W10 - Respiration II (3.3, 3.4., 3.6, 3.7) Flashcards
How do pressure and resistance in the pulmonary circulation differ from that in the systemic circulation?
Values.
Consequence?
in supine position
- driving P in the syst. circuit 90 - 3 = 87 mmHg
- driving P in the pul. circuit 14 - 8 = 6 mm Hg
BUT: cardiac output can be pumped bc resistance is proportionately low to pressure (10% of systemic R)
What are the pressure values in
- the pulmonary aa.
- mean pressure in pulmonary aa.
- pulmonary capillaries
- pulmonary vv.
- left aftrium
?
- the pulmonary aa. = 24/9 mmHg
- mean pressure in pulmonary aa. = 14 mmHg
- pulmonary capillaries = 10 mmHg
- pulmonary vv. = 9 mmHg
- left aftrium = 8 mmHg
How does the blood flow in the lungs vary?
Why?
in supine position → gravitational effect on pulmonary blood flow = perfusion
- lowest blood flow at apex
- highest blood flow at base of lung
⇒ increases in craniocaudal direction
→ zoning: 1 - 3
Describe the pulmonary blood flow in zone 1.
When can such behavior be observed?
pathological condition, e.g. as a result of hemorrhage
Palv > Part > Pven
⇒ high alveolar P compresses capillaries → ↓Q
Describe the pulmonary blood flow in zone 2.
When can such behavior be observed?
anywhere moving down toward base of lung
Part > Palv > Pven
⇒ Q driven by ΔPart-alv
Describe the pulmonary blood flow in zone 3.
When can such behavior be observed?
base of lung
Part > Pven > Palv
⇒ Q driven by ΔPart<span>-</span>ven
How is pulmonary blood flow mainly regulated?
by hypoxic vasoconstriction
→ blood redirected from poorly ventilated, hypoxic regions toward well-ventilated regions
NOTE: in fetuses generalized hypoxic vasoconstriction, so only little blood flow through lung, reversed after first breath
(instead of vasodilation like in other organs)
What is the V/Q ratio?
Standard value?
ratio of alveolar ventilation V and pulmonary blood flow Q (perfusion)
→ important to achieve ideal exchange of O2 and CO2
usually ∽ 0.8
How does the perfusion, ventilation and V/Q ratio differ in different regions of the lung?
Graph.
- perfusion = lowest at apex
- ventilation = lowest at apex, but regional differences are lower than for perfusion
⇒ V/Q ratio is highest at apex, lowest at base of lung
BUT: at base of lung closer to optimal value
What is the reason for increased ventilation in the base of the lung?
Values.
gravity
- pleural pressure at apex - 10 mmHg
- pleural pressure at the base -2 mmHg
↓ transalveolar P → ↓ alveolar volume → ↑ compliance
⇒ capable of wider O2 exchanges with the external environment
at apex obviously vice versa, higher volume, lower compliance, lower ventilation
What is a shunt?
Consequence?
Reason?
vessel where V/Q ratio = 0, hence no gas exchange
bc ventilation does not occur
⇒ PO2 and PCO2 in pulm. capillary blood will approach values in mixed venous blood
e.g. in case of food being stuck in the trachea
What is dead space?
Consequence?
Reason?
lung tissue where V/Q = infinite, hence no gas exchange
bc perfusion is absent
⇒ PO2 and PCO2 of alveolar gas will approach values in inspired air
e.g. in case of pulmonary embolism
What are the 2 forms how O2 is transported in blood?
- physically transported: dissolved in blood
- chemically transported: bound to hemoglobin (increases O2-carrying capacity 70-fold)
What does Fick’s law of diffusion state?
Formula.
the diffusion of a gas across a sheet of tissue is
directly related to the
- A = surface area of the tissue
- D = diffusion constant of the specific gas
- ΔP = partial pressure difference of the gas on each side of the tissue
inversely related to
- T = tissue thickness
<u>NOTE:</u> CO2 diffuses more easily than O2 at same partial P
Fick’s law can be simplified.
How?
DL = lung diffusing capacity
equivalent of permeability of alveolar-pulmonary capillary barrier
- directly proportional to D and A
- inversely proportional to T
Which conditions change the value of the lung diffusion coefficient?
