Download Burns Pulm Lect 1 Physiol 2017

OPTO 5331 General Pathology and Medicine
Respiratory Physiology
Dr. Alan Burns
Room 2168
[email protected]
Spring 2017
1
Reading
Chapters 27-31 in Principles of Physiology
(4th ed.) by Berne & Levy
2
Respiratory System Anatomy
3
Respiratory System Anatomy
Long narrow
curled shelf of
bone
Turbinates
– smooth air
flow
Cartilage flap depressed when
swallowing
Protects
trachea
against food
aspiration
cord
4
Respiratory System Anatomy
• lung is lined by a
visceral pleura
(mesothelium)
• lung lies within
the pleural cavity
which is lined by
parietal pleura
(mesothelium)
• fluid-filled space
within pleural
cavity exerts
suction on lungs
and helps prevent
collapse
5
Respiratory System Anatomy
Alveolar cell types
• Type I pneumocytes
are squamous epithelial
cells through which gas
exchanges – 95%
surface area
•Type II pneumocytes
are cuboidal epithelial
cells that secrete
surfactant – 5%
surface area
• Other cells:
macrophages, capillary
endothelial cells,
fibroblasts and blood
6
elements
Respiratory System Anatomy
Type II
pneumocytes store
surfactant in
“lamellar” bodies
7
Respiratory System Anatomy
8
Respiratory System Anatomy
Surfactant
• Mix of phospholipid,
protein, carbohydrate
• Major component is
dipalmitoylphosphatidyl
choline
• Reduces surface
tension so prevents
collapse of alveoli
• Lack of surfactant
causes respiratory
distress syndrome in
premature infants
(surfactant production
begins at 32 weeks) 9
Functions of Respiratory System
Primary Function
Secondary Functions
• Gas exchange
•
•
•
•
•
– entry of O2
– elimination of CO2
Acid-base balance in blood
Speech
Defense against microbes
Circulatory filter
Blood Reservoir
Acid - Base Balance
Carbonic Acid (H2CO3) and
Bicarbonate (HCO3-) Buffer
System
In blood:
CO2 + H2O ↔ H2CO3 ↔ H+ + HCO3-
Response to change in pH is INSTANTANEOUS and
constitutes the body’s first line of defense against
acid-base imbalance
11
Acid - Base Balance
CO2 + H2O ↔ H2CO3 ↔ H+ + HCO3-
•Henderson-Hasselbalch equation:
pH=6.1 + log([HCO3-]/PCO2)
Substitute normal blood values and multiply mm Hg PCO2
by 0.03 to convert to mEq/L PCO2:
7.4=6.1+ log(24 mEq/L/(0.03 x 40 mm Hg))= 6.1 + log 20/1
mEq = molar equivalent = amount of substance that reacts with or
supplies one mole of H+ ions
*As long as the ratio of bicarbonate (HCO3-)
to CO2 is 20:1, pH will be 7.4
12
Acid - Base Balance
-
Lungs:
regulate blood CO2 level by eliminating or retaining CO2
pH regulated by altering rate and depth of respiration
Allows for RAPID pH response
Normal CO2 level (35-45 mm Hg)
Kidneys:
- Long-term regulators of acid-base balance
- Maintain balance by excreting or conserving blood
bicarbonate (HCO3-) and hydrogen ions (H+)
- SLOW pH response (hours or days to correct pH)
- Normal bicarbonate level (22-26 mEq/L)
13
Acid - Base Balance
CO2 + H2O ↔ H2CO3 ↔ H+ + HCO3Arterial [H+] can change for many reasons:
- If the change does not involve the lungs:
Metabolic acidosis – pH decreases
Metabolic alkalosis – pH increases
- If the lungs are the cause:
Respiratory acidosis/alkalosis
14
Acid - Base Balance
CO2 + H2O ↔ H2CO3 ↔ H+ + HCO3• Because the CO2-bicarbonate buffer system plays a
significant role in regulating pH, the lungs can alter
arterial pH by changing PCO2
• Ventilation is increased in response to metabolic
acidosis (arterial↑H+ / acidemia)
