Respiratory System I PDF

RESPIRATORY SYSTEM Dimitrios N. Kanakis, MD, PhD Pathologist & Neuropathologist Professor & Head of Pathology University of Nicosia Medical School  Learning Objectives  Describe the infectious, immunologic and inflammatory disorders of the upper airways.  Describe the t...

RESPIRATORY SYSTEM Dimitrios N. Kanakis, MD, PhD Pathologist & Neuropathologist Professor & Head of Pathology University of Nicosia Medical School  Learning Objectives  Describe the infectious, immunologic and inflammatory disorders of the upper airways.  Describe the traumatic and mechanical disorders of the upper airways.  Describe the benign and malignant tumours of the upper respiratory tract.  Explain congenital structural disorders of lungs and diaphragm.  Describe pulmonary embolism and infarct.  Describe pulmonary hypertension.  List the causes of pulmonary oedema. DISORDERS OF THE UPPER RESPIRATORY TRACT  Acute Rhinitis  Common Cold  Cause: Adenoviruses  Clinical picture: “Runny nose”, sneezing, nasal congestion, mild sore throat  Allergic Rhinitis  IgE type I immune reaction  Involvement of mucosal and submucosal mast cells  ↑ Eosinophils in peripheral blood and nasal discharge  Acute Rhinitis  Bacterial infection  Super-infection on acute viral or allergic rhinitis  Cause: Streptococci, Staphylococci, H. influenzae  Macro-/Microscopic picture:  Fibrous scarring  Atrophy of epithelium and mucous glands  Decreased vascularity Acute Rhinitis www.omicsonline.org Allergic Nasal Polyp Prominent eosinophilic Infiltrates Inflammatory Nasal Polyp ❖ Oedematous stroma with dilated capillaries ❖ Mixed inflammatory infiltrate ❖ Increased numbers of eosinophils  Chronic Sinusitis  Synonym: Chronic Rhinosinusitis  Definition: Common condition characterised by inflammation and swelling of the sinuses for at least 12 weeks, despite treatment attempts  Epidemiology: Most commonly affected, young and middle-aged adults  Cause: Infections or nasal polyps in the sinuses or a deviated nasal septum  Pathogenesis: Obstruction of drainage outlets from the sinuses → Accumulation of mucoid secretions or exudate  Chronic Sinusitis  Signs and Symptoms:  At least two of the four primary signs and symptoms of chronic sinusitis must be present with confirmation of nasal inflammation for a diagnosis of the condition. These are:  Thick, discoloured discharge from the nose or drainage down the back of the throat (postnasal drainage)  Nasal obstruction or congestion, causing difficulty breathing through nose  Pain, tenderness and swelling around the eyes, cheeks, nose or forehead  Reduced sense of smell and taste in adults or cough in children  Chronic Sinusitis  Other Signs and Symptoms can include:  Ear pain  Aching in the upper jaw and teeth  Cough that might worsen at night  Sore throat  Bad breath (halitosis)  Fatigue or irritability  Nausea  Acute vs. Chronic Sinusitis  Similar signs and symptoms  Acute Sinusitis: A temporary infection of the sinuses, often associated with a cold  Chronic Sinusitis: The signs and symptoms last longer and often cause more fatigue  Fever: Not common sign of chronic sinusitis, but maybe present in acute sinusitis Sinusitis www.entandsleep.com  Laryngitis  Acute inflammation of the larynx  Cause: Inhalation of irritants, allergic reactions, viruses, bacteria, voice overuse  Clinical manifestations: Inflammation and oedema of the vocal cords → Hoarseness  Uncommon forms: A. Tuberculous Laryngitis: Consequence of protracted active Tbc; Infected sputum is coughed up  Laryngitis Viral Bacterial www.app1.unmc.edu www.app1.unmc.edu  Laryngitis B. Diphtheritic Laryngitis:  Pathogenesis: Inhalation of Corynobacterium diphtheriae → Implantation on the upper-airways’ mucosa → Release of exotoxin → Necrosis of the epithelium → Dense fibrino-purulent exudate (superficial dirty-gray pseudo-membrane)  Laryngitis B. Diphtheritic Laryngitis:  Clinical Features:  Tonsils & Pharynx:  Sore throat, low fever, malaise, dysphagia  “Bull-neck” appearance with a distinct collar of swelling and lymphadenopathy  Larynx: Symptoms similar to laryngotracheo- bronchitis; Initially hoarseness → Loss of voice and severe respiratory tract obstruction  Skin: Pain, tenderness and erythema → Ulcers with sharply defined borders and brownish-grey membrane Diphtheritic Laryngitis “Bull-neck” appearance  Laryngitis B. Diphtheritic Laryngitis:  Complications:  Sloughing and aspiration of the pseudo-membrane → Obstruction of major airways  Absorption of bacterial exotoxins → Myocarditis, peripheral neuropathy  Diphtheritic Laryngitis Membrane Ulcer with sharply defined borders of Diphtheria  Acute