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Albinism, phenylketonuria, and cystic ibrosis are described here as representative examples. After the impulse is generated in the Purkinje or nodal cell, it can be conducted backward to the atria (retrograde P wave). Calcium ions are actively pumped in to the mitochondria using the energy of the proton (H+) gradient. Septic shock is characterized by immunemediated mechanisms of cellular injury and organ dysfunction. More often, an embolism leaving the right ventricle lodges in the pulmonary vasculature. In the absence of cellular oxygen, the citric acid cycle is inhibited and pyruvate accumulates in the cytoplasm. The capacitation process occurs over a period of 1 to 10 hours and occurs in sperm only after they have been introduced in to the vagina of the female. Cells of the liver, pancreas, endocrine glands, and renal tubules are also able to regenerate when necessary. Oxygen binds when there is a high afinity of hemoglobin for oxygen (at the lungs) and releases when the afinity is decreased at the tissue level to maintain adequate metabolic processes. Cells of the renal tubules reabsorb the excess iltered glucose and store it intracellularly as glycogen. Bacteria that incorporate the desired gene are identiied by hybridization with a labeled probe. Postoperative pneumatic leg compression also reduces the risk of thrombus formation. Beginning in the early 1970s researchers started to examine gender differences related to stress and recent research has continued to expand what is known about these differences between men and women. Ion channels are responsible for the development of membrane potentials and are of vital importance in nerve and muscle function, as discussed in the next section. Collagen is composed of tough, nonelastic bundles of protein ibers that are secreted by ibroblasts. It is important to remember that the pH measured clinically is that of the blood and may not relect the pH inside cells or in cerebrospinal luid. Biofeedback, visualization, and meditation are examples of therapies that use this principle. Heart rate and diastolic and systolic blood pressures are more affected by gravitational effects of position change than is normally expected. The particular structure of the protein channel ensures that only ions of a certain size and charge can move through the membrane. Damaged Clinical Presentation of Acute Tubular Necrosis Prerenal kidney injury can be reversed if treated before perfusion drops to below 20% of normal and ischemia occurs. The primary transporter responsible for this process is the Na+-K+ pump in the basolateral cell membrane. When present in blood and bone marrow, lymphoid neoplasms are called leukemias, and when they are localized in lymphoid tissues they are called lymphomas. Some membrane proteins are involved in the transport of speciic molecules in to and out of the cell; others function as enzymes or respond to external signals; and some serve as structural links that connect the plasma membrane to adjacent cells. What is needed instead is some notion of positive health or physical "wholeness" that extends beyond the absence of ill health. Thereafter it is important to continue the treatment for 4 to 6 months to build iron stores. Neutrophils have a limited capacity to phagocytose foreign and inlammatory debris. The Digitalis Investigation Group: the effect of digoxin on mortality and morbidity in patients with heart failure. The atherosclerotic process described previously with coronary artery disease (Chapter 15) is likely to be the basis for the damage to the microcirculation of the kidneys that develops with chronic hypertension.

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Treatment Avoid soap and detergents, use bath oils, apply regular urea-containing emollients, or mild keratolytics. It is dificult to achieve these goals because interventions to increase cardiac output tend to increase myocardial oxygen demands. At this point an urgent sensation to void Physiology of Micturition Micturition is often taken for granted by health care providers and patients, but is a complicated process. Movement of ions across the sarcolemma is an essential part of cellular excitation and the subsequent contraction of intracellular elements. In Scotland, all children and adolescents may consent to treatment irrespective of age, so long as they are deemed competent to do so. They may arise from simultaneous dysfunction of the respiratory system and kidneys. Cell lysis may be mediated by activated complement fragments (membrane attack complex) or by phagocytic cells that are attracted to target cells by the attached antibodies. At home, peak low monitoring is helpful to parents or patients in determining a treatment plan and when to seek medical assistance. He noticed that milkmaids who developed cowpox from working with cows did not develop smallpox disease. In patients with a urinary tract infection, drainage of urine with a urethral or occasionally a suprapubic catheter is necessary. The initial segment repolarizes as sodium channels close and potassium ions move out of the cell. Management of adolescents: key areas to consider Communication issues Appreciation of adolescent-relevant issues. If the extracellular K+ level is increased, more K+ ions will stay in the cell, owing to the reduced concentration gradient. Thus the relationship of the immune system to stress is quite multifaceted and our understanding of it is evolving. Thus, hypokalemia may coexist with a total body potassium deicit, a total body potassium excess, or a normal total body potassium ion concentration. Treatment goals for ureterocele include controlling infection, preserving urinary tract