• Ventilation is decreased in response to metabolic
alkalosis (arterial↓H+ / alkalemia)
15
Acid - Base Balance
CO2 + H2O ↔ H2CO3 ↔ H+ + HCO3Inability of lungs to remove CO2 → elevated arterial
PCO2 → respiratory acidemia
• elevated PCO2 increases acid (H+ + HCO3-) production
Inappropriate removal of CO2→ lowered arterial
PCO2 → respiratory alkalemia
• because lowered PCO2→ decreases acid production
16
Functions of Respiratory System
•
•
•
•
•
•
Entry of O2 - elimination of CO2
Acid-base balance
Speech
Defense against microbes
Circulatory filter
Blood reservoir
17
Speech
• air passing over larynx causes it to
vibrate and produce sound. Sound is
modified by tongue, lips, etc. to make
speech
Defense against microbes
• alveolar macrophages, antibacterial peptides
(epithelial) & BALT (lymphocytes, dendritic cells,
macrophages….immune response)
18
Circulatory filter
• filters small blood clots & destroys them
• endothelial-derived tissue plasminogen activator (TPA)
converts circulating plasminogen to plasmin which
dissolves fibrin in clots
Blood reservoir
• lung blood volume (500 ml) = 10% of total blood volume
• stabilizes left ventricle stroke volume when going from
supine to standing
19
Overview of Respiration
•
•
•
•
Ventilation (breathing)
Gas exchange
Transport of gases in blood
Control of breathing
20
Ventilation
•
•
•
•
Mechanics
Pressure Changes
Lung Volumes and Capacities
Dead Space
21
Mechanics
• Conducting zone
- nose, mouth, pharynx,
larynx, trachea,
bronchi, bronchioles &
terminal bronchioles
- Warms, humidifies and
filters air
“muco-ciliary escalator”
- No gas exchange,
volume is known as
anatomical dead space
22
Mechanics
• Conducting zone
- nose, mouth, pharynx,
larynx, trachea,
bronchi, bronchioles &
terminal bronchioles
- No gas exchange
• Respiratory Zone
- respiratory bronchioles,
alveolar ducts and
alveolar sacs
- Site of gas exchange
Generations (n)
(0)
(1-3)
(4-16)
(17-19)
(20-22)
(23)
23
Mechanics
•
Lungs are held against the
chest wall by pleural fluid
surface tension
•
Natural elastic forces
– chest wants to expand
and lung wants to
contract
•
Opposing forces between
lung and chest wall
generate a subatmospheric (negative)
pressure within the
pleural cavity
(intrapleural pressure)
24
Mechanics
Inspiration (thoracic volume
increases- active process)
•
Diaphragm, main muscle
of inspiration, contracts,
flattens and descends
•
Rib cage moves up and
outwards facilitating lung
expansion
•
External intercostal
(between ribs) & neck
accessory muscles are
important during forced
inspiration
25
Mechanics
Expiration (thoracic volume
decreases - passive process)
•
Diaphragm relaxes and
becomes more rounded
•
Natural recoil lung, chest
and abdominal structures
help compress lungs
•
Internal intercostal &
abdominal muscles
important during forced
expiration
26
Mechanics
Respiratory or Breathing Cycle
•
One inspiration + one
expiration constitute one
breathing cycle
•
Average 12-15
breaths/minute
27
Pressure Changes in Ventilation
• Pressure gradient is required to move air into
and out of the lungs
• Gases move from areas of higher to lower
pressure
• Behavior of gases during ventilation conform
to Boyle’s Law :
“volume is inversely related to pressure”
28
Boyle’s Law
29
Pressure Changes in Ventilation
• Inspiration
- Lung expansion increases alveolar volume, alveolar pressure
