Respiratory System
By
Dr. Carmen Rexach
Physiology
Mt San Antonio College
External vs. internal
respiration
• External respiration
– ventilation
– gas exchange
• Internal respiration
– cellular respiration
Structure
• Conducting zone
– Nasal cavity to
respiratory
bronchioles
• Respiratory zone
– Respiratory bronchi
– Alveoli
Thoracic cavity
• Diaphragm
• Pleura
• Potential space
Intrapulmonary and intrapleural pressures
• Boyle’s law
– pressure of a given quantity of gas is
inversely proportional to volume
• Interpleural space = intrapleural space
• Intrapulmonary (intraalveolar) pressure
– Pressure in alveoli
• Intrapleural pressure
– Pressure in pleural cavity
• Transpulmonary pressure
– Intrapleural pressure – intrapulmonary pressure
– Keeps lungs inflated
Relationship between intrapulmonary and intrapleural pressure
Pneumothorax
• Air in interpleural
space is below atm
• When wall is
breached, air rushes
in
– GSW, stabbing,
trauma
• Result: collapsed
lung
Spontaneous pneumothorax
• Lung collapses due to air or gas collecting in
chest without any sign of traumatic injury
• Usually occurs when patient is resting
• Symptoms
– Sudden chest pain with breathlessness,
exaccerbated with deep breathing or coughing
• Risk factors
– Male gender (7x’s more likely than in females)
• Smoking (22x’s more likely than nonsmokers)
– Smoking females 9x’s more likely than nonsmoking
females
Inspiration
• Pressure of air exceeds
intrapulmonary pressure
• Steps:
– expansion of thoracic cage
– pulls on parietal pleura = increase intrapleural
cavity volume
– pressure decreased by (subatmospheric)
– increased transpulmonary difference
– alveoli expand = decreased pressure in alveoli
– air moves from high to low pressure = moves in
Expiration
• Intrapulmonary pressure greater than
atmospheric pressure = air moves out
• Steps:
– diaphragm & inspiratory intercostals relax
– chest wall recoils
– intrapleural pressure approaches
preinspirational value
– intrapulmonary pressure exceeds atmospheric
pressure
– air goes out
Physical properties of
the lungs
• Three properties
– Compliance
– Elasticity= tendency to recoil
– Surface tension
• Two forces resist distension
– Surface tension and recoil
• surfactant
Pulmonary ventilation
• Normal inspiration = active
• Normal expiration = passive
• Forced inspiration
– Scalenes, pectoralis major,
sternocleidomastoid
• Forced expiration
– Internal intercostals,abdominals
Pulmonary function tests
• Measured by spirometry
• Lung volumes and capacities (approximate volume)
– Tidal volume = volume of each breath (500ml)
– Vital capacity = largest possible tidal volume; amount of
gas that can be forcefully exhaled after maximum inhalation
(5000ml)
– Inspiratory reserve volume = volume of gas that can be
forcefully inhaled after a normal inhalation (3000ml)
– Expiratory reserve volume = volume of gas that can be
forcefully exhaled after an unforced exhalation (1500ml)
– Residual volume = amount of gas remaining in the lungs
after a forced expiration (100ml)
– Dead space volume = volume of air in the conduction
passageways that is not exchanged (150ml)
Differences by gender
Pulmonary disorders
•
•
•
•
Dyspnea
Asthma
Emphysema
COPD =chronic bronchitis +
emphysema
• Pulmonary fibrosis
bronchi
Normal lung
Chronic
bronchitis
asthma
Emphysema
alveoli
Partial pressure of gases
• Dalton’s law
• PN2 + PO2 + PCO2+ PH2O = PATM = 760mmHg
• air = 21% O + 78% N
0.21
760
159mm Hg
0.78
760
593mm Hg
0.0004
760
0.3mm Hg
Other factors influencing pressure
• Altitude
– Increased = decreased atmospheric
pressure
– Decreased = increased atmospheric
pressure
• 1 atm increase for every 33 feet below sea level
• Temperature
– determinant of water vapor composition of
air
– in body
• water vapor = 47mm Hg
• effects the partial pressure of O2 = 105 mm Hg
in alveoli
Partial pressure of gases in the
blood
• Gases diffuse quickly due to:
– surface area, large capillary bed, short diffusion distance
• Henry’s law = The maximum value of a gas
dissolved in a fluid depends on:
– the solubility of the gas in fluid
– temperature of the fluid
– partial pressure of the gases
• Oxygen content of the blood depends on
– PO2, # of RBC’s, hemoglobin content
– Remember: Oxygen is primarily bound to Hb in RBC’s keeping
the amount of O2 in the plasma low
How oxygen is carried in the
blood
• Normal resting oxygen consumption =
250ml/min
• PO2 = 100mm Hg in PV = 20ml O2/100 ml
blood
– 0.3ml O2 dissolved in plasma
– 19.7ml O2 in RBC’s
Partial pressure
of CO2 and O2
in circulation
Vascular resistance in lungs
• Vascular resistance
– fetal = collapsed lungs, resistance is high
– birth = drops
• subatmospheric intrapulmonary pressure opens blood
vessels
• stretching of lungs at inspiration
• dilation of pulmonary arterioles due to increased
alveolar PO2
• foramen ovale and ductus arteriosus close
– adult = low pressure/low resistance
• blood flows to lungs and to systemic circulation at
same rate
• pulmonary 1/10th of systemic vascular resistance
Ventilation/perfusion ratios (V/P)
– Ventilation = respiration rate x tidal volume
– Perfusion = pulmonary blood flow = heart
rate x right ventricular SV
– Nearly matched under normal conditions
• apex of lung
– overventilated & underperfused
– apex =3.4:1
– larger alveoli
• base of lung
– underventilated & overperfused
– base = 0.6:1
Disorders caused by high
partial pressures of gases
• Oxygen toxicity
– PO2 > 2.5 atm
– oxidation of enzymes, nervous system damage,
coma, death
• Nitrogen narcosis
– > one hour down
– rapture of the deep, drowsiness, “intoxication”
• Decompression sickness
– formation of N2 bubbles in blood
– channels blocked, joint & muscle pain = the
bends
Hyperbaric oxygen therapy
• 100% oxygen at >1atm (US
= 2.0-2.4 atm abs)
• Duration:60-90 min.