REMEMBER:
- directly proportional to D and A
- inversely proportional to T
hence:
- ↑DL: during exercise bc more capillaries open → ↑A
- ↓DL: during emphysema (↓A), in fibrosis/pulm. edema (↑T)
Which structures contribute to the alveolar-pulmonary capillary barrier?
- alveolar epithelium
- epithelial basement membrane
- interstitial space
- capillary basement membrane
- capillary endothelium
What are the PO2 and PCO2 values in
- dry inspired air
- humified tracheal air
- alveolar air
- systemic arterial blood
- mixed venous blood
? Explain.
What is the driving pressure for diffusion of CO2 and O2 across the alveolar-pulmonary capillary barrier?
- ΔPO2 = 100 - 40 = 60 mmHg
- ΔPCO2 = 46 - 40 = 6 mmHg
BUT: [CO2] in capillary = 20* [O2]
due to incr. solubility of CO2
Differentiate btw types of limited gas exchange.
Examples.
Graph.
perfusion-limited exchange
- N2O, CO2, O2 under normal conditions
- gas equilibrates early along length of cap.
- diffusion can be incr. if blood flow incr.
diffusion-limited exchange
- CO, O2 during strenous exercise/disease states
- gas does not equilibrate by the time it reaches end of capillary → ΔP maintained
BUT: diffusion can be limited in tissue if capillary length is not sufficient
How much dissolved O2 can be found in art. blood?
1 mmHg O2 = 0.03 ml O2/l blood
95 mmHg O2 = 95 * 0.03 = 3 ml O2/l blood
What is the average [Hb] in blood?
How much O2 can be transported this way?
2.3 mmol/l
→ 9.2 mmol/l O2 can be transported
in ml: 2.3 * 4 * 22.4 = 206 ml O2/l blood
= O2 binding capacity of blood
Describe the general structure of hemoglobin.
globular protein of 4 subunits, each subunit:
- contains heme = iron containing porphyrin
→ Fe2+ binds O2 - either α or β → normal adult hemoglobin has 2 each, hence called α2β2
What is hemoglobin S?
causes sickle cell disease
- normal α subunits, but abnormal β subunits
→ α2Aβ2S - in deoxygenated form HbS forms sickle-shaped rods that deform RBCs
What is methemoglobin?
iron in Fe3+ state, hence cannot bind O2
xWhat is P50?
Values in art. and venous blood.
Why are they different?
PO2 when 50% of Hb is saturated
- art. P50 = 26 mmHg
- ven. P50 = 29 mmHg
In the lung (arteries), the effect of the shift to the left caused by decreased [H+] enhances O2 uptake.
The rising [H+] caused by the entry of CO2 (veins) shifts the curve to the right, enhancing O2 dissociation
Define O2 content of blood.
It depends on… ?
total amount of O2 carried in blood, including bound and dissolved O2
depends on:
- [Hb]
- P50<strong> </strong>(determines %O2 saturation)
- PO2
Explain the important points on the Hb-O2 dissociation curve.
Draw it.
percent saturation of Hb as a function of PO2
-
at PO2 = 100 mmHg, e.g. art. blood
Hb is 100% saturated, all 4 heme groups bind O2 -
at PO2 = 40 mmHg, e.g. mixed venous blood
Hb is 75% saturated, 3-4 heme groups bind O2 -
at PO2 = 26 mmHg
Hb is 50% saturated → P50, 2 heme groups bind O2
How would you describe the shape of the Hb-O2 dissociation curve?
Explain.
= sigmoidal, bc
change in affinity of Hb as successive O2 molecules bind = positive cooperativity
→ highest affinity for fourth O2
⇒ facilitates loading of O2 in lungs, unloading of O2 in peripheral tissues
What happens with Hb in the lungs?
Explain w/r/t the Hb-O2 dissociation curve.
alveolar gas has PO2 = 100 mmHg
diffusion of O2 from alveoli into blood
→ “arterialized” PO2 of 100 mmHg
- high affinity of Hb at 100 mmHg (flat portion of curve)
- low free [O2] + PO2 → maintain pressure gradient that drives diffusion
What is the physiological relevance of the almost flat portion of the Hb-O2 dissociation curve?
btw 60 and 100 mmHg
changes in atmospheric pressure (→ PO2) can be tolerated w/o compromising O2-carrying capacity of Hb
What happens with Hb in peripheral tissue?
Explain w/r/t the Hb-O2 dissociation curve.
