Chronic Obstructive Disease✅ .pdf

passive process → inflation deflation ,...

passive process → inflation deflation , b. energy no Chronic Obstructive * * &iW 548%1 ~ " - Normal tissue sift ←ik EW ! Pulmonary Disease )COPD( &Ñ% → ' HAHA → it Is#. Objective evidence of persisting and progression irreversible airway obstruction, usually ! evident in all cases presenting by the d§§É time dyspnea had developed ‫ حييجوا‬COPD ‫ *االشي المشترك بينهن انه كل المرضى يلي عندهم‬ ‫ بتختلف بيناتهم‬level of obstruction ‫ ولكن ال‬dyspnea ‫ب‬ :‫وبنقسموا الى‬ by morphological features – Emphysema & destruction ( Lossofelastirrecoit ) of elastic wall radiological E. ① ridge % Restrictive clinical features c- – Chronic bronchitis is # Timo *⇐ – Bronchiectasis FVC normal slightly : or ↓ – Cystic Fibrosis FEY decreased : ↓↓ " / FEY f- VC ration : – Bronchiolitis Sm:↑ñÉiwM acini bronchi - Asthma → narrowing of bronchi i. → COPD : = Irreversible obstruction = while asthma Reversible -  "* ¥" Asthma : sever dyspnea Asthma is a chronic inflammatory disorder of the airways that causes recurrent episodes of wheezing, breathlessness, chest tightness, and cough, particularly at night and/or early in the morning. The hallmarks of asthma are inter- mittent, reversible airway obstruction; chronic bronchial inflammation with eosinophils; bronchial smooth muscle cell hypertrophy and hyperreactivity; and increased mucus secretion. Sometimes trivial stimuli are sufficient to trigger attacks in patients, because of airway hyper- reactivity. Many cells play a role in the inflammatory response, in particular eosinophils, mast cells, macro- phages, lymphocytes, neutrophils, and epithelial cells. Of note, asthma has increased in incidence significantly in the Western world over the past 4 decades. One explanation for this troubling trend is the hygiene hypothesis, accord- ing to which a lack of exposure to infectious organisms (and possibly nonpathogenic microorganisms as well) in early childhood results in defects in immune tolerance and subsequent hyperreactivity to immune stimuli later in life. ]→ Asthma can be derided into atopic & Non atopic - bronchospasm t after irretant Stress cold Allergy ( Type hypersensing I. , air the most common cell→ eosinophil viral infection. excessive classic atopic form cells (sensitizes) IgEwill coat mast ]. for eosinophil It 4,13 → IgE production hyperactive TH2→P IlIt -513 - ~ mucus secretion In 2° exposure ofantigen mast cell will release mediators 2 phases histannin PGA tea Cu DD : reflex Broncho spasm ( neural. ,. , , 1- early phase : mucus secretion Vasodilation 2- Late phase : inflammatory in nature i nflam- matory mediators stimulate epithelial cells to produce chemokines (including eotaxin, a potent chemoattrac- tant and activator of eosinophils) that promote the recruitment of TH2 cells, ECP. MBP ← eosinophils, and other leuko- cytes, thus amplifying an inflammatory reaction that is initiated by resident immune cells. Repeated bouts of inflammation lead to structural changes in the bronchial wall that are collectively referred to as airway remodeling. These changes include hypertrophy of bronchial smooth muscle and mucus glands and increased vascularity and deposition of sub- epithelial collagen, whichcellsmay occur as early as several years before initiation of symptoms. + metaplasia of goblet that code of way thickness p - gene genetics). ( asthma families Receptor Cleary involvedin Pathogen - Asthma in It -4. run. Atopic the most common,radioallergosorbent tests (RASTs) that identify the presence of IgEs that recognize specific allergens.  Asthma nonatopic no allergen sensitization, skin test negative. A positive family history of asthma is less common. Respiratory infections due to viruses (e.g., rhino- and inhaled air pollutants (e.g., sulfur dioxide, ozone, nitrogen dioxide) are common trig- gers. It is thought that virus- induced inflammation of the respiratory mucosa lowers the threshold of the subepithe- lial vagal receptors to irritants. Although the connections are not well understood, the ultimate humoral and cellular mediators of airway obstruction (e.g., eosinophils) are common to both atopic and nonatopic variants of asthma, so they are treated in a similar way. D-spMYFin.edu ON T bronchi Mi → intrinsic →.?