function, maintaining urinary continence, and removing obstruction. Allergic causes may be the result of drug reactions or the development of seborrheic dermatitis, psoriasis, or skin-colored papular eruptions. Management of posterior valves involves initial management of the metabolic abnormalities with appropriate luid management and electrolyte replacement. Urethral strictures are usually diagnosed by cystoscopy or retrograde urethrography, which would demonstrate a narrowing of the urethra. Symptoms of circulatory inadequacy, including fatigue, restlessness, anxiety, and weakness, may be present. Pathologic changes in the airway include chronic inlammation and swelling of the bronchial mucosa resulting in scarring, increased ibrosis of the mucous membrane, hyperplasia of bronchial mucous glands and goblet cells, hypertrophy of bronchial glands and goblet cells, and increased bronchial wall thickness, which potentiates obstruction to airlow. Gonococcal and nongonococcal urethritis and syphilis are effectively managed with antibiotics. The external intercostal muscles elevate the ribs for inspiration, whereas the internal intercostal muscles cannot lift the chest wall and do not help with inspiration. Several courses of chemotherapy are generally necessary to ensure that all tumor cells have been killed. Research likewise substantiates physical inactivity as a risk factor for cardiovascular disease. Infarcted myocardium is particularly weakened and susceptible to rupture at this time. Elevations in erythrocyte sedimentation rate and the level of C-reactive protein are often present. They usually disseminate in a stepwise manner, irst involving the retroperitoneal lymph nodes lying adjacent to the great vessels. The speciic agents tested in clinical trials included -carotene, vitamin E, vitamin C, selenium, retinol, zinc, ribolavin, and molybdenum.

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Immunocompromised individuals are prone to disseminated infections called bacteremia (the term septicemia is still in clinical use, but is discouraged because of imprecise meaning). Management of torsion involves an operation to open the scrotum, untwist the testis, and "pex" (secure) it to the scrotal wall. This may be accomplished by reductions in heart rate, preload, afterload, and contractility. If hypoxia continues and ischemia lasts more than a few hours, prerenal kidney injury will progress to acute tubular necrosis (intrinsic kidney injury). The purpuric lesions associated with inherited connective tissue disorders, such as Ehlers-Danlos syndrome, often are accompanied by large ecchymoses and hematomas. When the lymphatic circulation is altered, the resulting luid and pressure changes may be visible locally or systemically. Blood is propelled through the circuit, pushed by the force of left ventricular contraction, and moves forward toward the low-pressure side of the pump on the right side of the heart. However, other medications, such as anesthetics, alcohol, antibiotics, and steroids, also affect the immune response and can lead to secondary immunosuppression. Shock resulting from head trauma has a poor prognosis, whereas acute neurogenic shock associated with spinal cord injuries may resolve as spinal cord relexes return in the weeks following the injury. These innate pattern-recognition receptors bind to particular molecules prevalent in the bacterial cell wall. The treatment implications discussed in pathophysiology texts usually are general statements rather than speciic prescriptions. Some tissues, such as skin and bone marrow, maintain large numbers of stem cells, which have great capacity to proliferate. The development of hypercapnia is related to inadequate alveolar ventilation in relation to production of carbon dioxide. The descending limb receives iltrate from the proximal convoluted tubule and delivers it to the ascending limb. The Paco2 relects the respiratory component of an acid-base imbalance; the plasma bicarbonate concentration relects the metabolic (renal) component of an acid-base imbalance. The convoluted turbinates (cone-shaped bones) of the nasal cavity are highly vascular, and their blood low forms an eficient heat exchanger. Cancer is a complex, multifaceted disorder with each individual cancer having some unique properties. A more severe attack requiring medical assistance may be accompanied by the use of accessory muscles of respiration, intercostal retractions, distant breath sounds with inspiratory wheezing, orthopnea, agitation, tachypnea, and tachycardia. It is one of several enzyme deiciencies that are often referred to as inborn errors of metabolism. Cervical dysplasia has no symptoms, but the cell changes can lead to neoplasia (cancer). Circumscribed areas of the skin are absent, usually on scalp, which presents at birth with raw, red ulcer that heals with scarring and later absent hair growth. Severe congenital immunodeiciency disorders are less common, but clinically signiicant. Cellular Membrane Potentials Animal cells typically have a difference in the electrical charge across the plasma membrane. This characteristic allows new spermatozoa to be continuously produced across the male life span. Advanced ibrous plaque is thought to produce intermittent ischemia when 75% or more of the arterial lumen is occluded. Maintenance of weight in children with cystic ibrosis often requires an intake of 150% of the normal calories recommended for healthy children. Inheriting a defective Rb gene predisposes an individual to the development of cancer because only a single mutational event is required to inactivate pRb function. Hemophilia is rare in the general population, but it is the most common severe inherited coagulation disorder.

