Chapter 1 Cell Structure and Function The cell is the building block. Each cell is a self-contained system. Cells tissues organs body systems. Physiologic Concepts Cell Structure A cell is made up of internal structures bound together inside one cell membrane. All cells contain the same internal structures. The inside of each cell can be divided into cytoplasm and snucleus. Cytoplasm The cytoplasm includes everything inside the cell but outside the nucleus. mitochondria energy sources of the cell, endoplasmic reticulum and ribosomes, protein synthesis. The Golgi apparatus secretion of proteins synthesized on the ribosomes. Intracellular lysosomes are vesicles that contain potent digestive enzymes. The internal skeleton, called cytoskeleton, supports the cell from the inside and allows for the movement of substances inside the cell. The Nucleus: a large, membranebound organelle that contains deoxyribonucleic acid (DNA), the genetic material of the cell. To protect itself from breakage, the DNA is folded up inside the nucleus. Proteins responsible for folding and protecting the DNA are called histones. Cell Membrane; encircles each cell, semipermeable barrier composed of a bilayer of phospholipids, with interspersed, freely moving, protein molecules. Diffusion through the lipid bilayer is limited to lipidsoluble substances. Movement through the Membrane - Lipid-soluble substances, such as oxygen, carbon dioxide, alcohol, and urea, move across the lipid bilayer by simple diffusion. - Other substances that are not lipid soluble, move through pores provided by the integral proteins or through carrier-mediated transport systems. Through the Cell Membrane This process does not require energy, a substance that is permeable across the cell membrane will diffuse into or out of the cell until its concentration is equal on both sides Osmosis The diffusion of water into the cell is called osmosis; water moves down its concentration gradient (i.e., from high concentration to low). According to osmotic pressure. The osmotic pressure of a solution depends on the number of particles or ions present in the water solution. The more ions that are present in the solution, the less the water concentration and the greater the osmotic pressure (i.e., the pressure for water to diffuse into the solution). A cell also has osmotic pressure. A dehydrated cell has high osmotic pressure, Water would diffuse into this cell if possible. An overhydrated cell has low osmotic pressure , Water would diffuse out of this cell if possible. Simple Diffusion through Protein Pores These protein channels are usually selective about which ions they allow to pass. Like all types of simple diffusion, diffusion through a gate continues until the concentrations on either side of the membrane are equal or the gate is shut. Mediated Transport For many substances like glucose and amino acids, simple diffusion is impossible. These molecules are too charged large to pass through a pore. Instead, these substances, are transported across the membrane with the assistance of a carrier. This type of movement is called mediated transport . . With active transport, energy is used by the cell to maintain a substance at higher concentration on one side of the membrane than the other. Examples of substances moved by active transport include Na, K, Ca, and the amino acids. Facilitated diffusion is similar to simple diffusion in that no energy is used by the cell to transport a substance but differs from simple diffusion in that it is assisted (facilitated) by a carrier and so can cross the membrane. Glucose moves into most cells by facilitated diffusion. Endocytosis When large substances cannot enter the cell by diffusion or mediated transport, endocytosis (engulfment) of the substance by the cell membrane occurs. - Pinocytosis is the engulfment of macromolecules, such as protein, by vesicles. - Phagocytosis is the engulfment of dead cells or bacteria. Both processes require energy. Only cells of the immune system (i.e., macrophages and neutrophils) perform phagocytosis. Energy Production Cells are required to produce energy for their own use. Cells do this by extracting the energy contained in the chemical bonds of food molecules by combining the food molecules with oxygen inside the mitochondria of the cell. The food molecules used are glucose from carbohydrate metabolism, amino acids from protein metabolism, and fatty acids and glycerol from fat metabolism. The Sodium-Potassium Pump An important example of active transport is the pumping of sodium and potassium across cell membranes. This transport depends on an integral carrier protein known as the sodiumpotassium pump. Associated with the pump is an enzyme that splits ATP and provides the energy needed for the pump to function. This enzyme is known as the sodium-potassium ATPase. The sodium-potassium pump transports sodium ions out of and potassium ions into the cell. This transport causes greater sodium concentration in the extracellular fluid (142 mEq/L) compared to the intracellular fluid (14 mEq/L), and greater potassium concentration in the intracellular fluid (140 mEq/L) compared to the extracellular fluid (4 mEq/L). The Effects of Pumping Sodium and Potassium 1- allows nerve and muscle function and action potentials to occur . Because sodium and potassium are cations (carrying a positive charge), the transport of three sodium ions out of the cell and only two potassium ions into the cell creates an electrical gradient across the cell membrane. 