22-1 chapter 22 lecture outline see powerpoint image slides for all figures and tables pre-inserted...
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22-1
Chapter 22
Lecture Outline
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22-2
Respiratory System
• Anatomy of the Respiratory System
• Pulmonary Ventilation
• Gas Exchange and Transport
• Respiratory Disorders
22-3
General Aspects
• Airflow in lungs– bronchi bronchioles alveoli
• Conducting division– passages for airflow, nostrils to bronchioles
• Respiratory division– distal gas-exchange regions, alveoli
• Upper respiratory tract– organs in head and neck, nose through larynx
• Lower respiratory tract– organs of thorax, trachea through lungs
22-4
Alveolar Blood Supply
22-5
Alveolus
Fig. 22.11
b and c
22-6
Pleurae and Pleural Fluid
• Visceral (on lungs) and parietal (lines rib cage) pleurae
• Pleural cavity - space between pleurae, lubricated with fluid
• Functions– reduce friction– create pressure gradient
• lower pressure assists lung inflation
– compartmentalization• prevents spread of infection
22-7
Pulmonary Ventilation
• Breathing (pulmonary ventilation) – one cycle of inspiration and expiration (respiratory cycle)– quiet respiration – at rest– forced respiration – during exercise
• Flow of air in and out of lung requires a pressure difference between air pressure within lungs and outside body
22-8
Respiratory Muscles• Diaphragm (dome shaped)
– contraction flattens diaphragm
• Scalenes - hold first pair of ribs stationary
• External and internal intercostals– stiffen thoracic cage; increases diameter
• Pectoralis minor, sternocleidomastoid and erector spinae muscles– used in forced inspiration
• Abdominals and latissimus dorsi– forced expiration (to sing, cough, sneeze)
22-9
Respiratory Muscles
22-10
Neural Control of Breathing
• Breathing depends on repetitive stimuli from brain
• Neurons in medulla oblongata and pons control unconscious breathing
• Voluntary control provided by motor cortex• Inspiratory neurons: fire during inspiration• Expiratory neurons: fire during forced expiration• Fibers of phrenic nerve go to diaphragm;
intercostal nerves to intercostal muscles
22-11
Respiratory Control Centers• Respiratory nuclei in medulla
– Ventral Respiratory Group- primary generator of the respiratory rhythm
– Inspiratory neurons and expiratory neurons, p 877, 878– Dorsal Respiratory Group, integrating center that
receives input from other areas (pons, cehmosensitive area in medulla, peripheral chemoreceptors, and stretch and irritant receptors
• Pons– Pontine respiratory group– Receives input from higher brain centers and
transmits signals to VRG and DRG that modify timing of transition from inspiration to expiration
22-12
Respiratory Control Centers
22-13
Input to Respiratory Centers
• From limbic system and hypothalamus– respiratory effects of pain and emotion
• From airways and lungs– irritant receptors in respiratory mucosa
• stimulate vagal afferents to medulla, results in bronchoconstriction or coughing
– stretch receptors in airways - inflation reflex• excessive inflation triggers reflex• stops inspiration
• From chemoreceptors– monitor blood pH, CO2 and O2 levels
22-14
Chemoreceptors
• Peripheral chemoreceptors – found in major blood vessels
• aortic bodies – signals medulla by vagus nerves
• carotid bodies – signals medulla by glossopharyngeal nerves
• Central chemoreceptors – in medulla
• primarily monitor pH of CSF
22-15
Peripheral Chemoreceptor Paths
22-16
Voluntary Control
• Neural pathways– motor cortex of frontal lobe of cerebrum sends
impulses down corticospinal tracts to respiratory neurons in spinal cord, bypassing brainstem
• Limitations on voluntary control– blood CO2 and O2 limits cause automatic
respiration
22-17
Pressure and Flow
• Atmospheric pressure drives respiration– 1 atmosphere (atm) = 760 mmHg
• Intrapulmonary pressure and lung volume
Boyle’s Law: pressure is inversely proportional to volume
• for a given amount of gas, as volume , pressure and as volume , pressure
• Pressure gradients– difference between atmospheric and
intrapulmonary pressure– created by changes in volume thoracic cavity
Inspiration
Put your hands on your rib cage. Inhale. Notice that the thoracic cage moves up and out. Diaphragm moves down (Fig 22-8, A and C Herlihy)
• This movement increases the volume of the thoracic cavity and lungs.
