Patho Final( digestive, cardiovascular, pulmonary, renal, neurologic)

Discuss how the structure, form, and integrity of the chest wall influence pulmonary function.

• If the chest is deformed or traumatized, the work of breathing increases and ventilation may be compromised because of decreased tidal volume • Trauma to the chest can impair the ability of the chest to expand normally • Can progress to hypercapnic respiratory failure

Compare and contrast the clinical symptoms and underlying mechanisms of bacterial pneumonia, viral pneumonia, and tuberculosis.

First of all, Pneumonia is an infection within the lower respiratory tract caused by all kinds of microorganisms (bacterial, viruses, fungi, etc). RF: older age, compromised immunity, and smoking. The causative microorganism influences how the individual presents clinically. Nosocomial infections refers to pneumonia that occurs during hospitalization. Community-acquired pneumonia is caused by Streptococcus pneumoniae, which sometimes results in hospitalization. Aspiration of oropharyngeal secretions is the most common route of infection. Another route is through the inhalation of microorganisms that have been released into the air when an infected individual coughs, sneezes, or talks. Pneumonia can also result when bacteria is spread to the lungs in the blood from bacteremia that can result from infection elsewhere in the body. Viral pneumonia is usually mild and self-limiting, but can set the stage for a secondary bacterial infection through the immunocompromised system. Viral pneumonia also can be a complication of another viral illness, such as chickenpox or measles (spread from the blood). Viruses destroy the ciliated epithelial cells and invade the goblet cells and bronchial mucous glands. Sloughing of destroyed bronchial epithelium occurs throughout the respiratory tract and bronchial walls become edematous and infiltrated with leukocytes. In severe cases, the alveoli are involved with decreased compliance and increased work of breathing. S/S: fever, chills, productive or dry cough, malaise, pleural pain, and sometimes dyspnea and hemoptysis. Physical examination may show signs of pulmonary consolidation, such as dullness to percussion, inspiratory crackles, increased tactile fremitus, egophony (hoarseness), and whispered pectoriloquy. Individuals also may demonstrate symptoms and signs of underlying systemic disease or sepsis. Tuberculosis (TB) is an infection caused by Mycobacterium tuberculosis, an acid-fast bacillus that usually affects the lungs. TB spreads easily and occurs commonly thru emigration of infected individuals from high-prevalence countries, transmission in crowded institutional settings (prisons), and homelessness (shelters). Patho: TB is highly contagious and transmitted from person to person via airborne droplets. In healthy individuals, the microorganism is usually contained by the inflammatory and immune response systems, resulting in a latent infection. The latent form of TB is associated with no clinical evidence of disease. Microorganisms lodge in the lung periphery, usually in the upper lobe. Some bacilli migrate through the lymphatics and become lodged in the lymph nodes, where they encounter lymphocytes and initiate the immune response. Patho for latent TB: Bacilli that are inspired into the lung multiply and cause localized inflammation, which causes activation of alveolar macrophages and neutrophils. These phagocytes engulf the bacilli, isolating it to prevent spread. The neutrophils and macrophages seal off the colonies of bacilli, forming a granulomatous lesion called a tubercle. Infected tissues within the tubercle die, forming cheese-like material called caesous necrosis. Scar tissue then grows around the tubercle, completing isolating the bacilli. The immune response is complete after about 10 days, preventing further multiplication of the bacilli. Once the bacilli are isolated in tubercles and immunity develops, tuberculosis may remain latent for life. S/S: Latent TB is asymptomatic. Symptoms of active TB often develop gradually until the disease is advanced. S/S: fatigue, weight loss, lethargy, anorexia (loss of appetite), and a low-grade fever that usually occur in the afternoon. A cough that produces purulent sputum develops slowly and becomes more frequent over several weeks or months. Night sweats and general anxiety are often present. Dyspnea, chest pain, and hemoptysis may occur as the disease progresses.

Describe the significance of the body temperature "set point" within the hypothalamus.

Fever is a temporary resetting of the hypothalamic "thermostat" to a higher level in response to infectious disease. W/o set point, fever becomes uncontrolled and leads to death and nerve damage

Define "HbA1c", including what "glycated hemoglobin" is, and identify the significance of this lab value.

HbA1c is the best indicator of the average blood glucose level for the past 120 days.

Describe the different types of lung cancer.

Lung cancer (bronchogenic carcinomas) cell types include non-small cell carcinoma (squamous cell, adenocarcinoma, and large cell) and, less commonly, neuroendocrine tumors (small cell carcinoma, large cell neuroendocrine carcinoma, and typical carcinoid and atypical carcinoid tumors). Each type arises in a characteristic site or type of tissue, causes distinctive clinical manifestations, and differs in likelihood of metastasis and prognosis.

Define malabsorption syndrome and maldigestion; characterize pancreatic insufficiency and lactase and bile salt deficiency.

Malabsorption syndromes result in impaired digestion or absorption of nutrients and usually cause diarrhea. Maldigestion is failure of the chemical processes of digestion that take place in the intestinal lumen or at the brush border of the intestinal mucosa. *Pancreatic exocrine insufficiency causes malabsorption associated with impaired digestion. The pancreas does not produce sufficient amounts of the enzymes that digest protein, carbohydrates, and fats into components that can be absorbed by the intestine. A large amount of fat in the stool (steatorrhea) is the most common sign of pancreatic insufficiency. There is also a deficit of fat-soluble vitamins (A, D, E, and K) and weight loss. *Deficient lactase production in the brush border of the small intestine inhibits the breakdown of lactose. This prevents lactose absorption and causes osmotic diarrhea. Clinical manifestations of lactose consumption with lactase deficiency are bloating, crampy pain, diarrhea, and flatulence. *Bile salt deficiency causes fat malabsorption and steatorrhea (fatty stools). Bile salt deficiency can result from inadequate secretion of bile, excessive bacterial deconjugation of bile, or impaired reabsorption of bile salts caused by ileal disease. Clinical manifestations of bile salt deficiency are related to poor intestinal absorption of fat and fat-soluble vitamins (A, D, E, and K). Increased fat in the stools (steatorrhea) leads to diarrhea and decreased levels of plasma proteins. The losses of fat-soluble vitamins and their effects include the following: 1. Vitamin A deficiency results in night blindness. 2. Vitamin D deficiency results in decreased calcium absorption with bone demineralization (osteoporosis), bone pain, and fractures. 3. Vitamin K deficiency prolongs prothrombin time, leading to spontaneous development of purpura (bruising) and petechiae. 4. Vitamin E deficiency has uncertain effects but may cause testicular atrophy and neurologic defects in children.

Identify the causes of low back pain.

Most causes of low back pain are unknown; however, some secondary causes are disk prolapse, tumors, bursitis, synovitis, degenerative joint disease, osteoporosis, fracture, inflammation, and sprain.

Explain the pathophysiology and clinical manifestations of multiple sclerosis.

Multiple sclerosis (MS) is a chronic inflammatory disease involving degeneration of CNS myelin, scarring (sclerosis or plaque formation), and loss of axons. MS is caused by an autoimmune response to self or microbial antigens in genetically susceptible individuals. The onset of MS is usually between 20 and 40 years of age and is more common in women. Men may have a more severe progressive course. The prevalence rate is higher in northern latitudes. Risk factors that may be involved include smoking, vitamin D deficiency, and Epstein-Barr virus infection.88 The etiology of MS is unknown. MS is a diffuse and progressive disease with patches of damage that can occur throughout the brain and spinal cord. Autoreactive T and B cells cross the blood- brain barrier and recognize myelin and oligodendrocyte autoantigens, triggering inflammation and loss of oligodendrocytes (myelin producing cells). Activation of microglia cells (brain macrophages) contributes to inflammation and injury with plaque formation and axonal degeneration. Loss of myelin disrupts nerve conduction with subsequent death of neurons and brain atrophy. Normal appearing white matter can be microscopically very abnormal and gray matter lesions and atrophy have been documented during later stages of the disease process. These degenerative processes begin before symptom onset and progress throughout a person's life. Myelin degeneration also can present as optic neuritis or involve the spinal cord. Spinal MS can occur concurrently or independently of brain lesions. The multifocal, multistaged features of MS lesions in established disease produce symptoms that are multiple and variable. The most common initial symptoms of MS are paresthesias of the face, trunk, or limbs; weakness; impaired gait; visual disturbances; or urinary incontinence, indicating diffuse CNS involvement. Cerebellar and corticospinal involvement presents as nystagmus, ataxia, and weakness with all four limbs involved. Intention tremor and slurred speech may also occur. The onset, duration, and severity of symptoms are different for each person. Disease exacerbations (also known as relapses or flares) are the temporary occurrence or worsening of symptoms. The symptoms may be mild or serious, may last for several days or weeks, and may be followed by progressive symptoms, including include paresthesias, difficulty speaking, ataxia, or visual changes. The mechanism of these exacerbations is related to delayed or blocked conduction caused by inflammation and demyelination. Various events can occur immediately before the exacerbation of symptoms and are regarded as precipitating factors or triggers, including trauma, emotional stress, and pregnancy. Painful sensory events, spastic paralysis, and bowel and bladder incontinence are common with spinal involvement. Recovery from symptoms during remissions is caused by down- regulation of inflammation and the restoration of axonal function, either by remyelination, the resolution of inflammation, or the restoration of conduction to demyelinated axons. The subtypes of MS are based on the clinical course: (1) remitting-relapsing, initial onset of symptoms followed by remission and exacerbations; (2) primary- progressive, a steady decline from onset; (3) secondary-progressive, initial remitting and relapsing symptoms with a steady decline in function; and (4) progressive- relapsing, a progressive course from onset with superimposed relapses. Initially, 85% to 90% of persons present with a remitting-relapsing course and without treatment transition to the progressive types with insidious neurologic decline. Early cognitive changes are common and may include poor judgment, apathy, emotional lability, and depression.

Describe the pathophysiology and clinical manifestations of myasthenia gravis.

Myasthenia gravis is a disorder of voluntary muscles characterized by muscle weakness and fatigability. It is considered an autoimmune disease and is associated with an increased incidence of other autoimmune diseases. Myasthenia gravis results from a defect in nerve impulse transmission at the postsynaptic membrane of the neuromuscular junction. IgG antibody is secreted against the "self" AChR receptors and blocks the binding of acetylcholine. The antibody action destroys the receptor sites, causing decreased transmission of the nerve impulse across the neuromuscular junction. Myasthenia gravis is an acquired chronic autoimmune disease mediated by antibodies against the acetylcholine receptor (AChR) at the postsynaptic membrane of the neuromuscular junction. The incidence is about 9 to 21 per million population and it is more common in women. Thymic tumors, pathologic changes in the thymus, and other autoimmune diseases are associated with the disorder. Ocular myasthenia, more common in males, involves weakness of the eye muscles and eyelids, and may include swallowing difficulties and slurred speech. Pathophysiology Myasthenia gravis results from a defect in nerve impulse transmission at the neuromuscular junction. The postsynaptic AChRs on the muscle cell's plasma membrane are no longer recognized as "self" and elicit T-cell-dependent formation of IgG autoantibodies. The autoantibodies fix onto ACh receptor sites, blocking the binding of acetylcholine. Eventually the antibody action destroys receptor sites. This loss of AChR sites causes diminished transmission of the nerve impulse across the neuromuscular junction and decreased muscle depolarization. Symptomatic individuals without anti-AChR antibodies may have antibodies against muscle- specific kinase (MuSK) with similar symptoms. Why this autosensitization occurs is unknown. Clinical manifestations Myasthenia gravis has an insidious onset. The variable distribution of ACh receptor sites or the number of and different isoforms of antibodies may determine when and which muscle groups are affected first. The muscles of the eyes, face, mouth, throat, and neck usually are affected first. There can be drooling and difficulty chewing and swallowing food. These problems can affect nutrition and put the person as risk for respiratory aspiration. The muscles of the neck, shoulder girdle, and hip flexors are less frequently affected but muscle fatigue is common after exercise and there can be progressive weakness. The respiratory muscles of the diaphragm and chest wall can become weak with impaired ventilation. Clinical manifestations may first appear during pregnancy, during the postpartum period, or in conjunction with the administration of certain anesthetic agents. The progression of myasthenia gravis varies, appearing first as a mild case that spontaneously remits, with a series of relapses and symptom-free intervals ranging from weeks to months. Over time, the disease can progress. Myasthenic crisis can develop as the disease progresses and occurs when severe muscle weakness causes extreme quadriparesis or quadriplegia, respiratory insufficiency with shortness of breath, and extreme difficulty in swallowing. The individual in myasthenic crisis is in danger of respiratory arrest. Cholinergic crisis may arise from anticholinesterase drug toxicity with increased intestinal motility, episodes of diarrhea and complaints of intestinal cramping, bradycardia, pupillary constriction, increased salivation, and diaphoresis. These symptoms are caused by the smooth muscle hyperactivity secondary to excessive accumulation of acetylcholine at the neuromuscular junctions and excessive parasympathetic-like activity. As in myasthenic crisis, the individual is in danger of respiratory arrest.

Discuss the clinical manifestations, treatment options, outcomes, and complications of acute renal failure.

Clinical manifestations: The clinical progression of AKI with recovery of renal function occurs in three phases: initiation phase, maintenance phase, and recovery phase. The initiation phase is the phase of reduced perfusion or toxicity in which kidney injury is evolving. Prevention of injury is possible during this phase. The maintenance phase is the period of established kidney injury and dysfunction after the initiating event has been resolved and may last from weeks to months. Urine output is lowest during this phase and serum creatinine and blood urea nitrogen (BUN) levels both increase. The recovery phase is the interval when kidney injury is repaired and normal renal function is reestablished. Diuresis is common during this phase with a decline in serum creatinine and urea concentrations and an increase in creatinine clearance. Oliguria begins within 1 day after a hypotensive event and lasts 1 to 3 weeks, but it may regress in several hours or extend for several weeks, depending on the duration of ischemia or the severity of injury or obstruction. Renal failure can present with nonoliguria, particularly with intrinsic kidney injury associated with nephrotoxins. The urine output may vary in volume, but the BUN and plasma creatinine concentrations increase (plasma creatinine concentration is inversely proportional to the GFR). Other early manifestations depend on the underlying cause of renal failure. As renal function improves, increase in urine volume (diuresis) is progressive. The tubules are still damaged early in the recovery phase but are recovering function. Fluid and electrolyte balance must be carefully monitored and excessive urinary losses replaced. Serial measurements of plasma creatinine concentration provide an index of renal function during the recovery phase. Return to normal status may take from 3 to 12 months, and some individuals do not have full recovery of a normal GFR or tubular function. Evaluation and treatment: The diagnosis of AKI is related to the cause of the disease. A history of surgery, trauma, or cardiovascular disorders is common, and exposure to nephrotoxins and obstructive neuropathies (e.g. enlarged prostate) must be considered. The diagnostic challenge is to differentiate prerenal AKI from intrarenal AKI, and some evidence is available from urinalysis and measurement of plasma creatine and BUN levels (table 29-12). Biomarkers are being developed to assess the extent of kidney injury. Prevention of AKI is a major treatment factor and involves avoidance of hypotension, hypovolemia, and nephrotoxicity. The primary goal of therapy is to maintain the individual's life until renal function has been recovered. Management principles directly related to physiologic alterations generally include (1) correcting fluid and electrolyte disturbances, (2) treating infections, (3) maintaining nutrition, and (4) remembering that drugs or their metabolites are not excreted. Continuous renal replacement therapy may be indicated. The mortality rate is greater than 50% with renal replacement therapy.

Explain what is meant by the term uremia.

Condition of urea in the blood

Describe similarities, clinical manifestations, underlying mechanisms, and consequences of obstructive pulmonary diseases.

Obstructive lung disease is characterized by airway obstruction that is worse with expiration. More force (i.e., use of accessory muscles of expiration) is required to expire a given volume of air and emptying of the lungs is slowed. The unifying symptom of obstructive lung diseases is dyspnea, and the unifying sign is wheezing. Individuals have an increased work of breathing, ventilation-perfusion mismatching, and a decreased forced expiratory volume in 1 second (FEV1). The most common obstructive diseases are asthma, chronic bronchitis, and emphysema. Because many individuals have chronic bronchitis with emphysema, these diseases together are often called chronic obstructive pulmonary disease (COPD). *Asthma is a chronic inflammatory disorder of the bronchial mucosa that causes bronchial hyperresponsiveness, constriction of the airways, and variable airflow obstruction that is reversible.Individuals are asymptomatic between attacks and pulmonary function tests are normal. At the beginning of an attack, the individual experiences chest constriction, expiratory wheezing, dyspnea, nonproductive coughing, prolonged expiration, tachycardia, and tachypnea. Severe attacks involve the accessory muscles of respiration and wheezing is heard during both inspiration and expiration. A pulsus paradoxus (decrease in systolic blood pressure during inspiration of more than 10 mm Hg) may be noted. Peak flow measurements should be obtained. Because the severity of blood gas alterations is difficult to evaluate by clinical signs alone, arterial blood gas tensions should be measured if oxygen saturation falls below 90%. Usual findings are hypoxemia with an associated respiratory alkalosis. In the late asthma response, symptoms can be even more severe than the initial attack. If bronchospasm is not reversed by usual treatment measures, the individual is considered to have acute severe bronchospasm or status asthmaticus.39 If status asthmaticus continues, hypoxemia worsens, expiratory flows and volumes decrease further, and effective ventilation decreases. Acidosis develops as the PaCO2 levelbegins to rise. Asthma becomes life-threatening at this point if treatment does not reverse this process quickly. A silent chest (no audible air movement) and a PaCO2 >70 mm Hg are ominous signs of impending death. *Chronic obstructive pulmonary disease (COPD) is defined as a common preventable and treatable disease characterized by persistent airflow limitation that is usually progressive and associated with an enhanced chronic inflammatory response in the airways and the lung to noxious particles or gases. -Chronic bronchitis is defined as hypersecretion of mucus and chronic productive cough for at least 3 months of the year (usually the winter months) for at least 2 consecutive years. -Emphysema is abnormal permanent enlargement of gas-exchange airways (acini) accompanied by destruction of alveolar walls without obvious fibrosis. Obstruction results from changes in lung tissues, rather than mucus production and inflammation as in chronic bronchitis. The major mechanism of airflow limitation is loss of elastic recoil.

Describe the manifestations of nephrotic syndrome, glomerulonephritis, immunoglobulin A nephropathy, and hemolytic uremic syndrome in children.

*Glomerulonephritis Manifestations: Glomerulonephritis includes a number of renal disorders in which proliferation and inflammation of the glomeruli are secondary to an immune mechanism (the pathophysiology is described in Chapter 30). Chronic glomerulonephritis accounts for about 14% of the cases of renal failure in children in the United States3 and is the causative factor for 9% to 35% of end-stage renal disease in children worldwide. Acute poststreptococcal glomerulonephritis (APGN) is one of the most common immune complex-mediated renal diseases in children. It most commonly occurs after a throat or skin infection with a nephritogenic strain of group A β-hemolytic streptococci, although other bacteria and viruses also may be responsible.25 Occurrences have been observed after bacterial endocarditis, which may be associated with streptococcal or staphylococcal microorganisms, or after viral diseases, such as varicella-zoster virus and hepatitides B and C. Glomerulonephritis develops with the deposition of antigen-antibody complexes in the glomerulus. The antigen-antibody complex activates complement and the release of inflammatory mediators that damage endothelial and epithelial cells lying on the glomerular basement membrane. Damage to the glomerular basement membrane leads to hematuria and proteinuria. *immunoglobulin A nephropathy manifestations:Immunoglobulin A (IgA) nephropathy is the most common form of glomerulonephritis worldwide and occurs more often in males. It is characterized by deposition primarily of immunoglobulin A and complement proteins in the mesangium of the glomerulus. Children with the disease have recurrent gross hematuria concurrent with a respiratory tract infection. Most continue to have microscopic hematuria between the attacks of gross hematuria and have a mild proteinuria as well. Treatment is supportive. Some children recover completely, whereas 20% or more will eventually require dialysis and transplantation. IgA nephropathy may recur following transplantation.Henoch-Schönlein purpura nephritis is a particular form of IgA nephropathy that involves a systemic vasculitis. Symptoms vary widely. In addition to palpable purpura, children may experience abdominal pain, arthralgia, hematuria, and/or proteinuria. Complete recovery may occur, but some children progress to end-stage kidney disease. *nephrotic syndrome manifestations: Onset of nephrotic syndrome can be insidious, with periorbital edema as the usual first sign. The edema is most noticeable in the morning and subsides during the day as fluid shifts to the abdomen, genitalia, and lower extremities. Parents may notice diminished, frothy, or foamy urine output; or when edema becomes pronounced with ascites, respiratory difficulty from pleural effusion or labial or scrotal swelling may occur. Edema of the intestinal mucosa may cause diarrhea, anorexia, and poor absorption. Edema often masks the malnutrition caused by malabsorption and protein loss. Pallor, with shiny skin and prominent veins, also is common. Blood pressure is usually normal. The child has an increased susceptibility to infection, especially pneumonia, peritonitis, cellulitis, and septicemia. Irritability, fatigue, and lethargy are common. Congenital nephrotic syndrome (Finnish type) is caused by an autosomal recessive mutation of the NPHS1 gene that encodes an immunoglobulin-like protein, nephrin, at the podocyte slit membrane.Congenital nephrotic syndrome (Finnish type) presents with heavy proteinuria, hypoproteinemia, and edema in the first 3 months of life. These babies do not respond to steroid treatment and require albumin infusion and diuretics *hemolytic uremic syndrome manifestations: A prodromal gastrointestinal illness (fever, vomiting, diarrhea) or, less frequently, an upper respiratory tract infection often precedes the onset of HUS by 1 to 2 weeks. After a symptom-free 1- to 5-day period, the sudden onset of pallor, bruising or purpura, irritability, and oliguria heralds the commencement of the disease. Slight fever, anorexia, vomiting, diarrhea (with the stool characteristically watery and blood stained), abdominal pain, mild jaundice, and circulatory overload are accompanying symptoms. Seizures and lethargy indicate central nervous system (CNS) involvement. Renal failure is apparent within the first days of onset. The renal failure causes metabolic acidosis, azotemia, hyperkalemia, and often hypertension.

Describe the types of sleep disorders and give an example of each.

(Common Dyssomnias) *Insomnia is the inability to fall or stay asleep; it is accompanied by fatigue during wakefulness and may be mild, moderate, or severe. It may be transient, lasting a few days or months (primary insomnia), and related to travel across time zones or caused by acute stress.73 Chronic insomnia can be idiopathic, start at an early age, and be associated with drug or alcohol abuse, chronic pain disorders, chronic depression, the use of certain drugs, obesity, aging, genetics, and environmental factors that result in hyperarousal. Obstructive sleep apnea syndrome (OSAS) is the most commonly diagnosed sleep disorder. An estimated 1% to 5% of children, 9% of women, and 24% of men younger than 65 years of age in the United States have diagnosable sleep-disordered breathing. The incidence increases in those older than 65 years. Major risk factors include obesity, male gender, older age, and postmenopausal status (not on hormone therapy) in women.A lack of daytime sleepiness often lessens awareness of a potential sleep disorder and many persons are never properly diagnosed and treated. OSAS results from partial or total upper airway collapse with obstruction to airflow recurring during sleep with excessive loud snoring, gasping, and multiple apneic episodes that last 10 seconds or longer. The periodic breathing eventually produces arousal, which interrupts the sleep cycle, reducing total sleep time and producing sleep and REM deprivation. Associated conditions include decreased sensitivity to carbon dioxide and oxygen tensions, upper airway obstruction, a small airway, and decreased airway dilator muscle activation. Obesity hypoventilation syndrome may be related to leptin resistance because leptin also is a respiratory stimulant. Sleep apnea produces hypercapnia and low oxygen saturation and eventually leads to polycythemia, pulmonary hypertension, systemic hypertension, stroke, right-sided congestive heart failure, dysrhythmias, liver congestion, cyanosis, and peripheral edema. Hypersomnia (excessive daytime sleepiness) is associated with OSAS. Individuals may fall asleep while driving a car,working, or even while conversing, with significant safety concerns. Sleep deprivation also can result in impaired mood and cognitive function characterized by impairments of attention, episodic memory, working memory, and executive functions. Polysomnography is needed to diagnose OSAS in addition to the history and physical examination. Treatments include use of nasal continuous positive airway pressure and dental devices, surgery of the upper airway and jaw in selected individuals, and management of obesity. Adenotonsillar hypertrophy is the major cause of obstructive sleep apnea in children and obesity increases risk. Adenotonsillectomy is the treatment of choice. *Narcolepsy is a primary hypersomnia characterized by hallucinations, sleep paralysis, and, rarely, cataplexy (brief spells of muscle weakness). Narcolepsy is usually sporadic or can occur in families. Narcolepsy without cataplexy is associated with immune-mediated destruction of hypocretin (orexin)-secreting cells in the hypothalamus. Orexins stimulate wakefulness. *Circadian rhythm sleep disorders are common disorders of the 24-hour sleep- wake schedule (circadian rhythm sleep disorders). They can result from having rapid time-zone changes (or jet-lag syndrome), alternating the sleep schedule (rotating work shifts) involving 3 hours or more in sleep time, changing the total sleep time from day to day, or being diagnosed either with advanced sleep phase disorder (early morning waking-early evening sleeping), resulting in sleep loss if social requirements are for late sleeping, or with delayed sleep phase disorder (late morning waking-late night to early morning sleeping), with loss of sleep because of required early morning rising (common in adolescents). These changes desynchronize the circadian rhythm, which can depress the degree of vigilance, performance of psychomotor tasks, and arousal. A circadian rhythm sleep disorder known as shift work sleep disorder affects many shift workers who rotate or swing long shifts (such as nurses), particularly between the hours of 2200 (10:00 AM) and 0600 (6:00 AM).86,87 Our sleep-wake cycle is driven by circadian rhythms and the disruption of this circadian influence may cause problems in the short term, such as cognitive deficits and difficulty concentrating. However, long-term health consequences of shift work sleep disorder may be quite serious and include depression/anxiety, increased risk for cardiovascular disease, and increased all- cause mortality. Sleep cycle phenotype also has a genetic basis and influences the timing and cycles of sleep and can affect advances or delays in sleep-wake times. (Common Parasomnias) Parasomnias are unusual behaviors occurring during NREM stage 3 (slow wave) sleep. These behaviors include sleepwalking, having night terrors, rearranging furniture, eating food, and exhibiting sleep sex or violent behavior, and having restless legs syndrome. REM sleep behavior disorder is manifested by loss of REM paralysis, leading to potentially injurious dream enactment. Two dysfunctions of sleep (somnambulism and night terrors) are common in children and may be related to central nervous system immaturity. Somnambulism (sleepwalking) is a disorder primarily of childhood and appears to resolve within a few years. Sleepwalking is therefore not associated with dreaming, and the child has no memory of the event on awakening. Sleepwalking in adults is often associated with sleep disordered breathing. Night terrors are characterized by sudden apparent arousals in which the child expresses intense fear or emotion. However, the child is not awake and can be difficult to arouse. Once awakened, the child has no memory of the night terror event. Night terrors are not associated with dreams. Although this problem occurs most often in children, adults also may experience it with corresponding daytime anxiety. *Restless Leg Syndrome (RLS)/Willis Ekbom disease is a common sensorimotor disorder associated with unpleasant sensations (prickling, tingling, crawling) and nonvolitional periodic leg movements that occurs at rest and is worse in the evening or at night. There is a compelling urge to move the legs for relief with a significant effect on sleep and quality of life. The disorder is more common in women, during pregnancy, the elderly, and individuals with iron deficiency. RLS has a familial tendency and is associated with a circadian fluctuation of dopamine in the substantia nigra. Iron is a cofactor in dopamine production and some individuals respond to iron administration as well as dopamine agonists. Diagnostic and treatment guidelines have been established to assist with disease management.

Discuss the major types of seizures seen in children and describe their clinical manifestations.

(Generalized Seizure) First clinical manifestations indicate that seizure activity starts in or involves both cerebral hemispheres; consciousness may be impaired; bilateral manifestations; may be preceded by an aura *Tonic-clonic Musculature stiffens, then intense jerking as trunk and extremities undergo rhythmic contraction and relaxation *Atonic Sudden, momentary loss of muscle tone; drop attacks *Myoclonic Sudden, brief contractures of a muscle or group of muscles *Absence seizure Brief loss of consciousness with minimal or no loss of muscle tone; may experience 20 or more episodes a day lasting approximately 5 to 10 sec each; may have minor movement, such as lip smacking, twitching of eyelids ---------------------------------------- Partial (Focal) Seizure Seizure activity that begins and usually is limited to one part of left or right hemisphere; an aura is common *Simple Seizure activity that occurs without loss of consciousness *Complex Seizure activity that occurs with impairment of consciousness ------------------------------ Epilepsy Syndromes Seizure disorders that display a group of signs and symptoms that occur collectively and characterize or indicate a particular condition *Infantile spasms (West syndrome) Form of epilepsy with episodes of sudden flexion or extension involving neck, trunk, and extremities; clinical manifestations range from subtle head nods to violent body contractions (jackknife seizures); onset between 3 and 12 months of age; may be idiopathic, genetic, result of metabolic disease, or in response to CNS insult; spasms occur in clusters of 5 to 150 times per day; EEG shows large-amplitude, chaotic, and disorganized pattern called "hypsarrhythmia" *Lennox- Gastaut syndrome Epileptic syndrome with onset in early childhood, 1 to 5 years of age; includes various generalized seizures—tonic-clonic, atonic (drop attacks), akinetic, absence, and myoclonic; EEG has characteristic "slow spike and wave" pattern; results in mental retardation and delayed psychomotor developments *Juvenile myoclonic epilepsy Onset in adolescence; multifocal myoclonus; seizures often occur early in morning, aggravated by lack of sleep or after excessive alcohol intake; occasional generalized convulsions; require long-term medication treatment *Benign rolandic epilepsy Epileptic syndrome typically occurring in the preadolescent age (6 to 12 years); strong association with sleep (seizures typically occur few hours after sleep onset or just before waking in morning); complex partial seizures with orofacial signs (drooling, distortion of facial muscles); characteristic EEG with centrotemporal (Rolandic fissure) spikes *Status Epilepticus Continuing or recurring seizure activity in which recovery from seizure activity is incomplete; unrelenting seizure activity can last 30 min or more; medical emergency that requires immediate intervention

Describe the differences between brain death and cerebral death.

*(criteria for brain death) 1. Completion of all appropriate diagnostic and therapeutic procedures with no possibility of brain function recovery 2. Unresponsive coma (no motor or reflex movements) 3. No spontaneous respiration (apnea) 4. No brainstem functions (ocular responses to head turning or caloric stimulation; dilated, fixed pupils; no gag or corneal reflex [see Figures 15-3 and 15-4]) 5. Isoelectric (flat) EEG (electrocerebral silence) 6. Persistence of these signs for an appropriate observation period Brain death (total brain death) occurs when the brain is damaged so completely that it can never recover (irreversible) and cannot maintain the body's internal homeostasis. State laws define brain death as irreversible cessation of function of the entire brain including the brainstem and cerebellum. On postmortem examination, the brain is autolyzing (self-digesting) or already autolyzed. Brain death has occurred when there is no evidence of brain function for an extended period. The abnormality of brain function must result from structural or known metabolic disease and must not be caused by a depressant drug, alcohol poisoning, or hypothermia. An isoelectric, or flat, electroencephalogram (EEG) (electrocerebral silence) for 6 to 12 hours in a person who is not hypothermic and has not ingested depressant drugs indicates brain death. ------------------------------------------------- *Cerebral death, or irreversible coma, is death of the cerebral hemispheres exclusive of the brainstem and cerebellum. Brain damage is permanent, and the individual is forever unable to respond behaviorally in any significant way to the environment. The brainstem may continue to maintain internal homeostasis (i.e., body temperature, cardiovascular functions, respirations, and metabolic functions). The survivor of cerebral death may remain in a coma or emerge into a persistent vegetative state (VS) or a minimally conscious state (MCS). In coma, the eyes are usually closed with no eye opening. The person does not follow commands, speak, or have voluntary movement

Describe the alterations in vascular flow (including thrombus formation, emboli, traumatic injury, atherosclerotic plaques, vasospastic disease, and varicosities) that result in outcomes such as stasis ulcers, chronic arterial and venous insufficiencies, and superior vena cava syndrome.

