新整合課程 課程講義 肺臟呼吸系統 100 學年度第二學期 肺臟呼吸系統 之 解剖 組織 胚胎 生理 病理 藥理學 中國醫藥大學 吳政訓 曾拓榮 陳雅雯 張菡 謝文聰 編著 1
目錄 Chapter 1 Lungs and Pleura --------------------------------------------------------- 3 Chapter 2 Histology of Respiratory system --------------------------------------- 5 Chapter 3 Respiratory Physiology --------------------------------------------------11 Chapter 4 Pathology of Respiratory system --------------------------------------14 Chapter 5 Drug in Respiratory System --------------------------------------------16 2
Chapter 1 Lungs and Pleura Outline: 1. Location- In the thoracic cavity, locating pleura cavity of the thoracic cavity. 2. Pleura structure- Having two layers. 3. Lung structure- A. Pleura (2) (i) Development --- (ii) Border--- Apex: Above the 1/3 medial of the clavicle (2.5 cm). Ant.: Begin in the sterno-clavicle joint----sternal angle----xiphi- (iii) Structural--- sternal joint. (left --in forth rib level form the cardiac notch) Inf.: 8th, 10ht, 12th rib. Visceral layer ( Innervate by the auto vasomotor n.) (Pleura cavity: With pleura fluid) Parietal layer. Cervical pleura Four part Costal pleura ( Innervate by intercostal n.) Diaphragmatic p.(central---phrenic n.; peripheral---intercostal n.) Mediastinum p. (Innervate by phrenic n.) Note: 1. Pulmonary ligament: Pleural cuff locate the pulmonary root, between the parietal and visceral junction. 2. Costo-diaphragmatic recesses: A potential space between the lung (6, 8, 10) and pleura (8, 10, 12) (iv) Contain: Lung (a) Border: Apex---Above the 1/3 medial of the clavicle (2.5 cm). Ant.--- Begin in the sterno-clavicle joint----sternal angle----xiphisternal 3
joint. (left --in forth rib level form the cardiac notch) Inf. --- 6th, 8th, 10 th rib. (b) Surface: Apex--- Which projects upward into the neck for about 2.5 cm above the clavicle. Basal --- Sit on the diaphragm. Costal--- Which corresponds to the concave chest wall. Mediastinal ---Which molded to the pericardium and other mediastinal structure. (c) Blood supply: Bronchial a. (arise from ascending aorta) Bronchial v. drain into azygo and hemi-azygo vein. (d) Structure: Root---Include bronchi, pulmonary v., pulmonary a., lymphoid v. and bronchial a., v., and n. Investing by pleura capsule, which connect the parietal pleura and visceral pleura. Lobe---R, 3; L, 2; dividing many branchus pulmonary segment. (bronchus, a., v. locating inter-segmental connective tissue septa) Air pathway---conducting division + Respiratory division. Conducting division: Intrapulmonary, segmental bronchi, bronchioles, terminal bronchioles. Respiratory division: Respiratory bronchioles, alveolar duct, alveolus 4
Chapter 2 Histology of Respiratory System 學習目標 (Learning objectives): 1. 呼吸道鼻腔內的呼吸與嗅覺上皮組織與腺體 2. 呼吸道咽部與喉部的上皮組織與腺體 3. 呼吸道氣管管狀的分層構造與上皮細胞的種類與功能 4. 呼吸道支氣管管狀分層構造漸進性的改變與上皮細胞的種類與功能 5. 