇔ H + HCO3
Strong base A base that completely dissociates
+ -
For example NaOH à Na + OH completely
Weak Base A base that partially dissociates
+ +
For example ammonia NH3 + H ⇔ NH4
Conjugate acid When an acid looses its proton, it forms a conjugate base
-
For example HCO3 is the conjugate base of carbonic acid, H2CO3
Conjugate base When a base gains a proton, it forms a conjugate acid
+
For example NH4 is the conjugate acid of ammonia, NH3
pK The pH at which the acid or base is 50% dissociated.
+ - -
So if the acid HA ⇔ H + A , then the pH at which [A ]/[HA] = 1 (i.e. where
-
there is the same concentration of A as HA) is the pK.
+
Buffer A substance that resists a change in pH by absorbing H when an acid is
+
added, and releasing H when a base is added
A buffer consists of a weak acid and it’s conjugate base
Marc Huttman 2
,• What is Chvostek’s sign? When you tap on the facial nerve, the
muscles on that side of the face will all twitch. It’s a sign of low free
Calcium levels in the blood.
• Why can you get it if you’re hyperventilating?
o Ca2+ and H+ compete for binding onto albumin in the blood
o When you hyperventilate, you drive off CO2 and cause the [H+]
to fall
o Since there is less H+ about, more Ca2+ binds to albumin.
o Therefore, there is less free Ca2+ in the blood
o Ca2+ has a membrane stabilizing effect for neurons, so if there’s
less of it around, the neurons become hyper excitable
o So when you tap the nerve, they all fire off action potentials and
make the face twitch
• Why can you also get tingling in the fingers and around the lips when you hyperventilate? For the
same reason as above, the neurons become hyper excitable and start firing of action potentials.
• What other clinical sign can be seen when you have low free Ca2+? Trousseau’s sign where the hand
spasms after a blood pressure cuff is left on for a few minutes
• What are the extracellular buffers found in the body?
1. Bicarbonate
2. Haemoglobin
3. Phosphate
4. Plasma proteins
• What is the isohydric principle? The way all the extracellular buffers work together to resist changes
in pH
• How does bicarbonate buffer the blood? In the simplest way:
o CO2 + H2O ⇔ H2CO3 ⇔ H+ + HCO3-
o When acid is added, the system shifts left and excess CO2 is removed from the lungs by
hyperventilation. HCO3- levels are then replenished by the kidneys.
o When base is added, the OH- is mopped up by the H+ to form H2O. Excess HCO3- is removed by
the kidneys. CO2 levels are maintained by hypoventilation.
• Hence, what regulates the amount of CO2 in the blood? The lungs
• And what regulates the amount of HCO3- in the blood? The kidneys
• What is Henry’s law and why is it relevant? States that the amount of gas that dissolves in a liquid is
directly proportional to the partial pressure of that gas on the liquid. Hence, the amount of CO2 that
dissolves in blood is directly proportional to PCO2. For every mmHg of PCO2 per litre of blood, 0.03
mmol will dissolve. Hence, [H2CO3] = 0.03 x PCO2
• When might we have to use that in a question? If it gives you the pK, PCO2 and [HCO3-] and asks you
to calculate the pH. For example, what is the pH of blood in which [HCO3-] = 24, PCO2 is 40 and pK =
6.1?
o Use Henderson-Hasselbach equation (which will be given), pH = pK + log([A-]/[HA])
o pK = 6.1
o [A-] = 24
o [HA] = [H2CO3] = 0.03 x PCO2 = 0.03 x 40 = 1.2
o Hence pH = 7.4
Marc Huttman 3
, • How does pH relate to [HCO3-] and PaCO2? This you need to remember:
o pH α [HCO3-] / PaCO2
o This makes sense as the higher [HCO3-], the more the equation CO2 + H2O ⇔ H2CO3 ⇔ H+ +
HCO3- will shift left so the lower the [H+] and the higher the pH
o The higher the PaCO2, the more the equation CO2 + H2O ⇔ H2CO3 ⇔ H+ + HCO3- will shift right
so the higher the [H+] and the lower the pH
• Does the body produce acid or alkali products? It’s a net producer of
acid:
o The Kreb’s cycle produces CO2 which is an acid.
