– Hypoxia = decr’d oxygen at tissues
– Hypoxemia = low PaO
2
– Ratio ventilation rate(V) compared to perfusion rate(Q) of blood through lung capillaries at alveoli
– Normal (healthy) ratio = 0.8

CO2
A
– If CO
2 removal =/= CO increase
2 prod'n, Pa
CO2 will
– If decr’d V
A
(hypoventilation) incr’d Pa
(hypercapnia)
CO2
• Ventilation not adequate to meet metabolic demands (cells producing more CO can get rid of)
2 than lungs

• If CO
2 removed faster than produced, Pa will decrease
CO2
– If incr’d V
A
(hyperventilation), decr’d Pa
(hypocapnia)
CO2
• Ventilation exceeds metabolic demands
– Occurs with
• Anxiety
• Head injury
• Insufficient O
2 faster?) in blood (Why would you now breathe
– Remember acid/base imbalances: what happens to acid/base balance if you breathe too little? What compound is increased in the blood? Why is this bad?
What would your body do to compensate?

– Blood “shunted” past alveoli w/out adequate gas exchange
– Due to impaired ventilation
– PaO2 decr’d
– PaCO2 incr’d

– Shunting - alveolar spaces nonfunctional
• If extreme physiologic shunt (if alveoli collapsed, edematous, filled w/ exudates), get extreme V/Q mismatch (V=0)
• Can cause:
– Severe hypoxemia
– Administration oxygen does not correct

• If V/Q > 0.8, called dead-space disease
– Q = 0 (again, extreme V/Q mismatch; now due to no perfusion)
– Ventilation not effected physiologically, BUT see incr’d work of breathing
• Also hypercapnia, hypoxemia
• Clinical - variable response
– Hypoxemia if Pa
O2
= 40-50 mm Hg
• Impairment of
– Brain – headache, confusion,    unconsciousness
– Heart – tachycardia, dysrhythmias, incr’d bp
– Hypercapnia
• CNS depressed (headache    coma)
• Body fluids become acidotic


– Incr’d pressures in lung vasculature (pulmonary hypertension)
• W/ valve disorders, CHF, etc.
•  pulmonary arteriosclerosis
 decr
’ d blood volume at lung (hypoperfusion)
– So decr’d Q and V/Q mismatch
• Note: not the same as incr’d perfusion
• Actually, more similar to ischemia to lung tissues

• Pulmonary embolism  hypoperfusion
– Material in pulmonary circulation  “plugged” vessel
– Thromboembolism most common
• Often w/ thrombi from lower extremities
– Same risk factors as w/ systemic thromboembolism
(smoking, hyperlipidemia, hypertension, etc.)
– Most common cause of acute pulmonary disease in US
• ½ deaths occur w/in 2 hrs of embolism in pulmonary circulation
– Pathophysiology
• V/Q mismatch (decr’d Q)  incr’d Pa
CO2 and decr’d Pa
O2
• Also pulmonary hypertension may result (Why?) and/or decr’d CO

• Pulmonary embolism – cont’d
– Clinical – severity varies
• Massive
–  shock, chest pain, tachypnea, tachycardia
• With lung infarct, see pleural pain, pleural effusion, dyspnea
– What does the term infarct mean?
– Treatment
• Prevention
– Eliminate risks associated w/ thrombus formation (stop smoking, etc.)
• Anticoagulants
– Prevent clot formation

• Pulmonary edema
– Excess fluid in lung, so decr’d ventilation
– Lung usually kept “dry” by 3 mechanisms:
1) lymph drainage
2) capillary exchange
3) surfactant lining the alveoli
– Predisposing factors to pulmonary edema related to 3
• Heart disease
– LV failure  incr’d pressures in L heart  incr’d pressures in respiratory (gas exchange) capillaries
– Fluid gets forced out of capillaries  alveoli and between lung cells
– So decr’d gas exchange ability and decr’d lung compliance
– Lymph drainage compensates for awhile

• Capillary injury
– Injury incr’s capillary permeability  fluid forced more easily out of capillaries into alveoli and between cells (as above)
– Decr’s compliance and gas exchange
– Injury to cap’s may be due to chemical, physical lung injury
• Obstruction of lymph system
– If lymph vessels or nodes blocked  little/no drainage of ISF
(so builds up between lung cells and into alveoli)
– Again  decr’d compliance and gas exchange
– Clinical
• Dyspnea, hypoxemia, incr’d work of breathing
– Treatment
• Depends on cause