呼吸道呼吸細支氣管的肺泡管 肺泡囊結構與肺泡細胞類型 Respiratory system Component: I. Structure: Upper air-passage: Nose (nasal cavity, sinuses), Pharynx Lower air-passage: Larynx, trachea, bronchi, lung II. Function: A. Conducting portion: Nose (nasal cavity, sinuses), pharynx, larynx, trachea, bronchi, bronchioles, terminal bronchioles B. Respiratory portion: The tissues within the lungs (Respiratory bronchioles, alveolar ducts, alveolar sacs and alveoli) Nasal cavity Vestibule: Stratified squamous epithelium vibrissae - large, short coarse hairs Respiratory portion: Ciliated pseduostratified columnar epithelium Olfactory portion: Olfactory epithelium Respiratory portion Respiratory mucosa Epithelium Goblet cells - apocrine secretion of mucin/mucus Ciliated cells - numerous cilia Basal cells - undifferentiated Brush cells - apical microvilli (brush border): receptor cells Small granule (APUD) cells - catecholamine, serotonin, calcitonin Lamina propria 5
Respiratory submucosa Submucosal nasal glands Olfactory portion Olfactory mucosa Olfactory receptor cells Olfactory nerve (CN 1), Smell, Bipolar neurons, Olfactory vesicle with cilia, Life-span: 1 month Sustentacular cells Brush cells Basal cells Olfactory submucosa Bowman s glands: Tubuloalveolar serous glands Nasopharynx: Uvala, Pharyngeal tonsil, Pharyngeal-tympanic tube Oropharynx: Palatine tonsil, Lingual tonsil, Fauces Laryngopharynx: Epithelium Ciliated pseudostratified columnar epi., Stratified squamous epi. Larynx Glottis: Laryngeal aperture Vocal folds (cords): Upper ventricular (false) & lower caudal (true) Epithelium Stratified squamous epi., Ciliated pseudostratified columnar epi. Trachea Mucous membrane Ciliated pseudostratified columnar epithelium Submucosa Seromucous glands, Trachealis muscle Adventitia C - shaped hyaline cartilage Trachea Mucosa Goblet cells - apocrine secretion of mucin/mucus 6
Ciliated cells - numerous cilia Basal cells - undifferentiated Brush cells - apical microvilli (brush border): receptor cells Small granule (APUD) cells - catecholamine, serotonin, calcitonin Submucosa Mucous glands with serous demilunes Goblet cells Constitute about 30% of the total cell population It produce mucinogen mucin Contain rich network of rer, GA, mitochondra, ribosomes, apical microvilli Trachea Basement membrane 25~40 um Lamina propria areolar connective tissue, irregular weave of collagen & elastic fibers; many fibroblasts; also lymphocytes, plasma cells Elastic membrane between mucosa & submucosa Submucosa collagen, fibroblasts, blood vessels, lymphatics Cartilages C-shaped hyaline cartilages; open portion directed posteriorly, bridged by connective tissue & bundles of smooth muscle fibers Bronchus Main (primary) bronchi Lobar (secondary) bronchi Segmental (tertiary) bronchi Bronchial tree: increased branching decreased diameter Small bronchi and bronchioles epithelial changes (columnar to cuboidal) decreased goblet cells decreased cartilage increased smooth muscle increased elastic fibers Large Bronchus Mucous membrane Pseudostratified columnar epi. Lamina propria 7