o Also, the majority of gut segments below the pylorus secretes
HCO3- into the lumen, and hence H+ into the gut. This ‘acid tide’ is
greater than the ‘alkaline tide’ in the stomach (revise GI if that
doesn’t make sense).
o Metabolism of proteins also requires bicarbonate (as the side
chains like phosphate and sulphate get metabolised into
sulphuric and phosphoric acid which need to be neutralised)
• How do the lungs regulate CO2 levels? By the amount of breathing. The more you breathe, the more
CO2 you will loose. Changes in PaCO2 will stimulate chemoreceptors and triggers changes in
breathing.
• How does the kidney regulate
bicarbonate levels?
1. Reabsorption of HCO3- in the PCT (pg
19 renal)
2. Making new HCO3- in the
intercalated cells of the DCT by
pumping H+ into the urine (pg 23
renal)
• Is there a link between K+ reabsorption and acid/base regulation? Yes,
because remember in the intercalated cell K+ is reabsorbed via a
countertransporter Apical H+/K+ ATPase (pg 23 renal)
• Look at this schematic to summarise this first lecture:
Marc Huttman 4
Systems 2
Table of Contents
Integrated Physiology 2
Lectures 1 & 2: Acid Base 1 & 2 2
Lecture 3: Temperature Regulation 9
Lecture 4: Physiological Adaptations to High Altitude 11
Lecture 5: Stress Response to Traumatic Injury, Surgery and Critical Illness 14
Lecture 6: Aging and Changes in Homeostatic Mechanisms 17
, Integrated Physiology
Lectures 1 & 2: Acid Base 1 & 2
• Why does hyperventilation lead to light headedness? When you hyperventilate you drive off CO2.
Remember PACO2 α Rate of CO2 production / Alveolar ventilation rate, so if you increase alveolar
ventilation rate you decrease PACO2. Since CO2 is a natural vasodilator, when you drive off lots of CO2
the arterioles tend to vasoconstrict. When this happens to the cerebral arterioles you feel light
headed.
• Why does hyperventilation lead to alkalosis? Because CO2 when dissolved in water forms carbonic
acid, CO2 + H2O à H2CO3. This is a weak acid that dissociates into H+ + HCO3-. Hence, when you
remove CO2 from the equilibrium CO2 + H2O ⇔ H2CO3 ⇔ H+ + HCO3-, the whole thing shifts left. This
reduced the amount of H+ in the blood, raising pH.
• What is the equation relating pH to [H+]? pH = -log[H+], and rearranging [H+] = 10-pH
• What are the following things?
Term Description
Acid A proton donor.
+ -
For example HCl is an acid because it dissociates into H + Cl
Base A proton acceptor
+
For example NH3 is a base because it accepts a proton to become NH4
Strong Acid An acid that completely dissociates.
+ -
For example HCl à H + Cl happens almost entirely, leaving practically
+ -
no HCl left in the solution. All of it becomes H + Cl
Weak Acid An acid that partially dissociates.
+ -
For example H2CO3 ⇔ H + HCO3
Strong base A base that completely dissociates
+ -
For example NaOH à Na + OH completely
Weak Base A base that partially dissociates
+ +
For example ammonia NH3 + H ⇔ NH4
Conjugate acid When an acid looses its proton, it forms a conjugate base
-
For example HCO3 is the conjugate base of carbonic acid, H2CO3
Conjugate base When a base gains a proton, it forms a conjugate acid
+
For example NH4 is the conjugate acid of ammonia, NH3
pK The pH at which the acid or base is 50% dissociated.
+ - -
So if the acid HA ⇔ H + A , then the pH at which [A ]/[HA] = 1 (i.e. where
-
there is the same concentration of A as HA) is the pK.
+
Buffer A substance that resists a change in pH by absorbing H when an acid is
+
added, and releasing H when a base is added
A buffer consists of a weak acid and it’s conjugate base
Marc Huttman 2
,• What is Chvostek’s sign? When you tap on the facial nerve, the
muscles on that side of the face will all twitch. It’s a sign of low free
Calcium levels in the blood.