2- controlling cell volume The presence of intracellular proteins and other organic substances that cannot cross the cell membrane increases intracellular osmotic pressure and creates a tendency for water to diffuse into the cell. This diffusion of water, if unlimited, would cause the cell to swell and eventually burst. However, with the active transport of sodium ions out of the cell, the osmotic pressure inside the cell is reduced and the diffusion of water into the cell is contained. Cellular Reproduction Many cells of the body reproduce and make copies of themselves throughout an organism's lifetime. To reproduce, a cell has to replicate its genetic material and then split in two. Replication and division of a cell occurs during the cell cycle . Replication To replicate, the DNA double helix uncoils and each strand of DNA serves as a template for a new strand. Replication of the chromosome pairs and the DNA occurs in the nucleus of the cell. Various enzymes participate in DNA replication, which results in each chromosome being exactly copied or duplicated. Cell Division Once duplicated, the chromosome pairs pull apart and the original cell splits into two cells. Each new cell contains the entire genetic information in 23 pairs of chromosomes. The process whereby a cell divides to produce two identical daughter cells is called mitosis. Meiosis, another type of cell division, occurs in the reproductive cells, the egg and sperm. Meiosis involves two cell divisions resulting in a total of four daughter cells produced, each containing 23 single chromosomes rather than 23 pairs. Cellular Replication and Division - Some cells, such as liver, bone marrow, and gut cells, undergo replication and mitosis frequently. - Nerve and cardiac muscle cells, do not replicate or divide except during fetal development or in the neonatal period. - Pathophysiologic Concepts Cells are continually exposed to changing conditions and potentially damaging stimuli. If these changes and stimuli are minor or brief, the cell adapts to them. Cellular adaptations include atrophy, hypertrophy, hyperplasia, metaplasia and dysplasia. More prolonged or intense stimuli can cause cell injury or death. Atrophy Atrophy is a decrease in the size of a cell or tissue. Atrophy can occur as a result of - disuse, for instance, as seen in the muscles of an individual who is immobilized . - decreased hormonal or neural stimulation of a cell or tissue, which is seen in the breasts of women after menopause or in skeletal muscle after spinal cord injury . - nutritional deficiency and is seen in malnourished or starving people. - insufficient blood supply to cells, which cuts off vital nutrient and oxygen supply. Hypertrophy Hypertrophy is the increase in the size of a cell or tissue. Hypertrophy is an adaptive response that occurs when there is an increase in the workload of a cell. The cell's demand for oxygen and nutrients increases, causing growth of most intracellular structures. Hypertrophy is primarily seen in cells that cannot adapt to increased work by increasing their numbers through mitosis. Examples of cells that cannot undergo mitosis but experience hypertrophy are cardiac and skeletal muscle cells. There are three main types of hypertrophy: -Physiologic hypertrophy occurs as a result of a healthy increase in the workload of a cell (i.e., increased muscle bulk through exercise). -Pathologic hypertrophy occurs in response to a disease state, for example, hypertrophy of the left ventricle in response to longstanding hypertension . -Compensatory hypertrophy occurs when cells grow to take over the role of other cells that have died. For example, the loss of one kidney causes the cells of the remaining kidney to undergo hypertrophy. Hyperplasia Hyperplasia is the increase in cell number as a result of increased mitosis stimulated by an increased workload, or by hormonal signals. It can only occur in cells that undergo mitosis, such as liver, kidney, and connective tissue cells. Hyperplasia may be: Physiologic hyperplasia occurs monthly in uterine endometrial cells . Pathophysiologic hyperplasia can occur with excessive hormonal stimulation, which is seen in acromegaly . Compensatory hyperplasia occurs