HISTOLOGY OF RESPIRATORY BRONCHI, ALVEOLAR DUCT, ALVEOLI AND BLOOD-AIR BARRIER
LEARNING OBJECTIVES:
At the end of the lecture, the student should be able to:
Describe the microscopic anatomy of respiratory bronchiole.
Discuss the microscopic picture of alveolar ducts, alveolar sacs and alveoli.
Know the different types of cells found in respiratory tract like type 1 and type2 cells found in alveoli
Discuss surfactant, alveolar septum, alveolar pores and alveolar macrophages
Describe blood-air barrier.
Discuss the clinical aspects related to the topic.
RESPIRATORY SYSTEM:
1) Conducting Zone:
(Air passages; air conditioning)
1. Nasal cavities
2. Nasopharynx and oropharynx
3. Larynx.
4. Trachea.
5. Paired primary bronchi.
6. Bronchiole tree.
A. internal bronchi.
B. bronchioles.
II). Respiratory Zone
A). Respiratory Bronchioles
B). Alveolar ducts
C). Alveolar Sacs
D). Alveoli
1). Type 1 cells
2). Pulmonary Capillaries
3). Respiratory Membrane
4). Type II cells
Surfactant
5). Alveolar Pores
6). Alveolar macrophages
BRONCHIOLES:
Bronchioles, intralobular airways with diameters of 5 mm or less, have neither cartilage nor glands in their mucosa; there are only scattered goblet cells within the epithelium of the initial segments.
In the larger bronchioles, the epithelium is ciliated pseudostratified columnar, which decreases in height and complexity to become ciliated simple columnar or cuboidal epithelium in the smaller terminal bronchioles.
The epithelium of terminal bronchioles also contains Clara cells which are devoid of cilia, have secretory granules in their apex, and are known to secrete proteins that protect the bronchiolar lining against oxidative pollutants and inflammation.
RESPIRATORY COMPONENTS:
The respiratory portions of the lungs are the structures that are directly involved in the transfer of oxygen from the air into the blood and carbon dioxide from the blood into the air.
The alveolus is the structural unit of gas exchange:
It is a spherical or polygonal air space about 250 micro m in diameter
Its thin walls are surrounded by a rich network of pulmonary capillaries
All respiratory components are characterized by the presence of alveoli.
RESPIRATORY BRONCHIOLES:
Each terminal bronchiole (subdivides into two or more respiratory bronchioles that serve as regions of transition between the conducting and respiratory portions of the respiratory system).
The respiratory bronchiolar mucosa is structurally identical to that of the terminal bronchioles, except that their walls are interrupted by numerous saclike alveoli where gas exchange occurs.
Portions of the respiratory bronchioles are lined with ciliated cuboidal epithelial cells and Clara cells, but at the rim of the alveolar openings the bronchiolar epithelium becomes continuous with the squamous alveolar lining cells (type I alveolar cells);
Proceeding distally along these bronchioles, the alveoli increase greatly in number, and the distance between them is markedly reduced.
Between alveoli, the bronchiolar epithelium consists of ciliated cuboidal epithelium; however, the cilia may be absent in more distal portions.
Smooth muscle and elastic connective tissue lie beneath the epithelium of respiratory bronchioles.
Respiratory bronchioles are the smallest bronchioles and are considered to be part of both the conducting and respiratory portions. They are characterized by interspersed alveoli in theirwalls.
Arecharacterized by occasional alveoli in their walls
Arise from the branching of terminal bronchioles.
Are lined by mainly cuboidal ciliated epithelium and Clara cells.
Have smooth muscle in their walls
Undergo further branching (~3 orders) ultimately forming ill-defined alveolar ducts (~3 orders) whose walls are mainly composed of alveoli and little smooth muscle.
Alveolar ducts terminate in two or three alveolar sacs whose walls are comprised completely of alveoli.
LUNGS
Stained with haematoxylin and eosin:
1 - Middle diameter bronchus.
2 - Epithelium of the mucosa.
3 - Lamina propria of the mucosa.
4 - Lamina muscularis of the mucosa.
5 - Tunica submucosa.
6 - fibro-elastic layer.
7 - Tunica adventitia.
8 –Alveoli.
9 - Interstitial connective tissue of the lung.
10 - Glands in tunica submucosa.
LUNGStained with haematoxylin and eosin:
1 - Small diameter bronchus.
2 –Alveoli.
3 - Epithelium of the mucosa.
4 - Lamina propria of the mucosa.
5 - Tunica muscularis.
6 - Tunica adventitia.
HISTOLOGICAL STRUCTURE OF ALVEOLI:
The structure of the alveolar walls is specialized for enhancing diffusion between the external and internal environments.
Generally, each wall lies between two neighboring alveoli and is therefore called an interalveolar septum, or wall.
The wall of the alveoli is formed by a thin sheet (~2µm) of tissue separating two neighbouring alveoli.
This sheet is formed by epithelial cells and intervening connective tissue. Collagenous (few and fine), reticular and elastic fibres are present.Between the connective tissue fibres we find a dense,anastomosing network of pulmonary capillaries.
The capillaries and connective tissue constitute the interstitium.
Within the interstitium of the interalveolar septum is found the richest capillary network in the body.
The walls of the capillaries are in direct contact with the epithelial lining of the alveoli.
The basal laminae of the epithelium and endothelium may actually fuse.
Neighbouring alveoli may be connected to each other by small alveolar pores.
PULMONARY LOBULE:
ALVEOLAR TYPE I CELLS:
The epithelium of the alveoli is formed by two cell types:
(Small alveolar cells or type I pneumocytes) are extremely flattened (the cell may be as thin as 0.05 µm) and form the bulk (95%) of the surface of the alveolar walls.
The shape of the cells is very complex, and they may actually form part of the epithelium on both faces of the alveolar wall.
