RESPIRATORY SYSTEM lecture 1&2

THE LUNG LECT-1

NORMAL LUNG Double arterial supply. Progressive branching of the bronchi till reach R. bronchioles = no cartilage and SMG. The terminal bronchiole is less than 2 mm, and give the terminal R. unit formed of respiratory bronchiole and alveoli. 3-5 T Bro. give pulmonary lobule. Layers : capillary endothelium, basement membrane, interstitial tissue and alveolar pneumocytes type I and II (from surfactant and repair damaged cells). Pores of Kohn.

Normal Lung. These show the alveolar spaces (air sacs) at low and high power.

CONGENITAL ANOMALIES 1- Agenesis or hypoplasia of both lungs, one lobe or single lobes. 2- tracheal and bronchial anomalies. 3- vascular anomalies. 4- congenital lobar over inflation (emphysema). 5- congenital cysts. 6- intra-lobar and extra-pulmonary lobar sequestrations.

ATELESTASIS: It is an incomplete expansion of the lungs or collapse of previously inflated lung substance, producing areas of relatively airless pulmonary parenchyma. Divided into: 1- obstructive: airway obstruction with oxygen absorption, reduced volume and shift of mediastinum to the same side. (caused by secretions, neoplasm and foreign body. 2- Compressive: pleural cavity is partially or completely filled by fluid exudate, tumor, blood or air. (mediastinum shift to other side). 3- contractive: local or generalized fibrotic changes.

DISEASES OF VASCULAR ORIGIN 1- Pulmonary congestion and edema: Can be caused by: 1- Hemodynamic pulmonary edema: *Due to increased hydrostatic pressure as in left sided heart failure causing heavy wet lungs, and fluid accumulation mainly in the basal lower lobes. MICRO. Alveolar capillary engorgement and intra alveolar pink precipitate. Also there is alveolar micro-hemorrhage and hemosiderin -laden macrophages. At late stages there is fibrosis with thick walls. 2- Edema due to micro-vascular injury: *there is normal pulmonary hydrostatic pressure but there is primary injury to the vascular endothelium or damage to alveolar epithelial cells, with leak of fluid and protein to interstitium and then to alveoli.

Pulmonary edema – Fluid and RBCs in the alveolar air spaces

2- ADULT RESPIRATORY DISTRESS SYNDROME: Def: A syndrome caused by diffuse alveolar capillary damage and characterized clinically by the rapid onset of severe arterial hypoxemia that is refractory to oxygen therapy, and that frequently progresses to extra pulmonary multi-system organ failure. Etiology: 1- diffuse pulmonary infections. 2- inhalation of smoke or irritant gases. 3- drug. 4- aspiration of gastric contents. 5- Near drowning. 6- massive embolism. 7- radiation. 8- shock.9- sepsis. 10- extensive burn. 11- DIC. 12- acute pancreatitis. 13- uremia and other metabolic disorders.

Morphology: the lungs are firm, red, heavy and boggy. And micros. There is hyaline membrane formed of fibrin rich edema fluid and mixed with remnants of dead cells, with proliferation of epithelial cells and late fibrosis.

SHOCK LUNG-GROSS

Pathogenesis: 1- There is initial capillary endothelial and alveolar epithelial cell injury by different mediators: Bacterial products Reactive oxygen intermediates Proinflammatory cytokines (high mobility group protein 1) Activated neutrophils, macrophages, epithelium, endothelium, and platelets. Complements. 2- And there is different mechanisms in injury: Activation of transcriptional factors Initiation of Proinflammatory cytokine cascades Activation of coagulation cascades Activation of pulmonary cell population

Clinical course: *profound dyspnea and tachypnea. *increased cyanosis and respiratory failure. *Therapy by high concentrations of oxygen

3- Pulmonary embolism, hemorrhage and infarction: Arteries by blood clot almost always embolic in origin. In situ thrombosis is rare. More than 95 % of emboli arise from deep veins of the legs. Causes: 1- cardiac disease. 2- Cancer. 3- prolonged immobilization. 4- primary hypercoagulable state. 5- Secondary hypercoagulable state (obesity, recent surgery, cancer, oral contraceptive pills, pregnancy). 6- Central venous lines.

Pathophysiology: 1- respiratory compromise: due to the non perfused segment. 2- Hemodynamic compromise: due to increased resistance to pulmonary blood flow, with pulmonary hypertension and acute heart failure.

1- death. 2- if survive: severe chest pain, dyspnea, shock, elevation of body temperature. 3- small emboli, causes chest pain, pulmonary hemorrhage without infarction, and if recurrent end with pulmonary hypertension. Clinical course:

Morphology: 1- large emboli= saddle embolus. 2- smaller emboli with normal cardiopulmonary function= no infarction. 3- in 10 % there is pulmonary infarction: ¾ in lower lobes, over half are multiple, wedge shaped with apex pointed to the hilus, hemorrhagic raised red blue with fibrinous exudate on the pleural surface. Histologically ischemic necrosis affecting the alveolar walls, bronchioles and blood vessels. If infected embolus = abscess.

