Exam 4: Respiratory L4 Flashcards
Oxygen Transport in the Blood:
Oxygen is carried in the blood in two forms:
1.
2.
Oxygen is carried in the blood in two forms
- Dissolved
- Bound to Hemoglobin
Dissolved Oxygen:
- Measured clinically as ______
- Amount that can be dissolved follows ____ Law
- Per 1 mmHg of PO2 —–> ______ mL 02/100 mL blood
- normal blood —–> ____ mL O2/ 100 mL blood
Dissolved Oxygen:
- measured clinically as PaO2 (blood gas analysis)
- amount that can be dissolved follows henry’s law (concentration of solute in gas is directly proportional to partial pressure)
- Per 1 mmHg of PO2 —> 0.003 mL O2 per 100 mL blood
- normal blood has 0.3 mL O2/ 100 mL
How much oxygen do we use per minute in the blood?
How much of that does dissolved O2 provide?
Normal O2 consumption is roughly 250 mL O2/min
Dissolved gives us 15 mL of O2 per minute
(dissolved O2 is not enough)
Dissolved Oxygen:
- ______ percentage of total O2
- Under normal conditions it is _____
Calculation sample question: What is the PAO2 if you breathe 100% oxygen and the PAco2 is 45 mmHg (R = 0.8)
Dissolved Oxygen:
- SMALL percentage of total O2 in blood
- Under normal conditions its almost negligible
Final answer: 657 mmHg
Hemoglobin:
How many heme groups are there?
How many polypeptide chains? Which kind?
What is adult hemoglobin vs fetal hemoglobin
The binding/dissociation of O2 occurs in ____ and changes ______
Hemoglobin:
4 heme groups containing iron (this is where oxygen binds)
There are four polypeptide chains (2 alpha and two beta), this is for HbA
For kids less than a year old, HbF has 2 alpha globin and 2 gamma globin chains
The binding/dissociation of O2 occurs in milliseconds and changes light absorption of Hb (red means oxygenated, blue means deoxy)
Explain the two states of Hb related to O2 binding
Explain O2 binding on heme
Hb has two states, tense and relaxed
Tense State (T) : no oxygen bound, low affinity for O2
Relaxed State (R): oxygen bound, high affinity
Oxygen binding is reversible, and also the oxygen binding on Hb is cooperative (sigmoidal curve)
That means the likelihood of oxygen binding goes up with each oxygen bound
How much Hb is bound to oxygen within the normal range of PO2 ? Draw the oxygen dissociation curve to help.
What is the normal unloading of oxygen by hemoglobin (in mL O2 per 100 mL blood)
Most Hb is oxygen bound within the range of normal PO2 .
Curve is shown in attached picture.
Normal unloading is approx 4.5 mL O2 per 100mL
Oxyhemoglobin Dissociation Curve:
At PO2 > 60 mmHg what are the changes in Hb saturation
(what does that mean at those pressures)
At PO2 < 60 mmHg : small changes in pressures lead to _____
(what does that mean?)
At PO2 > 60 mmHg , small canges in Hb saturation (loading and transport at these pressures… facilitates normal oxygen transport to organs/cells)
At PO2 < 60 mmHg: small changes in pressure lead to release of large amounts of O2
(facilitates release of oxygen to organs and cells)
The oxyhemoglobin saturation curve is NOT static.
The curve responds to the local enviornment to ______
Explain what a right ward vs leftward shift means
Also explain P50 and how that is effected by left or rightward shift
The oxyhemoglobin saturation curve is NOT static. The curve responds to the local enviornment to modulate loading and unloading.
