Sonia Blome, MD

Remember that these two processes often occur simultaneously antibiotic for bacterial vaginosis order revectina 12 mg on line, and in conjunction with inflammation as a three-pronged attack on the same pathogen bacteria 30 degrees celsius discount 12 mg revectina mastercard. Fawcett/Science Source Serum antibody titer IgG IgG IgM IgM 0 (b) 5 10 15 20 Days from reexposure to same antigen 25 Why does the secondary immune response prevent a pathogen from causing disease antibiotics for urine/kidney infection buy discount revectina 6 mg line, while the primary immune response does not Note the differences in the speed of response antibiotics for bladder infection during pregnancy buy 6 mg revectina mastercard, the height of the antibody titer antibiotic resistance of bacillus subtilis buy generic revectina from india, and the rate of decline in antibody titer. The immune response may be too vigorous, too weak, or misdirected against the wrong targets. Such antigens, called allergens, occur in mold, dust, pollen, vaccines, bee and wasp venoms, animal dander, toxins from poison ivy and other plants, and foods such as nuts, milk, eggs, and shellfish. Drugs such as penicillin, tetracycline, and insulin are allergenic to some people. One classification system recognizes four kinds of hypersensitivity, distinguished by the types of immune agents (antibodies or T cells) involved and their methods of attack on the antigen. In this system, type I is also characterized as acute (immediate) 24 23 allergies. Some authorities use the word allergy for type I reactions only, and others use it for all four types. Type I is an IgE-mediated reaction that begins within seconds of exposure and usually subsides within 30 minutes, although it can be severe and even fatal. Allergens bind to IgE on the membranes of basophils and mast cells and stimulate them to secrete histamine and other inflammatory and vasoactive chemicals. These chemicals trigger glandular secretion, vasodilation, increased capillary permeability, smooth muscle spasms, and other effects. The clinical signs include local edema, mucus hypersecretion and congestion, watery eyes, a runny nose, hives (red itchy skin), and sometimes cramps, diarrhea, and vomiting. Some examples of type I hypersensitivity are food allergies and asthma,24 a local inflammatory reaction to inhaled allergens (see Deeper Insight 21. Anaphylactic shock is a severe, widespread acute hypersensitivity that occurs when an allergen such as bee venom or penicillin is introduced to the bloodstream of an allergic individual, or when a person ingests certain foods (such as peanuts) to which he or she is allergic. It is characterized by bronchoconstriction, dyspnea (labored breathing), widespread vasodilation, circulatory shock, and sometimes sudden death. Antihistamines are inadequate by themselves to counter anaphylactic shock, but epinephrine relieves the symptoms by dilating the bronchioles, increasing cardiac output, and restoring blood pressure. It is the leading cause of school absenteeism and childhood hospitalization in the United States. In the United States, it affects about 5% of adults and up to 10% of children, and takes about 3,400 lives per year. Moreover, asthma is on the rise; there are many more cases and deaths now than there were decades ago. In allergic (extrinsic) asthma, the most common form, a respiratory crisis is triggered by allergens in pollen, mold, animal dander, food, dust mites, or cockroaches. The allergens stimulate plasma cells to secrete IgE, which binds to mast cells of the respiratory mucosa. Reexposure to the allergen causes the mast cells to release a complex mixture of inflammatory chemicals, which trigger intense airway inflammation. This form is more common in adults than in children, but the effects are much the same. Within minutes, the bronchioles constrict spasmodically (bronchospasm), causing severe coughing, wheezing, and sometimes suffocation. Interleukins attract eosinophils to the bronchial tissue, where they secrete proteins that paralyze the respiratory cilia, severely damage the epithelium, and lead to scarring and extensive long-term damage to the lungs. Asthma is treated with epinephrine and other -adrenergic stimulants to dilate the airway and restore breathing, and with inhaled corticosteroids or nonsteroidal anti-inflammatory drugs to minimize airway inflammation and long-term damage. The treatment regimen can be very complicated, often requiring more than eight different medications daily, and compliance is therefore difficult for children and patients with low income or educational attainment. Asthma runs in families and seems to result from a combination of heredity and environmental irritants. Asthma is also more common in countries where vaccines and antibiotics are widely used. It is less common in developing countries and in farm children of the United States. The reaction leads to complement activation and either lysis or opsonization of the target cell. Macrophages phagocytize and destroy opsonized platelets, erythrocytes, or other cells. At the sites of deposition, these complexes activate complement and trigger intense inflammation, causing tissue destruction. Autoimmunity is usually prevented by negative selection of developing T and B cells, but there are at least three reasons why self-tolerance may fail: 1. In rheumatic fever, for example, a streptococcus infection stimulates production of antibodies that react not only against the bacteria but also against antigens of the heart tissue. It often results in scarring and stenosis (narrowing) of the mitral and aortic valves. Viruses and drugs may change the structure of self-antigens and cause the immune system to perceive them as foreign. One theory of type 1 diabetes mellitus is that a viral infection alters the antigens of the insulin-producing beta cells of the pancreatic islets, which leads to an autoimmune attack on the cells. In immunodeficiency diseases, by contrast, the immune system fails to respond vigorously enough. The most publicized case was David Vetter, who spent his life in sterile plastic chambers and suits (fig. David contracted the fatal virus from his sister through a bone marrow transplant. External to this is a viral envelope composed of phospholipids and glycoproteins derived from the host cell. Each virus can now invade a new helper T cell and produce a similar number of descendants. As the virus destroys more and more cells, however, the signs and symptoms become more pronounced: night sweats, fatigue, headache, extreme weight loss, and lymphadenitis. White patches may appear in the mouth, caused by Candida (thrush) or Epstein­Barr27 virus (leukoplakia). It can be transmitted from mother to fetus through the placenta or from mother to infant during childbirth or nursing. The most common means of transmission are sexual intercourse (vaginal, anal, or oral), contaminated blood products, and drug injections with contaminated needles. Barr (1932­2016), British virologist Moritz Kaposi (1837­1902), Austrian physician through heterosexual, predominantly vaginal intercourse. The sharing of needles for drug use remains the chief means of transmission in urban ghettos. It is not transmitted by kissing or by mosquitoes or other blood-sucking arthropods. It is destroyed by laundering; dishwashing; exposure to heat (50°C [135°F] for at least 10 minutes); chlorination of swimming pools and hot tubs; and disinfectants such as bleach, Lysol, hydrogen peroxide, rubbing alcohol, and germicidal skin cleansers such as Betadine and Hibiclens. Since it hides within host cells, it usually escapes recognition by the immune system. Such rapid mutation is a barrier to both natural immunity and development of a vaccine. In 1996, a family of drugs called protease inhibitors became available, typically used in a "triple cocktail" combining these with two reverse transcriptase inhibitors. Compliance is difficult for some, especially the homeless, drug abusers, the poorly nourished, and persons unable to pay for treatment. One obstacle to treatment and prevention is the lack of animal models for vaccine and drug research and development. The chimpanzee is an exception, but chimpanzees are difficult to maintain, and there are economic barriers and ethical controversies surrounding their use. We have surveyed the major classes of immune system disorders and a few particularly notorious immune diseases. Aside from the time required for a reaction to appear, how does delayed hypersensitivity differ from the acute and subacute types State some reasons why antibodies may begin attacking self-antigens to which they did not previously respond. An allergic skin reaction characterized by a "wheal-and-flare" reaction-white blisters (wheals) surrounded by reddened areas (flares), usually with itching. Can be triggered by food or drugs, but sometimes by nonimmunological factors such as cold, friction, or emotional stress. A lymph node malignancy, with early symptoms including enlarged painful nodes, especially in the neck, and fever; often progresses to neighboring lymph nodes. Enlargement of the spleen, sometimes without underlying disease but often indicating infections, autoimmune diseases, heart failure, cirrhosis, Hodgkin disease, and other cancers. The enlarged spleen may "hoard" erythrocytes, causing anemia, and may become