Alveolar Lining Regeneration

Daily turnover of about 1G/o of the type II cells, whose mitotic progeny form both type I and type 11 cells, allows for normal alveolar lining renewal. When these lining cells are destroyed by inhalation of toxic gases, replacements for both types of cells are similarly derived from the surviving type II cells. Respiratory system

Pulmonary Surfactant

Respiratory system :
It is continuously synthesized and secreted by type II alveolar cells onto the alveolar surfaces, pulmonary surfactant is removed from these surfaces by alveolar macrophages and by type I and II alveolar cells. Its composition and continuous turnover allow it to serve 2 major functions. Not only does it reduce surface tension in the alveoli, but also it is thought to have some bactericidal effects, cleaning the alveolar surface and preventing bacterial invasion of the many capillaries in the septa.

The surfactant forms a thin 2-layer film over the entire alveolar surface. The film consists of an aqueous basal layer (bypopbase) composed mainly of protein, which is covered by a monomolecular film of phospholipid (mainly di palmitoyl lecithin) whose fatty acid tails extend into the lumen. By reducing surface tension, the surfactant helps prevent collapse of the alveoli during expiration. It thus eases breathing by decreasing the force required to reopen the alveoli during the next inspiration.

Because surfac tant secretion begins in the last weeks of fetal development, premature infants often suffer a condition called hyaline membrane disease, evidenced by respiratory distress (labored Ibreathing) caused by the lack of surfactant. Surfactant secretion can be induced by administering glucocorticoids, significantly improving the infant's condition and chances for survival.

Pulmonary Surfactant:

Continuously synthesized and secreted by type II alveolar cells onto the alveolar surfaces, pulmonary surfactant is removed from these surfaces by alveolar macrophages and by type I and II alveolar cells. Its composition and continuous turnover allow it to serve 2 major functions. Not only does it reduce surface tension in the alveoli, but also it is thought to have some bactericidal effects, cleaning the alveolar surface and preventing bacterial invasion of the many capillaries in the septa. in Respiratory system the surfactant forms a thin 2-layer film over the entire alveolar surface. The film consists of an aqueous basal layer (bypopbase) composed mainly of protein, which is covered by a monomolecular film of phospholipid (mainly di palmitoyl lecithin) whose fatty acid tails extend into the lumen. By reducing surface tension, the surfactant helps prevent collapse of the alveoli during expiration. It thus eases breathing by decreasing the force required to reopen the alveoli during the next inspiration. Because surfac tant secretion begins in the last weeks of fetal development, premature infants often suffer a condition called hyaline membrane disease, evidenced by respiratory distress (labored Ibreathing) caused by the lack of surfactant. Surfactant secretion can be induced by administering glucocorticoids, significantly improving the infant's condition and chances for survival.

RESPONSE OF NERVE TISSUE TO INJURY

ØA. Damage to the Cell Body: Because mature neurons cannot divide, dead neurons cannot be replaced. Neurons not connected with otherfunctioning neurons or end organs are useless, and mechanisms have evolved to dispose of them. Thus, if a neuron makes synaptic contact with Only one other neuron and the latter is destroyed, the former undergoes autolysis, a process termed transneuronal degeneration. Most neurons, however, have multiple connections.

ØB. Damage to the Axon: Regeneration can occur in axons injured or severed Far enough from the soma to spare the cell. Such injuries are followed by partial degeneration and then regeneration. Nerve system

1. Degeneration. A crushed or severed axon degenerates both distal and proximal to the injury. Distal to the site Of injury, both the axon and myelin sheath undergo complete degeneration connection with the soma has been lost. During this Wallerian, descendent, or secondary degeneration, whichusually lakes about 2-3 days, nearby Schwann cells proliferate, phagocytose degenerated tissue, and invade the remaining endoneurial channel. Proximal to the site of injury, degeneration of the axon and myelin sheath is similar but incomplete. This retrograde, ascendent, orprimary degeneration proceeds for about 2 internodes before the injured axon is sealed. The cell body also changes in response to injury. The perikaryon enlarges; chromatolysis, or dispersion of Nissl substance, occurs; and the nucleus moves to an eccentric position. Proximal degeneration and cell body changes fake about 2 weeks.

2. Regeneration. This begins in the third week after the injury. As the perikaryon gears up for increased protein synthesis, the Nissl bodies 'eappear. The axon's proximal stump gives off a profusion of smaller processes called neurites; one of these encounters and grows into the endoneurial channel, while the others degenerate. In the channel, the neurite grows 3-4 mm/d, guided and then myelinated by the Schwann cells. Growth is maintained by orthograde axoplasmic transport of material synthesized in the soma. When the tip of the neurite reaches its termination, it connects with its end organ or another neuron in the chain. If the cut ends of a severed nerve are matched by by fascicle size and arrangement and sutured together by their epineurial sheaths within 34 weeks after injury, sensory and motor innervation can often be restored. If the gap between the cut ends is too wide, the neurites may fail to find endoneurial sheaths to grow into and may grow out in a potentially painful disorganized swelling called a neuroma. Target organs deprived of innervation often atrophy.

Alveolar Cell Types:

1. Type I cells. Also called type I alveolar cells, type I pneumocytes, and squamous alveolar cells, these are squamous epithelial cells that make up 97% of the alveolar surfaces.

They are specialized to serve as very thin (often only 25 nm in width) gas-permeable components of the blood-air barrier. Their organelles leg, Golgi complex, endoplasmic reticulum, mitochondria) cluster around the nucleus.

