Respiratory System Flashcards
external respiration
- O2 and Co2 exchange
i) between lungs and atmosphere
ii) between avleoli and blood
iii) blood transport
iv) between blood and cells
internal respiration
-O2 utilization by mitochondria to regenerate ATP, forming CO2 (where oxygen is the electron donor)
what are the 6 primary functions of the respiratory system?
1) respiration
2) homeostatic regulation of body pH
3) defends against microbes
4) modifies arterial concentrations of chemical messengers
5) vocalization
6) sense of smell
how does the respiratory system homeostatically regulate body pH
–by selectively retaining or releasing CO2 (which is an acid generator - creates bicarbonate in protons - climate change in the long term is a problem because of acidity of lakes because of this)
how does the respiratory system defend against microbes?
- traps and destroys harmful pathogens before they enter the body
- lungs are a perfect place for bacteria (warm and moist) - major defense is protecting in the capillaries of the lungs to keep bad things out of blood stream
how does the respiratory system modify arterial [ ] of chemical messengers?
- removes and inactivates some messengers/enzymes
- produces or activates others (ex: angiotensin I to angiotensin II
the lungs and heart are located in which cavity?
thoracic cavity
each lung is divided into lobes, how many?
right lung into 3 lobes and left into 2
through where does air enter the lungs?
upper airways and a network of tubes called the respiratory tract
each lung is completely surrounded by a double layered _____
pleural sac (serous membrane)
what is the pleural sac of the lungs attached to?
- inner visceral pleura is attached to the lung by connective tissue
- outer parietal pleura is attached to the thoracic wall and diaphragm
what fills the pleural sac? what is the purpose of this?
this sac filled by a very thin layer of fluid that holds the pleural layers close together and lubricates them during breathing
-reduces friction - any kind of pulling causes pressure changes to be high
why is it critical that the pleural sac is attached to the diaphragm?
the lungs are not a muscle and therefore if they were not attached to the diaphragm, they would not move on their own - movement of air relies on the diaphragm
how many branches does the respiratory tract have? From where to where?
23 generations of branches
-from trachea to alveoli
the respiratory system is divided into 2 functional zones. What are they?
the conducting zone and the respiratory zone
how much air volume is in the conducting zone of the respiratory system?
total air volume of 150 mL (ish)
-anatomical dead space (where air that is breathed in does not serve any purpose because it does not reach the lungs)
what happens to air as soon as it enters our lungs? Why does this happen?
air is warmed and humidified as it enters our lungs to help with diffusion
-the humidity inside our lungs is 100%
the walls of the conducting zone of the respiratory system consist of what?
- SM, elastic tissue, and cartilage
- lined by a mucus-secreting, ciliated epithelium (first line of defense)
- as we go down in the zone, we get less cartilage and more SM
how much air does the respiratory volume hold?
about 3000 mL (at rest)
only about 10% of the capillaries in the respiratory zone of the respiratory system are open at all times
true or false?
false, unlike other capillaries of the body, these are always open (most of the time) (especially towards the bottom)
which zone of the respiratory system acts as a huge, thin surface area for gas exchange?
respiratory zone
the diffusion of gases between adjacent alveoli is facilitated by what?
pores of Kohn (these can be blocked in the case of some diseases)
there is plenty of cartilage and SM in the respiratory zone
true or false?
false, there is no cartilage and little SM (none in alveoli)
what sits between alveolar cells to provide tensile strength and stretch/recoil properties?
elastin fibers
how is foreign matter engulfed/destroyed in the respiratory zone?
by phagocytotic macrophages
what is the approximate diameter of a single alveoli? what is their shape?
