NURS 6501 Knowledge Check Concepts of Psychological Disorders

Acute lymphoblastic leukemia (ALL) is a malignant (clonal) disease of the bone marrow in which early lymphoid precursors proliferate and replace the normal hematopoietic cells of the marrow. ALL is the most common type of cancer and leukemia in children in the United States. 

The malignant cells of acute lymphoblastic leukemia (ALL) are lymphoid precursor cells (ie, lymphoblasts) that are arrested in an early stage of development. This arrest is caused by an abnormal expression of genes, often as a result of chromosomal translocations or abnormalities of chromosome number. 

These aberrant lymphoblasts proliferate, reducing the number of the normal marrow elements that produce other blood cell lines (red blood cells, platelets, and neutrophils). Consequently, anemia, thrombocytopenia, and neutropenia occur, although typically to a lesser degree than is seen in acute myeloid leukemia. Lymphoblasts can also infiltrate outside the marrow, particularly in the liver, spleen, and lymph nodes, resulting in enlargement of the latter organs. 

Renal failure as a result of hyperuricemia can be associated with ALL, particularly at diagnosis or during active treatment. Uric levels rise as an end product of purine metabolism from cellular destruction. Because the major excretory pathway is through the kidneys, urates can precipitate in renal tubules or ureters and can lead to oliguria and acute renal failure. 

Approximately half the individuals with homozygous HbS disease experience vaso-occlusive crises. The frequency of crises is extremely variable. Some individuals have as many as 6 or more episodes annually, whereas others may have episodes only at great intervals or none at all. Each individual typically has a consistent pattern for crisis frequency. Triggers of vaso-occlusive crisis include the following: 

• Hypoxemia: May be due to acute chest syndrome or respiratory complications 
• Dehydration: Acidosis results in a shift of the oxygen dissociation curve 
• Changes in body temperature (eg, an increase due to fever or a decrease due to environmental temperature change) 

Many individuals with HbSS experience chronic low-level pain, mainly in bones and joints. Intermittent vaso-occlusive crises may be superimposed, or chronic low-level pain may be the only expression of the disease. 

Sickle RBCs express higher than normal amounts of adhesion molecules and are sticky. During inflammatory reactions, leukocyte release of mediators increases the expression of adhesion molecules on endothelial cells. These reactions further promote sickled erythrocytes to be come arrested during movement through the microvascular. The sluggish and stagnant red cells within the inflamed vascular vessels result in extended exposure to low oxygen tension, sickling, and vascular obstruction. Lysed sickle erythrocytes release hemoglobin and free hemoglobin can bind and inactivate nitic oxide (NO), which is a powerful vasodilator and inhibitor of platelet aggregation. Decreased blood pH reduces hemoglobin affinity for oxygen leading to an increasing fraction of deoxygenated HbS at any oxygen tension and predisposition to sickling. As less oxygen is taken up by hemoglobin in the lungs, the PO2 drops promoting additional sickling. 

The intense pain of an acute crisis is due to lack of oxygen to major organs and bones. The lack of oxygen leads to ischemia and organ death. 

SCD denotes all genotypes containing at least one sickle gene, in which HbS makes up at least half the hemoglobin present. Major sickle genotypes described so far include the following: 

• HbSS disease or sickle cell anemia (the most common form) – Homozygote for the S globin with usually a severe or moderately severe phenotype and with the shortest survival 
• HbS/b-0 thalassemia – Double heterozygote for HbS and b-0 thalassemia; clinically indistinguishable from sickle cell anemia (SCA) 
• HbS/b+ thalassemia – Mild-to-moderate severity with variability in different ethnicities 
• HbSC disease – Double heterozygote for HbS and HbC characterized by moderate clinical severity 
• HbS/hereditary persistence of fetal Hb (S/HPHP) – Very mild or asymptomatic phenotype 

Sickle cell trait or the carrier state is the heterozygous form characterized by the presence of around 40% HbS, absence of anemia, inability to concentrate urine (isosthenuria), and hematuria. Under conditions leading to hypoxia, it may become a  pathologic risk factor. Sickle cell disease produces illness, while sickle cell trait usually does not. People who inherit two genes for sickle hemoglobin (one from each parent) have sickle cell disease. With a few exceptions, a child can inherit sickle cell disease only if both parents have one gene for sickle cell hemoglobin 

Deficiencies in factor VIII, IX, and XI are associated with 90% of hemorrhagic bleeding disorders. Hemophilia A and hemophilia B are inherited in an X-linked recessive pattern. The genes associated with these conditions are located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is enough to cause the condition. A son inherits his mother’s other X chromosome, he will have normal blood clotting. A carrier’s son has a 50% chance of having hemophilia. A baby girl will inherit an X chromosome with a dominant gene for normal blood clotting from her father. Therefore, the daughter will not have hemophilia. 