fragile and subject to rupture. Causes fever, fatigue, joint pain, weight loss, intolerance of bright light, and a "butterfly rash" across the nose and cheeks. Hodgkin30 disease Splenomegaly31 Systemic lupus erythematosus32 You can find other lymphatic and immune system disorders described in the following places: Rheumatoid arthritis in Deeper Insight 9. The sympathetic nervous system issues nerve fibers to the spleen, thymus, lymph nodes, and aggregated lymphoid nodules of the ileum, where nerve fibers contact T cells, B cells, and macrophages. These neurotransmitters have been shown to influence immune cell activity in various ways. Cortisol, another stress hormone, inhibits T cell and macrophage activity, antibody production, and the secretion of inflammatory chemicals. It also induces atrophy of the thymus, spleen, and lymph nodes and reduces the number of circulating lymphocytes, macrophages, and eosinophils. Thus, it is not surprising that prolonged stress increases susceptibility to illnesses such as infections and cancer. The existence of lymphatic vessels in the central nervous system, discovered only recently, has intriguing implications for direct effects of the brain on the immune system. Immune cells synthesize numerous hormones and neurotransmitters that we normally associate with endocrine and nerve cells. It remains uncertain and controversial whether the quantities of some of these substances produced by immune cells are enough to have far-reaching effects on the body, but it seems increasingly possible that immune cells influence nervous and endocrine functions in ways that affect recovery from illness. People under stress, such as medical students during examination periods and people caring for relatives with Alzheimer disease, show more respiratory infections than other people and respond less effectively to hepatitis and flu vaccines. Attitudes such as optimism, cheer, depression, resignation, or despair in the face of disease significantly affect immune function. Indeed, ardent believers in voodoo sometimes die just from the belief that someone has cast a spell on them. The stress of hospitalization can counteract the treatment one gives to a patient, and neuroimmunology has obvious implications for treating patients in ways that minimize their stress and thereby promote recovery. All systems are subject to a variety of hypersensitivity and autoimmune disorders. Autoimmunity damages heart valves in rheumatic fever, and immune hypersensitivity causes circulatory failure in anaphylactic shock. Alveolar macrophages remove debris from the lungs; pulmonary lymphatic vessels are especially abundant and are needed to prevent fluid accumulation in the lungs. Immune hypersensitivity has effects ranging from respiratory congestion to asthma. Lymphatics absorb fluid and proteins in the kidneys, which is essential to enabling kidneys to concentrate the urine and conserve water. Immunity to cells that are genetically different from other body cells requires the testes and ovaries to have barriers that protect sperm and eggs from immune destruction. Location, gross anatomy, and histology of the spleen; the difference between the red and white pulp; and functions associated with each type of pulp 17. How hyperemia, bradykinin, and other factors account for the four cardinal signs of inflammation 19. Mechanisms of tissue repair carried out after a pathogen is defeated Assess Your Learning Outcomes To test your knowledge, discuss the following topics with a study partner or in writing, ideally from memory. How lymph is produced; characteristics of lymphatic capillaries that allow cells and other large particles to enter the lymph 4. Lymphatic collecting vessels, trunks, and collecting ducts; the similarity of lymphatic vessels to some blood vessels; and their relationship to the lymph nodes 5. Names of the 11 lymphatic trunks and two collecting ducts; the body regions drained by them; and the two points at which lymph empties into the bloodstream 6. How lymphatic nodules differ from diffuse lymphatic tissue; the name of the clusters of lymphatic nodules found in the distal small intestine 10. How lymphatic organs differ from diffuse lymphatic tissue and lymphatic nodules; the two primary lymphatic organs and three secondary lymphatic organs, and why they are called this 11. The location, gross anatomy, and histology of the thymus; the functional difference between its cortex and medulla; the functions of its epithelial cells; and the necessity of the thymus to immunity 13. Structure and function of lymph nodes; the significance of lymph nodes having both afferent and efferent lymphatic vessels, unlike any other lymphatic organs; the approximate number of lymph nodes and seven regions in which they are especially concentrated; and the meaning of lymphadenitis and lymphadenopathy 14. Types of tonsils, where they are located, and their structure and function; the most common cause of tonsillitis 21. Differences between innate and adaptive immunity; defining characteristics of the former 4. Three properties of the skin that make it an effective barrier to pathogens; the roles of organic acids and antimicrobial peptides in its barrier function 5. Three pathways of complement activation; how each is initiated; which pathways function in innate and adaptive immunity; and four mechanisms of pathogen destruction aided by complement 12. The actions of natural killer cells and the roles of perforins and granzymes in defense 13.

The first breath of a baby and the last gasp of a dying person are two of the most dramatic moments of human experience antibiotic vertigo purchase cheap revectina on-line. The respiratory system consists essentially of tubes that deliver air to the lungs infection thesaurus buy 6 mg revectina free shipping, where oxygen diffuses into the blood and carbon dioxide diffuses out fish antibiotics for acne cheap revectina online amex. The respiratory and cardiovascular systems collaborate to deliver oxygen to tissues throughout the body and transport carbon dioxide to the lungs for elimination xnl antibiotic generic revectina 3 mg otc. A disorder that affects the lungs has direct and pronounced effects on the heart virus 000 buy revectina online now, and vice versa. The respiratory zone consists of the alveoli and other gas-exchange regions of the distal airway. The airway from the nose through the larynx is often called the upper respiratory tract (that is, the respiratory organs in the head and neck), and the regions from the trachea through the lungs compose the lower respiratory tract (the respiratory organs of the thorax). However, these are inexact terms and various authorities place the dividing line between the upper and lower tracts at different points. Its superior half is supported by a pair of small nasal bones medially and the maxillae laterally. By palpating your own nose, you can easily find the boundary between the bone above and 1 the more flexible cartilage below. The dividing wall is a vertical plate, the nasal septum, composed of bone and hyaline cartilage. The vomer forms the inferior part of the septum, the perpendicular plate of the ethmoid bone forms its superior part, and the septal cartilage forms its anterior part. Draw a line across part (a) of this figure to indicate the boundary between the upper and lower respiratory tract. The palate separates the nasal cavity from the oral cavity and allows you to breathe while chewing food. The paranasal sinuses and the nasolacrimal ducts of the orbits drain into the nasal cavity (see figs. The nasal cavity begins with a small dilated chamber called the vestibule just inside the nostril, bordered by the ala nasi. The narrowness of these passages and the turbulence caused by the conchae ensure that most air contacts the mucous membrane on its way through. As it does, most dust in the air sticks to the mucus and the air picks up moisture and heat from the mucosa. The conchae thus enable the nose to cleanse, warm, and humidify the air more effectively than if the air had an unobstructed flow through a cavernous space. Past the vestibule, the mucosa (mucous membrane) of the nasal cavity consists of a ciliated pseudostratified columnar epithelium overlying a loose connective tissue lamina propria (see figs. Its ciliated cells are capped with a fringe of about 200 motile cilia per cell and coated with a layer of mucus. The second most abundant cells of the epithelium are the wineglass-shaped goblet cells, which secrete most of the mucus. In lesser numbers, the respiratory epithelium also contains endocrine cells, chemosensory brush cells, and basal stem cells. Inhaled dust, pollen, bacteria, and other foreign matter are trapped in the sticky blanket of mucus covering the epithelium. The cilia of the epithelium beat in waves that drive this debris-laden mucus posteriorly to the pharynx, where it is swallowed. The particulate debris is either digested or passes through the digestive tract rather than contaminating the lungs. A small area of nasal mucosa has an olfactory epithelium, concerned with the sense of smell. It covers about 5 cm2 in the roof of the nasal fossa and adjacent parts of the septum and superior concha. A notable contrast with the respiratory epithelium is that the cilia of the olfactory epithelium are immobile. They lie flattened against the mucosal surface like