• As the volume in the lung increases, the pressure in the lung decreases (Boyle’s Law)
• P in the lung < atmospheric P so air flows in 22-18
22-19
Respiratory Cycle
22-20
Passive Expiration
• During quiet breathing, expiration achieved by elasticity of lungs and thoracic cage
• Diaphragm relaxes, moves up. Rib cage moves down and in.
• As volume of thoracic cavity , intrapulmonary pressure and air is expelled
22-21
Forced Expiration
• Internal intercostal muscles – depress the ribs
• Contract abdominal muscles intra-abdominal pressure forces
diaphragm upward pressure on thoracic cavity
22-22
Pneumothorax
• Presence of air in pleural cavity– loss of negative intrapleural pressure allows
lungs to recoil and collapse
• Collapse of lung (or part of lung) is called atelectasis
22-23
Resistance to Airflowthe greater the resistance, the slower the flow
• Pulmonary compliance– The ease with which the lungs expand– change in lung volume relative to a change in
transpulmonary pressure
• Bronchiolar diameter– primary control over resistance to airflow– Bronchoconstriction (reduce airflow)
• triggered by airborne irritants, cold air, parasympathetic stimulation, histamine
– Bronchodilation (increase airflow)• sympathetic nerves, epinephrine
22-24
Alveolar Surface Tension
• Thin film of water needed for gas exchange– creates surface tension that acts to collapse
alveoli and distal bronchioles
• Pulmonary surfactant (great alveolar cells)
– decreases surface tension
• Premature infants that lack surfactant suffer from respiratory distress syndrome
22-25
Alveolar Ventilation• Dead air
– fills conducting division of airway, cannot exchange gases
• Anatomic dead space– conducting division of airway
• Physiologic dead space– sum of anatomic dead space and any
pathological alveolar dead space
• Alveolar ventilation rate– air that ventilates alveoli X respiratory rate– directly relevant to ability to exchange gases
22-26
Measurements of Ventilation
• Spirometer - measures ventilation
• Respiratory volumes– tidal volume: volume of air in one quiet breath– inspiratory reserve volume
• air in excess of tidal inspiration that can be inhaled with maximum effort
– expiratory reserve volume• air in excess of tidal expiration that can be exhaled
with maximum effort
– residual volume (keeps alveoli inflated)
• air remaining in lungs after maximum expiration
22-27
Lung Volumes and Capacities
22-28
• Vital capacity– total amount of air that can be exhaled with
effort after maximum inspiration• assesses strength of thoracic muscles and
pulmonary function
• Inspiratory capacity– maximum amount of air that can be inhaled
after a normal tidal expiration
• Functional residual capacity– amount of air in lungs after a normal tidal
expiration
Respiratory Capacities
22-29
Respiratory Capacities
• Total lung capacity– maximum amount of air lungs can hold
• Forced expiratory volume (FEV)– % of vital capacity exhaled/ time– healthy adult - 75 to 85% in 1 sec
• Peak flow– maximum speed of exhalation
• Minute respiratory volume (MRV)– TV x respiratory rate, at rest 500 x 12 = 6 L/min– maximum: 125 to 170 L/min
22-30
Respiratory Volumes and Capacities
• Age - lung compliance, respiratory muscles weaken
• Restrictive disorders compliance and vital capacity (limit amt
lungs can be inflated)
• Obstructive disorders– interfere with airflow by narrowing or blocking
the airway
22-31
Composition of Air• Dalton’s Law: total atmospheric pressure is a sum of the