*A thrombus is a blood clot that remains attached to a vessel wall (see Figure 21-20). A detached thrombus is a thromboembolus. Venous thrombi are more common than arterial thrombi because flow and pressure are lower in the veins than in the arteries. Deep venous thrombosis (DVT) occurs primarily in the lower extremity. Three factors (triad of Virchow) promote venous thrombosis: (1) venous stasis (e.g., immobility, age, congestive heart failure), (2) venous endothelial damage (e.g., trauma, intravenous medications), and (3) hypercoagulable states (e.g., inherited disorders, malignancy, pregnancy, use of oral contraceptives or hormone replacement therapy). Deep venous thrombosis results from stasis of blood flow, endothelial damage, or hypercoagulability. The most serious complication of deep venous thrombosis is pulmonary embolism. *Superior vena cava syndrome (SVCS) is a progressive occlusion of the superior vena cava (SVC) that leads to venous distention in the upper extremities and head. Causes include bronchogenic cancer (75% of cases) followed by lymphomas and metastasis of other cancers. Other less common causes include tuberculosis, mediastinal fibrosis, and cystic fibrosis. Invasive therapies (pacemaker wires, central venous catheters, and pulmonary artery catheters) with associated thrombosis now account for nearly 40% of cases.The SVC is a relatively low- pressure vessel that lies in the closed thoracic compartment; therefore tissue expansion can easily compress the SVC. Because this syndrome is usually caused by bronchogenic cancer, it is generally considered an oncologic emergency rather than a vascular emergency. *Varicosities- A varicose vein is a vein in which blood has pooled, producing distended, tortuous, and palpable vessels. Veins are thin-walled, highly distensible vessels with valves to prevent backflow and pooling of blood. Varicose veins typically involve the saphenous veins of the leg and are caused by (1) trauma to the saphenous veins that damages one or more valves or (2) gradual venous distention caused by the action of gravity on blood in the legs. Circulation to the extremities can become so sluggish that the metabolic demands of the cells to obtain oxygen and nutrients and to remove wastes are barely met. Chronic venous insufficiency (CVI) is inadequate venous return over a long period. Venous hypertension, circulatory stasis, and tissue hypoxia cause an inflammatory reaction in vessels and tissue leading to fibrosclerotic remodeling of the skin and then to ulceration. Any trauma or pressure can therefore lower the oxygen supply and cause cell death and necrosis (venous stasis ulcers) A thrombus is a clot that remains attached to a vascular wall. An embolus is a mobile aggregate of a variety of substances that occludes the vasculature. Sources of emboli include clots, air, amniotic fluid, bacteria, fat, and foreign matter. These emboli cause ischemia and necrosis when a vessel is totally blocked. The most common source of arterial thrombotic emboli is the heart as a result of mitral and aortic valvular disease and atrial fibrillation, followed by myxomas. Tissues affected include the lower extremities, the brain, and the heart. Emboli to the central organs cause tissue death in lungs, kidneys, and mesentery. Atherosclerotic plaque progression can be gradual and cause stable angina pectoris, which is predictable chest pain caused by myocardial ischemia in response to increased demand (e.g., exercise) without infarction. Atherosclerosis is a form of arteriosclerosis characterized by thickening and hardening of the vessel wall. It is caused by the accumulation of lipid-laden macrophages within the arterial wall, which leads to the formation of a lesion called a plaque. Atherosclerosis is not a single disease entity but rather a pathologic process that can affect vascular systems throughout the body, resulting in ischemic syndromes that can vary widely in their severity and clinical manifestations. Vasospastic disease: Thromboangiitis obliterans (Buerger disease) is characterized by the formation of thrombi filled with inflammatory and immune cells accompanying vasospasm. Over time, there thrombi become organized and fibrotic and result in permanent occlusion and obliteration of portions of small- and medium-sized arteries in the feet and sometimes in the hands.

Describe the difference between the two major types of nociceptors.

*A-delta (Aδ) fibers and C fibers. Aδ fibers are larger myelinated fibers that rapidly transmit sharp, well- localized "fast" pain sensations such as a burn or pinprick to the skin. Activation of these fibers causes a spinal reflex withdrawal of the affected body part from the stimulus, before a pain sensation is perceived. *C fibers are the most numerous, are smaller and unmyelinated, and are located in muscle, tendons, body organs, and in the skin. They slowly transmit dull, aching, or burning sensations that are poorly localized and often constant

Describe the pathophysiology, symptoms, and evaluation for the pericardial disorders.

*Acute Pericarditis is acute inflammation of the pericardium. The etiology of acute pericarditis is most often idiopathic or caused by viral infection by coxsackie, influenza, hepatitis, measles, mumps, or varicella viruses. It also is the most common cardiovascular complication of human immunodeficiency virus (HIV) infection. Other causes include myocardial infarction, trauma, neoplasm, surgery, uremia, bacterial infection (especially tuberculosis), connective tissue disease (especially systemic lupus erythematosus and rheumatoid arthritis), or radiation therapy. The pericardial membranes become inflamed and roughened, and a pericardial effusion may develop that can be serous, purulent, or fibrinous Symptoms may follow several days of fever and usually begin with the sudden onset of severe retrosternal chest pain that worsens with respiratory movements and when assuming a recumbent position. The pain may radiate to the back as a result of irritation of the phrenic nerve (innervates the trapezius muscles) as it traverses the pericardium. Individuals with acute pericarditis also report dysphagia, restlessness, irritability, anxiety, weakness, and malaise. Physical examination often discloses low-grade fever (<38° C [<100.4° F]) and sinus tachycardia. A friction rub—a scratchy, grating sound—may be heard at the cardiac apex and left sternal border and is highly suggestive of pericarditis. Acute pericarditis requires at least two of the following four criteria for diagnosis: (1) chest pain characteristics of pericarditis, (2) pericardial rub, (3) characteristic electrocardiographic (ECG) changes, and (4) new or worsening pericardial effusion. Treatment for uncomplicated acute pericarditis consists of relieving symptoms and includes administration of anti-inflammatory agents, such as salicylates and nonsteroidal anti-inflammatory drugs, and colchicine. *Pericardial Effusion Pericardial effusion is the accumulation of fluid in the pericardial cavity and can occur in all forms of pericarditis. Most are idiopathic (20%) but other causes, such as neoplasm and infection, must be considered.100 Analysis of the fluid obtained through pericardiocentesis allows for identification of the likely source of the fluid.102 The fluid may be a transudate, such as the serous effusion that develops with left heart failure, overhydration, or hypoproteinemia. An important clinical finding is pulsus paradoxus, in which arterial blood pressure during expiration exceeds arterial pressure during inspiration by more than 10 mm Hg.Other clinical manifestations of pericardial effusion are distant or muffled heart sounds, poorly palpable apical pulse, dyspnea on exertion, and dull chest pain. A chest x-ray film may disclose a "water-bottle configuration" of the cardiac silhouette. Treatment of pericardial effusion or tamponade generally consists of pericardiocentesis (aspiration of excessive pericardial fluid) and treatment of the underlying condition. Persistent pain may be treated with analgesics, anti- inflammatory medications, or steroids. Surgery may be required if the underlying cause of tamponade is trauma or aneurysm. A pericardial "window" may be surgically created to prevent tamponade *Constrictive Pericarditis Constrictive pericarditis, or restrictive pericarditis (chronic pericarditis), was synonymous with tuberculosis years ago, and tuberculosis continues to be an important cause of pericarditis in immunocompromised individuals. In constrictive pericarditis, fibrous scarring with occasional calcification of the pericardium causes the visceral and parietal pericardial layers to adhere, obliterating the pericardial cavity. The fibrotic lesions encase the heart in a rigid shell . Like tamponade, constrictive pericarditis compresses the heart and eventually reduces cardiac output. Unlike tamponade, however, constrictive pericarditis always develops gradually. Symptoms tend to be exercise intolerance, dyspnea on exertion, fatigue, and anorexia. Clinical assessment shows edema, distention of the jugular vein, hepatic congestion, and systemic hypotension. Restricted ventricular filling may cause a pericardial knock (early diastolic sound). Initial treatment for constrictive pericarditis consists of restriction of dietary sodium intake and administration of diuretics to improve cardiac output. Management also may include use of anti-inflammatory drugs and treatment of any underlying disorder. If these modalities are unsuccessful, surgical excision of the restrictive pericardium is indicated (pericardial decortication)

Discuss childhood diarrhea.

*Acute diarrhea in infants and children is three or more watery or loose stools in 24 hours; it is commonly caused by viral or bacterial enterocolitis. *Chronic diarrhea (diarrhea persisting longer than 4 weeks) can be caused by a wide variety of underlying conditions and often leads to growth failure and slow development.

Distinguish between acute and chronic mesenteric arterial insufficiencies.

*Acute mesenteric arterial insufficiency results in a significant reduction in mucosal blood flow to the large and small intestines and can be acute or chronic. *Chronic mesenteric ischemia is rare but can develop with atherosclerotic stenosis or occlusion or secondary to congestive heart failure, acute myocardial infarction, hemorrhage, thrombus formation, or any condition that decreases arterial blood flow.

Differentiate between acute and chronic pain.

*Acute pain (nociceptive pain) is a normal protective mechanism that alerts the individual to a condition or experience that is immediately harmful to the body and mobilizes the individual to take prompt action to relieve it. Acute pain is transient, usually lasting seconds to days, sometimes up to 3 months. It begins suddenly and is relieved after the chemical mediators that stimulate pain receptors are removed. Stimulation of the autonomic nervous system results in physical manifestations including increased heart rate, hypertension, diaphoresis, and dilated pupils. Anxiety related to the pain experience, including its cause, treatment, and prognosis, is common as is the hope of recovery and expectation of limited duration. *Chronic or persistent pain has been defined as lasting for more than 3 to 6 months and is pain lasting well beyond the expected normal healing time. It varies with type of injury. Chronic or persistent pain serves no purpose and is poorly understood and causes suffering. It often appears to be out of proportion to any observable tissue injury. It may be ongoing (e.g., low back pain) or intermittent (e.g., migraine headaches). Changes in the peripheral and central nervous systems that cause dysregulation of nociception and pain modulation processes (peripheral and central sensitization) are thought to lead to chronic pain Neuroimaging studies have demonstrated brain changes in individuals with chronic pain, which may lead to cognitive deficits and decreased ability to cope with pain. These negative manifestations of chronic pain are thought to be due, in part, to the stress of coping with continuous pain and may be reversible when pain is controlled. Because it is not yet possible to predict when acute pain will develop into chronic pain, early treatment of acute pain is encouraged. Physiologic responses to intermittent chronic pain are similar to those for acute pain, whereas persistent pain allows for physiologic adaptation, producing normal heart rate and blood pressure. This leads many to mistakenly conclude that people with chronic pain are malingering because they do not appear to be in pain. As chronic pain progresses, certain behavioral and psychologic changes often emerge, including depression, difficulty eating and sleeping, preoccupation with the pain, and avoidance of pain-provoking stimuli. The desire to relieve pain and the need to hide it become conflicting drives for those with chronic pain, who fear being labeled complainers. Chronic pain is perceived as meaningless and is often associated with a sense of hopelessness as more time elapses and no cure seems possible.

Describe the pathogenesis of pancreatitis.

*Acute pancreatitis (pancreatic inflammation) is a serious but relatively rare disorder. Pancreatic duct obstruction and injury permits leakage of digestive enzymes into pancreatic tissue, where they become activated and begin the process of autodigestion, inflammation, and destruction of tissues. Release of pancreatic enzymes into the bloodstream or abdominal cavity causes damage to other organs. * Chronic pancreatitis results from structural or functional impairment of the pancreas. It causes recurrent abdominal pain and digestive disorders.

Describe the clinical manifestations and potential treatments for aortic and pulmonic stenosis.

*Aortic stenosis (AS) is a narrowing or stricture of the left ventricular outlet, causing resistance of blood flow from the left ventricle into the aorta. Manifestations:Infants with significant AS demonstrate signs of decreased cardiac output with faint pulses, hypotension, tachycardia, and poor feeding. A loud, harsh systolic ejection murmur is expected. Older children also may have complaints of exercise intolerance and, rarely, chest pain. Children are at risk for bacterial endocarditis, although prophylaxis with antibiotics is no longer routinely recommended . Aortic stenosis, when severe, also can be complicated by coronary insufficiency, ventricular dysfunction, and, rarely, sudden death. Potential treatments:Treatment of severe valvular AS varies, with nonsurgical palliation the initial treatment of choice by many interventional cardiologists. Dilation of the stenotic valve with balloon angioplasty, which is performed in the cardiac catheterization laboratory, still carries a high morbidity and mortality in the critically ill neonate; however, in older infants and children it compares favorably with surgical valvotomy. Balloon angioplasty is, however, associated with the risk of aortic regurgitation (insufficiency). Children undergoing this procedure almost always require surgical intervention at some time to relieve recurrent narrowing or worsening regurgitation. *Pulmonic stenosis (PS) is a narrowing or stricture of the pulmonary valve that causes resistance to blood flow from the right ventricle to the pulmonary artery. Manifestation:Most infants are asymptomatic if the PS is mild to moderate. Newborns with severe PS or pulmonary atresia will be cyanotic (from a right-to-left shunt through an atrial septal defect [ASD]) and may have signs of decreased cardiac output. A harsh systolic murmur is expected with PS. Pulmonary atresia produces a continuous murmur. Treatment:The treatment of choice for infants with moderate to severe pulmonary stenosis is balloon angioplasty (see Figure 25-5, B). A catheter with a special balloon device is used to dilate the area of narrowing. Multiple studies have proven the effectiveness and safety of balloon angioplasty in reducing the pressure gradient across the pulmonic valve. In rare cases, surgical valvotomy may be required. Pulmonary blood flood is supported with prostaglandin E1 infusion to maintain the patency of the ductus arteriosus in cases of pulmonary atresia with right ventricle-dependent coronary circulation in the neonatal period until surgery is performed to supply pulmonary blood flow. Both balloon dilation and surgical valvotomy leave the pulmonary valve incompetent (insufficient); however, most children are usually able to tolerate pulmonary valve incompetence and are asymptomatic. Long-term problems with restenosis are rare for uncomplicated PS . However, clinically significant valve incompetence that results in right ventricle dilation and dysfunction may occur, requiring surgical intervention.

Describe the clinical manifestations and potential treatments for atrial and ventricular septal defects.

*Atrial Septal Defect Clinical manifestations: Children with an ASD are usually asymptomatic. Infants with a large ASD may, in rare cases, develop pulmonary overcirculation and slow growth. Some older children and adults will experience shortness of breath with activity as the right ventricle becomes less compliant with age. Pulmonary hypertension and stroke are associated rare complications. A systolic ejection murmur and a widely split second heart sound are the expected findings on physical examination. Potential treatments: The ASD may be closed surgically with primary repair (sutured closed) or with a patch (pericardium or Dacron). Surgical repair involves open-heart surgery with cardiopulmonary bypass. Catheterization device closure offers a less invasive alternative for children with an ASD that meets anatomic and size criteria. All options have low morbidity and mortality. Atrial dysrhythmias persist in about 5% to 10% of individuals in both groups after closure. *Ventricular Septal Defect Clinical manifestations: Depending on the size, location, and degree of shunting and pulmonary vascular resistance, children may have no symptoms or have clinical effects from excessive pulmonary blood flow. In the infant, excessive pulmonary blood flow from left-to- right shunting causes dyspnea and tachypnea symptoms, commonly referred to as heart failure (HF), even though the heart muscle functions well with a VSD. A holosystolic (pansystolic) murmur is expected.If the degree of shunting is significant and not corrected, the child is at risk for developing pulmonary hypertension. Irreversible pulmonary hypertension can result in Eisenmenger syndrome, a condition in which shunting of blood is reversed because of high pulmonary pressure and resistance (right-to-left shunt with cyanosis). Treatment: Cardiac catheterization may be needed to calculate the degree of shunting and to directly measure the pressures in the heart. Smaller VSDs require minimal treatment and may close completely or become small enough that surgical closure is not required. If the infant has severe HF or failure to thrive that is unmanageable with medical therapy, early surgical repair is performed. Surgical repair involves open-heart surgery with cardiopulmonary bypass. The opening is either sutured closed (primary) or covered with a patch (pericardium or Dacron). Nonsurgical device closure is available but only under restricted conditions.Endocarditis prophylaxis is only recommended for 6 months after surgical or device closure and indefinitely with a residual VSD after patch closure.

Discuss the four unique characteristics of the myocardial cells and conduction system: automaticity, rhythmicity, conductivity, and contractility.

*Automaticity, or the property of generating spontaneous depolarization to threshold, enables the SA and AV nodes to generate cardiac action potentials without any external stimulus *Rhythmicity is the regular generation of an action potential by the heart's conduction system. *Contractility is the potential for myocardial fiber shortening during systole. It is determined by the amount of stretch during diastole (i.e., preload) and by sympathetic stimulation of the ventricles.

Discuss the causation, treatment options, and prognosis for biliary cirrhosis.

*Biliary cirrhosis differs from alcoholic cirrhosis in that the damage and inflammation leading to cirrhosis begin in bile canaliculi and bile ducts, rather than in the hepatocytes. -Primary biliary cirrhosis is a chronic, autoimmune, cholestatic liver disease. It is caused by autoimmune T-lymphocyte and highly specific antimitochondrial antibody destruction of the small intrahepatic bile ducts and primarily affects middle-aged women. - Treatment with ursodeoxycholic acid slows disease progression and pruritus may be relieved by cholestyramine, which binds bile salts in the intestine. Liver transplant is highly effective. *Secondary biliary cirrhosis is caused by prolonged partial or complete obstruction of the common bile duct or branches by gallstones, tumors, fibrotic strictures, or chronic pancreatitis; biliary atresia and cystic fibrosis are causative in children. Necrotic areas develop and lead to proliferation and inflammation of portal ducts, producing edema, fibrosis, and cirrhosis if not treated. Surgery or endoscopy relieves obstruction, prolongs survival, and diminishes or resolves symptoms.

Distinguish between the pleural abnormalities of bronchiectasis, bronchiolitis, and bronchiolitis obliterans.

*Bronchiectasis Persistant abnormal dilation of bronchi. In adults it usually occurs in conjuction with other respiratory conditions that cause chronic inflammation of the bronchial wall. Symptoms: chronic productive cough that may date back to a childhood illness or infection. This is commonly associated with recurrent lower respiratory infections & large amount of foul-smelling spit. *Bronchiolitis -Inflammatory obstruction of the small airways. -Most common in children. -Occurs in adults with chronic bronchitis, in association with a viral infection, or with inhalation of toxic gases. Also a serious complication of stem cell and lung transplantation and can progress to bronchiolitis obliterans. Presents with a rapid ventilatory rate; marked use of accessory muscles; low grade fever; dry, nonproductive cough; and hyperinflated chest. A decrease in the ventilation-perfusion ratio results in hypoxemia. *Bronchiolitis obliterans A fibrotic process that occludes airways and causes permanent scarring of the lungs.

Identify and describe the different types of shock.

*Cardiogenic -Heart not pumping effectively *Hypovolemic Volume Loss (V, D, dehydration) Hemorrhagic (Blood loss) *Distributive Septic Neurogenic Anaphylactic *Obstructive Major obstruction of blood flow (NOT the Heart itself) -Shock is a widespread impairment of cellular metabolism involving positive feedback loops that places the individual on a downward physiologic spiral leading to multiple organ dysfunction syndrome. - Multiple organ dysfunction syndrome can develop from all types of shock. - The final common pathway in all types of shock is impaired cellular metabolism —cells switch from aerobic to anaerobic metabolism. Energy stores drop, and cellular mechanisms relative to membrane permeability, action potentials, and lysozyme release fail. - Cardiogenic shock is decreased cardiac output, tissue hypoxia, and the presence of adequate intravascular volume. - Hypovolemic shock is caused by loss of blood or fluid in large amounts. The use of compensatory mechanisms may be vigorous, but tissue perfusion ultimately decreases and results in impaired cellular metabolism. -Neurogenic shock results from massive vasodilation, causing a relative hypovolemia even though cardiac output may be high, and leads to impaired cellular metabolism. - Anaphylactic shock is caused by physiologic recognition of a foreign substance. The inflammatory response is triggered, and a massive vasodilation with fluid shift into the interstitium follows. The relative hypovolemia leads to impaired cellular metabolism. -Septic shock begins with impaired cellular metabolism caused by uncontrolled septicemia. The infecting agent triggers the inflammatory and immune responses. This inflammatory response is accompanied by widespread changes in tissue and cellular function.

Compare cholecystitis with cholelithiasis.

*Cholelithiasis (the formation of gallstones) is a common disorder of the gallbladder. Gallstones form in the bile as a result of the aggregation of cholesterol crystals (cholesterol stones) or precipitates of unconjugated bilirubin (pigmented stones). Gallstones that fill the gallbladder or obstruct the cystic or common bile duct cause abdominal pain and jaundice. *Cholecystitis is an acute or chronic inflammation of the gallbladder usually associated with obstruction of the cystic duct by gallstones.

Briefly explain what is meant by cirrhosis of the liver, and describe the progression of alcoholic fatty liver disease to alcoholic cirrhosis.

*Cirrhosis is an inflammatory disease of the liver that causes disorganization of lobular structure, fibrosis, and nodular regeneration. Cirrhosis can result from hepatitis or exposure to toxins, such as acetaldehyde (a product of alcohol metabolism). The disease causes progressive irreversible liver damage, usually over a period of years. -Alcoholic liver disease includes fatty liver and alcoholic steatohepatitis from accumulations of fat in the liver and is a precursor to alcoholic cirrhosis. -Alcoholic cirrhosis impairs the hepatocytes' ability to oxidize fatty acids, synthesize enzymes and proteins, degrade hormones, and clear portal blood of ammonia and toxins. The inflammatory response includes excessive collagen formation, fibrosis, and scarring, which obstruct bile canaliculi and sinusoids. Bile obstruction causes jaundice. Vascular obstruction causes portal hypertension, shunting, and varices.

Describe the pathophysiology and treatment of cleft lip and palate.

*Cleft lip is caused by the incomplete fusion of the nasomedial or intermaxillary process beginning the fourth week of embryonic development, a period of rapid development. The cleft causes structures of the face and mouth to develop without the normal restraints of encir cling lip muscles. The nature and extent of the cleft, the infant's condition, and the method of surgical correction proposed determine the course of treatment. Surgical correction is planned at about the third to sixth month and may be performed in stages *Cleft palate is often associated with cleft lip but may occur without it. The fissure may affect only the uvula and soft palate or may extend forward to the nostril and involve the hard palate and the maxillary alveolar ridge. It may be unilateral or bilateral, with the cleft occupying the midline posteriorly and as far forward as the alveolar process, where it deviates to the involved side.

Differentiate between conductive and sensorineural hearing losses.

*Conductive hearing loss occurs when a change in the outer or middle ear impairs conduction of sound from the outer to the inner ear. Conditions that commonly cause a conductive hearing loss include impacted cerumen, foreign bodies lodged in the ear canal, benign tumors of the middle ear, carcinoma of the external auditory canal or middle ear, eustachian tube dysfunction, otitis media, acute viral otitis media, chronic suppurative otitis media, cholesteatoma (accumulation of keratinized epithelium), and otosclerosis. Symptoms of conductive hearing loss include diminished hearing and soft speaking voice. The voice is soft because often the individual hears his or her voice, conducted by bone, as loud. *Sensorineural hearing loss is caused by impairment of the organ of Corti or its central connections. The loss may occur gradually or suddenly. Conditions causing sensorineural loss include congenital and hereditary factors, noise exposure, aging, Ménière disease, ototoxicity, systemic disease (syphilis, Paget disease, collagen diseases, diabetes mellitus), neoplasms, and autoimmune processes. Congenital and neonatal sensorineural hearing loss may be caused by maternal rubella, ototoxic drugs, prematurity, traumatic delivery, erythroblastosis fetalis, bacterial meningitis, and congenital hereditary malfunction. Diagnosis often is made when delayed speech development is noted. Sudden onset bilateral sensorineural hearing loss is a medical emergency. Presbycusis is the most common form of sensorineural hearing loss in elderly people. Its cause may be atrophy of the basal end of the organ of Corti, loss of auditory receptors, changes in vascularity, or stiffening of the basilar membranes. Drug ototoxicities (drugs that cause destruction of auditory function) have been observed after exposure to various chemicals; for example, antibiotics such as streptomycin, neomycin, gentamicin, and vancomycin; diuretics such as ethacrynic acid and furosemide; and chemicals such as salicylate, quinine, carbon monoxide, nitrogen mustard, arsenic, mercury, gold, tobacco, and alcohol. In most instances, the drugs and chemicals listed initially cause tinnitus (ringing in the ear), followed by a progressive high-tone sensorineural hearing loss that is permanent *Conductive hearing loss occurs when sound waves cannot be conducted through the middle ear. * Sensorineural hearing loss develops with impairment of the organ of Corti or its central connections. Presbycusis is the most common form of sensorineural hearing loss in elderly people.

Distinguish between diverticular disease and appendicitis.

*Diverticula are outpouchings of colonic mucosa through the muscle layers of the colon wall. Diverticulosis is the presence of these outpouchings; diverticulitis is inflammation of the diverticula. *Appendicitis is the most common surgical emergency of the abdomen. Obstruction of the lumen leads to increased pressure, ischemia, and inflammation of the appendix. Without surgical resection, inflammation may progress to gangrene, perforation, and peritonitis.

Define dyspnea, orthopnea, hemoptysis, and the breathing patterns eupnea, Kussmaul, and Cheyne-Stokes.

*Dyspnea is a subjective experience of breathing discomfort that is comprised of qualitatively distinct sensations that vary in intensity. Dyspnea is an individual experience and derives from interactions among multiple physiologic, psychologic, social, and environmental factors, and it may induce secondary physiologic and behavioral responses.1 It is often described as breathlessness, air hunger, shortness of breath, labored breathing, and preoccupation with breathing. Dyspnea may be the result of pulmonary disease, or many other conditions such as pain, heart disease, trauma, and psychogenic disorders. *Orthopnea *Hemoptysis-Hemoptysis is the coughing up of blood or bloody secretions. This is sometimes confused with hematemesis, which is the vomiting of blood. Blood produced with coughing is usually bright red, has an alkaline pH, and is mixed with frothy sputum. Blood that is vomited is dark, has an acidic pH, and is mixed with food particles. Hemoptysis usually indicates infection or inflammation that damages the bronchi (bronchitis, bronchiectasis) or the lung parenchyma (pneumonia, tuberculosis, lung abscess). Other causes include cancer, pulmonary infarction, or pulmonary venous stenosis. The amount and duration of bleeding provide important clues about its source. Bronchoscopy, combined with chest computed tomography (CT), is used to confirm the site of bleeding. -The breathing patterns *Eupnea-Normal breathing (eupnea) is rhythmic and effortless. The resting ventilatory rate is 8 to 16 breaths per minute, and tidal volume ranges from 400 to 800 ml. A short expiratory pause occurs with each breath, and the individual takes an occasional deeper breath, or sighs. Sigh breaths, which help to maintain normal lung function, are usually 1.5 to 2 times the normal tidal volume and occur approximately 10 to 12 times per hour. *Kussmaul-Kussmaul respiration (hyperpnea), which is characterized by a slightly increased ventilatory rate, very large tidal volumes, and no expiratory pause. The rate, depth, regularity, and effort of breathing undergo characteristic alterations in response to physiologic and pathophysiologic conditions. Patterns of breathing automatically adjust to minimize the work of respiratory muscles. Strenuous exercise or metabolic acidosis induces hyperpnea. *Cheyne-Stokes-Cheyne-Stokes respirations are characterized by alternating periods of deep and shallow breathing. Apnea lasting from 15 to 60 seconds is followed by ventilations that increase in volume until a peak is reached; then ventilation (tidal volume) decreases again to apnea. Cheyne-Stokes respirations result from any condition that reduces blood flow to the brainstem, which in turn slows impulses sending information to the respiratory centers of the brainstem. Neurologic impairment above the brainstem is also a contributing factor.

Discuss the effects of the three major alterations in body temperature: fever, hyperthermia and hypothermia.

*Fever involves the "resetting of the hypothalamic thermostat" to a higher level. When the fever breaks, the set point returns to normal. *Fever production aids responses to infectious processes. Higher temperatures kill many microorganisms, promote immune responses, and decrease serum levels of iron, zinc, and copper, which are needed for bacterial replication. *Fever of unknown origin is a body temperature greater than 38.3° C (101° F) for longer than 3 weeks that remains undiagnosed after 3 days of investigation. *Hyperthermia (marked warming of core temperature) can produce nerve damage, coagulation of cell proteins, and death. Forms of accidental hyperthermia include heat cramps, heat exhaustion, heat stroke, and malignant hyperthermia. Heat stroke and malignant hyperthermia are potentially lethal. *Hypothermia (marked cooling of core temperature) slows the rate of chemical reaction (tissue metabolism), increases the viscosity of the blood, slows blood flow through the microcirculation, facilitates blood coagulation, and stimulates profound vasoconstriction. Hypothermia may be accidental or therapeutic. Fever (febrile response) is a temporary resetting of the hypothalamic thermostat to a higher level in response to exogenous or endogenous pyrogens. Exogenous pyrogens (endotoxins produced by pathogens; see Chapter 8) stimulate the release of endogenous pyrogens from phagocytic cells, including tumor necrosis factor- alpha (TNF-α), interleukin-1 (IL-1), interleukin-6 (IL-6), and interferon (IFN). These pyrogens raise the thermal set point by inducing the hypothalamic synthesis of prostaglandin E2 (PGE2). This produces an integrated response that raises body temperature through an increase in heat production and conservation. The individual feels colder, dresses more warmly, decreases body surface area by curling up and may go to bed in an effort to get warm. Body temperature is maintained at the new level until the fever "breaks," when the set point begins to return to normal with decreased heat production and increased heat reduction mechanisms. The individual feels very warm, dons cooler clothes, throws off the covers, and stretches out. Once the body has returned to a normal temperature the individual feels more comfortable and the hypothalamus adjusts thermoregulatory mechanisms to maintain the new temperature. 1. Raising of body temperature kills many microorganisms and adversely affects their growth and replication. 2. Higher body temperatures decrease serum levels of iron, zinc, and copper— minerals needed for bacterial replication. 3. Increased temperature causes lysosomal breakdown and autodestruction of cells, preventing viral replication in infected cells. 4. Heat increases lymphocytic transformation and motility of polymorphonuclear neutrophils, facilitating the immune response. 5. Phagocytosis is enhanced, and production of antiviral interferon is augmented. *Hyperthermia is elevation of the body temperature without an increase in the hypothalamic set point. Hyperthermia can produce nerve damage, coagulation of cell proteins, and death. At 41° C (105.8° F), nerve damage produces convulsions in the adult. Death results at 43° C (109.4° F). Hyperthermia may be therapeutic, accidental, or associated with stroke or head trauma. Prevention of hyperthermia in stroke and head trauma assists in limiting brain injury. Therapeutic hyperthermia is a form of local, regional, or whole-body hyperthermia used to destroy pathologic microorganisms or tumor cells by facilitating the host's natural immune process or tumor blood flow. The forms of accidental hyperthermia are summarized as follows: 1. Heat cramps—severe, spasmodic cramps in the abdomen and extremities that follow prolonged sweating and associated sodium loss. Usually occur in those not accustomed to heat or those performing strenuous work in very warm climates. Fever, rapid pulse rate, and increased blood pressure accompany the cramps. 2. Heat exhaustion—results from prolonged high core or environmental temperatures, which cause profound vasodilation and profuse sweating, leading to dehydration, decreased plasma volumes, hypotension, decreased cardiac output, and tachycardia. Symptoms include weakness, dizziness, confusion, nausea, and fainting. 3. Heat stroke—a potentially lethal result of an overstressed thermoregulatory center. Heat stroke can be caused by exertion, by overexposure to environmental heat, or from impaired physiologic mechanisms for heat loss. With very high core temperatures (>40° C; 104° F), the regulatory center ceases to function and the body's heat loss mechanisms fail. Symptoms include high core temperature, absence of sweating, rapid pulse rate, confusion, agitation, and coma. Complications include cerebral edema, degeneration of the CNS, swollen dendrites, renal tubular necrosis, and hepatic failure with delirium, coma, and eventually death if treatment is not under taken. 4. Malignant hyperthermia—a potentially lethal hypermetabolic complication of a rare inherited muscle disorder that may be triggered by inhaled anesthetics and depolarizing muscle relaxants. The syndrome involves altered calcium function in muscle cells with hypermetabolism, uncoordinated muscle contractions, increased muscle work, increased oxygen consumption, and a raised level of lactic acid production. Acidosis develops, and body temperature rises, with resulting tachycardia and cardiac dysrhythmias, hypotension, decreased cardiac output, and cardiac arrest. Signs resemble those of coma—unconsciousness, absent reflexes, fixed pupils, apnea, and occasionally a flat electroencephalogram. Oliguria and anuria are common. It is most common in children and adolescents. *Hypothermia (core body temperature less than 35° C [95° F]) produces depression of the central nervous and respiratory systems, vasoconstriction, alterations in microcirculation and coagulation, and ischemic tissue damage. Hypothermia may be accidental or therapeutic. Most tissues can tolerate low temperatures in controlled situations, such as surgery. However, in severe hypothermia, ice crystals form on the inside of the cell, causing cells to rupture and die. Tissue hypothermia slows cell metabolism, increases the blood viscosity, slows microcirculatory blood flow, facilitates blood coagulation, and stimulates profound vasoconstriction

Decribe the pathophysiology and potential complications related to gastroesophageal reflux.