a plate of spaghetti noodles and serve to bind odor molecules, not to propel mucus. In the respiratory mucosa, it contains glands that supplement the mucus produced by the goblet cells. These secrete a watery serous fluid that bathes the olfactory cilia and facilitates the diffusion of odor molecules from inhaled air to their receptors on the cilia. The inferior concha has an especially extensive venous plexus called the erectile tissue (swell body). Every 30 to 60 minutes, the erectile tissue on one side swells with blood and restricts airflow through that fossa. Most air is then directed through the other nostril, allowing the engorged side time to recover from drying. Thus, the preponderant flow of air shifts between the right and left nostrils once or twice each hour. If one nostril is blocked and the other nasal fossa is over-ventilated for several days, its pseudostratified columnar epithelium changes to stratified squamous, which better resists drying. The nasopharynx is distal to the posterior nasal apertures and superior to the soft palate. It receives the auditory (pharyngotympanic or eustachian) tubes from the middle ears and houses the pharyngeal tonsil. They collide with the wall of the nasopharynx and stick to the mucosa near the tonsil, which is well positioned to respond to airborne pathogens. The oropharynx is a space between the posterior margin of the soft palate and the epiglottis. The nasopharynx passes only air and is lined by pseudostratified columnar epithelium, whereas the oropharynx and laryngopharynx pass air, food, and drink and are lined by more abrasion-resistant stratified squamous epithelium. Its primary function is to keep food and drink out of the airway, but it evolved the additional role of sound production (phonation) in many animals; hence, we colloquially think of it as the "voice box. During swallowing, however, extrinsic muscles of the larynx pull the larynx upward toward the epiglottis, the tongue pushes the epiglottis downward to meet it, and the epiglottis closes the airway and directs food and drink into the esophagus behind it. The vestibular folds of the larynx, discussed shortly, play a greater role in keeping food and drink out of the airway, however. In infants, the larynx is relatively high in the throat and the epiglottis touches the soft palate. This creates a more or less continuous airway from the nasal cavity to the larynx and allows an infant to breathe continually while swallowing. The epiglottis deflects milk away from the airstream, like rain running off a tent while it remains dry inside. By age 2, the root of the tongue becomes more muscular and forces the larynx to descend to a lower position. It then becomes impossible to breathe and swallow at the same time without choking. The most superior one, the epiglottic cartilage, is a spoon-shaped supportive plate of elastic cartilage in the epiglottis. Testosterone stimulates the growth of this prominence, which is therefore larger in males than in females. The thyroid and cricoid cartilages essentially constitute the "box" of the voice box. The arytenoid and corniculate cartilages function in speech, as explained shortly. A group of fibrous ligaments binds the cartilages of the larynx together and forms a suspension system for the upper airway. A broad sheet called the thyrohyoid membrane suspends the larynx from the hyoid bone above it. Below, the cricothyroid ligament suspends the cricoid cartilage from the thyroid cartilage. This is the most clinically important of all these ligaments, as this is where emergency incisions are made in a tracheotomy to restore breathing when the airway above it is obstructed (see Deeper Insight 22. All of these are collectively called the extrinsic ligaments because they link the larynx to other organs. The intrinsic ligaments are contained entirely within the larynx and link its nine cartilages to each other; they include ligaments of the vocal cords and vestibular folds. The interior wall of the larynx has two folds on each side that stretch from the thyroid cartilage in front to the arytenoid cartilages in back. The inferior vocal cords (vocal folds) produce sound when air passes between them. The vocal cords and the opening between them are collectively called the glottis (fig. The superficial extrinsic muscles connect the larynx to the hyoid bone and elevate the larynx during swallowing. The deeper intrinsic muscles control the vocal cords by pulling on the corniculate and arytenoid cartilages, causing the cartilages to pivot. Depending on their direction of rotation, the arytenoid cartilages abduct or adduct the vocal cords (fig. Air forced between the adducted vocal cords vibrates them, producing a high-pitched sound when the cords are relatively taut and a lower-pitched sound when they are more slack. In adult males, the vocal cords are usually longer and thicker, vibrate more slowly, and produce lower-pitched sounds than in females. The crude sounds from the larynx are formed into words by actions of the pharynx, oral cavity, tongue, and lips. The intrinsic muscles are much more numerous and complex than these two pairs isolated for illustration. Why do inhaled objects more often go into the right main bronchus than into the left Like the wire spiral in a vacuum cleaner hose, the cartilage rings reinforce the trachea and keep it from collapsing when you inhale. The open part of the C faces posteriorly, where it is spanned by a smooth muscle, the trachealis (fig. The gap in the C allows room for the esophagus to expand as swallowed food passes by. The inner lining of the trachea is a pseudostratified columnar epithelium composed mainly of mucus-secreting goblet cells, ciliated cells, and short basal stem cells (figs. The mucus traps inhaled particles and the upward beating of the cilia drives the debris-laden mucus toward the pharynx, where it is swallowed. The connective tissue beneath the tracheal epithelium contains lymphatic nodules, mucous and serous glands, and the tracheal cartilages. The outermost layer of the trachea, called the adventitia, is fibrous connective tissue that blends into the adventitia of other organs of the mediastinum, especially the esophagus. If the upper airway is obstructed, it may be necessary to make a temporary opening in the trachea inferior to the larynx and insert a tube to allow airflow-a procedure called tracheotomy. They prevent asphyxiation, but the inhaled air bypasses the nasal cavity and thus is not humidified. If the opening is left for long, the mucous membranes of the respiratory tract dry out and become encrusted, interfering with the clearance of mucus from the tract and promoting infection. When a patient is on a ventilator and air is introduced directly into the trachea (intubation), the air must be filtered and humidified by the apparatus to prevent respiratory tract damage. A deep groove called the horizontal fissure separates the superior and middle lobes, and a similar oblique fissure separates the middle and inferior lobes. The Bronchial Tree Each lung has a branching system of air tubes called the bronchial tree, extending from the main bronchus to about 65,000 terminal bronchioles. It is slightly wider and more vertical than the left one; consequently, aspirated (inhaled) foreign objects lodge in the right bronchus more often than in the left. The right main bronchus gives off three branches-the superior, middle, and inferior lobar (secondary) bronchi-one to each lobe of the lung. The left main bronchus is about 5 cm long and slightly narrower and more horizontal than the right. It gives off superior and inferior lobar bronchi to the two lobes of the left lung. Each one ventilates a functionally independent unit of lung tissue called a bronchopulmonary segment. The main bronchi are supported, like the trachea, by rings of hyaline cartilage, whereas the cartilages transition to overlapping crescent-shaped plates by the time we reach the lobar and segmental bronchi. All of the bronchi are lined with ciliated pseudostratified columnar epithelium, but the cells grow shorter and the epithelium thinner as we progress distally. All divisions of the bronchial tree have a substantial amount of elastic connective tissue, which contributes to the recoil that expels air from the lungs in each respiratory cycle. The mucosa also has a well-developed layer of smooth muscle, the muscularis mucosae, which contracts or relaxes to constrict or dilate the airway, thus regulating airflow. The portion of the lung ventilated by one bronchiole is called a pulmonary lobule. Bronchioles have a ciliated cuboidal epithelium and a well-developed layer of smooth muscle in their walls. Spasmodic contractions of this muscle at death cause the bronchioles to exhibit a wavy lumen in most histological sections. Each bronchiole divides into 50 to 80 terminal bronchioles, the final branches of the conducting zone (fig. They do have cilia, however, so that mucus draining into them from the more proximal air passages can be driven back by the mucociliary escalator, preventing congestion of the terminal bronchioles and alveoli. At the level of the sternal angle, the trachea ends at a fork called the tracheal bifurcation, where it gives off the right and left main bronchi. The broad costal surface is pressed against the rib cage, and the smaller concave mediastinal surface faces medially.