4-PULMONARY HYPERTENSION AND VASCULAR SCLEROSIS Causes: 1- Primary or Idiopathic Pulmonary Hypertension. 2- Secondary: include: Hypoxic: chronic lung disease. Pulmonary Venous Hypertension mitral stenosis, left ventricular failure Congenital Heart Disease PDA, ASD, VSD Vascular Obstruction Thrombo-embolism, systemic vasculitis. muscle cells and elaboration of extra cellular matrix.

Pathogenesis: *In primary, there is endothelial cell injury. (idiopathic dysfunction). *In secondary: the endothelial dysfunction caused by the causative disease, due to mechanical factors or secretion of chemical materials or even decrease in secretion of prostacyclin, and nitric oxide and increased production of endothelin and this cause pulmonary vasoconstriction. Finally there is production of growth factors and cytokines which promote migration and replication of smooth muscle fibers.

THE LUNG LECT-2

DIFFUSE PULMONARY DISEASE Lung function tests Resistance Total lung and capacity Expiratory flow rates ObstructiveRestrictive disease disease a) Acute b) Chronic

CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) Emphysema DYSPNEA + Chronic Bronchitis OBSTRUCTION TO AIR FLOW Asthma (chronic or recurrent) Bronchiectasis

OBSTRUCTIVE LUNG DISEASE Definition: A group of conditions that share the same major symptom (dyspnea) due to increased resistance to airflow due to partial or complete obstruction at any level from trachea to respiratory bronchioles.

Emphysema: Definition: Abnormal permanent abnormal enlargement of air spaces distal to the terminal bronchioles, accompanied by destruction of walls, and without obvious fibrosis. Overinflation: is the distension of the airspaces in the opposite lung following unilateral pneumonectomy, unaccompanied by destruction. TYPES OF EMPHYSEMA a) Centriacinar (centrilobular). b) Panacinar (panlobular). c) Distal acinar (paraseptal). d) Irregular.

a) Centriacinar emphysema Involve the central or proximal parts of the acini, formed by the respiratory bronchioles. Upper lobes, apical segments. Male smokers, often in association with chronic bronchitis. Coal-workers pneumoconiosis, give lesions similar to it. (tobacco products and coal share in pathogenesis).

b) Panacinar emphysema Lower lobes, and anterior margins of the lungs. Alpha 1-antitrypsin deficiency. Whole acinus (from the respiratory bronchiole to the blind alveoli).

c) Paraseptal emphysema Distal acinus Pleura and lobular septa Fibrosis, scarring, atelectasis Spontaneous pneumothorax caused by it in young adults

d) Irregular emphysema Acinus irregularly involved Associated with scarring Mostly asymptomatic

INCIDENCE OF EMPHYSEMA 50% at autopsy 6.5 % of deaths of these patients

Morphology Gross examination of lungs after fixation in inflated state, show voluminous lungs, and shape vary according to type. Microscopy: abnormal fenestrations in the walls of the alveoli, destruction of the septal walls and distribution of the damage within the pulmonary lobule. Adjacent alveoli fuse producing larger abnormal airspaces and bullae. The vasculature are deformed and compressed.

Lungs overlapped the heart and hiding it.

Decrease anti elastase (alpha 1 anti trypsin) Occasional respiratory Infection + smoking +PMN + Mac Elastic damage + Emphysema PATHOGENESIS: protease-anti protease mechanism

PATHOGENESIS: Cause remain unsettled, with a hypothesis of destruction of the walls in protease –antiprotease mechanism. clinical evidence: patients with genetic deficiency of alpha 1 antitrypsin have a markedly enhanced tendency to develop emphysema. Experimental evidence: intratracheal instillation of proteolytic enzyme (papain) causes it.

Alpha 1 AT has an antielastase effect so any deficiency of it result in enhanced effect of elastase result in destruction of the alveolar wall. This enzyme is secreted from neutrophils during infections to destruct the bacteria and resolved by the alpha 1 AT to balance any residual enzyme. In smokers this mechanism is interrupted by many mechanisms result in emphysema.

Effects of cigarette smoking: 1- greater number of neutrophils and macrophages in alveoli by chemotactic action of nicotine and activation of alternative pathway of complement by smoke. 2- stimulate release of elastase from neutrophils. 3- Enhance elastolytic protease activity in macrophages. 4- oxidants and free radicals in smoke inhibits alpha 1 anti trypsin.

