Extrinsic diseases - extraparenchymal diseases - affect chest wall, pleura, and respiratory muscles.</li></ul>Physiologic Changes in Restrictive Lung Disease <br /><ul><li>Characterized by reduced lung volume >> reduced total lung capacity (TLC)
Decreased measures of forced vital capacity (FVC) and forced expiratory volume (FEV1). Ratio of FEV1/FVC remains normal
Consequence of reduced pulmonary compliance >> attributed to accumulation of parenchymal scar tissue
Impaired gas exchange --- Resting arterial blood gas is normal >> Exercise-induced hypoxemia </li></ul>Idiopathic Pulmonary Fibrosis<br /><ul><li>Chronic, progressive and lethal --- characterized by fibrosis of pulmonary interstitium of unknown etiology.</li></ul>Epidemiology: Affects elderly persons with mean age of 66 years --- more frequent in men.<br />Clinical Manifestations<br /><ul><li>Latency period
May last one decade --- asymptomatic but have histologically-proven IPF >> progresses toward symptomatic IPF.
Chronic fibrosing interstitial pneumonia associated with a histological pattern of usual interstitial pneumonia (UIP).
Patchy interstitial fibrosis, often in subpleural and/or paraseptal distribution, alternating with areas of normal lung.
Fibrosis is heterogeneous (different ages) with architectural destruction, and dense scarring with honeycombing</li></ul>Disease Course<br /><ul><li>Survival is poor --- mean survival ranging from 2 to 4 years after diagnosis.
Suppressing inflammation prevents progression to pulmonary fibrosis --- However, response to steroids is usually poor </li></ul>Pathogenesis<br /><ul><li>Original hypothesis --- unknown stimuli injure lung resulting in chronic inflammation, fibrogenesis and end-stage fibrotic scar.
Recent studies challenged the concept that inflammation is driving force in development of IPF.
Evident from disappointing effects of anti-inflammatory treatment
Increasing evidence that changes present in IPF result from sequential alveolar epithelial injury and abnormal wound repair.
Injuries induce alveolar epithelial damage resulting in necrosis, fibrin deposition (hyaline membranes) and hemostasis
Secrete growth factors and induce proliferation and differentiation to myofibroblasts that secrete proteins (collagens)
Myofibroblasts --- expression of alpha-smooth muscle actin
Responsible for wound contraction, which takes place during development of pulmonary fibrosis.
Production and secretion of collagen and a variety of cytokines, including profibrotic TGF-beta.
Imbalance of pro- and antifibrotic factors >> deposition of extracellular matrix within alveoli >> pulmonary fibrosis.
TGF-beta1 is known to be fibrogenic and is released from injured type I alveolar epithelial cells.
Favors transformation of fibroblasts into myofibroblasts and deposition of collagen
Down-regulates caveolin-1 (inhibitor of pulmonary fibrosis -- restoring alveolar epithelial repair processes)</li></ul>Pneumoconioses<br /><ul><li>Caused by inhalation of mineral dust, nearly always in occupational settings.
Develop after many years of cumulative exposure; often diagnosed in older individuals, long after onset of exposure. </li></ul>Coal Worker’s Pneumocoiosis<br /><ul><li>Accumulation of coal dust in lungs and tissue's reaction to its presence.
Leading to pulmonary dysfunction, respiratory insufficiency, pulmonary hypertension, and cor pulmonale </li></ul>Silicosis <br /><ul><li>Potentially fatal, irreversible, fibrotic pulmonary disease --- develop subsequent to inhalation of large amounts of silica dust.
Decades of exposure >> slowly-progressing, nodular, fibrosing pneumoconiosis.
Dyspnea is usually first manifestation; at first, it is provoked by exertion, but later it is present even at rest.
Accompanied by a cough associated with production of sputum.
Chest x-rays reveal irregular linear densities, particularly in both lower lobes.
With advancement of pneumoconiosis, a honeycomb pattern develops.
May remain static or progress to respiratory failure, cor pulmonale, and death. </li></ul>Granulomatous Diseases<br />Sarcoidosis <br /><ul><li>Systemic disease of unknown cause characterized by noncaseating granulomas in many tissues and organs.
Unpredictable course characterized by either progressive chronicity or periods of activity interspersed with remissions
Usually recover with minimal or no residual manifestations.</li></ul>Hypersensitivity pneumonitis <br /><ul><li>Immunologically mediated lung disorders caused by intense, prolonged exposure to inhaled organic antigens.
Farmer's lung results from exposure to dusts generated from harvested humid, warm hay
Permits rapid proliferation of the spores of thermophilic actinomycetes.
Pigeon breeder's lung (bird fancier's disease) is provoked by proteins from serum, excreta, or feathers of birds.
Humidifier or air-conditioner lung is caused by thermophilic bacteria in heated water reservoirs.
Categorized as acute, subacute, and chronic progressive -- based on length and intensity of exposure
Epidemiology: Prevalence varies by region, climate, and farming practices --- mean age is 53 years.
