Pseudocolumnar ciliated cells extend to respiratory broncioles; goblet cells extend only to the terminal bronchioles.

Type I cells (97% of alveoloar surfaces) line the alveoli

Type II cells (3%) secrete pulmonary surfactant (dipalmitoyl phosphatidylcholine) which decreases alveolar surface tension. Also serves as precursors to type I and other type II cells. Type II cells prolierate during lung damage. 

Mucous secretions swept out of lungs by ciliated cells. 

Lecithin to sphingomyelin ration of greater tha 2.0 in amniotic fluid is indciative of fetal lung maturity.

EAch bronchopulmonary segment has a 3 degree (segmental) bronchus and 2 arteries (bronchial and pulmonary) in teh center; veins and lymphatics drain along the borders.

Arteries run with Airways

Right lung has 3 lobes; Left lung has 2 lobes and Lingula (homologue of right middle lobe).

Right lung is more common site for inhaled foreign body owing to less acute angle of right main stem bronchus.

Relationship of pulmonary artery to the bronchus at each lung hilus is described by RALS-Right Anterior; Left Superior

4th rib at Horizontal fissure

T8: IVC

T10: Esophagus, vagus (2 trunks)

T12: Aorta (red), thoracic duct (white), azygous vein (blue).

Diaphragm innervated by C 3, 4, 5 (phrenic nerve). Pain from diaphragm can be referred to shoulder.

Quiet breathing:

inspiration-diaphragm

expiration-passive

Exercise:

Inspiration-external intercostals, sclaene muscles, sternomastoids

Expiration-rectus abdominis, internal and external obliques, transversus abdominis, internal intercotals

1. Acute increase in ventilation

2. Chronic increase in ventilation

3. Increase erythropoietin-->Increase hematocrit adn hemoglobin (chronic hypoxia)

4. Increase 2,3-DPG (binds to hemoglobin so that hemoglobin releases more O2)

5. Cellular changes (Increase mitochondria)

6. Increase renal excretion ofbicarbonate (can augment by use of acetazolamide) to compensate for the respiratory alkalosis

7. Chronic hypoxic pulmonary vasoconstriction results in RVH. 

1. Surfactant--produced by type II pneumocytes, decreases alveolar surface tension, increases compliance

2. Prostaglandins

3. Histamine

4.  Angiotensi-converting enzyme (ACE)--angiotensin I-->angiotensin II; inactivates bradykinin (ACE inhibitors increase bradykinin and cause cough, angioedema)

5. Kallikrein--activates bradykinin

 Surfactant--dipalmitoyl phosphatidylcholine (lecithin) deficient in neonatal RDS. Collapsing pressure = 2(tension)/Radius

1. Residual volume (RV)--air in lung after max expiration

2. Expiratory reserve volume (ERV)--air that can stil be breathed out after normal expiration

3. Tidal volume (TV)--air that movesinot lung with each quiet inspiration, typically 500 mL

4. Inspiratory reserve volume (IRV)--air in excess of tidal volume that moves into lung on max inspiration

5. Vital capacity (VC)--TV+IRV+ERV

6. Functional reserve capacity (FRC)--RV+ERV (volume in lungs after normal expiration)

7. Inspiratory capacity (IC)--IRV +TV

8. Total lung capacity--TLC=IRV+TV+ERV+RV

CADET faces right:

CO2

Acid/Altitude

DPG (2,3-DPG)

Exercise

Temperature

Normally lllow resistance, high-compliance system.

PO2 and PCO2 exert opposite effects on pulmonary and systemic circuation. A decrease in PaO2 causes hypoxic vasoconstriction that shifts blood away from teh poorly ventilated regions of the lung to well-ventilated regions of the lung.

1. Perfusion limited--O2 (normal health), CO2, N2O. Gas equlibrates early along the length o fthe capillary. Diffusion can be increased only if blood flow increases. 

2. Diffusion limited--O2 (exercise, emphysema, fibrosis), CO. Gas does not equilibrate by the time the blood reaches the end of the capillary. 

Consequence of pulmonary hypertension is cor pulmonale and subsequent right ventricular failure (jugular venous distention, edema, hepatomegaly). 

V(D)=V(T)x (PaCO2-PeCO2)/PaCO2

Arterial versus expired

Ideally ventilation is matched by to perfusion (ie V/Q=1) in order for adequate gas exchange.