Submucosa Smooth muscle, Serous glands Adventitia Cartilage Terminal Bronchiole Simple ciliated columnar to cuboidal Smooth muscle Clara cells - No cilia, Secretory granules secrete proteins to protect against oxidative pollutants and inflammation No cartilage No goblet cells No glands Transition: Terminal Bronchiole to Respiratory Bronchiole Simple columnar to cuboidal epithelium Respiratory Bronchiole Resp. bronchioles will open into alveolar duct alveolar sac Epithelium: - simple cuboidal ciliated - Clara cells (simple cuboidal non-ciliated) Lamina propria: blood vessels - number of blood vessels (for gas exchange) smooth muscles: - less than the terminal - no cartilage - no glands - elastic tissue appears red in color. @ macrophages: dust cells (black dots) Alveolar duct: - A long thin-walled tube, containing the many alveoli - Low cuboidal epithelium - Smooth muscle (knob) - Elastic fibers The alveoli permit gaseous exchange to occur within. Alveolar Sac and Alveolus Alveolar sac: 8
are dilatations at the distal section of individual alveolar ducts Typically, 20-30 alveoli open into each sac. Alveolus: Arranged along and around alveolar ducts and sacs Simple squamous epithelium (< 1mm thick) Two types of epithelial cells: - Type I - Type II (cuboidal epithelial cells; produce surfactant) Elastic fibers (no smooth muscle) Macrophages Alveolar wall Type I cell - Squamous epithelial cell Squamous epithelial cells - (95% of the total alveolar area) which present a very thin diffusion barrier for gases. They are connected to each other by tight junctions. Type II cell - Surfactant-secreting making up 5% of the total alveolar area, but 60% of total number of cells These cells secrete 'surfactant' which decreases the surface tension and stops alveoli collapsing between the thin alveolar walls These cells are connected to the epithelium and other constituent cells by tight junctions. Pulmonary Alveolar Macrophages (Dust cell) Alveolar macrophages phagocytose microbes and particulate matter They raised from monocytes. Fixed: trapped within the connective tissue of the alveolar walls Free: mobile and scavenge for particles which are trapped within the surfactant layer Alveolar macrophages may phagocytose erythrocytes Interalveolar septum Present between two alveoli. Composed of A) Cell: Type I alveolar cells. (simple squamous epithelium) Type II alveolar cells mostly present in the corners. B) Connective tissue: Collagen fiber (type III) Elastic fibers Blood-Air-Barrier (BAB): Type I alveolar cells + endothelial cells + fused laminae 9
REVISION Trachea Ciliated pseudostratified columnar epithelium Goblet cells Sero-mucous glands Cartilage rings Bronchi Ciliated pseudostratified columnar epithelium(shorter) Goblet cells (fewer) Sero-mucous glands Cartilage Smooth muscle Bronchioles Simple columnar or cuboidal & ciliated epithelium No goblet cells Smooth muscle (relatively abundant) Clara cells Respiratory Bronchiole Simple cuboidal, ciliated epithelium (shorter) Clara cells Alveolar openings Alveoli Type I Pneumocyte Flattened for gas exchange Covers 95% of alveolar surface (but only accounts for about 40% of pneumocyte population) Type II Pneumocyte Cuboidal Produces surfactant Constitutes about 60% of the pneumocytes (but only 5% of the surface area) 10