Epiglottitis  Definition: Acute inflammation of the epiglottis  Epidemiology: Young children  Cause: Haemophilus inluenzae  Clinical features: Pain and airway obstruction  Prognosis: Failure to appreciate the need to maintain an open airway for a child → Life-threatening condition with fatal consequences Acute Laryngotracheobronchitis  Synonym: Croup  Inflammation of the larynx, trachea and epiglottis  Cause: Children: Parainfluenza Virus (most common), Respiratory Syncytial Virus  Clinical picture:  Harsh, persistent cough  Inspiratory stridor  Complications:  Occasionally, laryngeal inflammatory reaction → Prominent airway narrowing → Respiratory failure  Secondary bacterial infection (Staphylococci, Strepto- cocci, H. influenzae) of upper respiratory tract Acute Laryngotracheobronchitis  TRAUMATIC AND MECHANICAL DISORDERS OF THE UPPER AIRWAYS  Epistaxis  Definition: Nosebleed, which can range from a trickle to a strong flow  Types: 1. Anterior: Most common; Originate from a plexus of vessels in the antero-inferior septum (Kiesselbach’s area) 2. Posterior: Less common, but more serious; Originate in the posterior septum overlying the vomer bone, or laterally on the inferior or middle turbinate. Associated with atherosclerosis or bleeding disorders www.merckmanuals.com Epistaxis www.hughston.com  Epistaxis  Causes:  Local trauma (e.g. nose blowing and picking)  Drying of the nasal mucosa  Less common: Local infections, foreign bodies, arteriosclerosis, septal perforation, coagulopathy  Particular attention for:  Signs of hypovolaemia or haemorrhagic shock  Anticoagulant drug use  Cutaneous signs of a bleeding disorder  Bleeding not stopped by direct pressure  Multiple recurrences, with no clear cause www.merckmanuals.com  Epistaxis  Treatment:  Anterior epistaxis:  Pinching the nasal alae together for 10min; patient sits upright  Cotton pledget impregnated with vasoconstrictor (phenylephrine) and a topical anaesthetic (lidocaine) inserted and nose pinched for another 10min  Cauterization of the bleeding point with electro- cautery or silver nitrate on an applicator stick  Insertion of a nasal tampon of expandable foam, after being coated with a topical ointment (e.g. bacitracin) www.merckmanuals.com  Epistaxis  Treatment:  Posterior epistaxis:  Commercial balloons  Posterior gauze pack  Occasionally, ligation of internal maxillary artery and its branches  Alternatively, angiographic embolisation www.merckmanuals.com  Barotrauma  Definition: Tissue injury caused by a pressure related change in body compartment gas volume  Affected organs: Lungs, ears, sinuses, GI tract, etc.  Risk conditions: Those interfering with equilibration of pressure (e.g. sinus congestion, Eustachian tube blockage, structural anomaly, infection)  Pathogenesis: Entrapment of air or other gas within the lungs → Over-inflation of them → Pulmonary barotrauma  Barotrauma  Symptoms: Immediate occurrence, after pressure changes  Ear pain  Vertigo  Hearing loss  Sinus pain  Epistaxis  Abdominal pain  Alveolar rupture and pneumothorax → Dyspnoea and loss of consciousness  Barotrauma  Diagnosis:  Clinical evaluation  Imaging tests  Treatment:  Symptomatic treatment and outpatient follow-up  Life threatening conditions: Alveolar or GI rupture a. Abnormal vital signs → High flow 100% O2 b. In case of respiratory failure → Endotracheal intubation  Barotrauma  Treatment (cont.): c. Neurologic symptoms → Recompression chamber d. Pneumothorax → Chest decompression with a large bore needle (2nd intercostal space, mid- clavicular line) & subsequent thoracostomy Laryngeal/Pharyngeal Obstruction  Blockage of upper airway, occurs when the upper breathing passages become narrowed or blocked → Impairment of breathing  Affected parts: i. Trachea, ii. Larynx, iii. Pharynx Laryngeal/Pharyngeal Obstruction  Causes:  Allergic reactions to various agents and substances  Chemical burns and reactions  Epiglottitis  Fire or burns from breathing in smoke  Injury or infections of the upper airways  Peritonsillar or retropharyngeal abscess  Laryngeal cancer Laryngeal/Pharyngeal Obstruction  Symptoms:  Agitation or fidgeting  Cyanosis  Changes in consciousness → Unconsciousness  Choking  Confusion and panic  Difficulty in breathing and gasping for air  Unusual breathing noises: Wheezing, crowing, whistling Laryngeal/Pharyngeal Obstruction  Exams and Tests:  Physical examination:  Decreased breath sounds in the lungs  Rapid, shallow, or slowed breathing  Bronchoscopy  Laryngoscopy  X-rays Laryngeal/Pharyngeal Obstruction  Treatment:  Removal of stacked objects with special instruments  Insertion of a tube into the airway (endotracheal tube)  Tracheostomy or cricothyrotomy Laryngeal/Pharyngeal Obstruction  Tracheomalacia  Congenital Tracheomalacia: Weakness and floppiness of the walls of trachea at birth  Causes:  Improper development of the cartilage in the trachea  Instead of being rigid, the walls of the trachea are floppy → Difficulties in the passage of air www.medlineplus.gov  Tracheomalacia  Acquired Tracheomalacia: Weakness and floppiness of the walls of trachea after birth  Causes: When normal cartilage in the wall of trachea begins to break down, in following cases:  Large blood vessels compressing the airway  Complications of reparative surgical procedures for birth defects in the trachea and esophagus  After prolonged tracheostomy www.medlineplus.gov  Tracheomalacia  Symptoms:  Breathing noises that may change with position and improve during sleep  Breathing problems, getting worse with coughing, crying, feeding or upper respiratory infections  High-pitched breathing  Rattling or noisy breaths www.medlineplus.gov  Tracheomalacia  Exams and Tests:  X-ray: Narrowing of the trachea, when breathing in  Laryngoscopy; Estimation of trachea’s narrowing  Bronchoscopy  Barium swallow  CT and MRI scan  Lung function tests  Treatment:  Infants: Humidified air, careful feedings and administration of antibiotics (in case of infections) www.medlineplus.gov  Tracheomalacia  Prognosis:  With time, cartilage gets stronger and trachea grows → Improvement of the noisy and difficult breathing, by the age of 18-24 months  Complications:  Often, tracheomalacia is associated with other congenital anomalies, such as: heart defects, developmental delay, oesophageal atresia and tracheo-oesophageal fistula www.medlineplus.gov  Foreign Body  Inhalation of a foreign object into the nose, mouth, or lower respiratory tract → Stuck within the respiratory system → Breathing problems or choking → Inflammation and infection  Epidemiology: Mostly children, 1-3 years old  Causes: Certain foods (e.g. nuts, seeds, popcorn) and small objects (e.g. buttons, beads) → Partial or total airway blockage  Foreign Body  Symptoms:  Patients with complete airway obstruction require immediate medical attention and typically are aphonic and unable to breathe  Patients who are coughing, gagging, and vocalising have partial obstruction  Management:  Use of the Heimlich manoeuvre has improved the mortality rate of patients with complete airway obstruction, but use of it in patients with partial obstruction may produce complete obstruction TUMOURS OF THE UPPER RESPIRATORY TRACT TUMOURS OF THE NOSE AND NASAL SINUSES  Papilloma  Epidemiology:  Most common benign neoplasm of nasal cavity and paranasal sinuses  Male, 50-60 years  Clinical features: Nasal obstruction, epistaxis  Types:  Exophytic: Grows outward from epithelial surface; Lateral walls  Endophytic: Grows inward into tissues in finger-like projections from a superficial site of origin; Nasal diaphragm  Papilloma  Microscopic features:  Cylindrical epithelium of airway tract with increase in the number of cellular rows  Squamous metaplasia of cylindrical epithelium  Resemblance to transitional (cell) epithelium  Papilloma Exophytic Endophytic  Tumours of the Nose and Nasal Sinuses  Angiofibroma  Epidemiology: Rare, prominent vascularised lesion  Clinical manifestation: Mainly with epistaxis  Localisation: In the posterior nasal wall of adolescent males  Microscopic findings: Numerous blood vessels in a marked fibrotic matrix  Prognosis: Histologically benign, but locally aggressive Angiofibroma Marked fibrotic stroma  Tumours of the Nose and Nasal Sinuses  Squamous Cell Carcinoma:  Epidemiology: Most frequent malignant nasal tumour  All types of differentiation (well-, moderately- and poorly-differentiated tumours)  Tumours of the Nose and Nasal Sinuses  Squamous Cell Carcinoma (cont.):  Microscopic findings:  Large, eosinophilic and polygonal cells  Cells are layered in an architectural pattern that looks like squamous cell epithelium  Frequently, keratin production (in the centre of a group of epithelial cells with a whorled appearance; This type of keratin is known as “keratin pearl”) Squamous Cell Carcinoma of Nasopharynx  Well differentiated Squamous Cell Carcinoma Keratin pearl  Tumours of the Nose and Nasal Sinuses  Nasopharyngeal Carcinoma (Undifferentiated):  Synonym: Lymphoepithelioma  Epidemiology: Common in Southeast Asia and East Africa  Cause: Epstein-Barr virus  Localisation: Pharyngeal fossa of Rosenmüller  Tumours of the Nose and Nasal Sinuses  Nasopharyngeal Carcinoma (Undifferentiated):  Microscopic features:  Tumours composed of sheets or