Respiratory II Flashcards
Pulmonary System is a ___ flow, ___ resistance, ___ pressure system
high flow, low resistance, low pressure system
Ventilation
how gas gets from the atmosphere to the alveoli
What does Boyle’s Law mean and how does it apply to us?
a gas in a closed container has a given pressure → ⇡ volume, ⇣ pressure
when the diaphragm contacts the volume of the thoracic cavity ⇡ and intrapleural pressure ⇣
⇣ in Pip causes lungs to expand
Henry’s Law
- the amount of gas that dissolves into a fluid is related to:
- the solubility of the gas into the fluid → CO2 is more soluble than O2
- the temperature of the fluid → the higher the temp the lower the solubility
- the partial pressure of the gas → the greater the pp gradient the better we can get a gas into a fluid
Dalton’s Law
the total pressure of a gas mixture is equal to the sum of the pressures that each gas exerts independently
What does Dalton’s Law mean for respiratory physio?
- air is composed of multiple gases → mostly N2 and O2
- each gas has a pressure (partial pressure) that is independent of other gasses
- add up partial pressures of all gases for total pressure
total partial pressure: PB = PO2 + PN2…
to calculate PP
PO2 = PB x FO2 (fraction of gas that is oxygen)
What happens to PO2 as you go up in altitude?
it decreases
Why does the function of inspired air stay the same but atmospheric pressure drop as you go up?
because gravity decreases as you go up
Inspiration begins
- ambient air brought into airways warmed and humidified
- by larynx, saturated with water vapor (water vapor = a gas (PH2O = 47 mmHg)
- PP of other gases diluted
- PO2 in a humidified mixture → PO2trachea = 150 mmHg
water vapor does not change the % of O2, it decreases PP
Total ventilation (VE)
VE (ml/min) = tidal volume (VT) (ml/breath) x respiratory rate (f)(breaths/min)
rest: 6,000 mL = 500 mL/breath X 12 breaths/min
Max: 150L (2X rest) = ⇡⇡ X ⇡ → both VT and f ⇡ but depth of breathing increases more because of anatomical dead space
Dead Space
- Not all inspired air gets to site of gas exchange
- part remains in conducting pathway
- useless for gas exchange
- anatomical dead space (= 150 mL)
- Pronounced effect on efficiency of VE
- 500 mL air moved in and out/breath → only 350 mL exchanged between atmosphere and alveoli
must be considered to determine alveolar ventilation
2 types of dead space
- anatomical dead space (=150mL)
- in conducting airways → everyone has it
- Alveolar dead space (later)
- in alveoli with poor circulation
- insignificant in healthy lung; lethal in diseased lung
physiological dead space (anatomical + alveolar dead space) is the same as anatomical in healthy people
What is more important: Tidal Volume or Total Ventilation?
Tidal volume
Alveolar Ventilation (VA)
Alveolar Ventilation (VA) = (tidal volume (VT) - anatomic dead space (VD)) x respiratory rate (f)
4200 mL = (500 ml/breath - 150 ml) x 12 breaths/min
- at the end of expiration → old air from previous breath is in dead space
- next inspiration → old air is pushed into alveoli
Alveolar ventilation is best increased by….
increasing tidal volume
Wasted ventilation
drawing air in and out of dead space and not inspiring fresh air
PCO2 Equation
PaCO2 = (VECO2 x 0.863)/VA
PCO2 in arterial blood is inversely related to alveolar ventilation (VA)
- if you hyperventilate (high level of ventilation), PaCO2 goes down
- if you hypoventilate (under ventilate), PaCO2 goes up
How do you regulate PaCO2 and pH?
changing VA
- if PaCO2 is high, VA is not adequate for level of CO2
- not enough ventilation (CNS depression or respiratory muscle weakness)
- too much ventilation ending up as dead space ventilation (COPD or rapid, shallow breathing
Eucapnia
PaCO2 = 35-45 mmHg
alveolar ventilation = normal
Hypercapnia
PaCO2 = >45 mmHg
alveolar ventilaiton = hypoventilation
Hypocapnia
PaCO2 = < 35 mmHg
alveolar ventilation = Hyperventilation
How do we measure the amount of O2 reaching the alveoli?