Leukocytosis and neutrophilia, elevated ESR, and C-reactive protein, and hypergammaglobulinemia
Precipitating antibodies to offending antigen are commonly present --- marker or exposure</li></ul>Pulmonary alveolar proteinosis (PAP) <br /><ul><li>Characterized radiologically by bilateral patchy asymmetric pulmonary opacifications
Characterized histologically by accumulation of acellular surfactant in the intra-alveolar and bronchiolar spaces. </li></ul>Classification: Primary (or acquired), secondary and congenital PAP --- different pathogenesis but similar histologic changes <br />Epidemiology: Rare --- M:F = 4:1. Age of onset varies from 20-50 years old <br />Morphology<br /><ul><li>Characterized by a peculiar granular precipitate within alveoli, causing focal-to-confluent consolidation of large areas of lungs
On section, turbid fluid exudes from these areas >> increase in size and weight of lung.
Alveolar precipitate is periodic acid-Schiff positive and also contains cholesterol clefts.
Develops with conditions involving functional impairment or reduced numbers of alveolar macrophages.
Hematologic malignancies, particularly chronic myeloid leukemia and lymphomas
Occupational exposures, particularly mineral dusts (silica) and fumes
Infections, including those caused by Nocardia, Mycobacterium tuberculosis, and fungal infections</li></ul>Clinical Manifestations<br /><ul><li>Nonspecific respiratory difficulty of insidious onset, cough, and abundant sputum containing chunks of gelatinous material.
Progressive dyspnea, cyanosis, and respiratory insufficiency may occur, but some patients tend to have a benign course.
Congenital PAP: fatal respiratory disorder that is usually immediately apparent in the newborn.
Develops progressive respiratory distress shortly after birth</li></ul>Prognosis<br /><ul><li>Very good, with achievement of complete remissions in many patients with whole-lung lavage, but relapses may occur.
GM-CSF therapy is effective in 50% of patients
Congenital PAP responds favorably to lung transplantation.</li></ul>RESTRICTIVE LUNG DISEASES 2<br />Pulmonary Surfactant<br /><ul><li>Dipalmitoyl phosphatidylcholine (DPPC), or lecithin, is functionally the primary phospholipid.
Four surfactant proteins (SPs) expressed by respiratory epithelial cells, designated as SP-A, SP-B, SP-C and SP-D.
Surfactant components are synthesized, secreted and recycled by type II pneumocytes in alveolus. </li></ul>Lung Immaturity in Premature Infants <br /><ul><li>Immaturity of the lungs poses one of most common and immediate threats to viability of low-birth-weight infant.
Lining cells of fetal alveoli do not differentiate into type I and type II pneumocytes until late pregnancy.
Composition of lung surfactant changes as fetus matures:
Concentration of lecithin increases rapidly at beginning of 3rd trimester and rises rapidly to reach a peak near term
Most of lecithin in mature lung is dipalmitate -- in immature lung it is less-surface-active alpha-palmitate species
Phosphatidylglycerol starts to increase only at 35 weeks and is found to be predictive of fetal lung maturity
Before 35th week, immature surfactant contains a higher proportion of sphingomyelin than adult surfactant.
Pulmonary surfactant is released into amniotic fluid, which can be sampled by amniocentesis to assess maturity of fetal lung.
Lecithin-to-sphingomyelin ratio (L/S ratio) above 2:1 >> fetus will survive without respiratory distress syndrome.
After 35th week, appearance of phosphatidylglycerol in amniotic fluid is best proof of the maturity of fetal lungs.</li></ul>Hyaline Membrane Disease (HMD) <br /><ul><li>Acute lung disease of premature newborns caused by surfactant deficiency.</li></ul>Epidemiology<br /><ul><li>Associated with prematurity --- related to a relative lack of mature type II epithelial cells of alveolus (type II pneumocytes).
Twice as common in boys as in girls at every gestational age.</li></ul>Pathogenesis<br /><ul><li>Result of anatomic pulmonary immaturity and a deficiency of surfactant.
Absence of surfactant results in poor pulmonary compliance, atelectasis (failure of pulmonary alveoli to expand).
Atelectasis results in perfused but not ventilated alveoli >> decreased gas exchange, severe hypoxia and acidosis.</li></ul>Pathology<br /><ul><li>Gross appearance.
Microscopy confirms atelectasis, with air limited to bronchioles.
Interstitial edema --- result of transudation of fluid into the interstitium from capillary leak.
Hyaline membranes are found at boundary of air-filled bronchioles and collapsed alveoli.
Separate from bronchial wall at 36–48 hours and are cleared by alveolar macrophages.
Airways containing hyaline membranes are surrounded by collapsed acini of surfactant-deficient lungs.
Consequence of injury to bronchiolar and alveolar lining.
Physical: shear forces on epithelium at the air-liquid interface >> alveoli collapse.</li></ul>Clinical Presentation<br /><ul><li>First symptom within an hour of birth: increased respiratory effort -- forceful intercostal retraction and use of neck muscles.
Respiratory rate > 100 breaths/min, expiratory grunting (due to partial closure of glottis), nasal flaring and cyanosis.