Hemophilia A is caused by an inherited or acquired genetic mutation that results in dysfunction or deficiency of factor VIII, or by an acquired inhibitor that binds factor VIII. Of genetic cases, up to approximately one third are the result of de novo mutations not present in the mother’s X chromosome. 

Inadequate factor VIII results in the insufficient generation of thrombin by the FIXa and FVIIIa complex by means of the intrinsic pathway of the coagulation cascade. This mechanism, in combination with the effect of the tissue-factor pathway inhibitor, creates an extraordinary tendency for impaired clotting in response to trauma and, especially in persons with severe hemophilia, with spontaneous bleeding. 

Neural tube defects are the result of a teratogenic process that causes failed closure and abnormal differentiation of the embryonic neural tube. Neural tube defects occur between the 17th and 30th day of gestation, at a time when the mother may not be aware that she is pregnant, and the fetus is estimated to be about the size of a grain of rice. 

The most common neural tube defects are anencephaly and myelomeningocele. Anencephaly results from failed closure of the rostral end of the neural tube, resulting in incomplete formation of the brain and skull. 

Myelomeningocele results from failed closure of the caudal end of the neural tube, resulting in an open lesion or sac that contains dysplastic spinal cord, nerve roots, meninges, vertebral bodies, and skin. The anatomic level of the myelomeningocele sac roughly correlates with the patient’s neurologic, motor, and sensory deficits. 

Myelomeningocele is associated with abnormal development of the cranial neural tube, which results in several characteristic CNS anomalies. The Chiari type II malformation is characterized by cerebellar hypoplasia and varying degrees of caudal displacement of the lower brainstem into the upper cervical canal through the foramen magnum. This deformity impedes the flow and absorption of cerebrospinal fluid (CSF) and causes hydrocephalus, which occurs in more than 90% of infants with myelomeningocele. 

The ductus arteriosus is normally patent during fetal life; it is an important structure in fetal development as it contributes to the flow of blood to the rest of the fetal organs and structure. From the 6th week of fetal life onwards, the ductus is responsible for most of the right ventricular outflow, and it contributes to 60% of the total cardiac output throughout the fetal life. Only about 5-10% of its outflow passes through the lungs. 

This patency is promoted by continual production of prostaglandin E2 (PGE2) by the ductus. Closure of the ductus before birth may lead to right heart failure. Prostaglandin antagonism, such as maternal use of nonsteroidal anti-inflammatory medications (NSAIDs), can cause fetal closure of the ductus arteriosus. 

Thus, a patent ductus arteriosus (PDA) produces a left-to-right shunt. In other words, it allows blood to go from the systemic circulation to the pulmonary circulation. Therefore, pulmonary blood flow is excessive (see the image below). Pulmonary engorgement results with decreased pulmonary compliance. The reaction of the pulmonary vasculature to the increased blood flow is unpredictable. 

Prematurity or immaturity of the infant at the time of delivery contributes to the patency of the ductus. Several factors are involved, including immaturity of the smooth muscle within the structure or the inability of the immature lungs to clear the circulating prostaglandins that remain from gestation. These mechanisms are not fully understood. Conditions that contribute to low oxygen tension in the blood, such as immature lungs, coexisting congenital heart defects, and high altitude, are associated with persistent patency of the ductus. 

The neurological system is most vulnerable to lead toxicity.  Children are more likely to develop central nervous system toxicity while the peripheral nervous system is more often affected in adults. Lead inhibits sulfhydryl enzymes, which causes increase membrane permeability which causes increased intracranial pressure (ICP) and cerebral edema, tissue ischemia followed by irreversible necrosis and tissue atrophy with the final outcome of behavioral changes, decreased IQ, convulsions and eventually coma and death. 

The manifestations in children include temperamental lability, irritability, behavioral changes, hyperactivity or decreased activity, loss of developmental milestones and language delay. Lower IQ and ADHD like symptoms may be present. Severe toxicity can cause delirium, convulsions and encephalopathy. Depression and anxiety are more common in patients. Lead causes demyelination of the peripheral nervous system and the abnormalities mostly affect the extensor motor nerves and may result in hand and foot drop. 

Anemia may develop with lead poisoning due to impaired synthesis of heme, hemolysis of red cells and shortened red cell survival. Lead impairs uptake and utilization of iron. 

The skeletal system is affected as lead is accumulated as tertiary lead phosphate and calcium. This interferes with longitudinal bone growth in the metaphases in long bones which decreased growth rate. 