*GERD is influenced by genetic, environmental, anatomic, hormonal, and neurogenic factors. Although transient lower esophageal sphincter relaxations (TLESRs) are the most common pathophysiologic cause of GER, inadequate adaptation of sphincter tone to changes in abdominal pressure also may be implicated. *Factors that maintain lower esophageal sphincter integrity in children include the location of the gastroesophageal junction in a high-pressure zone within the abdomen, mucosal gathering within the sphincter, and the angle at which the esophagus is inserted into the stomach. Reflux persists if any one of these pressure- maintaining factors is altered. Other mediators of GER are esophageal peristalsis or clearance, mucosal resistance that mediates the noxiousness of the refluxate, and delayed gastric emptying. *Esophageal complications of GERD can be significant, such as esophagitis, hemorrhage, stricture, Barrett esophagus (metaplasia) (see Chapter 36), and, rarely, adenocarcinoma.

Describe the function and location of the components of the cardiac conduction system.

*Group of specialized, highly exciteable cells that give the heart its rhythmicity The conduction system of the heart generates and transmits electrical impulses (cardiac action potentials) that stimulate systolic contractions. The autonomic nerves (sympathetic and parasympathetic fibers) can adjust heart rate and force of contraction, but they do not originate the heartbeat. *SA Node *AV Node *AV Bundle (Bundle of His) *Purkinje Fibers Specialized cardiac muscle cells in the heart wall rapidly conduct an electrical impulse throughout the myocardium. The signal is initiated by the sinoatrial (SA) node (pacemaker) and spreads through the atrial myocardium to the atrioventricular (AV) node. The AV node then initiates a signal that is conducted through the ventricular myocardium by way of the atrioventricular bundle (of His) and Purkinje fibers.

Define diagnostic parameters for prediabetes.

*HbA1C, hemoglobin A1C or glycosylated hemoglobin; *OGTT, oral glucose tolerance testing; PG, plasma glucose. - Impaired fasting glucose (FPG 100 - 125 mg/dL) - Impaired glucose tolerance (2 hour plasma glucose 140 - 199 mg/dL after 75g OGTT) - HgbA1C 5.7 - 6.4%

Differentiate hypoglycemia, diabetic ketoacidosis, and hyperglycemic nonketotic syndromes.

*Hypoglycemia in diabetes is a complication related to insulin treatment. *Diabetic ketoacidosis (DKA) develops when there is an absolute or relative deficiency of insulin and an increase in the insulin counterregulatory hormones of catecholamines—cortisol, glucagon, and growth hormone. DKA presents with hyperglycemia, acidosis, and ketonuria. *Hyperosmolar hyperglycemic nonketotic syndrome is pathophysiologically similar to diabetic ketoacidosis, although levels of free fatty acids are lower in hyperosmolar nonacidotic diabetes and lack of ketosis indicates some level of insulin action. Severe dehydration and electrolyte imbalance are present.

Describe the acute complications of diabetes mellitus with a focus on differential detection and treatment.

*Hypoglycemia in diabetes is sometimes called insulin shock or insulin reaction. Individuals with type 2 diabetes are at less risk for hypoglycemia than those with type 1 diabetes because they retain relatively intact glucose counterregulatory mechanisms. However, hypoglycemia does occur in type 2 diabetes when treatment involves insulin secretogogues (e.g., sulfonylureas) or exogenous insulin. Treatment requires immediate replacement of glucose either orally or intravenously. *Diabetic ketoacidosis (DKA) is a serious complication related to a deficiency of insulin and an increase in the levels of insulin counterregulatory hormones (catecholamines, cortisol, glucagon, growth hormone).It is characterized by hyperglycemia, acidosis, and ketonuria. Insulin normally stimulates lipogenesis and inhibits lipolysis, thus Older adults or very young individuals with type 2 diabetes, nondiabetic persons with predisposing factors, such as pancreatitis; individuals with undiagnosed diabetes preventing fat catabolism. DKA is managed with a combination of fluids, insulin, and electrolyte replacement. *Hyperosmolar hyperglycemic nonketotic syndrome (HHNKS) is an uncommon but significant complication of type 2 diabetes mellitus with a high overall mortality. It occurs more often in elderly individuals who have other comorbidities, including infections or cardiovascular or renal disease. HHNKS differs from DKA in the degree of insulin deficiency (which is more profound in DKA) and the degree of fluid deficiency (which is more marked in HHNKS). The clinical features of HHNKS include a very high serum glucose concentration and osmolarity and a near-normal serum bicarbonate level and pH. Glucose levels are considerably higher in HHNKS than in DKA because of volume depletion. Management includes fluid, insulin, and electrolyte replacement.

Describe the common congenital anomalies that occur within the renal and urologic systems.

*Hypospadias is a congenital condition in which the urethral meatus is located on the ventral side or undersurface of the penis. The meatus can be located anywhere on the glans, on the penile shaft, at the base of the penis, at the penoscrotal junction, or in the perineum (Figure 31-1). This is the most common anomaly of the penis; it occurs in about 1 in 300 infant boys.The cause of this condition is multifactorial and includes genetic, endocrine, and environmental factors. Advanced maternal age and low birth weight also have been implicated.7,8 Chordee (penile torsion) may accompany cases of hypospadias. In chordee, skin tethering and shortening of subcutaneous tissue cause the penis to bend or "bow ventrally" (Figure 31-2). Penile torsion is rotation of the penile shaft to either the right or the left. Partial absence of the foreskin and cryptorchidism (undescended testes; see Chapter 32) are associated with the anomaly. *Epispadias and exstrophy of the bladder are the same congenital defect expressed to differing degrees. In male epispadias, the urethral opening is on the dorsal surface of the penis. In females, a cleft along the ventral urethra usually extends to the bladder neck. The incidence of epispadias is about 9.25 per 100,000 in-hospital live births.1 This is seen predominantly in males. In boys, the urethral opening may be small and situated behind the glans (anterior epispadias), or a fissure may extend the entire length of the penis and into the bladder neck (posterior epispadias). Continence is determined in part by the location of the defect, with urinary incontinence rates of up to 75% in children with distal epispadias. Treatment is surgical reconstruction. Exstrophy of the bladder is a rare, extensive congenital anomaly of herniation of the bladder through the abdominal wall. The bony part of the pelvis remains open (Figure 31-3), and the posterior portion of the bladder mucosa is exposed through the abdominal opening and appears bright red. The incidence of bladder exstrophy in the United States is about 1.7 per 100,000 live births. 10 Studies vary widely concerning male versus female prevalence. Bladder Outlet Obstruction Congenital causes of bladder outlet obstruction are rare and include urethral valves and polyps. A urethral valve is a thin membrane of tissue that occludes the urethral lumen and obstructs urinary outflow in males. Most valves occur in the posterior urethra, although a few arise from the embryologically distinct anterior urethra. Urethral polyps are rare.14 The timing and presentation of these conditions depend on the degree of obstruction they cause. Severe obstruction may impair renal embryogenesis and lead to renal failure.15 Urethral valves or polyps are resected as soon as they are diagnosed. Ureteropelvic junction (UPJ) obstruction is a blockage of the tapered point where the renal pelvis transitions into the ureter. UPJ obstruction is the most common cause of hydronephrosis in neonates. An intrinsic malformation of smooth muscle or urothelial development produces obstruction in the majority of cases. Extrinsic compression abnormalities are less common.16 Secondary ureteropelvic junction obstruction is caused by kinking or secondary scarring in the presence of high- grade vesicoureteral reflux (see p. 775). There is an increased risk of vesicoureteral reflux in children with UPJ obstruction in the obstructed or contralateral kidney, or both; whether this represents a sequela of the embryonic defect leading to the UPJ defect is not known. Diagnosis of a UPJ obstruction can be made by ultrasound. Obstruction of the distal ureter (ureterovesical junction obstruction) causes dilation of the entire ureter, renal pelvis, and calyceal system. An ureterocele is a cystic dilation of the intravesical ureter. Open or endoscopic surgery to relieve an obstruction occurs if there is decline of renal drainage or function. Hypoplastic/Dysplastic Kidneys During embryologic development, the ureteric duct grows into the metanephric tissue, triggering the formation of the kidneys. If this growth does not occur, the kidney is absent—a condition called renal aplasia. A hypoplastic kidney is small with a decreased number of nephrons. These conditions may be unilateral or bilateral; the occurrence may be incidental or familial. Bilateral hypoplastic kidneys are a common cause of chronic renal failure in children.18 Segmental hypoplasia— the Ask-Upmark kidney—may be congenital or secondary to vesicoureteral reflux. Systemic hypertension is a common presentation. Renal dysplasia usually results from abnormal differentiation of the renal tissues; for example, primitive glomeruli and tubules, cysts, and nonrenal tissue (such as cartilage) are found in the dysplastic kidney. Dysplasia may be secondary to antenatal obstruction of the urinary tract from ureteroceles, posterior urethral valves, or prune-belly syndrome (congenital absence of abdominal muscles). Polycystic kidney disease (PKD) is an autosomal dominant disease (PDK1 or PDK2 gene) occurring in 1 of 1000 live births, or an autosomal recessive (PKHD1 gene) inherited disorder with an incidence of 1 in 20,000 to 1 in 40,000.20 Affected kidneys have multiple cysts that interfere with renal function. Autosomal dominant PKD (ADPKD) usually presents in late childhood or adulthood with the development of cysts. Defects in the formation of epithelial cells and their cilia result in cyst formation in all parts of the nephron. Cysts in other organs, including the liver, pancreas, and ovaries, may occur. Hypertension, aortic and intracranial aneurysms, and heart valve defects may develop. Autosomal recessive PKD (ARPKD) is often first suspected on a prenatal ultrasound. Epithelial hyperplasia and fluid secretion result in collecting duct cysts. Hepatic disease and hypertension typically accompany PKD. Clinical trials for various potential treatment modalities are ongoing. Renal agenesis (the absence of one or both kidneys) may be unilateral or bilateral, and may occur randomly or be hereditary. It may be an isolated entity or be associated with anomalies in other organs. Unilateral renal agenesis occurs in approximately 1 in 1000 live births. Males are more often affected, and it is usually the left kidney that is absent. The single remaining kidney is often completely normal so that the child can expect a normal, healthy life. By the time the child is several years old, the volume of this kidney may approach twice the normal size to compensate for the absence of a second kidney. In some instances, however, the single kidney is abnormally formed and associated with abnormalities of its collecting system. Because the child has a decreased number of nephrons, there is a risk of "hyperfiltration injury," increasing the chance of developing proteinuria, hypertension, and chronic kidney disease.22 Extrarenal congenital abnormalities of the urogenital, skeletal, cardiac, and other systems may coexist. Bilateral renal agenesis is a rare disorder incompatible with extrauterine life. Approximately 75% of affected children are males. Oligohydramnios (low amount of amniotic fluid) resulting from inadequate fetal urine production leads to underdeveloped lungs and Potter syndrome (wide-set eyes, parrot-beak nose, low- set ears, and receding chin). Approximately 40% of affected infants are stillborn. Infants with this condition rarely live more than 24 hours because of pulmonary insufficiency. Renal agenesis can be detected prenatally by ultrasound.

Describe the structural defect and pathophysiology associated with pyloric stenosis.

*Infantile hypertrophic pyloric stenosis (IHPS) is an acquired narrowing and distal obstruction of the pylorus and a common cause of postprandial vomiting. *Individual muscle fibers thicken, so the entire pyloric sphincter becomes enlarged and inflexible. The mucosal lining of the pyloric opening is folded and narrowed by the encroaching muscle. Because of the extra peristaltic effort necessary to force the gastric contents through the narrow pylorus, the muscle layers of the stomach may become hypertrophied as well. generally do not occur until the infant is 2 to 3 weeks; projectile vomiting is the outstanding sign, child will appear dehydrated with sunken fontanelles, inelastic skin, decreased urination, and always hungry despite frequent feedings, and an olive shaped mass will be felt by the parents or the physician during examination in the RUQ

Describe intussusception.

*Intussusception is the telescoping of a proximal segment of intestine into a distal segment, causing an obstruction. *It is the most common cause of small bowel obstruction in children *In intussusception, the ileum commonly telescopes into the cecum and part of the ascending colon by collapsing through the ileocecal valve, although intussusception can occur anywhere from the duodenum to the rectum. *The proximal portion of the intestine (the intussusceptum) collapses into the distal portion (the intussuscipiens) in the direction of peristaltic flow. *Unless the intussusception is treated, ischemia and necrosis ensue. -A 6-month-old male infant is brought to the ER after the sudden development of abdominal pain, irritability, and vomiting followed by passing of "currant jelly" stool. Ultrasound reveals intestinal obstruction in which the ileum collapsed through the ileocecal valve and invaginated into the large intestine. This type of obstruction is referred to as

Discuss the pathophysiology of Kawasaki disease in childhood.

*Kawasaki disease is an acute systemic vasculitis that also may result in the development of coronary artery aneurysms and thrombosis if untreated. Kawasaki disease progresses pathologically and clinically in the following stages. -In the early or acute phase, small capillaries, arterioles, and venules become inflamed, as does the heart itself. -In the subacute state, inflammation spreads to larger vessels and aneurysms of the coronary arteries may develop. -In the convalescent stage, medium-sized arteries begin the granulation process and may cause coronary artery thickening with increased risk for thrombosis. -After the convalescent stage, inflammation wanes with potential scarring of the affected vessels, calcification, and stenosis.

Explain the pathophysiology of the degenerative disorders of the spine.

*LOW BACK PAIN- Most cases of LBP are idiopathic or nonspecific, and no precise diagnosis is possible. Acute LBP is often associated with muscle or ligament strain and is more common in individuals younger than 50 years of age without a history of cancer. Common causes of chronic LBP include degenerative disk disease, spondylolysis, spondylolisthesis (vertebra slides forward or slips in relation to a vertebra below), spinal osteochondrosis, spinal stenosis, and lumbar disk herniation. Other causes include tension caused by tumors or disk prolapse, bursitis, synovitis, rising venous and tissue pressures (found in degenerative joint disease), abnormal bone pressures, spinal immobility, inflammation caused by infection (as in osteomyelitis), and pain referred from viscera or the posterior peritoneum. Systemic causes of LBP include bone diseases, such as osteoporosis or osteomalacia, and hyperparathyroidism. Anatomically, low back pain must originate from innervated structures, but deep pain is widely referred and varies. The nucleus pulposus has no intrinsic innervation, but when extruded or herniated through a prolapsed disk, it irritates the spinal nerve dural membranes and causes pain referred to the segmental area *Herniated Intervertebral Disk- In a herniated disk, the ligament and posterior capsule of the disk are usually torn, allowing the nucleus pulposus to extrude and compress the nerve root. The vascular supply may be compromised and cause inflammatory changes in the nerve root (radiculitis). Occasionally, the injury tears the entire disk loose, causing the disk capsule and nucleus pulposus to protrude onto the nerve root or compress the spinal cord. Multiple nerve root compression may be found at the L5-S1 level, where the cauda equina may be compressed, causing cauda equina syndrome ------------------------------- (Degenerative Joint Disease (DJD)) Degenerative disk disease (DDD) is common in individuals 30 years of age and older. It is, in part, a process of normal aging as a response to continuous vertical compression of the spine (axial loading). DDD includes a genetic component, involving genes that code the cartilage intermediate layer protein (CILP). The combination of environmental interactions and genetic predisposition increases susceptibility to lumbar disk disease by disrupting normal building and maintenance of cartilage. Causes include biochemical (e.g., inflammatory mediators) and biomechanical alterations (e.g., mechanical loading and compression) of the intervertebral disk tissue. For example, loss of disk proteoglycans and collagen with disk dehydration and loss of hydrostatic pressure alters disk structure and function. The annulus can tear and the disk can herniate, pinching nerves or placing strain on the spine. The pathologic findings in DDD include disk protrusion, spondylolysis and/or subluxation (spondylolisthesis), degeneration of vertebrae, and spinal stenosis. Lumbar disk disease causes one third of all back pain that affects 70% to 90% of adults at some point in their lives. However, only a small percentage of people with degenerative disk disease have any functional incapacity because of pain. *Spondylolysis is a structural defect (degeneration, fracture, or developmental defect) in the pars interarticularis of the vertebral arch (the joining of the vertebral body to the posterior structures). The lumbar spine at L5 is affected most often. Mechanical pressure may cause an anterior or posterior displacement of the deficient vertebra (spondylolisthesis). Heredity plays a significant role, and spondylolysis is associated with an increased incidence of other congenital spinal defects. Symptoms include lower back and lower limb pain. *Spondylolisthesis, an osseous defect of the pars interarticularis, allows a vertebra to slide anteriorly in relation to the vertebra below, commonly occurring at L5-S1. Spondylolisthesis is graded from 1 to 4 based on the percentage of slip that occurs. Grades 1 and 2 have symptoms of pain in the lower back and buttocks, muscle spasms in the lower back and legs, and tightened hamstrings. Conservative management includes exercise, rest, and back bracing. Vertebral slippage in grades 3 and 4 usually requires surgical decompression, stabilization, or both. Spinal stenosis. *Spinal stenosis is a narrowing of the spinal canal that causes pressure on the spinal nerves or cord and can be congenital or acquired (more common) and associated with trauma or arthritis. It is categorized by the area of the spine affected: cervical, thoracic, or lumbar. Acquired conditions include a bulging disk, facet hypertrophy, or a thick ossified posterior longitudinal ligament. Symptoms are related to the area of the spine affected and can produce pain; numbness; and tingling in the neck, hands, arms, or legs with weakness and difficulty walking. Surgical decompression is recommended for those with chronic symptoms and those who do not respond to medical management.

Identify the risk factors for atherosclerosis and the progression to myocardial infarction.

*Leading cause of Coronary Artery Disease (CAD) & Cardiovascular Disease (#1 cause of MI) Non Modifiable Risk Factors: Age, gender, family history. Modifiable risk factors: smoking, hypertension, diabetes, increased levels of low-density lipoprotein (LDL), decreased levels of high-density lipoprotein (HDL), and autoimmunity. Other "nontraditional" risk factors include increased serum markers for inflammation and thrombosis (such as high-sensitivity C-reactive protein [hs-CRP], troponin I, adipokines, infection, and air pollution). Atherosclerosis*Formation of "plaque" Caused by accumulation of LIPID-LADEN macrophages(Within the arterial wall)

Describe meconium ileus: note other intestinal obstructions or malformations.

*Meconium ileus (MI) is an intestinal obstruction in the neonatal period caused by meconium formed in utero that is abnormally thick and sticky, which leads to a partial or complete obstruction at the level of the terminal ileum. There are two forms of MI: simple and complex. Complex MI is a surgical emergency and there is usually an associated gastrointestinal pathology, such as bowel atresia, necrosis, or perforation. MI occurs in up to 20% of infants with cystic fibrosis, and is thought to result from abnormal mucus production in the intestine or impaired pancreatic enzymes, or both. *Meconium plug syndrome (MPS), also termed functional immaturity of the colon, is a transient disorder of the newborn colon characterized by delayed passage (>24 to 48 hours) of meconium and intestinal dilatation. *Meconium disease (MD) is often associated with severe prematurity and low birth weight. It results from a combination of extremely sticky meconium in the colon or terminal ileum and poor intestinal motility, resulting in mechanical bowel obstruction. In both MPS and MD, plugs of meconium are found in the distal ileum and proximal colon, resulting in obstruction of passage of meconium from the rectum. *Distal intestinal obstruction syndrome (DIOS), formerly called meconium ileus equivalent, is seen in about 7.4% of children and adults with cystic fibrosis. It is characterized by complete or incomplete intestinal obstruction of viscid fecal accumulation in the terminal ileum and proximal colon. *Idiopathic intestinal pseudo-obstruction is a disorder of impaired intestinal motility. The pseudo-obstruction is caused by nerve or peristaltic muscle dysfunction that affects the movement of food, fluid, or air through the intestine. Children present with abdominal swelling or bloating, crampy abdominal pain, nausea, vomiting, constipation, or diarrhea. *Anorectal malformations (ARMs) represent a spectrum of anomalies of the anus and rectum ARMs include anorectal stenosis, imperforate anus, anorectal atresia, and rectal atresia. Persistent cloaca is the most severe type of anorectal malformation and occurs exclusively in girls. The rectum, urethra, and vagina fail to develop separately; instead, they drain through a single, common channel onto the perineum. Approximately 40% of infants with anorectal malformations have other developmental anomalies (i.e., Down syndrome, Hirschsprung disease, and duodenal atresia).

Differentiate the motor and sensory pathways of the spinal cord.

*Motor Pathways Clinically relevant motor pathways are the lateral corticospinal and corticobulbar pyramidal tracts; and the extrapyramidal reticulospinal, vestibulospinal, and rubrospinal tracts. The corticospinal and corticobulbar pathways are essentially the same tract and consist of a two-neuron chain. The cell bodies (upper motor neurons) originate in and around the precentral gyrus; pass through the corona radiata of the cerebrum, the internal capsule, middle three fifths of the cerebral pedunculus, pons, and pyramid; and decussate (cross contralaterally) in the medulla oblongata and form the lateral corticospinal tract of the spinal cord and thus control the opposite side of the body. The corticobulbar tract axons synapse on motor cranial nuclei within the brainstem that control muscles of the face, head, and neck. The lateral corticospinal tract axons leave the tract to go to specific interneurons or motor neurons in the anterior horn. The lateral corticospinal tract has the same somatotopic organization as the body . These lower motor neurons project through nerves to specific muscles. These tracts are involved in precise motor movements. The reticulospinal tract modulates motor movement by inhibiting and exciting spinal activity. The vestibulospinal tract arises from a vestibular nucleus in the pons and causes the extensor muscles of the body to rapidly contract, most dramatically witnessed when a person starts to fall backward. The rubrospinal tract originates in the red nucleus, decussates, and terminates in the cervical spinal cord. It is important for muscle movement and fine muscle control in the upper extremities. *Sensory Pathways The three clinically important spinal afferent pathways are the posterior column, anterior spinothalamic tract, and lateral spinothalamic tract. The posterior (dorsal) column (fasciculus gracilis and fasciculus cuneatus) carries fine-touch sensation, two-point discrimination, and proprioceptive information (i.e., epicritic information). The posterior column is formed by a three-neuron chain. The first neuron of the chain is the primary afferent neuron. It also is the sensory neuron of the reflex arc. After entering the spinal cord it sends its axon ipsilaterally up the spinal cord to a specific part of the posterior column and synapses in the three posterior column nuclei in the medulla oblongata. A basketball playing center has primary afferent neurons that could be more than 6 feet long, running from the great toe up to the medulla oblongata. The axon of the second-order neuron crosses contralaterally at the medial lemniscus and ascends and synapses with a specific nucleus of the thalamus. The third-order neuron, originating in the thalamus, continues the tract into the internal capsule, corona radiata, and postcentral gyrus (Brodmann areas 3, 1, 2) The anterior and lateral spinothalamic tracts are responsible for vague touch sensation and for pain and temperature perception, respectively . These modalities are referred to as protopathic. These tracts also form a three- neuron chain. However, their primary afferent neurons synapse in the posterior horn of the spinal cord, not just at the level they enter the intervertebral foramen but in a number of spinal segments above and below their point of entry. This is an example of divergence. The axons of the second-order neurons in the posterior horn cross to the contralateral side in the spinal cord in the lateral column, ascend to the same thalamic nucleus as the posterior column pathway, and continue with the posterior column pathway to the postcentral gyrus.

Describe necrotizing enterocolitis.

*Necrotizing enterocolitis (NEC) is an ischemic, inflammatory condition that causes bowel necrosis and perforation. NEC is not a specific diagnosis but a constellation of signs and symptoms with several proposed etiologies. It is the most common severe neonatal gastrointestinal emergency that predominantly affects the smallest and most premature infants. *Factors contributing to the development of NEC include infections, abnormal bacterial colonization, intestinal ischemia, immature immune responses, exaggerated inflammatory responses, immature intestinal motility and barrier function, perinatal stress, effects of medications and feeding practices, and genetic predisposition.

Define nephrotic syndrome, and compare and contrast nephrotic vs. nephritic syndromes. (See p. 759-760 and p. 773.)

*Nephrotic Syndrome(aka Nephrosis) , disturbances in the glomerular basement membrane and podocyte injury lead to increased permeability to protein and loss of electrical negative charge. Loss of plasma proteins, particularly albumin and some immunoglobulins, occurs across the injured glomerular filtration membrane. Loss of plasma proteins decreases plasma oncotic pressure, resulting in edema. The predominant cause of nephrotic syndrome is minimal change nephropathy, which is common in children (see Chapter 31). Hypoalbuminemia results from urinary loss of albumin combined with a diminished synthesis of replacement albumin by the liver. Albumin is lost in the greatest quantity because of its high plasma concentration and low molecular weight. Decreased dietary intake of protein from anorexia or malnutrition or accompanying liver disease may also contribute to lower levels of plasma albumin. Loss of albumin stimulates lipoprotein synthesis by the liver and hyperlipidemia and can promote progression of glomerular disease. Loss of immunoglobulins may increase susceptibility to infections. Sodium retention is common. Protein excretion caused by glomerular injury Excretion of 3.5 g of protein in the urine per day ( loss of serum proteins & increased Na+ retention) Findings: Hypoalbuminemia Edema Hyperlipidemia and lipiduria Vitamin D deficiency (loss of carrier proteins) *Nephritic Syndrome Hematuria (blood in urine) Some Protein (not severe) Cause: Increase permeability of Glomerular Filtration Membrane Allows larger molecules to pass through Glomerulonephritis (postinfection) Rapidly progressive glomerulonephritis (crescent) IgA nephropathy Lupus nephritis Diabetic Nephropathy In nephritic syndrome, hematuria (usually microscopic) is present and red blood cell casts are present in the urine in addition to proteinuria, which is not severe. It is caused by increased permeability of the glomerular filtration membrane with pore sizes large enough to allow the passage of red blood cells and protein. Nephritic syndrome is associated with postinfectious glomerulonephritis, rapidly progressive (crescentic) glomerulonephritis, IgA nephropathy, lupus nephritis, and diabetic nephropathy. The pathophysiology is related to immune injury of the glomerulus as previously described. Hypertension and uremia occur in advanced stages of disease.

Characterize disorders of overnutrition and undernutrition.

*Obesity is a metabolic disorder with an increase in body fat mass and a BMI greater than 30. The causes of obesity are complex and involve the interaction of adipokines produced by fat cells and other body weight control signals at the level of the hypothalamus. Metabolic dysregulation includes leptin resistance, insulin resistance, and a proinflammatory state that contribute to the complications of obesity. Visceral obesity and normal weight obesity increase the risk of developing systemic inflammation, dyslipidemia, and insulin resistance with predisposition to atherosclerosis, hypertension, cardiovascular disease, cancer, and type 2 diabetes mellitus. Metabolically healthy obesity delays obesity-related complications until an older age. *Malnutrition is lack of nourishment from inadequate amounts of calories, protein, vitamins, or minerals. Starvation is an extreme state of malnutrition. Cachexia is physical wasting associated with chronic disease. *Short-term starvation, or lack of dietary intake for 3 or 4 days, stimulates mobilization of stored glucose by two metabolic processes: glycogenolysis (splitting of glycogen into glucose) and gluconeogenesis (formation of glucose from noncarbohydrate molecules). * Long-term starvation triggers the breakdown of ketone bodies and fatty acids. Eventually proteolysis (protein breakdown) begins, and death ensues if nutrition is not restored.

Differentiate between parietal pain, visceral pain, and referred pain.

*Parietal pain, from the parietal peritoneum, is more localized and intense than visceral pain, which arises from the organs themselves. Parietal pain lateralizes because, at any particular point, the parietal peritoneum is innervated from only one side of the nervous system. *Visceral pain arises from a stimulus (distention, inflammation, ischemia) acting on an abdominal organ. Inflammatory mediators associated with chronic low-grade inflammation can cause pain hypersensitivity.11 The pain is usually poorly localized, diffuse, or vague with a radiating pattern because nerve endings in abdominal organs are sparse and multisegmented. Pain arising from the stomach, for example, is experienced as a sensation of fullness, cramping, or gnawing in the midepigastric area. *Referred pain is visceral pain felt at some distance from a diseased or affected organ. It is usually well localized and is felt in the skin dermatomes or deeper tissues that share a central afferent pathway with the affected organ. For example, acute cholecystitis may have pain referred to the right shoulder or scapula.

Describe the pathophysiology and manifestations of a patent ductus arteriosus.

*Pathophysiology -Patent ductus arteriosus (PDA) is failure of the fetal ductus arteriosus (artery connecting the aorta and pulmonary artery) to functionally close within the first 15 hours after birth. However, several weeks after birth may be needed for attainment of true anatomic closure, in which the ductus loses the ability to reopen. The continued patency of this vessel allows blood to flow from the higher pressure aorta to the lower pressure pulmonary artery, causing a left-to-right shunt. -Infants may be asymptomatic or show signs of pulmonary overcirculation, such as dyspnea, fatigue, and poor feeding. There is a characteristic machinery-like murmur in both systole and diastole. Aortic flow (run-off) into the lower pressure pulmonary circulation produces low diastolic blood pressure, widened pulse pressure, and bounding pulses. Children are at risk for bacterial endocarditis and may develop pulmonary hypertension in later life from chronic excessive pulmonary blood flow.

Describe the differences between persistent vegetative state, minimally conscious state, and locked-in syndrome.

*Persistent vegetative state-A persistent vegetative state is complete unawareness of the self or surrounding environment and complete loss of cognitive function. The individual does not speak any comprehensible words or follow commands. Sleep-wake cycles are present, eyes open spontaneously, and blood pressure and breathing are maintained without support. Brainstem reflexes (pupillary, oculocephalic, chewing, swallowing) are intact but cerebral function is lost. There is bowel and bladder incontinence. Recovery is unlikely if the state persists for 12 months. *Minimally conscious state-In a minimally conscious state (MCS) individuals may follow simple commands, manipulate objects, gesture or give yes/no responses, have intelligible speech, and have movements such as blinking or smiling Locked-in syndrome-With locked-in syndrome there is complete paralysis of voluntary muscles with the exception of eye movement. Content of thought and level of arousal are intact, but the efferent pathways are disrupted (injury at the base of the pons with the reticular formation intact, often caused by basilar artery occlusion). Thus, the individual cannot communicate through speech or body movement but is fully conscious, with intact cognitive function. Vertical eye movement and blinking are a means of communication.