P50 is the pressure at which 50% of the Hb are oxygen saturated
A left shift of the curve means an INCREASE in Hb-O2 binding (decrease in P50, meaning an increase in Hb O2 affinity)
A rightward shift of the curve means a DECREASE in Hb-O2 binding. (increase in P50, meaning Hb has a decrease in O2 affinity)
Explain which physiological factors cause a leftward shift of the Hb-O2 saturation curve
Explain which factors cause a rightward shift in the curve
Leftward Shift in the Curve (meaning increase in Hb-O2 affinity) : Decrease in temp, Decrease PCO2 , Decrease in 2,3-DPG, and a decrease in H+ ions (meaning increased pH)
Rightward Shift in the Curve (meaning decreased O2 affinity): Increased temp, Increased PCO2 , Increase in 2,3-DPG, Decrease in pH ( increase in H+ ions)
Explain the Bohr Effects on the Hb-O2 saturation curve
Bohr studied the effects of pH and PCo2 on the Hb-O2 saturation curve
An increase in pH (decrease in H+ ions) and a decrease in PCO2 causes a leftward shift of the curve (increased oxygen affinity)
A decrease in pH (increase in H+ ions), and an increase in PCO2 cause a rightward shift in the curve (decreased oxygen affinity)
Cheat code for hemoglobin oxygen saturation curve:
As X factor increases, Hb binding of oxygen ____
Just be aware of pH relationship to H+ ions
Cheat code:
As X factor increases, the Hb binding of oxygen decreases (shifts curve to the right)
(factors include temp, PCO2, 2,3-DPG, and H+ ions)
Just remember that decrease in pH means increase in H+ and vice versa
Metabolically active tissues will have an _____ in all of the factors, causing the dissociation curve to shift to the _____
Metabotically active tissues will have an increase in all of the factors, causing the dissociation curve to shift to the right and causing a decrease in the O2 affinity
Explain what happens to the hemoglobin oxygen saturation curve when the temperature drops vs rises
When the temperature drops, the curve shifts to the left, and oxygen affinity for Hb increases. Thus, not only does the blood get redistributed in cold weather, but also the blood that does get to the extremities does NOT unload its oxygen
When temperature rises, the sat curve gets shifted to the right, meaning more O2 is being unloaded in the tissues because the Hb o2 affinity decreased
What two factors constitute the Bohr Effect?
Bohr Effect: pH and CO2
The Bohr Effect: pH and CO2
What is hypercapnia?
How does CO2 react with Hb and affect O2 binding?
How does it compare to the effects of pH?
Hypercapnia = high CO2
CO2 does not directly compete for binding sites with O2. Instead, CO2 binds to amino groups and creates a carbamino Hb which decreases O2 binding
Therefore, high CO2 will shift the curve to the right, decreasing O2 affinity
The effects of CO2 are minor compared to pH
The Bohr Effect:
High CO2 leads to ____ pH
Respiratory acidosis ______ O2 affinity
Combo of both pH and CO2 constitutes the Bohr Effect: explain what needs to happen for a left or rightward shift
High CO2 leads to lower pH
Respiratory acidosis decreases O2 affinity
Bohr Effect:
low pH and high CO2 decreases Hb oxygen affinity and shifts the curve to the right
Higher pH and lower CO2 levels increase the HB O2 affinity and shifts curve to the left
2,3 DPG
Preferentially binds to ____
_____ affinity of Hb for oxygen (allosterically)
Increased DPG in _____ conditions
2,3 DPG preferentially binds to deoxygenated Hb
Decreases affinity of Hb for oxygen (allosterically)
Increase of DPG shifts curve to the right
There is Increased DPG in low oxygen conditions (where you want more oxygen dropped off)
Final RECAP on Hb-O2 saturation curves:
Explain what causes left ward vs rightward shift in the following conditions, and note how each shift affects affinity and P50
Temp
PCO2
2,3 DPG
pH
Leftward Shift: Increased Affinity (Decreased P50 )
- Decreased temp, decreased PCO2, decreased 2,3-DPG, and increase in pH (essentially a decrease in H+ ions)
Rightward shift: Decreased O2 affinity (increased P50)
- Increased temp, increased PCO2, increased 2,3-DPG, and decreased pH (increase in H+ ions)
Carbon Monoxide:
Hb affinity for CO is ______ than the affinity of O2
At 1 mmHg CO _____ binding sites are occupied
In the presence of CO: Hb affinity for O2 is ____, causing ________
What does the CO Hb saturation curve look like?
CO and Hb:
Hb has a 200x greater affinity for CO than O2
At 1 mmHg CO, ALL binding sites are occupied
In the presence of CO: Hb affinity for oxygen is ENHANCED, which prevents oxygen unloaded on the tissues
“it’s a double whammy”.. not only is CO going to bind and occupy the binding sites, but the O2 that stays bound will not be unloaded in the tissues either
Hb and CO:
CO binding “mimics” oxygen binding into the _____ state for _____oxygen affinity.
