Histology of Respiratory Syste

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### Respiratory System The respiratory system is divided into two main portions: the conducting portion and the respiratory portion. #### Conducting Portion - **Function:** Conducts or conveys air during inspiration. - **Components:** Nasal cavities, nasopharynx, larynx, trachea, paired primary bronchi up to the level of bronchioles. #### Respiratory Portion - **Function:** Where gas exchange occurs between capillaries and thin alveoli. - **Components:** Respiratory bronchioles, alveolar ducts (walls composed of openings of alveolar sacs), alveolar sacs (collection of alveoli), alveoli. ### Nose - **Framework:** Bone and hyaline cartilage. - **Covering:** Externally by skin, internally by mucosa. - **Nasal mucosa:** Lined by ciliated pseudostratified columnar epithelium (respiratory epithelium), except: - Junction of vestibule and nasal cavity: Non-ciliated cuboidal or columnar epithelium. - Roof of nasal cavity: Olfactory epithelium. ### Respiratory Epithelium Most regions are lined by ciliated pseudostratified columnar epithelium, composed of 6 cell types: - #### Ciliated Columnar Cell - Most abundant cell type. - Up to 300 cilia on its free surface. - #### Goblet Cell - Produces and secretes mucus. - #### Brush Cell - Sensory function. - Columnar cell with numerous microvilli on its free surface. - Associated with afferent nerve endings. - #### Serous Cell - Produces watery secretion. - Columnar non-ciliated cell with dense apical granules containing watery secretion. - #### Basal Cell - Small, rounded, conical, deeply staining cells. - Stem cells that differentiate into sustentacular and olfactory cells. - #### Granule / Kulchitsky Cell - Small neuroendocrine cell with endocrine function. - Resembles a basal cell with electron dense secretory granules containing catecholamines. - Regulates function of secretory cells. ### Olfactory Epithelium - Tall pseudostratified columnar epithelium. - No goblet cells. - Indistinct basement membrane. - Thick lamina propria containing Bowman's glands (branched tubuloalveolar glands whose serous secretion moistens the epithelial surface). - Composed of 3 cell types: #### 1. Sustentacular Cell - Tall, slender cells, broad apically and narrow at bases. - Apical surface has microvilli bathed in mucus. - Ovoid nuclei above the center of the cell. - Cytoplasm contains lipofuscin granules (responsible for yellowish-brown color). - Provides structural and functional support for olfactory cells. #### 2. Olfactory Cell - Spindle-shaped bipolar neurons between sustentacular and basal cells. - **Dendrite:** Passes between sustentacular cells, terminating into an olfactory vesicle with non-motile olfactory cilia (receptor elements). - **Axon:** Unmyelinated, situated on basal end, forms fila olfactoria in the lamina propria, which penetrate the cribriform plate to terminate in the olfactory bulb. #### 3. Basal Cell - Small, rounded, conical, deeply staining cells between sustentacular and olfactory cells. - Stem cells that differentiate into sustentacular and olfactory cells. #### Pathway of Olfactory Stimuli 1. Olfactory epithelium 2. Axons of olfactory cells 3. Lamina propria (axons penetrate) 4. Formation of the olfactory nerve 5. Cribriform plate (olfactory nerve penetrates) 6. Olfactory bulb (nerve terminates) 7. Primary olfactory cortex (signals interpreted) ### Paranasal Sinuses - **Function:** Makes face lighter, serves as a resonating chamber for speech. - **Lining:** Mucous membrane consisting of respiratory epithelium. #### Four Paranasal Sinuses - **Frontal:** Commonly affected in respiratory tract infections. - **Maxillary** - **Ethmoidal** - **Sphenoidal:** Not usually assessed due to deep location. **Clinical Note: Sinusitis** - Occurs when mucus clogs paranasal sinuses, leading to bacterial growth and inflammation. - Symptoms: Headache, colds, nasal congestion, purulent discharge, greenish-yellow mucus. ### Epiglottis - **Framework:** Elastic cartilage. - **Mucosa:** Epithelium and underlying lamina propria. - Anterior surface and upper half of posterior surface: Nonkeratinized stratified squamous epithelium. - Elsewhere: Respiratory epithelium. - **Function:** Covers trachea during swallowing to prevent food entry; opens during inhalation. ### Pharynx - Funnel-shaped fibromuscular tube from skull base to hyoid bone, continuous with esophagus. - **Mucosa:** Epithelium and lamina propria. - **Lining Epithelium:** - Oropharynx and laryngopharynx: Nonkeratinized stratified squamous. - Nasopharynx: Ciliated pseudostratified columnar (respiratory). - **Lamina Propria:** - Glands are pure mucous in stratified squamous areas. - Glands are mixed in respiratory epithelium areas. - **Submucosa:** Present in lateral wall of nasopharynx and terminal laryngopharynx. #### Muscularis Externa of the