large bands of large undifferentiated cells that also contain a population of non-neoplastic small (predominantly T) lymphocytes  Tumour cells with vesicular nuclei and prominent cytoplasm  No signs of keratinisation  Immunohistochemistry: [+] PANCKs, CK-8, -18, -19, ΕΜΑ, B-, T-cell, LCA and EBV (EBER in-situ hybridisation) Lymphoepithelioma  Tumours of the Nose and Nasal Sinuses  Adenocarcinoma:  Epidemiology: 5% of malignant tumours of the nose and throat  Microscopic classification:  Intestinal-Type Adenocarcinoma (Neoplastic intestinal glands resembling Colonic Adeno-Ca)  Non-Intestinal Type Adenocarcinoma  Salivary gland-like Carcinomas (Adenoid Cystic Carcinoma) Intestinal-Type Adenocarcinoma Intestinal-Type Adenocarcinoma Non Intestinal-Type Adenocarcinoma Tubulo-lobular Tubulo-papillary Solid-cribriform with Comedo necrosis Solid ribbon Adenoid Cystic Carcinoma  Tumours of the Nose and Nasal Sinuses  Olfactory Neuroblastoma:  Synonym: Aesthesioneuroblastoma  Usually, older male patients (paediatric tumours: adrenals/abdomen of infants and young children)  Microscopic picture:  Small round blue cells in a neurofibrillary matrix  Characteristic Flexner-Wintersteiner rosettes  Immunohistochemistry: Positivity for: Chromogranin, ACTH, Neurofilament (NF), Neuron Specific Enolase (NSE), S-100 and Cytokeratins (CKs) Olfactory Neuroblastoma Flexner-Wintersteiner rosettes http://www.cttr.org  Olfactory Neuroblastoma Chromogranin S-100  Tumours of the Nose and Nasal Sinuses  Plasmacytoma:  Localisation: Upper airway tract  Most common extra-medullary site  Either as a regional manifestation of Multiple Myeloma or as a primary lesion  Macroscopic features:  Sub-mucosal localisation  Airway tract obstruction  Ulceration and haemorrhage Plasmacytoma Tumour occupying the nasal cavity and right maxillary sinus  Tumours of the Nose and Nasal Sinuses  Plasmacytoma (cont.)  Microscopic findings:  Diffuse cellular population  Round to ovoid cells  “Cart-wheel” chromatin  Basophilic cytoplasm  Immunohistochemistry:  Positivity in one of the light chains (κ, λ) and in one immunoglobulin (IgG, IgM)  Positive staining for: CD38, CD79A, CD138, VS38c Plasmacytoma  Tumours of the Nose and Nasal Sinuses  Embryonal Rhabdomyosarcoma:  Aggressive mesenchymal malignancy of skeletal muscle origin  Epidemiology:  Most common soft tissue sarcoma of childhood and adolescence  Approximately 87% of patients 40 years  Predisposing factors:  Combination of cigarette smoking and alcoholism  NO association to HPV infection  Clinical picture: Persistent hoarseness Low grade dysplasia Middle grade dysplasia High grade dysplasia Ca in situ  Tumours of the Larynx  Glottic Carcinoma:  Originates from the true vocal cords  Most common and best prognosis  Supra- and Subglottic Carcinomas:  Less common and worse prognosis Squamous Cell Carcinoma Glottic Carcinoma Sub-Glottic Carcinoma  Squamous Cell Carcinoma Supra-Glottic Carcinoma Supra-Glottic Carcinoma Squamous Cell Carcinoma Well differentiated Poorly differentiated  SUMMARY  Infectious, Immunologic and Inflammatory Disorders of the Upper Airways:  Acute Rhinitis  Sinusitis (Acute and Chronic)  Laryngitis (e.g. viral, bacterial, diphtheritic)  Acute Epiglottitis  Acute Laryngotracheobronchitis  SUMMARY  Traumatic and Mechanical Disorders of the Upper Airways:  Epistaxis  Barotrauma  Laryngeal/Pharyngeal Obstruction  Tracheomalakia  Foreign Body  SUMMARY  Tumours of the Upper Respiratory Tract:  Tumours of the Nose and Nasal Sinuses  Tumours of the Oropharynx  Tumours of the Larynx Thank you for your attention! CONGENITAL DISORDERS  Bronchogenic Cysts  Lesions of congenital origin derived from the primitive foregut  Epidemiology:  Mediastinum: Majority; Lung parenchyma: 15-20%  Most common primary cysts of the mediastinum  Imaging studies:  Uni-locular, non-calcified masses  Sphaerical or oval, with smooth outlines  DD: Lung abscess, Tbc, infected bullas, neoplasms, etc. Sarper A et al. Texas Heart Institute Journal. 2003; 30:105-108  Bronchogenic Cysts  Macroscopic features:  Uni-locular cyst (cyst with a single sac)  Content: Clear fluid, haemorrhagic secretions or air  Microscopic features:  Cyst’s internal lining: Columnar ciliated epithelium  Cyst’s wall: Cartilage and bronchial mucous glands Sarper A et al. Texas Heart Institute Journal. 2003; 30:105-108  Bronchogenic Cysts Schattauer Verlag Schattauer Verlag  Bronchogenic Cysts Bronchial-type epithelium Ciliated respiratory epithelium Cartilage Sarper A et al. Texas Heart Institute Journal. 