The alveolar gas equation → PAO2 = PIO2 - (PACO2/R)
R = respiratory exchange ratio → ratio of how much CO2 is produced and how much O2 is taken in
PAO2 = 102
Respiratory Quotient
Ratio of CO2 produced (VCO2) to O2 taken up (VO2)
depends on the rate of metabolism and substrate burned (0.7-1); assumed to be 0.8
Alveolar Gas Composition
PP of gases and H2O from atmosphere to blood
- in healthy individuals, PAO2 is very close to PaO2
- difference is the A-a gradient
- 50% due to regional differences in VA/Q (⇡ at top of lung)
- 50% due to anatomic shunt (blood bypasses alveoli); bronchial veins drain into pulmonary veins
- due to high diffusibility, PACO2 = PaCO2
Systemic circulation
Left ventricle → aorta → rest of body → returns to right atria
Pulmonary circulation
right ventricle → the main pulmonary artery → lungs → pulmonary veins → left atria
the lungs receive the entire right ventricle cardiac output
Dual circulation in the lungs: Pulmonary Circulation
blood comes from heart → oxygenated by lungs → returns to heart
- job: perfuse alveoli for gas exchange
- arises from RV
- receives 100% of RV output
Dual circulation in the lungs: bronchial circulation
bring nutrients and O2 to areas not involving gas exchange
- Job: meet the needs of the lung; similar to coronaries for the heart
- nourishes conducting airways and parenchyma up to terminal bronchioles
- arises rom aorta
- part of systemic circulation
- receives 2% of LV output
blood from bronchial circulation (deoxygenated) mixes with O2 enriched blood in the pulmonary vein → contributed to the small A-a O2 difference
Pulmonary Blood Flow
blood coming from RV going to lungs
- High flow → 5 L/min
- flow rate = flow rate thru systemic circulation
- Low pressure → weak pump, doesn’t pump as hard or long
- only need to pump to top of lungs
- not redirect blood flow like systemic circulation
- minimal smooth muscle in arteries
- less resistance
What contributes to the low resistance of the Pulmonary Circulation System?
- Pulmonary arteries are shorter, and in a dilated state (large diameter)
- Pulmonary arterioles are thin walled, have less smooth muscle and lower resting tone
- more distensible (7X more compliant)
- highly compliant state required less work (lower pressures)
- enormous number of capillaries, in a unique arrangement (like a sheet → parallel) to create sheets of blood flowing past alveoli
all these factors contribute to a very compliant, low resistance circulatory system which relied on a weak pump (RV)
3 factors that alter pulmonary vascular resistance
- changes in blood flow (perfusion)
- ⇡ pulmonary artery pressure → ⇣ pulmonary vascular resistance (PVR) due to recruitment and distention
- changes in lung volume
- pulmonary resistance follows a U shape curve with resistance lowest a FRC
- changes in local O2 concentration
- hypoxia has the opposite effect on pulmonary vascular smooth muscle that it does in systemic smooth muscle
pulmonary vasculature is not significantly regulated by the ANS
Pulmonary Vascular Resistance and Perfusion
⇡ CO (exercise) → ⇡ pulmonary blood flow → ⇣ resistance (R)
⇣ CO (heart failure) → ⇣ pulmonary blood flow → ⇡ R
⇡ SA (for diffusion) and no high capillary pressure → pulmonary edema
- why?