In severe cases, infant becomes progressively obtunded and flaccid.
Long periods of apnea ensue, and the infant eventually dies of asphyxia.</li></ul>Laboratory Studies<br /><ul><li>Arterial blood gas studies show hypoxemia, hypercapnia, and mixed respiratory and metabolic acidosis.
Respiratory acidosis due alveolar atelectasis (decreased gas exchange >> increased blood carbon dioxide and decreased pH)
Metabolic acidosis results from poor tissue perfusion and anaerobic metabolism (hypoxemia >> production of lactic acid). </li></ul>Imaging<br /><ul><li>Mild to moderate cases of HMD.
Generalized acinar collapse that results from surfactant deficiency.
Chest radiographs demonstrate granularity that evolved to generalized hazy opacities to clearing</li></ul>Evaluation of Lung Maturity by Amniotic Fluid Analysis <br /><ul><li>Tests of fetal lung maturity -- which measure surfactant obtained by amniocentesis or collected from vagina.
Risk of HMD is low when lecithin/sphingomyelin ratio is > 2, and phosphatidylglycerol is present.</li></ul>Prevention: Giving mother betamethasone or dexamethasone at least 48h before premature delivery induces fetal surfactant production<br />Complications<br /><ul><li>Major complications related to anoxia and acidosis:
Results from oxygen toxicity --- infants maintained on a positive-pressure respirator with high oxygen tensions
Respiratory distress reflected in hypoxia, acidosis, oxygen dependency, and onset of right-sided heart failure.
Radiographs: change from complete opacification >> spongelike appearance (lucent areas with denser foci).
Microscopic examination: hyperplasia of bronchiolar epithelium and squamous metaplasia in bronchi and bronchioles.
Atelectasis, interstitial edema, and thickening of alveolar basement membranes </li></ul>Evolving Nomenclature <br /><ul><li>‘Hyaline membrane disease’ is now less commonly used in clinical practice
‘Respiratory distress syndrome’ is used to denote surfactant, but ‘surfactant deficiency disorder’ has been proposed.</li></ul>Risk Factors for Hyaline Membrane Disease <br /><ul><li>Cesarean section
Poor glycemic control leads to preterm delivery
Hyperglycemia induces endothelial dysfunction and nitric oxide-depended vasodilatation.
NO is a uterine relaxant -- decreased synthesis of NO in uterus is associated with initiation of labor.</li></ul>Acute Respiratory Distress Syndrome (Synonym: adult respiratory distress syndrome)<br /><ul><li>Initiated by damage to alveolar epithelium and pulmonary capillary endothelium (diffuse alveolar damage)
Followed by increased permeability into lung interstitium and alveolar spaces (noncardiogenic pulmonary edema).
High mortality rate, survivors appear to recover completely but tests of lung function show mild restrictive or diffusion defect.
Hypoxemia from intrapulmonary shunting manifests clinically as cyanosis refractory to oxygen therapy. </li></ul>Pathogenesis of Diffuse Alveolar Damage <br /><ul><li>Type I alveolar pneumocyte and capillary endothelial cell are exceptionally thin >> vulnerable to non-specific damage.
Necrosis of type I alveolar pneumocyte and capillary endothelial cell.
Type I alveolar epithelial cells show cytoplasmic blebbing >> necrosis resulting in denudation of basement membrane
Similar blebbing seen in alveolar capillary endothelium but denudation of basement membrane is seldom observed
Increase in alveolar and pulmonary capillary permeability.
Escape of protein-rich exudates into interstitial and alveoli, loss of alveolar lining film and pulmonary collapse.
Decrease in lung compliance increases work of breathing and leads to respiratory muscle fatigue.</li></ul>Clinical Presentation<br /><ul><li>Characterized by acute dyspnea and hypoxemia after event (trauma, sepsis, drug overdose, transfusion, or aspiration)
Onset of lung injury >> dyspnea with exertion >> progresses to severe dyspnea at rest, tachypnea, anxiety, agitation
Associated hypotension, peripheral vasoconstriction with cold extremities, cyanosis of lips and nailbeds may occur.</li></ul>Diffuse Alveolar Damage <br /><ul><li>Exudation.
Lasts about 1 week -- lungs are wet, heavy, dark and airless -- cut surface exudes heavily bloodstained watery fluid.
Collapse of alveoli, intense congestion of capillaries, interstitial edema and distension of lymphatics.
At air/tissue interface respiratory movements deposit a fibrin-rich exudate mixed with necrotic epithelial debris
Compact into a thin layer that covers an epithelial basement membrane >> formation of hyaline membranes.
Honeycombing suggests extensive lung fibrosis with alveolar destruction >> Presence of thick-walled, air-filled cysts.
Myofibroblasts contracture -- results in harmful distortion of bronchioloalveolar architecture and shrinkage of lungs.
Fibroblasts proliferate and lay down collagen, leading to development of interstitial fibrosis.
Fibrosis by accretion: incorporation of alveolar collagen into interstitium as basement membrane is formed.