In view of these potentially lifethreatening hazards 027 infection cheap revectina 3 mg on-line, Dick [7] and emergency medical specialists recommend use of the jaw thrust airway manoeuvre antibiotics vs antibacterial order discount revectina line, which hyperextends the neck by using the hands on the jaws and is incapable of causing airway occlusion or vagal stimulation infection zit buy revectina australia. Various types of neck hold have been used by police during attempted subdual virus like ebola buy discount revectina on line, but most have fallen into desuetude because of the associated risks (Table 32 antibiotic resistance prevention order cheap revectina line. Because the risk of injury or death from the carotid sleeper is deemed by police to be less than the application of fists and batons, this form of restraint is considered appropriate for younger people. It requires 7734 kgf/m 2 of pressure to occlude the carotid arteries; if both are firmly compressed by a neck hold, loss of consciousness ensues in 10­15 seconds; 3094 kgf/m 2 of pressure occlude the jugular veins, effectively compromising outflow of blood from the brain and face [6]. The theory of carotid sinus stimulation inducing bradycardia and asystole to date has rested on a matter of exclusion [15,16], as there is no anatomical expression at autopsy to support this pathophysiology, and there are no reports of death [30]. Virtual absence of death related to carotid sinus syndrome ­ even in the more susceptible elderly ­ strongly militates against this mechanism in the younger population [19]. On a form of disease resembling some advanced stages of mania and fever, but so contradistinguished from any ordinary observed or described combination of symptoms, as to render it probable that it may be an overlooked and hitherto unrecorded malady. Frequency of signs of excited delirium syndrome in subjects undergoing police use of force: Descriptive evaluation of a prospective, consecutive cohort. Fatal excited delirium following cocaine use: Epidemiologic findings provide new evidence for mechanisms of cocaine toxicity. Cocaine-associated rhabdomyolysis and excited delirium: Different stages of the same syndrome. Factors associated with sudden death of individuals requiring restraint for excited delirium. Ventilatory and metabolic demands during aggressive physical restraint in healthy adults. Optimizing prone cardiopulmonary resuscitation identifying the vertebral level correlating with the largest left ventricle cross-sectional area via computed tomography scan. On the weight force used in chest compression in the prone position (Letter to editor). The effect of the prone maximal restraint position with and without weight force on cardiac output and other hemodynamic measures. The forensic pathologist has mainly to rely on the findings of the death scene investigation in conjunction with the external and internal findings of the body. In most cases the original scene has already been altered by the caretakers or other persons who recovered the child, thus demanding a careful reconstruction. It must be taken into consideration that a reconstruction can be stressful and traumatizing for the caretakers and therefore must be undertaken with empathy and thoughtfulness. External findings on the body may be subtle but are nonetheless of great importance. Petechial haemorrhages, abrasions, bruises, skin reddening (sometimes patterned) and distribution of postmortem lividity can guide the forensic pathologist to the reconstruction of the posture and to the cause of the asphyxia. Petechiae make it possible not only to deduce venous congestion but, by their topographic distribution, also to reconstruct the level in which the congestion occurred. However, like most findings in asphyxiation cases, facial petechiae are not specific for asphyxiation as such. They occur in different circumstances, some of which are not associated with accidents or violence Since mechanisms involved in suffocation do not necessarily lead to venous congestion, the absence of petechiae does not exclude asphyxiation. Autopsy findings in cases of asphyxiation depend largely on the underlying mechanism. Internal findings such as petechial haemorrhages of the serous layers, fluid blood, dilation of the right heart, cyanosis and congestion are also non-specific [6] and therefore must be evaluated taking into account the external findings and circumstantial evidence. Especially in cases of sudden and unexpected deaths of infants, the clear-cut differentiation between natural and non-natural death poses great difficulties for medicolegal experts. In contrast to older children, who often display the same physical signs of violent asphyxiation as adults One of the reasons is that it does not take a great physical effort to effectively close the breathing orifices of an infant, thus leading to no or minor external and internal injuries. Asphyxiation In principal, those mechanisms leading to asphyxiation in infants and children are the same as in adults. Causes of asphyxiation include obstruction of arterial blood supply to the brain Besides those mechanically influenced causes, sometimes referred to as external asphyxiation (although the nomenclature is not unambiguous, see Chapter 21), there are non-mechanical or internal causes, which occur in the young Even though there are no fundamental pathophysiological differences between the various forms of asphyxiation between children and adults, children are more prone to the risk of asphyxiation due to their relative physical weakness and the underdeveloped competence in recognizing potential hazards and acting properly. By detecting injury patterns, reconstructing individual accidents, and identifying previously unrecognized dangers, the forensic pathologist can be an important player in preventive medicine [4,13]. In England and Wales in a 2-yearperiod, 136 children died of mechanical asphyxia, 65 per cent of whom were under 3 years of age [23]. In an Australian study the annual rate of accidental asphyxiation in children under the age of 15 due to upper airway interference such as facial occlusion, head and neck entrapment, rope or cord strangulation or foreign body aspiration was 0. The most frequent cause of death in this study was strangulation due to ropes and cords. However, there have been other proposals on how to implement asphyxiation in the classification of sudden unexpected deaths in infancy [26]. A baby cannot oppose the perpetrator and therefore defensive injuries are frequently absent. Finally, even macroscopic and microscopic autopsy findings are often of minor value due to their limited specificity. Inevitably, these diagnostic challenges lead to a certain dark field of unrecognized infanticides, even if all sudden deaths in infancy undergo a meticulous autopsy (which is not the case in many jurisdictions). There are also fatalities of small children that are clearly attributable to accidental strangulation or positional asphyxia, sometimes raising the question of legal responsibility and consumer safety when transportation devices or restraint systems are involved. Obviously, any babies in potentially hazardous sleeping conditions remain at risk despite the success of prevention campaigns. The surroundings in which the infant is recovered often suggests a mechanical asphyxia. In these cases, it is not always possible to reconstruct the original situation accurately, because the original scene has often been changed by the person recovering the baby. Often it remains unclear whether the mouth and nose were covered or closed by the body of a co-sleeping person, bed clothing or the back rest of the sofa. Arrangement and blanching of postmortem lividity can be helpful in cases with a postmortem interval