Respiratory System Stephen Bagley, MD, Resident Physician, University of Pennsylvania RE01-1 RE01-1 Respiratory System: Objectives To understand the following topics and how they may be tested on USMLE Step 1: – – – – – – – – Basic pulmonary anatomy and histology Respiratory physiology Mechanisms of hypoxemia Obstructive lung disease Restrictive lung disease Pneumonia Lung cancer Pulmonary hypertension RE01-1 RE01-2 Respiratory System Lecture 1: Anatomy and Histology RE01-1 RE01-3 The Diaphragm Pain referred to the shoulders due to cervical innervation of diaphragm (C3, C4, C5) Inferior vena cava (T8) Esophagus (T10) Vagus nerve Aorta (T12) Thoracic duct Azygos vein` Kaplan Anatomy 2011 : Figure III-2-36 •FA 2013: 545.2 • FA 2012: 560.2 • FA 2011: 503.3 • ME 3e: 276 • ME4e: 276 RE01-2 • Respiratory Muscles – Diaphragm contracts to increase the size of thoracic cavity – Quiet inspiration mediated via the diaphragm and external intercostals (possibly the scalenes) – Labored breathing: • Inspiration : Scalenes, Sternocleidomastoids and external intercostals • Expiration: Abdominal muscles and internal intercostals •FA 2013: 546.1 • FA 2012: 560.3 • FA 2011: 504.1 • ME 3e: 278 • ME4e: 278 RE01-2 • Paradoxical Breathing – Diaphragmatic fatigue – Abdominal contents move in with inspiration – Sign of impending respiratory failure •FA 2013: 546.1 • FA 2012: 560.3 • FA 2011: 504.1 • ME 3e: 278 • ME4e: 278 RE01-2 • Anatomy of the Respiratory Tree – Conducting zone: • Starts from nose and ends at the terminal bronchioles • Comprises the anatomic dead space – Respiratory zone: gas exchange area • Respiratory bronchioles – These are periodically interrupted by alveoli making gas exchange possible • Alveolar ducts • Alveoli Kaplan Anatomy 2011 : Figure III-2-8 •FA 2013: 544.1 • FA 2012: 558.1 • FA 2011: 502.1 • ME 3e: 274 • ME4e: 274 RE01-3 • Clinical Importance of Respiratory Landmarks – Trachea can be compressed by: • Aortic arch aneurysm • Goiter – Carina can be displaced by: • Left atrial enlargement (CHF) • Metastasis to carinal lymph nodes Kaplan Anatomy 2011 : Figure III-2-8 •FA 2013: 544.1 • FA 2012: 558.1 • FA 2011: 502.1 • ME 3e: 274 • ME4e: 274 RE01-3 • Cartilage in Airways – U-shaped cartilage in trachea to accommodate esophagus posteriorly – Circular cartilage in all sized bronchi – No cartilage in any bronchioles Kaplan Anatomy 2011 : Figure III-2-8 •FA 2013: 544.1 • FA 2012: 558.1 • FA 2011: 502.1 • ME 3e: 274 • ME4e: 274 RE01-3 • Smooth Muscles in Airways – No smooth muscles in trachea – Smooth muscles are found in bronchi and all-sized bronchioles, including respiratory bronchioles – No smooth muscles in alveolar ducts or alveoli – Smooth muscles in the bronchi contribute the most to airway resistance Kaplan Anatomy 2011 : Figure III-2-8 •FA 2013: 544.1 • FA 2012: 558.1 • FA 2011: 502.1 • ME 3e: 274 • ME4e: 274 RE01-3 • Paraneoplastic syndromes – ACTH production: • Cushing syndrome • Associated with small cell carcinoma of the lungs – ADH production: • SIADH (hyponatremia) • Associated with small cell carcinoma of the lungs – PTHrP production: • Hypercalcemia • Associated with squamous cell carcinoma of the lungs •FA 2013: 223.2 • FA 2012: 255.2 • FA 2011: 229.3 • ME 3e: 162 • ME4e: 162 RESP10_11- • Paraneoplastic syndromes (cont’d) – Erythropoetin production: • Renal cell carcinoma • Hepatocellular carcinoma • Hemangioblastoma – Lambert Eaton Syndrome: • Antibodies against pre-synaptic Ca+2 channels • Associated with small cell carcinoma of the lungs and thymoma – Hyperuricemia/urate nephropathy: • Leukemias and lymphomas • Chemotherapy •FA 2013: 223.2 • FA 2012: 255.2 • FA 2011: 229.3 • ME 3e: 162 • ME4e: 162 RESP10_11- Respiratory System Lecture 11: • Pulmonary hypertension • Deep venous thrombosis • Pulmonary embolism RESP11_1RESP11_1-1 • Pulmonary hypertension – Pulmonary artery pressure > 25 mm Hg at rest or >35mm Hg during exercise – Primary & secondary causes – Pathology: • Medial hypertrophy • Intimal fibrosis •FA 2013: 549.2 • FA 2012: 564.2 • FA 2011: 507.2 • ME 3e: 297 • ME4e: 297 RESP11_1- • Primary pulmonary hypertension – – – – Inactivating mutation of BMPR-2 gene Uncontrolled smooth muscle hypertrophy Associated with poor prognosis Pulmonary HTN right