Increase in lung collagen can be detected --- Survivors of ARDS may suffer from debilitating fibrotic lung disease.</li></ul>Etiology of Adult Respiratory Distress Syndrome <br /><ul><li>Entrance to lungs directly via airways, e.g. high oxygen, poisonous gases and metallic fumes.
Penetrate chest wall to damage lungs (e.g. ionizing radiation) or reach lungs via bloodstream, (ingested or injected).
Due to high partial pressure of oxygen for hypoxemia treatment >> intracellular production of active oxygen radicals.
Earliest ultrastructural change is swelling of endothelial cells; cytoplasm becomes grossly edematous and vacuolated.
Swelling and fragmentation of type I epithelial cells follows --- become separated from their basement membrane</li></ul>Prognosis<br /><ul><li>Survivors frequently have significant functional impairment even 1 year after discharge.
Spirometry and lung volumes normalize within 6 months, but diffusing capacity remains diminished at 1 year.
Health-related quality of life is below normal, however, no patient remains oxygen-dependent at 12 months</li></ul>NON INFECTIOUS UPPER RESPIRATORY TRACT DISORDERS<br /> <br />Vocal Cord Nodules and Vocal Cord Polyps<br /><ul><li>Tissue growths that develop on vocal cords --- most often in heavy smokers or those who impose great strain on vocal cords </li></ul>Vocal Cord Nodules (synonym: singer’s nodule)<br /><ul><li>Localized, benign growths on medial surface of true vocal folds that are commonly believed result of phonotrauma.
Smooth, rounded, and sessile --- Bilateral with location at junction of anterior and middle third of vocal cord.
Most often observed in women aged 20-50 years, but are also found commonly in children (Boys>Girls) prone to shouting</li></ul>Vocal Cord Polyps<br /><ul><li>Unilateral with broad spectrum of appearances -- hemorrhagic to edematous, pedunculated to sessile, gelatinous to hyalinized
Pedunculated -- involve free edge of anterior third of vocal cord mucosa.
Result from phonotrauma; however, event that triggers formation is vocal cord bleeding. </li></ul>Histopathology<br /><ul><li>Both covered by squamous epithelium
Core is a loose myxoid connective tissue -- fibrotic or punctuated by numerous vascular channels.
Characteristically change character of voice with progressive hoarseness >> never give rise to cancers. </li></ul>DIagnosis<br /><ul><li>Videostrobolaryngoscopy (or stroboscopy) is most sensitive for detecting laryngeal lesions
Demonstrate subtle differences in appearance, pliability, and mucosal wave characteristics.
Remains clinical gold standard for assessing properties of glottal phonatory function. </li></ul>Squamous Papilloma of Larynx<br /><ul><li>Most common benign laryngeal tumor -- located on true vocal cords -- form soft, raspberry-like excrescences
Histologically -- slender, finger-like projections supported by fibrovascular cores and covered by stratified squamous epithelium
Arise as multiple tumors, usually in children -- tendency to recur frequently and to spread downward >> trachea, and bronchi.
Known as ‘recurrent respiratory papillomatosis’. </li></ul>Epidemiology<br /><ul><li>Bimodal distribution -- initial peak in childhood (juvenile-onset SP) and a second peak in adulthood (adult-onset SP).
Children: diagnosed at 2–3 years of age, male-to-female ratio is approximately equal
Adult: manifests in age range of 20-40 years. Male-to-female ratio is estimated to be 4:1</li></ul>Clinical Presentation<br /><ul><li>Larynx is most frequently affected site and hoarseness is most common presenting symptom.
Other symptoms include: voice change, foreign body sensation, cough, choking episodes, inspiratory wheezing
Stridor: whistling sound with inspiration resulting from turbulent air flow; indicates obstruction of larynx</li></ul>Etiology: Caused by low-risk human papillomavirus (HPV) types 6 and 11. <br />Pathogenesis<br /><ul><li>Juvenile-onset SP results from peripartum transmission of virus from an infected mother.
Condylomas during pregnancy and vaginal delivery appear to be at greatest risk of infecting their newborn.
Mode of transmission of virus in adults is unknown, but sexual transmission is probable.</li></ul>Laryngeal Carcinoma<br /><ul><li>Malignant tumor of epithelial origin that arises from laryngeal mucosa -- Most common cancer of upper aerodigestive tract. </li></ul>Epidemiology: Most commonly affects men (African Americans > Caucasians) 50 - 60 years old who are smokers and use alcohol<br />Etiology<br /><ul><li>Smoking and alcohol.
Palpation of neck looking for enlarged lymph nodes is paramount in patient's evaluation.
Patients presenting with hoarseness should undergo a flexible laryngoscope evaluation.
Malignant lesions appear as friable, fungating, ulcerative masses or as subtle changes in mucosal color.
Extremely vulnerable to secondary infection of ulcerating lesion.
With surgery, irradiation, or combination therapy, many patients can be cured, but ~1/3 die of disease.
Usual causes of death are infection of distal respiratory passages or widespread metastases and cachexia.</li></ul>Sequence of Hyperplasia-Dysplasia-Carcinoma <br /><ul><li>The concept of preinvasive stages
Encompassed within laryngeal squamous epithelium -- not breach basement membrane to reach lamina propria.
