IUHS Student-2-Student USMLE Step 1 Recall

                                                    Respiratory

                                         Obstructive Lung Diseases

Asthma

Status Asthmaticus - a condition of severe, prolonged asthma...

mediators release histamine, bradykinin, the leukotrienes C, D, and E...

platelet activating factor...

prostaglandins (PGs) E2, F2alpha, and D2...

these all produce an intense, immediate inflammatory reaction involving bronchoconstriction, vascular congestion, and edema formation...they also evoke prolonged contraction of airway smooth muscle and mucosal edema, the leukotrienes may also account for some mucus production and impaired mucociliary transport...

these cells also amplify bronchoconstriction by elaborating endothelin-1 and promoting vasodilatation through the release of nitric oxide, PGE2, and the 15-hydroxyeicosatetraenoic acid products of arachidonic acid metabolism...

eosinophilic infiltrates...

dependent on IgE controlled by B and T lymphocytes...dendritic cells capture and process the antigen...after taking antigen to lymph node, T cells in the presence of IL-4 lead to differentiation into Th2...B lymphocytes start producing IgE instead of IgM or IgG...

allergic asthma is frequently seasonal, and it is most often observed in children and young adults...feathers, animal danders, dust mites, molds, and other antigens can exacerbate an attack...

30-50% of patients experience a second wave of  bronchocontriction 6-10 hours later...

Causes of Asthma - most commonly tartrazine (coloring agent), beta-adrenergic antagonists, and sulfiting agents...aspirin 10% of the time can be the offending agent...beta-adrenergic antagonists regularly obstruct the airways in individuals with asthma as well as in others with heightened airway reactivity and should be avoided by such individuals...even the selective beta-1 agonists have this perpensity...

bacteria are not usually the cause, viral in almost all cases...

in young children, respiratory syncytial virus and parainfluenza virus are most common virus' that cause asthma...

in adults, rhinovirus and influenza virus predominate as pathogens...

mechanism of induction of asthma is most probably related to T cell - derived cytokines that potentiate the infiltration of inflammatory cells into already susceptible airways...

gross overdistension and failure to collapse when the pleural cavities are opened...

numerous gelatinous plugs of exudate are found in most of the bronchial branches down to the terminal bronchioles...

histologic examination shows hypertrophy of the bronchial smooth muscle, hyperplasia of mucosal and submucosal vessels, mucosal edema, denudation of the surface epithelium, pronounced thickening of the basement membrane, and eosinophilic infiltrates in the bronchial wall...

also, Charcot-Leyden crystals and Curschmann's spirals are present within the spectrum and emanate from the eosinophils...

Curschmann spirals: twisted mucous plugs admixed with sloughed epithelium...

Charcot-Leyden Crystals: eosinophil membrane protein...

Bronchiectasis

chronic necrotizing infection of the bronchi and bronchioles leading to or associated with abnormal dilation of these airways...

manifested clinically by cough, fever, and expectoration of copious amounts of foul-smelling, purulent sputum...suppuration (production of pus)...

to be considered bronchiectasis, the dilation should be permanent; reversible bronchial dilation often accompanies viral and bacterial pneumonia...

usually develops from:

1) bronchial obstruction, owing to tumor, foreign bodies, and occasionally mucous impaction...

2) congenital or hereditary conditions, including congenital bronchiectasis (caused by a development of bronchi), cystic fibrosis, intralobar sequestration of the lung, immunodeficiency states, and immotile cilia and Kartagener syndromes...

