Файл: Kaplan USMLE-1 (2013) - Anatomy.pdf

After passing through the white pulp, the central artery gives rise to smaller peni­ cillar arteries that enter the red pulp. Other radial artery and arteriolar branches of the central arteries empty into marginal located at the margin or outer zone of the white pulp, at its interface with red pulp. This provides an opportunity for blood-borne antigens to be removed from the blood by neighboring macro­ phages, making them available to antigen-processing cells, T and B lymphocytes of the white pulp, and initiating an immune response. These marginal sinuses eventually drain into splenic veins.

Chapter 6 • Immune Tissues

Note

95% of developingT cells die in the thymic cortex.

THYMUS

Like the lymph node, the thymus is divided into a distinct cortex and medulla. The thymus serves as a site ofmaturation ofT-lymphocyteprecursorsafter they exit from the bone marrow and arrive at the thymus via blood circulation. As these T cells develop, they are in intimate contact with epithelial cells of the thymus, also connected by desmosomes called dendritic epithelial cells because they have extensive thin branches oftheir cytoplasm extending out from the cell bodies. Because of the extensive branching of the epithelial cytoplasm there is extensive surface interaction possible between the developing T lymphocytes and thymic epithelial cells.

The thymic epithelial cells ofthe cortex are involved in clonal selection ofT cells. As the cells complete this process, the second set of dendritic epithelial cells in­ volved in clonal deletion of self-reactive T cells is located deeper in the medulla. The cortex is recognized by its darker staining. It has a high concentration of close-packed small lymphocytes with little cytoplasm and only a few epithelial cells and other cells. The medulla appears paler due to higher content of epithe­ lial and other cells with more cytoplasm separating the lymphocyte nuclei. Med­ ullary thymic epithelial cells form small aggregates of squamous epithelial cells called Hassall's corpuscles. Hassall's corpuscles are a reliable histologic marker for thymic medulla.

Another aspect ofthe thymus is that in the early stages ofT-cell maturation when positive and negative selection are taking place, there is a functional blood-thy­ mic barrier created by cortical thymic epithelial cells. These cells interact with the endothelium of thymic cortical blood vessels that "protects" the developing thymic lymphocytes from exposure to foreign antigens.

Note

The blood-thymus barrier consists of cortical thymic reticular cells joined by desmosomes, a dual basal lamina, and endothelial cells joined by tight junctions.

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ChapterSummary

The thymus contains trabeculae and has a cortical and medullary region.

Epithelial reticular cells and Hassall's corpuscles are located within the medulla. The cortex lacks germinal centers. The thymus protects developing T cells by the blood-thymus barrier.

The lymph node has 3 layers: outer cortial, inner cortical (paracortical), and medullary. The outer cortical layer contains most ofthe nodules and germinal centers. Most ofthe B lymphocytes reside here, whereas T lymphocytes reside in the paracortical layer. Dendritic cells within lymph nodes are antigen-presenting cells. High endothelial venules are the site of repopulation of lymph nodes and are located within the paracortical zones.

The spleen is very vascular and has red and white pulp. White pulp is composed of lymphoid tissue. T lymphocytes are located in the periarterial sheaths, while peripheral white pulp and germinal centers contain B lymphocytes. Red pulp consists of splenic cords and venous sinusoids. Its function is to delay passage of defective red blood cells to enable their elimination through phagocytosis by macrophages.

Clinical Correlate

If mucosa! clearance is ineffective, or the mechanism overwhelmed, infection (pathogenic bacteria) or

pneumoconiosis (dust-related disease) may follow.

In cystic fibrosis, the secreted mucus is thick or viscous and the cilia have a difficult time moving it toward the pharynx. Patients with this disease have frequent infections of the respiratory system.

Clinical Correlate

Patients lacking dynein have immotile cilia or Kartagener syndrome.

With immotile cilia, patients are subject to many respiratory problems because their cilia cannot move this mucus layer with its trapped bacteria. Males also possess immotile sperm.