Transition from a normal epithelium to squamous cell carcinoma of larynx is a lengthy, multistage process
Progressive accumulation of genetic changes >> selection of a clonal population of transformed epithelial cells.
Histological changes ranges from simple squamous hyperplasia to atypical hyperplasia to carcinoma in situ.
Undulating outer densely keratinized layer covering large papillary fronds
Sharply circumscribed deep margin composed of rows of bulbous extremely well-oriented downgrowths.
Stroma is infiltrated by abundance of chronic inflammatory cells.
Well circumscribed and clearly demarcated from adjacent mucosa.
Metastasis is rare, but growth is inexorable if untreated and the tumor can result in the patient's death.
Etiology and clinical presentation is same as laryngeal squamous cell carcinoma. </li></ul>Metastases<br /><ul><li>Cervical lymph nodes: Single most important prognostic factor in squamous cell carcinoma of head and neck.
Distant metastases from laryngeal SCC are significantly less frequent than from other human malignancies
Lung metastases are the most commonly found, followed by metastases to bone and liver. </li></ul>Imaging: Neck instrumental investigation is mandatory -- CT scanning and MRI -- accurate in clinical staging <br />Nasopharyngeal Carcinoma<br /><ul><li>Carcinoma arising in nasopharyngeal mucosa that shows microscopic evidence of squamous differentiation</li></ul>Epidemiology<br /><ul><li>Uncommon in U.S., but common among Southeast Asians
Bimodal age distribution: peak in late childhood (10-20 years of age), and a second peak occurs in people aged 50-60 years.
Occurs more frequently in men, with a 2:1 male-to-female ratio. </li></ul>Morphology<br /><ul><li>Gross appearance: Discrete raised nodule or a frankly infiltrative fungating mass.
Common site of origin is lateral wall of nasopharynx (fossa of Rossenmüller - behind opening of Eustachian tube)
HLA locus A and B antigen association in Chinese with nasopharyngeal carcinoma is well established.
HLA B17 and HLA Bw46 are associated with increased risk.</li></ul>Clinical Presentation<br /><ul><li>Painless neck mass representing unilateral or bilateral enlargement of upper cervical lymph nodes (lymph node metastases)
Ear pain, serous otitis media, and ipsilateral hearing loss may occur (due to Eustachian tube obstruction)
Nasal obstruction with rhinorrhea and epistaxis (due to presence of tumor mass in the nasopharynx).
Features of more advanced disease associated with superior extension of tumor
Headaches indicate invasion of the base of skull.
Ophthalmoplegia (paralysis of motor nerves of eye) indicates cavernous sinus invasion with damage of cranial nerves
Palsy of 5th and 6th CNs causes diplopia, facial pain and numbness; palsy of 3rd CN causes ptosis </li></ul>Laboratory Studies<br /><ul><li>Positive serology against Epstein-Barr virus is found in close to 100% of nonkeratinizing squamous cell carcinoma types
IgA against viral capsid antigen and IgG/IgA against early antigens -- most extensively used diagnostic tool
Test for elevated levels of circulating Epstein-Barr virus DNA or RNA by quantitative PCR in the plasma or serum </li></ul>Pathogenesis<br /><ul><li>Epstein-Barr virus infection -- early event in multistep carcinogenesis of nasopharyngeal carcinoma
Leads to increased expression of EBNA1, LMP1, LMP2, and EBERs in epithelial cells.
EBNA1 is important in replication and maintenance of viral genome during cell division.
LMP1 acts as an oncogenic factor: it upregulates several cellular proteins that inhibit apoptosis
Activation of transcription factors, cellular adhesion molecules, and cytokines.
LMP2 prevents reactivation of the virus by blocking phosphorylation by tyrosine kinases.
EBERs do not encode proteins, but they may be important for oncogenesis and resistance to apoptosis.
Inactivation of the p16 tumor suppressor gene by homozygous deletion -- most common molecular alteration
Cyclin-dependent kinase (CDK) inhibitor - inactivates CKD4 enzyme that phosphorylates and activates Rb protein
Rendering retinoblastoma protein inactive >> removes inhibition provided by Rb protein (cell cycle)</li></ul>Tumor Spread<br /><ul><li>Highly malignant behavior, with extensive loco-regional infiltration, early lymphatic spread, and hematogenous dissemination.
Most common sites of hematogenous deposits are, in descending order of frequency, bone, liver, and lung.
Natural history of disease is short, with most metastases diagnosed within 18 months after appearance of first symptoms</li></ul>Imaging<br /><ul><li>CT scanning and MRI of head and neck used to determine tumor extent, base of skull erosion, and cervical lymphadenopathy. </li></ul>Prognosis<br /><ul><li>Nasopharyngeal carcinomas with no distant metastasis are typically treated with nonsurgical means
Surgery is usually reserved for tumors that fail to regress after irradiation.