What does that mean for Hb O2 binding?
CO binding “mimics” oxygen binding into the relaxed state for enhanced oxygen affinity.
Hb not necessarily binding more O2 due to higher affinity, it’s just that the oxygen that is bound is less likely to unload/dissociate?
Sickle Cell:
Which form of Hb is it?
It is a ___ AA substitution in the ___ chain
It is normal with oxygen: it ____ at low oxygen
The sickle cell shape causes ___ and ___
Sickle Cell:
HbS
Single AA subsitution in the BETA chain
It is normal with oxygen; crystallizes at low oxygen
Sickle cell shape, hemolysis, anemia
Explain Hb within diabetes
Diabetes: Hemoglobin A1c
Increased blood glycose leads to increased cell glucose 6-P which increases the amount of glycosylated Hb
This glycosylation is irreversible. RBCs last for three months (120 days) so HbA1c gives an accurate 3 month running average of your blood glucose level
For PaO2, which level of partial pressure of oxygen in the arteries is hypoxia, and which level is in danger?
Give both the mmHg level and the o2 saturation percentage
PaO2 > 80 mmHg means HYPOXEMIA (97.5%)
PaO2 = 60 mmHg means DANGER (90%)
Altering Hb saturation is just as dangerous as altering your oxygen intake
How do you calculate the oxygen content in arterial blood…“CaO2”?
To calculate CaO2, you simply multiply O2 capacity by SO2.
1 g of Hb can bind to 1.34 mL of O2
That means at 100%, we have 20.1 mL O2/100 mLs
In order to calculate the oxygen content in arterial blood, you take the SpO2/SO2% as a decimal and multiply it by 20.1 mL O2/ 100mL
CO2 is carried in the blood in three forms:
1.
2.
3.
Which one is the VAST majority of how CO2 is carried in blood?
CO2 is carried in the blood in three different forms:
- Dissolved
- Bicarb
- Carbamino compounts
BICARB is mainly how CO2 is transported in blood, at 69%
Carbamino compounds as Co2 in blood:
How much in plasma
How much in RBCs
Carbamino compounds as CO2 transport within blood:
11% in plasma
89% in RBCs
Dissolved CO2:
Measured clinically as ______
Within the blood, how many mLs of CO2 per 100mLs of blood?
How does that compare to oxygen?
Dissolved CO2 is measured clinically as PaCo2
remember little a is for arteries, big A is for alveoli
Within blood: 0.067 mLs CO2/ 100 mLs of blood
Remember O2 was 0.003 mLs/100mL of blood
There is 20x more disssolved CO2 than O2 in blood
The Bicarb Equation:
CO2 + H2O <-> H2CO3 <–> H+ + HCO3-
In plasma:
the conversion of CO2 to carbonic acid is ___
But what happens in RBCs?
In plasma: the conversion of CO2 to carbonic acid is SLOW, so in plasma the majority of CO2 will exist as CO2
BUT, RBCs have an enzyme called Carbonic Anhydrase which rapidly converts the CO2 to carbonic acid, which rapidly diffuses to bicarb
Haldane Effect:
Increasing PO2 ______ Hb affinity for CO2, meaning CO2 is ________ where O2 is high.
Decreasing PO2 ______ Hb affinity for CO2, meaning CO2 is _____ where O2 is low.
At any PCO2, total CO2 content rises as ______.
Haldane Effect:
Increasing PO2 decreases Hb affinity for CO2. CO2 is released in the lungs where O2 is high.
Decreasing PO2 increases Hb affinity for CO2, meaning that CO2 is picked up in the systemic tissue where O2 is low.
At any PCO2, total CO2 content rises as PO2 falls.
Haldane vs Borh
Haldane: Effects of ___ on Hb to increase/decrease ___ binding.
Bohr: Effect of ___ on Hb to increase/decrease ___ binding.
