1.5
Tissues are the collective organization of many cells with similar origin and/or function. These tissues associate with other, dissimilar tissues to form the various organs of the body.
There are four types of tissue:
1. Epithelial tissue covers the body’s outer surface, lines the inner surfaces, and forms glandular tissue. Epithelial tissue has three distinct surfaces and the basal surface is attached to an underlying basement membrane. It is avascular, meaning it is lacking its own blood vessels. It draws oxygen and nutrients from the capillaries of the connective tissue on which it rests.
Epithelial tissues are classified according to their shape: squamous (thin and flat), cuboidal (cube shaped), and columnar (resembling a column). They are also classified according to the arrangement or number of layers present: simple (single layer of cells), stratified (more than one layer of cells), and pseudostratified (all cells are in contact with the basement membrane, but some do not extend to the surface).
2. Connective tissue produces the extracellular matrix that supports and holds tissues together. Connective tissue is divided into two types: (1) connective tissue proper and (2) specialized connective tissue, which includes cartilage, bone, and blood cells. The four types of connective tissue proper include (1) loose (areolar), (2) adipose, (3) reticular, and (4) dense connective tissue.
3. Muscle tissue functions to move the skeletal structures, pump blood through the heart and contract the blood vessels and visceral organs. Muscle tissue can accomplish this by contraction. The two types of fibers that produce these contractions are called thin and thick filaments. Thin filaments are called actin; the thick filaments are myosin. The three types of muscle tissue are skeletal, cardiac, and smooth.
4. Nervous tissue is found throughout the body and is used for communication between peripheral tissues and the central nervous system. It provides the means for controlling body function and for sensing and moving about the environment in response to internal and external stimuli. The two types of nervous tissue cells are neurons and glial cells. Neurons function in communication, while glial (meaning glue) cells support the neurons.
Within tissues, cells are held together by cell junctions, spaces between cells filled with extracellular matrix. Adhesion molecules form intercellular contacts. These are important to form the shape of the body and to create pathways for communication. Cell junctions are made mostly of epithelial tissue.
There are three basic types of intercellular junctions:
1. Tight junctions are found in epithelial tissue. They keep fluids from entering the intercellular spaces by connecting neighboring cells.
2. Adhering junctions prevent cell separation by forming a strong adhesion between cells.
3. Gap junctions join neighboring cell membranes by forming channels in the cytoplasm of each cell.
Cellular Adaptation
The cell is able to adapt to changes in the internal environment when stressors arise. If the stress becomes too great, or the cell cannot adapt effectively, cell injury and death can occur. The remainder of the module will discuss cellular adaptation, injury, and death.
Cells can adapt in a variety of ways: (1) by changing in size (atrophy and hypertrophy), (2) by changing in number (hyperplasia), and/or (3) by changing type or form (metaplasia and dysplasia).
Atrophy is a decrease in the size of an organ or tissue resulting from a decrease in the mass of pre-existing cells. It is usually a result of disuse, nutritional or oxygen deprivation, aging, diminished endocrine stimulation, or denervation (lack of nerve stimulation in peripheral muscles caused by injury to motor nerves). Notably, atrophy can be caused by a decrease in cell number or a decrease in cell size. Figure 1.14 depicts atrophy of cells in the endometrium.
Figure 1.14 Atrophy of cells in endometrium. Left: A woman of reproductive age has a normal thick endometrium. Right: a 75-year-old woman's endometrium shows atrophic cells and cystic glands.
Hypertrophy is an increase in the size of an organ or tissue due to the increase in size of the cells that comprise it. As cell size is often related to workload, an increase in workload (stress) brings about an increase in cell size. During this time, protein synthesis and the size and/or number of intracellular organelles are all increased. Hypertrophy can occur under normal physiologic or pathologic conditions as seen with the enlargement of the left ventricle in someone with a diagnosis of heart disease (Figure 1.15).
Figure 1.15 Myocardial hypertrophy. Cross section of the heart with left ventricular hypertrophy
Hyperplasia is an increase in the size of an organ or tissue caused by an increase in the number of cells making up that organ or tissue. An example of this is glandular proliferation in the breast tissue during pregnancy. In some cases, hyperplasia can occur in conjunction with hypertrophy. During pregnancy, uterine enlargement is caused by both hypertrophy and hyperplasia of the smooth muscle cells in the uterus. Notably, pathologic hyperplasia can progress to dysplasia (see below) and eventually cancer.
Metaplasia is the replacement of one differentiated tissue by another. Metaplasia usually occurs in response to chronic irritation and inflammation. This transformation of cells allows for a higher likelihood of survival in a less than optimal environment. Barrett esophagus is a classic example of this. In people with chronic gastroesophageal reflux disease (GERD), the normal squamous epithelium in the lower esophagus changes to columnar-lined epithelium to better handle the stress of acid. Barrett esophagus is the primary risk factor for developing esophageal adenocarcinoma. While metaplasia is reversible, in theory, with the removal of the stressor, under persistent stress, it can progress to dysplasia.
Dysplasia is abnormal cellular growth, resulting in cells that vary in size, shape, and organization. It most often refers to proliferation of precancerous cells. For example, cervical intraepithelial neoplasia (CIN) represents dysplasia and is a precursor to cervical cancer. Because cervical cancer develops in a series of epithelial changes, early detection with annual Papanicolaou (Pap) smears are key. Dysplasia is often a byproduct of longstanding pathologic hyperplasia or metaplasia secondary to chronic irritation and/or inflammation. Dysplasia is reversible, in theory, with alleviation of inciting stress. If stress persists, dysplasia progresses to carcinoma (irreversible).