- 25 mm
- polyhedral in shape
alveolar type I cells
single layer of type I epithelial cells
- 80-90% of all surface area -take up most of the surface
- underlying basement membrane
- very thin - diffusion of respiratory gases
- large gradient for CO2 and O2 (highest oxygen content meets lowest oxygen content)
type II alveolar cells
- secrete surfactant: reabsorb Na+ and H2O
- these hold everything together but do not have a big role in gas exchange
- make sure lungs don’t get too wet (no lymphatic system here to drain fluid)
more surfactant is released when we take larger breaths
true or false?
true
tidal volume
- volume of air that moves into and out of lungs per breath (approx 500 mL at rest)
- females is about 25% lower
- very small fraction of our total lung volume
inspiratory reserve volume
- maximal air volume that can be inspired following a normal inspiration
- just under 6L in volume (double the air volume at rest)
expiratory reserve volume
- maximal air volume that can be expired following a normal expiration
- (about 1 L)
residual volume
-volume of air in lungs following maximal expiration
vital capacity
-maximal volume of air that can be exchanged per breath
how can we measure total ventilation per minute or ‘minute ventilation’?
total ventilation = tidal volume X respiratory rate
= 500 mL/breath X 12 breaths/min = 6000 mL/min
how much fresh air do we get in our lungs every breath? why?
tidal volume is approx 500 mL but we only get 350 mL of fresh air per breath because of the anatomical dead space
-this leads to only 4L of fresh air entering our lungs per minute instead of 6
because the volume of the dead space does not change, _____ is far more important in increasing alveolar ventilation than respiratory rate
depth of breath
both blood flow and air flow follow gradients, but what is the difference between them?
we have tidal flow in breathing, blood goes one way, air goes both ways
all pressures are expressed relative to what?
atmospheric pressure (about 760 mmHg at sea level)
intra alveolar pressure (Palv)
pressure within alveoli (-1 to +1 mm Hg)
-this is what DRIVES ventilation by creating the gradient
how can we calculate inspiration/expiration volume
volume = Patm - Palv / R (resistance)
why is the pressure within alveoli so low? this is what drives ventilation so why isn’t it higher?
there is almost no resistance to air flow therefore the pressure gradient does not need to be that high
there are no muscles attached to the lung surface, therefore lung volume is largely dependent upon changes in what?
pleural sac pressure
transpulmonary (transmural) pressure
Tp = Palv - Pip
- pressure gradient between the alveoli and the intrapleural sac
- this sac is constantly being pulled from both directions
intrapleural pressure (Pip)
- pressure within the pleural sac (-4 to -7 mm Hg)
- ALWAYS negative during normal breathing and ALWAYS less than Palv
the lungs and chest wall are both elastic
true or false?
true
between breaths, the chest wall is ______ , whereas the lungs are ______
compressed (pulling outwards), stretched (pulling inwards)
according to Boyle’s law, any increase or decrease in pleural sac volume will cause a corresponding decrease or increase in _______
Pip
-intrapleural pressure
pressure inside the lung _______ as lung volume increases during inspiration
decreases
pressure inside the lung ______ during expiration
increases
pleural cavity pressure becomes more _______ as chest wall expands during inspiration
negative
the diaphragm is auto rhythmic
true or false?
false, the diaphragm relies 100% on signals from the medulla
-this is why a high enough neck break can affect breathing if the medulla is affected
-release of ACh at the diaphragm (which flattens and moves downward) and external intercostal muscles (pivots ribs up and outwards) expand the thoracic cavity
is expiration passive or active during quiet breathing?
elastic recoil of the lungs and thoracic cage return the ribs and the diaphragm to their original position, this is passive expiration
is expiration passive or active during exercise?
the contraction of the internal intercostals and abdominal muscles are invoked during exercise or forced heavy breathing, this is active expiration
which muscles are active during expiration?
internal intercostals and abdominal muscles
which muscles are contracted during inspiration?
diaphragm and external intercostals
what would happen if you were stabbed in the chest?
if the pleural sac is punctured, Pip equilibrates with the pressure of the atmosphere, causing the lungs to collapse and the chest wall to expand
-this is called a pneumothorax
-if you heal the wound, gases will diffuse and go back to equilibrium themselves
explain the pressure changes that happen in the lungs during inspiration
- contraction of diaphragm and external intercostal muscles
- chest wall expands
- decreases in intrapleural pressure
- increase in transpulmonary pressure
- increase in lung volume
- decrease in alveolar pressure
- increase in the difference between alveolar pressure and atmospheric pressure
- air flows into alveoli until pressure is equal
what are the two factors affecting pulmonary ventilation?