Discuss the five major complications of liver dysfunction: portal hypertension, ascites, hepatic encephalopathy, jaundice, and hepatorenal syndrome.

*Portal hypertension is an elevation of portal venous pressure to at least 10 mm Hg. It is caused by increased resistance to venous flow in the portal vein and its tributaries, including the sinusoids and hepatic vein. Portal hypertension is the most serious complication of liver disease because it can cause potentially fatal complications, such as bleeding varices, ascites, and hepatic encephalopathy. *Ascites is the accumulation and sequestration of fluid in the peritoneal cavity, often as a result of portal hypertension and decreased concentrations of plasma proteins. *Hepatic encephalopathy (portal-systemic encephalopathy) is impaired cerebral function caused by blood-borne toxins (particularly ammonia) not metabolized by the liver. Toxin-bearing blood may bypass the liver in collateral vessels opened as a result of portal hypertension, or diseased hepatocytes may be unable to carry out their metabolic functions. Manifestations of hepatic encephalopathy range from confusion and asterixis (flapping tremor of the hands) to loss of consciousness, coma, and death *Jaundice (icterus) is a yellow or greenish pigmentation of the skin or sclera of the eyes caused by increases in plasma bilirubin concentration (hyperbilirubinemia). - Obstructive jaundice is caused by obstructed bile canaliculi (intrahepatic obstructive jaundice) or obstructed bile ducts outside the liver (extrahepatic obstructive jaundice). Bilirubin accumulates proximal to the sites of obstruction, enters the bloodstream, and is carried to the skin and deposited. -Hemolytic jaundice is caused by destruction of red blood cells at a rate that exceeds the liver's ability to metabolize unconjugated bilirubin. *Hepatorenal syndrome is functional kidney failure caused by advanced liver disease, particularly cirrhosis with portal hypertension. Renal failure is caused by a sudden decrease in blood flow to the kidneys usually caused by massive gastrointestinal hemorrhage, liver failure, or inadequate circulating blood volume associated with ascites. The chief clinical manifestation is oliguria.

restrictive vs. obstructive pulmonary disease. (What is the defining characteristic of each?)

*Restrictive lung diseases are characterized by decreased compliance of the lung tissue. This means that it takes more effort to expand the lungs during inspiration, which increases the work of breathing. Individuals with lung restriction have dyspnea, an increased respiratory rate, and a decreased tidal volume. Pulmonary function testing reveals a decrease in FVC. Restrictive lung diseases can cause mismatch and affect the alveolocapillary membrane, which reduces the diffusion of oxygen from the alveoli into the blood and results in hypoxemia. Some of the most common restrictive lung diseases in adults are aspiration, atelectasis, bronchiectasis, bronchiolitis, pulmonary fibrosis, inhalation disorders, pneumoconiosis, allergic alveolitis, pulmonary edema, and acute respiratory distress syndrome. *CANT GET AIR IN* *COMPLIANCE= INHALE* *Obstructive lung disease is characterized by airway obstruction that is worse with expiration. More force (i.e., use of accessory muscles of expiration) is required to expire a given volume of air and emptying of the lungs is slowed. The unifying symptom of obstructive lung diseases is dyspnea, and the unifying sign is wheezing. Individuals have an increased work of breathing, ventilation-perfusion mismatching, and a decreased forced expiratory volume in 1 second (FEV1). The most common obstructive diseases are asthma, chronic bronchitis, and emphysema. Because many individuals have chronic bronchitis with emphysema, these diseases together are often called chronic obstructive pulmonary disease (COPD). * CANT GET AIR OUT* *ELASTIC RECOIL= EXHALE*

Compare left and right heart failure, including causation, manifestations, treatment, and complications.

*Right sided heart failure(to body) Right heart failure is defined as the inability of the right ventricle to provide adequate blood flow into the pulmonary circulation at a normal central venous pressure. It can result from left heart failure when an increase in left ventricular filling pressure is reflected back into the pulmonary circulation. As pressure in the pulmonary circulation rises, the resistance to right ventricular emptying increases . The right ventricle is poorly prepared to compensate for this increased afterload and will dilate and fail. When this happens, pressure will rise in the systemic venous circulation, resulting in peripheral edema and hepatosplenomegaly. --Cannot move deoxygenated blood from periphery to lungs Congestion in systemic circulation results • Peripheral edema (dependent) - limbs, liver, spleen, GI tract Causes include cor pulmonale Structural defect related to lungs Also lung infections, injury, inflammation, pulmonary edema - Treatment relies on management of the left ventricular dysfunction as just outlined. When right heart failure occurs in the absence of left heart failure, it is typically attributable to diffuse hypoxic pulmonary disease such as chronic obstructive pulmonary disease (COPD), cystic fibrosis, and acute respiratory distress syndrome (ARDS). These disorders result in an increase in right ventricular afterload. The mechanisms for this type of right ventricular failure (corpulmonale) are discussed in Chapter Finally, myocardial infarction, cardiomyopathies, and pulmonic valvular disease interfere with right ventricular contractility and can lead to right heart failure. *Left sided heart failure(to lungs) "Congestive Heart Failure" Causes: MI Myocarditis Cardiomyopathies Increased ischemia Increased workload (high afterload) -Left ventricle failure Forward movement of blood from heart to system (body) is impeded Fluid backs into the lungs 2 Types of problems: Loss of Contractility: Systolic failure Can't pump well Loss of Relaxation: Diastolic failure Can't fill ventricle well - further categorized as heart failure with reduced ejection fraction or heart failure with preserved ejection fraction. heart failure with reduced ejection fraction, or systolic heart failure, is defined as an ejection fraction of <40% and an inability of the heart to generate an adequate cardiac output to perfuse vital tissues. -The clinical manifestations of left heart failure are the result of pulmonary vascular congestion and inadequate perfusion of the systemic circulation. Individuals experience dyspnea, orthopnea, cough of frothy sputum, fatigue, decreased urine output, and edema. Physical examination often reveals pulmonary edema (cyanosis, inspiratory crackles, pleural effusions), hypotension or hypertension, an S3 gallop, and evidence of underlying CAD or hypertension. Treatment includes ACE inhibitors, ARBs, Beta blockers, diuretics, aldosterone agonists. (treatments to strengthen the heart) Complications include kidney damage, heart valve problems, heart rhythm problems, liver damage.

Use the Frank-Starling law and the law of Laplace to demonstrate the interrelationship between preload, afterload, and contractility.

*The Frank-Starling law of the heart indicates that the volume of blood in the heart at the end of diastole, as the volume determines the length of its muscle fibers, is directly related to the force of contraction during the next systole. *Laplace law states that wall tension generated in the wall of the ventricle (or any chamber or vessel) to produce a given intraventricular pressure depends directly on ventricular size or internal radius and inversely on ventricular wall thickness. Ventricular end-diastolic volume, which determines the size of the ventricle and the stretch of the cardiac muscle fibers, therefore affects the tension (or force) for contraction.

Compare and contrast dilated, hypertrophic, and restrictive cardiomyopathy in terms of etiology, pathophysiology, and clinical manifestations.

*The cardiomyopathies are a diverse group of diseases that primarily affect the myocardium itself. -In the dilated type of cardiomyopathy, the heart has a globular shape and the largest circumference of the left ventricle is not at its base but midway between apex and base. Dilated cardiomyopathy is usually the result of ischemic heart disease, valvular disease, diabetes, renal failure, alcohol or drug toxicity, peripartum complications, or infection. There is a strong genetic basis for dilated cardiomyopathy and it can be associated with inherited disorders, such as muscular dystrophy. It is characterized by impaired systolic function leading to increases in intracardiac volume, ventricular dilation, and heart failure with reduced ejection fraction. Individuals complain of dyspnea, fatigue, and pedal edema. Findings on examination include a displaced apical pulse, S3 gallop, peripheral edema, jugular venous distention, and pulmonary congestion. Diagnosis is confirmed by chest x-ray and echocardiogram, and management is focused on reducing blood volume, increasing contractility, and reversing the underlying disorder if possible. Heart transplant is required in severe cases. -In the hypertrophic type, the wall of the left ventricle is greatly thickened; the left ventricular cavity is small, but the left atrium may be dilated because of poor diastolic relaxation of the ventricle. Hypertrophic cardiomyopathy refers to two major categories of thickening of the myocardium: (1) hypertrophic obstructive cardiomyopathy (asymmetric septal hypertrophic cardiomyopathy or subaortic stenosis) and (2) hypertensive or valvular hypertrophic cardiomyopathy. Hypertrophic obstructive cardiomyopathy is the most commonly inherited cardiac disorder. It is characterized by thickening of the septal wall , which may cause outflow obstruction to the left ventricle outflow tract. Obstruction of left ventricular outflow can occur when the heart rate is increased and the intravascular volume is decreased. This type of hypertrophic cardiomyopathy is a significant risk factor for serious ventricular dysrhythmias and sudden death. There are other conditions that cause hypertrophic changes in the ventricles; hypertensive and valvular hypertrophic cardiomyopathies are the most common. These occur because of increased resistance to ventricular ejection, which is commonly seen in individuals with hypertension or valvular stenosis (usually aortic). In this case, hypertrophy of the myocytes is an attempt to compensate for increased myocardial workload. Long-term dysfunction of the myocytes develops over time, with diastolic dysfunction appearing first and leading eventually to systolic dysfunction of the ventricle. Individuals with hypertrophic cardiomyopathy may be asymptomatic or may complain of angina, syncope, dyspnea on exertion, and palpitations. Examination may reveal extra heart sounds and murmurs. Echocardiography and cardiac catheterization can confirm the diagnosis. - In the restrictive (constrictive) type, the left ventricular cavity is normal size, but, again, the left atrium is dilated because of the reduced diastolic compliance of the ventricle. characterized by restrictive filling and increased diastolic pressure of either or both ventricles with normal or near-normal systolic function and wall thickness. It may occur idiopathically or as a cardiac manifestation of systemic diseases, such as amyloidosis, scleroderma, sarcoidosis, lymphoma, and hemochromatosis, or a number of inherited storage diseases.100 The myocardium becomes rigid and noncompliant, impeding ventricular filling and raising filling pressures during diastole. The most common clinical manifestation of restrictive cardiomyopathy is right heart failure with systemic venous congestion. Cardiomegaly and dysrhythmias are common. A thorough evaluation for the underlying cause should be initiated (and may include myocardial biopsy). Treatment is aimed at the underlying cause. Death occurs as a result of heart failure or dysrhythmias.

Describe the GI and digestive abnormalities associated with cystic fibrosis.

*The hallmark pathophysiologic triad of CF includes obstruction, infection, and inflammation that are evident throughout the gastrointestinal tract and within the airways. *Newborn-Viscid meconium-Meconium ileus with intestinal obstruction- Meconium peritonitis; growth failure *Older child and adult-Inspissated (dried out) mucofecal masses (intestinal sludging)- Partial intestinal obstruction with severe cramping pains Volvulus (obstruction), intussusception (prolapse)- Distal intestinal obstruction syndrome Growth failure *Pancreas (enzyme deficiency) Inspissation and precipitation of pancreatic secretions, causing obstruction of pancreatic ducts- Insulin deficiency-Absence of pancreatic enzymes, causing malabsorption of food and fatty, bulky stools-Decreased vitamin A, D, E, and K absorption-Glucose intolerance Hypoproteinemia; iron deficiency anemia; malnutrition-Vitamins A, D, E, and K deficiency and rectal prolapse-Diabetes mellitus *Liver Inspissation and precipitation of bile and biliary system Focal biliary cirrhosis; shrunken, "hobnail" liver; fatty liver Portal hypertension with esophageal varices and hematemesis *Salivary glands Inspissation and precipitation of secretions in small ducts of submaxillary and sublingual salivary glands Mild patchy fibrosis of salivary glands

Define retrograde amnesia, anterograde amnesia, and executive attention deficits.

*The person experiencing retrograde amnesia has difficulty retrieving past personal history memories or past factual memories. *Anterograde amnesia is the inability to form new personal or factual memories but memories of the distant past are retained and retrieved *Executive attention deficits include the inability to maintain sustained attention and a working memory deficit. Sustained attention deficit is an inability to set goals and recognize when an object meets a goal. A working memory deficit is an inability to remember instructions and information needed to guide behavior. Executive attention deficits may be temporary, progressive, or permanent. Attention-deficit/hyperactivity disorder (ADHD) is a common disorder of childhood that can continue through adulthood

Describe the symptoms and pathophysiology of Buerger and Raynaud disease.

*Thromboangiitis obliterans (Buerger disease) is an inflammatory disease of the peripheral arteries. It is strongly associated with smoking. Thromboangiitis obliterans is an autoimmune condition characterized by the formation of thrombi filled with inflammatory and immune cells.The chief symptom of thromboangiitis obliterans is pain and tenderness of the affected part, usually affecting more than one extremity. Clinical manifestations are caused by sluggish blood flow and include rubor (redness of the skin), which is caused by dilated capillaries under the skin, and cyanosis, which is caused by tissue ischemia *Raynaud phenomenon is characterized by attacks of vasospasm in the small arteries and arterioles of the fingers and, less commonly, the toes. Primary Raynaud phenomenon is a common primary vasospastic disorder of unknown origin. Secondary Raynaud phenomenon is associated with systemic diseases, particularly collagen vascular disease (scleroderma), vasculitis, malignancy, pulmonary hypertension, chemotherapy, cocaine use, hypothyroidism, thoracic outlet syndrome, trauma, serum sickness, or long-term exposure to environmental conditions such as cold temperatures or vibrating machinery in the workplace. The clinical manifestations of the vasospastic attacks of either disorder are changes in skin color and sensation caused by ischemia. Vasospasm occurs with varying frequency and severity and causes pallor, numbness, and the sensation of coldness in the digits. Attacks tend to be bilateral, and manifestations usually begin at the tips of the digits and progress to the proximal phalanges. Sluggish blood flow resulting from ischemia may cause the skin to appear cyanotic. Rubor, throbbing pain, and paresthesias follow as blood flow returns. Skin color returns to normal after the attack, but frequent, prolonged attacks interfere with cellular metabolism, causing the skin of the fingertips to thicken and the nails to become brittle.

Compare and contrast type 1, type 2, and gestational diabetes mellitus (DM).

*Type 1 diabetes mellitus is characterized by loss of beta cells, presence of islet cell antibody, lack of insulin, excess of glucagon, and altered metabolism of fat, protein, and carbohydrates. -Type 1 diabetes mellitus is caused by a gradual process of autoimmune destruction of beta cells in genetically susceptible individuals. -In type 1 diabetes mellitus, hyperglycemia causes polyuria and polydipsia resulting from osmotic diuresis. -Ketoacidosis is caused by increased levels of circulating ketones without the inhibiting effects of insulin. Increased levels of circulating fatty acids and weight loss are both manifestations of type 1 uncontrolled diabetes mellitus. *Type 2 diabetes mellitus is caused by genetic susceptibility that is triggered by environmental factors. The most compelling environmental risk factor is obesity. -In the obese, many factors, including metabolic syndrome, altered adipokines, increased fatty acids, inflammation, and hyperinsulinemia, contribute to the development of insulin resistance and hyperglycemia. -Some insulin production continues in type 2 diabetes mellitus, but the weight and number of beta cells decrease. There are decreased levels of insulin, amylin, ghrelin, and incretins and glucagon concentration is increased. All contribute to chronic hyperglycemia. *Gestational diabetes is glucose intolerance during pregnancy.

Identify the factors essential to successful ventilation, perfusion, and diffusion.

*Ventilation: mechanical movement of gas or air into and out of the lungs - Ventilatory rate: the number of times gas is inspired and expired per minute - Dependent on the structure of the conducting airways 1. Mouth, nasopharynx, oropharynx, 2. Larynx has supporting cartilages to prevent collapsing and muscles to help with swallowing, ventilation, and vocalization 3. Trachea - connects the larynx with the bronchi 4. Bronchi contain goblet cells 5. Ciliated mucosa - warms and humidifies inspired air and removes foreign particles from it - Normal arterial CO2 pressure of 40 mm Hg (Paco2) - Adequate ventilation - maintain normal Paco2 1. If not adequate, will result in CO2 retention 2. Perform an arterial blood gas analysis to determine adequacy - Muscles 1. Major accessory muscles of inspiration and expiration a. Diaphragm, external intercostal muscles (Inspiration) b. Accessory muscles: sternocleidomastoid and scalene muscles 2. Elastic properties of the lungs and chest wall ---- compliance 3. Resistance to airflow through the conducting airways a. Bronchoconstriction, edema of bronchial mucosa, airway obstruction * Diffusion: the movement of gases between air spaces and the lungs and the bloodstream - Use of the gas-exchange airways - Surface tension: tendency for liquid molecules that are exposed to air to adhere to one another - fluid in the alveoli make breathing difficult 1. Surfactant - decreases alveolar surface tension - The partial pressure of oxygen is greater in the alveoli than in the capillaries, thus oxygen travels from the alveoli into the capillaries (oxygen diffuses across the alveolocapillary membrane 1. Diffuses until the pressure of the capillary and the alveoli are equal 2. 97% of oxygen is bound to hemoglobin 3. the remaining 3% stays in the plasma and creates the partial pressure of oxygen 4. Oxygen Saturation: percentage of available hemoglobin that is bound to oxygen a. Changes in hemoglobin concentration affect the oxygen content of the blood b. Increased hemoglobin is a major compensatory mechanism in pulmonary diseases that impairs gas exchange *Perfusion: the movement of blood into and out of the capillary beds of the lungs to body organs and tissues - Chemoreceptors monitor the pH, Paco2, and Pao2 (arterial pressure of oxygen) of arterial blood - Central chemoreceptors 1. CSF - hydrogen ion concentration, carbon dioxide in arterial blood crosses over blood brain barrier 2. Decrease in pH as a result of increased concentrations of carbon dioxide and hydrogen ions stimulate respiratory center to increase the depth and rate of ventilation - Peripheral chemoreceptors 1. Sensitive to oxygen levels in arterial blood d. Effective gas exchange depends on an approximately even distribution of gas (ventilation) and blood (perfusion) in all portions of the lungs

Identify normal and abnormal diagnostic laboratory results for DM.

- A1c ≥ 6.5% (by NGSP certified lab & DCCT standardized) - Fasting Plasma Glucose ≥ 126 mg/dL - 2 hour OGTT ≥ 200 mg/dL (75g load) - Random plasma glucose ≥ 200 mg/dL plus symptoms of DM (polyuria, polydipsia, weight loss, blurred vision)

Compare and contrast croup (laryngotracheobronchitis), acute epiglottitis, and aspiration of a foreign body, with reference to the differential diagnosis, treatment, and prognosis.

- Croup ( acute laryngotracheobronchitis) o breathing difficulty and a "barking" cough o Diagnosis the sound of the cough is enough o Treatment There's no treatment per say Steam inhalation, ice masks Glucocorticoids (improved symptoms) - Acute Epiglottitis o Caused by bacterial and viral infections (H. influenza) o Diagnosis DO NOT do a throat examination o Treatment Anitbiotics • Racemic epinephrine • Corticosteroids • Postexposure prophylaxis - Aspiration of a Foreign Body o Coughing up large objects (food) o Diagnosis The child is choking, coughing or gaging o Treatment Removal of the obstruction

Describe the inheritance pattern, pathophysiology, clinical manifestations, and treatment for a child with cystic fibrosis.

- Cystic Fibrosis o Pathophysiology Autosomal recessive inherited that is defective of chlorine ion transport Chlorine dehydrates the mucous of the airways which impairs the cilia and then airway is blocked o Clinical Manifestations What are the GI clinical features of CF? - meconium ileus - abdominal distension - intestinal obstruction - failure to thrive - flatulence - steatorrhea - recurrent abdo pain - jaundice - GI bleeding What are the respiratory clinical features of CF? - cough - recurrent wheezing - recurrent pneumonia - atypical asthma - dyspnea on exertion - chest pain - nasal polyps - clubbing - cyanosis o Treatment Managed diet - pancreatic enzyme supplements - multivitamins including fat soluble - mucolytics - antobiotics; cefaclor/ciprofloxacillin for pseudomonas, flucloxacillin for staph. areus - bronchodilaters - anti-inflammatory agents - enteric-coated supplements (creons)

Define the different types of head injury and give examples of the type of force needed to produce each.

- Primary brain injury is caused by direct impact and involves neural injury, primary glial injury, and vascular responses. - Primary brain injuries can be focal or diffuse. +Focal brain injury includes contusion, laceration, extradural hematoma, subdural hematoma, intracerebral hematoma, and open-head trauma. +Diffuse brain injury (diffuse axonal injury [DAI]) results from shearing forces that result in axonal damage ranging from concussion to a severe DAI state. - Secondary brain injury develops from systemic and intracranial responses to primary brain trauma that result in further brain injury and neuronal death. (Primary Brain Injury) Focal Brain Injury- Localized injury from impact Closed injury-Blunt trauma Coup-Injury is directly below site of forceful impact Contrecoup-Injury is on opposite side of brain from site of forceful impact Epidural (extradural) hematoma Vehicular accidents, minor falls, sporting accidents Subdural hematoma Forceful impact: vehicular accidents or falls, especially in elderly persons or persons with chronic alcohol abuse Subarachnoid hemorrhage Bleeding caused by forceful impact, usually vehicular accidents or long distance falls Open injury Penetrating trauma: missiles (bullets) or sharp projectiles (knives, ice picks, axes, screwdrivers) Compound fracture Objects strike head with great force or head strikes object forcefully; temporal blows, occipital blows, upward impact of cervical vertebrae (basilar skull fracture) Diffuse Axonal Injury (can occur with focal injury) Traumatic shearing forces; tearing of axons from twisting and rotational forces with injury over widespread brain areas; moving head strikes hard, unyielding surface or moving object strikes stationary head; torsional head motion without impact (Secondary Brain Injury) Secondary brain injury Decrease in CBF caused by edema, hemorrhage, IICP; neuroinflammation Cell death Release of excitatory neurotransmitters (glutamate); failure of cell ion pumps, mitochondrial failure

Explain spinal shock and autonomic hyperreflexia.

- Spinal shock: When a spinal cord injury occurs, areas along the spine below the injury will no longer function b/c of loss of the continuous tonic discharge from the brain or brain stem - Hyperreflexia: develop after spinal shock resolves and is associated with an uncompensated cardiovascular response (r/t to stimulation of sympathetic nervous system). The condition is life threatening Autonomic hyperreflexia (dysreflexia) is a syndrome of sudden, massive reflex sympathetic discharge associated with spinal cord injury at level T6 or above. Flexor spasms are accompanied by profuse sweating, piloerection, and automatic bladder emptying.

Differentiate between congenital heart defects that increase, decrease, or do not change pulmonary blood flow.

-Defects with Increased Pulmonary Blood Flow *Patent Ductus Arteriosus-Patent ductus arteriosus (PDA) is failure of the fetal ductus arteriosus (artery connecting the aorta and pulmonary artery) to functionally close within the first 15 hours after birth. *Atrial Septal Defect-atrial septal defect (ASD) is an opening in the septal wall between the two atria. This opening allows blood to shunt from the left atrium to the right atrium. There are three types of ASDs. An ostium primum ASD is an opening low in the atrial septum and may be associated with abnormalities of the mitral valve. An ostium secundum ASD is an opening in the middle of the atrial septum and is the most common type. A sinus venosus ASD is an opening usually high in the atrial wall near the junction of the superior vena cava and may be associated with partial anomalous pulmonary venous connection. Left-to-right shunting of blood can occur with a large ASD. Another opening in the atrial septal wall that is part of normal fetal communication, which usually closes after birth, is the foramen ovale. When the lungs become functional at birth, the pulmonary pressure decreases and the left atrial pressure exceeds that of the right. The pressure change forces the septum to functionally close the foramen ovale. If it does not close, it is called a patent foramen ovale (PFO). About one out of four adults has a PFO without CHD; however, in children with CHD the foramen ovale often remains open. *Ventricular Septal Defect-A ventricular septal defect (VSD) is an opening of the septal wall between the ventricles. VSDs are the most common type of congenital heart defect and account for 15% to 20% of all such defects.2 VSDs are classified by location. Perimembranous VSDs are located high in the ventricular septal wall underneath the atrioventricular valves, and VSDs located under the aortic valve are subarterial. Muscular VSDs are located low in the septal wall. VSDs also can be located in the inlet or outlet portion of the ventricle. VSDs are similar to ASDs in that blood will shunt from left to right. Left-to-right shunting of blood can occur with a large VSD. Depending on the size and location, many VSDs close spontaneously, most often within the first 2 years of life. *Atrioventricular Canal Defect-Atrioventricular canal (AVC) defect, also known as atrioventricular septal defect (AVSD) or by the traditional term endocardial cushion defect (ECD), is the result of incomplete fusion of endocardial cushions . AVC defect consists of an ostium primum ASD and inlet VSD with associated abnormalities of the atrioventricular valve tissue. These valve abnormalities range from a cleft in the mitral valve to a common mitral and tricuspid valve. The directions and pathways of flow are determined by pulmonary and systemic resistance, left and right ventricular pressures, and the compliance of each chamber. Flow is generally from left to right. AVC is a common cardiac defect in children with Down syndrome. However, children with this defect can have a normal karyotype. -Defects with Decreased Pulmonary Blood Flow *Tetralogy of Fallot-The classic form of tetralogy of Fallot (TOF) includes four defects: (1) VSD, (2) PS, (3) overriding aorta, and (4) right ventricular hypertrophy (Figure 25-8). The pathophysiology varies widely, depending not only on the degree of PS but also on the pulmonary and systemic vascular resistance to flow. If total resistance to pulmonary flow is greater than systemic resistance, the shunt is from right to left. If systemic resistance is more than pulmonary resistance, the shunt is from left to right. PS decreases blood flow to the lungs and, consequently, the amount of oxygenated blood that returns to the left heart. Physiologic compensation to chronic, severe hypoxia includes production of more red blood cells (polycythemia), development of collateral bronchial vessels, and enlargement of the nail beds (clubbing). *Tricuspid Atresia-Tricuspid atresia is failure of the tricuspid valve to develop; consequently, there is no communication from right atrium to right ventricle. Blood flows through an ASD or a patent foramen ovale (PFO) to the left atrium and through a VSD to the right ventricle. This condition is often associated with PS or transposition of the great arteries. There is complete mixing of unoxygenated and oxygenated blood in the left side of the heart, resulting in systemic desaturation and mild cyanosis. The physiologic process that causes lesion development is variable, depending on the great vessel anatomy and amount of pulmonary stenosis. *do not change pulmonary blood flow ???

Explain the difference between a dendrite and an axon.

-Dendrites are extensions that carry nerve impulses toward the cell body. -Axons are long, conductive projections that carry nerve impulses away from the cell body.

Describe the mechanisms of heat production and loss as well as heat conservation.

-The hypothalamus also triggers heat conservation by stimulating the sympathetic nervous system, which stimulates the adrenal cortex and results in increased skeletal muscle tone, initiating the shivering response and producing vasoconstriction. By constricting peripheral blood vessels, centrally warmed blood is shunted away from the periphery to the core of the body where heat can be retained. This involuntary mechanism takes advantage of the insulating layers of the skin and subcutaneous fat to protect core temperature. The hypothalamus relays information to the cerebral cortex about cold and voluntary responses result. Individuals typically bundle up, keep moving, or curl up in a ball. These types of voluntary physical activities respectively provide insulation, increase skeletal muscle activity, and decrease the amount of skin surface available for heat loss through radiation, convection, and conduction. The hypothalamus responds to warmer core and peripheral temperatures by reversing the same mechanisms resulting in heat loss. -Heat loss is achieved through (1) radiation, (2) conduction, (3) convection, (4) vasodilation, (5) evaporation (sweating), (6) decreased muscle tone, (7) increased respiration, (8) voluntary measures, and (9) adaptation to warmer climates (i.e., increasing or decreasing the volume of sweat). Radiation Heat loss through electromagnetic waves emanating from surfaces with temperature higher than surrounding air Conduction Heat loss by direct molecule-to-molecule transfer from one surface to another, so that warmer surface loses heat to cooler surface Convection Transfer of heat through currents of gases or liquids; exchanges warmer air at body's surface with cooler air in surrounding space Vasodilation Diverts core-warmed blood to surface of body, with heat transferred by conduction to skin surface and from there to surrounding environment; occurs in response to autonomic stimulation under control of hypothalamus Evaporation Body water evaporates from surface of skin and linings of mucous membranes; major source of heat reduction connected with increased sweating in warmer surroundings Decreased muscle tone Exhausted feeling caused by moderately reduced muscle tone and curtailed voluntary muscle activity Increased respiration Air is exchanged with environment through normal process; minimal effect Voluntary mechanisms "Stretching out" and "slowing down" in response to high body temperatures; increasing body surface area available for heat loss; dressing in light-colored, loose-fitting garments Adaptation to warmer climates Gradual process beginning with lassitude, weakness, and faintness; proceeding through increased sweating, lowered sodium content, decreased heart rate, and increased stroke volume and extracellular fluid volume; and terminating in improved warm weather functioning and decreased symptoms of heat intolerance (work output, endurance, and coordination increase; subjective feelings of discomfort decrease) Heat Production; -Chemical reactions of metabolism: Occur during ingestion and metabolism of food and while maintaining body at rest (basal metabolism); occur in body core (e.g., liver -Skeletal muscle contraction Gradual increase in muscle tone or rapid muscle oscillations (shivering) -Chemical thermogenesis Epinephrine is released and produces rapid, transient increase in heat production by raising basal metabolic rate; quick, brief effect that counters heat lost through conduction and convection; involves brown adipose tissue, which decreases markedly in older adults; thyroid hormone increases metabolism

Identify the clinical indicators of pulmonary disease.

-Dyspnea: is defined as "a subjective experience of breathing discomfort that is comprised of qualitatively distinct sensations that vary in intensity. Its often described as breathlessness, air hunger, shortness of breath, labored breathing, and preoccupation with breathing. -Orthopnea: is dyspnea that occurs when an individual lies flat and is common in individuals with heart failure. The recumbent position redistributes body water, causes the abdominal contents to exert pressure on the diaphragm, and decreases the efficiency of the respiratory muscles. -Cough: is a protective reflex that helps clear the airways by an explosive expiration. Inhaled particles, accumulated mucous, inflammation, or the presence of a foreign body initiates the cough reflex by stimulating the irritant receptors it the airway. -Abnormal sputum: Changes in the amount, color, and consistency of sputum provides information about progression of disease and effectiveness of therapy. The gross and microscopic appearances of sputum enable the clinician to identify cellular debris or microorganisms, which aids in diagnosis and choice of therapy. -Hemoptysis: is the expectoration of blood or bloody secretions. This is sometimes confused with hematemesis, which is the vomiting of blood. Blood produced with coughing is usually bright red, and has an alkaline pH, and is mixed with frothy sputum. Blood that is vomited is dark, has an acidic pH, and is mixed with food particles. -Kussmaul respiration (hyperpnea): is characterized by a slightly increased ventilatory rate, very large tidal volumes (Tidal volume is the lung volume representing the normal volume of air displaced between normal inhalation and exhalation when extra effort is not applied), and no expiratory pause. Labored breathing occurs whenever there is increased work or breathing, especially if the airways are obstructed. Strenuous exercise or metabolic acidosis induces hypernea. -Cheyne-stokes respirations: characterized by alternating periods of deep and shallow breathing. Apnea lasting from 15 to 60 seconds is followed by ventilations that increase in volume until a peak is reached; the ventilation (tidal volume) decreases again to apnea. Cheyne-stokes respirations result from any condition that reduces blood flow to the brain stem. -Cyanosis: is a bluish discoloration of the skin and mucous membranes caused by increased amounts of desaturated or reduced hemoglobin (which is bluish) in the blood. It generally develops when 5 g of hemoglobin is desaturated, regardless of hemoglobin concentration. -Clubbing: is the selective bulbous enlargement of the end (distal segment) of a digit (finger or toe) (Fig 26-1); its severity can be graded from 1 to 5 based on the extent of nail bed hypertrophy and the amount of changes in the nails themselves or as early, moderate, or severe. -Pain: Pain caused by pulmonary disorders originates in the pleurae, airways, or chest wall. Infection and inflammation of the parietal pleura cause sharp or stabbing pain when the pleura stretches during inspiration. The pain is usually localized to a portion of the chest wall, where a unique breath sound called a pleural friction rub may be heard over the painful area. Laughing or coughing makes pleural pain worse. Pleural pain is common with pulmonary infarction (tissue death) caused by pulmonary embolism and emanates from the area around the infarction.