O2 diffuses from art. blood to cells
- O2 gradient is maintained bc cells consume O2
- lower affinity of Hb at low PO2 (steep portion of curve)
Which parameters must be changed to cause a right shift of the Hb-O2 curve?
Consequence?
↓ affinity of Hb for O2
⇒ ↑ unloading in peripheral tissues
because:
- ↑ PCO2 → ↓ pH (= Bohr effect)
- ↑ T
- ↑ [2,3-BPG]
What does 2,3-BPG do?
Which situation would cause an increased synthesis of 2,3-BPG?
binds to β chains of deoxygenated Hb
→ ↓ affinity for O2 → ↑ unloading in tissue
(right shift of curve)
↑ synthesis in case of adaptation to chronic hypoxemia (e.g. living in high altitude) to facilitate unloading of O2 in tissues
Which parameters must be changed to cause a left shift of the Hb-O2 dissociation curve?
Consequence?
↑ affinity of Hb for O2
⇒ ↓ unloading in peripheral tissues
because:
- ↓ PCO2 → ↑ pH
- ↓ T
- ↓ [2,3-BPG], e.g. HbF
- CO
= opposite of causes for right shift
How is fetal hemoglobin different from that of adults?
fetal hemoglobin = HbF
- β chains replaced by γ chains → α2γ2
-
higher O2 affinity than adult hemoglobin bc 2,3-BPG binds less strongly to γ chains
→ O2 movement from mother to fetus
higher O2 affinity implicates left shift on graph
Explain the effects of CO w/r/t the Hb-O2 dissociation curve.
-
affinity of CO = 200* affinity of O2
→ occupies binding sites on Hb, ↓ O2 content -
binding of CO incr. affinity for rem. sites for O2
→ left sheft of Hb-O2 dissociation curve
⇒ characteristic curve
What is the A-a gradient?
Normal range?
difference btw alveolar PO2 and arterial PO2
-
under normal conditions: 0 - 10 mmHg
→ equilibration btw alveolar and arterial PO2 -
if > 10 mmHg
→ no equlibration, usually leads to hypoxemia
What is hypoxemia?
Causes?
How is the A-a gradient affected?
↓ arterial PO2
(often a result of non-equilibration btw alveolar and arterial PO2)
What is O2 delivery?
Formula + unit.
amount of O2 delivered to the capillaries per minute
O2 delivery = cardiac output * O2 content
What is hypoxia?
Causes + mechanisms?
= reduced level of O2 in tissue
- hypoxic hypoxia: inadequate saturation of blood O2 (due to a reduced supply of oxygen in the air, decr. lung ventilation or resp. disease)
- anemic hypoxia: capacity of the blood to carry O2 is reduced (due to <span>anemia, CO poisoning)</span>
- histotoxic hypoxia: cells fail to utilize it effectively because they cannot absorb O2 from blood (due to overuse of alcohol or drugs and is also seen in Cn poisoning)
- stagnant hypoxia: decrease in blood flow preventing adequate blood supply to tissues (due to Heart attack, heart failure, or cardiac arrest)
What is EPO?
Explain its effect.
growth factor synthesized in kidney in response to hypoxia
- ↓ O2 delivery to kidney
- ↑ production of hypoxia-inducible factor 1α
- ↑ synthesis of EPO
⇒ promotes development of mature RBCs
What are the 3 forms how CO2 produced in tissues is transported to the lung?
- dissolved CO2 (small amount)
- carbaminohemoglobin (small amount) = bound to Hb
- HCO3- from hydration of CO2 in RBCs = 90%
Explain the process how CO2 is transported in form of HCO3- in the blood.
- CO2 generated in tissues, diffuses into venous plasma, then into RBCs
-
carbonic anhydrase in RBCs:
CO2 + H2O → H2CO3 → H+ + HCO3- - chloride shift: HCO3- exported back into plasma, Cl- imported into RBC
- in the lungs: reverse reaction, then CO2 exhaled
Explain how H+ is buffered inside the RBC.
deoxygenated Hb at venous end of capillaries binds H+ → no major changes in pH
Which nerves are mainly responsible for the 2 phases of respiration?
Explain.
different activites during different phases
- n. phrenicus: during inspiration, increasing activity btw 0.5 and 2s → smooth increase in lung V
- nn. intercostales: during expiration
Which structures contribute to the central control of breathing?