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According to the American Society for Apheresis, this type of therapy has been effective in the management of diseases such as myasthenia gravis, thrombocytopenia purpura, multiple sclerosis, and Rh-negative hemolytic disease of the newborn. Support for the theory of a genetically programmed life span comes primarily from studies of cells in culture. In contrast, acquired disorders of platelet function are common; they are often associated with drugs, especially aspirin; with renal failure; or with a coexisting hematologic disease, such as leukemia. Under normal circumstances, the adult bladder contains less than 50 to 100 ml following voiding. In young children with sickle cell anemia, there is a 30% incidence of splenic sequestration crisis with a 15% death rate. Those infants who are breast feeding will obtain secretory IgA, which does provide additional protection. The median age at presentation is about 55 years and there is a 5-to-1 predominance of males. The left ventricle contains numerous abscesses formed by seeding from vegetations traveling in the coronary arteries. Reabsorption is the process of transporting a substance from the iltrate in to the renal capillaries and requires several transport steps. Mechanism of Micturition the softness, pliability, mucosal secretions, and submucosal cushioning of the urethra are responsible for the maintenance of a water-tight seal or "compression" of the urethra. Common clinical features include wheezing attributable to bronchospasm, crackles, decreased breath sounds, retractions, increased sputum, dyspnea, tachypnea (rapid, shallow respirations), and low-grade fever. The cardiomyopathies are a diverse group of disorders that may be classiied as primary (having unknown cause) and speciic (caused by a known disease process). Coping is another term used and is most often seen as a behavioral adaptive response to a stressor. Stress and mental health have historically received considerable attention as risk factors for atherosclerosis, and this continues to be the case. Dendritic cells derive their name from an unusual shape that has extensive projections from the surface. B-cell responses to nonprotein antigens are T-cell independent because T cells respond only to peptide antigens. They are not cells but are circulating cytoplasmic fragments of megakaryocytes and are incapable of mitotic division. B cells migrate from the outer edges toward the center of the bone marrow as they develop. In this way the migratory cell can be guided along particular paths and induced to settle in particular areas. When the target hematocrit is achieved, adult patients can be maintained by administering 50 to 100 units per kilogram per week in divided doses. Most of the symptoms of Rh sensitization occur in the fetus, including signs of anemia, hypoxia, decreased fetal activity, ascites, congestive heart failure, and an elevated baseline heart rate of 180 beats/minute or greater with late decelerations. A characteristic murmur occurs during ventricular systole and varies in intensity, progressively getting louder and then diminishing (crescendo-decrescendo). Thrombin time measures the time needed to convert ibrinogen to ibrin; this relects the quantity and quality of ibrinogen as well as the inluence of any inhibitors. As diagnostic methods become more cost-effective, general screening for other risk factors may be undertaken. The approach described here is intended for routine use in a general paediatric setting. Those without complete response may consider stem cell transplantation to prolong the duration of remission. In the brain, the increased blood low and availability of glucose lead to increases in mental attention and alertness. Both categories of genes result in similar effects in enhancing cell proliferation and survival. Rapid spread of tissue damage and the release of toxins in to the bloodstream make wet gangrene a life-threatening problem. Generally, the natural history of the disease leads to recovery, with minor residual motor deicits occurring in 15% to 20% of patients. Cancer cells, however, do not obey the rules; they have escaped the normal mechanisms of growth control. Because humans exhibit considerable diversity, healthy structure and function are not precisely the same in any two individuals.