2003; 30:105-108  Bronchogenic Cysts  Clinical features:  Cough  Fever  Pain  Dyspnoea  Tracheobronchial compression and lung infections (in children; because of the soft tracheo-bronchial tree) Sarper A et al. Texas Heart Institute Journal. 2003; 30:105-108  Bronchogenic Cysts  Complications:  Infections (in cysts with bronchial communications)  Rapture of cyst into trachea, pleural or pericardial cavity  Pneumothorax, accompanied by pleuritis Sarper A et al. Texas Heart Institute Journal. 2003; 30:105-108  Congenital Cystic Lesions of the Lung  Most common malformations of the lower respiratory tract:  Congenital Cystic Adenomatoid Malformation [CCAM] (= congenital pulmonary airway malformation)  Broncho-Pulmonary Sequestration [BPS]  Pathogenesis:  Abnormalities that occur during the branching and proliferation of the bronchial structures  Abnormal proliferation of tissues, airway obstruction, dysplasia and metaplasia of the normal tissue Sfakianaki AK. Rev Obstet Gynecol 2012;5:85-93  Congenital Cystic Lesions of the Lung  Hamartomatous lesion containing tissue from different pulmonary origins Congenital Cystic Adenomatoid Malformation classification, based on presumed site of develop- ment of the malformation: 0 = Tracheo-bronchial 1 = Bronchial/bronchiolar 2 = Bronchiolar 3 = Bronchiolar/alveolar 4 = Distal acinar Sfakianaki AK. Rev Obstet Gynecol 2012;5:85-93  Congenital Cystic Adenomatoid Malformation  Type 0:  Rarest form  Arises from trachea or bronchus  Severe, usually lethal presentation  Type 1:  Most common form (50-70%)  Arises from the distal bronchus or proximal bronchiole  Small number of large echolucent cysts (3-10 cm)  Thin walls, lined by ciliated pseudo-stratified epithelium  Can cause mass effect → Results in hydrops Sfakianaki AK. Rev Obstet Gynecol 2012;5:85-93  Congenital Cystic Adenomatoid Malformation  Type 2:  15-30% of cases  Arise from terminal bronchioles  Highest incidence (60%) of associated anomalies (e.g. patent ductus arteriosus, tetralogy of Fallot, renal agenesis/dysgenesis, gastrointestinal atresia, etc.)  Composed of smaller cysts (0.5-2cm) and solid areas  Lined by ciliated cuboidal or columnar epithelium  Presence of elements of bronchioles or alveoli Sfakianaki AK. Rev Obstet Gynecol 2012;5:85-93  Congenital Cystic Adenomatoid Malformation Type 2 Sfakianaki AK. Rev Obstet Gynecol 2012;5:85-93  Congenital Cystic Adenomatoid Malformation  Type 3:  5% of cases  Arise from acinar-like tissue  Composed of very small cysts  Highly echogenic on ultrasound  Adenomatoid elements, consistent with distal airway  Type 4:  5-15% of cases  Large cysts (up to 10cm)  Alveolar origin  Associated with malignancy (specifically, pleuro- pulmonary blastoma) Sfakianaki AK. Rev Obstet Gynecol 2012;5:85-93  Congenital Cystic Adenomatoid Malformation Type 3 Sfakianaki AK. Rev Obstet Gynecol 2012;5:85-93  Congenital Cystic Adenomatoid Malformation  Antenatal classification:  Microcystic (5mm): Types 1, 2 & 4  Microcystic lesions larger and with less favorable outcome than macrocystic lesions Sfakianaki AK. Rev Obstet Gynecol 2012;5:85-93  Broncho-Pulmonary Sequestration  Made of peripheral and non-functioning lung tissue, separated from the normal pulmonary structure  Localisation: Intralobar or extralobar  Intralobar:  Observed within the lung  Without own pleura  Extralobar:  Completely covered with pleura  May be extrathoracic; 10% subdiaphragmatic, left side  Both intra- and extralobar: Solid, well-circumscribed and echogenic masses (US), similar to Type 3 CCAM Sfakianaki AK. Rev Obstet Gynecol 2012;5:85-93  Broncho-Pulmonary Sequestration Schattauer Verlag Schattauer Verlag Congenital Cystic Lesions Sfakianaki AK. Rev Obstet Gynecol 2012;5:85-93 Congenital Diaphragmatic Hernia  Rare but severe condition, affecting 1 in 2000-3000 newborns with a survival rate of 67%  Types: 1. Postero-lateral Bochdalek-type (70%) 2. Anterior Morgagni-type (27%) 3. Central septum transversum-type (2-3%)  CDH defects range from small subcentimeter defects to complete diaphragmatic agenesis  Bochdalek hernias: Left side (85%); Right side (13%); Bilateral (2%) Haroon J. CPJ 2012;52:115-124 Types of Hernia Haroon J. CPJ 2012;52:115-124 Congenital Diaphragmatic Hernia  Beginning of diaphragm’s development: 4 weeks of gestation  Genesis:  Fusion of several distinct parts → Formation of a solitary membrane → Separation of the thoracic from the abdominal cavity  Anterior central tendon arises from the ventral body wall as the septum transversum  Pleuro-peritoneal membrane arises from the postero- lateral body wall, and fuses with the esophageal mesentery to close off the pleuro-peritoneal canals  Right side closes before the left side Haroon J. CPJ 2012;52:115-124 