of at least several hours before discovery of the dead baby, thus leaving enough time for the lividity to be fixed in adjacent body parts. Some sudden infant deaths in maternity wards might be explained by mechanisms leading to oppression of the tender newborn resulting in insufficient ventilation of the lungs [15]. However, dangerous sleeping situations also occur in older infants and apart from bed-sharing situations. Inflicted asphyxiation under soft covering Inflicted asphyxia of an infant by closing the nose and mouth is often hard to diagnose or even undetectable by the external examination as well as by the autopsy. That is why subcutaneous haematomas, scratches or abrasions in the perioral region, in the mouth or at the nose are often absent. Facial or conjunctival petechiae are not a common feature, because closing of the mouth and nose results in an obstruction of the air flow but not of the venous return of blood. In histology the lungs may present with hyperinflated areas, tears of the alveolar septae and haemorrhages. These findings are also not specific for inflicted asphyxia and might also occur in accidental closure of the airways or as a sequel of mechanical ventilation in resuscitation attempts. Case 1 A 9-month-old male infant was found dead after sleeping alone in a double bed in prone position. Obviously, the boy was not capable of disengaging himself from a situation in which, on the one Case 2 A 9-week-old baby boy allegedly was found dead by his mother in the morning hours in a supine position. Histologically, minor intra-alveolar haemorrhages were present but no haemosiderin was found. A couple of days after the autopsy the mother confessed to friends and relatives to having actively smothered her son by closing his mouth and nose with a blanket. In court she withdrew her confession and attributed it to the exceptional psychological state that she was in after she had found her baby dead. Case 4 A 16-month-old boy played around in a café while his mother had a cup of tea and chatted with a friend. Reconstruction of the events with a 12-month-old boy of similar stature (height 82 cm) in a flexible box with the dimensions of the toy box showed that a toddler can climb in the box on his own. Positional asphyxia due to a hindered venous return from the head was the most likely diagnosis. Case 3 A 6-year old boy allegedly was found lifeless by his parents in the top of a pram in the early morning hours without any previous illness. In addition, haematomas at the mandible, behind the right auricle and in the right palm were obvious. At autopsy, 18 bone fractures of different ages, thymic involution, alveolar haemorrhages and a healing brain contusion of the right parietal lobe were the main findings. The facial subcutaneous tissue showed discrete haemorrhages underneath the abrasions. Confronted with these findings, the father confessed to having smothered his son by closing his mouth and nostrils using his hands. Case 5 An 8-month-old boy fell asleep after lunch in a pushchair without the safety belts fastened. Two hours later, he was found unresponsive and hanging out of the pushchair with his chin held in position by the bumper bar. At autopsy, no specific signs of asphyxiation such as petechial bleedings or marks on the neck were present. Positional asphyxia and wedging Mobile infants, toddlers as well as older children are at risk of manoeuvring their bodies into positions which might result in impaired breathing, restriction of the venous return of blood from the head or narrowing of the respiratory passages. Petechial haemorrhages in the face but also in the region of the pectoral girdle are a common feature. For the medicolegal reconstruction of the accident, the distribution and the pattern of postmortem lividity and pressure marks play an important role. Apparently, he had tried to free himself and finally got trapped in this situation. Nine sheets of plasterboard, measuring 125 cm in height and each weighing 10 kg, had been stored in the basement, leaning upright on the wall of a narrow corridor. The whole pile fell from the wall towards the opposite wall, where it got caught on the neck of the boy just underneath the chin. Suffocation/Asphyxiation in Childhood 321 Foreign body aspiration and suction-type suffocation Infants and small toddlers are at high risk of aspirating any kinds of object that are small enough to fit into larynx and trachea [12,14]. Small, rounded food such as peanuts, raisins and pills, as well as small parts of toys, can be dangerous objects if they fit into the airways of the child. In the absence of the aspirated object, it can be very difficult to establish the diagnosis at autopsy. Furthermore, some household devices can also lead to the accidental closure of mouth and nostrils. He was taken to a nearby hospital in which intubation and tracheotomy efforts were unsuccessful due to a rigid resistance in the airway. The boy showed an intensive upper venous congestion and haematoma of the anterior part of the neck. At autopsy the epiglottis was found moderately swollen and compromised by the rather large palatine tonsils. Self-strangulation Apart from a large proportion of homicidal cases [30], strangulation in infants and children can occur accidentally as well as by suicide. One might assume that suicides are more frequent in older children and adolescents. However, there might be a grey zone of cases that might be either suicides or accidents due to autoerotic behaviour. An Austrian study found 171 cases of self-hanging in adolescents aged 14 years or younger (with the vast majority older than 9 years), of which 88 per cent were boys [10]. The Case 8 the parents assumed that their 18-month-old, previously healthy son had choked on a pretzel stick. In accidental cases, even strangulation of infants by human hair while co-sleeping with the mother are reported [21]. Children on playgrounds are at risk of being strangulated by drawstrings on clothing [25]. To avoid such accidents of self-strangulation it is recommended that clothing of infants and toddlers is not too wide and has no ribbons or drawstrings, and that small children do not wear any chains or toys attached to cords or dummy ribbons round their neck. String-like articles should be kept out of the reach of unsupervised playing or sleeping children. Children should always sleep in undamaged cots with appropriately normed distances between bars and/or grids. Infants and small children should not be left unattended in baby swings or baby buggies and it should always be ensured that the tethering straps are short and firmly applied and that there is no one-sided fastening. Suffocation/Asphyxiation in Childhood 323 Case 9 A 13-year-old boy was found dead by his mother in a store room. His body was suspended in an upward position from a hook on the door with his feet in contact with the ground. Only a few petechial bleedings in the conjunctive and haemorrhages at the origins of the sternocleidomastoid muscles as well as in the frontal parts of the intervertebral discs were present as a sign of vital hanging. It could not be clarified fully whether the boy died from suicidal hanging or from an autoerotic accident. Non-intentional asphyxiation deaths due to upper airway interference in children 0 to 14 years. Unnatural causes of sudden deaths initially thought to be sudden infant death syndrome. Intra-alveolar pulmonary siderophages in sudden infant death: A marker for previous imposed suffocation. Unintentional suffocation by rebreathing in a one-year study of infant deaths in St. Sudden infant death syndrome and unclassified sudden infant deaths: A definitional and diagnostic approach. Sequential arousal and airway defensive behavior of infants in asphyxial sleep environments.