ventricular hypertrophy right heart failure •FA 2013: 549.2 • FA 2012: 564.2 • FA 2011: 507.2 • ME 3e: 297 • ME4e: 297 RESP11_1- • Secondary pulmonary hypertension ─ Diseases leading to destruction of lung parenchyma, including: ─ Mitral stenosis ─ Tricuspid stenosis ─ Left-sided heart failure (most common cause of right heart failure) ─ Recurrent thromboembolism ─ Autoimmune diseases scleroderma / vasculitis ─ Long-standing left-to-right shunts Eisenmenger syndrome ─ Living at high altitude ─ Sleep apnea ─ Chronic rejection of lung transplant bronchiolitis obliterans •FA 2013: 549.2 • FA 2012: 564.2 • FA 2011: 507.2 • ME 3e: 297 • ME4e: 297 RESP11_1- • Presentation of pulmonary hypertension – Exertional angina • Right ventricular ischemia – Exertional syncope •FA 2013: 549.2 • FA 2012: 564.2 • FA 2011: 507.2 • ME 3e: 297 • ME4e: 297 RESP11_1- • Sleep Apnea – Recurrent periods of apnea during sleep lasting more than 10 seconds – Central sleep apnea: • Cessation of signals from medullary center – Obstructive sleep apnea: • Obstruction to airflow •FA 2013: 556.3 • FA 2012: 570.3 • FA 2011: 512.2 • ME 3e: 11 • ME4e: 11 RESP11_2- • Obstructive sleep apnea – Associated with: • Obesity • Small jaws (micrognathia) – Presentation: Snoring Daytime somnolence Ventricular arrythmia (due to CO2 retention) Pulmonary hypertension results from chronic hypoxic vasoconstriction • Cor pulmonale • Can result in sudden death • • • • •FA 2013: 556.3 • FA 2012: 570.3 • FA 2011: 512.2 • ME 3e: 11 • ME4e: 11 RESP11_2- • Obstructive sleep apnea (cont’d) – Diagnosed with polysomnography: • Brief stage non-REM rapid induction • Stages & light sleep • Shorter stage & non-REM sleep deep/delta wave sleep • Short REM sleep duration “paralyzed”/dreams – Treatment: • Weight loss • Continuous positive airway pressure (CPAP): – Keeps airways patent during breathing cycle • Surgery •FA 2013: 556.3 • FA 2012: 570.3 • FA 2011: 512.2 • ME 3e: 11 • ME4e: 11 RESP11_2- • Treatment of pulmonary hypertension: – Goal is to promote dilation of pulmonary vasculature – Prostaglandins – Sildenafil: Phosphodiesterase inhibitionà ↑cAMP pulmonary vasodilation – Bosentan: Endothelin receptor antagonist ↓hypoxic vasoconstriction •FA 2013: 549.2 • FA 2012: 564.2 • FA 2011: 507.2 • ME 3e: 297 • ME4e: 297 RESP11_3- • Thromboembolism – Fat emboli: • Following long bone fractures • Respiratory distress • Petechial rash – Air embolism: • Air can be accidentally introduced into the system through a central venous line • Embolism to coronary arteries can be fatal •FA 2013: 553.2 • FA 2012: 567.3 • FA 2011: 510.1 • ME 3e: 260 • ME4e: 260 RESP11_4- • Thromboembolism (cont’d) – Bacterial emboli: • Cardiac valvular vegetations • Septic emboli to brain can lead to stroke and cerebral infections – Amniotic fluid embolism: • Postpartum cardiac arrest • Pulmonary embolism • DIC – Tumor embolism: • Hepatocellular carcinoma: • Tumor invades hepatic vein inferior vena cava embolism – Deep venous thrombosis in the deep veins of lower limbs •FA 2013: 553.2 • FA 2012: 567.3 • FA 2011: 510.1 • ME 3e: 260 • ME4e: 260 RESP11_4- • Pulmonary embolism – Presentation: • Chest pain • Tachypnea • Tachycardia – Diagnosed with CT-angiogram of the pulmonary arteries •FA 2013: 553.2 • FA 2012: 568.1 • FA 2011: 510.2 • ME 3e: 297 • ME4e: 297 RESP11_4- • Deep venous thrombosis – Virchow’s triad: • Stasis • Hypercoagulability • Endothelial injury – Homan’s sign: • Calf pain on dorsiflexion of the foot – Diagnosed with Doppler ultrasound of lower limbs – Anticoagulation with heparin and warfarin •FA 2013: 553.1 • FA 2012: 568.1 • FA 2011: 510.2 • ME 3e: 297 • ME4e: 297 RESP11_4- ... • FA 2011: 505.1 • ME 3e: 277 • ME4e: 277 RE02-3 Lung Compliance -20 Pressure Volume Curve •FA 2013: 5 47. 1 • FA 2012: 562.2 • FA 2011: 505.2 • ME 3e: 274 • ME4e: 274 -10 Compliance of lungs and... 504.2 • FA 2010: 502 ME 3e: 274 RE02-1 Lung Volumes •FA 2013: 546.2 • FA 2012: 561.2 • FA 2011: 504.3 • ME 3e: 277 • ME4e: 277 RE02-2 • Dead Space – Areas of the respiratory system that not participate... 3e: 274 • ME4e: 274 Kaplan Anatomy 2011 : Figure I -73 Clara cells RE01-5 Pneumocytes Kaplan Anatomy 2011 : Figure I -7- 6 •FA 2013: n/a • FA 2012: 559.2 • FA 2011: 502.3 • ME 3e: 274 • ME4e: 274