Fetal Development of the Diaphragm Haroon J. CPJ 2012;52:115-124 Congenital Diaphragmatic Hernia  Hypothetical pathogenetic mechanisms: 1. Result from a non-fusion of different parts of the diaphragm (failed fusion) → Herniation of abdominal contents into the thorax → Compression and dysgenesis of the lungs 2. Abnormal lung development → Results in abnormal diaphragmatic development 3. Failure of the pleuro-peritoneal fold to fuse with the post-hepatic mesenchyme Haroon J. CPJ 2012;52:115-124 Congenital Diaphragmatic Hernia Congenital Diaphragmatic Hernia  Diagnosis:  Ultrasound:  Assessment of the extent of herniation and associated mediastinal shift  Inadequate to identify a herniated liver because of its comparable echogenicity to the foetal lung  Doppler US: Assessment of blood flow to the ipsila- teral lung, which closely parallels lung development  MRI:  Provides detail of the herniated viscera  Allows for precise measurements for prognostic calculation Haroon J. CPJ 2012;52:115-124 Congenital Diaphragmatic Hernia  Major Factors Determining Severity  When CDH is the only problem, severity and thus, outcome is determined by two factors: 1. Liver position: Foetuses with the liver up in the chest  More severe form of CDH and lower survival rate 2. Lung-to-Head Ratio or LHR: Numeric estimate of the size of the foetal lungs, based on measurement of the amount of visible lung; High LHR values >1.0  Better outcomes Congenital Diaphragmatic Hernia  Management:  Ventilation  Extracorporeal membrane oxygenation  Management of pulmonary hypertension  Surgical management  Patch repair  Foetal surgery Haroon J. CPJ 2012;52:115-124  Immotile Cilia Syndrome  Synonyms: Primary Ciliary Dyskinesia, Kartagener Syn.  Genetics: Mutations in the DNAI1 [Dynein Axonemal Intermediate chain 1] & DNAH5 [Dynein Axonemal Heavy chain 5]  30% of cases; Autosomal recessive inheritance  Disorder characterised by: a. Chronic respiratory tract infections b. Abnormally positioned internal organs c. Infertility www.ghr.nlm.nih.gov  Immotile Cilia Syndrome  Signs and Symptoms: Caused by abnormal cilia and flagella: ▪ Babies: Breathing problems at birth ▪ Early childhood: Frequent respiratory tract infections → Bronchiectasis ▪ 50% of patients: Situs inversus totalis (mirror-image reversus) www.ghr.nlm.nih.gov  Immotile Cilia Syndrome  Signs and Symptoms (cont.): ▪ 12% of patients: Heterotaxy syndrome or situs ambiguus  Structurally abnormal or improperly positioned organs (heart, liver, intestines, spleen). May also be accompanied by asplenia or polysplenia ▪ Infertility (males: due to flagella dysfunction of sperms; females: due to abnormal cilia in the fallopian tubes) www.ghr.nlm.nih.gov Immotile Cilia Syndrome Dextrocardia Situs inversus Gupta S, et al. Indian J Hum Genet. 2012 May;18(2):263-7 Immotile Cilia Syndrome Chronic Sinusitis Bronchiectasis Gupta S, et al. Indian J Hum Genet. 2012 May;18(2):263-7  Immotile Cilia Syndrome  Treatment:  Antibiotics  Infections (caused commonly by Hemophilus influenzae or Staphylococcus aureus)  Inhaled bronchodilators, mucolytics, and chest physiotherapy  Obstructive lung disease/ bronchiectasis  Surgical care: Tympanostomy tubes → Reduction of recurrent infections and conductive hearing loss Gupta S, et al. Indian J Hum Genet. 2012 May;18(2):263-7  PULMONARY VASCULAR DISEASE  Pulmonary Embolism  Causes: Venous thrombosis (lower extremities or pelvis), fat, amniotic fluid, clumps of tumour cells or bone marrow  Risk factors: Stasis of blood flow (prolonged bed rest or immobilisation), hypercoagulable states, use of oral contraceptives, etc.  Size of embolus  Size of occluded pulmonary vessel  Large emboli → Major vessels (Saddle embolus)  Small emboli → Medium sized and small pulmonary arteries  Pulmonary Embolism www.library.med.utah.edu www.library.med.utah.edu “Saddle embolus" Robbins & Cotran. Pathologic basis of disease  Thrombo-Embolism "lines of Zahn" www.library.med.utah.edu  Thrombo-Embolism Thrombus with recanalisation www.library.med.utah.edu  Pulmonary Embolism  Clinical findings:  Saddle embolus:  Sudden increase in Pulmonary Artery pressure  Acute right ventricular strain → Sudden death  Pulmonary infarction:  Sudden onset of dyspnoea and tachypnoea  Pleuritic chest pain  Friction rub  Effusion  Expiratory wheezing  Embolism Bone Marrow Embolism Amniotic Fluid Embolism  Pulmonary Embolism  Laboratory findings:  Respiratory alkalosis (arterial PCO2 25mmHg at rest (normal: 15 mmHg) b. Mean pulmonary artery pressure >30mmHg with exercise (normal: 20 mmHg)  Pulmonary Hypertension Primary Pulmonary Hypertension:  Rare  Unknown aetiology; Genetic