lung compliance and airway resistance
lung compliance is equivalent to elasticity of lungs
true or false?
false, it’s stretchability, not elasticity
stretchability of lung tissue increases with age
true or false?
false, it decreases with age, and due to ‘restrictive lung diseases’
-ex: fibrotic lung disease
fibrotic lung disease
- chronic inhalation of fine particulate matter (asbestos, coal dust, cigarette smoke) deep into lungs
- resulting inflammatory process leads to a build up of collagen (inelastic, fibrous scar tissue) that decreases lung compliance thus impairing inspiration
- thicker alveolar membranes also slow gas exchange
if lung compliance goes down, we need a massive increase in pressure differences, need to breath harder - air does not diffuse as easily either
lung compliance is affected by which 2 things?
stretchability of lungs and surface tension at the air-water interface with alveoli
how does surface tension at the air-water interface within alveoli affect lung compliance?
attractive forces (H+ bonds) between adjacent H2O molecules resist alveolar expansion and increase the work of inspiration -the water in the alveoli resist the alveoli from expanding
which substance is in our lungs that reduces surface tension at the air-water interface within alveoli, thus increasing lung compliance?
the amphipathic phospholipid surfactant decreases the cohesive forces between H2O molecules on the surface of alveoli
how is surfactant released in the circulation?
release is stimulated via the stretching of type II cells
-therefore, deeper breaths release more surfactant
when does surfactant synthesis start?
begins about the 24th week of fetal development and reaches adequate levels by the 34th week
why are premature babies subject to respiratory distress syndrome?
if babies are born prematurely, the surfactant in their system has not fully developed which decreases the compliance of their lungs
-60% of babies born before 28 weeks develop this syndrome - this used to lead to 50% mortality but now we can artificially administer surfactant or use artificial ventilation (administering the mother with cortisol also increases surfactant productivity in the fetus)
how does transpulmonary pressure affect airway resistance while breathing?
Tp is the major effector on airway resistance
- exerts a distending force on small, cartilage-free airways
- because Tp increases during inspiration, airway radius also increases and vice versa
how does lateral traction affect airway resistance?
- small airways are physically connected to surrounding alveolar tissue by elastic connective tissue fibers
- outward expansion of alveolar sacs during inspiration pulls the airway more open
- the opposite occurs when we breath out - part of the reason why we have residual volume - takes a lot of pressure to get that last bit of air out
transpulmonary pressure and lateral traction are both examples of _______ forces that affect airway resistance
passive
what are the 3 major factors that affect airway resistance?
1) passive forces
2) bronchial SM tone
3) pathological states
parasympathetic stimulation causes bronchioles to _______. explain this in more detail
constrict, ACh released from parasympathetic neurons increases Ca++ levels
sympathetic innervation is most common in bronchiolar SM
true or false?
false, there is little sympathetic innervation of bronchiolar SM, however, stimulation of SM B2 receptors by epinephrine relaxes the airway
-ex: during exercise (more oxygen circulating)
the lungs are primarily innervated by which branch of the ANS?
parasympathetic
which 3 things affect bronchiole SM tone?
1) nervous and endocrine control
2) paracrine agents
3) PCO2 levels
______ released by mast cells causes _____ of SM and stimulates mucus secretion, increasing airflow resistance
histamine, contraction
histamine is a paracrine agent
true or false?
true
how does PCO2 affect bronchiole SM tone?
increased PCO2 concentration causes bronchioles to dilate, decreased PCO2 concentrations causes bronchioles to constrict
how does asthma affect airway resistance?