É inflammation persistence As, i Stimuli x-HWGC-t-n.ph#my-pasmrMmucusT human ↓ Canty : uh , contractility↑ permeability Secretions ↑ Later , mediators ↑ eosinophil ¥5 (Y¥ⁿf) IX. ← biopsy * * tenacious - - ↳ ÑJ aystus ← mediators a toxicity shedding ← ↑ eosinophil ← sputum ← cytology ↳& of mucus bronchial thermoplasty, which involves controlled , * luman jog edema , ← delivery of thermal energy during bronchoscopy to Aggie expatiate c- reduce the mass of smooth muscle and airway responsiveness, is being evaluated in patients with severe, poorly controlled asthma. Conieosknkk SABA , LABA. transducers exudate it diuretics f- b thickness dg-qmuui-wjdehyd.MU  24.1 Ew aluoli Is elastic , thin postfix Alveoli * connective fiber Emphysema tissue diffuser lead "wÉ- it ?Ñ ¥0 b effectiveness Irreversible elasticity ↓ Permanent enlargement of air spaces distal to terminal ( Acini) bronchioles with destruction of their walls Septum of fibers + expiration Loss elastic → Recoil ↓ → × FEW ¥ without fibrosis alveolar sacs to ‫ (يعني من ال‬ ‫ حيكون ال‬terminal bronchioles )pathology – Condition identified by morphologic criteria – According to distribution in the lung lobule and acinus, emphysema is classified into level 7) as distal component f 1-Centriacinar (centrilobular), most More common clinically in respiratory common bronchioles fox than ) 2-Panacinar (panlobular( from alveoli to terminal bronchioles 3-Distal acinar in more peripheral location 4-Irregular  Emphysema Centriacinar (A) – Involvement of central portions of the acine, the ¥541M respiratory bronchioles – In severe cases, a.br ski distends to distal Alveoli portions ✓ panacinar – More common and severe in upper lobes Hg a – In cigarette smokers lower ~ § the center of acini con. highest con. on -116s acini * New.az * u ¥5 -1 chronic bronchitis & Dilated airways according to permanent destruction of elastic walls  Emphysema Panacinar (Panlobular) aCÑ genetics # ✓ – Involvement of entire acinus, from the terminal bronchiole to terminal alveoli –✓ More common in lower lung zones neutrophil I :-# µgiµg1d –✓ Mostly associated with α-1 antitrypsin deficiency elastase ↑ from neutrophil ↓ elastic fibers Micro exam E centni I panacinar : Macroscopic of wall without pinkisshtpfibrosis.IE?tvesslesbtnnglvduminolung destruction \ " " Less voluminous Large # upper 213T lower lobes surface ared↓  pneumothorax ← wñ¥sÑ → g Emphysema jpix-myu.im#sdistalpartpleura.o-a.d-s iWgIM' a Distal Acinar (Paraseptal( pneumothorax ← rupture ← Push ← fibrosis ← ¥Ñ ' wing outside : – Predominant involvement of distal part of the acinus near to pleura – More apparent adjacent to pleura, along lobular connective tissue septa, at the margins of the lobules, and near areas of fibrosis, scarring and atalectasis – Usually more sever in upper half of the lung – Multiple contiguous enlarged air spaces (bullae( ‫فقاعات‬ – May lead to spontenous pneumothorax when bullae ruptured into pleura  @ I Total surface area dyspnea Alveoli with destructed wall fibrosis] (collagenous wall instead of elastic wall)  ① oxidation ↑ Emphysema, Pathogenesis Anti oxidation - ↓ AIAT Over inflation o ✓ 1- defect in alpha 1 AT → activation of 2- smoking → necotine (functional - i elastase → destruction of elastic walls → panacinar emphysema. inhibitor for alpha 1 AT)→ elastase activation →Centriacinar lobes Lower Lobe emphysema In upper  Emphysema, Pathogenesis ✓ Protease-antiprotease imbalance → Panacinar – Αlpha1-antitrypsin inhibits elastase in neutrophils – Normal Pi MM phenotype coded for Αlpha1- antitrypsin by Piproti locus on chromosome 14 noise inhibitor – Codominant expression of genes on the proteinase inhibitor )Pi) locus – Homozygous state for PiZZ or PiSS (abnormal phenotypes) associated with emphysema ✓Oxidant-antioxidant imbalance (smoking) → Centriacinar (free radicals )  hyperplasia hypertrophy ↳ hyperinflation , µ @ is) { i. ¥ HAI lung 't -40£ § is a destruction €6K ✓ Partial obstruction → hyperinflation Emphysema, but No Emphysema ✓Compensatory (i.e., following removal of a lobe of a lung, the other lobes expand; this is a misnomer, as there is no destruction of