• Result: Arterial PO2 =
1200mmHg
• Benefits:
– Enhanced fibroblast
replication
– Activation of osteoclasts
– Stimulation of capillary
growth
– Upregulation vascular
endothelial growth factor
– Upregulation of platelet
derived growth factor
CID: 2006 (43):188-192
Hyperbaric treatment for
diabetic foot ulcers
40 days after hyperbaric treatment
& skin graft
Before hyperbaric treatment
Brain stem respiratory centers
• Medulla oblongata
– rythmicity center
• dorsal group (phrenic nerve) & ventral group
(intercostals)
• I neurons = inspiration = spinal motor neurons innervate
respiratory muscle
• E neurons = fire during expiration and inhibit I neurons
• Pons
– apneustic center -- constant I neuron stimulation
– pneumotaxic center -- inhibitory = cyclic inhibition
• Chemoreceptors -- respond to changes in PCO2, pH, PO2
– central
– peripheral = aortic and carotid bodies
Irritant and Inflation Reflex
• Pulmonary irritant reflexes
– Reflex constriction to prevent particulates
from entering lungs
– Stimulate cough in trachea & bronchi, sneeze in
nasal cavity
• Inflation reflex
– Stretch receptors respond to lung inflation
– Inhibitory signals sent to allow expiration to
occur
– Hering-Breuer Reflex
Control of ventilation: blood CO2
• Chemoreceptors control rate & depth of
breathing by measuring PCO2, PO2, pH
– Hypoventilation = hypercapnia
– Hyperventilation = hypocapnia
• reflex control of ventilation
– goal: to maintain relatively constant PCO2 = 40 mm Hg
• chemoreceptors in ventral medulla
–
–
–
–
–
increased arterial PCO2 = inc [H+] blood
CSF = CO2 crosses blood blain barrier to stimulate receptors
Periphery = rise in [H+] decreases blood pH = stimulus
In the brain, CO2 levels directly stimulate receptors
in the periphery, H+ levels provide the stimulus
Peripheral
chemoreceptors
Effects of blood PO2 on
ventilation
• Indirect influence by changing
chemoreceptor sensitivity to CO2
– low PO2 = increased sensitivity
– high PO2 = decreased sensitivity
• effect of breathing pure oxygen
– dilutes effect of CO2
• Chronic CO2 exposure
– diminished response (emphysema)
Hemoglobin
Hemoglobin
• 2 α & 2 β chains = quaternary structure
• 4 hemes = each heme has one Fe and will
bind with one oxygen molecule
• 280 million Hb per RBC x 4 = >1 billion
molecules of oxygen per RBC
• Hb + O2 = oxyhemoglobin
• Hb - O2 = deoxyhemoglobin
• oxygen saturation = statistical average of
all oxygen bound relative to total amount
that can be bound
What binds to hemoglobin?