when cells of a tissue reproduce to make up for a previous decrease in cells as what occurs in liver cells after surgical removal of sections of liver tissue. The compensation is striking in its rapidity. Metaplasia Metaplasia is the change in a cell from one subtype to another, i.e change in the cells of the respiratory passages from ciliated columnar epithelial cells to stratified squamous epithelial cells (smokers). Stratified epithelial cells are better able to survive smoke damage. Unfortunately, they do not assume the vital protective role of ciliated cells. Dysplasia Dysplasia is a derangement in cell growth that results in cells that differ in shape, size, and appearance from their predecessors, due to exposure to chronic irritation and inflammation. (dangerous, mey be precancerous). Again, respiratory tract (especially the squamous cells is the most common site as well as the cervix. Cervical dysplasia usually results from infection of the cells with the human papilloma virus (HPV). Dysplasia is usually rated on a scale to reflect its degree, from minor to severe. Cell Injury Cell injury occurs when a cell can no longer adapt to stimuli. This can occur if the stimuli are too long or too severe. Hypoxia, microorganism infection, temperature extremes, physical trauma, and radiation, cause cell injury. Cell Death There are two main categories of cell death: 1-necrotic cell death, characterized by cell swelling and rupture of internal organelles. Common causes of necrotic cell death include prolonged hypoxia and infection . 2- apoptosis, is not characterized by that dying cell shrinks on itself and then is engulfed by neighboring cells. Programmed cell death begins during embryogenesis and continues throughout the lifetime of an organism. Viral infection of a cell will often turn on apoptosis. Deficiencies in apoptosis have been implicated in the development of cancer . Results of Cell Death Dead cells are removed from the area or isolated from the rest of the tissue by immune cells in the process of phagocytosis. If mitosis is possible and the area of necrosis is not too large, new cells of the same type fill in the empty space. Scar tissue will form in the vacated space if cell division is impossible or if the area of necrosis is extensive. Gangrene refers to the death of a large mass of cells. Gangrene may be classified as dry or wet. Dry gangrene spreads slowly with few symptoms and is frequently seen in the extremities, often as a result of prolonged hypoxia. Wet gangrene is a rapidly spreading area of dead tissue, often of internal organs, and is associated with bacterial invasion of the dead tissue. It exudes a strong odor and is usually accompanied by systemic manifestations. Gas gangrene is a special type of gangrene that occurs in response to an infection of the tissue by a type of anaerobic bacteria called clostridium. It is seen most often after significant trauma. Gas gangrene rapidly spreads to neighboring tissue as the bacteria release deadly toxins that kill neighboring cells. Muscle cells are specially susceptible and release characteristic hydrogen sulfide gas when affected. This type of gangrene may prove fatal. Wound Repair Destroyed or injured tissues must be repaired by regeneration of the cells or the formation of scar tissue. The goal of both types of repair is to fill in the areas of damage.Tissues that heal cleanly and quickly are said to heal by primary intention. Large wounds that heal slowly and with a great deal of scar tissue heal by secondary intention. Delayed Healing and Repair Tissue repair can be delayed if the host has: malnutrition, systemic disease, poorly functioning immune system or if there is reduced blood flow to the injured tissue or if an infection develops. Conditions of Disease or Injury 1-Hypoxia Hypoxia is the decreased concentration of oxygen in the tissues. Causes: inadequate intake of oxygen by the respiratory system, inadequate delivery of oxygen by the cardiovascular system, or a lack of hemoglobin. Oxygen is required by the mitochondria for oxidative phosphorylation and the production of ATP. Without oxygen, this process cannot occur. Consequences of Hypoxia When cells are deprived of ATP, they can no longer maintain cellular functions, including the transport of sodium and potassium through the sodiumpotassium pump. Without sodium-potassium pumping, cells begin to accumulate sodium as it diffuses into the cell down its concentration and electrical gradients. Osmotic pressure inside the cell increases, drawing water into the cell and begins to swell and burst. Another consequence of hypoxia is the production of lactic acid, (which occurs during anaerobic glycolysis). Decreased ph causes damage to the nuclear structures. The effects of hypoxia are reversible if oxygen is returned within a certain period of time, the amount of which varies and depends on the tissue. Clinical Manifestations If the source of hypoxia is respiratory failure or myocardial infarct, all tissues will be affected. Cell death may occur. - Increased heart rate. - Increased respiratory rate. - Muscle weakness. - Decreased level of consciousness. Complications - Altered consciousness progressing to coma and death if prolonged cerebral (brain) hypoxia occurs. -Organ failure, including adult respiratory distress syndrome, cardiac failure, or kidney failure, may occur if hypoxia is prolonged. Treatment Increase oxygen in inspired air through a mask or mechanical ventilation. 