Haldane: Effects of O2 on Hb to increase/decrease CO2 binding. (unloading of CO2 in the lungs)
Bohr: Effects of CO2 on Hb to increase/decrease O2 binding. (unloading of O2 in the tissue)
O2 transport is mostly bound to _____
O2 transport is mostly bound to hemoglobin
Oxyhemoglobin binding is ____ and ____
(Hb is mostly oxygen bound; binding falls off significantly below ___ mmHg, facilitating ____)
Oxyhemoglobin binding is cooperative and reversible
Hb is mostly bound to oxygen; binding falls off significantly below 60 mmHg, facilitating transport and release
Which physiological factors shift the oxyhemoglobin dissociation curve?
Temp, 2,3- DPG and then pH and CO2 (bohr effect)
CO binds ____ more tightly than O2 and inhibits _____
CO binds 200x more tightly than O2 and inhibits O2 unloading
CO2 transport is mostly as _____, also ___ and ___
_______ (enzyme) facilitates CO2 to bicarb in RCCs
CO2 transport is mostly bicarb ; also dissolved CO2, and as carbamino compounds
Carbonic Anhydrase facilitates CO2 to bicarb in erythrocytes/RBCs
Hb-CO2 binding ______ with increasing PO2 (Haldane Effect)
Hb-CO2 binding decreases with increases PO2
This is called the Haldane effect
Control of Respiration:
Two main tasks:
1.
2.
In order for the brain to control respiration, it has two primary tasks:
- Establish automatic rhythmic breathing
- Accomodate Changing Demand
Draw the flowchart of control of respiration:
Central controllers
Effectors
Sensors
What are the major sites of respiratory control:
- For Automatic Respiration
- For Voluntary Respiration
Automatic Respiration:
- Respiratory Control Center (medulla)
- Central Chemoreceptors
- Peripheral Chemoreceptors
- Pulmonary mechanoreceptors/sensory nerves
Voluntary Respiration:
Motor cortex ——> Corticospinal tracts
What are the two areas within the medulla that help generate a breathing pattern?
Dorsal Respiratory Group (DRG): primarily inspiratory
Ventral Respiratory Group (VRG): inspiratory and expiratory
the DRG and the VRG act together to generate a breathing pattern
Eupnea vs dyspnea
Eupnea: normal rhythmic breathing via alternating inspiratory and expiratory neuron activity
Dyspnea: not normal breathing pattern
Overall the ____ and the ___ (areas within the brain) control breathing pattern
Overall, the pons and the medulla control breathing patterns
Central Chemoreceptors:
located on the ______
Sensitive to changes in _______ (which comes from where?)
Central Chemoreceptors:
- Located on the ventrolateral surface of the medulla oblongata
- Sensitive to changes in pH within CSF (the CO2 within blood passes over the blood brain barrier, gets converted to H+ within the CSF and that’s what is being detected by these central chemoreceptors)
Central Chemoreceptors respond to changes in ____ but not changes in _____
Central Chemoreceptors respond to changes in PCO2 but NOT to changes in PO2
Where are the peripheral chemoreceptors located?
What do they respond to?
_____ cells are like neuro-clusters of cells responsible for chemoreception
Peripheral Chemoreceptors: Carotid Sinus and Aortic Arch
Respond to: Decreases in PO2, Decreases in pH (carotid only), and increases in PCO2
Glomus cells are like neuroclusters of cells responsible for chemoreception
What are the only chemoreceptors that respond to changes in PO2?
Peripheral chemoreceptors (aortic arch and carotid sinus) are the only ones that respond to changes in PO2
At what level of PaO2 do the peripheral chemoreceptors start firing?
Remember, a PaO2 of 60 mmHg or less is DANGER zone
So peripheral chemoreceptors start firing robustly at a PaO2 of less than 70-80 mmHg
What is one of the only negative feedback loops within respiratory control?
Hering-Breuer Reflex (stretch receptors in the lungs)
Pulmonary stretch receptors:
Prevent the lungs from ____
Explain inflation reflex vs deflation reflex
The Hering-breuer reflexes are largely inactive in ___, unless _____
Pulmonary stretch receptors:
Prevent the lungs from over-inflation
Inflation of lungs inhibits inspiratory muscle activity (HB inflation reflex)
Deflation of lung initiates inspiratory activity (deflation reflex)
Hering Breuer reflexes are largely inactive in adults, unless tidal volumes are very high
Irritant Receptors:
That are they stimulated by?