alveoli, and no loss of elasticity( ✓ "Irregular" or "tractional" )‫) (بتكرمش‬i.e., after the ☒¥ scarring, abscess, etc.; another misnomer( £ KAMEN Recoil. ✓ "Senile" (loss of elasticity (loss of recoil) a stillness without loss of lung substance, from "old of wall age( mediastinum Subcutaneous. then to intersticem of may. ① air in lung + release air → lead to alveolar rupture In vomiting ② violent fracture rib "Interstitial emphysema" doesn't even refer cough It slog air is dbsorpedto lung. It means air has been forced into usually after the site entry seat. of the fibrous tissues of the body,  - Lecture 4 Record name: COPD cont.URL Emphysema  % In emphysema from terminal bronchioles (distal portion of airways) to acini, at some point of level from this area permanent destruction of the alveolar wall occurred  Which means the damage of elastic recoil by Elastase  For this patient, inspiration is done easily without any difficulty, but this air will not come out, according to the absence of the elastic recoil # a Obstruction. functional obstruction not real ~  On X-ray, there is an hyperinflation of the lung  clinically dgsined ↓Raiio, weight-loss Emphysema, Clinical. / Hibi c. bronchitis : wheezing cough / Emphysema With no bronchitis component : barrel-chested and dyspneic, with obviously prolonged expiration, sitting forward in a hunched-over position  We call to emphysemas' patient (Pink Puffers): because this patient will inspired the oxygen but can not do good exchange between O2 and CO2, and then will lead to hypercarbic drive (this returned CO2 in the patient will lead to compensatory hyperventilation to prevent the occurrence of respiratory acidosis As much as possible). Puffers mean (puff, puff, puff.. According to hyperventilation to loss the CO2) Hdmi  Hyperventilation, ABG (arterial blood gases) are relatively normal until late in the disease (So the CO2 becomes trapped and difficult to remove from the body and the occurrence of respiratory acidosis )  Emphysema, Clinical :O  So emphysema patients make an effort to take a breath (for respiration) that will lead to Weight loss (those patients are often thin).  Reduced FEV1 with normal or near normal FVC  Insidious, but steadily progressive dyspnea (still on specific level at early course of the disease), but later on may have combined pathology specially in patients with COPD Emphysema With no bronchitis component : ✓  Emphysema, Clinical Emphysema With bronchitis component -  Chronic bronchitis patients have productive cough (More - - cough with sputum) For a period of 3 consecutive months, - at least for two consecutive years  Chronic bronchitis patients They differ from emphysema in that there is no hypercarbic drive rn  Less prominent dyspnea and less respiratory drive, Their chest is filled with CO2  So They have Retain CO2, no gas exchange, no hyperventilation, become hypoxic and cyanotic and will have respiratory acidosis  Obese patient wat  ! Blue Bloaters (cyanotic according to the loose of hypercarbic drive )  Emphysema, Clinical EOPD  The hypoxemia will lead to blood vessels spasm and then pulmonary hypertension and then core pulmonale and right ventricular hypertrophy RHF ✓  So the main differences: patients in pure emphysema (without COPD) will have hypercarbic drive and hyperventilation, will be good until to a new pathology developed in those patient like chronic bronchitis Here they will lose the hypercarbic drive which lead to CO2 retention Emphysema With bronchitis component Broch in 's ! - § sperm = ABU Abnormal cot hypoxic , cyanosis ] *ñ0zW  Emphysema, Clinical Later manifestations (in both cases): II pulmonary hypertension will be the final outcome.  