Pharynx - 2 layers of involuntary skeletal muscle fibers: - Inner layer: Longitudinally arranged. - Outer layer: Circular/obliquely arranged. ### Larynx - Connects pharynx to trachea. - Role in phonation (voice production). - **Framework:** - **Unpaired (3):** Thyroid, cricoid, epiglottic. - **Paired (3):** Corniculate, cuneiform, arytenoid. #### Larynx Framework Cartilage Types - **Hyaline Cartilage:** Thyroid, cricoid, arytenoids (except tips). - **Elastic Cartilage:** Corniculate, cuneiform, epiglottic, tips of arytenoids. #### Groups of Skeletal Muscles - **Extrinsic Muscles:** Connect larynx to surrounding structures, raise larynx during deglutition. - **Intrinsic Muscles:** Originate and insert within larynx, open and close rima of the glottis. #### Lining Epithelium - **Respiratory Epithelium:** Respiratory part, aryepiglottic folds, vocal cords (both true and false). - **Non-Keratinized Stratified Squamous:** Internal surface of vocal cords, anterior surface and upper half of posterior surface of epiglottis. #### Glands - Only present in the lamina propria of false vocal cords. - Large tubuloalveolar glands (serous and mucous, mainly mucous). #### Vocal Cords - #### False Vocal Cords - Not main sound producers. - Glands in lamina propria. - #### True Vocal Cords - Lamina propria has numerous elastic fibers (vocalis ligament) and muscle fibers (vocalis muscle). - Has muscle, not gland. - Open and close to produce sound. ### Trachea - **Notable feature:** C-shaped hyaline cartilage rings. - **4 histologic layers:** Mucosa, submucosa, cartilage and muscle, adventitia. #### Layers of Wall of Trachea - #### Tracheal Mucosa - Respiratory epithelium with very thick basement membrane. - #### Tracheal Submucosa - Loose connective tissue with mixed tubuloalveolar glands (tracheal and bronchial submucosal glands). - #### Cartilage and Muscle Layer - 16-20 C-shaped hyaline cartilage rings keep lumen open. - Posterior ends of cartilages are open, bridged by fibroelastic ligaments and trachealis muscle (smooth muscle fibers). ### Main Bronchi - Divides from trachea into right and left primary bronchus. - Smaller caliber, thinner respiratory epithelium, fewer submucosal glands than trachea. - Discontinuous thin smooth muscle layer separates mucosa from submucosa (instead of elastic tissue). - As airways get smaller, C-shaped cartilage becomes islands, then disappears in bronchioles (replaced by pure muscle). - Bronchioles have scallop-shaped lumens due to smooth muscle contraction. **Clinical Note: Smoking** - Smokers have morning coughs with phlegm due to asynchronous beating of cilia. - Accumulation of phlegm and hypertrophy can lead to COPD/chronic bronchitis. - Damage to interalveolar septum, elastic tissue, and loss of normal alveolar sacs leads to dilation (emphysema). ### Lungs - Composed of pleura. #### Pleura - Double layer of fibrous connective tissue with abundant elastic fibers. - Consists of fibroblasts and macrophages. - Surface lined with mesothelium, which produces serous fluid (lubricant). - Excess serous fluid (pleural effusion) can compress lung tissue. - Has nerve supply, explaining pain during deep breaths in pneumonia. - **Layers:** - **Parietal pleura:** Outer layer. - **Visceral pleura:** Inner layer. ### Bronchial Tree - **Bronchopulmonary segment:** Composed of tertiary bronchus and lung area it supplies. - Respiratory bronchioles end by giving off alveolar ducts. #### Bronchiole Terminologies - **Terminal Bronchiole:** Last part of conducting portion; no gas exchange. - **Respiratory Bronchiole:** Part of respiratory portion; gas exchange takes place. #### Additional Information - **Alveolar Ducts:** Tiny tubes from which numerous alveolar sacs and alveoli arise; wall composed of alveolar sac or alveoli. - **Extrapulmonary bronchi:** Main bronchi (outside lungs). - **Intrapulmonary bronchi:** All bronchi within lungs. - **Bigger intrapulmonary bronchi:** Similar to extrapulmonary, but lower epithelium and folded mucosa due to smooth muscle contraction. - **Smaller intrapulmonary bronchi:** Cartilages as irregular plates, more prominent circular smooth muscle layer. - Airway diameter decreases and cartilage changes from continuous rings to irregular plates as branching occurs. ### Bronchioles - Walls lack cartilage. - Epithelium changes from ciliated pseudostratified proximally to simple columnar and then simple cuboidal distally. If squamous, it's alveolar ducts. **Clinical Note: Bronchial Asthma** - Muscle presence in bronchioles explains bronchoconstriction and wheezing. - Inhalers target bronchiolar muscles to relax them. #### Clara Cells - Tall cuboidal, slender, non-ciliated cells with round apices and microvilli. - Dense secretory cytoplasmic granules containing surface active lipoproteins (similar to pulmonary surfactant). - **Function:** Reduces surface tension, prevents luminal adhesion