• Why can you get it if you’re hyperventilating?
o Ca2+ and H+ compete for binding onto albumin in the blood
o When you hyperventilate, you drive off CO2 and cause the [H+]
to fall
o Since there is less H+ about, more Ca2+ binds to albumin.
o Therefore, there is less free Ca2+ in the blood
o Ca2+ has a membrane stabilizing effect for neurons, so if there’s
less of it around, the neurons become hyper excitable
o So when you tap the nerve, they all fire off action potentials and
make the face twitch
• Why can you also get tingling in the fingers and around the lips when you hyperventilate? For the
same reason as above, the neurons become hyper excitable and start firing of action potentials.
• What other clinical sign can be seen when you have low free Ca2+? Trousseau’s sign where the hand
spasms after a blood pressure cuff is left on for a few minutes
• What are the extracellular buffers found in the body?
1. Bicarbonate
2. Haemoglobin
3. Phosphate
4. Plasma proteins
• What is the isohydric principle? The way all the extracellular buffers work together to resist changes
in pH
• How does bicarbonate buffer the blood? In the simplest way:
o CO2 + H2O ⇔ H2CO3 ⇔ H+ + HCO3-
o When acid is added, the system shifts left and excess CO2 is removed from the lungs by
hyperventilation. HCO3- levels are then replenished by the kidneys.
o When base is added, the OH- is mopped up by the H+ to form H2O. Excess HCO3- is removed by
the kidneys. CO2 levels are maintained by hypoventilation.
• Hence, what regulates the amount of CO2 in the blood? The lungs
• And what regulates the amount of HCO3- in the blood? The kidneys
• What is Henry’s law and why is it relevant? States that the amount of gas that dissolves in a liquid is
directly proportional to the partial pressure of that gas on the liquid. Hence, the amount of CO2 that
dissolves in blood is directly proportional to PCO2. For every mmHg of PCO2 per litre of blood, 0.03
mmol will dissolve. Hence, [H2CO3] = 0.03 x PCO2
• When might we have to use that in a question? If it gives you the pK, PCO2 and [HCO3-] and asks you
to calculate the pH. For example, what is the pH of blood in which [HCO3-] = 24, PCO2 is 40 and pK =
6.1?
o Use Henderson-Hasselbach equation (which will be given), pH = pK + log([A-]/[HA])
o pK = 6.1
o [A-] = 24
o [HA] = [H2CO3] = 0.03 x PCO2 = 0.03 x 40 = 1.2
o Hence pH = 7.4
Marc Huttman 3
, • How does pH relate to [HCO3-] and PaCO2? This you need to remember:
o pH α [HCO3-] / PaCO2
o This makes sense as the higher [HCO3-], the more the equation CO2 + H2O ⇔ H2CO3 ⇔ H+ +
HCO3- will shift left so the lower the [H+] and the higher the pH
o The higher the PaCO2, the more the equation CO2 + H2O ⇔ H2CO3 ⇔ H+ + HCO3- will shift right
so the higher the [H+] and the lower the pH
• Does the body produce acid or alkali products? It’s a net producer of
acid:
o The Kreb’s cycle produces CO2 which is an acid.
o Also, the majority of gut segments below the pylorus secretes
HCO3- into the lumen, and hence H+ into the gut. This ‘acid tide’ is
greater than the ‘alkaline tide’ in the stomach (revise GI if that
doesn’t make sense).
o Metabolism of proteins also requires bicarbonate (as the side
chains like phosphate and sulphate get metabolised into
sulphuric and phosphoric acid which need to be neutralised)
• How do the lungs regulate CO2 levels? By the amount of breathing. The more you breathe, the more
CO2 you will loose. Changes in PaCO2 will stimulate chemoreceptors and triggers changes in
breathing.
• How does the kidney regulate
bicarbonate levels?
1. Reabsorption of HCO3- in the PCT (pg
19 renal)
2. Making new HCO3- in the
intercalated cells of the DCT by
pumping H+ into the urine (pg 23
renal)
• Is there a link between K+ reabsorption and acid/base regulation? Yes,
because remember in the intercalated cell K+ is reabsorbed via a
countertransporter Apical H+/K+ ATPase (pg 23 renal)
• Look at this schematic to summarise this first lecture:
Marc Huttman 4