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Prerenal or postrenal kidney injury will ultimately progress to intrinsic kidney injury if not corrected within a few hours. Malignancies of the blood-forming tissues and lymphatic structures often present with nonspeciic symptoms. These lysosomes lack nearly all of the hydrolases normally present and thus are unable to perform lysosomal digestion. The presence of fever increases the metabolic rate, requiring more energy and micronutrients. Smooth muscle encircling the vessel relaxes in response to the presence of the chemicals, increasing vessel diameter. The growth and activity of B cells that recognize protein antigens are regulated by helper T cells. Autoregulation is effective when arterial blood pressure varies between 75 and 160 mm Hg. Low hemoglobin level and low hemoglobin saturation profoundly affect the O2 content in the blood. Pulmonary Stenosis or Atresia Isolated pulmonary stenosis and atresia are included in the category of acyanotic defects because they do not themselves result in cyanosis. The pulmonary arteries further divide in to smaller arteries and arterioles that feed in to the capillary network where gas exchange occurs from the alveolar-capillary membrane. Active male germinal cells continue to produce spermatozoa (spermatogenesis), although the number of sperm produced declines proportionally over time. A high concentration (partial pressure) of O2 in the pulmonary capillaries causes O2 to bind to the hemoglobin molecule. The basement membrane is an important selectivity barrier of the glomerulus, preventing plasma proteins, erythrocytes, leukocytes, and platelets from passing through. Urine is approximately 95% water and contains varying amounts of water-soluble waste products. Stages and Clinical Course Early in the development of a disease, the etiologic agent or agents may provoke a number of changes in biological processes that can be detected by laboratory analysis, although no recognition of these changes by the patient has occurred. Blood low through the left and right heart chambers is connected in series such that the output of one becomes the input of the other. Red Cell Destruction While the red cell ages, the various enzyme activities decrease, amounts of membrane lipids decrease, levels of hemoglobin A2 and methemoglobin increase, and changes in cell size occur. A, During inspiration, the respiratory muscles contract, the chest wall expands, and air lows in to the lungs. Columns of cortical tissue are found between the medullary pyramids and provide the passageway for the interlobar arteries. Urinary tract infections with certain bacterial species capable of splitting urea in to two ammonium ions and one bicarbonate ion neutralize the urine and support bacterial proliferation as well as stone formation. Phase 3: Rapid repolarization attributable to closure of calcium channels and increased potassium eflux. Unmanaged polycythemia vera has a poor prognosis, with a survival of less than 2 years. Immunosuppressive agents have been useful in reducing the dosage of corticosteroids required. Speciic recommendations regarding all aspects of indirect measurement are provided by the American Heart Association,6 and sources of error within pediatric populations also have been documented. The axis may shift left as a result of left ventricular muscle thickening (hypertrophy). Autocrine communication provides a feedback signal to the secreting cell and is commonly linked to pathways that regulate ligand secretion rates. Although these disorders develop from many speciic causes in different patient populations, these speciic causes fall in to general categories that arise from the principles of normal luid and electrolyte homeostasis. No classiication system is truly comprehensive and some diseases fall in to multiple categories.