•
•
•
•
•
oxyhemoglobin = Hb + O2
deoxyhemoglobin = Hb - O2
carbaminohemoglobin = Hb + CO2
carboxyhemoglobin = Hb + CO
methemoglobin = Fe3+ instead of Fe2+
– cannot bind oxygen
– normally represents 1-2% of Hb
• Sulfhemoglobin = Hb + Sulfur
Unusual conditions
• Sulfhemoglobinemia
– Increased amounts of sulfur, usually drug induced
– Blood is green due to binding of sulfur to Hb
• Methemoglobinemia
–
–
–
–
Increased amount of Fe3+ on Hb
Blood appears chocolate brown in color
Patients look “blue”
NOTE: Venous blood is not blue in normal people!! It just looks blue
through skin because veins run deeper than arteries
Hemoglobin concentration
• oxygen carrying capacity of the blood
= maximum amount that can be bound by
Hb
• <normal =anemia
• >normal = polycythemia (common at high
altitudes)
• RBC/Hb production
– erythropoietin
– androgens
Properties of Hb:O2 binding
• Hb binds reversibly with O2
• Molecular oxygen associates and
dissociates from Hb very rapidly
– Blood is in the exchange capillaries less
than one second
• The sigmoid shape of the
oxyhemoglobin dissociation curve is
caused by molecular interactions of
the four heme groups
Loading and unloading
reactions
• Loading reaction
• Unloading reaction
• Determined by:
– PO2 of the environment
– Affinity of Hb for oxygen
Oxyhemoglobin dissociation curve
• Relationship between PO2 and oxygen saturation of Hb
• Oxygen reserve
– 80% saturation even at PO2 of 40 mm Hg
• Effects of high PO2
• Can be modified by physiological and pathological
factors
– pH
– temperature
– 2,3-DPG
Oxyhemoglobin
dissociation curve
Effect of pH, temperature, &2,3 DPG
on Oxygen transport
• incr [H+], PCO2, 2,3-DPG, temperature = decr
affinity of Hb for oxygen = incr unloading
– entire curve shifts to the right of the standard
curve
• decr [H+], PCO2, 2,3-DPG, temperature = incr
affinity of Hb for oxygen = incr loading
– entire curve shifts to the left of the standard
curve
2,3-DPG (diphosphoglyceric acid)
• Product of anaerobic respiration in RBC’s
• increases with decrease in oxyhemoglobin
• result: increased unloading of oxygen at
tissues
• conditions
– anemia
– high altitudes
– transfer maternal to fetal circulation (Hbf)
Shifts in oxyhemoglobin
dissociation curve
Inherited defects in hemoglobin
structure/function
• Sickle cell anemia (HbS)
– valine replaces glutamic acid on β chain
• thalassemia
– Mediterranean ancestry
– 2 forms; α & β thalassemia
– increased γ chain production, decreased
oxygen unloading
Muscle myoglobin
• Special functions
– middleman
– oxygen storage function
• Slow twitch fibers & cardiac muscle cells
• rhabdomyolysis
How is CO2 carried in blood?
• 1/10 = dissolved
• 1/5 = carbaminohemoglobin
• 7/10 = bicarbonate
– CO2 + H20
H2CO3
• Carbonic anhydrase
– in RBC’s
H+ + HCO3-
Chloride shift: tissue level
• Equation shifts to the right
– H2O + CO2
• Steps:
H2CO3
H+ + HCO3-
– CO2 diffuses out of the tissue cells into the blood
– CO2 moved into the red blood cells
– Combines with H2O in the presence of carbonic
anhydrase to produce carbonic acid
– Carbonic acid dissociates producing H+ + HCO3– H+ buffered by hemoglobin, facilitating the offloading
of O2
– net positive charge in RBC results in chloride shift
– Chloride moves into the RBC in exchange for HCO3– Bohr effect
• increased oxygen unloading
• continued H2CO3 production
• enhanced transport of CO2
Chloride Shift: Tissue Level
Chloride shift: Pulmonary capillaries
• Hb oxygenated
• decrease in affinity for H+
• Reverse chloride shift as Cl- moves out and
HCO3- moves in
• HCO3- + H+
H2CO3
• Carbonic acid dissociates to CO2 & H2O
• CO2 expired out
• Remember:
– H+ is buffered by Hb in RBC
– HCO3- goes into the plasma and buffers
incoming H+
Reverse Chloride Shift
Ventilation and acid-base
balance
• Acidosis and alkalosis
• Regulated by respiratory system
– Respiratory acidosis
– Respiratory alkalosis
• Regulated by the kidneys
– Metabolic acidosis
– Metabolic alkalosis
Ventilation during exercise
• Neurogenic
– sensory nerve activity = stimulates respiratory muscles
– cerebral cortex = brain stem alteration of ventilation
• humoral
– cyclic variations in values of PCO2 & pH stimulates
chemoreceptors (small amounts)
• anaerobic threshold and endurance training
– anaerobic threshold = maximum rate of oxygen consumption
attained before blood lactic acid levels rise due to anaerobic
respiration
– adaptations in athletes =incr mitochondria, aerobic
enzymes; incr oxygen utilization by muscles, lower %
oxyhemoglobin in venous blood
Higher altitudes
• Conditions differ
– rapid fatigue: decreased PO2, oxygen content of blood
decreased (PO2 =69-74mmHg, oxyhemoglobin saturation = 9293%)
• Changes in ventilation
– hypoxic ventilatory response: decr arterial PO2 =
hyperventilation = respiratory alkalosis
• mediated by incr in pH, stabilizes after a few days
– cannot increase PO2 greater than inspired air
• Hemoglobin affinity for oxygen decreased
– greater unloading due to 2,3-DPG
• Hemoglobin and RBC production
– tissue hypoxia stimulates increased erythropoietin
– increased viscosity due to increase in RBC’s