falls. Now alveolar pressure is lower than the pressure at
the airway opening (atmospheric) so air flows into the lungs
- Air continues to flow in until pressure gradient dissipates
• Expiration
- Lung contraction decreases alveolar volume, alveolar pressure
increases. Now alveolar pressure is greater than the
pressure at the airway opening, so air flows out of the lungs
- Air continues to flow out until pressure gradient dissipates
30
Pressure Changes
in Ventilation
• Under physiologic conditions,
transpulmonary pressure (Ptp) = alveolar
pressure (Palv) minus pleural pressure
(Ppl). Hence, Ptp is always positive;
pleural pressure is negative and large
and alveolar pressure moves from
slightly negative to slightly positive
during breathing
• When Ptp = 0 (i.e., Palv = Ppl), such as
when the lungs are removed from the
chest or air enters the pleural space
(pneumothorax), the lungs collapse due
to inherent elastic recoil (modulates Ptp)
• For a given lung volume, Ptp is equal
and opposite to the elastic recoil
pressure of the lung
31
Pressure Changes in Ventilation
Compliance
• Change in lung volume/unit change
in pressure across the lung
• Normal is 0.2L/1cm of water
• Measure of expansibility
• Increased compliance
(emphysema) lungs expand
more
• Decreased compliance (fibrosis)
lungs expand less
32
Lung Volumes
• Four terms describe specific lung
volumes:
• VT (Tidal volume)
- volume inspired or expired with each
breath
• IRV (Inspiratory Reserve Volume)
- additional volume inspired above VT
• ERV (Expiratory Reserve Volume)
- additional volume expired above VT
• RV (Residual Volume)
- volume remaining in lungs after
maximal forced expiration
33
Lung Volumes → Capacities
Four terms describe lung capacities:
IC
Inspiratory Capacity (VT + IRV)
FRC
Functional Residual Capacity (ERV + RV)
VC
Vital Capacity (IC+ERV)
TLC
Total lung capacity (VT + IRV + ERV + RV)
34
Lung Volumes and Capacities
Volumes:
IRV
VT
ERV
RV
Capacities: IC = VT + IRV = 3.5 liters
FRC = ERV + RV = 2.4 liters
VC = IC + ERV = 4.7 liters
TLC = VT + IRV + ERV + RV = 5.9 liters
35
Lung Volumes and Capacities
Changes RV/TLC ratio are early indicators of lung disease
• Normal
- 0.2-0.35
• Obstructive lung disease
- airway obstruction (asthma, bronchitis,COPD)
- >0.35 when RV increased because of increased gas
trapping out of proportion to any increase in TLC
• Restrictive lung disease
- reduced lung volume due to parenchymal disease or
disease of pleura, chest wall or neuromuscular apparatus
- >0.35 because TLC decreased out of proportion to any
36
decrease in RV
Dead Space
- Areas not participating in gas exchange
• Anatomic = conducting zone
• Alveolar = alveoli receiving inadequate blood flow
• Physiologic = anatomic + alveolar
(i.e. alveoli not exchanging gas)
37
Dead Space
• Ventilation rate
Minute ventilation
(VT x breaths/min)
– normal value 7.5 L/min (500ml x 15bpm)
Alveolar ventilation (VA)
(VT - physiologic dead space) x breaths/min
- (500ml – 150ml) x 15bpm = 5.25 L/min (normal)
- VA is the actual amount of air available
for gas exchange
38
Dead Space
•Various combinations of tidal volume and breathing frequency
can produce the same minute ventilation but not the same
alveolar ventilation
•At the extreme, if tidal volume is < dead space volume,
alveolar ventilation will be zero and no gas exchange is possible.