Because of the high doses of radiotherapy used in this disease, these late toxicities can be significant. </li></ul>ASTHMA 1<br /> <br /><ul><li>Chronic lung disease caused by increased responsiveness of airways > bronchiolar smooth muscle contraction/bronchospasm
Obstruction to air flow – maximal in expiration – and a high pitched wheeze
Lack of early childhood exposure to infectious agents and parasites increases susceptibility to allergic disease
Global microbial burden in early life could deviate immune responses away from allergic responses.
Suspect polymorphisms in CD14 could be protective against allergies in people with high levels of exposure</li></ul>Morphology<br /><ul><li>Sputum: Viscous and yellow (due to myeloperoxidase within eosinophils)
Severe bronchoconstriction that does not respond to drugs that usually abort acute attack.
Begins with mild symptoms of dyspnea >> as airway obstruction worsens, respiratory distress may all be observed.
Abnormally prolonged expiratory phase with audible wheezing. Vital signs show tachycardia and hypertension.
Airflow obstruction might be so extreme as to cause severe cyanosis and even death.
Hypoxemia and hypercapnia develop >> seizures and coma (late signs of respiratory compromise). </li></ul>Imaging: Chest radiography findings are normal or may indicate hyperinflation. <br />Laboratory Studies – non-specific<br /><ul><li>Blood eosinophilia supports diagnosis
Elevated total serum IgE levels observed in allergic patients</li></ul>Arterial Blood Gases<br /><ul><li>Important to determine severity of asthma attack. 4 stages of blood gas progression in status asthmaticus are as follows:
First stage: characterized by hyperventilation with a normal partial pressure of oxygen (PO2).
Second stage: characterized by hyperventilation accompanied by hypoxemia (low PO2) and normal PCO2.
Third stage: hypoxemic (low PO2) but not hyperventilating because of respiratory muscle fatigue. Normal PCO2
Last stage: characterized by a low PO2 and a high PCO2, which occurs with respiratory muscle insufficiency. </li></ul>Pulmonary Function Testing (Spirometry) <br /><ul><li>Primary test to establish asthma diagnosis -- include measurements before and after inhalation of a short-acting bronchodilator
Measures forced vital capacity (FVC), maximal amount of air expired from point of maximal inhalation, and FEV1.
Reduced ratio of FEV1 to FVC, when compared with predicted values, demonstrates the presence of airway obstruction.
Reversibility is demonstrated by increase of 12% and 200 mL after administration of a short-acting bronchodilator. </li></ul>Allergy Skin Test<br /><ul><li>Useful adjunct in individuals with atopy -- Results help guide indoor allergen mitigation.
Two methods: allergy skin tests and blood radioallergosorbent tests (RAST). </li></ul>Loading, Please Wait ... <br />ASTHMA 2<br /> <br />Asthma and Chronic Obstructive Pulmonary Disease <br /><ul><li>Adults with asthma may have an increased risk of developing COPD
Coexisting signs of asthma (reversibility, atopy), chronic bronchitis (sputum) and emphysema (hyperinflation).
Factors such as smoking and repeated episodes of acute bronchitis may facilitate evolution of asthma into COPD.
Coexisting asthma and COPD >> most severe disease based on degree of airflow limitation. </li></ul>Pathogenesis<br /><ul><li>Atopic asthma -- genetic predisposition to type I hypersensitivity (atopy) and exposure to environmental triggers.
Th2 reactions -- bronchial inflammation in which type 2 helper T (Th2) cells (type of CD4 helper T cell) are prominent.
Preceded by IgE-mediated sensitization to common aeroallergens.
Formation of IgE Abs -- inhaled aeroallergens are engulfed by dendritic cells lining airway.
Dendritic cells migrate to lymph nodes >> present antigen to T-cells
Stimulated T-cells (Th2) secrete cytokines >> promote inflammation and stimulate B cells to produce IgE
Usually in episodes associated with temperature inversions -- associated with bronchospasm
SO2, oxides of nitrogen, and ozone are commonly implicated environmental pollutants.
Emotional factors: Psychological stress >> bronchospasm due to vagal efferent stimulation.</li></ul>Bronchiectasis <br /><ul><li>Abnormal and permanent dilatation of conducting bronchi or airways, most often secondary to an infectious process.
Involved bronchi are dilated, inflamed, and easily collapsible >> airflow obstruction and impaired clearance of secretions. </li></ul>Epidemiology: Uncommon in U.S. - more common in females and most commonly presents in their 60s and 70s.<br />Pathogenesis<br /><ul><li>Bronchial obstruction leads to impaired normal clearing mechanisms >> pooling of secretions distal to obstruction
Infection and inflammation of the airway >> necrosis and destruction of surrounding tissue.
Fibrosis causes bronchi to dilate, leading to dilatation of affected bronchi >> vicious cycle of recurrent infections </li></ul>Etiology<br /><ul><li>Categorized as idiopathic, postinfectious, or due to an underlying anatomic or systemic disease
Most patients have no history of lung injury prior to the onset (idiopathic bronchiectasis).
Patients with known history of lung diseases (postinfecitous bronchiectasis) >> pneumonia, childhood infections, TB.
Minimal or silent infections caused by nontuberculous mycobacteria, Mycobacterium avium complex (MAC).