- episodes of inflammation and strong bronchiocontriction due to hyper-responsiveness of bronchiolar SM to irritants
- also get a chronic increase int he number of mast cells (thus, increased histamine release)
- epipens release epinephrine which bind to B2 receptors and cause dilation
emphysema
- 5th leading cause of death
- destruction and collapse of alveoli and smaller airways due to the loss of elastic fibers, which increases lung compliance but impairs expiration trapping air in lungs (abnormally high residual volume)
- this is progressed by smoking
- “suffocation with lungs full of air”
- increases in CO2 lead to pulmonary hypertension = right side heart disease
chronic bronchitis
- often co-exists with emphysema
- inflammation of airways, accumulation of mucus
- can’t breath in, can’t breath out
total pressure
sum of the partial pressures that EACH gas exerts independently
when a liquid is exposed to air, gas molecules can enter the liquid and dissolve into it, therefore, at equilibrium, Pgas(air) = Pgas(fluid)
true or false?
true, even thought the []’s are radically different
gases, both within (and between) the air and liquid states, diffuse down _______ gradients
partial pressure
read about alveolar gas pressures
look at graph too?
the PO2 of pulmonary vein blood is more than PO2 of expired air
true or false?
false, it is less
why is it important to match the rate of air flow (ventilation) into groups of alveoli with the rate of blood flow (perfusion past those alveoli?
otherwise, blood draining poorly ventilated alveoli will mix with that form well-ventilated alveoli, decreasing the average PO2 of systemic arterial blood
how does standing affect the matching of ventilation with alveolar blood flow?
standing diverts more blood flow past the lower lung alveoli (due to gravity) leading to ventilation/perfusion mismatch
-this explains why mean alveolar PO2 is bigger than pulmonary vein PO2
the slight increase in pulmonary blood pressure during exercise opens the lower lung capillary beds, increasing O2 uptake capacity
true or false?
false, it opens the upper capillary beds, the lower ones are often already open due to gravity
is ventilation/perfusion matching with alveolar blood flow and local or an extrinsic regulation?
local
the ventilation/perfusion matching in alveolar blood pressure involves the local regulation of SM in which 2 vessels?
both bronchioles and pulmonary arterioles in response to PCO2 and PO2 in the interstitial fluid bathing these structures
how does an increase in PCO2 affect blood flow in the bronchioles, pulmonary arterioles, and systemic arterioles?
- bronchioles dilate to lower resistance of air flow to get rid of CO2
- pulmonary arterioles constrict, since there is no O2 in the blood, it would be useless for the blood to go here
- systemic arterioles dilate
what would an increase in PO2 affect blood flow in bronchioles, pulmonary arterioles, and systemic arterioles?
- bronchioles constrict
- pulmonary arterioles dilate to pick up oxygen
- systemic arterioles constrict (weak response) because they don’t need oxygen
why do the same stimuli (ex: increase in PCO2 or PO2) cause contrasting effects at the pulmonary versus systemic arterioles?
so that the most oxygen can reach our muscles
since O2 diffuses so poorly in aqueous solutions, what helps this molecule diffuse through our system?
Hemoglobin
how many units in a Hb molecule?
4
- 2 alpha chains
- 2 beta chains
each of which is bound to a Fe++ -containing heme group
where is hemoglobin found?
ONLY within erythrocytes (RBCs)
-in each one, there is about 200 million Hb molecules
which part of the Hb does oxygen bind to?
Fe++ containing heme group
where is the site on the Hb molecule where the binding and unbinding of Hb occur?
Fe++ site
what are the 2 main functions of Hb?
1) binds O2 when plasma PO2 is high (in pulmonary capillaries)
2) releases O2 when plasma PO2 is low (in systemic capillaries)
hemoglobin facilitaites O2 delivery within skeletal muscle
true or false?
false, myoglobin facilitates O2 delivery within skeletal muscle
what happens to PO2 of the fluid once O2 binds to Hb?
once O2 binds to Hb, it NO LONGER CONTRIBUTES to PO2 of the fluid
-thus, plasma PO2 is entirely dictated by the amount of O2 dissolved in the plasma
law of mass action
increasing the [ ] of one substance involved in a reversible reaction drives that reaction towards the opposite side
how is it that diffusion from alveoli to the plasma is maintained, despite the large net transfer of O2?
because O2 binds to Hb until it becomes saturated, keeping this gradient
Hb carries about ___% of all the oxygen your cells consume, without using any of it
99
what are the two states of Hb?