Hypoxia induced pulmonary vasospasm  Loss of pulmonary capillary surface area  Pulmonary failure with respiratory acidosis  Right sided heart failure (core pulmonale) death Respiratory failure/ : RHF The main risk factor in both 2 cases (emphysema and chronic bronchitis) is smoking  Chronic Bronchitis Clinical based diagnosis: persistent productive cough for at least - → three consecutive months, in at least two consecutive years howE- £ In chronic bronchitis The main pathology will be in major bronchi In it has Lots of staging and clinical manifestation ✓ early → 1. Simple: mucoid sputum with no airway obsturction stage 2. Chronic Mucopurulent bronchitis: cough + sputum with pus (purulent sputum) Allergic / infectious * ✓ new 3. Chronic asthmatic attack: intermittent episodes of Wheeling + bronchospasm with airway hyperresponsiveness (similar to asthma), in addition to chronic bronchitis ✓Chronic obstructive: bronchitis with outflow obstruction. Airways obstruction specially in more distal airways (bronchioles are small in size, so any inflammation and fibrosis may lead to obstruction quickly). (the affection will be in main bronchus + ② ①Mucus ③ distal bronchioles). (Inflammation, fibrosis and narrowing of small airway bronchioles ,Coexistent emphysema) disease  Chronic Bronchitis ⇐ I &' -96 spetum+ ¥ cough infection → pneumonia/ Acute Bronchitis Irritation) ↑ Causes → The transcription of the mucin gene in bronchial epithelium and the production of neutrophil elastase – Smoking (most common) are increased as a consequence of exposure to tobacco smoke. Microbial infection often is present – Air pollution but has a secondary role, chiefly by maintaining inflammation and exacerbating symptoms. – Irritant gases: sulfur dioxide, nitrogen dioxide Pathogenesis – Hypersecretion of mucus, beginning in large airways Hypertrophy of mucus glands 9 ÷ ↑ mucus Goblet cell metaplasia in surface epithelium – Inflammation, growth factor upregulation – Secondary microbial infection squama metaplasia * s w.IM ix. mucus  Chronic Bronchitis The distinctive feature of chronic bronchitis is Morphology&Pathogenesis hyperse- cretion of mucus, beginning in the large airways.  Mucosa (mucosal damage) ÷  In case of presence of tobacco, will lead to Squamous metaplasia, and loss of cilia  Increased number of inflammatory cells  Increase number of goblet cells and increased secretions  Loss of ciliated cells  Mucopurulent secretions Vasodilation% infusion ↑ ✓Swelling and hyperemia according to hyper perfusion  Submucosa ✓  Hyperplasia of submucosal glands, and Enlargement of mucus secreting glands (Reid index)  Chronic Bronchitis small airwaydisease gooletcdl metaplasia to  In small bronchioles: bronchiolitis (not bronchitis) Mucus, Inflammation, fibrosis and smooth muscle hyperplasia in ↳ submucosal fibrosis bronchioles  with time Peribronchial fibrosis, and then luminal narrowing and airflow obstruction (chronic obstructive bronchitis) COB COB ← bronchi.dg←fi6rosis← :-# Bronchiolitis ← $81  EH Normal histology of bronchus postpartum → mucus gland ¥sÑbE Goblet cells cartilage  Chronic Bronchitis Ratio of thickness of submuwsd / Bronchial wall. Normally 44 , Reid Index: (diagnostic for chronic bronchitis) thickness of submucosa We calculate it from basement membrane to the beginning of perichondrium (cartilage) According to enlargement of submucosal mucous glands in patients with chronic bronchitis, the Reid Index will increased Yh 3m 'D C. bronchitis alone : productive cyanosis poor prognosis hypoxia hypercapnia , - cough wheezing , RHF , emphysema PHT → : , - ~ ~ +  Productive cough ÷ Chronic bronchiolitis may ✓ be on top if Emphysema: chronic bronchitis The level of destruction from terminal or after viral bronchiole to acini and infection (like the main pathology is influenza virus) loss of elastic recoil  II. lung { ex Bronchiectasis. & wall is 25 b¥ bronchi MPYʳmᵈ ji±ñ- § sputum ¥ *.gl#6.gy!w.s ← dilated ← wall ↓ Ms ' % ↳ Is a COPD with a Permanent destruction of major (large) airways. (bronchus, main bronchi, bronchioles) and dilatation and destruction of elastic and muscular supporting tissue, resulting from or associated with chronic necrotizing infection specially staph aurous bacteria. (the infection may be the cause, or may be the final outcome) The location mainly very peripheral Clinical :  Cough with expectoration of copious sputum, sometimes with blood (hemoptysis) according to the destruction of supportive tissue that is vascularized, or according to blood production. -9¥  Clubbing of fingers hypoxia  In severe cases: high level of CO2 and low level of O2 (hypoxemia), hyeprcapnia , then pulmonary acidosis and pulmonary hypertension then core pulmonale and PHT  Characteristic radiographic