- capillary recruitment
- capillary distention
they keep pressure low
Capillary recruitment
all available vessels not open at rest (esp. apex) because low perfusion pressure
Capillary distension
⇡ diameter with minimal pressure
Pulmonary Vessels: Extra-alveolar
arteries and veins
by virtue of their location, not influenced directly by PA
subject to Pip
Pulmonary Vessels: Alveolar
arterioles, caps, venules
capillaries within interalveolar septa
subject to PA
At high lung volumes (inspiration)…
Pip more negative → ⇡ transmural pressure → distended extra-alveolar vessels → ⇣R
alveolar diameter increases, crushing alveolar vessels (⇡R)
At low lung volumes (expiration)…
Pip more positive → compresses extra alveolar vessels (⇡R)
alveolar diameter decreases (⇣R)
When is PVR lowest?
at FRC and increases at lower and higher lung volumes
resistance additive because vessels in series
Hypoxia and Hypoxemia
low O2 in alveoli or in blood
trigger vasoconstriction
Why would we want to deliver blood to a region of lung that has low O2?
NO synthase needs O2 to produce NO
Types of alveolar hypoxia: Regional
vasoconstriction localized to specific region of lungs
often caused by bronchial obstruction
little effect on pulmonary arterial pressure
when hypoxia gone, vessels dilate, BF returns
Types of alveolar hypoxia: Generalized
vasoconstriction throughout both lungs
leads to significant increases in R and pulmonary arterial pressure
causes by high altitudes and chronic hypoxia (asthma, emphysema)
can leas to pulmonary hypertension
What happens to blood flow in the lungs in an upright person?
BF is highest near the base and lowest near the apex
What happens to hydrostatic pressure as blood travels towards the apex of the lungs?
every 1 cm above the heart, hydrostatic pressure ⇣ 0.74 mmHg
What happens to arterial pressure as blood travels through the pulmonary system?
10 cm above the heart, arterial pressure = 6.6 → capillaries at apex, reduced blood flow
10 cm below the heart, arterial pressure = 21.4 → capillaries at base, distended and flow increased
regional distribution of blood flow is due to..
effects of gravity on hydrostatic pressure
influence of alveolar pressure on alveolar vessels
Pressures affecting pulmonary blood flow: Zone 1
occurs when PA > Pa
pulmonary capillaries collapse; no flow
usually small/nonexistent in healthy people
increases alveolar dead space: ventilated, not perfused
When is zone 1 created?
when alveolar pressure is increased (positive pressure ventilation) or arterial pressure is decreased (hemorrhage)
Pressures affecting pulmonary blood flow: Zone 2
middle ⅓ of lung
Pa (from ⇡ hydrostatic pressure) > PA
flow driven by this difference
B/c PA > Pv, PA partially collapses downstream caps
primary area of distention, recruitment of vessels during exercise
Pressures affecting pulmonary blood flow: Zone 3
Pa > Pv > PA
optimal gas exchange; V/Q = 0.8 - 1.0
gravities effects and alveolar pressure influence how much blood flow perfuse different regions of the lungs in an upright person
Gas Movements in the Lungs: Bulk Flow
how gas moves in airways from trachea to alveoli
due to mass movement → like water out of a faucet
occurs when there are differences in total pressure
Gas Movements in the Lungs: Diffusion
how has moves in us from air → liquid; liquid → air
gases moving due to their individual pressure gradients
Gas diffusion determined by 2 factors:
- Diffusion properties of membrane (Fick’s Law)
- Vgas α (A*D*(P1-P2))/T
- Pulmonary Capillary Blood Flow
Fick’s Law of Diffusion: Partial pressure gradients (ΔP)
rate of diffusion ⇡s as partial pressure ⇡s
Fick’s Law of Diffusion: Surface area of membrane (A)
rate of diffusion ⇡s as surface area ⇡s
constant at rest
increases with exercise
Fick’s Law of Diffusion: Thickness of the membrane (T)
rate of diffusion ⇣s as thickness ⇡s
thickness ⇡s with edema, pneumonia, fibrosis
Fick’s Law of Diffusion: Diffusion constant (D)
rate of diffusion ⇡s as D ⇡s
D for CO2 20x > than O2; changes in diffusion seen in O2 first
Major determinant of rate of diffusion is…
Partial Pressure gradient
Transport of Gases in the Blood: O2 has 2 forms
- Physically dissolved
- O2 is poorly soluble in body fluids
- amount dissolves is directly proportional to PO2
- 1.5% of O2 is free
- Bound to Hemoglobin (Hb) → storage
- O2 bound to Hb does not contribute to PO2 in blood
- 98.5% of O2 is chemically bound to Hb
Total O2 content
20 mL O2/100 mL blood → 19.7 mL O2 bound to Hb, 0.3 mL free
Binding of O2 to hemoglobin is readily…..