and collapse of bronchioles during expiration. - Also function as stem cells. - Present only in bronchioles. ### Terminal Bronchioles - Last segment of the conducting portion. - Epithelium: Simple cuboidal, usually non-ciliated, no goblet cells. ### Respiratory Bronchioles - Epithelium: Initially simple cuboidal, becomes simple squamous distally. - Populated by granule cells, basal cells, brush cells, and numerous Clara cells. ### Alveolar Ducts - Thin-walled conical tubes. - Epithelium: Simple squamous. - Numerous alveoli and alveolar sacs arise, occupying practically the entire wall. - Wall consists of knob-like structures guarding entrances to alveoli and sacs. ### Alveolar Sacs and Alveoli - **Alveoli:** Thin-walled polyhedral sacs, open on one side for air entry. #### Interalveolar Septum - Common wall between adjacent alveoli, perforated by alveolar pores (up to 7 per alveolus). - Pores are clogged with pulmonary surfactant and serve as: - Alternate route for air passage. - Migration route for pulmonary alveolar macrophages (dust cells). - Storage site of pulmonary surfactant. - Core of connective tissue lined by simple squamous epithelium. ##### Portions of the Interalveolar Septum - **Thin:** Air easily diffuses, forms blood-air barrier, responsible for gas exchange. - **Thick:** Site of effusion, important for fluid distribution, contains connective tissue cells (fibroblasts, macrophages). ##### Connective Tissue Core Contains: - Collagen fibers, elastic fibers, reticular fibers. - Inflammatory cells (mast, pulmonary alveolar macrophages, plasma, lymphocyte). - Interstitial fibroblasts (contractile due to actin filaments). - Blood or pulmonary capillaries. ##### Epithelial Cells of the Interalveolar Septum - Two types of cells comprising the simple squamous epithelium: ###### a) Pneumocyte Type I (Small Alveolar Cell) - Covers 95% of alveolar surface. - Forms tight junctions with each other and Type II cells. - Rests on basal lamina. - Smaller and less numerous than Type II. ###### b) Pneumocyte Type II (Great Alveolar Cell) - 60% of epithelial cells, but cover only 5% of alveolar surface. - Larger than Type I. - Bulges into alveolar lumen. - Cuboidal or round cells with large round nucleus and prominent nucleolus. - Free surface has short microvilli. - **Distinctive Feature:** Lamellar bodies (ovoid membrane-bound inclusions) are secretory granules for pulmonary surfactant. - **Clinical Significance:** Pulmonary surfactant reduces alveolar surface tension, preventing collapse at end of expiration. - **Pediatric Significance:** Absence in premature infants leads to alveolar collapse; CPAP improves patency. ### Pulmonary Alveolar Macrophages - Also known as **dust cells**. - Contain bound cytoplasmic inclusions of phagocytosed material (mainly dust). - Most numerous cells in alveoli, first line of defense. - Not part of interalveolar septum (some attached, most float freely). - When numerous, they contain brown pigment hemosiderin from phagocytosed RBCs. - Hemosiderin-laden macrophages are called **heart failure cells** (found in heart failure causing pulmonary congestion/edema). ### Pulmonary Arteries - Arise from pulmonary trunk. - Bring venous blood to lungs for oxygenation. - Form pulmonary capillaries. - Oxygenated blood collected by venules, then pulmonary veins. ### Bronchial Arteries - Arise directly or indirectly from aorta. - Carry oxygenated blood to supply walls of bronchial tree segments. - Smaller lumen with thick walls compared to pulmonary artery. ### Blood-Air Barrier Consists of structures from lumen of alveoli to lumen of pulmonary capillaries: 1. Pneumocyte type I cells (lining of alveoli) 2. Basal lamina of alveolar epithelium 3. Basal lamina of capillary endothelium (fused with alveolar basal lamina) 4. Capillary endothelial cells (lining of pulmonary capillaries) - **Function:** Where gas exchange occurs; thin walls allow easy diffusion. ### Clinical Correlation #### A. Emphysema - Partial destruction of interalveolar septa. - Permanent enlargement of air spaces. - Thickening of pulmonary vessel walls. #### B. Pneumonia - Air spaces filled with exudate (WBCs, neutrophils, RBCs, fibrin). - Enlargement and congestion of capillaries in alveolar septum. #### C. Squamous Cell Metaplasia and Squamous Cell Carcinoma - Change from ciliated pseudostratified columnar epithelium to stratified squamous. - Altered epithelium is more resistant to physical stress but less functionally effective. - Occurs with altered airflow or forceful airflow (e.g., chronic coughing, common in smokers). ##### Progression of Squamous Cell Metaplasia 1. Cilia lose synchronous beating, impairing mucus removal, leading to coughing. 2. Chronic coughing reduces ciliated cells. 3. Reduced ciliated cells further impairs respiratory epithelium. 4. Normal epithelium replaced by squamous epithelium (squamous metaplasia).