Much of the cytoplasm is thus unobstructed by organelles, except for the abundant small pinocytotic vesicles that are involved in the turn over of pulmonary surfactant and the removal of small particles from the alveolar surfaces. They attach to neighboring epithelial cells by desmosomes and occluding junctions.

The latter reduce pleural effusion--leakage of tissue fluid into the alveolar lumen. Type I cells can be distinguished from the nearby capillary endothelial cells by their position bordering the alveolar lumen and by their slightly more rounded nuclei.

2. Type II cells. These cells, which are also called type II alveolar cells, type II pneumocytes, great alveolar cells, and alveolar septal cells, cover the remaining 3% of the alveolar surface. They are interspersed among the type I cells, to which they attach by desmosomes and occluding junctions.

Type II cells are roughly cuboidal with round nuclei; they occur most often in small groups at the angles where alveolar septal walls converge. At the electron microscope level, they contain many mitochondria and a well-developed Golgi complex, but they are mainly characterized by the presence of large (0.2-um), membrane-limited lamellar (mutlilamellar) bodies. These structures, which exhibit many closely apposed concentric or parallel membranes (lamellae), contain phospholipids, glycosaminoglycans, and proteins.

Type II cells are secretory cells. Their secretory product, pulmonary surfactant, is assembled and stored in the lamellar bodies, which also carry it to the apical cytoplasm. There, the bodies fuse with the apical plasma membrane and release surfactant onto the alveolar surface. 3. Alveolar marcrophages. Known also as dust cells, these large monocytc-derived repre sentatives of the mononuclear phagocyte system are found both on the surface of alveolar septa and in the interstitium. Macrophages are important in removing any debris that escapes the mucus and cilia in the conducting portion of the system.

They also phagocytose blood cells that enter the alveoli as a result of heart failure. These alveolar macrophagcs, which stain positively for iron pigment (hemosiderin), are thus designated heart failure cells.

ALVEOLI

Occurring only in the respiratory portion (which their presence distinguishes from the conducting portion), these small (about 200 um in diameter) sacs open into a respiratory bronchiole, an alveolar duct, an atrium, or an alveolar sac. They are separated by thin walls termed interalveolar (or alveolar) septa.

A. Interalveolar Septa: The structural features of these septa, which are specialized for gas exchange, are critical to respiratory function. The septa consist of 2 simple squamous epithelial layers with the interstitium sandwiched between them. The interstitium consists of continuous (nonfenestrated) capillaries embedded in an elastic connective tissue that includes elastic and collagen fibers, ground substance, fibroblasts, mast cells, macrophages, leukocytes, and contractile interstitial cells that contract in response to epinephrine and histamine. This elastic tissue is an important component of the ventilating mechanism. Gas exchange occurs between the air in the alveolar lumen and the blood in the interstitial capillaries.

1. Blood-air barrier. This term refers to the structures that oxygen and CO2, must cross to be exchanged. Varying from 0. 1-1.5 um in thickness, it includes the following layers: a. The film of pulmonary surfactant on the alveolar surface. b. The cytoplasm of the squamous cpithelial (type I alveolar) cells. c. The fused basal laminae sandwiched between the type I alveolar and capillary endothelial cells. d. The cytoplasm of the squamous endothelial cells lining the intcrstitial capillaries.

2. Alveolar pores. Each septum may be interrupted by one or more pores from 10 to 15 um in diameter. These connect adjacent alveoli and may help to equalize pressure and allow collateral air circulation, thus maximizing the use of available alveoli when some small airways are blocked.

BRONCHIAL TREE - 2

D. Bronchioles: These are branches of the smallest bronchi. The largest bronchioles differ from the smallest bronchi only by the absence of cartilage and glands in their walls. Large bronchioles are lined by typical respiratory epithelium; as they branch further, the epithelial height and complexity decrease to simple ciliated columnar or cuboidal. Each bronchiole gives rise to 5-7 terminal bronchioles.

E. Terminal Bronchioles: The smallest components of the conducting portion of the respiratory system, these are lined by ciliated cuboidal or columnar epithelium and have few or no goblet cells. The lining here also includes dome-shaped cilia-free Clara cells, whose cytoplasm contains glycogen granules, lateral and apical Golgi complexes, elongated mitochondria, and a few secretory granules. The function of these cells is unclear. Each terminal bronchiole branches to form 2 or more respira tory bronchioles.

F. Respiratory Bronchioles: These are the first part of the respiratory portion, with a cuboidal epithelial lining which resembles that of the terminal bronchioles but which is interrupted by thin-walled saccular evaginations called alveoli. The number of alveoli increases as the respiratory bronchioles proceed distally. As the alveoli increase in number, the cilia decrease until they disappear. Goblet cells are absent.


G. Alveolar Ducts: These are simply the distal extensions of the respiratory bronchioles where the alveoli are so dense that the wall consists almost entirely of these sacs, and the lining has been reduced to small knobs of smooth muscle covered by cilia-free simple cuboidal cells.

H. Atria and Alveolar Sacs: Atria are the distal terminations of alveolar ducts. The arrangement is comparable to a long hallway (alveolar duct) leading to a rounded foyer (atrium). The foyer has small doorways leading to some small rooms (alveoli), but also has 2 or more larger doorways leading into short, dead-end hallways (alveolar sacs). The short hallways are also lined by small rooms (alveoli). Put simply, the difference between atria and alveolar sacs is that the atria open into alveolar ducts, alveoli, and alveolar sacs, while the alveolar sacs open only into alveoli and atria.