OTHER TYPES OF EMPHYSEMA Compensatory hyperinflation Senile Obstructive overinflation Bullous Interstitial

Bullous emphysema

CHRONIC BRONCHITIS Definition: Persistent productive cough for at least three months in at least two consecutive years

Morphology: Grossly: hyperemia, swelling, and mucus secretions in mucous membrane.

Microscopy: Enlargement of mucus secreting glands in trachea and bronchi -Reid Index (normally less than 40%) - Sub mucosal glands: (enlarged and hyperplastic) (mucous glands thickness / bronchial wall thickness) Goblet cell metaplasia result in narrowing of the bronchiole, associated with mucous plugging, inflammation and fibrosis. In severe cases (bronchiolitis obliterans). Squamous metaplasia and dysplasia

pathogenesis EFFECTS of cigarette in infections predisposition: 1- interfere with ciliary action. 2- direct damage to airway epithelium. 3- inhibits the ability of bronchi and alveolar macrophages to clear bacteria.

Bronchospasm Infection Hypersection of mucusContinued and repeated injury repeated infection (smoking) Bronchiolar and bronchial injury Reversible obstruction in bronchioles and small bronchi Chronic bronchitis

BRONCHIECTASIS Chronic necrotizing infection Abnormal irreversible dilatation of bronchi and bronchioles

BRONCHIECTASIS Etiology and predisposing conditions: Obstruction Infection Congenital cystic fibrosis Kartagener’s syndrome Immunodeficiency states

Obstruction and infection Tumor or F.B. (air reso. Atelec., secre., dilata., still reversible). If persistent obstr. And infection, be irreversible). Causes bronchial wall inflammation with weakening and dilatation. Followed by extensive damage.

KARTAGENER’S SYNDROME 1. Sinusitis 2. Bronchiectasis 3. Situs inversus 4. (Infertility)

Morphology Gross: Affects lower lobes proximal bronchi mainly, and usually bilaterally. Distal bronchi and bronchioles affected in severe cases and only single lobes seen in FB or TB. The airways are dilated may be up to 4 times the normal size and appear tube like, cylindrical, fusiform or saccular. Cut section show cystic changes. Microscopy: There is intense acute and chronic inflammatory cell exudate within the walls of the bronchi and bronchioles. Associated with desquamation of the lining epithelium with extensive areas of ulceration. Late stages show fibrosis of walls and peribronchial tissues. Lung abscess can also be seen. Squamous metaplasia.

BRONCHIECTASIS Complications: Respiratory insufficiency Cor pulmonale Brain abscesses Amyloidosis

BRONCHIAL ASTHMA Definition: Episodic, reversible bronchoconstriction due to increased responsiveness of the tracheobronchial tree to various stimuli

pathogenesis i) Extrinsic: (atopic or allergic) (factors) type I hypersensitivity reaction (Atopic) Begins in childhood with positive family history of atopy. Triggered by environmental antigens such as dust, pollen, animal dander and foods. Occupational Allergic bronchopulmonary aspergillosis. * Evidence of allergy by he presence of high serum IgE and positive skin test by immediate wheal and flare. *the sensitive patients has IgE on mast cells found in the bronchi which on second exposure of same antigen to release of chemical mediators result in immediate phase response and late phase reaction.

Immediate reaction Associated with opening of the tight junctions that enhances the penetration of more antigens to the more numerous submucosal mast cells. Also there is direct stimulation of subepithelial vagal receptors causing bronchoconstriction. (parasympathetic). Secretion of primary mediators: 1- Histamine (involved in bronchoconstriction, increased venular permeability, and increase bronchial secretions). 2- Eosinophilic and neutrophilic chemotactic factors (e.g. Leukotriens B4).

Secondary mediators 1- Leukotriens C4, D4 and E4. )causes extreme and prolonged bronchoconstriction, increased vascular permeability and increased secretions). 2- Prostaglandin D2 (bronchocons, and vasodil) 3- Platelet activating factor (increase secretion of histamine and serotonin). 4- Cytokines as IL-1, tumor necrosis factor and IL-6.

Late phase reaction Started after 4-8 hours and persist hours. Caused by a second wave of mediators. Main effect by major basic protein that causes severe epithelial damage.

ii) Intrinsic non atopic: It is non immune and has no family history of atopy. Also associated with normal serum levels of IgE. It is triggered by respiratory tract infection especially viruses as rhinovirus, parainfluenza virus. MORPHOLOGY: Gross : overdistended lungs with small areas of atelectasis. Also there is occlusion of bronchi and bronchioles by thick tenacious mucus plugs. Microscopy: The mucous plugs is seen as whorls of shedded epithelium called as Curshman’s spirals. Numerous Eosinophils, edema and inflammatory infiltrate. Thickening of basement membrane, huge submucosal glands. Hypertrophy of bronchial wall muscle.

BRONCHIAL ASTHMA COMPLICATIONS Emphysema Chronic bronchitis Pneumonia Bronchiectasis Cor pulmonale