Chapter 3 Respiratory Physiology 學習目標 (Learning objective): 1. How lung ventilation and lung mechanics 2. How exchange and transport of gases in alveolar and tissues and blood 3. How surfactant works 4. How control repiration 上課內容 (Content): 1. Overview of Respiration (1) Internal respiration (cellular respiration) (2) External respiration 2. Organization of the respiratory system:pulmonary, alveolus, airway 3. Functions of respiratory system (1) Zones of airways a. conducting zone b. respiratory zone (2) Functions of airways (3) Functions of Alveolus a. site of gas and blood exchange b. production and secretion of surfactant 4. Relation of the lungs to the chest wall (1) Structures of the Thoracic Cavity (2) Chest walls and pleural sac (3) Muscles of breathing (4) Intrapleural pressure, Pip 5. Ventilation and lung mechanics: (1) Inspiration and expiration (2) Alveolar pressure (3) Bulk flow (4) Airway resistance:physical factors, neural factors, chemical factors (5) Boyle s law and respiration 11
(6) transpulmonary pressure (7) Mechanisms of inspiration (8) Mechanisms of expiration (9) lung compliance (10) airway resistance (11) lung volume capacities (12) alveolar ventilation (13) surfactant and surface tension (14) importance of measuring FEV1 a. obstructive lung diseases b. restrictive lung diseases 6. Ventilation (1) Minutes ventilation (2) Alveolar ventilation (3) Effect of Breathing Patterns on Alveolar Ventilation 7. Dead spaces (1) Anatomic dead space (2) Alveolar dead space (3) Physiologic dead space 8. Exchange and transport of gases in alveoli and tissues and blood (1) The steps of gases exchange in alveoli and tissues (2) Respiratory quotient (RQ) (3) Partial pressure of gases (4) Alveolar gas pressure (5) Gas exchange 9. The relationship between metabolism and alveolar ventilation (1) Hypoventilation (2) Hyperventilation 10. Ventilation-perfusion inequality (1) Effects of decreasing or increasing the ventilation/perfusion ratio (VA/Q) on the PCO 2 and PO 2 in an alveolus. (2) Local control of ventilation-perfusion matching 12
11. Transport of oxygen in blood (1) Oxygen-carrying capacity of blood (2) Oxygen-hemoglobin dissociation curve (3) Oxygen movement (4) Carbon monoxide (CO) (5) Factors influence the degree of hemoglobin saturation (6) Carbondioxide movement (7) Nitric oxide (NO) 12. Control of respiratory: (1) Neural generation of rhythmical breathing (2) Control of ventilation by PO 2, PCO 2 and H + concentration 13. Hypoxia: (1) Ventilation-perfusion abnormalities effect (2) Acclimatization to high altitude 13
Chapter 4 Pathology of Respiratory system 學習目標 (Learning objectives): 1. 複習解剖學及組織學重點 2. 病理學內容大綱 1) 肺塌陷 (Atelectasis,collapse) 2) 肺水腫 (Pulmonary edema) 3) 急性呼吸窘迫症候群 (Acute lung injury and acute respiratory distress syndrome (diffuse alveolar damage)) 4) 阻塞性肺疾病 (Obstructive pulmonary diseases) 5) 限制性肺疾病 (Chronic diffuse interstitial (restrictive) diseases) 6) 血管相關肺疾病 (Diseases of vascular origin) 7) 感染性肺疾病 (Pulmonary infection) 8) 肺臟移植 (Lung transplantation) 9) 肺腫瘤 (Tumors) 10) 肋膜疾病 (Pleural diseases) Pathology of the lung I. 肺塌陷 (Atelectasis,collapse) II. 肺水腫 (Pulmonary edema) Hemodynamic puolmonary edema Edema casused by microvascular injury III. 急性呼吸窘迫症候群 (Acute lung injury and acute respiratory distress IV. syndrome (diffuse alveolar damage)) 阻塞性肺疾病 (Obstructive pulmonary diseases) Emphysema Chronic bronchitis 14