Cellular Damage, Injury, and Death
Cells can be damaged in several ways, of which there are five common categories: (1) Injury from physical agents; (2) Injury from biologic agents; (3) Chemical injury; (4) Radiation injury; and (5) Injury from nutritional imbalances.
Injury from physical agents include mechanical forces, most notably seen in a fractured bone, extremes of temperature (burns), and electrical forces. Figure 1.16 depicts an electrical burn of the skin.
Injury from biologic agents include viruses, parasites, and bacteria.
Chemical injuries include (but are not limited to) drug toxicities (alcohol, Rx/OTC drugs, street drugs), carbon tetrachloride, lead toxicity, and mercury toxicity.
Radiation injuries can occur as a result of ionizing (cancer treatment), ultraviolet (sunburn), or nonionizing (thermal burns) radiation.
Injury from nutritional imbalances can be caused by nutrient excess or deficiency.
Figure 1.16 Electrical burn of the skin. The victim was electrocuted after attempting to stop their fall from a ladder by grasping a high-voltage line.
The mechanisms of cell injury can be complex. The three types of injury that will be discussed here are as follows: (1) free radical formation; (2) hypoxia; and (3) disruption of intracellular calcium homeostasis.
Free radicals are highly reactive chemical species with an unpaired electron in their outer orbit. This makes them unstable, enabling them to disrupt and damage cells and tissues. Reactive oxygen species (ROS) are oxygen-containing molecules that include free radicals and nonradicals. Oxidative stress occurs when the generation of ROS exceeds the body’s ability to neutralize and eliminate them. Oxidative damage is seen in many diseases, including cancer, amyotrophic lateral sclerosis (ALS), and age-related functional declines. Antioxidants (vitamins A, C, E) are molecules that inhibit the reactions of ROS. Examples include enzymes (catalase), nonmetal elements (selenium), metals (zinc) and vitamins (A, C and E).
A hypoxic cell injury is due to low oxygen delivery to the tissues. Decreased oxygen impairs oxidative metabolism, resulting in the decreased production of ATP. As ATP is the primary source of energy for a cell, the lack of ATP during hypoxia leads to cellular injury as necessary metabolic processes cannot be efficiently carried out. Causes include anemia (reduced oxygen-carrying red blood cells), ischemia (obstruction of arterial blood flow), carbon monoxide poisoning, decreased perfusion of tissues (heart failure, shock), or poor oxygenation of blood (from lung disease). The longer tissue is without an oxygen supply, the greater the chance of permanent cellular injury. Brain cells, for example, undergo irreversible damage after 4-6 minutes of oxygen deprivation. Hypoxia also causes failure of the ATP-dependent sodium/potassium cell membrane pump. Inactivation of this critical membrane pump leads to an increase in intracellular Na+ (and consequently water) levels, resulting in cellular and organelle swelling. Leakage of intracellular enzymes through the permeable cell membrane into the extracellular fluid is a key clinical indicator of cell injury and death.
Calcium functions as a second messenger for many cell reactions. Under normal conditions, intracellular calcium levels are lower than extracellular levels. Thus, a rise in intracellular calcium can inappropriately activate several enzymes leading to potentially damaging effects.
Apoptosis is often referred to as programmed cell death. This process eliminates cells that are worn out, have been produced in excess, have developed improperly, or are genetically damaged. Apoptosis is also responsible for several normal physiologic processes, as shown in the collection of Figure 1.17.
Use the navigation below to navigate through the image collection
Figure 1.17 Examples of apoptosis: Slide 1: separation of webbed fingers and toes in embryo; Slide 2: development of neural connections; neurons that do not establish synaptic connections and receive survival factors may be left to undergo apoptosis; Slide 3: removal of cells from intestinal villi; new epithelial cells continuously form in the crypt, migrate to the villus tip as they age, and undergo apoptosis at the end of their life span; Slide 4: removal of aging blood cells.
Necrosis refers to cell death in an organ or tissues that is still part of a living person. However, unlike apoptosis, necrosis sets off an inflammatory immune response. The cell death associated with necrosis often interferes with cell replacement and tissue regeneration. Coagulative necrosis results most often from a sudden cutoff of blood supply to an organ (ischemia), particularly in the heart and kidney. Liquefactive necrosis occurs when some of the cells die but their catalytic enzymes are not destroyed. It is commonly seen with brain infarcts or abscesses. Caseous necrosis occurs as part of granulomatous inflammation and is most often associated with tuberculosis.
Gangrenous necrosis is when a significant amount of tissue undergoes necrosis and can be characterized as either dry or moist. This typically occurs due to blockage of arterial blood supply and normally affects the lower extremities or the bowels. In dry gangrene, the affected tissue becomes dehydrated. It shrinks back and becomes dark brown or black in color. The spread of dry gangrene is slow. In wet gangrene, the affected area is cold, swollen, and pulseless. The skin is moist, black, and distended. Blebs (small blisters) form on the skin’s surface; liquefaction occurs, and a foul odor is caused by bacterial action. The spread of tissue damage is rapid.