reversible
critical in the delivery of O2 to tissues
Oxyhemoglobin (HbO2)
Hb attached to O2
when attached to four oxygen → saturated
saturated Hb is relatively unstable and easily releases O2 in regions where the PO2 is low
blood is bright red color
Deoxyhemoglobin
Non-O2 bound Hb
blood is deep maroon color
The amount of HbO2 depends on…
the amount of PO2 in the blood
When blood PO2 is high (pulmonary capillaries) → form HbO2 → ⇡ % saturation
When blood PO2 is low (systemic capillaries) → O2 released from Hb → ⇣ % saturation
___ is the primary factor in determining the % of Hb saturation
PO2
PO2 is determined by where you are in the body
Binding of O2 to each heme group….
increases affinity of the Hb to bind additional O2
% of saturation of Hb with O2
SO2 = (HbO2 content/ HbO2 capacity) x 100
content = O2 actually bound to Hb
capacity = O2 potentially bound to Hb
Oxyhemoglobin Dissociation Curve
How plasma PO2 affects O2 loading and unloading from Hb
S shaped
when PO2 is high → hemoglobin is very saturated
small drops in PO2 → able to dump off a lot of O2
Oxyhemoglobin Dissociation Curve: Plateau
- enables O2 to saturate Hb in lungs (high PO2)
- At a PO2 of 60, Hb is 90% saturated
- increases above 60, have minor effect on Hb saturation
*is PO2 drops from 100 → 60, Hb saturation is still 90%
Oxyhemoglobin Dissociation Curve: Steep
Gives up large amounts of O2 in tissues (small change in PO2)
P50
the PO2 when hemoglobin is 50% saturated
~ 27 under normal conditions
Hb results in a Large net transfer of O2 by…
keeping PO2 Low
HB acts as a storage depot for oxygen
once bound to Hb oxygen molecules no longer exert any pressure
Hb soaks up O2 (keeping PO2 low) → more O2 can enter blood
Factors that shift the oxyhemoglobin dissociation curve RIGHT
- ⇣ in Hb’s affinity for O2
- decrease in Hb binding at a given PO2
- increase in P50
- Aids in release/unloading of O2
Factors that shift the oxyhemoglobin dissociation curve LEFT
- ⇡ in Hb’s affinity for O2
- ⇡ Hb binding at a given PO2
- lower P50
- Aids in uptake/binding of O2
Shifting the oxyhemoglobin dissociation curve has the greatest effect on which phase?
the steep phase
Factors that shift the oxyhemoglobin dissociation curve RIGHT: Hb Unloading of O2
Even though primary factor determining % Hb saturation is PO2 in blood, other factors ⇡ O2 unloading from Hb
- CADET face right
- CO2
- Acidity
- 2,3 diphosphoglycerate
- Exercise
- Temperature
- shift curve to right
Effects of carbon monoxide on the oxyhemoglobin curve
CO prevents O2 loading (via competition) and unloading (shifting)
CO and O2 compete for Hb binding sites
CO has higher affinity for Hb
HbCO shifts curve left
inhibits unloading/delivery of O2 to tissues
PO2 > 0.5, all Hb binding sites occupied by CO
Healthy: 1-2% HbCO at Hb binding sites
Smokers/urban residents: 10%
How is CO2 Transported in the blood
As bicarbonate ions (60%)
Physically dissolved (10%)
Chemically bound to Hb (30%)
total CO2 content in arterial blood is 59 mL CO2/100 mL blood
What tells us how much O2 is in the blood?