Congenital causes: associated with defects of mucociliary clearance >> first-line defense against pathogenic microorganisms
Generalized bronchiectasis: widespread dilation of bronchi and may be congenital or result from bacterial infection.
Inherited conditions: cystic fibrosis, primary ciliary dyskinesia, hypogammaglobulinemia, and IgG deficiencies </li></ul>Histopathology<br /><ul><li>Intense acute and chronic inflammatory exudation within walls of bronchi and bronchioles
Associated with desquamation of lining epithelium and extensive areas of necrotizing ulceration.
May be squamous metaplasia of remaining epithelium.
Mixed flora cultured from ectatic bronchi, including staph, strep, pneumococci, enteric, anaerobic and microaerophilic bacteria,
Particularly in children: Haemophilus influenzae and Pseudomonas aeruginosa. </li></ul> Diagnosis of Bronchiectasis <br /><ul><li>High-resolution CT scanning (HCRT) is able to detect airway abnormalities
Criteria are internal diameter of bronchus wider than its adjacent artery and failure of the bronchi to taper.
Bronchial wall thickening appears to indicate airway inflammation and may have prognostic implications. </li></ul>Pulmonary Function<br /><ul><li>Spirometry often shows a limitation of airflow, with:
Reduced ratio of forced expiratory volume in one second (FEV1) to forced vital capacity (FVC)
Normal or slightly reduced FVC - may indicate that airways are blocked by mucus, collapse with forced exhalation
FEV1 (in 1 sec): maximum volume that can forcibly blow out in first second after full inspiration, measured in liters.
Air flow can be reduced by increasing resistance to air flow or reducing outflow pressure.
Narrowed airways produce increased resistance, whereas loss of elastic recoil results in diminished pressure. </li></ul>Epidemiology: Men are more likely to have COPD than women -- predominantly in individuals older than 40 years. <br />Chronic bronchitis<br /><ul><li>Affects majority of patients with COPD
Presence of a chronic productive cough for 3 months during each of 2 consecutive years
Airflow limitation in chronic bronchitis is due to narrowing of airway caliber and increase in airway resistance. </li></ul>Differential with Acute Bronchitis <br /><ul><li>Most frequently in children younger than 5 years in association with viral respiratory tract infection
Caused by infections with influenza, parainfluenza, adenovirus, rhinovirus, and respiratory syncytial virus.
Mucosa is acutely inflamed, with acute inflammatory cells and copious secretion of mucus.
Symptoms include cough that produces phlegm that last for no more than 3 weeks.
Repeated viral infections may damage airway lining and lead to bacterial infections of the lower respiratory tract
Most common bacterial pathogen that causes lower respiratory tract infections is Streptococcus pneumoniae.
Also, infections with Mycoplasma, Chlamydia pneumoniae, Moraxella catarrhalis, and H. influenzae </li></ul>Epidemiology: More prevalent in people older than 50 years, and affects males more than females<br />Pathogenesis<br /><ul><li>Smoking
Impairs ciliary movement, inhibits alveolar macrophages, hypertrophy and hyperplasia of mucus-secreting glands.
Retained secretions predispose for infection -- increased risk for bacterial infections H. influenzae and S. pneumoniae
Increase airway resistance via vagally mediated smooth muscle constriction.
Air pollution: In particular traffic-related air pollution in urban areas
Correlate severity and duration of chronic bronchitis with size of bronchial glands.
Measure ratio of thickness of gland layer to thickness of wall. Normal value of 0.4.</li></ul>Emphysema <br /><ul><li>Abnormal, permanent enlargement of air spaces distal to bronchioles, with destruction of walls without fibrosis.
Airflow limitation in emphysema is due to loss of elastic recoil.
Blunt trauma with a fractured rib which punctures the lung. </li></ul>Epidemiology<br /><ul><li>Higher among males than females, among smokers and former smokers than nonsmokers, among those over 40 years old </li></ul>Types<br /><ul><li>Classified according to its anatomic distribution within the pulmonary lobule.
Early emphysematous changes can only be detected microscopically;
Include loss of alveolar walls, resulting in fewer alveolar attachments to bronchioles.
More severe changes characterized by complete loss of most of wall of air spaces, bronchiolar as well as alveolar. </li></ul>Pathogenesis<br /><ul><li>Destruction of alveolar walls due to protease-antiprotease mechanism, aided by imbalance of oxidants and antioxidants.
Results when elastolytic activity increases or antielastolytic activity is reduced.
Deficiency of antiprotease anzyme alpha-1 antitrypsin (AAT) -- enhanced tendency to develop pulmonary emphysema
AAT is a major inhibitor of proteases (particularly elastase) secreted by neutrophils during inflammation
Increases in leukocytes (neutrophils and macrophages) or release of granules >> increases pulmonary proteolytic activity.
With low levels of serum AAT, elastic tissue destruction is unchecked and emphysema results.
Emphysema results from the destructive effect of high protease activity in subjects with low antiprotease activity.