Identify risk factors for congenital cardiac defects.

-Environmental risk factors associated with the incidence of congenital heart defects typically are maternal conditions. Maternal conditions include viral infections, diabetes, drug intake, and advanced maternal age. - Genetic factors associated with congenital heart defects include, but are not limited to, Down syndrome, trisomy 13, trisomy 18, cri du chat syndrome, and Turner syndrome.

Describe how inhaling toxic or allergenic substances causes respiratory dysfunction.

-Exposure to toxic gases: Inhalation of gaseous irritants can cause significant respiratory dysfunction. Commonly encountered toxic gases include smoke, ammonia, hydrogen chloride, sulfur dioxide, chlorine, phosgene, and nitrogen dioxide. Inhalation injuries in burns can include toxic gasses from household or industrial combustants, heat, and smoke particles. Inhaled toxic particles cause damage to the airway epithelium, mucus secretion, inflammation, mucosal edema, ciliary damage, pulmonary edema, and surfactant inactivation. Acute toxic inhalation is frequently complicated by acute respiratory distress syndrome (ARDS) and pneumonia. Initial symptoms include burning of the eyes, nose, and throat; coughing; chest tightness; and dyspnea. Hypoxia is common. Treatment includes mechanical ventilation with PEEP, and support of the cardiovascular system. Steroids are sometimes used, although their effectiveness has not been well documented. Most individuals recover quickly. Some, however, may improve initially and then deteriorate as a result of bronchiectasis or bronchiolitis (inflammation of the bronchioles). -Allergic alveolitis: Inhalation of organic dusts can result in an allergic inflammatory response called extrinsic allergic alveolitis, or hypersensitivity pneumonitis. Many allergens can cause this disorder, including grains, silage, bird droppings or feathers, wood dust (particularly redwood and maple), cork dust, animal pelts, coffee beans, fish meal, mushroom compost, and molds that grow on sugarcane, barley, and straw. The lung inflammation, or pneumonitis, occurs after repeated, prolonged exposure to the allergen. Lymphocytes and inflammatory cells infiltrate the interstitial lung tissue, releasing a variety of autoimmune and inflammatory cytokines. Recent studies suggest an important role for interleukin-17, which promotes epithelial cell injury. Allergic alveolitis can be acute, subacute, or chronic. The acute form causes fever, cough, and chills a few hours after exposure. In the subacute form, coughing and dyspnea are common and sometime necessitate hospital care. ]

Differentiate among ischemia, hypoxia, hypercapnia, and hypoxemia.

-Ischemia: -an inadequate blood supply to an organ or part of the body, especially the heart muscles. -Hypoxia: Cells of the TISSUES are deprived of adequate oxygen Used for metabolism (Check signs of tissue organ damage) Brain, heart and lung vulnerable Brain cannot store oxygen but has high demand Forces cells to utilize anaerobic metabolism -Leads rapidly to metabolic acidosis Cellular death can result from extreme or prolonged hypoxia S/sx: restlessness, lethargy, coma, death NOTE: cells can become hypoxic from other causes, such as stroke, that do not involve the respiratory system -Hypercapnia: Increased CO2 in blood Presents only in cases of severe alveolar hypoventilation and hypoxia Conditions that inhibit ventilation or promote air trapping in alveoli Results in RESPIRATORY ACIDOSIS From CO2 retention Electrolyte disturbances that alter brain and heart function Dysrhythmias, coma, death -Hypoxemia: Decreased O2 in the Arterial Blood leading to decrease in partial pressure (PaO2) (Check ABG) Causes: oxygen deprivation, hypoventilation, problems with diffusion, inadequate uptake of oxygen in the blood Mild to severe Can lead to hypoxia

Describe the differences between types of headaches.

-Migraine headache is an episodic headache that can be associated with triggers, and may have an aura associated with a cortical spreading depression that alters cortical blood flow. Pain is related to overactivity in the trigeminal vascular system. - Cluster headaches are a group of disorders known as trigeminal autonomic cephalalgias and occur primarily in men. They occur in clusters over a period of days with extreme pain intensity and short duration, and are associated with trigeminal activation. - Tension-type headache is the most common headache. Episodic-type headaches involve a peripheral pain mechanism and the chronic type involves a central pain mechanism and may be related to hypersensitivity to pain in craniocervical muscles.

Differentiate among neuropathic pain, peripheral pain, and central pain.

-Neuropathic pain is chronic pain initiated or caused by a primary lesion or dysfunction in the nervous system and leads to long-term changes in pain pathway structures (neuroplasticity) and abnormal processing of sensory information. There is amplification of pain without stimulation by injury or inflammation. Neuropathic pain is often described as burning, shooting, shocklike, or tingling. It is characterized by increased sensitivity to painful or nonpainful stimuli with hyperalgesia, allodynia (the induction of pain by normally nonpainful stimuli), and the development of spontaneous pain. Neuropathic pain is classified as either peripheral or central and is associated with central and peripheral sensitization. -Peripheral neuropathic pain is caused by peripheral nerve lesions and an increase in the sensitivity and excitability of primary sensory neurons and cells in the dorsal root ganglion (peripheral sensitization). Examples include nerve entrapment, diabetic neuropathy, or chronic pancreatitis. -Central neuropathic pain is caused by a lesion or dysfunction in the brain or spinal cord. A progressive repeated stimulation of group C neurons (wind-up) in the dorsal horn leads to increased sensitivity of central pain signaling neurons (central sensitization). This results in pathologic changes in the CNS that cause chronic pain.Examples include brain or spinal cord trauma, tumors, vascular lesions, multiple sclerosis, Parkinson disease, postherpetic neuralgia, and phantom limb pain.

Compare and contrast pleural effusion and empyema.

-Pleural effusion is the presence of fluid in the pleural space. The source of the fluid is usually from blood vessels or lymphatic vessels lying beneath the pleural space, but occasionally an abscess or other lesion may drain into the pleural space. Pleural effusions that enter the pleural space from intact blood vessels can be transudative (watery) or exudative (high concentrations of white blood cells and plasma proteins). Other types of pleural effusion are characterized by the presence of pus (empyema), blood (hemothorax), or chyle (chylothorax). -Empyema (infected pleural effusion) is the presence of pus in the pleural space and develops when the pulmonary lymphatics become blocked, leading to an outpouring of contaminated lymphatic fluid into the pleural space. Empyema occurs most commonly in older adults and children and usually develops as a complication of pneumonia, surgery, trauma, or bronchial obstruction from a tumor. Commonly documented infectious organisms include Staphylococcus aureus, Escherichia coli, anaerobic bacteria, and Klebsiella pneumoniae. Individuals with empyema present clinically with cyanosis, fever, tachycardia (rapid heart rate), cough, and pleural pain. Breath sounds are decreased directly over the empyema.

List the structures contained within the central and peripheral nervous systems.

-The CNS is contained within the brain and spinal cord. -The PNS is composed of cranial and spinal nerves, which carry impulses toward the CNS (afferent—sensory) and away from the CNS (efferent—motor) to and from target organs or skeletal muscle.

Discuss the function of the upper and lower motor neurons.

-Upper motor neurons are completely contained within the CNS. Their primary roles are controlling fine motor movement and influencing/modifying spinal reflex arcs and circuits. Generally, upper motor neurons form synapses with interneurons, which then form synapses with lower motor neurons that project into the periphery. -Lower motor neurons directly influence muscles. Their cell bodies lie in the gray matter of the brainstem and spinal cord, but their processes extend out of the CNS and into the PNS. Destruction of upper motor neurons usually results in initial paralysis followed within days or weeks by partial recovery, whereas destruction of the lower motor neurons leads to paralysis unless peripheral nerve damage is followed by nerve regeneration and recovery

Discuss alterations in arterial blood gas values that indicate pulmonary disease.

-hypercapnia (Paco2 greater than 44mm Hg): Hypercapnia, or increased carbon dioxide concentration in the arterial blood (increased Paco2), is caused by hypoventilation of the alveoli. As described in Ch. 25, carbon dioxide is easily diffused from the blood into the alveolar space; thus minute volume (respiratory rate times tidal volume) determines not only alveolar ventilation but also Paco2. -hypocapnia (Paco2 less than 36 mm Hg) -The normal V/Q (ventilation-perfusion ratio) is 0.8 because perfusion is somewhat greater than ventilation in the lung bases and because some blood is normally shunted to the bronchial circulation.

List the common signs and symptoms of increased intracranial pressure in children.

1) Headache. 2) Vomiting: with or without nausea. 3) Seizures. 4) Diplopia (double vision) and/or blurred

Describe the pathogenesis of acute and chronic gastritis.

1. Acute gastritis is caused by injury of the protective mucosal barrier caused by drugs, chemicals, or Helicobacter pylori infection. Alcohol, histamine, digitalis, and metabolic disorders, such as uremia, are contributing factors. (NSAIDs; e.g., ibuprofen, naproxen, indomethacin, and aspirin) inhibit the action of cyclooxygenase-1 (COX-1) and cause gastritis because they inhibit prostaglandin synthesis, which normally stimulates the secretion of mucus. 2.Chronic gastritis tends to occur in older adults and causes chronic inflammation, mucosal atrophy, and epithelial metaplasia. Chronic gastritis is classified as type A, immune (fundal), or type B, nonimmune (antral), depending on the pathogenesis and location of the lesions. When both types of chronic gastritis occur, it is known as type AB, or pangastritis, and the antrum is more severely involved. Type C gastritis is associated with reflux of bile and pancreatic secretions into the stomach, causing chemical injury. Chronic immune (fundal) gastritis is the most rare form of gastritis and is associated with loss of T-cell tolerance and development of autoantibodies to gastric H+-K+ ATPase. The gastric mucosa degenerates extensively in the body and fundus of the stomach, leading to gastric atrophy. Loss of parietal cells diminishes acid and intrinsic factor secretion.

Describe common terms used in identifying the manifestations of gastrointestinal dysfunction.

1. Anorexia is lack of a desire to eat despite physiologic stimuli that would normally produce hunger. 2. Vomiting is the forceful emptying of the stomach effected by gastrointestinal contraction and reverse peristalsis of the esophagus. It is usually preceded by nausea and retching, with the exception of projectile vomiting, which is associated with direct stimulation of the vomiting center in the brain. 3. Constipation is difficult or infrequent defecation often caused by unhealthy dietary and bowel habits combined with lack of exercise. Constipation can result from a disorder that impairs intestinal motility or obstructs the intestinal lumen. 4. Diarrhea is the presence of frequent loose, watery stools and can be caused by excessive fluid drawn into the intestinal lumen by osmosis (osmotic diarrhea), excessive secretion of fluids by the intestinal mucosa (secretory or infectious diarrhea), or excessive gastrointestinal motility (motility diarrhea). 5. Abdominal pain is caused by stretching, inflammation, or ischemia (insufficient blood supply). Abdominal pain originates in the organs themselves (visceral pain) or in the peritoneum (parietal pain) and can be acute or chronic. Visceral pain is often referred to the back. 6. Obvious manifestations of gastrointestinal bleeding are hematemesis (vomiting of blood), melena (dark, tarry stools), and hematochezia (frank bleeding from the rectum). Occult bleeding can be detected only by testing stools or vomitus for the presence of blood.

Identify other childhood liver disorders.

1. Biliary atresia is a congenital malformation of the bile ducts that obstructs bile flow and causes jaundice, cirrhosis, and liver failure. 2. Acute hepatitis is usually caused by a virus, and hepatitis A is the most common form of childhood hepatitis. Chronic hepatitis B or C usually occurs by maternal transmission. 3. Cirrhosis results from fibrotic scarring of the liver and is rare in children, but it can develop from most forms of chronic liver disease. 4. Portal hypertension in children usually is caused by extrahepatic obstruction and the cause is often unknown. Intrahepatic obstruction is related to diseases that cause liver fibrosis. 5. The four most common metabolic disorders that cause liver damage in children are galactosemia, fructosemia, glycogen storage disease, and Wilson disease. All three are inherited as genetic traits and allow toxins to accumulate in the liver.

Identify the common types of central nervous system tumors found in children.

1. Brain tumors are the most common tumors of the nervous system and the second most common type of childhood cancer. 2. Tumors in children most often are located below the tentorial plate (infratentorial tumors). 3. Fast-growing tumors produce symptoms early in the disease, whereas slow- growing tumors may become very large before symptoms appear. 4. Symptoms of brain tumors may be generalized or localized. The most common general symptoms are the result of increased intracranial pressure and include headache, irritability, vomiting, somnolence, and bulging of fontanelles. 5. Localized signs of infratentorial tumors in the cerebellum include impaired coordination and balance. Cranial nerve signs occur with tumors in or near the brainstem. 6. Supratentorial tumors may be located near the cortex or deep in the brain. Symptoms depend on the specific location of the tumor. 7. Neuroblastoma is an embryonal tumor of the sympathetic nervous system and can be located anywhere there is sympathetic nervous tissue. Symptoms are related to tumor location and size of metastasis. 8. Retinoblastoma is a congenital eye tumor that has two forms: inherited and acquired. (Astrocytoma) Arises from astrocytes, often in cerebellum or lateral hemisphere Slow growing, solid or cystic Often very large before diagnosed Varies in degree of malignancy (Optic nerve glioma) Arises from optic chiasm or optic nerve (association with neurofibromatosis type 1) Slow-growing, low-grade astrocytoma (Medulloblastoma (infiltrating glioma) Often located in cerebellum, extending into fourth ventricle and spinal fluid pathway Rapidly growing malignant tumor Can extend outside CNS (Brainstem glioma) Arises from pons Numerous cell types Compresses cranial nerves V through X (Ependymoma) Arises from ependymal cells lining ventricles Circumscribed, solid, nodular tumors (Craniopharyngioma) Arises near pituitary gland, optic chiasm, and hypothalamus Cystic and solid tumors that affect vision, pituitary, and hypothalamic functions (Germ cell tumor) Arises from germ cells and are most common in pineal and suprasellar region, usually occurring during adolescence

Characterize the various cancers of the digestive system.

1. Cancer of the esophagus is rare and tends to occur in people older than 60 years of age. Alcohol and tobacco use, reflux esophagitis, and nutritional deficiencies are associated with esophageal carcinoma. Dysphagia and chest pain are the primary manifestations of esophageal cancer. Early treatment of tumors that have not spread into the mediastinum or lymph nodes results in a good prognosis. 2. Gastric adenocarcinoma(stomach) is associated with Helicobacter pylori that carries the CagA gene product cytotoxin-associated vacuolating antigen A, a diet high in salt and food preservatives (nitrates, nitrites), and atrophic gastritis. 3. Approximately 50% of all gastric cancers are located in the prepyloric antrum. Clinical manifestations (weight loss, upper abdominal pain, vomiting, hematemesis, anemia) develop only after the tumor has penetrated the wall of the stomach. 4. Cancer of the colon and rectum (colorectal cancer) is the third most common cause of cancer death in the United States. Preexisting polyps are highly associated with adenocarcinoma of the colon. Familial adenomatous polyposis accounts for about 3% to 5% of colorectal cancer cases. Tumors of the right (ascending or proximal) colon are usually large and bulky; tumors of the left (descending, sigmoid or distal) colon develop as small, button- like masses. Manifestations of colon tumors include pain, bloody stools, and a change in bowel habits. 5. Rectal carcinoma is located up to 15 cm from the opening of the anus. The tumor spreads transmurally to the vagina in women or the prostate in men. 6. Metastatic invasion of the liver is more common than primary cancer of the liver. 7. Primary liver cancers are associated with chronic liver disease (cirrhosis, hepatitis B). Hepatocellular carcinomas arise from the hepatocytes, whereas cholangiocellular carcinomas arise from the bile ducts. Primary liver cancer spreads to the heart, lungs, brain, kidney, and spleen through the circulation. 8. Cancer of the gallbladder is relatively rare and tends to occur in women older than 50 years. Adenocarcinoma is most common. Because clinical manifestations occur late in the disease, metastases to lymph channels have usually occurred by the time of diagnosis and the prognosis is poor. 9. Cancer of the pancreas is the fourth cause of cancer deaths. Most tumors are adenocarcinomas that arise in the exocrine cells of ducts in the head, body, or tail of the pancreas. Symptoms may not be evident until the tumor has spread to surrounding tissues. Treatment is palliative, and mortality is nearly 100% at 5 years.

Compare and contrast the various disorders of digestive motility.

1. Dysphagia is difficulty swallowing. It can be caused by a me chanical or functional obstruction of the esophagus. Functional obstruction is an impairment of esophageal motility. 2. Achalasia is a form of functional dysphagia caused by loss of esophageal innervation. 3. Gastroesophageal reflux disease is the regurgitation of chyme from the stomach into the esophagus, resulting in an inflammatory response (reflux esophagitis) when the esophageal mucosa is repeatedly exposed to acids and enzymes in the regurgitated chyme. 4. Hiatal hernia is the protrusion of the upper part of the stomach through the hiatus (esophageal opening in the diaphragm) at the gastroesophageal junction. Hiatal hernia can be sliding or paraesophageal. 5. Gastroparesis is delayed gastric emptying in the absence of mechanical gastric outlet obstruction. 6. Pyloric obstruction is the narrowing or blockage of the pylorus, which is the opening between the stomach and the duodenum. It can be caused by a congenital defect, inflammation and scarring secondary to a gastric ulcer, or tumor growth. 7. Intestinal obstruction prevents the normal movement of chyme through the intestinal tract. It can be mechanical (i.e., caused by torsion, herniation, or tumor) or functional as a result of paralytic ileus. The most severe consequences of intestinal obstruction are fluid and electrolyte losses, hypovolemia, shock, intestinal necrosis, and perforation of the intestinal wall.

Describe how the brain affects the following: level of consciousness, pattern of breathing, vomiting, pupillary changes, oculomotor responses, and motor responses.

1. Full consciousness is an awareness of oneself and the environment with an ability to respond to external stimuli with a wide variety of responses. 2. Consciousness has two components: arousal (level of awakeness) and awareness (content of thought). 3. An altered level of arousal occurs by diffuse bilateral cortical dysfunction, bilateral subcortical (reticular formation, brainstem) dysfunction, localized hemispheric dysfunction, and metabolic disorders. 4. An alteration in breathing pattern and the level of consciousness reflect the level of brain dysfunction. 5. Pupillary changes reflect changes in level of brainstem function, drug action, and response to hypoxia and ischemia. 6. Abnormal eye movements, including nystagmus and divergent gaze, reflect alterations in brainstem function. 7. Level of brain function manifests by changes in generalized motor responses or no responses. *Level of consciousness is the most critical clinical index of nervous system function, with changes indicating either improvement or deterioration of the individual's condition. A person who is alert and oriented to self, others, place, and time is considered to be functioning at the highest level of consciousness, which implies full use of all the person's cognitive capacities. From this normal alert state, levels of consciousness diminish in stages from confusion and disorientation (can occur simultaneously) to coma, each of which is clinically defined Confusion Loss of ability to think rapidly and clearly; impaired judgment and decision making Disorientation Beginning loss of consciousness; the person may exhibit restlessness, anxiety, and irritation; disorientation to time occurs first, followed by disorientation to place and familiar others (family members) and impaired memory; recognition of self is lost last Lethargy Limited spontaneous movement or speech; easy arousal with normal speech or touch; may or may not be oriented to time, place, or person Obtundation Mild to moderate reduction in arousal (awakeness) with limited response to environment; falls asleep unless stimulated verbally or tactilely; answers questions with minimal response Stupor Condition of deep sleep or unresponsiveness from which person may be aroused or caused to open eyes only by vigorous and repeated stimulation; response is often withdrawal or grabbing at stimulus Light coma Associated with purposeful movement on stimulation Coma Associated with nonpurposeful movement only on stimulation Deep coma Associated with unresponsiveness or no response to any stimulus ------------------------------------------------- *Patterns of breathing help evaluate the level of brain dysfunction and coma. Rate, rhythm, and pattern should be evaluated. Breathing patterns can be categorized as hemispheric or brainstem patternsWith normal breathing, a neural center in the forebrain (cerebrum) produces a rhythmic pattern. When consciousness decreases, lower brainstem centers regulate the breathing pattern by responding only to changes in PaCO2 levels; this is called posthyperventilation apnea. Cheyne-Stokes respiration is an abnormal rhythm of ventilation with alternating periods of tachypnea and apnea (crescendo-decrescendo pattern). Increases in PaCO2 levels lead to tachypnea. The PaCO2 level then decreases to below normal and breathing stops (apnea) until the carbon dioxide reaccumulates and again stimulates tachypnea. In cases of opiate or sedative drug overdose, the respiratory center is depressed so the rate of breathing gradually decreases until respiratory failure occurs. *Pupillary changes indicate the presence and level of brainstem dysfunction because brainstem areas that control arousal are adjacent to areas that control the pupils. For example, severe ischemia and hypoxia usually produce dilated, fixed pupils. Hypothermia may cause fixed pupils. Some drugs affect pupils and must be considered in evaluating individuals in comatose states. Large doses of atropine and scopolamine fully dilate and fix pupils. Doses of sedatives (e.g., glutethimide) in sufficient amounts to produce coma cause the pupils to become midposition or moderately dilated, unequal, and commonly fixed to light. Opiates cause pinpoint pupils. Severe barbiturate intoxication may produce fixed pupils. *Oculomotor responses (resting, spontaneous, and reflexive eye movements) change at various levels of brain dysfunction in comatose individuals. Persons with metabolically induced coma, except with barbiturate-hypnotic and phenytoin poisoning, generally retain ocular reflexes even when other signs of brainstem damage are present. Destructive or compressive injury to the brainstem causes specific abnormalities of the oculocephalic and oculovestibular reflexes. Injuries that involve an oculomotor nucleus or nerve cause the involved eye to deviate outward, producing a resting dysconjugate lateral position of the eye. *Assessment of motor responses helps to evaluate the level of brain dysfunction and determine the most severely damaged side of the brain. The pattern of response noted may be (1) purposeful; (2) inappropriate, generalized motor movement; or (3) not present. Motor signs indicating loss of cortical inhibition that are commonly associated with decreased consciousness include primitive reflexes and rigidity (paratonia). Primitive reflexes include grasping, reflex sucking, snout reflex, and palmomental reflex, all of which are normal in the newborn but disappear in infancy. *Vomiting/yawning/hiccups are integrated in the lower brainstem. They can be induced by compression or diseases involving the medulla oblongata or benign stimuli to the vagal nerve.

Identify age-related changes in gastrointestinal function.

1. Gastric motility, blood flow, and volume and acid content of gastric juice may be reduced, particularly with gastric atrophy, and gastric emptying may be delayed. 2. Protective mucosal barrier decreases. 3. There is a change in the composition of the intestinal microbiota and resultant increased susceptibility to disease. 4. Size of Peyer patches and degree of mucosal immunity decline with increased risk for infection and inflammation. 5.The brain-gut axis (bidirectional neuroendocrine communication) may be disrupted and enteric neurons may degenerate with changes in gastrointestinal motility, secretion, and absorption as well as the elder person's appetite, and overall nutritional status. 6. Intestinal villi may become shorter and more convoluted, with diminished reparative capacity. 7. Intestinal absorption, motility, and blood flow may decrease, prolonging transit time and altering nutrient absorption. 8. Rectal muscle mass decreases and the anal sphincter weakens. 9. Constipation, fecal impaction, and fecal incontinence may develop and is related to immobility, low-fiber diet, and changes in enteric nervous system structure and functions.

Discuss the significance of cerebrovascular disease in children.

1. Ischemic (occlusive) cerebrovascular disease is rare in children but can occur from embolism, sickle cell disease, cerebral arteriopathies, and cardiac anomalies. 2. Hemorrhagic stroke can occur in association with immature blood vessel associated with prematurity or cerebral arteriovenous malformations. 3. Moyamoya is a rare, progressive vascular stenosis of the circle of Willis that obstructs arterial blood flow to the brain.

Describe the mechanisms of carbon dioxide transport from the body tissues to the lungs and factors affecting carbon dioxide diffusion across the alveolar membrane.

1. Most carbon dioxide produced by our tissues is converted into bicarbonate and is transported to the lungs. Bicarbonate is reconverted into carbon dioxide and then exhaled. ((Reaction: CO2 + H2O yields HCO3 + H)) Which means that carbon dioxide plus water being converted into bicarbonate and hydrogen ion - is reversed in the lungs. This reaction is pulled to the left because the concentration of carbon dioxide in the lungs is decreased as we breathe it off. 2. Factors affecting diffusion = thickness of the membrane, the surface area of the membrane and the partial pressure differences of each gas in the lungs

List the major vessels that supply blood to the kidneys.

1. Renal arteries arise as the fifth branches of the abdominal aorta, divide into anterior and posterior branches at the renal hilum, and then subdivide into lobar arteries supplying blood to the lower, middle, and upper thirds of the kidney. 2. Interlobar artery subdivisions travel down renal columns and between pyramids and form afferent glomerular arteries. 3. Arcuate arteries consist of branches of interlobar arteries at the cortical- medullary junction; they arch over the base of the pyramids and run parallel to the surface. 4. Glomerular capillaries consist of four to eight vessels and are arranged in a fistlike structure; they arise from the afferent arteriole and empty into the efferent arteriole, which carries blood to the peritubular capillaries. They are the major resistance vessels for regulating intrarenal blood flow (see Autoregulation of Intrarenal Blood Flow, p. 735). 5. Peritubular capillaries surround convoluted portions of the proximal and distal tubules and the loop of Henle; they are adapted for cortical and juxtamedullary nephrons. 6. Vasa recta is a network of capillaries that forms loops and closely follow the loops of Henle; it is the only blood supply to the medulla (important for formation of concentrated urine). 7. Renal veins follow the arterial path in reverse direction and have the same names as the corresponding arteries; they eventually empty into the inferior vena cava. The lymphatic vessels also tend to follow the distribution of the blood vessels.

Explain the relationship between renal blood flow and glomerular filtration rate.

1. Renal blood flows at about 1000 to 1200 ml/min, or 20% to 25% of the cardiac output. 2. Blood flow through the glomerular capillaries is maintained at a constant rate in spite of a wide range of arterial pressures by autoregulation of the glomerular capillaries. 3. The glomerular filtration rate (GFR) is the filtration of plasma per unit of time and is directly related to the perfusion pressure of renal blood flow. 4. Renin is an enzyme secreted from the juxtaglomerular apparatus in response to decreased blood pressure and causes the generation of angiotensin II, a potent vasoconstrictor. The renin-angiotensin-aldosterone system is thus a regulator of renal blood flow. Therefore, RBF and GFR are relatively constant, a relationship maintained by an intrinsic autoregulatory myogenic mechanism of contraction when blood vessels are stretched.

Identify the functional divisions of the nervous system.

1. The divisions of the nervous system have been categorized as either structural (central nervous system [CNS] and peripheral nervous system [PNS]) or functional (somatic nervous system and autonomic nervous system [ANS]). Functionally, the PNS can be divided into the somatic nervous system and the autonomic nervous system. The somatic nervous system consists of pathways that regulate voluntary motor control (e.g., skeletal muscle). The autonomic nervous system (ANS) is involved with regulation of the body's internal environment (viscera) through involuntary control of organ systems. The ANS is further divided into sympathetic and parasympathetic divisions.

Describe the structure, function and secretions of the liver.

1. The liver is the second largest organ in the body. It has digestive, metabolic, hematologic, vascular, and immunologic functions. 2. The liver is divided into the right and left lobes and smaller units called liver lobules. The liver is supported by the falciform, round, and coronary ligaments. 3. Liver lobules consist of plates of hepatocytes, which are the functional cells of the liver. 4. The hepatocytes synthesize 700 to 1200 ml of bile per day and secrete it into the bile canaliculi, which are small channels between the hepatocytes. The bile canaliculi drain bile into the common bile duct and then into the duodenum through an opening called the major duodenal papilla (sphincter of Oddi). 5. Sinusoids are capillaries located between the plates of hepatocytes. Blood from the portal vein and hepatic artery flows through the sinusoids to a central vein in each lobule and then to the hepatic vein and inferior vena cava. 6. Kupffer cells, which are part of the mononuclear phagocyte system, line the sinusoids and destroy microorganisms in sinusoidal blood; they are important in bilirubin production and lipid metabolism. -The liver produces clotting factors and can store a large volume of blood. -The liver plays a major role in the metabolism of fats, proteins, and carbohydrates; and stores minerals, vitamin B12, and fat-soluble vitamins. - The liver metabolically transforms or detoxifies hormones, toxic substances, and drugs to less active substances. -The primary bile acids are synthesized from cholesterol by the hepatocytes. The primary acids are then conjugated to form bile salts. The secondary bile acids are the product of bile salt deconjugation by bacteria in the intestinal lumen. - Most bile salts and acids are recycled. The absorption of bile salts and acids from the terminal ileum and their return to the liver are known as the enterohepatic circulation of bile.

Discuss the cellular pathophysiology, manifestations, and treatment of central nervous system tumors.

1. Two main types of tumors occur within the cranium: primary and metastatic. Primary tumors are classified as intracerebral tumors (astrocytomas, oligodendrogliomas, and ependymomas) or extracerebral tumors (meningioma or nerve sheath tumors). Metastatic tumors can be found inside or outside the brain substance. 2. CNS tumors cause local and generalized manifestations. The effects are varied, and local manifestations include seizures, visual disturbances, loss of equilibrium, and cranial nerve dysfunction. 3. Spinal cord tumors are classified as intramedullary tumors (within the neural tissues) or extramedullary tumors (outside the spinal cord). Metastatic spinal cord tumors are usually carcinomas, lymphomas, or myelomas. 4. Extramedullary spinal cord tumors produce dysfunction by compression of adjacent tissue, not by direct invasion. Intramedullary spinal cord tumors produce dysfunction by both invasion and compression.

Describe the mechanisms and manifestations of the herniation syndromes.

1. Uncal herniation. Occurs when the uncus or hippocampal gyrus, or both, shifts from the middle fossa through the tentorial notch into the posterior fossa, compressing the ipsilateral third cranial nerve, the contralateral third cranial nerve, and the mesencephalon. Uncal herniation generally is caused by an expanding mass in the lateral region of the middle fossa. The classic manifestations of uncal herniation are a decreasing level of consciousness, pupils that become sluggish before fixing and dilating (first the ipsilateral, then the contralateral pupil), Cheyne-Stokes respirations (which later shift to central neurogenic hyperventilation), and the appearance of decorticate and then decerebrate posturing. 2. Central herniation. Occurs when there is a straight downward shift of the diencephalon through the tentorial notch. It may be caused by injuries or masses located around the outer perimeter of the frontal, parietal, or occipital lobes; extracerebral injuries around the central apex (top) of the cranium; bilaterally positioned injuries or masses; and unilateral cingulate gyrus herniation. The individual rapidly becomes unconscious; moves from Cheyne-Stokes respirations to apnea; develops small, reactive pupils and then dilated, fixed pupils; and passes from decortication to decerebration. 3. Cingulate gyrus herniation. Occurs when the cingulate gyrus shifts under the falx cerebri. Little is known about its clinical manifestations. 4. Transcalvarial. The brain shifts through a skull fracture or a surgical opening in the skull. This type of external herniation may occur during a craniectomy— surgery in which a flap of skull is removed. This type of herniation prevents the piece of skull from being replaced. Infratentorial Herniation 1. The most common syndrome is cerebellar tonsillar. The cerebellar tonsil shifts through the foramen magnum because of increased pressure within the posterior fossa. The clinical manifestations are an arched stiff neck, paresthesias in the shoulder area, decreased consciousness, respiratory abnormalities, and pulse rate variations. Occasionally the force produces an upward transtentorial herniation of a cerebellar tonsil or the lower brainstem. There is increased ICP but no specific set of clinical manifestations associated with infratentorial herniation

Describe the normal development of the nervous system in children (see p. 422-423).