Although multiple hypotheses have been proposed as the pathophysiologic mechanisms responsible for SIDS, none have been proven. A triple-risk model suggests that SIDS represents an intersection of factors, including the following: 

• A vulnerable infant possessing intrinsic abnormalities in cardiorespiratory control 
• A critical period in the development of homeostatic control mechanisms 
• Exogenous extrinsic stressors (triggering factors) 

Death occurs when vulnerable infants are subjected to stressors at times when normal defense mechanisms may be structurally, functionally, or developmentally deficient. Epidemiologic data suggest that genetic factors play a role, and many studies have attempted to identify SIDS-associated genes. 

Stage 1- edema of vascular media and endothelial cells.  

Stage 2-occurs within 7-9 days after fever starts, there’s infiltration of neutrophils, and an inflammatory cascade which secret cytokines  

Stage 3- replacement of inflammatory cells by  monocytes and fibroblasts, formation of fibrous connective tissue  in the blood vessel walls, proliferation and thickening of the intima. . 

Stage 4- blood vessels scar, the intima thickens and  the coronary arteries calcify.  

Kawasaki disease (KD), also known as mucocutaneous lymph node syndrome and Kawasaki syndrome, is an acute febrile illness of early childhood characterized by vasculitis of the medium-sized arteries. Laboratory findings include elevated erythrocyte sedimentation rate (ESR), elevated C-reactive protein (CRP), hypoalbuminemia, anemia, elevated alanine aminotransferase (ALT), thrombocytosis, leukocytosis, and pyuria. 

The disease has 4 recognized stages: 

Stage 1- endothelial cells and the vascular media become edematous, but the internal elastic lamina remains intact. 

Stage 2-approximately 7-9 days after the onset of fever, an influx of neutrophils occurs, which is quickly followed inflammatory cells that secrete various cytokines that target the endothelial cells and result in a cascade of events that lead to fragmentation of the internal elastic lamina and vascular damage 

Stage 3- the active inflammatory cells are replaced by fibroblasts and monocytes, and fibrous connective tissue begins to form within the vessel wall. The intima proliferates and thickens. 

Stage 4- The vessel wall eventually develops scarring, intimal thickening, and calcification of coronary arteries. 

The coronary arteries become narrowed or occluded owing to stenosis or a thrombus. Cardiovascular death may occur from a myocardial infarction secondary to thrombosis of a coronary aneurysm or from rupture of a large coronary aneurysm. The vessel wall eventually becomes narrowed or occluded owing to stenosis or a thrombus. The period during of the greatest vascular damage is when a concomitant progressive increase in the serum platelet count occurs, and this is the point of the illness when the risk of death is most significant. 

Hyperinflation is a compensatory mechanism for obstructed airflow and the uneven changes that occur in   resistance of the airflow, uneven air distribution, and changes in   circulation caused by intra-alveolar pressure cause a mismatch in ventilation-perfusion.  

Interactions between environmental and genetic factors result in airway inflammation, which limits airflow and leads to functional and structural changes in the airways in the form of bronchospasm, mucosal edema, and mucus plugs. 

Airway obstruction causes increased resistance to airflow and decreased expiratory flow rates. These changes lead to a decreased ability to expel air and may result in hyperinflation. The resulting overdistention helps maintain airway patency, thereby improving expiratory flow; however, it also alters pulmonary mechanics and increases the work of breathing. 

Hyperinflation compensates for the airflow obstruction, but this compensation is limited when the tidal volume approaches the volume of the pulmonary dead space; the result is alveolar hypoventilation. Uneven changes in airflow resistance, the resulting uneven distribution of air, and alterations in circulation from increased intra-alveolar pressure due to hyperinflation all lead to ventilation-perfusion mismatch. 

Cystic fibrosis (CF) is a disease of exocrine gland function that involves multiple organ systems but chiefly results in chronic respiratory infections, pancreatic enzyme insufficiency, and associated complications in untreated patients. Pulmonary involvement occurs in 90% of patients surviving the neonatal period. End-stage lung disease is the principal cause of death. 

Cystic fibrosis is caused by defects in the cystic fibrosis gene, which codes for a protein transmembrane conductance regulator (CFTR) that functions as a chloride channel and is regulated by cyclic adenosine monophosphate (cAMP). Mutations in the CFTR gene result in abnormalities of cAMP-regulated chloride transport across epithelial cells on mucosal surfaces. 

Defective CFTR results in decreased secretion of chloride and increased reabsorption of sodium and water across epithelial cells. The resultant reduced height of epithelial lining fluid and decreased hydration of mucus results in mucus that is stickier to bacteria, which promotes infection and inflammation. Secretions in the respiratory tract, pancreas, GI tract, sweat glands, and other exocrine tissues have increased viscosity, which makes them difficult to clear. 

Most deaths associated with cystic fibrosis result from progressive and end-stage lung disease. In individuals with cystic fibrosis, the lungs are normal in utero, at birth, and after birth, before the onset of infection and inflammation (except possibly for the presence of dilated submucosal gland ducts in the airways). Shortly after birth, many persons with cystic fibrosis acquire a lung infection, which incites an inflammatory response. Infection becomes established with a distinctive bacterial flora. A repeating cycle of infection and neutrophilic inflammation develops. 