Lung zones:

1. Apex of the lung V/Q =3 (wasted ventilation)

2. Base of the lung V/Q =.6 (wasted perfusion) 

Both ventilation and perfusion are greater and the base of the lung than at the apex. 

With exercise, increased cardiac output, vasodilation of apical capillaires, resulting in V/Q ratio approaching 1. 

Certain organisms thrive in high O2 (TB) flouris in apex.

V/Q--> O=airway obstruciton

V/Q-->infinity=blood flow obstruciotn (physiolgic dead space). 

CO2 trasnported from tissue to lungs in three forms:

1. Bicarbonate (90%)

2. Bound to hemoglobin as carbaminohemoglobin (5%)

3. Dissolved CO2 (5%)

In lungs oxygenation fo hemoglobin promotes dissociation of CO2 from hemoglobin (Haldane effect).

In peripheral tissue, increase H+ shifts curve ot right, unloading O2 (Bohr effect)

Normal alveolar-arterial O2 difference:

[(A-a)DO2]<10 mmHg.

Obstruction of air flow, resulting in air trappings in the lungs, PFTs--Decrease FEV1/FVC ratio (hallmark)

Types:

1. Chronic Bronchitis (Blue Bloater)--produces cough for greater htan three consecutive months in 2 or more years. Hypertorphy of mucous secreting glands in the bronchioles (Reid index >50%). Leading cause is smoking. FIndings: wheezing, crackles, cyanosis.

2. Emphysema (pink puffer)-enlargment of air spaces and decrease recoil resulting from destruction fo alveolar walls. Caused by smoking (centriacinar emphysema) and alpha-antitrypsin defiicency (panacinar emphysema and liver cirrhosis)-->increase elastase activity. FIndings: dyspnea, decrease breath soudns, tachycardia, decrease I/E ratio.

3. ASthma--bronchial hyperresponsiveness causes reversible bronchoconstriction. Can be triggered by viral URIs, allergens, and stress. Findings:  cough, wheezing, dyspnea, tachypnea, hypoxemia, decrease I/E ratio, pulsus paradoxus, Curschmann'sspirals, smooth muscle hypertrophy, mucous plugging.

4. Bronchiectasis--chronic necrotizing infection of bronchi-->dilated airways, purulent sputum, recurrent infections, hemoptysis. Associated with bronchial obstruction, CF, poor ciliary motility, Kartagener's syndrome.

Restricted lung expansion causes decreased lung volumes (decreased VC and TLC). PFTs--FEV1/FVC ratio >80%.

Types:

1. Poor breathing mechanisms (extrapulmonary):

a. poor muscular effort-polio, myasthenia gravis

b. Poor structural apparatus--scoliosis, morbid obesity

2. Interstitial lung disease (pulmonary):

a. Adult respiratory distress syndrome (ARDS)

b. Neonatla respiratory distress syndrome (hyaline membrane disease)

c. Pneumoconioses (coal miner's silicosis, asbestosis)

d. Sarcoidosis

e. Idiopathic pulmonary fibrosis

f. Goodpasturer's syndrome

g. Wegener's granulomatosis

h. Eosinophilic granuloma

Bronchial Obstruction

1. Breath soudns absent/decreased over affected area

2. Resonance decreased

3. Fremitus decreased

4. Trachial deviation toward side of lesion

Pleural effusion

1. Breath sounds decreased over effusion

2. Resonance is dullness

3. Fremitus is decreased

Pneumonia (lobar)

1. May have bronchial breath soudns over lesion

2. Dullness resonance

3. Increased Fremitus

Pneumothorax

1. Breath sounds decreassed

2. Hyperresonant 

3. Absent fremitis

4. Tracheal deviation away from sie of the lesion

Normal: FEV1/FVC=.8

Obstructive <.8

Restrictive: >.8

Obstructive lung volumes>normal (increased TLC, FRC, RV)

Restrictive lung volumes <normal.

In both FEV1 adn FVC reduced.

Diffuse pulmonary interstitial fibrosis cuased by inhaled asbestos fibers. Increased risk fo pleural mesothelioma and bronchogenic carcinoma. Long latency. Ferruginous bodies in lung (asbestos fibers coated with hemosiderin). Ivory-white pleural plaques.

Asbestosis and smoking greatly increase risk fo bronchogenic cancer (Smoking not additive with mesothelioma). Seen in shipbuilders and plumbers. 