Where are they located?
controlled by brainstem, influenced by cerebral cortex
- pneumotaxic center: upper pons
- apneustic center: lower pons
-
medullary respiratory center:
- dorsal respiratory group
- ventral respiratory group
- cerebral cortex
Which cranial nucleus froms the dorsal respiratory group?
What is its function?
Explain.
ncl. solitarius
integration of sens. information from resp. system + inspiration
mainly afferent role
- input from:
- n. IX: from per. chemoreceptors
- n. X: from per. chemoreceptors + mechanoreceptors in lung
- output mainly to inspiratory motor neurons in:
- VRG
- spinal cord
What is the function of the ventral respiratory group?
Which important structure is part of the VRG?
expiration + inspiration
mainly efferent role
3 areas w/ different functions:
- rostral VRG → expiration
- intermediate VRG → assists inspiration, contains pre-Bötzinger complex
- caudal VRG → expiration
What is the function of the pre-Bötzinger complex?
generates rhythmic motor output to n. phrenicus and n. XII
⇒ possible explanation for pacemaker activity of respiration
What is the function of the apneustic center?
Where is it located?
in lower pons
stimulates inspiration
→ deep + prolonged inspiratory gasp (apneusis)
What is the function of the pneumotaxic center?
Where is it located?
in upper pons
inhibits inspiration
→ regulates inspiratory volume + rate
BUT: not needed for eupnea
How does the cerebral cortex control breathing?
under voluntary control
→ voluntary hyperventilation or hypoventilation
obv. time of hypoventilation limited by PO2 and PCO2, can be extended by previous hyperventilation
What is described by the CO2-response curve?
Draw it.
ventilation as a function of inspired CO2
= test of CO2 sensitivity
-
ventilation increases as PCO2 increases
↑ 1 mmHg PCO2 → ↑ 3L/min. ventilation - sensitivity decr. during sleep (also: anesthesia, COPD)
- sensitivity incr. during acidosis
curve for acidosis looks similar
How does hypercapnia affect ventilation as the partial pressure of O2 is varied?
Graph.
increased sensitivity to PCO2 if the PO2 also decreased
→ left shift + steeper slope
Where are central chemoreceptors located?
Explain the exact mechanism of their function.
- *in ventrolateral medulla**
- *sensitive to pH in CSF**
-
CO2 diffuses from blood into CSF
(H+ cannot due to blood brain barrier) - hydrated → H2CO3 → H+ + HCO3-
- H+ acts directly on central chemoreceptor
- regulation to stabilize arterial PCO2
- ↑PCO2, [H+] → hyperventilation
- ↓PCO2, [H+] → hypoventilation
As a review…
Where can peripheral chemoreceptors be found?
- carotid bodies: in sinus caroticus
- aortic bodies: above and below arcus aorticus
How do peripheral chemoreceptors influence the rate of breathing?
-
decrease in art. PO2 (< 60 mmHg)
most important factor that stimulates rec. -
increase in art. PCO2
less important -
increase in art. [H+] = metabolic acidosis
direct stimulation of carotid bodies, ind. in changes of PCO2
⇒ hyperventilation
Which other types of receptors are involved in the control of breathing?
- lung stretch receptors
- irritant receptors
- J (juxtacapillary) receptors
- joint + muscle receptors
How do lung stretch receptors influence the rate of breathing?
Where are they located?
in the SMCs of the airway
stimulated by distension of the lung, produce Hering-Breuer reflex → ↓ rate of breathing
Explain the function of irritant receptors.
Where are they located?
btw airway epithelial cells
stimulated by noxious substances like dust, pollen
→ induce coughing, might induce bronchoconstriction in patients w/ asthma
Where are juxtacapillary receptors located?
When are they stimulated?
Example.
in the alveolar walls, close to capillaries
stimulated by engorgement of pulm. capillaries
→ rapid, shallow breathing
e.g. in case of left heart-failure
What is the function of joint and muscle receptors?
How do they affect the rate of breathing?
activated during movement of limbs
→ early stimulation of breathing during exercise
How does arterial PO2 and PCO2 change in response to decreasing atmospheric pressure?
Graph + values.
- PCO2 = constant (bc still same amount produced by per. tissue)
-
PO2 = decreaes as altitude increases
- = 60 mmHg at 480 mmHg (∽ 3000m)
- = 40 mmHg at 420 mmHg (∽ 6000m)