CaO2
content of O2
need to know how much O2 is also bound to Hb → given by SaO2a and Hb content
What does PaO2 tell us? (partial pressure)
- O2 molecules dissolved in plasma
- adequacy of gas exchange within the lungs when it is subtracted from the calculated PAO2
What does SaO2 tell us? (saturation)
Heme sites (on Hb) occupied by O2 molecules → saturated
the % of all the available heme binding sites saturated with oxygen
SaO2 is determined mainly by PaO2
What does CaO2 tell us?
directly reflects the total number of O2 molecules in arterial blood (both bound and unbound)
PaO2 is determined by…
PAO2 and the state of alveolar capillary membrane
PaO2 determines….
the O2 saturation of Hb (along with other factors that affect the position O2 disassociation curve
__ determines the total amount of O2 in blood or CaO2
The SaO2, the [] of hemoglobin (~15 gm/dl) and PaO2
CaO2 is…
20 ml O2/ d;
Effects of gravity on Upright Lung: Apex
⇣⇣ blood flow
⇣ ventilation (overventilated)
⇡ V/Q ratio
⇡ PaO2
⇣ PaCO2
Effects of Gravity on Upright Lung: Base
⇡⇡ blood flow (over perfused)
⇡ ventilation
⇣ V/Q ratio
⇣⇣ PaO2 (bl not fully oxygenated)
⇡ PaCO2
What is the functional importance of V/Q ratios?
matching Regional ventilation to blood flow (not total V and total Q)
Alveolar - arterial O2 difference
measure of gas exchange efficiency across alveolar-cap membrane
PAO2 = calculated (alveolar gas equation)
PaO2 = measured (sampling arterial blood)
Helps to determine cause of hypoxemia
What is the normal P(A-a)O2?
≤ 20 mm Hg
Normal V/Q mismatch (50% responsible)
return of bronchial and coronary blood (deoxygenated) through the Thesbesian veins to the left side of the heart (50%)
Predict normal: age/4+4; ⇡ with age
Five causes of hypoxemia
- hypoventilation → can’t ventilate sufficiently
- low inspired O2 → due to altitude or ventilator (under ventilating)
- Right-to-left shunt → blood from right side of heart goes to left side of the heart (Pulmonary AV malformation)
- V/Q mismatch → not doing a good job matching ventilation and perfusion
- diffusion impairment → i.e. ⇡ thickness, ⇣ diffusion
Divided into:
those with an ⇡ P(A-a)O2 vs. those with a normal P(A - a)O2
Hypoventilation
PaO2 →⇣
A-aO2 difference → normal
FIO2 = 1.0 → ⇡
Low PIO2
PaO2 →⇣
A-aO2 difference → normal
FIO2 = 1.0 → ⇡
Right to left shunt
PaO2 →⇣
A-aO2 difference → ⇡
FIO2 = 1.0 → No mostly
V/Q mismatch
PaO2 →⇣
A-aO2 difference → ⇡
FIO2 = 1.0 → ⇡
Diffusion Limitation
PaO2 →⇣
A-aO2 difference → ⇡
FIO2 = 1.0 → ⇡
Respiration demonstrates both:
Automaticity → begins at birth
Self-modulation (voluntary) allows us to → voluntarily hyperventilation, hold our breath, change breathing patterns for speech and singing
What makes up the ventilatory control system?
Sensors → chemoreceptors and mechanoreceptors = feedback
central controller → respiratory control center = the driver
Effectors → respiratory muscles = carries out
Neural Control of Breathing: Voluntary
Cerebral Cortex
Neural Control of Breathing: Autonomic
Medullary Centers → dorsal Respiratory Group, Ventral Respiratory Group
Pontine Centers → Pneumotaxic Center, Apneustic Center
Respiratory Control Centers: Medullary Centers
- Dorsal respiratory group (DRG) → comprised mainly of inspiratory neurons
- pre-botzinger complex → the anatomic location of the respiratory pattern generator; these neurons display pacemaker activity
- Ventral respiratory group (VRG) → responsible for both expiration and inspiration, but inactive during quiet breathing; active in exercise
Respiratory Control Center: Pontine Centers
Rhythm generated in the medulla can be modified by neurons in the pons
medulla is the major rhythm generator
What happens if you cut the spinal cord between the medulla and pons?
fairly normal ventilation but erratic
What happens if you cut below the medulla?
ventilation ceases
What controls the transition from inspiration and expiration?