1) oxyhemoglobin (HbO2) - R or relaxed state
2) deoxyhemoglobin (dHb) - T or tense state
what regulates the formation/breakage of Hb’s R state to T state?
R-T transition is regulated by the formation/breakage of salt bridges (weak ionic bonds) between adjacent globin subunits
-this causes structural changes in the protein chains that alter the shape of the heme gorups, thereby decreasing their affinity for O2
T state hemoglobin has a ____ shape and R state Hb has a _____ shape
cupped, flat
the R-T transition of Hb is not only affected by the binding of oxygen, it is also affected by what?
the binding of allosteric effectors to the Hb protein (Cl-, CO2, H+)
CO2 predominantly binds to beta chains in Hb
true or false?
false, it binds to alpha chains
oxygen equilibrium curve (OEC)
being a multi-subunit protein, Hb exhibits both cooperative oxygen binding and allosteric modulation of O2 affinity
-dramatically expands its effectiveness as an O2 transporter (wherever it is along this curve)
a conformational change in one subunits of Hb will NOT cause a conformational change in the others
true or false?
false, the four subunits of Hb are connected in such a way that a conformational change in one subunit is simultaneously conferred to the other 3 subunits - hence, oxygen binding at one site in the Hb increases the oxygen binding affinity at the other sites (and vice versa)
the binding affinity of Hb for the 4th O2 that is bound to the protein is the same as the first O2 that is bound
true or false?
false, after each O2 molecule binds to Hb, the affinity increases
-therefore, the binding afifnity for the 4th O2 molecule is approx. 300 times higher than that of the first
a Hb protein can bind to 1, 2, 3, or 4 O2 molecules
true or false?
false, it’s either bound to 0 or 4 O2 molecules, there’s no such thing as an “in between R and T state”
what shape is the oxygen equilibrium curve?
sigmoidal
why is it important that oxygen binding to Hb is a cooperative system?
-cooperative binding allows for a larger difference in % of Hb-O2 saturation between the lung capillaries compared to a non cooperative protein (ex: cooperative: 98%-32% = 66% vs non-cooperative = 68%-30% = 38%) - (these percentages refer to the amount of O2 offloaded from Hb from lungs to tissues)
over the same range of PO2 values, cooperative binding by Hb enables the blood to bind and offload approx. _____ more O2, relative to a non-cooperative protein per cycle through the circulation
1.7 times
how would a non-cooperative binding system in the Hb-O2 binding affect cardiac output?
our CO would need to be 70% higher AT REST to deliver the same amount of oxygen
what is the importance of the upper plateau portion of the oxygen equilibrium curve?
- this portion of the curve ranges from 60-100 mmHg
- is spans the plasma PO2 range found in the pulmonary capillaries over a wide range of conditions (pressures)
- ex: at sea level, alveolar PO2 = 100 mmHg - blood is about 98% saturated (approx. 20 mL O2/100 mL blood)
vs.
- at 3000m elevation, alveolar PO2 = 70 mmHg and blood is STILL about 92% saturated (19 mL O2/ 100mL blood)
- so we can drop the amount of available O2 by 30%, but Hb is still over 90% saturated (creates a large safety margin)
according to the oxygen equilibrium curve, drops in PO2 become problematic when they pass which point?
when PO2 drops below 70 mmHg (ex: fibrotic and obstructive lung diseases)
-this is the start of the steep part of the curve, less and less Hb is saturated
what is the importance of the steep portion of the oxygen equilibrium curve?