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Based on such a recurrence risk, parents of one affected child have a 2% to 3% chance of bearing a second affected child. Identiication of the tissue of origin has important implications for prognosis and selection of treatment options. This is relected in how the classiications of oral medications used in the treatment of hypertension are listed in Box 16-1. Cardiac function curves can be measured in persons with poorly functioning hearts to determine the best illing volume (preload) for optimizing cardiac output. The tumor necrosis factor- and interleukin-1 cytokines are promoters of inducible nitric oxide synthase. Finally, the tissue lushes red (reactive hyperemia) with the resumption of perfusion. Nonsteroidal antiinlammatory drugs such as indomethacin (Indocin), ibuprofen (Motrin, Advil), and related drugs may also induce asthma in the aspirin-intolerant patient. Ureters collect the urine formed in the kidneys from the renal pelvises and transport it to the bladder. In addition, a number of methods have been developed to quantify myocardial blood low. Cardiac disease may adversely affect contractility because of an inadequate oxygen supply or because of loss of myocardial pumping cells. Immunosuppressive therapy, including corticosteroids and certain cytotoxic chemotherapeutic agents, has become an increasingly important treatment choice. Mechanisms that cause the cardiac effects of hypermagnesemia include decreased cardiac conduction and depression of membrane excitability. The area of coagulative necrosis is composed of denatured proteins and is relatively solid. The catabolism of adipose tissue releases free fatty acids and glycerol that also can be used for gluconeogenesis and to create ketoacids for fuel. New diagnostic laboratory techniques provide deinitive information for the genetic counseling of parents. Beauchamp and Childress have championed moral decision-making in medicine based on principlism emphasizing four moral attributes: autonomy, non-maleficence, beneficence, and justice. Renal responses to changes in metabolic and carbonic acids are summarized in Table 25-3. Pain management with a variety of strategies, including narcotic and nonnarcotic drugs, distraction, and biofeedback, is generally helpful. To facilitate understanding of this development, the two systems will be discussed in several subdivisions. The right mainstem bronchus is normally more vertical than the left because it is the main continuation of the laryngotracheal tube and branches off the trachea at a 20-degree angle. Activated T cells may then migrate to lymph vessels and travel to the bloodstream, where they are dispersed throughout the system. Nasal laring is a physiologic response mechanism used to increase airway diameter in an attempt to overcome airway resistance. If metabolic acidosis is uncompensated, the pH also is below normal because the usual 20:1 ratio is decreased. The term urodynamic testing is used for procedures associated with diagnosing voiding dysfunction. Sympathetic antagonists, nitrates, and morphine sulfate are the mainstays of drug therapy. The immune system has other peripheral "checkpoints" to detect, limit, and control these "self" or "auto" reactive T cells. Because of the high energy requirements of contracting skeletal muscle, the cells are packed with energy-producing mitochondria. It has been suggested that the overall oxygen debt can be estimated clinically by the serum lactate level and degree of metabolic acidosis, both of which imply a switch to anaerobic metabolism by oxygen-deprived tissues. Common causes of cellular injury include hypoxic injury, nutritional injury, infectious and immunologic injury, chemical injury, and physical and mechanical injury.

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This system is thought to be particularly important in culling senescent cells and selfreactive lymphocytes. It is such a potent vasodilator that it can cause signiicant reductions in blood pressure when released in excessive amounts. Overproduction of stimulatory growth factors by a mutant proto-oncogene can shift the balance of signals and produce excessive self-stimulated growth (autocrine signaling). Approximately 30% to 40% of all birth malformations are associated with genetic factors-6% are associated with chromosomal abnormalities, 8% are associated with single-gene disorders, and 20% to 30% are most likely multifactorial. Circulating IgG antibodies can bind to special receptors (Fc) on the B-cell membrane and inhibit B-cell activity. Sites of increased turbulence and blood pressure tend to have increased immune complex deposition. Blood analysis demonstrates characteristic biochemical abnormalities (particularly very-long chained fatty acid, phytanic acid, and bile salt metabolites). Many of the protozoal infections are transmitted through contaminated water or food and require ingestion. As this immunity fades over approximately the irst 6 months of life, these newborns are more at risk of serious infection. Air movement from the nasal cavity through the large bronchi occurs by turbulent low, which creates friction and increases resistance. In some cases, the accumulated substances are not metabolized by normal intracellular enzymes. The pulmonary artery catheter could become wedged and necrosis could occur, or the catheter could slip back in to the ventricle and irritate the myocardium, causing ventricular dysrhythmias. Metabolic activity in different areas of the heart can then be tracked over time under different conditions. Dysrhythmias are generally treated if they produce signiicant symptoms or are expected to progress to a more serious level. It is the condition in which the amount of extracellular luid is abnormally increased. Right and left coronary artery openings are located in the sinuses of Valsalva, in the aortic root, just beyond the aortic valve. Initially, the walls of the small pulmonary vessels thicken because of an increase in the muscle. The high interstitial gradient of the medulla provides the osmotic force for water reabsorption. It helps to decrease the incidence of serious bacterial, minor bacterial, viral, and opportunistic infections. In men with varicoceles surgical repair or embolization can often improve fertility. One of the functions of the lymphatic system is to reabsorb luid that leaks out of the vascular network in to the interstitium and return it to the general circulation. There are no valves between the vena cavae and the right atrium, and the atrial pressure waves that are generated during the cardiac cycle cause characteristic visible pulsations in the jugular veins. Oral and genital herpes simplex infections, including shingles or candidiasis (yeast) infections, usually develop, as well as oral hairy leukoplakia. In general, the renogram is more useful for assessing function, whereas the renal scan is better at detecting structural anomalies. The major causes of acquired mitral and aortic valvular diseases are listed in Table 18-6. But the tubules can repair themselves within 10 to 20 days when the basement membrane is intact and new epithelial cells are produced on that surface. In contrast, the distribution of luid between the interstitial and intracellular compartments occurs by osmosis, rather than by iltration. Removal of calcium ions inhibits cross-bridge formation and allows the thick and thin ilaments of the sarcomere to passively slide apart. Apoptosis is not a rare event; large numbers of cells are continually undergoing programmed cell death as tissues remodel. After age 40 years, the number of glomeruli begins to decrease, and by age 70 years it is estimated that as many as 30% to 50% of the glomeruli have been lost. Bacteria of the genus Mycoplasma do not have a rigid cell wall and are pleiomorphic (many formed) in shape. The enzymes attack the cell membranes of fat cells, causing release of their stores of triglycerides.