In the 1950s antibiotics for sinus infection and strep throat revectina 12 mg order fast delivery, William Masters and Virginia Johnson daringly launched the first physiological studies of sexual response in the laboratory vanquish 100 antimicrobial revectina 3 mg overnight delivery. In 1966 antibiotic resistance what can be done purchase 12 mg revectina mastercard, they published Human Sexual Response infection nursing diagnosis revectina 3 mg fast delivery, which detailed measurements and observations on more than 10 don't use antibiotics for acne cheap revectina on line,000 sexual acts by nearly 700 volunteer men and women. Masters and Johnson then turned their attention to disorders of sexual function and pioneered modern therapy for sexual dysfunctions. The following discussion is organized around this model, although other authorities have modified it or proposed alternatives. Each internal iliac artery gives rise to an internal pudendal (penile) artery, which enters the root of the penis and divides in two. One branch, the dorsal artery, travels dorsally along the penis not far beneath the skin (see fig. The other branch, the deep artery, travels through the core of the corpus cavernosum and gives off smaller helicine33 arteries, which penetrate the trabeculae and empty into the cavernous spaces. When the penis is flaccid, most of its blood supply comes from the dorsal arteries. When the deep artery dilates, the cavernous spaces fill with blood and the penis becomes erect. There are numerous anastomoses between the dorsal and deep arteries, so neither of them is the exclusive source of blood to any one erectile tissue. It runs between the two dorsal arteries beneath the deep fascia and empties into a plexus of prostatic veins. The glans and foreskin have an abundance of tactile, pressure, and temperature receptors, especially on the frenulum and proximal margin of the glans. The receptors lead by way of a pair of prominent dorsal nerves to the internal pudendal nerves, then via the sacral plexus to segments S2 to S4 of the spinal cord. Sensory fibers of the shaft, scrotum, perineum, and elsewhere are also highly important to sexual stimulation. Both autonomic and somatic motor fibers carry impulses from integrating centers in the spinal cord to the penis and other pelvic organs. Sympathetic fibers arise from levels T12 to L2, pass through the hypogastric and pelvic plexuses, and innervate the penile arteries, trabecular muscle, spermatic ducts, and accessory glands. They dilate the penile arteries and can induce erection even when the sacral region of the spinal cord is damaged. They also initiate erection in response to input to the special senses and to sexual thoughts. Parasympathetic fibers extend from segments S2 to S4 of the spinal cord through the pudendal nerves to the arteries of the penis. They are involved in an autonomic reflex arc that causes erection in response to direct stimulation of the penis and perineal region. Conversely, emotions can inhibit sexual response and make it difficult to function when a person is anxious, stressed, or preoccupied with other thoughts. The most obvious manifestation of male sexual arousal is erection of the penis, which makes entry of the vagina possible. Erection is an autonomic reflex mediated predominantly by parasympathetic nerve fibers that travel alongside the deep and helicine arteries of the penis. Whether this is enough to cause erection, or whether it is also necessary to block the outflow of blood from the penis, is still debated. According to one hypothesis, as cavernous spaces near the deep arteries fill with blood, they compress the spaces closer to the periphery of the erectile tissue. This is where blood leaves the erectile tissues, so the compression of the peripheral spaces helps retain blood in the penis. Their compression is aided by the fact that each corpus cavernosum is wrapped in a tunica albuginea, which fits over the erectile tissue like a tight fibrous sleeve and contributes to its tension and firmness. In addition, the bulbospongiosus and ischiocavernosus muscles aid in erection by compressing the root of the penis and forcing blood forward into the shaft. As the corpora cavernosa expand, the penis becomes enlarged, rigid, and elevated to an angle conducive to entry of the vagina. Once intromission (entry) is achieved, the tactile and pressure sensations produced by vaginal massaging of the penis further accentuate the erection reflex. In the plateau phase, variables such as respiratory rate, heart rate, and blood pressure are sustained at a high level, or rise slightly, for a few seconds to a few minutes before orgasm. The excitement phase can be initiated by a broad spectrum of erotic stimuli-sights, sounds, aromas, touch-and even 27. From the standpoint of producing offspring, the most significant aspect of male orgasm is the ejaculation35 of semen into the vagina. The basis for developing them was a seemingly unrelated discovery: the role of nitric oxide in cell signaling. In emission, the sympathetic nervous system stimulates peristalsis in the smooth muscle of the ductus deferens, which propels sperm from the tail of the epididymis, along the ductus, and into the ampulla. Contractions of the ampulla propel the sperm into the prostatic urethra, and contractions of smooth muscle in the prostate force prostatic fluid into the urethra. Secretions of the seminal vesicles join the semen soon after the prostatic secretion. The contractions and seminal flow of this phase create an urgent sensation that ejaculation is inevitable. Semen in the urethra activates somatic and sympathetic reflexes that result in its expulsion. Sensory signals travel to the spinal cord via the internal pudendal nerve and reach an integrating center in the upper lumbar region. Sympathetic nerve fibers carry motor signals from here out to the prostate and seminal vesicles, causing the smooth muscle in their walls to express more fluid into the urethra. Somatic motor signals leave the third and fourth sacral segments of the cord and travel to the bulbospongiosus, ischiocavernosus, and levator ani muscles. Most sperm are ejected in the first milliliter of semen, mixed primarily with prostatic fluid. The seminal vesicle secretion follows and flushes most remaining sperm from the ejaculatory ducts and urethra. Some sperm may seep from the penis prior to ejaculation, and pregnancy can therefore result from genital contact even without orgasm. Although they usually occur together, it is possible to have all of the sensations of orgasm without ejaculating, and ejaculation occasionally occurs with little or no sensation of orgasm. Discharge of the sympathetic nervous system constricts the internal pudendal artery and reduces the flow of blood into the penis. It also causes contraction of the trabecular muscles, which squeeze blood from the erectile tissues. The resolution phase is also a time in which cardiovascular and respiratory functions return to normal. In men, resolution is followed by a refractory period, lasting anywhere from 10 minutes to a few hours, in which it is usually impossible to attain another erection and orgasm. Men and women have many similarities and a few significant differences in sexual response. Reproductive disorders specific to males and females are briefly summarized in table 27. Often quite advanced by the time of diagnosis, with poor prospects for recovery, because of denial and delay in seeking treatment. Can stem from aging and declining testosterone level as well as cardiovascular and neurological diseases, diabetes mellitus, medications, fear of failure, depression, and other causes. A congenital defect in which the urethra opens on the ventral side or base of the penis rather than at the tip; usually corrected surgically at about 1 year of age. Inability to fertilize an egg because of a low sperm count (lower than 20 to 25 million/mL), poor sperm motility, or a high percentage of deformed sperm (two heads, defective tails, etc. May result from malnutrition, gonorrhea and other infections, toxins, or testosterone or zinc deficiency. Accounts for 1% of male cancers in the United States; most common in black males ages 50 to 70 and of low income. Most often seen in men with nonretractable foreskins (phimosis) combined with poor penile hygiene; least common in men circumcised at birth. The most common solid tumor in men 15 to 34 years old, especially white males of middle to upper economic classes. Abnormal dilation of veins of the spermatic cord, so that they resemble a "bag of worms. Explain how penile blood circulation changes during sexual arousal and why the penis becomes enlarged and stiffened. State the roles of the sympathetic, parasympathetic, and somatic nervous systems in male sexual response. Galen, thinking the pus discharged from the penis was semen, named the disease gonorrhea ("flow of seed"). Gonorrhea causes abdominal discomfort, genital pain and discharge, painful urination, and abnormal uterine bleeding, but most infected women are asymptomatic. Most chlamydia infections are asymptomatic, but they may cause urethral discharge and pain in the testes or pelvic region. It can result in sterility and may require surgical removal of infected uterine tubes or