1.Growth and development of the brain occur most rapidly during fetal development and during the first year of life. 2. The bones of the skull are joined by sutures, and the wide, membranous junctions of the sutures (known as fontanelles) allow for brain growth and close by 18 months of age. 3. At birth neurologic function is primarily at the subcortical level with transition in reflexes as motor development progresses during the first year.

Describe the histology of the structural layers of the gastrointestinal tract.

4 layers (deep to superficial) *Mucosa- Mucous Epithelium, Lamina Propria, Muscularis Mucosae *Submucosa- Gland in submucosa, Duct from gland *Muscularis- Circular Muscle Layer/ Longitudinal Muscle Layer *Serosa/ Adventitia- Connective tissue layer, peritoneum

Describe the sensory and motor functions of the peripheral nervous system.

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Describe the differences between a thrombus and an embolus.

A thrombus is a blood clot that remains attached to the vessel wall. A embolus is a detached thrombus which circulates in the blood stream. (could also consist of an air bubble, an aggregate of amniotic fluid, an aggregate of fat, bacteria, cancer cells, or a foreign substance.)

Differentiate between prerenal, intrarenal, and postrenal causes of acute kidney injury.

AKI commonly results from extracellular volume depletion, decreased renal blood flow, or toxic/inflammatory injury to kidney cells resulting in alterations in renal function that may be minimal or severe. Acute kidney injury can be classified as prerenal (renal hypoperfusion), intrarenal (disorders involving renal parenchymal or interstitial tissue), or postrenal (urinary tract obstructive disorders) look at table 29-11 Prerenal: Prerenal acute kidney disease is the most common reason for AKI and is caused by renal hypoperfusion. The GFR declines because of the decrease in filtration pressure. Poor perfusion can result from renal vasoconstriction, hypotension, hypovolemia, hemorrhage, or inadequate cardiac output. AKI may occur during chronic renal failure if a sudden stress is imposed on already marginally functioning kidneys. Failure to restore blood volume or blood pressure and oxygen delivery can cause cell injury and acute tubular necrosis or acute interstitial necrosis, a more severe form of AKI. Intrarenal: Intrarenal (intrinsic) acute kidney injury usually results from ischemic acute tubular necrosis (ATN) related to prerenal AKI, nephrotoxic ATN (i.e., exposure to radiocontrast media), acute glomerulonephritis, vascular disease (malignant hypertension, disseminated intravascular coagulation, and renal vasculitis), allograft rejection, or interstitial disease (drug allergy, infection, tumor growth). ATN caused by ischemia occurs most often after surgery (40% to 50% of cases) but also is associated with sepsis, obstetric complications, and severe trauma, including severe burns. Hypotension associated with hypovolemia produces ischemia, generating toxic oxygen free radicals that cause cellular swelling, injury, and necrosis. Ischemic necrosis tends to be patchy and may be distributed along any part of the nephron. Nephrotoxic ATN can be produced by radiocontrast media and numerous antibiotics, particularly the aminoglycosides (neomycin, gentamicin, tobramycin) because these drugs accumulate in the renal cortex. Other substances, such as excessive myoglobin (oxygen-transporting substance from muscles), carbon tetrachloride, heavy metals (mercury,arsenic), or methoxyflurane anesthetic, and bacterial toxins may promote renal failure. Dehydration, advanced age, concurrent renal insufficiency, and diabetes mellitus tend to enhance nephrotoxicity. Necrosis caused by nephrotoxins is usually uniform and limited to the proximal tubules. Postrenal: Postrenal acute kidney injury is rare and usually occurs with urinary tract obstruction that affects the kidneys bilaterally (e.g., bladder outlet obstruction, prostatic hypertrophy, bilateral ureteral obstruction), tumors, or neurogenic bladder. A pattern of several hours of anuria with flank pain followed by polyuria is a characteristic finding. The obstruction causes an increase in intraluminal pressure upstream from the site of obstruction with a gradual decrease in GFR. This type of renal failure can occur after diagnostic catheterization of the ureters, a procedure that may cause edema of the tubular lumen.

Describe anatomic (shunt) defects and cyanotic and acyanotic congenital heart defects.

Abnormal movement from one side of the heart to the other is termed a shunt. Shunting of blood flow from the left heart into the right heart is called a left- to-right shunt and occurs in conditions such as atrial septal defect and ventricular septal defect. This increases blood flow into the pulmonary circulation. Because blood continues to flow through the lungs before passing into the systemic circulation, there is no decrease in tissue oxygenation or cyanosis. Thus defects that cause left-to-right shunt are termed acyanotic heart defects. Other types of acyanotic heart defects obstruct blood flow from the ventricles but do not cause shunting. Cyanotic heart defects frequently cause shunting of blood from the right side of the heart directly into the left side of the heart (right-to-left shunt). This type of shunt decreases blood flow through the pulmonary system, causing less than normal oxygen delivery to the tissues and resultant cyanosis

Compare and contrast acute, rapidly progressive, and chronic glomerulonephritis.

Acute glomerulonephritis: -Diffuse deposits of immune complexes (igG and complement) in glomerular capillary wall -infiltration of leukocytes -mesangial proliferation -Decrease capillary blood flow and GRF Rapidly progressive glomerulonephritis: -Accumulation of immune deposits and inflammatory cells and debris that proliferate into Bowman space and form crescent-shaped lesions -Decrease capillary blood flow and GRF -Can result in renal failure Chronic glomerulonephritis: -Decreased GFR and hematuria - usually focal, some diffuse lesions -Glomerular fibrosis and scarring, interstitial and tubular fibrosis and vascular sclerosis -Original glomerular lesions may not be definable -progression to end-stage kidney disease with uremia

Differentiate among somatic pain, visceral pain, and referred pain.

Acute pain arises from cutaneous, deep somatic, or visceral structures and can be classified as (1) somatic, (2) visceral, or (3) referred. -Somatic pain arises from the skin, joints, and muscles. It is either sharp and well localized (especially fast pain carried by Aδ fibers) or dull, aching, throbbing, and poorly localized as seen in polymodal C fiber transmissions. -Visceral pain is transmitted by C fibers and refers to pain in internal organs and the lining of body cavities; it tends to be poorly localized with an aching, gnawing, throbbing, or intermittent cramping quality. It is carried by sympathetic fibers and is associated with nausea and vomiting, hypotension, and, in some cases, shock. Visceral pain often radiates (spreads away from the actual site of the pain) or is referred. -Referred pain is felt in an area removed or distant from its point of origin—the area of referred pain is supplied by the same spinal segment as the actual site of pain. Referred pain can be acute or chronic. Impulses from many cutaneous and visceral neurons converge on the same ascending neuron, and the brain cannot distinguish between the different sources of pain. Because the skin has more receptors, the painful sensation is experienced at the referred site instead of at the site of origin. Referred pain can be acute or chronic.

Describe the risk factors, clinical manifestations, and pathophysiology of poststreptococcal glomerulonephritis.

Acute poststreptococcal glomerulonephritis (APGN) is one of the most common immune complex-mediated renal diseases in children. It most commonly occurs after a throat or skin infection with a nephritogenic strain of group A β-hemolytic streptococci, although other bacteria and viruses also may be responsible. Occurrences have been observed after bacterial endocarditis, which may be associated with streptococcal or staphylococcal microorganisms, or after viral diseases, such as varicella-zoster virus and hepatitides B and C. Glomerulonephritis develops with the deposition of antigen-antibody complexes in the glomerulus. The antigen-antibody complex activates complement and the release of inflammatory mediators that damage endothelial and epithelial cells lying on the glomerular basement membrane. Damage to the glomerular basement membrane leads to hematuria and proteinuria. Symptoms usually begin 1 to 2 weeks after an upper respiratory tract infection (more common during cold weather) and up to 6 weeks after skin infections such as impetigo (more common during warm weather). The onset of symptoms is abrupt, varying with disease severity. The child typically has gross or microscopic hematuria, proteinuria, edema, and renal insufficiency. Oliguria may be present. Hypertension occurs because of increased vascular volume. Acute hypertension may cause headache, vomiting, somnolence, and other central nervous system manifestations. Cardiovascular symptoms are related to circulatory overload and are compounded by hypertension. These include dyspnea, tachypnea, and an enlarged, tender liver. The most severely affected children develop acute renal failure with oliguria. As many as half of affected children are asymptomatic. The disease usually runs its course in 1 month, but urine abnormalities may be found for up to 1 year or longer after the onset. Prolonged proteinuria and abnormal glomerular filtration rate (GFR) indicate an unfavorable prognosis. More than 95% of affected children recover completely. Less than 1% of children develop end-stage renal disease.Treatment is supportive and symptom specific.

Describe acute and chronic pyelonephritis; include the pathophysiology, clinical manifestations, evaluation, and treatments of each.

Acute pyelonephritis: Pyelonephritis is an infection of one or both upper urinary tracts (ureter, renal pelvis, and interstitium). Common causes are summarized in table 29-5. Urinary obstruction and reflux of urine from the bladder (vesicoureteral kidneys) are most common underlying risk factors. One or both kidneys may be involved. Most cases occur in women. The responsible microorganism is usually E. coli, Proteus, or Pseudomonas. The latter two microorganisms are more commonly associated with infections after urethral instrumentation or urinary tract surgery. These microorganisms split urea into ammonia, making alkaline urine that increases the risk of stone formation. Patho: The infection is probably spread by ascending uropathic microorganisms along the ureters, but spread also may occur by way of the bloodstream. The inflammatory process is usually focal and irregular, primarily affecting the pelvis, calyces, and medulla. The infection causes medullary infiltration of white blood cells with renal inflammation, renal edema, and purulent urine. In severe infections, localized abscesses may form in the medulla and extend to the cortex. Primarily affected are the tubules; the glomeruli usually are spared. Necrosis of renal papillae can develop. After the acute phase, healing occurs with fibrosis and atrophy of affected tubules (fig. 29-5). The number of bacteria decreases until the urine again becomes sterile. Acute pyelonephritis rarely causes renal failure. Clinical manifestations: The onset of symptoms is usually acute, with fever, chills, and flank or groin pain. Symptoms characteristic of a UTI, including frequency, dysuria, and costovertebral tenderness, may precede systemic signs and symptoms. Older adults may have nonspecific symptoms, such as low grade fever and malaise. Evaluation and treatment: Differentiating symptoms of cystitis from those of pyelonephritis by clinical assessment alone is difficult. The specific diagnosis is established by urine culture, urinalysis, and clinical signs and symptoms. White blood cell casts indicate pyelonephritis, but they are not always present in the urine. Complicated pyelonephritis requires blood cultures and urinary tract imaging. Uncomplicated acute pyelonephritis responds well to 2 to 3 weeks of microorganism-specific antibiotic therapy. Follow-up urine cultures are obtained at 1 and 4 weeks after treatment if symptoms recur. Antibotic-resistant microorganisms or reinfection may occur in cases of urinary tract obstruction or reflux. Intravenous pyelography and voiding cystourethrography identify surgically correctable lesions. Chronic Pyelonephritis: It's a persistent or recurrent infection of the kidney leading to scarring of one or both kidneys. The specific cause of chronic pyelonephritis is difficult to determine. Recurrent infections from acute pyelonephritis may be associated with chronic pyelonephritis. Generally, chronic pyelonephritis is more likely to occur in individuals who have renal infections associated with some type of obstructive pathologic condition, such as renal stones and vesicoureteral reflux. Patho: Chronic urinary tract obstruction starts a process of progressive inflammation, altered renal pelvis and calyces, destruction of the tubules, atrophy or dilation and diffuse scarring, and finally impaired urine-concentrating ability, leading to chronic kidney failure. The lesions of chronic pyelonephritis are sometimes termed chronic interstitial nephritis because the inflammation and fibrosis are located in the interstitial spaces between the tubules (fig 29-5). Causes other than chronic pyelonephritis include drug toxicity from analgesics such as phenacetin, asprin, and acetaminophen; ischemia; irradiation; and immune complex diseases. Clinical manifestations: The early symptoms of chronic pyelonephritis are often minimal and may include hypertension, frequency, dysuria, and flank pain. Progression leads to kidney failure, particularly in the presence of obstructive uropathy or diabetes mellitus. Evaluation and treatment: Urinalysis, intravenous pyelography, and ultrasound are used diagnostically. Treatment is related to the underlying cause. Obstruction must be relieved. Antibiotics may be given, with prolonged antibiotic therapy for recurrent infection.

Describe how acute rheumatic fever is contracted and how it leads to rheumatic heart disease and valvular injury.

Acute rheumatic fever can develop only as a sequel to pharyngeal infection by group A β-hemolytic streptococcus Acute rheumatic fever is the result of an abnormal humoral and cell-mediated immune response to group A streptococcal cell membrane antigens called M proteins. This immune response cross-reacts with molecularly similar self-antigens in heart, muscle, brain, and joints, causing an autoimmune response that results in diffuse, proliferative, and exudative inflammatory lesions in these tissues. The inflammation may subside before treatment, leaving behind damage to the heart valves. RHD- Scarring of the areas affected by acute rheumatic fever. Leads to stenosis and endocarditis

Describe the common ocular pathophysiologies, including causation, manifestations, and complications.

Alterations in ocular movements. Abnormal ocular movements result from oculomotor, trochlear, or abducens cranial nerve dysfunction . The three types of eye movement disorders are (1) strabismus, (2) nystagmus, and (3) paralysis of individual extraocular muscles. In strabismus, one eye deviates from the other when the person is looking at an object. This is caused by a weak or hypertonic muscle in one eye. The deviation may be upward, downward, inward (entropia), or outward (extropia). Strabismus in children requires early intervention to prevent amblyopia (reduced vision in the affected eye caused by cerebral blockage of the visual stimuli). The primary symptom of strabismus is diplopia (double vision). Causes include neuromuscular disorders of the eye muscle, diseases involving the cerebral hemispheres, or thyroid disease. Nystagmus is an involuntary unilateral or bilateral rhythmic movement of the eyes. It may be present at rest or when the eye moves. Pendular nystagmus is characterized by a regular back and forth movement of the eyes. In jerk nystagmus, one phase of the eye movement is faster than the other. Nystagmus may be caused by imbalanced reflex activity of the inner ear, vestibular nuclei, cerebellum, medial longitudinal fascicle, or nuclei of the oculomotor, trochlear, and abducens cranial nerves . Drugs, retinal disease, and diseases involving the cervical cord also may produce nystagmus. Paralysis of specific extraocular muscles may cause limited abduction, abnormal closure of the eyelid, ptosis (drooping of the eyelid), or diplopia (double vision) as a result of unopposed muscle activity. Trauma or pressure in the area of the cranial nerves or diseases such as diabetes mellitus and myasthenia gravis also paralyze specific extraocular muscles. Visual acuity is the ability to see objects in sharp detail. With advancing age, the lens of the eye becomes less flexible and adjusts slowly, and there is altered refraction of light by the cornea and lens. Thus, visual acuity declines with age. contains a summary of changes in the eye caused by aging. Specific causes of visual acuity changes are (1) amblyopia, (2) scotoma, (3) cataracts, (4) papilledema, (5) dark adaptation, (6) glaucoma, (7) retinal detachment, and (8) macular degeneration. Amblyopia Reduced or dimmed vision; cause unknown Associated with strabismus Accompanies such diseases as diabetes mellitus, renal failure, and malaria and use of drugs such as alcohol and tobacco Scotoma Circumscribed defect of central field of vision Often associated with retrobulbar neuritis and multiple sclerosis, compression of optic nerve by tumor, inflammation of optic nerve, pernicious anemia, methyl alcohol poisoning, and use of tobacco Cataract Cloudy or opaque area in ocular lens Incidence increases with age because most commonly a result of degeneration; other causes are congenital Papilledema Edema and inflammation of optic nerve where it enters eyeball Caused by obstruction of venous return from retina by one of three main sources: increased intracranial pressure, retrobulbar neuritis, or changes in retinal blood vessels Dark adaptation With age, eye does not adapt as readily to dark Also, changes in quantity and quality of rhodopsin are causative; vitamin A deficiencies can produce this at any age Glaucoma Increased intraocular pressures (>12-20 mm Hg) Loss of acuity results from pressure on optic nerve, which blocks flow of nutrients to optic nerve fibers, leading to their death; sixth leading cause of blindness Retinal detachment Tear or break in retina with accumulation of fluid and separation from underlying tissue; seen as floaters, flashes of light, or a curtain over visual field; risks include extreme myopia, diabetic retinopathy, sickle cell disease *A cataract is a cloudy or opaque area in the ocular lens and leads to visual loss when located on the visual axis. It is the leading cause of blindness in the world. The incidence of cataracts increases with age as the lens enlarges. Cataracts develop because of alterations of metabolism and transport of nutrients within the lens. Although the most common form of cataract is degenerative, cataracts also may occur congenitally or as a result of infection, radiation, trauma, drugs, or diabetes mellitus. Cataracts cause decreased visual acuity, blurred vision, glare, and decreased color perception. *Glaucomas are the second leading cause of blindness and are characterized by intraocular pressures greater than 12 to 20 mm Hg with death of retinal ganglion cells and their axons. There are three primary types of glaucoma. 1. Open angle. This type of glaucoma is characterized by outflow obstruction of aqueous humor at the trabecular meshwork or canal of Schlemm even though there is adequate space for drainage; often this is an inherited disease and is a leading cause of blindness with few preliminary symptoms. 2. Angle closure. In this type of glaucoma there is displacement of the iris toward the cornea with obstruction of the trabecular meshwork and obstruction of outflow of aqueous humor from the anterior chamber; it may occur acutely with a sudden rise in intraocular pressure, causing pain and visual disturbances. 3. Congenital closure. This is a rare disease associated with congenital malformations and other genetic anomalies. Glaucoma is often asymptomatic and diagnosis may not occur until a late stage of disease. Both medical and surgical therapies are available. *Age-related macular degeneration (AMD) is a severe and irreversible loss of vision and a major cause of blindness in older individuals. Hypertension, cigarette smoking, diabetes mellitus, and family history of AMD are risk factors. The degeneration usually occurs after the age of 60 years. There are two forms: atrophic (dry, nonexudative) and neovascular (wet, exudative). The atrophic form is more common and is slowly progressive with inflammation and accumulation of lipofuscin (a lysosomal pigmented residue) and drusen (waste products from photoreceptors) in the retina and may include limited night vision and difficulty reading. The neovascular form includes accumulation of drusen and lipofuscin, abnormal choroidal blood vessel growth, leakage of blood or serum, retinal detachment, fibrovascular scarring, loss of photoreceptors, and more severe and rapid loss of central vision *Accommodation refers to changes in the thickness of the lens. Accommodation is needed for clear vision and is mediated through the oculomotor nerve. Pressure, inflammation, age, and disease of the oculomotor nerve may alter accommodation, causing diplopia, blurred vision, and headache. Loss of accommodation with advancing age is termed presbyopia, a condition in which the ocular lens becomes larger, firmer, and less elastic. The major symptom is reduced near vision, causing the individual to hold reading material at arm's length. *Alterations in refraction are the most common visual problem. Causes include irregularities of the corneal curvature, the focusing power of the lens, and the length of the eye. The major symptoms of refraction alterations are blurred vision and headache. Three types of refraction are as follows : Myopia—nearsightedness: Light rays are focused in front of the retina when the person is looking at a distant object. Hyperopia—farsightedness: Light rays are focused behind the retina when a person is looking at a near object. Astigmatism—unequal curvature of the cornea: Light rays are bent unevenly and do not come to a single focus on the retina. Astigmatism may coexist with myopia, hyperopia, or presbyopia. *Alterations in color vision; Normal sensitivity to color diminishes with age because of the progressive yellowing of the lens that occurs with aging. All colors become less intense, although color discrimination for blue and green is greatly affected. Color vision deteriorates more rapidly for individuals with diabetes mellitus than for the general population. Abnormal color vision also may be caused by color blindness and is an X-linked genetic trait. Color blindness affects 6% to 8% of the male population and about 0.5% of the female population. Although many forms of color blindness exist, most commonly the affected individual cannot distinguish red from green.In the most severe form individuals see only shades of gray, black, and white. *Neurologic disorders causing visual dysfunction. Vision may be disrupted at many points along the visual pathway, causing various defects in the visual field. Visual changes may cause defects or blindness in the entire visual field or in half of a visual field (hemianopia). Injury to the optic nerve causes same-side blindness. Injury to the optic chiasm (the X-shaped crossing of the optic nerves) can cause various defects, depending on the location of the injury. *Blepharitis is an inflammation of the eyelids caused by Staphylococcus or seborrheic dermatitis. *A hordeolum (stye) is an infection (usually staphylococcal) of the sebaceous glands of the eyelids usually centered near an eyelash. *A chalazion is a noninfectious lipogranuloma of the meibomian (oil-secreting) gland that often occurs in association with a hordeolum and appears as a deep nodule within the eyelid. These conditions present with redness, swelling, and tenderness and are treated symptomatically. *Entropion is a common eyelid malposition in which the lid margin turns inward against the eyeball. There are both surgical and nonsurgical treatments to reposition the lid margin. *Conjunctivitis is an inflammation of the conjunctiva (mucous membrane covering the front part of the eyeball) caused by viruses (most common), bacteria, allergies, or chemical irritants. *Acute bacterial conjunctivitis (pinkeye) is highly contagious and often caused by Staphylococcus, Haemophilus, Streptococcus pneumoniae, and Moraxella catarrhalis, although other bacteria may be involved. In children younger than 6 years, Haemophilus infection often leads to otitis media (conjunctivitis-otitis syndrome). Preventing the spread of the microorganism with meticulous handwashing and use of separate towels is important. The disease also is treated with antibiotics. *Viral conjunctivitis is caused by an adenovirus. Again, it is contagious, with symptoms of watering, redness, and photophobia. Allergic conjunctivitis is associated with a variety of antigens, including pollens. *Chronic conjunctivitis results from any persistent conjunctivitis. Trachoma (chlamydial conjunctivitis) is caused by Chlamydia trachomatis and often is associated with poor hygiene. It is the leading cause of preventable blindness in the world. *Keratitis is an infection of the cornea caused by bacteria or viruses. Bacterial infections can cause corneal ulceration, and type 1 herpes simplex virus can involve both the cornea and the conjunctiva. Acanthamoeba keratitis can occur from contact lens wear because of poor hygiene. Severe ulcerations with residual scarring require corneal transplantation.

Explain the pathophysiology of amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS, sporadic motor neuron disease, sporadic motor system disease, motor neuron disease [MND], Lou Gehrig disease) is a worldwide neurodegenerative disorder that diffusely involves lower and upper motor neurons, resulting in progressive muscle weakness. Amyotrophic (without muscle nutrition or progressive muscle wasting) refers to the predominant lower motor neuron component of the syndrome. Lateral sclerosis, scarring of the corticospinal tract in the lateral column of the spinal cord, refers to the upper motor neuron component of the syndrome. ALS may begin at any time from the fourth decade of life; its peak occurrence is between 60 and 69 years, with about 3.9 cases per 100,000 population in the United States. The prevalence is higher in males.42 Most cases of ALS are sporadic. A subset (about 10%) of persons has a familial form with genetic mutations in superoxide dismutase (SODI) that contribute to the neurotoxicity affecting motor neurons. Mutated TAR RNA-binding protein (TDP-43) is a major constituent of the neuronal protein inclusions in ALS. Gene and environmental interactions are being evaluated as a cause of ALS. Pathophysiology The cause of ALS is unknown. Oxidative stress, mitochondrial dysfunction, defects in axonal transport, excitotoxicity and glutamate transport, neuronal cytoplasmic inclusions (i.e., TDP-43 protein), and neuroinflammation as causes of neuron degeneration are under investigation. The principal pathologic feature of ALS is degeneration of lower and upper motor neurons. There is a decrease in large motor neurons in the spinal cord, brainstem, and cerebral cortex (premotor and motor areas), with ongoing degeneration in the remaining motor neurons. Death of the motor neuron results in axonal degeneration and secondary demyelination with glial proliferation and sclerosis (scarring). Widespread neural degeneration of nonmotor neurons in the spinal cord and motor cortices, as well as in the premotor, sensory, and temporal cortices, has been found. Lower motor neuron degeneration denervates motor units. Adjacent, still viable lower motor neurons attempt to compensate by distal intramuscular sprouting, reinnervation, and enlargement of motor units.

List the anatomic causes of resistance to urine flow and the signs of urinary obstruction.

Anatomic causes of resistance to urine flow include urethral stricture (narrowing of its lumen), prostatic enlargement in men (caused by acute inflammation, benign prostatic hyperplasia, or prostate cancer), and pelvic organ prolapse in women. Symptoms of obstruction are more common in men and include (1) frequent daytime voiding (urination more than every 2 hrs while awake); (2) nocturia (awakening more than once each night to urinate for adults less than 65 years of age or more than twice for older adults); (3) poor force of stream; (4) intermittency of urinary stream; (5) bothersome urinary urgency, often combined with hesitancy; and (6) feelings of incomplete bladder emptying despite micturition.

List the most common factors that cause injury to the nervous system during the perinatal and postnatal periods.

Anoxia, trauma, and infections are the most common factors that cause injury to the nervous system in the perinatal period. Infections, metabolic disturbances (acquired or genetic), trauma, toxins, and vascular disease may injure the nervous system in the postnatal period.

Identify hormones which act on, and which are secreted by, the kidney and describe their actions.

Antidiuretic Hormone The distal tubule in the cortex receives the hypoosmotic urine from the ascending limb of the loop of Henle. The concentration of the final urine is controlled by antidiuretic hormone (ADH), which is secreted from the posterior pituitary or neurohypophysis. ADH increases water permeability and reabsorption in the last segment of the distal tubule and along the entire length of the collecting ducts, which pass through the inner and outer zones of the medulla. The water diffuses into the ascending limb of the vasa recta and returns to the systemic circulation. The excreted urine can have a high osmotic concentration, up to 1400 mOsm. The volume is normally reduced to about 1% of the amount filtered at the glomerulus. (The mechanism for the regulation of ADH and plasma osmolality is described in Chapters 5 and 18.) Aldosterone Aldosterone is synthesized and secreted by the adrenal cortex under the regulation of the renin-angiotensin-aldosterone system (see Chapter 18, and the previous discussion of the renin-angiotensin-aldosterone system on p. 736). Aldosterone stimulates the epithelial cells of the distal tubule and collecting duct to reabsorb sodium (promoting water reabsorption) and increases the excretion of potassium and hydrogen ion. Natriuretic Peptides Natriuretic peptides are a group of peptide hormones, including atrial natriuretic peptide (ANP), secreted from myocardial cells in the atria, and brain natriuretic peptide (BNP), secreted from myocardial cells in the cardiac ventricles. When the heart dilates during volume expansion or heart failure, ANP and BNP inhibit sodium and water absorption by kidney tubules, inhibit secretion of renin and aldosterone, vasodilate the afferent arterioles, and constrict the efferent arterioles. The result is increased urine formation leading to a decrease in blood volume and blood pressure. C-type natriuretic peptide is secreted from the vascular endothelium and causes vasodilation in the nephron. Urodilatin is secreted by the distal convoluted tubules and collecting ducts and causes vasodilation and natriuretic and diuretic effects. Certain hormones are either activated or synthesized by the kidney. These hormones have significant systemic effects and include urodilatin (see earlier text), the active form of vitamin D, and erythropoietin. Urodilatin -A hormone that causes diuresis through increasing renal blood flow Vitamin D is a hormone that can be obtained in the diet or synthesized by the action of ultraviolet radiation (sun exposure) on cholesterol in the skin. These forms of vitamin D3 (cholecalciferol) are inactive and require two hydroxylations to establish a metabolically active form. The first step occurs in the liver and the second in the kidneys. Vitamin D is necessary for the absorption of calcium and phosphate by the small intestine. Erythropoietin Erythropoietin (Epo) stimulates the bone marrow to produce red blood cells in response to tissue hypoxia and may have tissue protective effects

Discuss the clinical manifestations and underlying mechanisms of atelectasis.

Atelectasis is the collapse of lung tissue. There are three types of atelectasis: 1. Compression atelectasis-is caused by external pressure exerted by tumor, fluid, or air in pleural space or by abdominal distention pressing on a portion of lung, causing alveoli collapse. 2. Absorption atelectasis- results from removal of air from obstructed or hypoventilated alveoli or from inhalation of concentrated oxygen or anesthetic agents 3. Surfactant impairment-results from decreased production or inactivation of surfactant, which is necessary to reduce surface tension in the alveoli and thus prevent lung collapse during expiration. Surfactant impairment can occur because of premature birth, acute respiratory distress syndrome, anesthesia induction, or mechanical ventilation. Atelectasis tends to develop after surgery and is estimated to occur in more that 90% of individuals administered a general anesthetic. Postoperative persons are often in pain, breathe shallowly, are reluctant to change position, and produce viscous secretions that tend to pool in dependent portions of the lung. Clinical manifestations of atelectasis are similar to those of pulmonary infection including dyspnea, cough, fever, and leukocytosis. Prevention and treatment of postoperative atelectasis usually include deep-breathing exercises, frequent position changes, and early ambulation. Deep breathing and the use of an incentive spirometer help open connections between patent and collapsed alveoli, called pores of Kohn (fig 26-5). This allows air to flow into the collapsed alveoli (collateral ventilation) and aids in the expulsion of intrabronchial obstructions.

Discuss synaptic transmission of impulses by neurotransmitters, including the regulation mechanisms of the process.

Because the neurotransmitter is normally stored on one side of the synaptic cleft and the receptor sites are on the other side, chemical synapses operate in one direction. Therefore action potentials are transmitted along a multineuronal pathway in one direction. The binding of the neurotransmitter at the receptor site changes the permeability of the postsynaptic neuron and, consequently, its membrane potential. Two possible scenarios can then follow: (1) the postsynaptic neuron may be excited (depolarized; excitatory postsynaptic potentials [EPSPs]) or (2) the postsynaptic neuron's plasma membrane may be inhibited (hyperpolarized; inhibitory postsynaptic potentials [IPSPs]). Cannabinoid transmitters have been discovered that are released from postsynaptic neurons and modulate neurotransmitter release from the presynaptic neurons (retrograde transmission). (Chapter 1 reviews electrical impulses and membrane potentials.) Usually a single EPSP cannot induce a neuron's action potential and the propagation of the nerve impulse. Whether this occurs depends on the number and frequency of potentials the postsynaptic neuron receives—a concept known as summation. Temporal summation (time relationship) refers to the effects of successive, rapid impulses received from a single neuron at the same synapse. Spatial summation (spacing effect) is the combined effects of impulses from a number of neurons onto a single neuron at the same time. Facilitation refers to the effect of EPSP on the plasma membrane potential. The plasma membrane is facilitated when summation brings the membrane closer to the threshold potential and decreases the stimulus required to induce an action potential. The effect that a chemical neurotransmitter has on the plasma membrane potential depends on the balance of these effects. The mechanisms of convergence (many neurons firing and converging on one neuron), divergence (one neuron firing and diverging on many neurons), summation, and facilitation allow for the integrative processes of the nervous system.

Discuss factors that regulate the flow of blood in the coronary circulation.

Blood flow through the coronary circulation is governed by the same principles as flow through other vascular beds plus two adaptations dictated by cardiac dynamics. First, blood flows into the coronary arteries during diastole rather than systole, because during systole the cusps of the aortic semilunar valve block the openings of the coronary arteries. Second, systolic contraction inhibits coronary artery flow by compressing the coronary arteries. Several unique anatomic factors influence coronary blood flow. Because of their anatomic location, the aortic valve cusps can obstruct coronary blood flow by occluding the openings of the coronary arteries during systole. Also during systole, the coronary arteries are compressed by ventricular contraction. The resulting systolic compressive effect is particularly evident in the subendocardial layers of the left ventricular wall and can greatly increase resistance to coronary blood flow with the result that most left ventricular coronary blood flow occurs during diastole. During the period of systolic compression, when flow is slowed or stopped, myoglobin, a protein in heart muscle that binds oxygen, provides the supply of oxygen to the myocardium. Myoglobin's oxygen levels are replenished during diastole. *Autoregulation (automatic self-regulation) enables organs to regulate blood flow by altering the resistance (diameter) in their arterioles. Autoregulation in the coronary circulation maintains the blood flow at a nearly constant rate at perfusion pressures (mean arterial pressure) between 60 and 140 mm Hg when other influencing factors are held constant. Thus autoregulation helps to ensure constant coronary blood flow despite shifts in the perfusion pressure within the stated range. Autoregulation enables the coronary vessels to maintain optimal perfusion pressure despite systolic compression. *Autonomic Regulation Although the coronary vessels, themselves, contain sympathetic (α- and β- adrenergic) and parasympathetic neural receptors, coronary blood flow during regular activity is regulated locally by the factors that cause autoregulation. During exercise, however, the vasodilating effects of β2-receptors on the smaller coronary resistance arteries are responsible for about 25% of any increase in blood flow. At the same time, α-adrenergic receptors in larger arteries cause vasoconstriction to direct the blood flow to the inner layers of the myocardium.