Animals take advantage of this and pant (shallow rapid breaths)
to enable heat radiated by conducting airways to be removed
while not altering gas composition of blood
39
Gas Exchange
Gas exchange (i.e., diffusion of O2
from air into capillaries and diffusion
of CO2 in opposite direction) occurs
across the “respiratory membrane”
Fick’s law of diffusion Gas movement across a
sheet of tissue is:
• directly proportional
to surface area,
diffusion constant and
the partial pressure
gradient
Surface area x Diffusion constant x Partial Pressure Gradient
Thickness
• inversely proportional
to surface thickness
40
Gas Exchange
The respiratory
membrane
41
Gas Exchange
The lung generates a large surface area by
dividing the “respiratory membrane” into
many units (alveoli or alveolar sacs)
42
Gas Exchange
•300 x 106 alveoli in the human lung
•Each alveolus is 1/3mm in diameter
•Alveolar surface area (~160 m2) – nearly
the size of a tennis court
•Alveolar capillaries unwound and laid
end-end extend for 620 miles
•The alveolar blood-gas barrier (wall) is
also very, very thin (0.3-0.5 µm)
43
Gas Exchange
• Occurs across “respiratory membrane”
• Oxygen and carbon dioxide move between
air (gas) and blood (liquid) by simple diffusion
• Driving force is partial pressure difference
• Dalton’s Law: “Total pressure exerted by a
mixture of gases equals the sum of individual
partial pressures” *
• Net diffusion of gas is from higher to lower
partial pressure
*Dry air has 21% Oxygen. Its partial pressure
(PO2) at sea level is 21/100 x 760 = 160 mm Hg. 44
Partial Pressure (Dalton’s Law)
“Total pressure exerted by a mixture of gases equals
the sum of the individual partial pressures”
Po2 in dry air
= 760 mmHg x 0.21
= 160 mmHg
Po2 in humid* air = (760 mmHg - 47 mmHg) x 0.21
= 150 mmHg
* Inhaled air is warmed and moistened and the water
45
vapor pressure is 47 mmHg
Partial Pressure
Net diffusion of a gas from area of higher
partial pressure to one of lower partial
pressure.
78% N2
21% O2
0.3% CO2
Alveolar gas
exchange results in
decreased alveolar O2
(PAO2) and increased
CO2 (PACO2)
46
Gas Exchange
Oxygen
• Partial pressure in alveolar
air (PAo2) is greater than in
capillaries so O2 diffuses
across respiratory membrane
from alveoli to capillaries
• At tissues, Pao2 is greater
in capillaries than tissue so
O2 diffuses from capillaries
into tissue
47
Gas Exchange
Carbon Dioxide
• Partial pressure (PAco2) in
alveolar air is lower than in
capillaries so CO2 diffuses
across respiratory membrane
from capillaries to alveoli
• At tissues, Paco2 is lower
in capillaries than tissue so
CO2 diffuses from tissue
into capillaries
48
Factors affecting gas exchange
• Rate of gas diffusion (Fick’s law) decreases if:
Increase in thickness of respiratory membrane
Decrease in surface area of respiratory membrane
• Alveolar ventilation rate
Alveolar ventilation inversely related to PAco2:
Increase rate (hyperventilate) lowers PAco2, so increases
partial pressure difference, facilitates exchange
Decreased rate (hypoventilate) raises PAco2, so decreases
partial pressure difference, inadequate exchange
49
Factors affecting gas exchange
• Amount of gas dissolved in blood can be limited by
pulmonary blood flow (perfusion limited)
• It takes 0.75 seconds for blood to flow through a
pulmonary capillary, and only 0.25 seconds for alveolar
O2 to equilibrate with blood O2; for the remaining
0.5 seconds, the blood will not take on more O2
• The amount of oxygen and carbon dioxide in the blood
is limited by perfusion (i.e., the only way to transfer
more dissolved gas would be to add more blood (increase
flow)
50
Ventilation (V)/ Perfusion (Q) Ratio
• V and Q not evenly matched
in normal lung (V/Q mismatch)
due to gravity
• Normal lung V/Q ratio is 0.8