Pneumotaxic Center and Apneustic center in the pons
Pneumotaxic Center
dominants
Terminates Inspiration
this has a secondary effect of ⇡ing the rate of breathing, because limiting inspiration also shortens expiration
Apneustic center
prevent inspiratory neurons from being shut off; prolongs inspiration
Mechanoreceptors
detect distention and irritation → airways and lung parenchyma
Chemoreceptors
chemical content of blood or CSF
PO2
PCO2
H+
Central Chemoreceptors
- lose sensitivity to CO2
- located on surface of medulla; separate from respiratory center
- sensitive to pH
- BBB impermeable to H+,but CO2 readily diffuses
- When PaCO2 increases, CO2 crosses the BBB, not H+
- Lass of mass action ⇡s H+
- Synaptic connection to respiratory control center ⇡s ventilation
- Excess CO2 blown off; decreased PaCO2 slows ventilation rate
Most important mechanism controlling ventilation at rest:
CO2-induced H+ in CSF
What happens to chemoreceptors during prolonged hypoventilation (chronic lung disease)?
- some lose sensitivity to elevated PaCO2
- the increased H+ gets buffered by HCO3- (actively transported across BBB)
- central chemoreceptors no longer “aware” of elevated PCO2
- Hypoxic drive becomes primary respiratory stimulus
should you administer O2? No
How do central chemoreceptors respond to hypoxia?
They adapt
Peripheral Chemoreceptors
glomus cells in the carotid* and aortic bodies → increase ventilation during hypoxia
not sensitive to modest reductions in PaO2
Peripheral Chemoreceptors: Hypoxia
when PaO2 < 60 mmHg
important emergency mechanism
respond to PaO2 not oxygen content → anemia and CO = normal PO2; no response
inhibit K+ channel; depolarizes cell
Peripheral Chemoreceptors: Hypercapnia
central receptors more sensitive
CO2 diffuses into glomus; H+ inhibits K+ channel
Peripheral Chemoreceptors: Acidosis
Arterial H+ inhibits K+ channel
The effect of dangerously low PaO2 on peripheral chemoreceptors
The activity of all other nervous tissue becomes reduced with O2 deprivation
If not for stimulatory effect on peripheral chemoreceptors, ventilation would cease
Arterial PCO2
The most important regulator of ventilation
Response primarily arises from central chemoreceptors with added input from peripheral chemoreceptors
Arterial PO2
when PO2 ⇣⇣⇣ low, ventilation increases
response from peripheral chemorects (central do not directly sense PO2)
Arterial pH
As h+ increase, ventilation increases, but H+ cannot diffuse into CSF as well as CO2
Pulmonary Stretch Receptors
Mechanoreceptors in smooth muscle of conducting airways
keep from over expanding lungs
respond to lung distention → excites inspiratory off switch, shortens inspiration when VT large
Joint and Muscle Receptors
Mechanoreceptors in joints and muscles signal DRG to increase breathing frequency
activated during movement when O2 demand is or will be high
possibly part of a feed forward mechanism with exercise to prepare
Irritant Receptors
Mechanoreceptors in airway epithelium of larger conducting airways
respond to irritation of the airways by touch, dust, smoke
protects by inducing a cough and hypernea
Juxtapulmonary Capillary Receptors (J receptors)
- Stimulated by distortion
- pulmonary C-fibers
- next to alveoli
- accessible to pulmonary circulation
- sensitive to mechanical events (edema and embolism)
- pulmonary C-fibers
- high yield info in boxes and handouts