3) necrotizing pneumonia, most often caused by the tubercle bacillus or staphylococci or mixed infections...

viral causes include influenza virus and adenovirus...

obstruction and infection are the major influences associated with bronchiectasis, and it is likely that both are necessary for the development of full-fledged lesions..

after bronchial obstruction, air is resorbed from the airways distal to the obstuction, with resultant atelectasis...often accompanying atelectasis are early bronchial wall inflammation and the presence of intraluminal secretions that result in dilation of the walls of those airways that are patent...

these changes are reversible, the changes become irreversible (1) if the obstruction persists, especially during periods of growth, b/c the airways will not be able to develop normally, (2) if there is added infection...

infection plays a role in the pathogenesis of bronchiectasis in two ways (1) it produces bronchial wall inflammation, with weakening, and further dilation, and (2) the extensive bronchial and bronchiolar damage causes endobronchial obliteration, with atelectasis distal to the obliteration and subsequent bronchiectasis around atelectatic areas...neutrophils are responsible for inflammation in bronchiectasis...

bronchiectasis can be caused by abnormal motility of the cilia, which is due to abnormalities of the ATPase containing dynein arms...abnormal cilia inhibit the normal functioning of the respiratory epithelium, which is to clear microorganisms and foreign particles within the respiratory mucus...

causes severe, persistent cough, expectoration of foul-smelling, sometimes bloody sputum, and dyspnea and orthopnea in severe cases...

Kartagener Syndrome

characterized by bronchiectasis, sinusitis, and situs inversus, there is a defect in ciliary motility, associated with structural abnormalities of cilia, most commonly absent or irregular dynein arms, the structures on the microtubular doublets of cilia that are responsible for the generation of ciliary movement...

the lack of ciliary activity interferes with bacterial clearance, predisposes the sinuses and bronchi to infection, and affects cell motility during embryogenesis, resulting in the situs inversus...

males with this condition tend to be infertile, owing to ineffective mobility of the sperm tail...

the syndrome is inherited as an autosomal recessive trait...

Chronic Bronchitis

(1) may be associated with chronic obstructive airway disease...

(2) lead to cor pulmonale and heart failure...

(3) cause atypical metaplasia and dysplasia of the respiratory epithelium, providing possible soil for cancerous transformation...

Chronic Bronchitis

patient who has persistent cough with sputum production for at least 3 months in at least 2 consecutive years...

Simple Chronic Bronchitis - patients have a productive cough but no physiologic evidence of airflow obstruction...

Chronic Asthmatic Bronchitis - hyperreactive airways with intermittent bronchospasm and wheezing...

Obstructive Chronic Bronchitis - heavy smokers, develop chronic airflow obstruction, usually with evidence of associated emphysema...

 (1) chronic irritation...

(2) microbiologic infections...

the hallmark finding is hypersecretion of mucus in the large airways, and it is associated with hypertrophy of the submucosal glands in the trachea and bronchi...

as chronic bronchitis persists, there is also a marked increase in goblet cells of small airways, small bronchi and bronchioles, leading to excessive mucus production that contributes to airway obstruction...

associated with the terminal bronchioles...

Emphysema

condition of the lung characterized by abnormal permanent enlargement of the airspaces distal to the terminal bronchiole, accompanied by destruction of their walls, and without obvious fibrosis...

 in contrast, the enlargement of airspaces unaccompanied by destruction termed overinflation, for example, the distention of air spaces in the opposite lung after unilateral pneumonectomy...

if patient presents with hemoptysis, doctor should investigate another disease to find out what it really is, b/c emphysema does not present with hemoptysis...

Genetics - defective transport from hepatic (organ specific) ER to the serum...

destruction of alveolar walls is the protease-antiprotesase mechanism...patients with a genetic deficiency  of the protease inhibitor alpha1-antiprotease have a markedly enhanced tendency to develop pulmonary emphysema, which is compounded by smoking...

the normal alpha1-antiprotease phenotype, called PiMM is present in 90% of the population...of the several phenotypes associated with alpha1-AT deficiency, PiZZ is the most common...more than 80% of PiZZ phenotypes develop symptomatic emphysema that occurs at an earlier age and with greater severity if the individual smokes...

alpha1-antitrypsin deficiency is an autosomal dominant disorder...