Surfactant deficiency leading to increased surface tension, resulting in alveolar collapse. SUrfactant is made by type II pneumocytes most abundantly after 35th week of gestation. The lecithin to sphingomyelin ratio in the amniotic fulid, a measure of lung maturity, is usually <1.5 in neonatal respiratory distress syndrome.

Surfactant--dipalmitoyl phosphatidylcholine

Treatment: aternal steroids before birth; artificial surfactant for infant

Bronchogenic carcioma

Tumors that arise centrally:

1. Squamous cell carcinoma--clear link to Smoking; ectopic PTH related peptide production.

2. Small cell carcinoma--clear link to Smoking; associated with ectopic hormone production (ADH, ACTH); may lead to Lambert-Eaton syndrome

Tumors that arise peripherally:

1. Adenocarcinoma (most common)

2. Bronchioalveolar carcinoma (thought not to be related to smoking)

3. Large cell carcinoma--undifferentiated.

Carcinoid tumor: can cause carcinoid syndrome (flushing, diarrhea, wheezing, salivation)

Metastases: :Very common. Brain (epilepsy), bone (patholgoic fracture), and liver (jaundice, hepatomegaly). 

Small Squamous center

Lung cancer is leading cuase of cancer death. 

Presentation: cough, hemoptysis, bronchial obstruction, wheezing, pneumonic "coin" lesion on xray. 

SPHERE of compilcations:

Superior vena cava syndrome

Pancoast tumor

Horner syndromeEndocrine (paraneoplastic)

Recurrent laryngeal symptoms (hoarsness)

Effusions (pleural or pericardial)

Carcinoma that occurs in apex of lung adn may affect cervical sympathetic plexus, causing Horner's syndrome.

Horner's syndrome--ptosis, miosis anhidrosis

1. Lobar

Pneumococcus most frequently

Intra-alveolar exudate--> consolidation; may involve entire lung

2. Bronchopneumonia

S. aureus, H. flu, Klebsiella, S. pyogenes

Acute inflammatory infiltrates from bronchioles into adjacent alveoli; patchy distribution involving > or = 1 lobes. 

3. Interstitial (atypical) pneumonia

Viruses (RSV, adenoviruses), Mycoplasma, Legionella, Chlamydia

Diffuse patchy inflammation localized ot interstitail areas at alveolar walls; distribution involving > =1 lobes

Lipoxygenase pathway yields Leukotrienes (increase bronchial tone) (Zileuton, Zafirlukast, Montelukast inhibit)

LTB4 is a neutrophil chemotactic agent

LTC4, D4 and E4 function in bronchoconstriction, vasoconstriction, contraction of smooth muscle, and increases vascular permeability

PGI2 inhibits platelet aggregation and promotes vasodilation

Revrsible inhibitors of H1 histmine receptors

1st generation: Diphenhydrmine,dimenhydrinate, chlorpheniramine

Clinical uses: Allergy, motion sickness, sleep aid.

Toxicity: Sedation, antimuscarinic, anti-alpha andrenergic 

2nd generation: Loratadaine, fexofenadine, desloratadine

Clinical uses: Alergy

Toxicity: Far less sedating than 1st generation

Asthma drugs

 Nonspecific B-agonists, B2 agonists

1. Isoproternol-relaxes bronchial smooth muscle (B2). Adverse effect is tchycardia (B1)

2. Albuterol--relaxes bronchial smooth muscle (B2). Use during acute exacerbation.

3. Salmeterol--long-acting agent for prophylaxis. Adverse effects are tremor adn arrhythmia

Asthma drugs

Methylxanthines

Theophylline-likely causes bronchodilation by inhibiting phosphodiesterase, thereby decreasing cAMP hydrolysis. Usage is limited becauseof the narrow therapeutic index (cardiotoxicity, neurotoxicity).

Asthma drugs

Muscarinic Antagonists

Beclomethasone, prednisone--inhibit the sythesis of virtually all cytokines.

Inactivate NF-kB, the transcription factor that induces the production fo TNF-alpha among other inflammtory agents. 1st line therapy for chronic asthma.

1. Zileuton-A 5 lipoxygenase pathway inhibitor. Blocks conversion of arachidonic acid to leukotrienes.

2. Zafirlukast, montelukast-block leukotriene receptors