other organs. It disappears in 4 to 6 weeks, ending the first stage of syphilis and often creating an illusion of recovery. A second stage ensues, however, with a widespread pink rash, other skin eruptions, fever, joint pain, and hair loss. The disease may progress to a third stage, tertiary syphilis (neurosyphilis), with cardiovascular damage and brain lesions that can cause paralysis and dementia. After an incubation period of 4 to 10 days, the virus causes blisters on the penis of the male; on the labia, vagina, or cervix of the female; and sometimes on the thighs and buttocks of either sex. The initial infection may be painless or may cause intense pain, urethritis, and watery discharge from the penis or vagina. Here it can lie dormant for years, later migrating along the nerves and causing epithelial lesions anywhere on the body. An infected person is contagious to a sexual partner when the lesions are present and sometimes even when they are not. In the male, warts usually appear on the penis, perineum, or anus; and in the female, they are usually on the cervix, vaginal wall, perineum, or anus. Genital warts can be treated with cryosurgery (freezing and excision), laser surgery, or interferon. Food and Drug Administration recommends vaccination of girls and boys at the age of puberty in hopes of immunizing most before the onset of sexual activity. The arterial supply and venous drainage of the testis; testicular nerves and lymphatic vessels 6. Gross anatomy of the epididymis; the series of spermatic ducts from the efferent ductules to the ejaculatory duct; and differences in their anatomy and relationships to adjacent organs 7. Three sets of male accessory glands; their anatomy, functions, and relationships to adjacent organs 8. The root, shaft, and glans of the penis; the prepuce and frenulum distally; the bulb and the crura proximally 9. Essential characteristics of sexual reproduction; what defines male and female in any sexual species; and the names and defining characteristics of their respective gametes and gonads 2. Which organs of each sex are considered to be primary and secondary sex organs; which are considered to be internal and external genitalia; and how secondary sex characteristics differ from secondary sex organs 4. The difference between sex chromosomes and autosomes; the number of each; names of the sex chromosomes; and how males and females differ chromosomally 5. The male-determining gene on the Y chromosome; the name of the protein encoded by it; and the effect of that protein on embryonic development 6. Structures of the embryonic genital tubercle, urogenital folds, and labioscrotal folds; and mature structures of the male and female that arise from each 8. Descent of the gonads; similarities and differences in this process in the male and female fetus; and consequences for the male if it fails to occur to completion 4. Bodily changes of male adolescence, onset of the libido, and their respective hormonal causes 4. Blood vessels of the penis and how they function in the flaccid penis and in erection 2. The nerve supply of the penis and its relationship to the sacral plexus and spinal cord; three types of nerve fibers that the penis receives 3. Physiological changes that the male undergoes during the excitement phase of the sexual response 4. The mechanism of erection including the roles of parasympathetic stimulation, nitric oxide, and vasodilation; why the corpora cavernosa become more engorged than the corpus spongiosum 5. Characteristics of the male resolution phase; the mechanism of penile detumescence; and the refractory period 27. Why the testes must be kept cooler than the core body temperature, and three mechanisms for achieving this 3. Anatomy of the testis and functions of its seminiferous tubules and interstitial endocrine cells 4. The germinal epithelium of the seminiferous tubule; its cell types and their functions; the necessity and structure of the blood­testis barrier 27. The meaning of spermatogenesis and distinction between spermatogenesis and spermiogenesis 2. Why meiosis is necessary in sexually reproducing species, how it affects the chromosome number of gametes, and why chromosome number remains constant from one generation to the next 3. When it is necessary to reduce sperm production without reducing testosterone secretion, the nurse cells secrete a. Under the influence of androgens, the embryonic duct develops into the male reproductive tract. The, a network of veins in the spermatic cord, helps keep the testes cooler than the core body temperature.

The sympathetic nervous system loses adrenergic receptors with age and becomes less sensitive to norepinephrine antimicrobial list generic 12 mg revectina mastercard. This contributes to a decline in homeostatic control of such variables as body temperature and blood pressure virus free games cheap revectina 12 mg buy. Many elderly people experience orthostatic hypotension-a drop in blood pressure when they stand bacteria classification 12 mg revectina purchase, which sometimes results in dizziness virus evolution buy revectina 3 mg cheap, loss of balance virus facts revectina 6 mg order with visa, or fainting. Impaired balance and neuromuscular reflexes, slow baroreflexes, and fragile bones often combine tragically in a fall that breaks a hip and leads to death from pneumonia and other complications of immobility. Nerve deafness occurs as the number of cochlear hair cells and auditory nerve fibers declines. The greatest hearing loss occurs at high frequencies and in the frequency range of most conversation. The death of receptor cells in the semicircular ducts, utricle, and saccule, and of nerve fibers in the vestibular nerve and neurons in the cerebellum, results in dizziness and impaired balance-another factor in falls and bone fractures. The senses of taste and smell are blunted as the taste buds, olfactory cells, and second-order neurons in the olfactory bulbs decline in number. Food may lose its appeal, and declining sensory function can therefore be a factor in malnutrition. Endocrine System the endocrine system degenerates less than any other organ system. The reproductive hormones drop sharply and growth hormone and thyroid hormone levels decline steadily after adolescence. The pineal gland becomes increasingly calcified in old age and its melatonin output falls. Since melatonin is a sleep-inducing hormone, this may be a reason for the insomnia often experienced by the elderly. For example, the pituitary gland is less sensitive to negative feedback inhibition by adrenal glucocorticoids; consequently, the response to stress is more prolonged than usual. Diabetes mellitus is more common in old age, largely because target cells have fewer insulin receptors. Because of the blunted insulin response, glucose levels remain elevated longer than normal after a meal. Presbyopia (loss of flexibility in the lenses) makes it more difficult for the eyes to focus on nearby objects. Night vision is impaired as more and more light is needed to stimulate the retina. This has several causes: There are fewer receptor cells in the retina, the lens and vitreous body becomes less transparent, and the pupil becomes narrower as the pupillary dilators atrophy. Even without cataracts, the retina receives only one-third as much light at age 60 as it does at age 20. Dark adaptation takes longer as the enzymatic reactions of the photoreceptor cells become slower. Changes in the structure of the iris, ciliary body, or lens can block the reabsorption of aqueous humor, thereby increasing the risk of glaucoma. Having to give up reading and driving can be among the most difficult changes of lifestyle in old age. The tympanic membrane and the joints between the auditory ossicles become stiffer, so vibrations are transferred less effectively Circulatory System Cardiovascular disease is a leading cause of death in old age. Anemia may result from nutritional deficiencies, inadequate exercise, disease, and other causes. Evidence suggests that there is no change in the baseline rate of erythropoiesis in old age. Hemoglobin concentration, cell counts, and other variables are about the same among healthy people in their 70s as in the 30s. As the gastric mucosa atrophies, for example, it produces less of the intrinsic factor needed for vitamin B12 absorption. As the kidneys age and the number of nephrons declines, less erythropoietin is secreted. There may also be a limit to how many times the hematopoietic stem cells can divide and continue giving rise to new blood cells. Whatever its cause, anemia limits the amount of oxygen that can be transported and thus contributes to the atrophy of tissues everywhere in the body. Nearly everyone is affected to some degree in old age by arteriosclerosis and atherosclerosis (see the distinction in section 20. Coronary atherosclerosis leads to the degeneration of myocardial tissue; angina pectoris and myocardial infarction become more common; the heart wall becomes thinner and weaker; and stroke volume, cardiac output, and cardiac reserve decline. Like other connective tissues, the fibrous skeleton of the heart becomes less elastic. Arteries stiffened by arteriosclerosis cannot expand as effectively to accommodate the pressure surges of cardiac