Genetics - defective transport from hepatic (organ specific) ER to the serum...

destruction results from an imbalance between proteases (mainly elastase) and antiproteases in the lung...

principal cellular elastase activity is derived from neutrophils (others elastases are formed by macrophages, mast cells, pancreas, and bacteria)...

neutrophil elastase is capable of digesting human lung, and this digestion can be inhibited by alpha1-AT...

stimulated neutrophils also release oxygen free radicals, which inhibit alpha1-AT activity...with low levels of alpha1-AT, the process of elastic tissue destruction is unchecked, with consequent emphysema...thus emphysema is seen to result from the destructive effect of high protease activity in subjects with low antiprotease activity...

smokers have greater numbers of neutrophils and macrophages in their alveoli...the increased recruitment of neutrophils into the lung is likely to result, in part, from the release by activated alveolar macrophages of neutrophil chemotactic factors (IL-8), this release being stimulated by smoking...in addition, nicotine is chemotactic for neutrophils, and cigarette smoke activates the alternative complement pathway...

smoking stimulates release of elastase from neutrophils...

smoking enhances elastolytic protease activity in macrophages...macrophage elastase is not inhibited by alpha1-AT and can proteolytically digest enzyme...

oxidants in cigarette smoke and oxygen free radicals secreted by neutrophils inhibit alpha1-AT and thus decrease net anti-elastase activity in smokers...

clinical manifestations do not occur until 1/3 of the functioning pulmonary parenchyma is incapacitated...

dyspnea, cough, wheezing...weight loss is common...barrel chested and dyspneic...prolonged expiration, and sitting forward in a hunched-over position, attempting to squeeze the air out of the lungs with each expiratory effort...

patients have a pinched face and breathe through pursed lips...the only reliable and consistently present finding on physical examination is slowing of forced expiration...

Centriacinar (Centrilobular emphysema)

pattern of involvement of the lobules...the central proximal parts of the acini, formed by respiratory bronchioles, are affected, whereas distal alveoli are spared...

lesions are more common and usually more severe in the upper lobes, particularly in the apical segements...walls of emphysematous spaces often contain large amounts of black pigment...

inflammation around bronchi and bronchioles and in the septa is common...

centriacinar emphysema occurs predominantly in heavy smokers, often in association with chronic bronchitis...

Genetics - defective transport from hepatic (organ specific) ER to the serum...

impaction of smoke particles in the small bronchi and bronchioles, with the resultant influx of neutrophils and macrophages and increased elastase and decreased alpha1-AT activity, causes the centriacinar emphysema seen in smokers...

Panacinar (Panlobular) Emphysema

acini are uniformly enlarged from the level of the respiratory bronchiole to the terminal blind alveoli...

the prefix pan- refers to the entire acinus but not to the entire lung...

in contrast to centriacinar emphysema, panacinar emphysema tends to occur more commonly in the lower zones and in the anterior margins of the lung, and it is usually most severe at the bases...

this type of emphysema is associated with alpha-1 antitrypsin deficiency...

Genetics - defective transport from hepatic (organ specific) ER to the serum...

in contrast, it is postulated that the panacinar emphysema of alpha1-AT deficient individuals reflects total lack of antiprotease throughout the acinus and susceptibility to chronic low-level proteolysis from neutrophils in transit through the lung circulation...

Paraseptal (Distal Acinar) Emphysema

in this type, the proximal portion of the acinus is normal, but the distal part is dominantly involved...

the emphysema is more striking adjacent to the pleura, along the lobular connective tissue septa, and at the margins of the lobules...

it occurs adjacent to areas of fibrosis, scarring, or atelectasis and is usually more severe in the upper half of the lungs....

the characteristic findings are of multiple, continuous, enlarged airspaces from less than .5mm to more than 2 cm in diameter, sometimes forming cystlike structures...

this type of emphysema probably underlies many of the cases of spontaneous pneumothorax in young adults...

Genetics - defective transport from hepatic (organ specific) ER to the serum...