In smokers, neutrophils and macrophages accumulate in alveoli
Activate transcription of genes that encode TNF and chemokines >> attract and activate neutrophils.
Accumulated neutrophils are activated and release their granules, resulting in tissue damage.
Smoking enhances elastase activity in macrophages
Loss of elastic tissue in walls of alveoli that surround respiratory bronchioles causes bronchioles to collapse during expiration.
Leads to functional airflow obstruction despite the absence of mechanical obstruction.
Several changes are seen: narrow the bronchiolar lumen and contribute to airway obstruction
Goblet cell metaplasia with mucus plugging of the lumen
Inflammatory infiltration of the walls with neutrophils, macrophages, B cells, CD4 and CD8+ T cells
Thickening of the bronchiolar wall due to smooth muscle hypertrophy and peribronchial fibrosis.</li></ul>Clinical Course<br /><ul><li>Clinical manifestations of emphysema do not appear until at least 1/3 of functioning pulmonary parenchyma is damaged.
In advanced disease, signs of right heart failure (decompensated cor pulmonale)
Cyanosis, elevated jugular venous pressure, and peripheral edema can be observed.</li></ul>Laboratory Studies<br /><ul><li>ABG analysis: Mild-to-moderate hypoxemia without hypercapnia progresses to severe hypoxemia and hypercapnia
Hematocrit value: Chronic hypoxemia may lead to polycythemia. Values > 52% in men and > 47% in women
Serum levels below protective threshold of 11 mmol/L. Most common severe variant is the Z allele</li></ul>Imaging<br /><ul><li>Chest radiography.
Hyperinflation of lungs, flattening domes of hemidiaphragms, attenuation or absence of pulmonary vasculature, loss of vascular branching pattern, widened retrosternal space, large focal lucencies (bullae), bronchial wall thickening.
Attenuation of vascular shadows accompanied by hyperlucency of the lungs are signs of emphysema.
With complicating pulmonary hypertension, the hilar vascular shadows are prominent;
With right ventricular enlargement, opacity in the lower retrosternal air space may occur.
CT scanning and HRCT are even better for assessment</li></ul>Pulmonary Function Tests<br /><ul><li>Necessary for diagnosis of obstructive airway disease and for assessments of its severity.
Spirometry is helpful for assessing responses to treatment and disease progression.
Decrease of forced expiratory volume in 1 second (FEV1) is the key to diagnosis.
Increase in total lung capacity, functional residual capacity, and residual volume. The vital capacity is decreased.</li></ul>Clinical Phenotypes<br /><ul><li>Pink puffer.
Emphysema is the primary underlying pathology.
Results from destruction of airways distal to terminal bronchiole, includes gradual destruction of capillary bed
Less surface area for gas exchange -- but less ventilation-perfusion mismatch than blue bloaters.
Compensate by hyperventilation ("puffer" part) -- less hypoxemia (compared to blue bloaters) with "reddish"
Hypoxemia produces constriction of pulmonary arterioles and thus a rise in pulmonary artery pressure.
Increased afterload on the right ventricle causes hypertrophy and ultimately, right-sided heart failure (cor pulmonale)
Causes dilatation and thickening of the wall of main pulmonary artery. </li></ul>Progression of Disease<br /><ul><li>Inexorable decline in respiratory function and progressive dyspnea, for which no treatment is adequate.
Development of cor pulmonale and eventually congestive heart failure, related to secondary pulmonary vascular hypertension,
Death due to respiratory acidosis and coma, right heart failure, and massive collapse of lungs secondary to pneumothorax.
Treatment options include bronchodilators, steroids, bullectomy, and lung volume reduction surgery and lung transplantation. </li></ul>Loading, Please Wait ... <br />DISORDERS OF PLEURA, DIAPHRAGM AND CHEST WALL<br /> <br />Disorders of Pleura<br />Pleural Effusions <br /><ul><li>Accumulation of excess fluid in the pleural cavity
Detected radiologically as obliteration of costophrenic angle, to a massive accumulation that shifts mediastinum and trachea
Inflammation of pleura may result from extension of any pulmonary infection to the visceral pleura, rheumatoid arthritis, disseminated lupus erythematosus, collagen vascular disease, or pulmonary infarction
Sharp, stabbing chest pain on inspiration. Associated with pleural effusion (exudates)
Serous, serofibrinous and fibrinous pleuritis.
Fibrinous exudations generally reflect a later, more severe exudative reaction
Grossly, a grayish-white fibrinous membrane covers the inflamed pleura which lacks its normal luster.
There is frequently a small amount of fluid serous exudate that is cloudy in appearance.
Pleural fluid LDH more than two-thirds normal upper limit for serum
If exudative pleural effusion is determined, the following tests on the pleural fluid should be obtained:
Description of the fluid, glucose level, differential cell count, microbiologic studies, and cytology.</li></ul>Pneumothorax <br /><ul><li>Presence of air or gas in pleural cavity between the visceral and parietal pleura.
Air can enter intrapleural space through a communication from chest wall or through lung parenchyma across visceral pleura.
Classification: may be spontaneous, traumatic, iatrogenous or therapeutic.