•  incr’d resistance to air flow and decr’d vent’n
• Due to obstruction
– In lumen of airway (ex: incr’d secretions w/ asthma)
– In airway wall (ex: inflamm’n at bronchial epithelium w/ asthma, chronic bronchitis)
– In structures surrounding smooth muscle (ex: contraction bronchial smooth muscle w/ asthma)
• Most common obstructive diseases: chronic bronchitis, emphysema, asthma
– Difficult expiration

– Irritants (dominant – cigarette smoke)
– Also infection
– Increased mucus secretion
– AND thickening of mucus

– AND thickening of bronchial mucosa layer (w/ hypertrophy & hyperplasia of bronchial epithelium)
• Body’s compensations for chronic irritation
– Tries to guard cells that make up airways from irritation
– Get diffuse obstruction
– Lung defense mechanisms compromised
• Cilia impaired
• Thickened mucus can’t get rid of invaders
– Find incr’d acute respiratory infections

– Pathophysiology
• Airways collapse w/ expiration
• V/Q mismatch
• Pa
CO2 incr’d (hypercapnia); hypoxemia
– Clinical
• Wheezing, shortness of breath
• Exercise tolerance decr’d
• Productive cough (sputum coughed up)
• Incr’d risk respiratory infections
– Treatment
• Prevention -STOP SMOKING
• Bronchodilators open lumen
• Expectorants decr mucus thickness

•  destruction of alveolar walls, so decr’d elastic recoil of alveoli
– Causes decr’d ability to expire
– Note: obstruction not due to physical substance causing blockage; rather obstruction to gas exchange, air movement due to change in lung tissue
• Genetic predisposition
• Pathophysiology
– Destruction of alveolar septa (shared cell membr between
2 alveoli)
– Large air spaces develop (bullae)
– Airways enlarge

– Dyspnea on exertion developing to dyspnea at rest
• No cough; little sputum (REMEMBER: no incr’d mucus)
• Tachypnea (incr’d rate of breathing)
– Treatment - as per chronic bronchitis

– Unlike chronic bronchitis + emphysema
– Bronchospasm = prolonged contraction bronchial smooth muscle


– Hyperactive immune response to allergens
• Prod incr’d amounts of IgE
• Bind mast cells in airways
•  Much histamine released
•  Hyperactivated immune, inflammatory responses
• Also, bronchospasm, incr’d mucus and edema w/ incr’d capillary permeability

– Neural dysfunction with dysfunctional autonomic nervous system response
• Disrupted or hyperactive irritant receptors (?)
•  Bronchospasm, perhaps also due to mast cell involvement (so all histamine effects noted above)
– Approx 50% of all asthma cases
– Remission common (as adults) when asthma begins in childhood

• Pathophysiology
– Vascular congestion, edema
–  Formation of thick mucus  impaired ciliary function
–  Incr’d work of breathing
– Hyperventilation
• Clinical
– Wheezing, nonproductive cough, tachycardia, mucus formation
• Treatment
– Eliminate cause of attack
– Drugs to reverse bronchospasm

• Lung tissue is normal, other disorders affect ventilation
• Chest wall restrictions
– Work of breathing incr’s and ventilation decr’s
•  Hypoventilation, hypercapnia, hypoxemia
• Impaired lung defenses
– “Stagnant” air (doesn’t move out of body as it should)
– If contains microbes or invaders, incr’d risk of infecting airways -- more time to grow, replicate

– Due to
• Chest wall deformities
• Fat overlaying chest muscles in very obese patients
• Neuromuscular diseases (ex: polio, muscular dystrophy, others)
– Dyspnea
– Patients more susceptible to lower resp tract infections
– Over time, can  respiratory failure

• Intrinsic restrictions –
– Acute or chronic
– Chronic
• Chronic Intrinsic Restrictive Lung Disease (CIRLD)
– Excessive fibrous/connective tissue deposits in lung
»  Lung injury  scar tissue formation
»  Lung stiffness, so compliance decr’s
– Due to:
» Irritant inhalation, infection, autoimmune dysfunction
– Leads to
» Decr’d ventilation (harder to breathe)
» Hypoxemia
» V/Q mismatch

