1/2- gas exchange + transport/hemoglobin

definition of gas exchange

movement of gas between environment + blood, involving:

1. transport between atmosphere + alveolus (breathing)

2. diffusion across alveolar/capillary membranes → blood

how does Fick’s Law relate to diffusion of gases across air/blood barrier

rate of gas transfer is:

• directly proportional to the surface area (A), pressure gradient (ΔP), diffusion coefficient (D)

• inversely proportional to membrane thickness (T)

what’s Henry’s Law

a gas will dissolve in a liquid in proportion to the gas’s partial pressure over the liquid

how is Henry’s Law related to breathing

describes solubility of O₂ + CO₂ in plasma, CO₂ is 20x more soluble than O₂ + more rapidly even though its MW is higher

what is gas exchange in the alveoli driven by

partial pressure gradients: O₂ is driven into deoxygenated blood, CO₂ driven out

how do you calculate alveolar PO₂

alveolar gas equation: P_AO₂ = PIO₂ - (P_aCO₂/0.8)

PIO₂ = partial pressure of O₂ in inspired air (160 mmHg)

P_aCO₂ = arterial PCO₂

0.8 = respiratory exchange ratio

what’s A-aDO₂

difference between alveolar gas + mixed arterial blood even after complete equilibration, due to small amount of blood bypassing alveoli + not becoming oxygenated → combining w/ oxygenated blood, diluting the O₂

what’s normal A-aDO₂

~4 mmHg, under 30 years old

how does A-aDO₂ change w/ age

increases w/ age + lung compliance

abnormally high A-aDO₂ indicates what

pathological problem in which gas exchange is compromised

since O₂ is very poorly soluble in blood, how does it stay in the blood

via hemoglobin

describe the structure of hemoglobin + how it carries O₂

has 4 polypeptide chains, each chain has 1 heme group carrying 1 O₂ molecule → 1 Hb carries 4 O₂

T/F: once O₂ binds to Hb, O₂ no longer acts as gas + do not contribute to the pressure

true, Hb lowers PO₂ allowing more O₂ to go into the blood following the partial pressure gradient

T/F: once O₂ binds to Hb, Hb has a higher affinity to O₂

true

when oxygen is carried away into the tissues, how many of the O₂ are taken from the Hb

only 1 out of 4, therefore Hb returns to the lungs already 75% saturated + picks up 1 O₂ in the alveoli

the 3 remaining O₂ on Hb after becoming “deoxygenated” represent what

reserve capacity

T/F: dissolved oxygen represents only ~1.5% of the total content in arterial blood, the other 98.5% being bound to Hb

true

what’s the purpose of the small amount of dissolved oxygen in arterial blood

maintains the PO₂ necessary to keep the Hb saturated + only free O₂ can diffuse across cell membranesw

what 4 factors affect Hb binding to O₂

1. temperature

2. pH

3. PCO₂

4. 2,3-diphosphoglycerate

which has a higher affinity for O₂: fetal Hb or adult Hb

fetal Hb

what’s methemoglobin

normal Hb’s Fe²⁺ is oxidized → Fe³⁺ by drugs/chemicals → methemoglobin, which cannot bind O₂

how can methemoglobin return to being Hb

RBCs have an enzyme Met-Hb reductase that reduces Met-Hb → Hb

3 forms of CO₂ transport

1. dissolving in blood (~6%)

2. conversion into bicarbonate via carbonic anhydrase in RBCs (~70%)

3. conversion into carbamino compounds by reacting w/ free amines on proteins (~24%)

what role does Hb have in CO₂ transport

acts a buffer: Hb binds w/ the H⁺ produced from bicarbonate + carbamino compound rxns

T/F: Hb saturated w/ O₂ doesn’t bind as well to CO₂ , compared to Hb not saturated w/ O₂

true, increasing PO₂ facilitates release of CO₂ from Hb, while decreasing PO₂ allows Hb to take up more CO₂ + H⁺ (Haldane effect)

what’s myoglobin

protein in muscle that contains:

1. heme: a prosthetic group

2. proximal histidine: chelates iron directly

3. distal histidine: enables oxygen binding

meat turning brown is because of what

Fe²⁺ in myoglobin → Fe³⁺

what keeps heme in its Fe²⁺ state

O₂ + CO

3 important functions of myoglobin

1. increases solubility of O₂

2. facilitates O₂ diffusion

3. stores O₂

distinguish the subunits within Hb

Hb has 2 alpha + 2 beta subunits, alpha subunits in contact w/ beta subunits

T/F: once Hb/Mb binds to O₂, structure of Hb/Mb changes slightly

true

T/F: if Hb behaved like Mb, very little O₂ would be released in the capillaries

true

Hb exists in which 2 forms

1. T-state: taut, not bonded to O₂

2. R-state: relaxed, bonded to O₂

which Hb form is more stable

T-form, than R-form w/o O₂

R-form has increasing affinity for O₂ when

as it gains more O₂ molecules

describe what happens to the structure of Hb when it binds to O₂

Fe²⁺ ion moves → subtle conformational change in 1 subunit, which is in close contact w/ another subunit → causing other subunits to move

T/F: in addition to picking up O₂, Hb also unloads CO₂ from the blood → alveolus

true

what’s the Bohr effect

1. H⁺ is a negative allosteric effector: H⁺ causes Hb to drop O₂ aka lower pH causes Hb to drop O₂, lowering its affinity to bind O₂

2. CO₂ is a negative allosteric effector: CO₂ binds to Hb, lowering its affinity to bind O₂

describe the subunits of fetal Hb (HbF)

2 alpha subunits + 2 gamma subunits

what’s the main difference between HbA + HbF

HbF has the ability to bind to BPG, an allosteric effector of Hb → allowing HbF to have a higher O₂ binding affinity

what happens if BPG binds to HbA

lowers its O₂ binding affinity → allows you to adapt to high altitudes by delivering O₂ despite lower O₂ in the lungs

3 types of hemoglobinopathies

1. sickle cell

2. methemoglobin

3. thalassemias

sickle cell disease affects which subunit of Hb

glutamate mutates to valine on the exterior of beta subunit → making Hb insoluble (HbS)

T/F: Hb is normal in sickle-cell pts as long as it’s oxygenated

true

once deoxygenated, what happens to Hb in sickle cell pts

formation of deoxy-HbS-polymer → distorting the RBC shape

4 treatments of sickle cell

1. antibiotics

2. hydroxyurea: stimulates HbF production

3. bone marrow transplant

4. gene therapy

what are thalassemias

no mutation in Hb, but imbalance between the alpha + beta subunits

2 types of thalassemia

1. alpha: lack of alpha chain, too much beta

2. beta: lack of beta chain, too much alpha

alpha thalassemia predominates where vs. beta thalassemia

• alpha: Asian + African populations

• beta: Mediterranean populations

how is thalassemia treated

blood transfusion