contributions of the individual gases
• Mixture of gases; each contributes its partial pressure– at sea level 1 atm. of pressure = 760 mmHg– nitrogen constitutes 78.6% of the atmosphere so
• PN2 = 78.6% x 760 mmHg = 597 mmHg
• PO2 = 159
• PH2O = 3.7
• PCO2 = + 0.3
• PN2 + PO
2 + PH2O + PCO
2 = 760 mmHg
22-32
Composition of Air
• Partial pressures (as well as solubility of gas)
– determine rate of diffusion of each gas and gas exchange between blood and alveolus
• Alveolar air– humidified, exchanges gases with blood, mixes with
residual air – contains:
• PN2 = 569
• PO2 = 104
• PH2O = 47
• PCO2 = 40 mmHg
22-33
Air-Water Interface
• Important for gas exchange between air in lungs and blood in capillaries
• Gases diffuse down their concentration gradients
• Henry’s law– amount of gas that dissolves in water is
determined by its solubility in water and its partial pressure in air
22-34
Alveolar Gas Exchange
22-35
Alveolar Gas Exchange
• Time required for gases to equilibrate = 0.25 sec
• RBC transit time at rest = 0.75 sec to pass through alveolar capillary
• RBC transit time with vigorous exercise = 0.3 sec
22-36
Factors Affecting Gas Exchange• Concentration gradients of gases
– PO2 = 104 in alveolar air versus 40 in blood
– PCO2 = 46 in blood arriving versus 40 in alveolar
air
• Gas solubility– CO2 20 times as soluble as O2
• O2 has conc. gradient, CO2 has solubility
22-37
Factors Affecting Gas Exchange• Membrane thickness - only 0.5 m thick
• Membrane surface area - 100 ml blood in alveolar capillaries, spread over 70 m2
• Ventilation-perfusion coupling - areas of good ventilation need good perfusion (vasodilation)
22-38
Concentration Gradients of Gases
22-39
Ambient Pressure and Concentration Gradients
22-40
Lung Disease Affects Gas Exchange
22-41
Perfusion Adjustments
22-42
Ventilation Adjustments
22-43
Oxygen Transport
• Concentration in arterial blood– 20 ml/dl
• 98.5% bound to hemoglobin• 1.5% dissolved
• Binding to hemoglobin– each heme group of 4 globin chains may
bind O2
– oxyhemoglobin (HbO2 )
– deoxyhemoglobin (HHb)
22-44
Oxygen Transport
• Oxyhemoglobin dissociation curve– relationship between hemoglobin saturation
and PO2 is not a simple linear one
– after binding with O2, hemoglobin changes
shape to facilitate further uptake (positive
feedback cycle)
22-45
Oxyhemoglobin Dissociation Curve
22-46
Carbon Dioxide Transport
• As carbonic acid - 90%– CO2 + H2O H2CO3 HCO3
- + H+
• As carbaminohemoglobin (HbCO2)- 5% binds to amino groups of Hb (and plasma proteins)
• As dissolved gas - 5%
• Alveolar exchange of CO2
– carbonic acid - 70% – carbaminohemoglobin - 23%– dissolved gas - 7%
22-47
Systemic Gas Exchange• CO2 loading
– carbonic anhydrase in RBC catalyzes• CO2 + H2O H2CO3 HCO3
- + H+
– chloride shift• keeps reaction proceeding, exchanges HCO3
-
for Cl- (H+ binds to hemoglobin)
• O2 unloading– H+ binding to HbO2 its affinity for O2
• Hb arrives 97% saturated, leaves 75% saturated - venous reserve
– utilization coefficient • amount of oxygen Hb has released 22%
22-48
Systemic Gas Exchange
22-49
Alveolar Gas Exchange Revisited
• Reactions are reverse of systemic gas exchange
• CO2 unloading
– as Hb loads O2 its affinity for H+ decreases, H+ dissociates from Hb and bind with HCO3
-
• CO2 + H2O H2CO3 HCO3- + H+
– reverse chloride shift
• HCO3- diffuses back into RBC in exchange
for Cl-, free CO2 generated diffuses into alveolus to be exhaled
22-50
Alveolar Gas Exchange
22-51
Factors Affect O2 Unloading
• Active tissues need oxygen!