• Regional ratios : Apex 3
Base 0.6
• Where ventilation is insufficient (low V/Q),
blood not oxygenated (shunted blood)
• 2.5% of cardiac output is shunted
• Pathologic changes
Low V/Q blood not oxygenated - more shunted blood
High V/Q excess of oxygen - wasted ventilation
51
Ventilation (V)/ Perfusion (Q) Ratio
52
O2 Transport in Blood
• 2% dissolved in plasma
• 98% bound to iron in heme groups of hemoglobin (Hgb)
- O2 carrying capacity of blood increased 65 times
by binding to Hgb…..compared to O2 dissolved in plasma
• 1 molecule of Hgb binds 4 molecules of O2
• O2 binding capacity (maximum amount of O2 that can
be carried) = 20.1ml/100ml blood
53
O2-Hemoglobin (Hgb) Dissociation Curve
Percent saturation of Hgb reflects how many O2 molecules
are bound and this is dependent upon the Po2. The
relationship is described by the oxygen-Hgb dissociation curve
Flat part of
curve (60-100
mm Hg) shows a
drop in Po2 over a
wide range has
minimal effect on
Hgb saturation
Steep part of
curve (<60 mm
Hg) shows a large
amount of O2
released with
only a small
change in Po2,
which facilitates
diffusion of O2 to
the tissue
54
Factors affecting O2-Hgb Dissociation Curve
Right shift:
 blood Pco2 leads to  H+ and enhances O2
release from Hgb to tissue. Right shift is due
to the  pH and a direct effect of CO2 on
Hgb.
(Bohr effect)
Left shift:
Opposite of right shift. For example, as blood
passes through lungs, CO2 is exhaled ( blood
Pco2 ,  H+) and an  pH, which enhances
O2 binding to Hgb in the lung
55
Bohr effect
(simply stated)
• hemoglobin's oxygen binding affinity is
inversely related both to acidity and to
the concentration of carbon dioxide
56
CO2 Transport in Blood
• Dissolved gas (7%) in plasma
• Bound to carbamino (terminal lys or arg)
protein complexes
- Hgb (22%)
- plasma proteins (1%)
• Bicarbonate (HCO3-) formed within RBC
- HCO3- released into plasma (70%)
57
CO2 Transport in Blood
HALDANE EFFECT:
Deoxygenation of blood increases the tendency of
hemoglobin to bind carbon dioxide (and vice versa)
58
Control of Breathing
• Rate and depth of breathing tightly controlled to
ensure Po2 and Pco2 are appropriately maintained
over conditions ranging from rest to vigorous excerise
• Involuntary (usually)
• Basic rhythm is set and controlled by respiratory
centers in brain stem (medula and pons) which
control the muscles involved in respiration
59
Control of Breathing
Pneumotaxic center (upper pons)
- inhibits dorsal respiratory neurons
and apneustic center and this helps
regulate breathing depth and rate
Apneustic center (lower pons)
- activates dorsal respiratory neurons
of medulla
Medullary respiratory center
Dorsal respiratory neurons
- set inspiration frequency
- spontaneously active
- phrenic nerve goes to diaphragm
Ventral respiratory neurons
- for forced expiration
60
Fine tuning:
• Chemoreceptors
Control of Breathing
- Present in medulla, common carotid arteries, aortic arch
- Sensitive to Po2, Pco2, arterial pH
- Signal back to respiratory centers in medulla and pons
• Mechanoreceptors
- Stretch receptors present in airway smooth muscle
- Hering-Breuer reflex originates outside the brain
respiratory centers and prevents over-stretching of lung
(action potentials transmitted through vagus nerves inhibit
medulla inspiratory area and pons apneustic center; allows
expiration to occur)
• Irritant receptors
- Present beween epithelial cells lining airways
- Detect noxious chemicals, etc. (nociceptors) and cause
61
airway constriction and increase ventilation rate
Control of Breathing
Voluntary control:
- Commands from cerebral cortex can temporarily over-ride
respiratory centers so it is possible to increase rate and
depth of breathing (hyperventilate) or “hold breath”
(hypoventilate)……for a short time
62