Bronchial asthma Bronchiectasis V. 限制性肺疾病 (Chronic diffuse interstitial (restrictive) diseases) VI. Pneumoconiosis Sarcoidosis Idiopathic interstitial pneumonia Hypersensitivity pneumonitis Diffuse pulmonary hemorrhage syndromes 血管相關肺疾病 (Diseases of vascular origin) Embolism Pulmonary hypertension VII. 感染性肺疾病 (Pulmonary infection) Bacterial pneumonia Atypical pneumonia Others VIII. 肺臟移植 (Lung transplantation) IX. Acute rejection Chronic rejection 肺腫瘤 (Tumors) Bronchogenic carcinoma Neuroendocrine tumors Paraneoplastic syndromes X. 肋膜疾病 (Pleural diseases Pleural effusion Pneumothrorax Pleural tumors 15
Chapter 5 Drug in Respiratory System 支氣管擴張劑及氣喘治療藥氣喘是常見的呼吸道疾病之一, 其症狀包括呼吸道平滑肌收縮 腺體黏液分泌過量 發炎反應等 形成氣喘病因可包含基因異常 過敏原暴露 吸煙 感染和空氣污染等 臨床上治療氣喘的方法主要是抑制媒介物釋放和促進支氣管擴張 16
1. 媒介物釋放阻斷劑 A. 藥品 : Cromolyn sodium ; Nedocromil sodium B. 作用機轉 : 防止肥大細胞 (mast cells) 因抗原抗體相互作用所引起的 Ca 2+ influx, 進一步抑制 histamine 和 leukotrienes 釋放 C. 臨床使用 : 預防氣喘發作藥 預先服用 Cromolyn 或 Nedocromil 可阻斷運動和 aspirin 所引起的支氣管收縮且能預防工廠污染原引起的支氣管痙攣 D. 副作用 : 在於局部的吸入區, 易引起喉頭刺激 咳嗽 口乾 胸悶等 此現象可先以 2 -agonist 來避免之 2. 甲基黃 呤類 (Methylxathines) A. 藥品 : Theophylline, Theobromine and Caffeine B. 作用機轉 : 主要是抑制磷酸二酯 (Phosphodiesterase; PDE) 的活性, 而提高細胞內 camp 的量 進而使支氣管擴張 C. 臨床使用 : Theophylline 常以 aminophylline ( 或 oxtriphylline) 混合製劑來提高其水溶解性, 以增強支氣管擴張的效果 D. 副作用 : 中樞神經興奮作用 增強心跳速率和心肌收縮力 促進胃酸分泌 利尿作用等 3. 擬交感神經作用劑 (Sympathomimetics) 主要功能是舒張呼吸道平滑 增強呼吸道纖毛清潔運動以促進黏液排除 且可抑制 肥大細胞收縮物質的釋放 擬交感神經作用劑主要包括腎上腺素 (epinephrine) 麻黃素 17
(ephedrine) isoproterenol 和 2 -selective agonists A. 腎上腺素 (epinephrine) a. 作用機轉 : 活化 1 2 1 和 2 受體, 為非選擇性作用劑 b. 臨床使用 : 急性支氣管痙攣, 以皮下注射或噴霧式吸入給藥 c. 副作用 : 心跳過快 心率不整 惡化心絞痛 B. 麻黃素 (ephedrine) a. 作用機轉 : 活化 2 受體, 亦可促進神經末梢釋放 norepinephrine b. 臨床使用 : 防止急性氣喘發作, 發汗作用 c. 副作用 : 中樞神經興奮作用 心悸 血壓上升 C. Isoproterenol a. 作用機轉 : 活化 1 和 2 受體 b. 臨床使用 : 支氣管炎 支氣管性氣喘 c. 副作用 : 心臟功能異常 心悸 心率不整等 D. Beta 2 ( 2 )-selective agonists a. 藥品 : Metaproterenol, Albuterol, Terbutaline, Fenoterol b. 作用機轉 : 選擇性 2 受體作用劑 c. 臨床使用 : 慢性支氣管炎 支氣管氣喘 d. 副作用 : 心率不整 心跳過快 肌肉顫抖等現象 4. 蕈毒鹼拮抗劑 (muscarinic antagonists) A. 藥品 : Ipratropium B. 作用機轉 : 競爭性抑制蕈毒鹼受體 (muscarinic receptor),atropine-like C. 臨床使用 : 支氣管擴張劑, 治療氣喘 D. 副作用 : atropine-like 反應 5. 類固醇 (corticosteroids) A. 藥品 : Beclomethasone, Triamcinolone, prednisolone B. 作用機轉 : 抑制 PLA 2 的活性, 而阻斷 PGs, LTs 的合成 C. 臨床使用 : 治療氣喘, 及抗發炎藥 D. 副作用 : 腎上腺皮質抑制作用 (adrenal suppresion) 6. 其他 A. Calcium channel blockers: Nifedipine, Verapamil B. Potassium channel openers: Cromakalim 18
鎮咳劑 鎮咳劑具有抑制咳嗽中樞及鬆弛呼吸道平滑肌的作用, 一般分為麻醉性 (narcotic antitussives) 與非麻醉性鎮咳劑 (non-narcotic antitussives) 兩大類 1. 麻醉性鎮咳劑 (narcotic antitussives) A. 藥品 : Codeine, B. 作用機轉 : 抑制延腦 (medulla) 咳嗽中樞及咳嗽反射, 另具有止痛作用 C. 臨床使用 : 鎮咳劑 止痛 D. 副作用 : 抑制呼吸中樞, 具成癮性 2. 非麻醉性鎮咳劑 (non-narcotic antitussives) A. 藥品 : Dextromethorphan, Noscapine B. 作用機轉 : 抑制咳嗽中樞, 但無止痛效果及成癮性 C. 臨床使用 : 鎮咳劑 D. 副作用 : 思睡 頭痛 19
怯痰劑 怯痰劑的主作用是增加呼吸道漿液分泌 降低痰的黏稠度 1. Ammonium chloride (NH 4 Cl) A. 作用機轉及用途 : 促進支氣管漿液分泌增加, 作為怯痰 潤喉劑 ; 亦具有發汗利尿效果及 酸化尿液作用 B. 副作用 : 酸中毒, 胃腸障礙 2. Potassium iodide (KI) A. 作用機轉及用途 : 促進支氣管水分之分泌, 使濃痰稀釋利於排出 用於肺氣腫 乾咳之治 療 B. 副作用 : 碘中毒 3. Glyceryl guaiacolate A. 作用機轉及用途 : 促進支氣管漿液分泌增加, 稀釋分泌物 ; 鬆弛支氣管平滑肌 用於怯痰 鎮咳劑 B. 副作用 : 思睡 胃腸不適 4. Bromhexine (Bisolven ) A. 作用機轉及用途 : 促進支氣管漿液分泌增加, 並分解濃痰 B. 副作用 : 胃腸不適 5. Acetylcysteine (Mucomyst ) A. 作用機轉及用途 : 促進濃痰分解 B. 副作用 : 厭食 20
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