Alveolar type II cells:
(Large alveolar cells or type II pneumocytes) are irregularly (sometimes cuboidal) shaped.
They form small bulges on the alveolar walls.
Type II alveolar cells contain a large number of granules called cytosomes (or multilamellar bodies), which consist of precursors to pulmonary surfactant (the mixture of phospholipids which keep surface tension in the alveoli low.
ALVEOLI:
Cilia are absent from the alveolar epithelium and cannot help to remove particulate matter which continuously enters the alveoli with the inspired air.
Alveolar macrophages take care of this job. They migrate freely over the alveolar epithelium and ingest particulate matter.
Towards the end of their life span, they migrate either towards the bronchioles, where they enter the mucus lining the epithelium to be finally discharged into the pharynx, or they enter the connective tissue septa of the lung.
BLOOD-AIR BARRIER:
The blood-air barrier is formed by:
The Type I pneumocyte (alveolar epithelium
A single basement membrane*
Pulmonary capillary endothelium*the single basement membrane is formed by the fusion of the basement membranes belonging to the pneumocyte and the pulmonary capillary endothelium.
RESPIRATORY (CONDITIONING) EPITHELIA:
a) Ciliated cells:
i) columnar cells with 300 cilia/cell, 14 cycles/s, propel mucus at 2 cm/minii) cilia beat in one direction (towards oropharynx) propelling mucus and particulates to be removed (spit it out or swallow it)iii) loss of cilia activity results in respiratory infectionsiv) microvilli also at apex of cell
b) Mucous goblet cells:
i) Secrete mucus that traps particulate matterii) have sparse microvilli.
c) Brush cells:
i) Columnar cell with short, blunt microvilli on apical surfaceii) sensory receptor cell?
d) Basal (short) cells:
i) Located at the base of epith. And do not reach lumenii) stem cell function
e) Small granule cells (bronchial Kulchitsky cells):
i) contain granules at base of cellii) thought to have neuroendocrine function (similar to enteroendocrine cell of gut)
f) Clara cells [(distal elements of conducting portion (bronchioles and terminal bronchioles)]
i) Secrete lipoprotein that is a surface active agent.
GAS EXCHANGE EPITHELIA
a) Type I cells (pneumocytes):
i) very squamous (25 nm) epitheliaii) organelles are very near nucleus so that the extranuclear regions can be very thin iii) have occluding junctions and intercellular linkages via desmosomesiv) cover 95% of the gas exchange surface-reduces surface tension between alveolar wall and air.
b) Type II cells (septal cells, great alveolar cells):
i)simple cuboidal cells typically found at alveolar wall junctions (septa)ii) junctions like and with type I cellsiii) cover 5% of the gas exchange surfaceiv) has lamellar bodies containing phospholipids, GAGs, and proteins that constitute pulmonary surfactant-reduces surface tension between alveolar wall and air.
Secretion of surfactant by a type II cell. Surfactant is a protein–lipid complex synthesized in the rough endoplasmic reticulum and Golgi complex and stored in the lamellar bodies. It is continuously secreted by means of exocytosis (arrows) and forms an overlying monomolecular film of lipid covering an underlying aqueous hypophase. Occluding junctions around the margins of the epithelial cells prevent leakage of tissue fluid into the alveolar lumen.
c) Brush cells (sparse and the same as those found in air conditioning epithelia
THERESPIRATORY DISTRESS SYNDROME:
The RDS of the newborn is a life-threatening disorder of the lungs caused by a deficiency of surfactant.
It is principally associated with prematurity and is the leading cause of mortality among premature infants.
The incidence of respiratory distress syndrome varies inversely with gestation age.
The immature lung is deficient in both the amount and composition of surfactant.
In the normal newborn, the onset of breathing is associated with a massive release of stored surfactant, which reduces the surface tension of the alveolar cells. This means that less inspiratory force is needed to inflate the alveoli, and thus the work of breathing is reduced.
In the respiratory distress syndrome the alveoli are collapsed, and the respiratory bronchioles and alveolar ducts are dilated and contain edema fluid.
A fibrin-rich eosinophilic material called hyaline membrane lines the alveolar ducts. This explains why respiratory distress syndrome was initially named hyaline membrane disease.
Fortunately, synthesis of surfactant can be induced by administration of glucocorticoids, a medication used in cases of respiratory distress syndrome.
Recently, surfactant has also been suggested to have a bactericidal effect, aiding in the removal of potentially dangerous bacteria that reach the alveoli.
The surfactant layer is not static but is constantly being turned over. The lipoproteins are gradually removed from the surface by the pinocytotic vesicles of the squamous epithelial cells, by macrophages, and by type II alveolar cells.
Alveolar lining fluids are also removed via the conducting passages as a result of ciliary activity. As the secretions pass up through the airways, they combine with bronchial mucus, forming a bronchoalveolar fluid, which aids in the removal of particulate and noxious components from the inspired air.
The bronchoalveolar fluid contains several lytic enzymes (eg, lysozyme, collagenase, -glucuronidase) that are probably derived from the alveolar macrophages.
LUNG MACROPHAGES
Alveolar macrophages, also called dust cells, are found in the interior of the interalveolar septum and are often seen on the surface of the alveolus).
Numerous carbon- and dust-laden macrophages in the connective tissue around major blood vessels or in the pleura probably are cells that have never passed through the epithelial lining.
The phagocytosed debris within these cells was most likely passed from the alveolar lumen into the interstitium by the pinocytotic activity of type I alveolar cells.
The alveolar macrophages that scavenge the outer surface of the epithelium within the surfactant layer are carried to the pharynx, where they are swallowed.
Learning Resources:
1. Kieth L Moore.
2. June Queira LC. Carneiro J: Basic Histology.