– ambient PO2: active tissue has PO
2 ; O2 is
released
– temperature: active tissue has temp; O2 is
released
– Bohr effect: active tissue has CO2, which
lowers pH O2 is released
22-52
Oxygen Dissociation and Temperature
22-53
Oxygen Dissociation and pH
Bohr effect: release of O2 in response to low pH
22-54
• Haldane effect– low level of HbO2 (as in active tissue) enables
blood to transport more CO2
– HbO2 does not bind CO2 as well as deoxyhemoglobin (HHb)
– HHb binds more H+ than HbO2
• as H+ is removed this shifts the
CO2 + H2O HCO3- + H+
reaction to the right
Factors Affecting CO2 Loading
22-55
Blood Chemistry and Respiratory Rhythm
• Rate and depth of breathing adjusted to maintain levels of:– pH
– PCO2
– PO2
• Let’s look at their effects on respiration:
22-56
Effects of Hydrogen Ions
• pH of CSF (most powerful respiratory stimulus)
• Respiratory acidosis (pH < 7.35) caused by failure of pulmonary ventilation
– hypercapnia: PCO2 > 43 mmHg
• CO2 easily crosses blood-brain barrier
• in CSF the CO2 reacts with water and releases H+
• central chemoreceptors strongly stimulate inspiratory center
– “blowing off ” CO2 pushes reaction to the left CO2 (expired) + H2O H2CO3 HCO3
- + H+
– so hyperventilation reduces H+ (reduces acid)
22-57
Effects of Hydrogen Ions
• Respiratory alkalosis (pH > 7.45)
– hypocapnia: PCO2 < 37 mmHg
– Hypoventilation ( CO2), pushes reaction to the right CO2 + H2O H2CO3 HCO3
- + H+
H+ (increases acid), lowers pH to normal
• pH imbalances can have metabolic causes– uncontrolled diabetes mellitus
• fat oxidation causes ketoacidosis, may be compensated for by Kussmaul respiration
(deep rapid breathing)
22-58
Effects of Carbon Dioxide
• Indirect effects on respiration– through pH as seen previously
• Direct effects CO2 may directly stimulate peripheral
chemoreceptors and trigger ventilation more quickly than central chemoreceptors
22-59
Effects of Oxygen
• Usually little effect
• Chronic hypoxemia, PO2 < 60 mmHg,
can significantly stimulate ventilation– emphysema, pneumonia– high altitudes after several days
22-60
Hypoxia
• Causes:– hypoxemic hypoxia - usually due to inadequate
pulmonary gas exchange• high altitudes, drowning, aspiration, respiratory
arrest, degenerative lung diseases, CO poisoning
– ischemic hypoxia - inadequate circulation– anemic hypoxia - anemia– histotoxic hypoxia - metabolic poison (cyanide)
• Signs: cyanosis - blueness of skin
• Primary effect: tissue necrosis, organs with high metabolic demands affected first
22-61
Oxygen Excess
• Oxygen toxicity: pure O2 breathed at 2.5 atm or greater– generates free radicals and H2O2
– destroys enzymes– damages nervous tissue– leads to seizures, coma, death
• Hyperbaric oxygen– formerly used to treat premature infants,
caused retinal damage, discontinued
22-62
Chronic Obstructive Pulmonary Disease
• Asthma– allergen triggers histamine release– intense bronchoconstriction (blocks air flow)
• Other COPD’s usually associated with smoking
– chronic bronchitis – emphysema
22-63
Chronic Obstructive Pulmonary Disease
• Chronic bronchitis – cilia immobilized and in number– goblet cells enlarge and produce excess
mucus– sputum formed (mucus and cellular debris)
• ideal growth media for bacteria
– leads to chronic infection and bronchial inflammation
22-64
Chronic Obstructive Pulmonary Disease
• Emphysema (barrel chest)– alveolar walls break down
• much less respiratory membrane for gas exchange– healthy lungs are like a sponge; in emphysema, lungs are
more like a rigid balloon
– lungs fibrotic and less elastic– air passages collapse
• obstruct outflow of air• air trapped in lungs
22-65
Effects of COPD
pulmonary compliance and vital capacity
• Hypoxemia, hypercapnia, respiratory acidosis– hypoxemia stimulates erythropoietin release
and leads to polycythemia
• cor pulmonale – hypertrophy and potential failure of right heart
due to obstruction of pulmonary circulation
22-66
Smoking and Lung Cancer
• Lung cancer accounts for more deaths than any other form of cancer– most important cause is smoking (15
carcinogens)
• Squamous-cell carcinoma (most common)– begins with transformation of bronchial
epithelium into stratified squamous– dividing cells invade bronchial wall, cause
bleeding lesions– dense swirls of keratin replace functional
respiratory tissue
22-67
Lung Cancer
• Adenocarcinoma – originates in mucous glands of lamina propria
• Small-cell (oat cell) carcinoma– least common, most dangerous– originates in primary bronchi, invades
mediastinum, metastasizes quickly
22-68
Progression of Lung Cancer
• 90% originate in primary bronchi
• Tumor invades bronchial wall, compresses airway; may cause atelectasis
• Often first sign is coughing up blood
• Metastasis is rapid; usually occurs by time of diagnosis– common sites: pericardium, heart, bones, liver,
lymph nodes and brain
• Prognosis poor after diagnosis– only 7% of patients survive 5 years
22-69
Healthy Lung/Smokers Lung- Carcinoma