predisposition  NO heart or lung disease  Vascular hyper-reactivity with smooth muscle proliferation  Histologic picture: Characteristic plexiform lesions Pulmonary Hypertension Plexiform Lesions Pulmonary Hypertension Pulmonary Hypertension  Pulmonary Hypertension Secondary Pulmonary Hypertension:  More common than primary  Pathogenesis:  Endothelial cell dysfunction  Loss of vasodilators (e.g. NO)  Increase in vasoconstrictors (e.g. Endothelin)  Hypoxaemia & Respiratory Acidosis → Pulmonary arteries vasoconstriction → Smooth muscle hyperplasia and hypertrophy  Pulmonary Hypertension Secondary Pulmonary Hypertension (cont.):  Causes: ▪ Chronic hypoxaemia (e.g. Chronic lung disease) ▪ Chronic respiratory acidosis (e.g. Chronic bronchitis) ▪ Loss of pulmonary vasculature → Workload for remaining vessels (e.g. Emphysema, recurrent pulmonary emboli) ▪ Left-to-right cardiac shunts → Volume overloading pulmonary vasculature ▪ Left-sided valvular disease (e.g. Mitral stenosis) → Backup of blood into pulmonary veins → Venous hypertension  Pulmonary Hypertension Secondary Pulmonary Hypertension:  Histopathology:  Atherosclerotic changes of main pulmonary arteries (Result of ↑ pressure to endothelium → Endothelial injury)  Proliferation of myo-intimal and smooth muscle cells Artery vs. Vein  Pulmonary Oedema  Intra-alveolar accumulation of fluid  Pathogenesis: 1. Due to alterations in Starling forces (transudate) ▪ Increased hydrostatic pressure in pulmonary capillaries Left-sided heart failure Volume overload Mitral stenosis ▪ Decreased oncotic pressure Nephrotic syndrome Cirrhosis  Pulmonary Oedema  Pathogenesis (cont.): 2. Due to micro-vascular or alveolar injury (exudate)  Increased alveolar capillary permeability ▪ Infections (e.g. sepsis, pneumonia) ▪ Aspiration (e.g. drowning, gastric contents) ▪ Drugs (e.g. heroin) ▪ High altitude ▪ Acute Respiratory Distress Syndrome (ARDS) Pulmonary Oedema Pulmonary Oedema Schattauer Verlag  Pulmonary Oedema Air bubble Intra-alveolar Fluid accumulation Schattauer Verlag www.pathologyatlas.ro Adult Respiratory Distress Syndrome (ARDS)  Causes: Shock, sepsis, trauma, uraemia, aspiration of gastric contents, acute pancreatitis, inhalation of che- mical irritants, oxygen toxicity, heroin, bleomycin, etc.  Pathogenesis: Damage to alveolar capillary endo- thelium and alveolar epithelium (Diffuse alveolar damage) → ↑ in alveolar capillary permeability → Leakage of protein-rich fluid into alveoli Adult Respiratory Distress Syndrome (ARDS)  Pathogenic factors:  Neutrophils → Release of substances, toxic to alveolar wall  Activation of coagulation cascade → Micro-emboli  Oxygen-derived free radicals → Oxygen toxicity Adult Respiratory Distress Syndrome (ARDS) Adult Respiratory Distress Syndrome (ARDS)  ARDS can be a manifestation of the Severe Acute Respiratory Syndrome (SARS); SARS Coronavirus destroys type II pneumocytes and causes diffuse alveolar damage  Clinical feature: Impairment of respiratory gas exchange → Severe hypoxia  Histopathologic picture: Formation of intra-alveolar hyaline membranes (fibrin and cellular debris) Adult Respiratory Distress Syndrome (ARDS) Adult Respiratory Distress Syndrome (ARDS) www.utas.edu.au Schattauer Verlag  Neonatal Respiratory Distress Syndrome (NRDS)  Synonym: Hyaline Membrane Disease  Most common cause of respiratory failure in newborn  Most common cause of death in premature infants  Cause: Deficiency of surfactant, due to immaturity  Clinical features:  Dyspnoea  Cyanosis  Tachypnoea  Neonatal Respiratory Distress Syndrome (NRDS)  Surfactant:  Reduces surface tension within the lung → Facilitates expansion during inspiration and prevents atelectasis during expiration  Secreted by type II pneumocytes  Predisposing factors:  Prematurity  Maternal Diabetes Mellitus  Birth by caesarian section  Neonatal Respiratory Distress Syndrome (NRDS)  Macro-/Microscopic findings:  Heavy lungs, with alternating areas of atelectasis and alveolar or alveolar-ductal dilatation  Engorgement of small pulmonary vessels  Leakage of blood products into the alveoli → Formation of intra-alveolar hyaline membranes (fibrin and cellular debris)  Neonatal Respiratory Distress Syndrome (NRDS) www.pathologyatlas.ro www.pathologyatlas.ro  Neonatal Respiratory Distress Syndrome (NRDS) Hyaline membranes www.library.med.utah.edu  Neonatal Respiratory Distress Syndrome (NRDS)  Complications:  Broncho-Pulmonary Dysplasia: Result of treatment with high-concentration oxygen and mechanical ventilation  Patent ductus arteriosus: Due to immaturity and hypoxia  Intra-ventricular brain haemorrhage  Necrotising Enterocolitis: Fulminant inflammation of the small and large intestines  Broncho-Pulmonary Dysplasia www.library.med.utah.edu ❖ Interstitial fibrosis ❖ Inadequate alveolar development www.pathologyoutlines.com MISCELLANEOUS DISORDERS OF THE LUNGS  Acquired Atelectasis  Collapse of previously inflated lung, producing areas of relatively airless pulmonary parenchyma  Acquired atelectasis, divided into:  Resorption (or Obstruction) Atelectasis  Compression Atelectasis  Contraction Atelectasis  Acquired Atelectasis  Resorption (Obstruction) Atelectasis:  Consequence of complete obstruction of an airway → Resorption of the oxygen trapped in the dependent alveoli, without impairment of blood flow through the affected alveolar walls → Decrease in lung volume  Acquired Atelectasis  Resorption (Obstruction) Atelectasis (cont.):  Diminished lung volume → Shift of the mediastinum toward the atelectatic lung  Causes: Excessive secretions (e.g. mucous plugs) or exudates within smaller bronchi (e.g. bronchial asthma, chronic bronchitis, bronchiectasis, etc.)  Acquired Atelectasis  Compression Atelectasis:  Results whenever the pleural cavity is partially or completely filled by fluid exudate, tumour, blood or air  Shift of the mediastinum away from the affected lung  Contraction Atelectasis:  Occurrence when local or generalised fibrotic changes in the lung or pleura prevent full expansion Acquired Atelectasis www.ibrary.med.utah.edu www.springer.com  Atelectasis Neonatorum  Definition: Failure of alveolar spaces to expand adequately at birth  Failure of initial aeration of the lungs at birth → Persistence of collapsed alveoli → Respiration never fully established  Association with prematurity and intrauterine foetal anoxia Pulmonary Alveolar Proteinosis  Definition: Accumulation of amorphous (sometimes surfactant), PAS (+) material in the alveolar spaces  Etiology:  Most often idiopathic  Rare secondary forms: Occurrence in patients with acute silicosis, Pneumocystis jirovecii infection, haematologic malignancies, significant inhalation exposures to aluminium, titanium, cement and cellulose dusts www.merckmanuals.com Pulmonary Alveolar Proteinosis  Symptoms & Signs:  Progressive exertional dyspnoea  Weight loss  Fatigue  Malaise  Cough, occasionally producing chunky or gummy sputum (less common) www.merckmanuals.com  Pulmonary Alveolar Proteinosis  Diagnosis:  Chest X-Ray:  Bilateral mid- and lower-lung field opacities in a butter- fly distribution with normal hila www.merckmanuals.com  Pulmonary Alveolar Proteinosis  Diagnosis (cont.):  High-resolution CT (HRCT):  Ground-glass opacities  Thickened intra-lobular structures and inter- lobular septa in typically polygonal shapes (crazy- paving); DD: Lipoid pneumonia, broncho- alveolar carcinoma and Pneumocystis jirovecii pneumonia www.merckmanuals.com Pulmonary Alveolar Proteinosis  Diagnosis (cont.):  Pulmonary function tests:  Reduction in diffusing capacity for carbon monoxide (DLco) that is disproportionate to the decreases in vital capacity, residual volume, functional residual capacity, and total lung capacity  Laboratory test abnormalities:  Polycythemia  Hypergammaglobulinemia  Increased serum LDH levels  Increased serum surfactant proteins A and D www.merckmanuals.com Pulmonary Alveolar Proteinosis  Diagnosis (cont.):  Broncho-alveolar lavage: Lavage fluid:  Milky or opaque  PAS (+) staining  Presence of scattered surfactant-engorged macrophages  Increase in T-cells  Sometimes biopsy www.merckmanuals.com Pulmonary Alveolar Proteinosis Pulmonary Alveolar Proteinosis  Treatment:  Whole lung lavage:  General anesthesia  Double lumen endotracheal tube  Procedure: Lavage of one lung up to 15 times with 1-2L saline, while the other lung is ventilated. The process is then reversed www.merckmanuals.com Pulmonary Alveolar Proteinosis  Prognosis:  Without treatment, remission in up to 10%  Single whole lung lavage is curative in up to 40%; other patients require lavage every 6-12 months for many years  5 year survival: ~80%  Most common cause of death: Respiratory failure www.merckmanuals.com  SUMMARY  Congenital Disorders:  Bronchogenic Cysts  Congenital Cystic Lesions of the Lung  Congenital diaphragmatic Hernia  Immotile Cilia Syndrome  Pulmonary Vascular Disease:  Pulmonary Embolism & Infarction  Pulmonary Hypertension  Pulmonary Oedema  SUMMARY  Pulmonary Vascular Disease:  Adult Respiratory Distress Syndrome (ARDS)  Neonatal Respiratory Distress Syndrome (NRDS) and Broncho-Pulmonary Dysplasia  Miscellaneous Disorders of the Lungs:  Acquired Atelectasis  Atelectasis Neonatorum  Pulmonary Alveolar Proteinosis Thank you for your attention!