Compare and contrast the structure and function of arteries, veins, and capillaries.

Blood vessel walls are composed of three layers: (1) the tunica intima (innermost, or intimal, layer), (2) the tunica media (middle, or medial, layer), (3) the tunica externa or adventitia (outermost, or external, layer). Tunica Media- smooth mucle layer and elasic tissue(thicker in artieries, thinner in veins) Tunica Externa-connective tissue( thinner than tunica media in arteries, thickest layer in veins) An artery is a thick-walled pulsating blood vessel transporting blood away from the heart. In the systemic circulation, arteries carry oxygenated blood. Arterial walls are composed of elastic connective tissue, fibrous connective tissue, and smooth muscle. Capillaries are composed solely of a layer of endothelial cells surrounded by a basement membrane. Their thin walls and unique structure make possible the rapid exchange of water; small (low molecular weight) soluble molecules; some larger molecules, such as albumin; and cells of the innate and adaptive components of the immune system between the blood and the interstitial fluid. Compared with arteries, veins are thin walled with more fibrous connective tissue and have a larger diameter (see Figure 23-19). Veins also are more numerous than arteries.Veins contain valves to facilitate the one-way flow of blood toward the heart. These valves are folds of the tunica intima and resemble the semilunar valves of the heart. The venous tunica externa has less elastic tissue than that in arteries, so veins do not recoil as much or as rapidly after distention. Like arteries, veins receive nourishment from tiny vasa vasorum.

Discuss the symptoms, causes, and differential diagnosis of bronchiolitis.

Bronchiolitis is a common, viral respiratory tract infection of the small airways that occurs almost exclusively in infants and young toddlers and is a major reason for hospitalization. The most common associated pathogen is respiratory syncytial virus (RSV), but bronchiolitis also may be associated with human metapneumovirus and human bocavirus. Symptoms usually begin with significant rhinorrhea followed by a tight cough over the next several days, along with systemic signs of decreased appetite, lethargy, and fever. Infants typically have tachypnea, variable degrees of respiratory distress, and abnormal auscultatory findings of the chest. Wheezing is most common, but rales or rhonchi also may be present. Chest radiographs often reveal hyperexpanded lungs, patchy or peribronchial infiltrates, and, sometimes, atelectasis of the right upper lobe. Very young infants may present with severe apnea before lower respiratory tract symptoms appear, and these apneas frequently require mechanical ventilation. Many children also may present with conjunctivitis or otitis media. Diagnosis of bronchiolitis is made by review of history, signs, and symptoms (e.g., rhinitis, cough, wheezing, chest retractions, tachypnea). Laboratory and radiologic examination are not routinely performed.

Discuss the causes of bronchopulmonary dysplasia in the premature neonate.

Bronchopulmonary dysplasia (BPD), also known as chronic lung disease (CLD) of prematurity, is the major cause of pulmonary disease in infants It is associated with premature birth (usually before 28 weeks' gestation), prolonged (at least 28 days) perinatal supplemental oxygen, and positive pressure ventilation.

Compare and contrast the types of stones.

Calcium stones account for 70% to 80% of all stones requiring treatment. Calcium oxalate accounts for about 80% of these stones and calcium phosphate about 15%. Most individuals have idiopathic calcium urolithiasis (ICU), a condition whose exact etiology has not yet been defined. Stones can form freely in supersaturated urine or detach from interstitial sites within the tubules (Randall plaque formation) near the tip of the renal papillae. Hypercalciuria, hyperoxaluria, hyperuricosuria, hypocitraturia, mild renal tubular acidosis, or crystal growth inhibitor deficiencies and alkaline urine are associated with calcium stones. Hypercalciuria is attributable to intestinal hyperabsorption of dietary calcium and decreased renal calcium reabsorption. Hyperparathyroidism and bone demineralization associated with prolonged immobilization are also known to cause hypercalciuria. Although oxalate in the diet influences the risk of calcium stones, primary hyperoxaluria is a rare, inherited disorder. Struvite stones primarily contain magnesium-ammonium-phosphate as well as varying levels of matrix. Matrix forms in an alkaline urine and during infection with a urease-producing bacterial pathogen, such as a Proteus, Klebsiella, or Pseudomonas. Struvite calculi may grow quite large and branch into a staghorn configuration (staghorn calculus) that approximates the pelvicaliceal collecting system. Uric acid stones occur in persons who excrete excessive uric acid in the urine, such as those with gouty arthritis. Uric acid is primarily a product of biosynthesis of endogenous purines and is secondarily affected by consumption of purines (e.g., meat and beer) in the diet. A consistently acidic urine (pH <5.0) greatly increases this risk. Cystine and xanthine are amino acids that precipitate more readily in acidic urine. Cystinuria and xanthinuria are both genetic disorders of amino acid metabolism, and excess of these amino acids in urine can cause cystinuric, or xanthine, stone formation in the presence of a low urine pH of 5.5 or less.

Describe the pathophysiology of kidney stone formation.

Calculus formation is complex and related to (1) supersaturation of one or more salts in the urine, (2) precipitation of the salts from a liquid to a solid state, (3) growth through crystallization or agglomeration (sometimes called aggregation), and (4) the presence or absence of stone inhibitors (e.g., uromodulin [Tamm- Horsfall protein]).9 Supersaturation is the presence of a higher concentration of a salt within a fluid (in this case, the urine) than the volume is able to dissolve to maintain equilibrium. Human urine contains many ions capable of precipitating from solution and forming a variety of salts. The salts form crystals that are retained and grow into stones. Crystallization is the process by which crystals grow from a small nidus or nucleus to larger stones in the presence of supersaturated urine. Although supersaturation is essential for free stone formation, the urine need not remain continuously supersaturated for a calculus to grow once its nidus has precipitated from solution. Intermittent periods of supersaturation after the ingestion of a meal or during times of dehydration from limited oral intake or secondary to continued use of diuretics are sufficient for stone growth in many individuals. In addition, the renal tubules and papillae have many surfaces that may attract a crystalline nidus (Randall plaque) and add biologic material (matrix) forming a stone.10 Matrix is an organic material (i.e., mucoprotein) in which the components of a kidney stone are embedded. The temperature and pH of the urine also influence the risk of precipitation and calculus formation, and pH is most important. An alkaline urinary pH (pH >7.0) significantly increases the risk of calcium phosphate stone formation, whereas acidic urine (pH <5.0) increases the risk of uric acid stone formation. Cystine and xanthine also precipitate more readily in acidic urine. Stone or crystal growth inhibiting substances, such as potassium citrate, Tamm- Horsfall protein, pyrophosphate, and magnesium, are capable of crystal growth inhibition, thereby reducing the risk of calcium phosphate or calcium oxalate precipitation in the urine and preventing subsequent stone formation. The size of a stone determines the likelihood that it will pass through the urinary tract and be excreted through micturition. Stones smaller than 5 mm have about a 50% chance of spontaneous (painful) passage, whereas stones that are 1 cm have almost no chance of spontaneous passage. Retention of crystal particles occurs primarily at the papillary collecting ducts. Although most crystals are flushed from the tract through antegrade urine flow, urinary stasis (i.e., from benign prostatic hyperplasia, neurogenic bladder), anatomic abnormalities (strictures), or inflamed epithelium within the urinary tract may prevent prompt flushing of crystals from the system, thus increasing the risk of calculus formation.

Identify the causes of glomerulonephritis and the resulting changes in glomerular structure and function.

Causes: Glomerulonephritis is an inflammation of the glomerulus caused by primary glomerular injury, including immunologic responses, ischemia, free radicals, drugs, toxins, vascular disorders, and infection. Secondary glomerular injury is a consequence of systemic diseases, including diabetes mellitus, systemic lupus erythematosus, congestive heart failure, and human immunodeficiency virus (HIV)-related kidney disease. Changes in glomerular structure and function: The injury increases glomerular membrane permeability and reduces glomerular membrane surface area. The GFR decreases. There also may be swelling and proliferation of mesangial cells and expansion of the extracellular matrix in the Bowman space contributing to crescent formation (deposition of substances in the Bowman space, forming the shape of a crescent moon). The result is a decrease in glomerular blood flow, decreased driving hydrostatic pressure, decreased GFR, and hypoxic injury.

Describe gluten-sensitive enteropathy.

Celiac disease -genetically based permanent intolerance to ingested gluten which results in general malabsorption due to mucosal damage and loss of absorptive surface -autoimmune disorder -gluten(gliadin) exposure causes damage to villin in lining of small intestine -damage leads to malabsorption of nutrients

Discuss the importance of CNS malformations in infant mortality (see p. 423) , and identify the structural malformations that occur as a result of defects of neural tube closure.

Central nervous system (CNS) malformations are responsible for 75% of fetal deaths and 40% of deaths during the first year of life. CNS malformations account for 33% of all apparent congenital malformations, and 90% of CNS malformations are defects of neural tube closure. Spina bifida (split spine) is the most common neural tube defect and includes anencephaly (an, "without"; enkephalos, "brain"), encephalocele, meningocele, and myelomeningocele. Myelomeningocele is a form of spina bifida with incomplete development of the spine and protrusion of both the spinal cord and the meninges through the skin. Meningocele is a form of spina bifida in which there is protrusion of the meninges but the spinal cord remains in the spinal canal Anencephaly is an anomaly in which the soft, bony component of the skull and part of the brain are missing. This is a relatively common disorder, with an incidence of approximately 1 per 4859 total live births in the United States each year. These infants are stillborn or die within a few days after birth. The pathologic mechanism is unknown. Diagnosis is often made prenatally by using ultrasound or evaluating maternal serum alpha fetoprotein (AFP). Encephalocele refers to a herniation or protrusion of the brain and meninges through a defect in the skull, resulting in a saclike structure. The incidence is approximately 1.0 in 10,000 live births in the United States each year. Meningocele is a saclike cyst of meninges filled with spinal fluid and is a mild form of spina bifida (Figure 17-3). It develops during the first 4 weeks of pregnancy when the neural tube fails to close completely. The cystic dilation of meninges protrudes through the vertebral defect but does not involve the spinal cord or nerve roots and may produce no neurologic deficit or symptoms. Meningoceles occur with equal frequency in the cervical, thoracic, and lumbar spine areas. Myelomeningocele (meningomyelocele; spina bifida cystica) is a hernial protrusion of a saclike cyst (containing meninges, spinal fluid, and a portion of the spinal cord with its nerves) through a defect in the posterior arch of a vertebra. Eighty percent of myelomeningoceles are located in the lumbar and lumbosacral regions, the last regions of the neural tube to close. Myelomeningocele is one of the most common developmental anomalies of the nervous system, with an incidence rate ranging from 0.5 to 1.0 per 1000 pregnancies. Meningocele and myelomeningoceles are evident at birth as a pronounced skin defect on the infant's back. The bony prominences of the unfused neural arches can be palpated at the lateral border of the defect. The defect usually is covered by a transparent membrane that may have neural tissue attached to its inner surface. This membrane may be intact at birth or may leak cerebrospinal fluid (CSF), thereby increasing the risks of infection and neuronal damage. The spinal cord and nerve roots are malformed below the level of the lesion, resulting in loss of motor, sensory, reflex, and autonomic functions. A brief neurologic examination concentrating on motor function in the legs, reflexes, and sphincter tone is usually sufficient to determine the level above which spinal cord and nerve root function is preserved Myelomeningoceles are almost always associated with the Chiari II malformation (Arnold-Chiari malformation).12 This is a complex malformation of the brainstem and cerebellum in which the cerebellar tonsils are displaced downward into the cervical spinal canal; the upper medulla and lower pons are elongated and thin; and the medulla is also displaced downward and sometimes has a "kink" . The Chiari II malformation is associated with hydrocephalus from pressure that blocks the flow of cerebrospinal fluid; syringomyelia, an abnormality causing cysts at multiple levels within the spinal cord; and cognitive and motor deficits. Tethered cord syndrome may develop after surgical correction for myelomeningocele. The cord becomes abnormally attached or tethered as a result of scar tissue as the cord transcends the vertebral canal with growth

List the causes of cerebral edema and give examples of the pathophysiology producing each cause.

Cerebral edema is an increase in the fluid content of brain tissue. It occurs after brain insult from trauma, infection, hemorrhage, tumor, ischemia, infarction, or hypoxia. Three types of cerebral edema are (1) vasogenic edema, (2) cytotoxic (metabolic) edema, and (3) interstitial edema. Vasogenic edema is clinically the most important type and is caused by the increased permeability of the capillary endothelium of the brain after injury to the vascular structure. The selective permeability of capillaries that comprise the blood-brain barrier is disrupted. Plasma proteins leak into the extracellular spaces, drawing water to them and increasing the water content of the brain parenchyma. Vasogenic edema begins in the area of injury and spreads, with fluid accumulating in the white matter of the ipsilateral side because the parallel myelinated fibers separate more easily. Edema promotes more edema because of ischemia from the increasing ICP. Clinical manifestations of vasogenic edema include focal neurologic deficits, disturbances of consciousness, and a severe increase in ICP. Vasogenic edema resolves by slow diffusion. In cytotoxic (metabolic) edema, toxic factors directly affect the cellular elements of the brain parenchyma (neuronal, glial, and endothelial cells), causing failure of the active transport systems. The cells lose their potassium and gain larger amounts of sodium. Water follows by osmosis into the cells, so that the cells swell. Cytotoxic edema occurs principally in the gray matter and may increase vasogenic edema. Interstitial edema is seen most often with noncommunicating hydrocephalus. The edema is caused by transependymal movement of CSF from the ventricles into the extracellular spaces of the brain tissues. The brain fluid volume increases predominantly around the ventricles, with increased hydrostatic pressure within the white matter. The size of the white matter is reduced because of the rapid disappearance of myelin lipids.

which of the following is TRUE regarding cholelithiasis?

Cholesterol stones are the most common.

Discuss the clinical manifestations of chronic kidney disease, focusing on creatinine and urea clearance and fluid and electrolyte balance (p. 764-765).

Chronic kidney disease (CKD) is the progressive loss of renal function associated with systemic diseases, such as diabetes mellitus (most significant risk factor), hypertension, or systemic lupus erythematosus, or with intrinsic kidney diseases, such as acute kidney injury, chronic glomerulonephritis, chronic pyelonephritis, obstructive uropathies, or vascular disorders Creatinine and Urea Clearance Creatinine is constantly released from muscle and excreted primarily by glomerular filtration. In chronic kidney disease (CKD), as glomerular filtration rate (GFR) declines, the plasma creatinine level increases by a reciprocal amount to maintain a constant rate of excretion. As GFR continues to decline, plasma creatinine concentration increases. The clearance of urea follows a similar pattern, but urea is both filtered and reabsorbed and its level varies with the state of hydration; therefore urea concentration is not a good index of GFR. However, as the GFR decreases, plasma urea concentration also increases. Fluid and Electrolyte Balance Fluid and electrolyte and acid-base balance is significantly disturbed with chronic kidney disease. When the GFR decreases to 25%, there is an adaptive loss of 20 to 40 mEq of sodium per day with osmotic loss of water. Dietary intake must be maintained to prevent sodium deficits and volume depletion. As GFR continues to decline, there also is loss of tubular function to dilute and concentrate the urine and urine specific gravity becomes fixed at about 1.010. Ultimately the kidney loses its ability to regulate sodium and water balance. Both sodium and water are retained, contributing to edema, proteinuria, and hypertension. In early kidney failure, tubular secretion of potassium is maintained and larger amounts of potassium are lost through the bowel. With the onset of oliguria, total body potassium concentration can increase to life-threatening levels and must be controlled by dialysis. Metabolic acidosis develops when the GFR decreases to less than 20% to 25% of normal. The causes of acidosis are primarily related to decreased hydrogen ion elimination and decreased bicarbonate reabsorption. With end-stage kidney disease, metabolic acidosis may be severe enough to require alkali therapy and dialysis.

Compare and contrast microvascular and macrovascular complications of DM, including their pathologic mechanisms.

Diabetic microvascular complications (disease in capillaries) are a leading cause of blindness, end-stage kidney failure, and various neuropathies. *Retinopathy Nonproliferative Microaneurysms, capillary dilation, soft and hard exudates, dot and flame hemorrhages, arteriovenous shunts- May have no visual changes Proliferative-Formation of new blood vessels, vitreal hemorrhage, scarring, retinal detachment- Loss of visual acuity Maculopathy-Macular edema-Loss of central vision Hyperglycemic lens edema-Shunting of glucose to polyol pathway: hyperosmolar fluid in lens-Blurring of vision Cataract formation-Chronic hyperglycemia-Decreasing visual acuity Macrovascular disease (lesions in large- and medium-sized arteries) increases morbidity and mortality and increases risk for hypertension, accelerated atherosclerosis, cardiovascular disease, stroke, and peripheral vascular disease, particularly among individuals with type 2 diabetes mellitus. Cardiovascular-Endothelial dysfunction, hyperlipidemia, accelerated atherosclerosis, coagulopathies-Hypertension, coronary artery disease, cardiomyopathy, and heart failure Cerebrovascular-Same as above-Increased risk for ischemic and thrombotic stroke Peripheral vascular-Same as above- Claudication, nonhealing ulcers, gangrene Infection-Impaired immunity, decreased perfusion, recurrent trauma, delayed wound healing, urinary retention-Wound infections, urinary tract infections, increased risk for sepsis

Describe the structures of the mouth and esophagus, noting specific structures, function and secretions.

Digestion begins in the mouth, with chewing and salivation. The digestive component of saliva is α-amylase, which initiates carbohydrate digestion. The esophagus is a muscular tube that transports food from the mouth to the stomach. The tunica muscularis in the upper part of the esophagus is striated muscle, and that in the lower part is smooth muscle. The upper esophageal sphincter keeps air from entering the esophagus during respiration. The lower esophageal sphincter (cardiac sphincter) prevents regurgitation from the stomach and caustic injury to the esophagus.

Name the general class of receptors for the endogenous opioids.

Endogenous opioids are a family of morphine-like neuropeptides that inhibit transmission of pain impulses in the periphery, spinal cord, and brain by binding with specific opioid receptors (mu [μ], kappa [κ], and delta [δ]) on neurons.

Describe the cardiac cycle.

Each ventricular contraction and the relaxation that follows it constitute one cardiac cycle. (Blood flow through the heart during a single cardiac cycle is illustrated in Figure 23-5.) The pumping action of the heart consists of contraction and relaxation of the myocardial layer of the heart wall. Each ventricular contraction and the relaxation that follows it constitute one cardiac cycle -Systole: contraction phase -Move blood out of ventricles •Diastole: relaxation phase -Blood fills ventricles

Discuss how ventilation and perfusion are interrelated.

Effective gas exchange depends on an approximately even distribution of gas (ventilation) and blood (perfusion) in all portions of the lungs.

Describe how ions and membrane polarization are related.

Electrical activation of the muscle cells, termed depolarization, is caused by the movement of ions, including sodium, potassium, calcium, and chloride, across cardiac cell membranes. Deactivation, called repolarization, occurs the same way. (Movement of ions across cell membranes is described in Chapter 1; electrical activation of muscle cells is described in Chapter 38.) Movement of ions into and out of the cell creates an electrical (voltage) difference across the cell membrane, called the membrane potential.

Describe the basic effect that endorphins have on the transmission of pain impulses.

Endorphins (endogenous morphine) are produced in the brain. The best studied endorphin is β-endorphin, which binds to μ receptors and is purported to produce the greatest sense of exhilaration as well as substantial natural pain relief.

Describe the structural defects of esophageal atresia and tracheoesophageal fistula.

Esophageal atresia (EA) is the most common congenital atresia of the esophagus. The esophagus ends in a blind pouch. EA is usually accompanied by a fistula between the esophagus and the trachea (tracheoesophageal fistula [EA/TEF]).

Review the etiology, infectious agents, manifestations, treatments, and complications of urinary tract infections.

Etiology: A urinary tract infection (UTI) is an inflammation of the urinary epithelium usually caused by bacteria from gut flora. A UTI can occur anywhere along the urinary tract including the urethra, prostate, bladder,ureter, or kidney. At risk are premature newborns; prepubertal children; sexually active and pregnant women; women treated with antibiotics that disrupt vaginal flora; spermicide users; estrogen deficient postmenopausal women; individuals with indwelling catheters; and persons with diabetes mellitus, neurogenic bladder, or urinary tract obstruction. Cystitis is more common in women because of the shorter urethra and the closeness of the urethra to the anus (increasing the possibility of bacterial contamination). Up to 50% of women may have lower UTI at some time in their life. Generally, UTIs are mild, without complications, and occur in individuals with a normal urinary tract; these infections are termed uncomplicated UTI. A complicated UTI develops when there is an abnormality in the urinary system or a health problem that compromises host defenses or response to treatment. UTI may occur alone or in association with pyelonephritis, prostatitis or kidney stones. Infectious agents (patho): The most common infecting microorganisms are uropathic strains of Escherichia coli and the second most common is Staphylococcus saprophyticus. Less common microorganisms include Klebsiella, Proteus, Pseudomonas fungi, viruses, parasites, or tubercular bacilli. Schistosomiasis is the most common cause of parasitic invasion of the urinary tract on a global basis; it infects over 200 million people and has a strong association with bladder cancer. Bacterial contamination of the normally sterile urine usually occurs by retrograde movement of gram-negative bacilli into the urethra and bladder and then to the ureter and kidney. Uropathic strains of E. coli have type-1 fimbriae that bind to latex catheters and rreceptors on uroepithelium. They resist flushing during normal micturition. These strains also have P fimbriae (pyelonephritis-associated fimbriae) that bind to uroepithelial P-blood group antigen which is present in most of the human population and readily ascends the urinary tract. Some women may be genetically susceptible to certain strains of E. coli attachment. Hematogenous infections are uncommon and often preceded by septicemia. Infection initiates an inflammatory response and the symptoms of cystitis. The inflammatory edema in the bladder wall stimulates discharge of stretch receptors initiating symptoms of bladder fullness with small volumes of urine and producing the urgency and frequency of urination associated with cystitis. Manifestations/Complications: Many individuals with bacteriuria are asymptomatic and the elderly have the highest risk. Clinical manifestations of cystitis, however, usually include frequency, urgency, dysuria (painful urination), and suprapubic and low back pain. Hematuria, cloudy urine, and flank pain are more serious symptoms. Approximately 10% of individuals with bacteriuria have no symptoms, and 30% of individuals with symptoms are abacteriuric. Elderly persons with cystitis may be asymptomatic or demonstrate confusion or vague abdominal discomfort. The elderly with recurrent UTI and other current illness have a higher risk of mortality. Treatment: Evidence of bacteria from urine culture and antibiotic sensitivity warrants treatment with a micro-organism-specific antibiotic. A 3-day course may be effective for uncomplicated UTI. Three to 7 days of treatment is most common; complicated UTI requires 7 to 14 days of treatment. From 20% to 25% of women have relapsing infection within 7 to 10 days requiring prolonged antibotic treatment. Follow-up urine cultures should be obtained 1 week after initiation of treatment and at monthly intervals for 3 months. Clinical symptoms are frequently relieved, but bacteria may still be present. Repeat cultures should be obtained every 3 to 4 months until 1 year after treatment for evaluation of recurrent infection. See health alert: Urinary Tract Infection and Antibiotic Resistance.

Describe excitation-contraction coupling (ECC) in cardiac muscle cells (i.e., cardiomyocytes, myocardial cells or fibers).

Excitation-contraction coupling is the process by which an action potential arriving at the muscle fiber plasma membrane triggers the cycle, leading to cross- bridge formation and contraction.

Discuss factors influencing or regulating the systemic blood pressure and blood flow.

Factors the influence blood flow include pressure, resistance, velocity, turbulent versus laminar flow, and compliance, with the most important of these being pressure and resistance. *Pressure in a liquid system is the force exerted on the liquid per unit area and is expressed clinically as millimeters of mercury (mm Hg), or torr (1 torr = 1 mm Hg). Blood flow to an organ depends partly on the pressure difference between the arterial and venous vessels supplying that organ. Fluid moves from the arterial "side" of the capillaries where the pressure is higher to the venous side where the pressure is lower. *Resistance is the opposition to blood flow. Most opposition to blood flow results from the diameter and length of the vessels. Changes in blood flow through an organ result from changes in the vascular resistance within the organ because of increases or decreases in vessel diameter and the opening or closing of vascular channels. Resistance in a vessel is inversely related to blood flow—that is, increased resistance leads to decreased blood flow. *Blood velocity or speed is the distance blood travels in a unit of time, usually centimeters per second (cm/sec). It is directly related to blood flow (amount of blood moved per unit of time) and inversely related to the cross-sectional area of the vessel in which the blood is flowing (Figure 23-23). As blood moves from the aorta to the capillaries, the total cross-sectional area of the vessels increases and the velocity decreases. *Flow through a tubular system can be either laminar or turbulent. Blood flow through the vessels, except where vessels split or branch, is usually laminar. In laminar flow, concentric layers of molecules move "straight ahead" with each layer flowing at a slightly different velocity. Where flow is obstructed, the vessel turns, or blood flows over rough surfaces, the flow becomes turbulent with whorls or eddy currents that produce noise, causing a murmur to be heard on auscultation. Resistance increases with turbulence, which frequently occurs in areas with atherosclerotic plaque. *Vascular compliance is the increase in volume a vessel can accommodate for a given increase in pressure. Compliance depends on factors related to the nature of a vessel wall, such as the ratio of elastic fibers to muscle fibers in the wall. Elastic arteries are more compliant than muscular arteries. The veins are more compliant than either type of artery, and they can serve as storage areas for the circulatory system.

Define flail chest.

Flail chest results from the fracture of several consecutive ribs in more than one place or fracture of the sternum and several consecutive ribs. These multiple fractures result in instability of a portion of the chest wall, causing paradoxical movement of the chest with breathing

Identify the structures involved in gas exchange.

Gas exchange occurs in structures beyond the respiratory bronchioles: in the alveolar ducts and the alveoli. Together these structures compose the acinus.

Discuss the pathophysiology and manifestations of infective endocarditis.

General term used to describe infection and inflammation of the endocardium—especially the cardiac valves. Bacteria are the most common cause of infective endocarditis, especially streptococci, staphylococci, and enterococci, which account for more than 80% of cases. Other causes include viruses, fungi, rickettsia, and parasites. The "classic" findings are fever; new or changed cardiac murmur; and petechial lesions of the skin, conjunctiva, and oral mucosa. Characteristic physical findings include Osler nodes (painful erythematous nodules on the pads of the fingers and toes) and Janeway lesions (nonpainful hemorrhagic lesions on the palms and soles). Central nervous system complications are the most frequent and the most severe extracardiac complications and include stroke, abscess, and meningitis. Other manifestations include weight loss, back pain, night sweats, and heart failure. Endocardial damage. Trauma, congenital heart disease, valvular heart disease, and the presence of prosthetic valves are the most common risk factors for endocardial damage that leads to infective endocarditis. Turbulent blood flow caused by these abnormalities usually affects the atrial surface of atrioventricular valves or the ventricular surface of semilunar valves. 1. Endocardial damage exposes the endothelial basement membrane, which contains a type of collagen that attracts platelets and thereby stimulates sterile thrombus formation on the membrane. This causes an inflammatory reaction (nonbacterial thrombotic endocarditis). 2. Adherence of blood-borne microorganisms to the damaged endocardial surface. Bacteria may enter the bloodstream during injection drug use, trauma, dental procedures that involve manipulation of the gingiva, cardiac surgery, genitourinary procedures and indwelling catheters in the presence of infection, or gastrointestinal instrumentation, or they may spread from uncomplicated upper respiratory tract or skin infections. Bacteria adhere to the damaged endocardium using adhesins. 3. Formation of infective endocardial vegetations . Bacteria infiltrate the sterile thrombi and accelerate fibrin formation by activating the clotting cascade. These vegetative lesions can form anywhere on the endocardium but usually occur on heart valves and surrounding structures. Although endocardial tissue is constantly bathed in antibody-containing blood and is surrounded by scavenging monocytes and polymorphonuclear leukocytes, bacterial colonies are inaccessible to host defenses because they are embedded in the protective fibrin clots. Embolization from these vegetations can lead to abscesses and characteristic skin changes, such as petechiae, splinter hemorrhages, Osler nodes, and Janeway lesions.

Describe congenital aganglionic megacolon (Hirschsprung disease).

Hirschsprung disease, or aganglionic megacolon, is a functional obstruction of the colon. It is the most common cause of colon obstruction, accounting for about one third of all gastrointestinal obstructions in infants. The incidence is approximately 1 in 5000 live births, and varies among ethnic groups. There is a predominance in males. Hirschsprung disease is a multifactorial malformation. -A 2-month-old female with Down syndrome is diagnosed with Hirschsprung disease following family complaints of chronic constipation. The most likely cause of these symptoms is: Absence of ganglia along the length of the colon

Discuss the function of the renin-angiotensin-aldosterone system in regulating blood pressure.

Hormones influence blood pressure regulation through their effects on vascular smooth muscle and blood volume. By constricting or dilating the arterioles in organs, hormones can (1) increase or decrease the flow in response to the body's needs, (2) redistribute blood volume during hemorrhage or shock, and (3) regulate heat loss. The vasoconstrictor hormones include epinephrine; norepinephrine; angiotensin II, which is part of the renin-angiotensin-aldosterone system; and vasopressin (also known as antidiuretic hormone). Epinephrine, the catecholamine hormone released from the adrenal medulla, causes vasoconstriction in most vascular beds except the coronary, liver, and skeletal muscle circulations. Norepinephrine mainly acts as a neurotransmitter; however, some also is released from the adrenal medulla. When released into the circulation, it is a more potent vasoconstrictor than epinephrine. Although angiotensin II and vasopressin are vasoconstrictors they are not thought to have a major role in blood pressure control in normal circumstances. Vasopressin and aldosterone also affect blood pressure by increasing blood volume through their influence on fluid reabsorption in the kidney and by stimulating thirst. Vasopressin causes the reabsorption of water from tubular fluid in the distal tubule and collecting duct of the nephron. Aldosterone, the end product of the renin-angiotensin-aldosterone system, stimulates the reabsorption of sodium, chloride, and water from the same locations in the kidney

Describe the causes and manifestations of hydrocephalus.

Hydrocephalus may develop from infancy through adulthood. Communicating hydrocephalus is defective resorption of CSF from the cerebral subarachnoid space and is found more often in adults. Noncommunicating hydrocephalus (internal hydrocephalus, intraventricular hydrocephalus) is obstruction within the ventricular system and is seen more often in children (see Figure 17-6). Congenital hydrocephalus is ventricular enlargement before birth and is rare. (Pathophysiology) The obstruction of CSF flow associated with hydrocephalus produces increased pressure and dilation of the ventricles proximal to the obstruction. The increased pressure and dilation cause atrophy of the cerebral cortex and degeneration of the white matter tracts. Selective preservation of gray matter occurs. When excess CSF fills a defect caused by atrophy, a degenerative disorder, or a surgical excision, this fluid is not under pressure; therefore atrophy and degenerative changes do not occur. Manifestations: Most cases of hydrocephalus develop gradually and insidiously over time. Acute hydrocephalus presents with signs of rapidly developing IICP. The person quickly deteriorates into a deep coma if not promptly treated. Normal-pressure hydrocephalus (dilation of the ventricles without increased pressure) develops slowly, with the individual or family noting declining memory and cognitive function. The triad symptoms of an unsteady, broad-based gait with a history of falling; incontinence; and dementia is common and may be treated surgically

Discuss the differences between primary, secondary, complicated, and isolated systolic hypertension.

