Genetic Disorders
The existence of genetic diseases has been recognized for centuries. These disorders were described as running in a family. What was missing was an understanding of why these disorders ran in families. Abnormalities in a person’s genes can cause a genetic disorder. Within the DNA, genes carry the blueprint for protein production which is the life work of most cells. These proteins are essential to cell health.
If the DNA sequence of one gene is altered, called a mutation, then protein production can be altered. Examples of monogenic disorders include Marfan syndrome, sickle-cell anemia, and cystic fibrosis.
In some instances the entire chromosome is structurally defective. Gross breaks in some chromosomes with subsequent rejoinings at new locations, called translocations; extra copies of chromosomes; or missing copies of chromosomes leads to genetic disorders. Down syndrome is a common genetic disorder linked to having three copies of the 21st chromosome.26,27 A child with Down syndrome (Figure 11-8) may have a flattened nose and widely spaced eyes.
Figure 11-7 Obesity in the United States.
Figure 11-8 This child with Down syndrome is encouraged to develop psychomotor skills.
However, most genetic disorders are complex and involve a combination of environmental and multiple genetic mutations. Many chronic diseases—such as Alzheimer’s disease, heart disease, arthritis, and obesity—are thought to have genetic underpinnings.
Not all genetic differences necessarily lead to disease. In fact, some genetic changes may be evolutionary in nature. In an incredible case of genetic detective work, it has been discovered that some people cannot contract human immunodeficiency virus (HIV), the cause of AIDS. The reason is because of a genetic mutation which prevents the white blood cells from creating the receptor, CCR5, that permits the HIV virus to gain entrance into the white blood cell.
Infection
The majority of deaths during recorded history have been due to infectious diseases. Infectious diseases, referred to in medical circles as pathogens, stem from a number of sources. Listed from smallest to largest, they are prions, viruses, bacteria (Figure 11-9), fungi, protozoa, and helminthes (worms). All of these microorganisms are parasites, dependent on the host for survival.
Infectious diseases have three pathogenic mechanisms. Some infectious agents (e.g., herpes simplex) replicate themselves inside the host cells. Eventually these microorganisms destroy the cell’s structural integrity, thereby killing the cell, which is a direct cytopathic effect. The microorganisms are then released to infect other cells or other potential hosts.
Figure 11-9 Common microorganisms that can cause disease.
Other microorganisms are dangerous to the host because they produce a toxin that is harmful (poisonous) to the cell. Toxins can be categorized as either being exotoxins or endotoxins. Exotoxins are proteins that are produced by bacteria and released into the interstitial fluid where they are absorbed, because they are highly soluble, into surrounding cells. Exotoxins can be cell specific. For example, the toxins that produce tetanus and botulism affect nervous tissue whereas the toxins of the streptococcus bacteria affect vascular tissue.
Some bacteria produce toxins by their death. These toxins, called endotoxins, are the result of the breakdown of the bacteria’s cell wall membrane.28,29 Endotoxins are complex substances made up of polysaccharides or phospholipids and are attracted to other cell wall membranes. The bacteria Clostridium tetanus produces a phospholipase (phospholipids make up cell wall membranes and the suffix -ase means enzyme) which breaks down cell walls.
Finally, some infections are dangerous because they trigger an immune response that causes damage to the host, an autoimmune response. For example, the causative agent of rheumatic fever, streptococcus, triggers an undifferentiated immune response that destroys healthy tissue (frequently the heart valves) in the process.
Immune Reactions
Immune reactions can be classified as either exaggerated immune responses or autoimmune responses. In the first case,the body has a disproportionate response to a foreign protein or polysaccharide, an antigen (anti- – "not"; gen – "self") and the results are life-threatening to the patient. This exaggerated immune response, called an anaphylactic response, can lead to severe airway compromise and/or cardiovascular collapse secondary to relative hypovolemia. This may be exemplified by a patient with an allergic reaction (Figure 11-10).
Figure 11-10 Patient experiencing an allergic reaction.
In the case of the autoimmune response, described earlier, the body sets upon itself and starts to destroy normal cells along with infected cells. Autoimmune response has been implicated in the diseases multiple sclerosis, diabetes mellitus, scleroderma, Crohn’s disease, lupus erythematosus, rheumatoid arthritis, and gluten sensitivity.
Effect: Systemic Defense
The body’s defenses to disease start with general nonspecific barriers and end with targeted cellular attacks against the offending disease. If these defenses are overwhelmed, then the patient is diseased.
Patients with disease go into shock, a condition of deranged metabolic functions that have systemic effects described later in this topic. The shock syndrome, a predictable pattern of signs and symptoms, can either culminate with recovery or death. The Paramedic’s mission is to support the body in its struggle against shock.
Nonspecific Defenses
While the analogy is not glamorous, the truth is that the body is essentially two hollow tubes, with one tube being a cul de sac. The outside of the tube is covered by skin, the largest organ of the body. Skin is a barrier to physical attack by trauma, chemicals, and so on and from biological attack from microorganisms such as fungus, bacteria, and virus.
The key to the skin’s effectiveness as a barrier lies in the fact that the outermost layer of skin is dead. Most microorganisms depend on the host cells being alive. The layers of dead epithelial cells, contained in the epidermis, prevent infection from reaching the live cells deeper in the tissue. Barrier devices, such as gloves (Figure 11-11), are simply adjuncts to the first defense, the skin.
But the defense does not stop there. Sebaceous glands excrete acidic (pH 3-5) secretions—lactic acid and fatty acids—which act as a biochemical barrier and create a hostile environment for fungi and bacteria.
Finally, if any infection obtains a foothold in the skin it is only temporary. Skin is sloughed off, or mechanically abraded, continuously, and replaced as quickly. The combination of these three mechanisms culminates in a very effective barrier defense against outside sources of disease.
Internally, the body is lined with mucous membranes that cover the pulmonary tree, the cul de sac mentioned earlier, and the gastrointestinal tract that extends the length of the human torso. Mucous membranes secrete mucus, a sticky liquid that entraps foreign invaders, such as bacteria. Bacteria-laden mucus in the lungs is either expectorated, and thus sputum may be infectious, or ingested, where the bacteria meet their fate in the stomach’s acid.
Infectious trespassers in the oropharynx are first greeted by lysozyme-carrying saliva, which breaks down cell walls. If any remain alive, they are carried to the acidic environment of the stomach to be destroyed. Note that external bodily fluids such as perspiration, tears, and ear wax are either mucuslike, trapping potentially infectious materials, or contain the enzyme lysozyme.
Figure 11-11 Barrier devices, such as gloves, support the body’s own nonspecific defense, the skin.
Like the skin, the internal organs can be protected from foreign invaders by mechanical means such as regurgitation, defecation, menstruation, and urination.
Inflammatory Response
If the nonspecific defenses of the skin or the mucosa are breached and internal cells and tissues are injured, the second-string defenders, the inflammatory system, responds. The inflammatory system is made up of white blood cells and chemical intermediaries that act as messengers.
A variety of causes can stimulate the inflammatory response. Causes include infections that lead to systemic infections; trauma, such as burn trauma; anaphylactic reactions; complications of childbirth; and eclampsia, to name just a few.