systole. Blood pressure therefore rises steadily with age, although it is uncertain to what extent this is an inherent biological effect of aging versus an effect of culture and lifestyle. Atherosclerosis also narrows the arteries and reduces the perfusion of most organs. The effects of reduced circulation on the skin, skeletal muscles, and brain have already been noted. The combination of atherosclerosis and hypertension weakens the arteries and increases the risk of aneurysm and stroke. Atherosclerotic plaques trigger thrombosis, especially in the lower limbs, where flow is relatively slow and the blood clots more easily. Blood pools in the legs and feet, raises capillary blood pressure, and causes edema. Support hose can reduce edema by compressing the tissues and forcing tissue fluid to return to the bloodstream, but physical activity is even more important in promoting venous return. The elderly are also less capable of clearing the lungs of irritants and pathogens and are therefore increasingly vulnerable to respiratory infections. Pneumonia causes more deaths than any other infectious disease and is often contracted in hospitals and nursing homes. They are among the leading causes of death in old age, but are avoidable; they are much less common among nonsmokers than among smokers. Pulmonary obstruction also contributes to cardiovascular disease, hypoxemia, and hypoxic degeneration in all the organ systems. From ages 25 to 85, the number of nephrons declines 30% to 40% and up to a third of the remaining glomeruli become atherosclerotic, bloodless, and nonfunctional. The kidneys of a 90-year-old are 20% to 40% smaller than those of a 30-year-old and receive only half as much blood. The glomerular filtration rate is proportionately lower and the kidneys are less efficient at clearing wastes from the blood. Although baseline renal function is adequate even in old age, there is little reserve capacity; thus, other diseases can lead to surprisingly rapid renal failure. Water balance is more precarious in old age because the kidneys are less responsive to antidiuretic hormone and because the sense of thirst is sharply reduced. The enlarged prostate compresses the urethra and interferes with emptying of the bladder. Urine retention may cause pressure to back up in the kidneys, aggravating the failure of the nephrons. Older women are subject to incontinence (leakage of urine), especially if their history of pregnancy and childbearing has weakened the pelvic muscles and urethral sphincter. Senescence of the sympathetic nervous system and nervous disorders such as stroke and Alzheimer disease can also cause incontinence. Also, the lymphocytes produced in these tissues often fail to mature and become immunocompetent. As a result, an older person is less protected against cancer and infectious diseases. It becomes especially important in old age to be vaccinated against influenza and other acute seasonal infections. Older people have lower metabolic rates and tend to be less active than younger people and, hence, need fewer calories. The stomach Respiratory System Pulmonary ventilation declines steadily after the 20s and is one of several factors in the gradual loss of stamina. For many, food has less esthetic appeal in old age because of losses in the senses of smell, taste, and even vision. In addition, older people secrete less saliva, making food less flavorful and swallowing more difficult. Dentures are an unpleasant fact of life for many people over 65 who have lost their teeth to caries and periodontitis. Atrophy of the epithelium of the oral cavity and esophagus makes these surfaces more subject to abrasion and may further detract from the ease of chewing and swallowing. Even the ability to chew declines; the muscles of mastication lose about 40% of their mass and the mandibular bone loses about 20% over the course of a lifetime. Malnutrition is common among older people and is an important factor in anemia and reduced immunity. Heartburn becomes more common as the weakening lower esophageal sphincter fails to prevent the reflux of stomach contents into the esophagus. The most common digestive complaint of older people is constipation, which results from reduced muscle tone and weaker peristalsis of the colon. This seems to stem from a combination of factors: atrophy of the muscularis externa, reduced sensitivity to neurotransmitters that promote motility, less fiber and water in the diet, and less exercise. The liver, gallbladder, and pancreas show only slightly reduced function, but the drop in liver function reduces the rate of drug deactivation and can contribute to overmedication. Reproductive System In men, the senescent changes in the reproductive system are relatively gradual; they include declining testosterone secretion, sperm count, semen volume, and libido. Men remain fertile (capable of fathering a child) well into old age, but impotence (inability to maintain an erection) can occur because of atherosclerosis, hypertension, medication, and psychological reasons. Over the course of menopause, the ovarian follicles are used up, gametogenesis ceases, and the ovaries stop producing sex steroids. This may result in vaginal dryness, genital atrophy, and reduced libido and may make sex less enjoyable. With the loss of ovarian steroids, a postmenopausal woman has an elevated risk of osteoporosis and atherosclerosis. People who exercise moderately for as little as 10 to 15 minutes a day have been found to live, on average, 3 years longer than sedentary people, although it is difficult to separate causation from correlation in such studies. That is, it remains unclear how much of this is an effect of the exercise and how much results from correlation with other healthy lifestyle choices. There is no question, however, that regular exercise maintains endurance, strength, and joint mobility, and reduces the incidence and severity of hypertension, osteoporosis, obesity, and diabetes mellitus. This is especially true if you begin a program of regular physical exercise early in life and make a lasting habit of it. If you stop exercising regularly after middle age, the body rapidly becomes deconditioned, although appreciable reconditioning can be achieved even when an exercise program is begun late in life. A person in his or her 90s can increase muscle strength two- or threefold in 6 months with as little as 40 minutes of isometric exercise a week. The improvement results from a combination of muscle hypertrophy and neural efficiency. Resistance exercises may be the most effective way of reducing accidental injuries such as bone fractures, whereas endurance exercises reduce body fat and increase cardiac output and maximum oxygen uptake. A general guideline for ideal endurance training is to have three to five periods of aerobic exercise per week, each 20 to 60 minutes long and vigorous enough to reach 60% to 90% of your maximum heart rate. An exercise program should ideally be preceded by a complete physical examination and stress test. Warm-up and cool-down periods are especially important in avoiding soft tissue injuries and undue cardiovascular stress. Because of their lower capacity for thermoregulation, older people must be careful not to overdo exercise, especially in hot weather. The question actually comes down to two issues: (1) What are the mechanisms that cause the organs to deteriorate with age Mechanisms of Senescence Numerous hypotheses have been proposed and discarded to explain why organ function degenerates with age. Some authorities maintain that senescence is an intrinsic process governed by inevitable or even preprogrammed changes in cellular function. Others attribute senescence to extrinsic (environmental) factors that progressively damage our cells over the course of a lifetime. After reaching their maximum number of divisions, cultured cells degenerate and die. Much of the evidence points to the telomere,21 a "cap" on each end of a chromosome analogous to the plastic tip of a shoelace. One of its functions may be to stabilize the chromosome and prevent it from unraveling or sticking to other chromosomes. In old age, the telomere may be exhausted and the polymerase may then indeed fail to replicate some of the terminal genes. Old chromosomes may therefore be more vulnerable to damage, replication errors, or both, causing old cells to be increasingly dysfunctional. The long life of stem cells and "immortality" of cancer cells results from an enzyme called telomerase, lacking from healthy differentiated cells. Telomerase enables cancerous and stem cells to repair telomere damage and escape the limit on number of cell divisions. One striking genetic defect called progeria20 is characterized by greatly accelerated senescence (fig. In Werner syndrome, caused by a defective gene on chromosome 8, people show marked senescence beginning in their 20s and usually die by age 50. There is some controversy over the relevance or similarity of these syndromes to normal senescence, but they do demonstrate that many of the changes associated with old age can be brought on by a genetic anomaly. Skeletal muscle fibers and brain neurons exhibit pronounced senescence, yet these cells are nonmitotic.

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