2-Temperature Extremes - Exposure to very high temperatures can cause burn injuries, which directly kill cells or indirectly by causing coagulation of blood vessels or the breakdown of cell membranes (brain, boiled eggs). - Exposure to very cold temperatures injures cells in two ways: constriction of the blood vessels that deliver nutrients and oxygen to the extremities and the formation of ice crystals in the cells. These crystals directly damage the cells and can lead to cell lysis (bursting). Prolonged exposure to the cold can lead to hypothermia. Clinical Manifestations of Cold Exposure and Hypothermia - Numbness or tingling of the skin or extremities. - Pale or blue skin that is cool to the touch. - Shivering early on, then lack of shivering as condition worsens. - Decreased level of consciousness, drowsiness, and confusion. Complications - Blood clotting, characterized by pain and a decrease in pulse downstream from the clot. If blood flow is inadequate for an extended time, gangrene may result. - --- Frostbite. - Ventricular dysrhythmia. 3-Radiation Injury Radiation energy may be in the visible range of light, or it invisible light. High-energy radiation (UV) is called ionizing radiation because it has the capability of knocking electrons off atoms or molecules, thereby ionizing them. Low-energy radiation is called nonionizing radiation because it cannot displace electrons off atoms or molecules. Effects of Ionizing Radiation Ionizing radiation may injure or kill cells directly by destroying the cell membrane and causing intracellular swelling and cell lysis. As cells are killed or injured, the inflammatory response is stimulated, causing capillary leakiness, interstitial edema, white blood cell accumulation, and tissue scarring. Ionizing radiation may also lead to mistakes in DNA replication or transcription which may cause programmed cell death or subsequent cancer . cells Susceptible to Ionizing Radiation Cells most susceptible to damage by ionizing radiation are cells that undergo frequent divisions, including cells of the gastrointestinal (GI) tract, the integument (skin and hair), and the bloodforming cells of the bone marrow and FETUS. Ionizing radiation is emitted by the sun, in x- rays, and in nuclear weapons. Effects of Non-Ionizing Radiation Non-ionizing radiation includes microwave and ultrasound radiation. The energy of this radiation is too low to break DNA bonds or damage the cell membrane. Clinical Manifestations of Ionizing Radiation - Skin redness or breakdown. - With high doses, vomiting and nausea caused by GI damage. - Anemia if the bone marrow is destroyed. - Cancer may develop years after the exposure . Treatment - Damage caused by low doses will be repaired and does not require treatment. - Cancers should be treated . Pediatric Consideration Fetal cells rapidly undergo cellular division and are highly susceptible to the damaging effects of ionizing radiation. Infants and young children also experience periods of rapid cellular growth and are at risk of genetic damage from ionizing radiation. Studies suggest that there are no apparent health risks to fetuses exposed to non- ionizing radiation . 4-Injury Caused by Microorganisms Microorganisms infectious to humans include bacteria, viruses, mycoplasmas, rickettsiae, chlamydiae, fungi, and protozoa. Some of these organisms infect humans through: a. direct access, such as inhalation, b. intermediate vector, such as from an insect bite. Cells of the body may be destroyed : a. directly by the microorganism or b. by a toxin released from MO , or may be c. indirectly injured as a result of the immune and inflammatory reactions . Clinical Manifestations Infection by bacteria and viruses, often results in: - Regional lymph node enlargement - Fever (usually low-grade with a viral infection) - Body aches - Skin rash or eruption, especially with viral infections - Site-specific responses, such as pharyngitis, cough, otitis media Treatment - Bacteria and mycoplasmas are treated with antibiotics, preferably C&S - Certain viral infections may be treated with antiviral agents. Other viral infections usually are left to resolve on their own, with care taken that a subsequent bacterial infection does not infect the original site or elsewhere.