picture  Bronchiectasis diffuse / fowl. Causes – Bronchial obstruction tumors, Foreign body, mucus impaction. Usually localized form obstruction – Congenital or hereditary conditions. ↓ Ig ) ( Ab. Recurrent bacterial infection by ↑MUCUS , infection 2° ← Cystic fibrosis , immunodeficiency states, Kartagener tkthlihf Autosomal recessive M > f. syndrome (the cilia in those patient can not move) ↑ Infection – Necrotizing or suppurative pneumonia ↳ Staph. Aureus, Klebsiella. inflammation destruction of wall dilatation superimposed infection Pathogenesis , , obstruction ↑ secretions. : , , clearance →obstruction. _. suppurative : exudate poor or ;  Bronchiectasis bronchitis I Morphology ↓ thickness ↑ mucus – Usually involvement of lower lung lobes (it is the main affected area), and on both case sides in most of cases (bilateral) in – May be localized ( obstruction ) – Bronchi may be dilated up to four times their usual diameter, according to the permanent destruction of the airways and dilation, and may lead to abscess and supportive inflammation ( and it is one of the very common features of bronchiectasis hempysis clinically muwpurlntspetum : dyspnea ,. agent episodic upper airway infection new Micro → , – Desquamation (metaplasia in epithelium with sloughing of epithelium) and ulceration of lining epithelium, mixed inflammation, bronchial and Peribronchial fibrosis, scarring. Occasionally necrosis extends to lung abscess and secondary infection of lung Dilatation of airways (4 time they normal diameter)  Chronic Obstructive Pulmonary Diseases Chronic limitation to airflow in the lung (reduced FEV1, reduction of FEV1/ Forced Vital Capacity) – Anatomic airway narrowing Asthma Chronic bronchitis Bronochiectasis Cystic fibrosis Bronchiolitis – Loss of elastic recoil of the lung (reduced outflow pressure) – Emphysema  Bronchial Asthma Episodic, reversible bronchospasm resulting from exaggerated brochoconstrictor response to various stimuli Hyperresponsive bronchi due to persistent underlying bronchial inflammation  Bronchial Asthma Extrinsic asthma: initiated by type I hypersensitivity reaction due to exposure to an extrinsic antigen, occurs mostly in children – Atopic Driven by TH2 CD4+ Increased levels of IG E antibodies Blood eosinophilia – Occupational Allergic bronchopulmonary aspergillosis  Bronchial Asthma Intrinsic asthma (nonimmune) :Mostly adults, no associated atopy, or increased levels of IgE or blood eosinophils Infections: RCV € secretion of TH2 cytokines € eosinophilic infiltrate Inhaled air pollutants: slulfur dioxide, ozone, nitrogen dioxide Aspirin induced: leukotriene C4 Cold, psychological stress, exercise  Mediator Release Opening of Junctions Vagal Stimulation Ags to mucosal Mast cells Bronchocostrction.Early (mediator, humoral) phase Late (cellular) phase 30-60 minutes 4-8 hours C4,D4,E4€ constriction, Release more mediators permeability mucin secretion Cause damage of epithelial cells, that become a source PG s D2, E2, F2a € Bronchoconstriction of mediators (endothelin vasodilation and NO) Histamine€ increased permeability Eosinophils € MBP, ECP toxic to epithlial cells PA F € aggregation of PLT peroxidase, C4, PAF release of histamin Mast cell tryptase € inactivation of bornchodil peptide  Bronchial Asthma Morphology – Occlusion of bronchi by thick tenacious plug Whorls of shed epithelium (Cruschmann's spiarls) Charcot-Leyden crystals Eosinophils Edema, hyperemia and inflammatory infiltrate of the bronchial wall – Especially important are eosinophils, and TH2 lymphocytes secreting IL-4 and IL-5- – Goblet cell hyperplasia and hypertrophy of submucosal glands – Patchy epithelial necrosis – Increase in collagen beneath the BM – Hypertrophy and hyperplasia of smooth muscle  Bronchial Asthma Clinical – Attacks of severe dyspnea and wheezing – Difficulty in inspiration, more so in expiration – €Lung hyperinflation, with entrapment of air in distal to the bronchi that are constricted and plugged by mucus and debris – Attacks subside 1 to several hours  Bronchial Asthma Clinical – -Status Asthamticus: severe paroxysm not responding to treatment, that may last for days, or even weeks – Hypercapnia, acidosis, severe hypoxia – May be fatal