1,2&3 Respiratory Pathology

Obstructive vs. Restrictive Pulmonary Diseases

• Obstructive: Increased resistance to airflow caused by obstruction at any level

  • Decreased total lung volume (TLV)

  • Forced Vital Capacity (FVC) normal

  • Expiratory Flow Rate (FEV) decreased

  • FEV to FVC ratio decreased

• Restrictive: Reduced expansion of lungs and decreased total lung capacity

  • FEV and FVC both decreased

  • FEV to FVC ratio normal

Name the 4 Obstructive Lung Diseases

• Chronic Bronchitis

• Emphysema

• Asthma

• Bronchiectasis

Chronic Bronchitis

• Defined as

• Causes

• Pathogenesis

• Clinical Features

• Defined as persistent productive cough for at least 3 consecutive months in at least 2 consecutive years

• Causes include cigarette smokers (%90) and urban dwellers in smog-ridden cities

• Pathogenesis: exposure to noxious inhalants causes goblet cell hyperplasia, hyperplasia/hypertrophy in submucosal mucinous glands, inflammation, squamous metaplasia leading to fibrosis and narrowing of lumen in smaller airways

• Clinical Features: Mucus hypersecretion, productive cough for 3 months, “blue bloater” due to hypoxemia, may lead to Cor Pulmonale (Right Heart Failure) due to over-exertion of right ventricle

Emphysema

• Defined as

• Causes

• Pathogenesis

• Two types

• Clinical Features

• Emphysema is an irreversible enlargement of the air spaces distal to the terminal bronchioles (air sac, alveoli, alveolar ducts) accompanied by destruction of their walls without fibrosis

• Cigarette smoking is the primary cause, followed by alpha1 antitrypsin (At1) deficiency (antiproteases defective cant fight oxidative stress)

• Pathogenesis: Noxious inhalation (or infection) causes too much oxidative damage and destructs lung alveoli, leading to decreased elastic recoil and overexpanded lungs

• Types: Centrilobular emphysema affects primarily the upper lobes, Pacinar Emphysema affects both upper and lower

• Clinical Features: Lungs are overinflated (“barrel chest”), diaphragm is depressed, pursed lip breathing (“pink puffers”) due to exertional dyspnea, can lead to Cor pulmonale

What are the overlapping features of Bronchitis and Emphysema?

• Caused by smoking

• Can lead to pulmonary hypertension

Asthma

• Defined as

• Causes

• Pathogenesis

• Two types

• Clinical Features

• Defined as intermittent and reversible airway obstruction

• Caused by Type I hypersensitivity or Non-immune (non-atopic) things like infections, inhaled chemicals, drug induced, exercise and cold air

• Pathogenesis: Inhaled allergen is phagocytosed by DC, presented to TH2 cell, then IL-4 causes B cells to class-switch to IgE and bind mast cells, then upon second exposure the mast cells degranulate uncontrollably and goblet cells produce mucus. This all leads to momentary airway narrowing due to hypertrophy of bronchial walls smooth muscle and mucus overproduction

• Wheezing, dyspnea, chest tightness, cough, charcot-leiden crystals in sputum histologically

Bronchiectasis

• Defined as

• Causes

• Predisposing Factors

• Clinical Features

• Defined as permanent dilation of the bronchi and bronchioles due to destruction of smooth muscle and elastic tissue

• Caused by chronic necrotizing infections (Staph A. and Klebsiella)

• Predisposing factors include bronchial obstruction, congenital conditions and necrotizing pneumonia (caused by Staph A. or Klebsiella!)

• Clinical Features: Chronic cough, purulent sputum, dyspnea, hemoptysis and recurrent respiratory tract infections

Atelectasis

• Defined as

• Causes

• Defined as alveolar collapse

• Can be caused by Failure of expansion, obstruction, external constriction or lung immaturity in newborns (no surfactant)

Idiopathic Pulmonary Fibrosis (IPF)

• Defined as

• Causes

• Pathogenesis

• Clinical Features

• Patchy, progressive bilateral interstitial fibrosis and respiratory failure, CRPD

• Unknown etiology, said to have genetic component, seen after 50 yo

• Germline MUC5B gene has telomerase loss and results in reduced mucin production and excessive fibroblastic proliferation → can be associated with smoking

• Fibrotic lungs, patchy interstitial fibrosis, histology shows honeycomb shape, dry crackles during inspiration, dry cough, dyspnea on exertion, can lead to hypoxemia, cyanosis and clubbing