80 MEDICAL

•The submucosa is a vascular service area containing large blood vessels. Collagen fibers, lymphatic vessels and nerves are also present in this layer.

•The outside covering of the trachea, the adventitia, is composed of several layers of loose connective tissue.

The epithelial lining of the trachea and bronchi is pseudostratified columnar in which all cells lie on the same basal membrane but only some reach the luminal surface. The only other place in the body with this epithelium is the male repro­ ductive tract.

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Figure 1-7-3. Pseudostratified columnar epithelium with goblet cells (arrowhead) surrounded by ciliated cells (arrow)

Tracheal Epithelial CellTypes

Columnar cells extend from the basal membrane to the luminal surface. These cells contain approximately 200 to 300 apical cilia per cell that are intermingled with microvilli. The cilia are motile and beat to help move the secreted mucus layer over the lining of the trachea and out of the respiratory system.

Goblet cells secrete a polysaccharide mucous material into the lumen of tra­ chea. Mucus production is supplemented by secretions of the submucosal mixed glands. The mucus layer of the respiratory system traps particulate substances (dust, bacteria, and viruses) and absorbs noxious water-soluble gases such as ozone and sulfur dioxide. The mucus sticky layer is moved by the beating cilia toward the pharynx where it is swallowed. This movement is known as the mu­ cociliary escalator system. Most material (dust and bacteria) is trapped in the mucus layer, and is removed and digested.

Pulmonary neuroendocrine (PNE) cells are comparable to the endocrine cells in the gut. These epithelial neuroendocrine cells have been given various names:

•APUD cells (Amino-Precursor-Uptake-Decarboxylase) , DNES cells (Diffuse Neuro Endocrine System) and K (Kulchitsky) cells. The granules in these neuroendocrine cells contain hormones and active

peptides, bombesin (gastrin-releasing factor), leu-enkephalin, sero­ tonin, and somatostatin. These cells occur in clusters and are often located at airway branch points.

•Brush cells may represent goblet cells that have secreted their products or intermediate stages in the formation of goblet or the tall ciliated cells. They have short microvilli on their apical surfaces. Some of these cells have synapses with intraepithelial nerves, suggesting that these cells may be sensory receptors.

Basal cells are stem cells for the ciliated and goblet cells. The stem cells lie on the basal membrane but do not extend to the lumen ofthe trachea. These cells, along with the epithelial neuroendocrine cells, are responsible for the pseudostratified appearance ofthe trachea.

BRONCHI

The bronchial tree forms a branching airway from the trachea to the bronchioles. When the primary bronchi enter the lung, they give rise to 5 secondary or lobar bronchi-3 for the right lung and 2 for the left. The 5 lobes are further subdivided into 10 tertiary or segmental bronchi in each lung, which form bronchopulmo­ nary segments.

Chapter 7 • Respiratory System

Clinical Correlate

The columnar and goblet cells are sensitive to irritation. The ciliated cells become taller, and there is an increase in the number of goblet cells and submucosal glands.

Intensive irritation from smoking leads to a squamous metaplasia where

the ciliated epithelium becomes a squamous epithelium. This process is reversible.

Clinical Correlate

Bronchial metastatic tumors arise from Kulchitsky cells.

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Figure 1-7-4. Bronchus with a plate of cartilage (arrow)

The epithelial lining of the bronchi is also pseudostratified. It consists of cili­ ated columnar cells, basal cells, mucus cells, brush cells and neuroendocrine

(APUD,gul DNES, or K) cells. There are also seromucous glands in the submucosa that empty onto the epithelial surface via ducts. The walls of bronchi contain ir­ re ar plates of cartilage and circular smooth-muscle fascicles bound together by elastic fibers. The number ofgoblet cells and submucosa glands decreases from the trachea to the small bronchi.

Clinical Correlate

Cystic fibrosis that results in abnormally thick mucus is in part due to defective chloride transport by Clara cells.

Clinical Correlate

Chronic obstructive pulmonary disease (COPD) affects the bronchioles and includes emphysema and asthma.