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Thus, clinical indings may not be evident until late in the course of chronic kidney disease. Bubbles of air, having most likely entered the blood through an intravenous catheter, come to rest in small blood vessels and obstruct perfusion. Histologic examination of hearts with dilated cardiomyopathy reveals nonspeciic changes in the majority of cases. Less severe bronchiectasis of the varicose type is present in the right lower lobe (open arrows). Impairment in low through the venous system interferes with the removal of metabolic waste products and causes luid pressure to accumulate in the system, a condition known as venous engorgement or venous obstruction. Any drugs that suppress the bone marrow or immune function are also believed to predispose to the emergence of malignancies. However, it is of questionable value because it may act as a growth factor for cancers. As the tumor increases in size and spreads through the body, a number of symptoms typically become apparent, including pain, cachexia, immune suppression, and infection. The plasma fraction contains dissolved substances, including nutrients, ions, plasma proteins, metabolic wastes, hormones, and enzymes. Airborne transmission occurs with aerosols including suspensions of particles (smaller than the size of droplets), which can be carried great distances from the source for transmission. The epithelial cells that line the gut and kidney tubules have large numbers of these nutrient transporters present in the luminal (apical) surfaces of their cell membranes. Hypoxemia may be detected by arterial blood gas analysis or pulse oximetry and may be apparent clinically as cyanosis. The study of childhood processes and of changes that occur in this period of life is the domain of pediatrics; speciic diseases that occur during maturity (ages 15 to 60) are emphasized in this text. Undigested fat in the intestines binds calcium and magnesium ions that are secreted in to the gastrointestinal tract and prevents them from being reabsorbed. Injury associated with radiation therapy is generally localized to the irradiated area. Carbonic anhydrase present in the brush border of the proximal tubule cell catalyzes the reaction. Medical and health care personnel are at risk through occupational exposure to blood and body luids. Insuficient numbers of functional leukocytes leaves the patient at high risk for development of infection and the complete blood count is routinely monitored. Capillary hydrostatic pressure is the primary force promoting luid movement from the capillaries to the interstitial luid. The sympathetic ibers, originating mainly from the lower thoracic and upper lumbar segments (T11-T12 and L1-L2), innervate the bladder and urethra as the hypogastric nerves. Epinephrine is helpful in stabilizing mast cells to prevent further release of inlammatory mediators and increasing blood pressure. Conversely, a left-to-right shunt occurs when oxygenated blood from the left side of the heart or aorta lows back in to the right side to be recirculated through the lungs. Oxygen Transport Oxygen is transported to the tissues by two mechanisms: (1) dissolved in plasma and (2) bound to the hemoglobin molecule. Oxygenated blood leaves the pulmonic circulation and returns to the heart via the left atrium and then to the left ventricle. A lack of differentiated features in a cancer cell is called anaplasia, and a greater degree of anaplasia is correlated with a more aggressively malignant tumor. Any lung disorder that decreases the total cross-sectional area of the lung vasculature can increase pulmonary vascular resistance and produce right ventricular strain. Two types of second-degree block are identiied by the pattern of nonconducted impulses.