2. RESPIRATORY DISEASES

3. Hypoxemia/Hypercapnia
Hypoxemia =/= hypoxia
Hypoxia = decr’d oxygen at tissues
Hypoxemia = low PaO2
V/Q
Ratio ventilation rate(V) compared to perfusion rate(Q) of blood through lung capillaries at alveoli
Normal (healthy) ratio = 0.8

4. PaCO2 dependent on VA (alveolar ventilation rate)
If CO2 removal =/= CO2 prod'n, PaCO2 will increase
If decr’d VA (hypoventilation) incr’d PaCO2 (hypercapnia)
Ventilation not adequate to meet metabolic demands (cells producing more CO2 than lungs can get rid of)

5. If CO2 removed faster than produced, PaCO2 will decrease
If incr’d VA (hyperventilation), decr’d PaCO2 (hypocapnia)
Ventilation exceeds metabolic demands
Occurs with
Anxiety
Head injury
Insufficient O2 in blood (Why would you now breathe faster?)
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?

6. So, with respect to V/Q Ratio:
If V/Q < 0.8, body has “wasted perfusion” (physiologic shunt)
Blood “shunted” past alveoli w/out adequate gas exchange
Due to impaired ventilation
PaO2 decr’d
PaCO2 incr’d

7. 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

8. 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 PaO2 = mm Hg
Impairment of
Brain – headache, confusion,    unconsciousness
Heart – tachycardia, dysrhythmias, incr’d bp
Hypercapnia
CNS depressed (headache    coma)
Body fluids become acidotic

9. Pathologies  vent’n/ perfusion imbalance
Heart disease
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

10. 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 PaCO2 and decr’d PaO2
Also pulmonary hypertension may result (Why?) and/or decr’d CO

12. 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

13. 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

14. Clinical Treatment 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

17. Obstructive Respiratory Diseases
 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

18. Chronic bronchitis Inflammation of bronchi
Most common obstructive disease
Caused by
Irritants (dominant – cigarette smoke)
Also infection
Chronic bronchitis leads to:
Increased mucus secretion
AND thickening of mucus

19. Get diffuse obstruction Lung defense mechanisms compromised
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

20. Pathophysiology Clinical Treatment Airways collapse w/ expiration
V/Q mismatch
PaCO2 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

22. Emphysema
 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

23. Clinical
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
Together, chronic bronchitis + emphysema = Chronic Obstructive Pulmonary Disease (COPD) or Chronic Airway Obstruction (CAO)

25. Asthma Inflammatory disease Reversible
Unlike chronic bronchitis + emphysema
Bronchospasm + mucus hypersecretion + swelling w/ inflamm’n
Bronchospasm = prolonged contraction bronchial smooth muscle
 Obstruction of air flow

26. Due to: 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

27. Due to (cont’d) Common in children
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)
Common in children
Approx 50% of all asthma cases
Remission common (as adults) when asthma begins in childhood

28. Pathophysiology Clinical Treatment 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

31. Restrictive respiratory disease (extrapulmonary)
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

32. Patients more susceptible to lower resp tract infections
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

33. 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

35. 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

36. 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

37. Lung Infections 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

38. 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

39. Atelectasis = collapse of lung (alveoli)
Two types
Compression
External pressure pushes air out of alveoli
Alveoli can’t re-expand (because of increased pressure still on lung)

40. 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

41. Pleura, pleural space affected
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

44. Lung Cancers Bronchogenic carcinoma
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

45. 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)

46. Classification by histological type; each type treated differently
Non-Small Cell Lung Cancer
Treated surgically
Squamous cell carcinoma – most common
Centrally located
Remains localized
Metastasis relatively late
Associated w/ smoking

47. 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

49. Stages common to epithelial cancers
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)
Stages common to epithelial cancers
Irritation  hyperplasia, metaplasia, neoplasia, etc.

51. Clinical signs/symptoms
Coughing, hemoptysis (coughing up blood), dyspnea, chest/pleural pain, atelectasis, hoarseness
Metastasis mostly through lymphatic system
Commonly  adrenals, liver, brain, bone marrow
Treatment depends on tumor type, site