•Emphysema is caused by a loss of elastic fibers and results in chronic airflow obstruction.

•Asthma is a chronic process characterized by a reversible narrowing of airways.

•Asthma is reversible; emphysema is not.

BRONCHIOLES

The wall ofabronchioledoes not contain cartilage or glands. The smooth-muscle fascicles are bound together by elastic fibers. The epithelium is still ciliated, but is a simple cuboidal or columnar epithelium rather than pseudostratified. The epi­ thelial lining of the airway is composed of ciliated cells (goblet and basal cells are absent in the terminal bronchioles) and an additional type called the Clara cell.

Clara cells (also called bronchiolar secretory cells) are nonciliated and secrete a serous solution similar to surfactant. They aid in the detoxificationofairborne toxins, and serve as a stem cell for the ciliated cells and for themselves. The num­ ber of Clara cells increases in response to increased levels of pollutants like ciga­ rette smoke. Clara cells are most abundant in the terminal bronchioles, where theymake up about 80 % ofthe epithelial cell lining; they are also involved with chloride ion transport into the lumens of the terminal bronchioles.

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Figure 1-7-5. Terminal bronchiole lumen (asterisk) with epithelium containing ciliated cells and Clara cells (arrows)

Terminal Bronchioles

The terminalbronchiole is the last conducting bronchiole. This bronchiole is fol­ lowed by respiratory bronchioles which are periodically interrupted by alveoli in their walls. The goblet cells are absent from the epithelial linings of the respi­ ratory bronchioles, but are still lined with a sparse ciliated cuboidal epithelium that prevent the movement of mucous into the alveoli. After the last respiratory bronchiole, the wall of the airway disappears and air enters the alveoli.

Clinical Correlate

Surfactant is synthesized after week 35 of gestation. Coricosteroids

induce the fetal synthesis of surfactant. High insulin levels in diabetic

mothers antagonize the effects of corticosteroids.

Infants of diabetic mothers have a higher incidence of respiratory distress syndrome.

84 MEDICAL

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Figure 1-7-7. Alveoli with type I pneumocytes (arrowhead), type II pneumocytes (arrow), and alveolar macrophage (curved arrow) in the alveolar wall.

Surfactant

Surfactant is essential to maintain the normal respiratory mechanics ofthe alve­ oli. Production ofsurfactant in the fetus is essential for the survival ofthe neonate as it takes its first breath. Surfactant is composed of a mixture of phospholipids and surfactant proteins whose function is to aid in the spreading of the surfac­ tant at the alveolar air-water interface. The phospholipid in surfactant acts as a detergent which lowers the surface tension of the alveoli, and prevents alveolar collapse during expiration.

Most surfactant is recycled back to Type II cells for reutilization; some of it un­ dergoes phagocytosis by macrophages.

AlveolarWall

In the alveolarwallunder the alveolar epithelium is a rich network of capillaries arising from pulmonary arteries. The alveolar wall contains a variety of cells and extracellular fibers. The cells include fibroblasts, macrophages, myofibroblasts, smooth-muscle cells, and occasional mast cells. Type I and II collagens, as well as elastic fibers, are in the septa. Type I collagen is present primarily in the walls of the bronchi and bronchioles. Twenty percent of the mass of the lung consists of collagen and elastic fibers. Elastic fibers are responsible for the stretching and recoiling activities of the alveoli during respiration. These microscopic elements are responsible for the recoil of the lungs during expiration.

Gas exchange occurs between capillary blood and alveolar air across the blood­ gas barrier. This barrier consists ofsurfactant, the squamous Type I pneumocytes, a shared basal lamina, and capillary endothelium. The distance between the lu­ men of the capillary and the lumen of the alveolus can be as thin as 0. 1 microns. There are openings in the wall of most alveoli that from the poresofKohn. These pores are thought to be important in collateral ventilation. The diameter ofthese alveolar pores can be as large as l 0 to 15 microns.