Defects in CFTR lead to reduced chloride secretion with water following into the gut. This may result in meconium ileus at birth and in distal intestinal obstruction syndrome (DIOS) later in life. In addition, other pathologic disorders complicate the simple relationship between the apical chloride and water secretion and the disease. The pancreatic insufficiency decreases the absorption of intestinal contents. Mechanical problems associated with inflammation, scarring, and strictures may predispose the patient to sludging of intestinal contents, leading to intestinal obstruction by fecal impaction or to intussusception. Adhesions may form, leading to complete obstruction. A complete obstruction may require resection, leading to loss of absorptive epithelium of the distal ileum. 

Other factors, such as reduced water content of secretions, precipitation of proteins, and plugging of ductules and acini, prevent the pancreatic enzymes from reaching the gut. Autodigestion of the pancreas occasionally leads to pancreatitis. 

Most patients with cystic fibrosis (90-95%) have pancreatic enzyme insufficiency and present with digestive symptoms and/or failure to thrive early in life. Onset of pancreatic insufficiency varies, however, and may occur in patients older than 6 months. Some patients never develop pancreatic insufficiency. 

Patients with pancreatic insufficiency typically present with poor weight gain in association with frequent stools that are malodorous, greasy, and associated with flatulence and colicky pain after feeding. The combination of increased energy intake demand at baseline, the added energy intake demand of chronic disease, difficulty sustaining energy uptake because of malabsorption, and anorexia associated with ongoing lung inflammation leads to poor weight gain. 

It has been suggested that a posterior column lesion within the central nervous system might be present in patients who have idiopathic scoliosis. Such central nervous system (CNS) dysfunction was hypothesized to be manifested as decreased vibratory sensation and proprioception. The earliest pathologic changes occur in the soft tissues. The muscles, ligaments, and other soft tissues become shortened on the concave side of the curve. Vertebral deformity occurs as asymmetric forces are applied to the epiphyseal center of the ossification by shortened and tight soft tissue © 2020 Walden University 13 o the concave side of the curve. True curves involve not only bending but also twisting of the torso, leading to a rib hump seen when the child leans forward. 

The curve increases most rapidly during periods of rapid skeletal growth. If the curve is less than 40 degrees at skeletal maturity, the risk of progression is small. In curves greater than 50 degrees, the spine is biomechanically unstable, and the curve usually progresses. For curves in the thoracic region over 80 degrees, there is marked cardiopulmonary compromise. 

STEC-HUS is usually preceded by a colitis caused by Shiga toxin– producing Escherichia coli (STEC). Subsequent inflammation of the colon facilitates systemic absorption of the shiga toxin and lipopolysaccharide from the GI tract. The toxin binds to polymorphonuclear leukocytes in the gut and is transported to the kidney, causing a cascade of effects, including lysis of glomerular capillary endothelial cells, separation of endothelial cells from the basement membrane, activation and aggregation of platelets and the activation of the coagulation cascade. The glomerular arterioles become swollen and occluded with platelets and fibrin clots. There is decreased glomerular filtration and the damaged glomerular membrane results in hematuria and proteinuria. Narrow vessels injure passing erythrocytes. The damaged erythrocytes are removed by the spleen, causing acute hemolytic anemia. Severe thrombocytopenia ensues. 

Pituitary dwarfism is characterized by short stature, delayed dentition, and delayed skeletal maturation. Most cases of sporadic or isolated growth hormone deficiency have a normal-appearing pituitary gland on MRI, although a small adenohypophysis may be observed, particularly in cases of panhypopituitarism. 

Pituitary growth hormone secretion is stimulated by growth hormone–releasing hormone (GHRH) from the hypothalamus and possibly by another signal, which may be stimulated by certain growth hormone–releasing peptides (GHRPs). Receptors for the GHRPs have been identified, and the natural ligand for these receptors has been determined to be ghrelin. Somatostatin secreted by the hypothalamus inhibits growth hormone secretion. 

Growth hormone deficiency may result from disruption of the growth hormone axis in the higher brain, hypothalamus, or pituitary. This dysfunction can be congenital or acquired. 

Osteogenesis imperfecta (OI) is a disorder of bone fragility chiefly caused by mutations in the genes that encode type I procollagen. Severity ranges from mild forms to lethal forms in the perinatal period. Additional genes have been discovered in which mutations can also cause brittle bones. 

Other metabolic abnormalities are associated with OI. Some individuals have increased serum thyroxine levels that suggest hyperthyroidism, which is consistent with reports of excessive sweating, heat intolerance, resting tachycardia and tachypnea.