- this portion of the curve ranges from 10-50 mmHg
- spans the plasma PO2 range at the systemic capillaries, thereby automatically altering the amount of O2 unloaded by the blood to the tissues per trip through the circulation
- at rest, venous blood is still largely saturated, thus creating a large O2 reserve that can be tapped into during exercise
-ex: at rest, capillary PO2 = 40 mmHg, blood = 75% saturated (15 mL O2/ 100 mL of blood)
vs
- during exercise, capillary PO2 = 20 mmHg, blood is about 30% saturated (6mL/100mL blood)
- therefore, small drops in PO2 causes a large amount of O2 to be offloaded, the lower the PO2, the more PO2 is going to be offloaded by Hb (because there is a need)
the affinity of Hb (or blood) for O2 is often expressed as its ____
P50
-a.k.a. “half saturation oxygen pressure”
why is the affinity of Hb for O2 called P50?
plasma PO2 at which 50% of Hb molecules are saturated with oxygen (i.e. a 50:50 R-state, T-state mix)
what would an increase in P50 do to the oxygen equilibrium curve (OEC)?
decreases Hb-O2 affinity (which shifts the curve to the right)
what would a decrease in P50 do to the OEC?
increase Hb-O2 affinity (shifts the curve to the left)
at a pH of 7.2 (RBC pH) and 37 deg, the P50 of ‘pure’ adult Hb (HbA) is what? why is this problematic? what increases this?
it’s arounf 5 mmHg, which is FAR too low to effectively offload O2 at the tissues
-in blood, the icnrease in H+ [], CO2 [], DPG [], and Cl-[] increases this to about 27 mmHg
how do allosteric effectors increase the P50 of Hb?
H+, CO2, DPG, and Cl- bind to specific sites ont he globin chains, increasing the P50 of Hb to that of the blood (26-28 mmHg)
- these do NOT bind to Fe++ (O2 binding site)
- these stabilize the T state, shifting the curve to the right
what about the allosteric effectors play a key role in long term modulation (and short term) of whole blood O2 affinity?
their preferential binding
-the more numerous they are, the more Hb shares oxygen
increasing the [] of allosteric effectors bound to Hb shifts the OEC to the ______, while decreasing the [] of these shifts the curve to the _____ (decreasing P50)
right, left
the OEC can shift chronically on the long term
true or false? because of what?
true, this can be altered by DPG levels
what are the 5 factors that affect Hb-O2 affinity?
1) blood pH
2) 2,3 - diphosphoglycerate (DPG)
3) carbon dioxide (CO2)
4) chloride ions (Cl-)
5) temperature
which subunits of the globin chains can bind protons at physiological pH? how many binding sites is this?
the NH2 groups of the first aa of each globin chain, and the uncharged side chains of the 22 surface HISTADINE residues of Hb can reversibly bind protons
-this in total is 26 possible binding sites
where do the protons come from that bind to histadine and NH2 of Hb?
mostly come from lactic acid and CO2
-enzyme called ca catalyzes this reaction
how does blood pH affect Hb-O2 affinity?
protination at a few of the binding sites with declining pH creates the formation of salt-bridges with side-chains of nearby anionic residues, thus stabilizing the T state
-Bohr effect (LogP50/pH)
the lower the pH, the _____ the P50
higher
as a molecule moves to muscles (more H+) they can cause _____ to become positive, forming a salt bridge, stabilizing the T state which shifts the OEC to the right
histadine
most H+ binding residues cause the Bohr effect
true or false?
false, most do NOT cause the Bohr effect, but are the primary contributors to blood acid-base buffering
-most histadine biffer protons which don’t affect P50
protons have a large effect on P50
true or false?
false, they do have an effect but it is not massive
______ has a minimal effect on P50, whereas ____ has a large effect on P50
H+, DPG
DPG is a product of ______ in RBCs
glycolysis
what allows for the entry of DPG into Hb proteins?
the space between the two B chains increases during the R-T transition, allowing entry of DPG into this opening
-4 binding sites are: B1Val, B2His, B8sLys, B14His
how many bonds can DPG form with cationic residues of both B chains?
up to 5
the binding of DPG onto the B chains of Hb causes a stabilization in which state?
