Respiratory SystemRespiratory SystemRespiratory System

ByDr. Carmen Rexach

PhysiologyMt 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 interpleuralspace 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

alveoliNormal lung asthma

Chronic bronchitis

Emphysema

Partial pressure of gases

• Dalton’s law• PN2 + PO2 + PCO2+ PH2O = PATM = 760mmHg• air = 21% O + 78% N

0.21 760

0.78

0.0004 760

760

0.3mm Hg

593mm Hg

159mm 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 O2in 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 factorCID: 2006 (43):188-192

Hyperbaric treatment for diabetic foot ulcers

Before hyperbaric treatment

40 days after hyperbaric treatment & skin graft

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

Oxyhemoglobindissociation curve

Effect of pH, temperature, &2,3 DPG on Oxygen transport

• incr [H+], PCO2, 2,3-DPG, temperature = decraffinity of Hb for oxygen = incr unloading– entire curve shifts to the right of the standard

curve

• decr [H+], PCO2, 2,3-DPG, temperature = incraffinity 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 oxyhemoglobindissociation 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 H+ + HCO3-

• Carbonic anhydrase– in RBC’s

Chloride shift: tissue level• Equation shifts to the right

– H2O + CO2 H2CO3 H+ + HCO3-

• Steps:– 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 = 92-93%)

• 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