Irritant receptors
stimulated by noxious gas, cigarette smoke, dust, cold air
Impulses travel through vagus nerve
May play a role in asthma
J (juxtacapillary) receptors and bronchial C fibers:
Respond to _______
In alveoli and conducting airways
J receptors and bronchial C fibers respond to chemicals in pulmonary (J receptors) and bronchial (C fiber) circulation
Nose/upper airway receptors (irritant receptors)
respond to what?
What happens to airflow then?
Respond to diving, aspiration, sneeze reflex
Airflow: the radius decreases but the velocity increases more so more turbulent airflow happens
Ventilatory Response to CO2:
At higher PCO2, there will be ______ ventilation
The effect of CO2 on ventilation is independent of O2 at normal O2 levels,
BUT when we drop to lower O2 levels what happens?
At higher PCO2 there will be higher ventilation
At lower PaO2:
- Ventilation at a given CO2 level is even higher
- Ventilatory Response to CO2 (slope) becomes steeper
AKA at lower O2 levels, ventilatory response to CO2 increases more dramatically
Central chemoreceptors are located near the _______. They respond to changes in pH within the ____, caused by diffusion of ____ across the blood brain barrier into CSF.
Peripheral chemoreceptors respond to changes in ______, _____, and _____. The response to PO2 is _____ above 50-60 mmHg.
Central chemoreceptors are located near the ventral surface of the medulla.
They respond to changes in CSF, caused through diffusion of CO2 into CSF.
Peripheral chemoreceptors respond to changes in PO2, PCO2 and pH. Response to PO2 is amll above PO2 of 50-60 mmHg.
The _____ of the blood is the most important factor controlling ventilation., most of control is through the _______ chemoreceptors.
The PCO2 of the blood is most important factor controlling ventilation, most of control is through the central chemoreceptors.
_________ are clinically the most important breathing abnormalities
SLEEP APNEA syndromes are clinically most important breathing abnormalities
Explain the difference between Obstructive Sleep Apnea vs Central Sleep Apnea
Obstructive Sleep Apnea: pleural pressure is normal, but there’s an obstruction causing airflow to not get through upper airway
central Sleep Apnea/Ondine’s curse: NEURAL defect, where the airflow stops because you loose the rhythmic breathing/the pleural pressure changes stop
What are the three main responses the body does via the lung when its under extremely high altitude?
Lung Responses in High Altitude:
1. Hyperventilation
- Polycythemia
- Pulmonary Vasoconstriction
At high altitude, the atmospheric pressure is lower, which means the PAO2 ends up being _____
Explain what the peripheral chemoreceotors do in response
LOWER
which is why you compensate
Peripheral chemoreceptors will be firing on all cylinders since the PaO2 is less than 70-80mmHg
Therefore, you will hyperventilate. BUT that hyperventilation will in turn reduce your CO2 and increase the pH
Explain the effects of polychtemia
Polycthemia:
Increase in Hb and O2 carrying capacity
Stimulated by hypoxemia after 2-3 days in altitude
So even though people at high altitudes have low PO2 and low SpO2, they have more Hb than normal and therefore are able to unload just as much oxygen in the tissues
Hypoxic Vasoconstriction in Altitude:
Instead of being local, it’s now global
What affects does this have in the heart?
Global hypoxia will decrease the radius of all pulmonary vessels, heart will have to work harder, right side will be hypertropied after a prolonged period of time, and then the pt will get hypertension
Key Concepts: Altitude
- ____ is the most important problem
- ____ is the most immediate adaption
(hypoxia is induced by ______)
(CO2 is _____ over the coming days)
_______ develops slowly in high altitude, but increases the O2 concentration in blood
- Alveolar hypoxia at high altitude can result in pulmonary _____, right heart ____, and ___
Low PO2 is most important problem
Hyperventilation is most immediate adaptation
Hypoxia is induced by peripheral chemoceptors
CO2 is brought to normal over the coming days
Polycythemia develops slowly in high altitude
Alveolar hypoxia at high altitude can result in pulmonary vasoconstriction, right heart hypertrophy, and pulmonary edema