Simple Coal Worker’s Pneumoconiosis

• Defined as

• Causes

• Pathogenesis

• Clinical Features

• Lung disorder caused by inhalation of coal dust

• Caused by inhalation of carbon pigment

• Carbon pigment/coal is inhaled and engulfed my alveolar and interstitial macrophages, causes inflammation and eventually leads to fibrosis and other complications

• Starts as Pulmonary Anthracosis, a benign form → Progresses to Coal Worker’s Pneumoconiosis (CWP), where coal macules and coal nodules form, eventually leading to fibrosis and centrilobular emphysema → May complicate into Progressive Massive Fibrosis (PMF) which cause pulmonary dysfunction, pulmonary hypertension and Cor Pulmonale

• Clinical features include multiple black scars in lungs, dense collagen and pigment due to fibrosis

Silicosis

• Defined as

• Causes

• Pathogenesis

• Clinical Features

• Lung disorder caused by inhalation of crystalline silica (quartz)

• Inhalation of silica, most prevalent chronic occupational lung disease worldwide

  • Sandblasting and Hard-rock mining

• Macrophages engulf silica particles and activate inflammasome, results in fibrosis and lung damage

• Pale to black nodules in the upper zone of lungs, silicotic nodules arranged in whorled appearance and made of hyaline collagen fibers

  • Often asymptomatic until it has progressed to Progressive Massive Fibrosis (PMF) which includes pulmonary hypertension and cor pulmonale

Asbestosis

• Defined as

• Causes

• Pathogenesis

• Clinical Features

• Lung disorder (Pneumoconiosis)

• Caused by heavy inhalation of asbestos fibers especially occupationally

• Asbestos fibers are inhaled and phagocytosed by macrophages, which activates inflammasome → Also is a carcinogen

• Diffused pulmonary interstitial fibrosis, asbestos bodies histologically that look like golden brown beaded rods with knobbed ends, pleural plaques, Dyspnea worsening, mesothelioma linked

Sarcoidosis

• Defined as

• Cause

• Clinical Features

• Systemic Disease

• Unknown Etiology, said to be caused by dysregulated T cell response to the environment, viruses, bacteria, etc.

• Bilateral hilar lymphadenopathy, non-caseating granulomas in multiple organs, giant cells can be seen on microscope within the epithelioid granulomas → dyspnea, diffuse interstitial fibrosis and pulmonary hypertension, hypercalcemia and hypercalciuria, Langerhans cells have asteroid bodies

Pneumonia

• Defined as

• Predisposing Factors

• Two main anatomic patterns of bacterial pneumonia

• Routes of Infection

• Broad term for infection in the lung/s

• Predisposing factors include, pre-existing lung diseases, defects in immunity, loss of cough reflex/mucociliary apparatus, accumulation of secretions, things are easily inhaled

• Bronchopneumonia (consolidation in patchy consistency) and Lobar (Consolidation of entire lobe)

• Aspiration, Inhalation, Hematogenous

  • Community-acquired, Nosocomial, Opportunistic

Community-Acquired Bacterial Pneumonias

• Describe each

• Describe Clinical features of them as a group

• Strep pneumoniae: most common cause of community-acquired pneumoniae

  • gram +, diplococci

• Staphylococcus aureus: causes secondary pneumonia after viral respiratory illnesses

  • High incidence of lung abscess and empyema (pockets of pus)

  • Severe necrotizing pneumonia and infective endocarditis

• Klebsiella pneumoniae

  • gram -

  • Affects debilitated and malnourished individuals, particularly chronic alcoholics

  • Thick gelatinous sputum, empyema

• Legionella pneumophila

  • gram -

  • Causes Legionnaire disease and Pontiac fever (self limited U res tract infection)

  • Thrives in aquatic environments and spreads through aerosol

• Clinical features: fever, chills, cough and sputum, pleuritis, abcess formation, empyema, bacteremia

Viral Pneumonias

• Causes

• Affects

• Caused by Influenza types A and B → or any of the ones causing common colds

• Affects immunocompromised such as children and elderly

• Clinical Features: alveolar edema and fibrosis, affected areas are red-blue and congested, interstitial inflammation, may not include cough, fever, headache, myalgia

Tuberculosis

• Defined as

• Causes

• Pathogenesis

• Clinical Features

• Communicable chronic granulomatous disease

• Mycobacterium tuberculosis, an acid-fast bacilli

• Triggers cell-mediated immunity after inhalation. Enters macrophages and proliferate, causing bacteremia, most times it can be resolved by Th1 cells