T state
bonds between DPG and the B chain residues (cationic) are protination dependent
true or false?
true, DPG binding increases with declining pH
where is there more likely to be more DPG binding? in the lungs or in exercising muscles?
pH is very high in the lungs, a lot of protons will be ‘kicked off’ - DPG affinity will go down, so DPG is more likely to bind to exercising muscles where the pH is low (up to 5 bonds)
which is the primary allosteric effector responsible for increasing the P50 of ‘pure’ Hb (5mmHg) to that of whole blood (26-28 mmHg)?
DPG, only found in RBCs
what happens to the production of DPG when arterial blood is chronically under-saturated?
DPG production by RBCs increases, (ex: anemia, pulmonary disease)
-this increase the whole blood P50 above 28 mmHg, allowing more O2 to be extracted from Hb at the systemic capillaries without compromising O2 uptake in the lungs
how does DPG help us in cases where we’ve lost a lot of blood?
- losing blood lowers O2 affinity, which means we will have less Hb and more DPG which will offload more oxygen throughout the body
- so we pick up less oxygen but we offload about 10% more when going through capillaries
which allosteric effectors can reversibly bind to the amino group (NH3) of the 1st residue of each alpha and beta chain? What does this form?
CO2, this forms carbamino (CO2-) protein
binding CO2 increases the Bohr effect, but how?
protons released during carbamino formation are free to bind elsewhere on the Hb molecule, thus further contributing to the Bohr effect?
what does the binding of CO2 do to the OEC?
shifts the curve to the right, lowering affinity
how much CO2 in veins binds directly to Hb? Why?
only about 5%
-CO2 competes with one of the DPG binding sites (B1Val), hence B-chain carbamino formation is largely abolished in the presence of DPG (and also a lower pH)
the central cavity of Hb contains more anionic residues than cationic residues in the T state
true or false?
false, it contains more cationic than anionic
the fact that Hb contains more cationic residues than anionic residues in the T state suggests that this should increase electrostatic repulsion between the alpha nd beta dimers and destabilize this conformation. Why is this not the case?
-the entry of Cl- upon cavity widening during deoxygenation neutralizes this excess cationic charge, favouring the low O2 affinity state
chloride ions can bind to certain cationic residues (B1ValNH3+; B82Lys+), also stabilizing the T state
true or false?
true
Cl- has a major effect on P50
true or false?
false, these effects on P50 are largely masked in the presence of DPG, but Cl- still plays a major role in blood CO2 transport via the ‘chloride shift’
Cl- binding to Hb has a critical role in CO2 transport
true or false?
true
most allosteric effectors stabilize the S state
true or false?
false, most of them stabilize the T state
why do we get a larger Bohr effect at higher temperatures?
because an increase in temperature also decreases pH
O2 offloading absorbs 5% (rest) to 10% (exercise) of heat generated at the tissues, thus decreasing blood temperature here, where does this heat go?
this heat is released at the lungs upon Hb oxygenation
how does exercise affect the OEC?
- increased CO
- autoregulation; increased blood flow to exercising muscles (low O2, high CO2, high H+)
- increased temperature of Hb, lowers blood affinity (and pH)
- increased PCO2 and H+ [] decrease blood pH, increasing Bohr effect
- decreased pH increases DPG binding
this all shift the OEC to the right, causing O2 to be offloaded from Hb at a higher PO2, thereby increasing capillary-to-mitochondria PO2 gradients and hence O2 delivery
the main determinant of O2 delivery is Hb offloading O2
true or false?
false, the main determinant is blood flow, although Hb plays a massive role
the precise mechanism whereby Hb facilitates the endocrine transport of NO is unknown
true or false?
true
can Hb ‘sense’ low O2 levels, hence, directing the flow?
Hb likely facilitates the transport of NO
- by sensing low PO2 at the working tissues, Hb may better match local blood flow (and hence releasing O2) with O2 demand
- i.e. increased NO release - increased vasodilation, increased blood flow
does oxyHb and oxyMb play a role in lowering NO levels?
yes, following ischemia or during septic shock
- these scavange NO - binding to it and forming harmless nitrate (NO3-)
- this protects cells from dying
how does the Hemoglobin of a fetus differ from adult Hb?