– Acute restrictions
• ARDS - Adult Respiratory Distress Syndrome
– Due to injury to lung
» Direct: inhaling toxic gases, trauma
» Indirect: systemic disorder  incr’d chemical mediators of infection (thromboxanes, etc.)
» (Biochem’s similar to prostaglandins; patients either release in too high concentrations, or lung cells too sensitive to them)
– Pathophysiology:
» Acute lung inflammation 
» Severe pulmonary edema
»  Diffuse alveolo-capillary injury
»  Severe pulmonary edema, hemorrhage

– Pathophysiology – cont’d
» Get decr’d compliance, decr’d alveolar ventilation, incr’d pulmonary vasoconstriction
» Fibrosis within 7 days of injury  ARDS
– Clinical
» Rapid, shallow breathing
» Marked dyspnea
» Hypoxemia unrelieved by oxygen administration
» Fatal in ~ 70% of cases
– Treatment
» Mechanical vent’n to incr available oxygen
» Sedation to decr oxygen consumption
» Increase C.O., give diuretics to relieve edema

• When lung defenses decreased
• Pneumonia
– By bacteria or virus
• Common bacteria = strep pneumoniae
• Causes ~70% of all pneumonia
– Pathophysiology
• Pathogens multiply in lung
– Overall, due to decr’d immune response in lung
• Toxins released from microbes
• Bronchial mucosa becomes damaged

– Pathophysiology – cont’d
• Inflammation/edema results
• Exudate found in alveoli
• V/Q mismatch (decreased V)
– Clinical
• Infection  chills/fever/malaise
• Chest edema  cough, pleural pain
• Dyspnea
– Treatment
• Antibiotics – for bacterial infection
• Mechanical ventilation

– Compression
• External pressure pushes air out of alveoli
– Alveoli can’t re-expand (because of increased pressure still on lung)

– Absorption
• Occurs w/ obstruction, when no expiration/inspiration
• “Old” air absorbed from alveolus over time, not replaced
– So alveoli collapse
• Seen post-operatively
– Anesthetics cause incr’d mucus production  obstruction
– Clinical
• Dyspnea, cough, fever

• Pleural effusion = fluid (blood, lymph) in pleural space
– Can cause collapse of lung tissue
• Due to incr’d pressure of fluid pressing on alveoli
• Hemothorax = bleeding into pleural space
• Empyema = infected pleural effusion
– Seen w/ lymph blockage
• Pneumothorax = air/gas in pleural space
– Negative pressure in pleural space destroyed
• Pressure differential nec for proper pressures, recoil
– Due to trauma, secondary to thoracic surgery

– Malignant tumors of mucous membranes
– Larger bronchi
– ~90% of all primary lung cancers
– Epidemic in U.S.
• ~200,000 new cases per year
• Most common of all primary tumors; most frequent cause of cancer death

– Most common cause of bronchogenic carcinoma:
• Cigarette smoking
– Heavy smokers ~25X greater risk than nonsmokers
• Other causes
– Environmental, occupational (breathing in noxious/traumatizing agents, such as asbestos)

– Non-Small Cell Lung Cancer
• Treated surgically
• Squamous cell carcinoma – most common
– Centrally located
– Remains localized
– Metastasis relatively late
– Associated w/ smoking

– Non-small cell cancers – cont’d
• Adenocarcinoma
– Tumors arise in periphery of lung
– Most common in women
– One type = bronchioalveolar cell carcinoma
» Slow growing
» Weak association w/ cigarette smoking
» Low survival rate
» Asymptomatic w/ early metastasis

– Small Cell Lung Cancer
• Treatment by chemotherapy, radiation
• Strongest association w/ cigarette smoking
• 20-25% of all bronchogenic carcinomas
• Oat cell carcinoma
– Cells compressed
– Rapid growth, early metastasis
– Poor prognosis (<5% alive in 2 yrs)
• Irritation  hyperplasia, metaplasia, neoplasia, etc.

– Coughing, hemoptysis (coughing up blood), dyspnea, chest/pleural pain, atelectasis, hoarseness
– Commonly  adrenals, liver, brain, bone marrow