• Caseating granulomas and cavitation

Opportunistic Fungal Pneumonia

• Occurs in what kind of patient

• Cause

• Characteristics

• Occurs in AIDS patients because they are very vulnerable

• Caused by Pneumocystis jirovecii

• Characterized by pink frothy intraalveolar exudate and rounded-to-cup-shaped cysts with a central dimple → seen using silver stain

Pulmonary Embolism (PE)

• Defined as

• Pathophysiology

• Clinical Features

• Defined by thrombi that occludes the large pulmonary arteries

• Causes pulmonary hypertension and ischemia of downstream pulmonary parenchyma

• Most embolisms are clinically silent

  • Some are non-thrombotic, that means the blockage is not caused by blood, but by other things such as amniotic fluid, fat/marrow, foreign bodies and air

  • May result in right heart failure or shock/death

Pulmonary Edema

• Defined as

• Causes

• Clinical Consequences

• Symptoms

• Fluid accumulation in alveolar spaces that reduces gas exchange

• Causes include increased hydrostatic pressure, decreased osmotic pressure, lymphatic obstruction

• Clinical Consequences include hypoxia, hypercapnia

• Symptoms include dyspnea, cough, fluid retention, orthopnea

Acute Respiratory Distress Syndrome (ARDS)

• Define

• Causes

• Pathophysiology

• Clinical Features

• Respiratory failure due to injury to alveolar epithelial and capillary endothelial cells

• Causes include viral or bacterial responses, shock, trauma, drugs, etc

• Pathophysiology:

  • Acute Phase: destruction of type I and some type 2 pneumocytes, edema, hyaline membrane forms

  • Organizing Phase: increase in reactive type 2 pneumocytes, resorption of hyaline membrane and thickening of alveolar septum by fibroblasts

• Hypoxemia (fibrosis and edema impair oxygen exchange) and bilateral pulmonary infiltrates, diffuse alveolar damage (both lungs show “white out” on x-ray), presence of hyaline membrane

  

Neonatal Respiratory Distress Syndrome

• Define

• Causes

• Clinical Features

• Respiratory Failure in Newborn

• Caused by immaturity of the surfactant system in preterm babies

• Hyaline membrane, “white out” in both lungs on x-ray, collapsed lungs and inadequate gas exchange, tachypnea, cyanosis

Non-small cell carcinoma vs. Small-cell carcinoma

Non-small: slow spreading and includes adenocarcinoma, squamous cell carcinoma and large cell carcinoma

Small cell carcinoma: very aggressive and fast growing

Primary Lung Adenocarcinoma and Primary Lung Squamous Carcinoma

• Common in

• Location

• Characteristics

Adenocarcinoma

• Most common type in women and non-smokers

• Located peripherally

• Slow growing but metastases at an early stage

Squamous

• Same exact thing except it is centrally located

Large Cell Carcinoma

• Undifferentiated epithelial tumors with no microscopic features allowing classification into any other category

Small cell Carcinoma

• Location

• Characteristics

• Centrally located

• Small tumor cells, very aggressive and fast growing, may secrete hormones, unlike the other, it needs systemic therapy

Carcinoid Tumor

• Location

• Characteristics

• Most originate in the main bronchi

• Low grade neuroendocrine tumor, resectable and curable, carcinoid syndrome may occur (intermittent diarrhea, flushing and cyanosis)

Lung Cancer Related Phenomena

Paraneoplastic syndrome: remote effects such as hypercalcemia, ADH abnormal secretion, Corticotropic effects (cushing’s), neurologic syndromes

Pancoast Syndrome: tumor in apical segment of upper lung lobe compresses recurrent laryngeal nerve (hoarseness) and cervical plexus

• Horner Syndrome: tumor in apical segment of upper lung lobe compresses cervical sympathetic plexus and leads to miosis, ptosis, anhidrosis

Lung Cancer Clinical Features

• Most patients with symptoms already have advanced disease and metastasis

• Cough, hemoptysis, dyspnea, chest pain

Pleural effusion

• Two types

• Transudate: thin, watery with few cells/proteins, causes hydrothorax, most commonly caused by congestive heart failure

• Exudate: protein content is high and contains inflammatory cells, suggests pleuritis (inflammation of pleura)

Malignant Mesothelioma

• Strongly associated with asbestos exposure (80-90%)

• Has a long latent period of 25 to 40 years

• Preceded by pleural fibrosis and plaque formation