- this is called fetal Hb, of HbF
- both beta chains are replaced by gamma (y) chains
- four of the 8 cationic residues implicated in DPG binding in HbA are therefore replaced to uncharged amino acids in HbF (affecting DPG binding)
does HbF have an increased or decreased DPG affinity?
decreased, and hence, fetal blood P50 (around 21 mmHg)
is the bohr effect higher or lower in HbF?
lower
Carbon monoxide is produced in our bodies
true or false?
true
which has higher affinity, O2 or CO?
CO (carbon monoxide) has a 200 time higher affinity than O2, thus markedly lowering blood O2 content at any given PO2 and or Hb []
HbF has a similar CO affinity to HbA, so why is it more dangerous for a fetus to be exposed to CO than it is for an adult?
CO becomes trapped in fetal circulation ([COHb] levels are 2 x higher)
is CO an allosteric effector? why or why not?
it is NOT an allosteric effector because it binds at the SAME place as oxygen (Fe++)
CO binding to the heme group of Hb keeps the Hb protein in which state?
R state
what is the effect of CO on the fetus? (besides less O2 being delivered)
this makes babies smaller and grow much slower
-babies who are born at high elevations (less oxygen) have a greater risk of dying - CO decreases oxygen levels
how much CO2 is dissolved in blood fluids?
5% at rest, up to 15% during exercise
which is more soluble? O2 or CO2?
CO2 is 25 times more soluble than O2
how much of our body’s CO2 is bound to amino groups of plasma proteins OR Hb?
less than 1% to plasma proteins and about 5% to Hb
after binding to plasma proteins, Hb, and having dissolved in blood fluids, where does the remaining 90% of CO2 go?
-transformed into bicarbonate ions, can accumulate to very high []’s
what catalyzes the reaction to form bicarbonate ions from CO2? Where does this happen?
carbonic anhydrase (ca)
- this happens in RBCs (primarily)
- some ca also found on capillary endothelium
- this reaction follows the law of mass action
why is it important that bicarbonate ions are formed inside RBCs?
by lowering RBC PCO2, this mechanism promotes the rapid net transfer of CO2 from tissues to RBCs - this allows us to maintain massive gradients
breathing is under both voluntary and involuntary control
true or false?
true
what controls our breathing?
all controlled by the brain stem in the medulla - right beside cardiovascular control centre
which 4 factors can affect our breathing?
1) emotions and voluntary control
2) chemoreceptors
3) muscle and joint proprioceptors
4) pulmonary stretch receptors
which breathing pathway is only activated during active ventilation?
emotions and voluntary control - which go through the cerebral cortex
which factor affecting breathing does not go through the medulla? where does this go instead?
emotions and voluntary control - this goes through cerebral cortex
how do chemoreceptors affect breathing?
glomus cells of the carotid and aortic bodies are in direct contact with arterial blood and are strongly activated when plasma PO2 drops below 60 mmHg
- these release neurotransmitters onto sensory neurons projecting to the medulla, primarily inducing an increased rate of ventilation
- NOT TRIGGERED BY ANEMIA OR CO POISONING
what stimulates glomulus cells?
increases in both arterial PCO2 and [H+]
what sets our respiratory pace at rest?
central chemoreceptors located in the medulla - this is why you can never hold your breath until you die, these prevent that
what do central chemoreceptors respond to?
respond ONLY to pH changes of medulla interstitial fluid
what crosses the blood brain barrier?
a) CO2
b) H+
c) HCO3-
d) O2
CO2 crosses the blood brain barrier and is THEN converted to H+ and HCO3- in the cerebral spinal fluid
which receptors increase the DEPTH of our ventilation?
central chemoreceptors - stimulated by CO2 crossing the blood brain barrier
Bohr effect
The Bohr effect is a physiological phenomenon first described in 1904 by the Danish physiologist Christian Bohr, stating that hemoglobin’s oxygen binding affinity (see Oxygen–haemoglobin dissociation curve) is inversely related both to acidity and to the concentration of carbon dioxide.