Hypertension is consistent elevation of systemic arterial blood pressure. risk factors ; Family history Advancing age Cigarette smoking Obesity Heavy alcohol consumption Gender (men > women before age 55, women > men after 55) Black race High dietary sodium intake Low dietary intake of potassium, calcium, magnesium Glucose intolerance *Primary hypertension is the result of an extremely complicated interaction of genetics and the environment mediated by a host of neurohumoral effects. Multiple pathophysiologic mechanisms mediate these effects, including the sympathetic nervous system (SNS), the renin-angiotensin-aldosterone system (RAAS), and natriuretic peptides. Inflammation, endothelial dysfunction, obesity-related hormones, and insulin resistance also contribute to both increased peripheral resistance and increased blood volume. Increased vascular volume is related to a decrease in renal excretion of salt, often referred to as a shift in the pressure- natriuresis relationship. This means that for a given blood pressure, individuals with hypertension tend to secrete less salt in their urine. Pathophysiology:1. SNS stimulation Incr HR, Systemic vasoconstriction, Structural changes of blood vessels (remodeling),Renal sodium retention (secrete less salt in urine),Insulin resistance,Increased renin and angiotensin levels,Procoagulant effects *Secondary hypertension is caused by an underlying disease process or medication that raises peripheral vascular resistance or cardiac output. Examples include renal vascular or parenchymal disease, adrenocortical tumors, adrenomedullary tumors (pheochromocytoma), and drugs (oral contraceptives, corticosteroids, antihistamines). If the cause is identified and removed before permanent structural changes occur, blood pressure returns to normal. *Complicated Hypertension As hypertension becomes more severe and chronic, tissue damage can occur in the blood vessels and tissues leading to target organ damage in the heart, kidney, brain, and eyes. Cardiovascular complications of sustained hypertension include left ventricular hypertrophy, angina pectoris, heart failure, coronary artery disease, myocardial infarction, and sudden death. *Isolated Systolic Hypertension Systolic BP 140 Hg or ^ and diastolic BP below 90 Hg - Increased pule pressure is always present

Discuss the importance of malignant hypertension.

Hypertensive crisis (or malignant hypertension) is rapidly progressive hypertension in which diastolic pressure is usually greater than 140 mm Hg. It can occur in those with primary hypertension, but the reason why some people develop this complication and others do not is unknown. Besides encephalopathy, hypertensive crisis can cause papilledema, cardiac failure, uremia, retinopathy, and cerebrovascular accident and is considered a medical emergency

Define hyperventilation and hypoventilation.

Hypoventilation is inadequate alveolar ventilation in relation to metabolic demands. Hypoventilation occurs when minute volume (tidal volume × respiratory rate) is reduced. It is caused by alterations in pulmonary mechanics or in the neurologic control of breathing.6 When alveolar ventilation is normal, carbon dioxide (CO2) is removed from the lungs at the same rate as it is produced by cellular metabolism and arterial and alveolar PCO2 values remain at normal levels (40 mm Hg). With hypoventilation, CO2 removal does not keep up with CO2 production and PaCO2 increases, causing hypercapnia (PaCO2 greater than 44 mm Hg) This results in respiratory acidosis that can affect the function of many tissues throughout the body. Hypoventilation is often overlooked until it is severe because breathing pattern and ventilatory rate may appear to be normal and changes in tidal volume can be difficult to detect clinically. Blood gas analysis (i.e., measurement of the PaCO2 of arterial blood) reveals the hypoventilation. Pronounced hypoventilation can cause secondary hypoxemia, somnolence, or disorientation. Hyperventilation is alveolar ventilation exceeding metabolic demands. The lungs remove CO2 faster than it is produced by cellular metabolism, resulting in decreased PaCO2, or hypocapnia (PaCO2 less than 36 mm Hg). Hypocapnia results in a respiratory alkalosis that also can interfere with tissue function. Like hypoventilation, hyperventilation can be determined by arterial blood gas analysis. Hyperventilation commonly occurs with severe anxiety, acute head injury, pain, and in response to conditions that cause hypoxemia.

Discuss the most important cause of pulmonary vasoconstriction and how it relates to the matching of ventilation and perfusion.

Hypoxia is one of the main causes of pulmonary vasoconstriction. Ventilation and perfusion (V/Q) mismatch is caused by anything that increases or decreases ventilaiton of the lungs/alveoli. In other words, anything that interferes with the ability of fresh air to get to the alveoli, or anything that prevents blood flow to the capillaries. Both of these can disrupt the balance between ventilation and perfusion.

Identify how congestive heart failure in childhood differs from adulthood.

In general, the pathophysiologic mechanisms of HF in infants and children are similar to those in adults. It is most often a result of decreased left ventricular systolic function and the associated left atrial and pulmonary venous hypertension and pulmonary venous congestion. The same compensatory mechanisms are activated in the face of inadequate cardiac output. Right ventricular failure is rare in childhood.

Identify the different types of valvular dysfunction and describe the alterations in blood flow through the heart seen in each disorder; include the clinical manifestations of each disorder.

In valvular stenosis, the valve orifice is constricted and narrowed, so blood cannot flow forward and the workload of the cardiac chamber proximal to the diseased valve increases. In valvular regurgitation (also called insufficiency or incompetence), the valve leaflets, or cusps, fail to shut completely, permitting blood flow to continue even when the valve is presumably closed

Describe the pathology and causes of respiratory distress syndrome of the newborn.

Inadequate surfactant in lungs, do not expand normally during inspiration, collapse during expiration. There is no surfactant, or there is lung immaturity. This causes atelectasis and therefore V/Q mismatch because no oxygen is going to the area (hypoventilation). Hypoxia and hypercapnia develops, and then respiratory and metabolic acidosis. This whole thing is a shunt so vasoconstriction happens. Eventually, there is impaired endothelial and epithelial integrity. The paradoxical breathing and injuries to the endothelium cause proteinaceous exudates to form, and infant respiratory distress syndrome or as it was called, hyaline membrane disease develops. The hyaline membrane act as a barrier to gas exchange...vicious cycle

List the causes of increased intracranial pressure (IICP) and the associated clinical manifestations.

Increased intracranial pressure (IICP) may result from an increase in intracranial content (as occurs with tumor growth), edema, excess CSF, or hemorrhage. Stage 1 of intracranial hypertension results in vasoconstriction to decrease pressure. There may be no symptoms due to adequate compensation in stage 1. In stage 2 the pressure may exceed the brains compensatory mechanisms. Neuronal oxygenation may be compromised and vasoconstriction elevates systemic blood pressure. Confusion, restlessness, drowsiness, and slight pupillary and breathing changes may occur. In stage 3 ICP approaches arterial pressure causing hypoxia and hypercapnea. The patients condition rapidly deteriorates. Manifestations include decreased levels of arousal, central neruogenic hyperventilaion, widened pulse pressure, bradycardia, small sluggish pupils. In stage 4 brain tissue herniates from a compartment of great pressure to one of lesser pressure. Cerebral bloodflow ceases at this point.

Discuss insulin resistance, its causes and effects.

Insulin resistance is defined as a suboptimal response of insulin-sensitive tissues (especially liver, muscle, and adipose tissue) to insulin and is associated with obesity. Several mechanisms are involved in abnormalities of the insulin signaling pathway and contribute to insulin resistance. These include an abnormality of the insulin molecule, high amounts of insulin antagonists, down-regulation of the insulin receptor, and alteration of glucose transporter (GLUT) proteins.

Describe the pathophysiology of acute tubular necrosis (ATN). Primarily note that several of the diseases we've studied can lead to ATN. Also note that common radiocontrast media (i.e., substances used to enhance contrast in radioimaging and MRI) can be nephrotoxic.

Intrarenal (intrinsic) acute kidney injury usually results from ischemic acute tubular necrosis (ATN) related to nephrotoxic ATN (i.e., exposure to radiocontrast media); ATN caused by ischemia occurs most often after surgery (40% to 50% of cases) but also is associated with sepsis, obstetric complications, and severe trauma, including severe burns; Nephrotoxic ATN can be produced by radiocontrast media and numerous antibiotics, particularly the aminoglycosides (neomycin, gentamicin, tobramycin) because these drugs accumulate in the renal cortex. Other substances, such as excessive myoglobin (oxygen-transporting substance from muscles), carbon tetrachloride, heavy metals (mercury,arsenic), or methoxyflurane anesthetic, and bacterial toxins may promote renal failure.

Characterize irritable bowel syndrome.

Irritable bowel syndrome (IBS) is described as a functional disorder with recurring abdominal pain and bloating. IBS can be diarrhea prevalent or constipation prevalent or may alternate between diarrhea and constipation. Alterations in the brain-gut axis, gut microflora, gut immune responses, gut neuroendocrine cell function, genetic susceptibility, and epigenetic factors contribute to intestinal hypersensitivity, intestinal inflammation, increased permeability, and symptoms caused by alterations in motility and secretion.

Describe the disorders produced by interruption to cerebral vascular flow with reference to location, manifestations, and rehabilitation potential.

Ischemic stroke-invovles the arterial occlusions caused by thrombus, an embolus, or hypoperfusion formed in arteries supplying the brain or in the intracranial vessels. Manifestations: Inadequate blood supply include ischemia and can progress to cellular death. Rehab potential: restoring brain perfusion in a timeframe that does not contribute to reperfusion injury. Counteracting the ischemic cascade pathways. Lowering cerebral metabolic demand so that the susceptible brain tissue is protected against impaired perfusion. Promoting tissue restoration. Transient ischemic attacks-brief episode of neurologic dysfunction caused by focal disturbance of brain (lasting less than 1 hour). TIAs are thought to be the result of clumped platelets or vessel narrowing, which decreases/stops circulation and risk is high for future strokes. Brain infarction is a term of the past, but is the result of an ischemic event lasting less than 24 hours. Signs and symptoms include weakness, numbness, sudden confusion and loss of balance. Thrombotic stroke-from arterial occlusions caused by platelet formation in the arteries supplying blood to the brain blood vessels. Manifestations include different occlusion syndromes (carotid artery, dysphasia and contralateral motor). Rehab potential: Thrombolysis uses tissue-type plasminogen activator, given within 3 and up to 4.5 hours of onset of symptoms. Endovascular intraarterial thrombolysis may be used to treat those who cannot receive tPA. Supportive management is given to control cerebral edema and increased intracranial pressure and to provide neuroprotection. Embolic stroke-occurs when fragments from a thrombus (group of clots) breaks apart from outside the brain, usually in the heart. Manifestations:Same as Thrombotic. Rehab: Treatment to prevent further embolization by instituting anticoagulation therapy and correcting the primary problem. Hemorrhagic stroke-occurs within brain tissue or in the subarachnoid, subdural spaces. Manifestations:onset of an excruciating generalized headache with an almost immediate lapse into an unresponsive state. Headache but with consciousness maintained. Sudden lapse into unconsciousness. Rehab: Stopping or reducing the bleeding, controlled the increased intracranial pressure, preventing a rebleed, and preventing vasopasm.

Compare kwashiorkor to marasmus.

Kwashiorkor (deficiency of dietary protein) and marasmus (all forms of inadequate nutrient intake) are the two most common types of malnutrition in children. Marasmus- Severe wasting < 70% or <3SD weight/height No obvious pathology Looks very skinny

Describe intestinal malrotation

Malrotation is the term used to describe the spectrum of abnormalities of embryonic development of the midgut associated with abnormal intestinal rotation or fixation, or both. In malrotation, the small intestine lacks a normal posterior attachment. The mobile loops of intestine can twist upon themselves (volvulus), leading to symptoms of bowel obstruction. The twisting can partly or completely occlude the superior mesenteric artery, causing infarction and necrosis of the entire midgut. Peritoneal (Ladd) bands may press against and obstruct the duodenum. -A 2-month-old female is brought to the emergency room (ER) for persistent bile-stained vomiting after feeding. Physical examination reveals dehydration, and x-ray reveals that the colon is located in the upper right quadrant. What is the most likely cause of this condition?

Discuss the role of inflammation in asthma.

Many cells and cellular elements contribute to the persistent inflammation of the bronchial mucosa and hyperresponsiveness of the airways, including dendritic cells (antigen-presenting macrophages), T helper 2 (Th2) lymphocytes, B lymphocytes, mast cells, neutrophils, eosinophils, and basophils. There is both an immediate (early asthmatic response) and a late (delayed) response. During the early asthmatic response, antigen exposure to the bronchial mucosa activates dendritic cells, which present antigen to T-helper cells. T-helper cells differentiate into Th2 cells releasing inflammatory cytokines and interleukins that activate B lymphocytes (plasma cells) and eosinophils. Plasma cells produce antigen-specific IgE, which binds to the surface of mast cells. Subsequent cross- linking of IgE molecules with the antigen causes mast cell degranulation with the release of inflammatory mediators including histamine, bradykinins, leukotrienes and prostaglandins, platelet-activating factor, and interleukins. These inflammatory mediators cause vasodilation, increased capillary permeability, mucosal edema, bronchial smooth muscle contraction (bronchospasm), and mucus secretion from mucosal goblet cells with narrowing of the airways and obstruction to airflow. Eosinophils cause direct tissue injury and release of toxic neuropeptides that contribute to increased bronchial hyperresponsiveness

Discuss the risk factors and pathologic changes associated with pulmonary hypertension.

Mean pulmonary artery pressure 5 to 10mmHg above normal or above 20mmHg Primary pulmonary hypertension -Idiopathic Disease of the respiratory system and hypoxemia are more common causes. Pulmonary atrial hypertension is defined as a mean pulmonary artery pressure >25 mm Hg and is classified into several categories: Idiopathic, genetic, drug or toxin induced (weight loss medications, amphetamines, cocaine) Left heart disease Chronic lung disease, hypoxia, or both Chronic thromboembolic pulmonary HTN 5. Or caused by other multifactorial mechanisms including blood, metabolic, and systemic disorders. Patho: Idiopathic pulmonary arterial hypertension (IPAH) is characterized by endothelial dysfunction and overproduction of vasoconstrictors. Vascular growth factors are released, which cause remodeling within pulmonary smooth muscle. Fibrosis and vessel wall thickening occur, which causes luminal narrowing and a constriction of flow. These changes cause resistance to pulmonary artery blood flow, which increases the pressure in the pulmonary arteries. As resistance and pressure increase, the workload of the right ventricle increases and subsequent right ventricular hypertrophy, followed by right ventricular enlargement (cor pulmonale). Classifcations: Pulmonary arterial hypertension, pulmonary venous hypertension, pulmonary hypertension due to a respiratory disease or hypoxemia. Pulmonary hypertension due to thrombotic or embolic disease. Pulmonary hypertension due to diseases of the pulmonary vasculature. Pulmonary hypertension associated with lung disease, hypoxia, or both, is a serious complication of many acute and chronic pulmonary disorders, such as COPD, fibrosis, and hypoventilation associated with obesity. These conditions are complicated by hypoxic pulmonary vasoconstriction that further increases pulmonary artery pressures. S/S: Initially, pulmonary hypertension may be seen on x-ray (thru enlargement of the right heart) or an ECG reflects right ventricular hypertrophy. Fatigue, chest discomfort, tachypnea, and dyspnea (particularly with exercise) are common. Examination may reveal peripheral edema, jugular venous distention, a precordial heave, and accentuation of the pulmonary component of the second heart sound

Discuss the functional significance of myelin and the nodes of Ranvier.

Myelin, an insulating substance that speeds impulse propagation. The myelin acts as an insulting substance, which is a lipid like substance Referred to the myelin sheath -In the CNS myelin is produced by oligodendrocytes. In the PNS myelin is produced by Schwann cells There are interruptions within the sheath called nodes of Ranvier The nodes of Ranvier all the insulated neuron to have increased velocity with faster conduction

Describe the pathogenesis of nephroblastoma.

Nephroblastoma (Wilms tumor) is a rare embryonal tumor of the kidney arising from undifferentiated mesoderm and represents 5% of childhood cancers in the United States. Approximately 500 children are diagnosed each year in the United States, most younger than 5 years of age. The peak incidence occurs between 2 and 3 years of age. Nephroblastoma is slightly more common in black children than in white children. Maternal preconception toxin exposure (e.g., pesticides) may be associated with increased risk in offspring. Pathogenesis Nephroblastoma has both sporadic and inherited origins. The sporadic form occurs in children with no known genetic predisposition. Inherited cases, which are relatively rare, are transmitted in an autosomal dominant fashion. Syndromic and nonsyndromic causes of nephroblastoma have been linked to mutation of several tumor-suppressor genes (i.e., WT1 and WT2 mutations). Eighteen percent of children who have nephroblastoma also have other congenital anomalies. The anomalies associated with nephroblastoma include aniridia (lack of an iris in the eye), hemihyperplasia (an asymmetry of the body), and genitourinary malformations (i.e., horseshoe kidneys, hypospadias, ureteral duplication, polycystic kidneys). Children with both congenital anomalies and nephroblastoma are more likely to have the inherited bilateral form of the disease.

Describe the progression of nephrotic syndrome from causation through complications.

Nephrotic syndrome is the excretion of 3.5 g or more of protein in the urine per day and is characteristic of glomerular injury. Primary causes of nephrotic syndrome include minimal change disease (lipoid nephrosis) (see ch. 30), membranous glomerulonephritis, and focal segmental glomerulosclerosis. Secondary forms of nephrotic syndrome occur in systemic diseases, including diabetes mellitus, amyloidosis, systemic lupus erythematosus, and Henoch-Schonlein purpura. Nephrotic syndrome also is associated with certain drugs, infections, malignancies, and vascular disorders. When present as a secondary complication with renal diseases, nephrotic syndrome often signifies a more serious prognosis. Nephrotic syndrome is more common in children than adults. Patho: Disturbances in the glomerular basement membrane and podocyte injury lead to increased permeability to protein and loss of electrical negative charge. Loss of plasma proteins, particularly albumin and some immunoglobulins, occurs across the injured glomerular filtration membrane. Hypoalbuminemia results from urinary loss of albumin combined with a diminished synthesis of replacement albumin by the liver. Albumin is lost in the greatest quantity because of its high plasma concentration and low molecular weight. Decreased dietary intake of protein from anorexia or malnutrition or accompanying liver disease may also contribute to lower levels of plasma albumin. Loss of albumin stimulates lipoprotein synthesis by the liver and hyperlipidemia. Loss of immunoglobulins may increase susceptibility to infections. Sodium retention is common. Manifestations: Many clinical manifestations of nephrotic syndrome are related to loss of serum proteins and associated sodium retention. They include edema, hyperlipidemia, lipiduria, vitamin D deficiency, and hyperthyroidism. Vitamin D deficiency is related to loss of serum transport proteins and decreased vitamin D activation by the kidney. Hypothyroidism can result from urinary loss of thyroid-binding protein and thyroxine. Alterations in coagulation factors can cause hypercoagulability and may lead to thromboembolic events.

Describe the factors affecting nerve repair and regeneration after injury.

Nerve regeneration depends on many factors, such as location of the injury, the type of injury, the presence of inflammatory responses, and the process of scarring. The closer to the cell body of the nerve, the greater the chances that the nerve cell will die and not regenerate. -A crushing injury allows recovery more fully than does a cut injury. Crushed nerves sometimes recover fully, whereas cut nerves form connective tissue scars that block or slow regenerating axonal branches. -Peripheral nerves injured close to the spinal cord recover poorly and slowly because of the long distance between the cell body and the peripheral termination of the axon

List the risk factors associated neural tube defects.

Neural tube defects (NTDs) are caused by an arrest of the normal development of the brain and spinal cord during the first month of embryonic development. Folic acid deficiency during preconception and early stages of pregnancy increases the risk for neural tube defects, and supplementation (400 mcg of folic acid per day) ensures adequate folate status. Other risk factors include a previous NTD pregnancy, maternal diabetes or obesity, use of anticonvulsant drugs (particularly valproic acid), and maternal hyperthermia.

Describe what is meant by neurogenic bladder and overactive bladder syndrome.

Neurogenic bladder is a general term for bladder dysfunction caused by neurologic disorders (table 29-2). The types of dysfunction are related to the sites in the nervous system that control sensory and motor bladder function. Overactive bladder syndrome (OAB) is a syndrome of detrusor (muscle that forms a layer of the wall of the bladder) overactivity characterized by urgency with involuntary detursor contractions during the bladder filling phase that may be spontaneous or provoked. There is coordination between the contracting bladder and the external sphincter, but the detrusor is too weak to empty the bladder, resulting in urinary retention with overflow or stress incontinence.

Describe alterations in smell and taste with causation and effect.

Olfactory dysfunctions include the following: 1. Hyposmia—impaired sense of smell 2. Anosmia—complete loss of sense of smell 3. Olfactory hallucinations—smelling odors that are not really present 4. Parosmia—abnormal or perverted sense of smell The sense of taste can be impaired by injury. Altered taste may be attributed to impaired smell associated with injury near the hippocampus. *Hypogeusia is a decrease in taste sensation, *Ageusia is an absence of the sense of taste. These disorders result from cranial nerve injuries and can be specific to the area of the tongue innervated. Dysgeusia is a perversion of taste in which substances possess an unpleasant flavor (i.e., metallic). Alterations in taste may compromise adequate nutrition or cause anorexia. *The perception of flavor is altered if olfaction or taste dysfunctions occur. Sensitivity to odor and taste decreases with aging. *Hyposmia is a decrease in the sense of smell, and anosmia is the complete loss of the sense of smell. Inflammation of the nasal mucosa and trauma or tumors of the olfactory nerve lead to a diminished sense of smell. * Hypogeusia is a decrease in taste sensation, and ageusia is the absence of the sense of taste. Loss of taste buds or trauma to the facial or glossopharyngeal nerves decreases taste sensation.

Identify how obstructive sleep apnea in childhood differs from adulthood.

Partial or complete upper airway obstruction during sleep -Childhood causes: adenotonsilar hypertrophy -Adult: symptoms are different in adults, adults with short thick fatty necks are commonly seen with this

Identify the three systems involved in pain perception.

Pain perception is the conscious awareness of pain, which occurs primarily in the reticular and limbic systems and the cerebral cortex. Interpretation of pain is influenced by many factors including genetics, cultural preferences, gender roles, and life experience, including past pain experiences and level of health. Three systems interact to produce the perception of pain; *The sensory-discriminative system is mediated by the somatosensory cortex and is responsible for identifying the presence, character, location, and intensity of pain. *The affective-motivational system determines an individual's conditioned avoidance behaviors and emotional responses to pain. It is mediated through the reticular formation, limbic system, and brainstem. *The cognitive-evaluative system overlies the individual's learned behavior concerning the experience of pain and therefore can modulate perception of pain. It is mediated through the cerebral cortex. The integration of these three systems is referred to as the "pain matrix."

Describe the general physiological mechanism of pain transmission.

Pain transmission is the conduction of pain impulses along the Aδ and C fibers (primary order neurons) into the dorsal horn of the spinal cord. Here they form synapses with excitatory or inhibitory interneurons (second order neurons) in the substantia gelatinosa of the dorsal horn. The impulses then synapse with projection neurons (third order neurons), cross the midline of the spinal cord, and ascend to the brain through two lateral spinothalamic tracts. The neospinothalamic tract (anterior spinal thalamic tract) carries fast impulses for acute sharp pain. The paleospinothalamic tract (lateral spinothalamic tract) carries slow impulses for dull or chronic pain. The fast sharp pain is perceived first, followed by dull, throbbing pain. These tracts connect to the reticular formation, hypothalamus, thalamus (the major relay station of sensory information), and limbic system. The impulses are then projected to the somatosensory cortex for interpretation of location and intensity of pain, and to other areas of the brain for an integrated response to pain.

Discuss the pathophysiology, manifestations, and treatment for coarctation of the aorta.

Pathophysiology: Coarctation of the aorta (COA) is an abnormal localized narrowing of the aorta just proximal to the insertion of the ductus arteriosus. Before birth, the ductus arteriosus bypasses this obstruction and allows for blood to flow from the pulmonary artery into the distal aorta. However, once the ductus functionally closes within 15 hours after birth, blood flow to the lower extremities is then restricted by the coarctation. Clinically, there is increased blood pressure proximal to the defect (head and upper extremities, right greater than left) and decreased blood pressure distal to the obstruction (torso and lower extremities) Manifestations: The location and severity of the COA determine whether an infant will become symptomatic after the ductus arteriosus closes. If the COA is severe, infants will present with low cardiac output, poor tissue perfusion, acidosis, and hypotension. Physical examination of the infant will reveal weak or absent femoral pulses. Some infants with COA will remain asymptomatic after the closure of the ductus arteriosus. As they age, children with undiagnosed COA will present with unexplained upper extremity hypertension. Children may complain of leg pain or cramping with exercise. Although rare, they also may experience dizziness, headaches, fainting, or epistaxis from hypertension. Treatment: Physical examination and measurement of upper and lower extremity blood pressures will often suggest the diagnosis. Echocardiography, magnetic resonance imaging (MRI), and cardiac catheterization may be needed to confirm the diagnosis. Initial treatment in the symptomatic newborn consists of continuous intravenous infusion of prostaglandin E1 to maintain the patency of the ductus arteriosus. Once the symptomatic newborn is stabilized, surgical correction is indicated. Surgical correction consists of either resection of the narrowed portion of the aorta with an end-to-end anastomosis or enlargement of the constricted section using a graft taken from a portion of the left subclavian artery. Because this defect is outside the heart and pericardium, cardiopulmonary bypass usually is not required and a thoracotomy incision is used. However, coarctation repair may be part of a more complex operation, which might require a sternotomy incision and cardiopulmonary bypass. Postoperative hypertension is treated with intravenous medication, often a short-acting beta-blocker, followed by oral medications, such as an angiotensin-converting enzyme inhibitor. Residual hypertension after repair of COA seems to be related to age and time of repair.

Describe the pathophysiology and manifestations of hemolytic uremic syndrome.

Pathophysiology; HUS has been associated with bacterial and viral agents, as well as endotoxins, especially that from Escherichia coli 0157:H7 and more recently Escherichia coli 0104:H4 (Shiga toxins).In HUS, the endothelial lining of the glomerular arterioles becomes swollen and occluded with platelets and fibrin clots. Narrowed vessels damage passing erythrocytes. These damaged red blood cells are removed by the spleen, causing acute hemolytic anemia. Fibrinolysis, the process of dissolution of a clot, acts on precipitated fibrin, causing the fibrin split products to appear in serum and urine. Platelet thrombi develop within damaged vessels, and platelet removal produces thrombocytopenia. Varying degrees of vascular occlusion cause altered renal perfusion and renal insufficiency or failure. Clinical manifestations; A prodromal gastrointestinal illness (fever, vomiting, diarrhea) or, less frequently, an upper respiratory tract infection often precedes the onset of HUS by 1 to 2 weeks. After a symptom-free 1- to 5-day period, the sudden onset of pallor, bruising or purpura, irritability, and oliguria heralds the commencement of the disease. Slight fever, anorexia, vomiting, diarrhea (with the stool characteristically watery and blood stained), abdominal pain, mild jaundice, and circulatory overload are accompanying symptoms. Seizures and lethargy indicate central nervous system (CNS) involvement. Renal failure is apparent within the first days of onset. The renal failure causes metabolic acidosis, azotemia, hyperkalemia, and often hypertension.

Identify the characteristics of peripheral arterial disease.

Peripheral artery disease (PAD) refers to atherosclerotic disease of arteries that perfuse the limbs, especially the lower extremities. Pain with ambulation called intermittent claudication Evaluation for PAD requires a careful history and physical examination that focuses on finding evidence of atherosclerotic disease (e.g., bruits), determining a difference in blood pressure measured at the ankle versus the arm (ankle-brachial index), and measuring blood flow using noninvasive Doppler.

Discuss the progression of coronary artery disease from ischemia to infarction, including clinical symptoms, risk factors, diagnostic evaluation of myocardial infarction, and critical timing for intervention.

Persistent ischemia or the complete occlusion of a coronary artery causes the acute coronary syndromes including infarction, or irreversible myocardial damage. Infarction constitutes the potentially fatal event known as a heart attack. risk factors: Conventional or major risk factors for CAD that are nonmodifiable include (1) advanced age, (2) male gender or women after menopause, and (3) family history. Aging and menopause are associated with increased exposure to risk factors and poor endothelial healing. Family history may contribute to CAD through genetics and shared environmental exposures. Many gene polymorphisms have been associated with CAD and its risk factors. Modifiable major risks include (1) dyslipidemia, (2) hypertension, (3) cigarette smoking, (4) diabetes and insulin resistance, (5) obesity, (6) sedentary lifestyle, and (7) atherogenic diet. clinical symptoms: The first symptom of acute myocardial infarction is usually sudden, severe chest pain. The pain is similar to that of angina pectoris but more severe and prolonged. It may be described as heavy and crushing, such as a "truck sitting on my chest." Radiation to the neck, jaw, back, shoulder, or left arm is common. Some individuals, especially those who are elderly or have diabetes, experience no pain, thereby having a "silent" infarction. Infarction often simulates a sensation of unrelenting indigestion. Nausea and vomiting may occur because of reflex stimulation of vomiting centers by pain fibers. Vasovagal reflexes from the area of the infarcted myocardium also may affect the gastrointestinal tract. diagnostic evaluation of myocardial infarction: The diagnosis of acute myocardial infarction is made on the basis of history, physical examination, ECG results, and serial cardiac troponin elevations. The cardiac troponins (troponin I and troponin T) are the most specific indicators of MI. Myocardial Infarct (MI)Irreversible Myocardial damage Due to prolonged ischemia (20 minutes)Effects on the body depend on. What part of heart did that Coronary artery blood supply? oLeft ventricle—very serious for heart failure/CO Size of the damaged area (how much tissue affected) Includes Wall penetration (Check ECG) •Endothelial (non-STEMI) •Transmural (STEMI)—much more serious

Describe physiologic jaundice of the newborn.

Physiologic jaundice of the newborn is caused by mild hyperbilirubinemia that subsides in 1 or 2 weeks. Pathologic jaundice is caused by severe hyperbilirubinemia and can cause brain damage (kernicterus).

Discuss the signs and symptoms and physiologic response to acute gastrointestinal bleeding.

Physiologic- Changes in blood pressure and heart rate are the best indicators of massive blood loss in the GI tract Signs of large-volume blood loss are postural hypotension (a drop in blood pressure that occurs with a change from the recumbent position to a sitting or upright position), lightheadedness, and loss of vision. Tachycardia develops as a compensatory response to maintain cardiac output and tissue perfusion. If blood loss continues, hypovolemic shock develops

Define pneumothorax.

Pneumothorax is the presence of air or gas in the pleural space caused by a rupture in the visceral pleura (which surrounds the lungs) or the parietal pleura and chest wall. As air separates the visceral and parietal pleurae, it destroys the negative pressure of the pleural space and disrupts the equilibrium between elastic recoil forces of the lung and chest wall. The lung then tends to recoil by collapsing toward the hilum.

Describe the clinical manifestations of type 1 DM and the rationale for each.

Polydipsia-Because of elevated blood glucose levels, water is osmotically attracted from body cells, resulting in intracellular dehydration and stimulation of thirst in hypothalamus Polyuria-Hyperglycemia acts as an osmotic diuretic; amount of glucose filtered by glomeruli of kidney exceeds that which can be reabsorbed by renal tubules; glycosuria results, accompanied by large amounts of water lost in urine Polyphagia- Depletion of cellular stores of carbohydrates, fats, and protein results in cellular starvation and a corresponding increase in hunger Weight loss-Weight loss occurs because of fluid loss in osmotic diuresis and loss of body tissue as fats and proteins are used for energy Fatigue- Metabolic changes result in poor use of food products, contributing to lethargy and fatigue Recurrent infections (e.g., boils, carbuncles, and bladder infection)- Growth of microorganisms is stimulated by increased glucose levels and diabetes is associated with some immunocompromised individuals Prolonged wound healing- Impaired blood supply hinders healing Genital pruritus- Hyperglycemia and glycosuria favor fungal growth; candidal infections, resulting in pruritus, are a common presenting symptom in women Visual changes- Blurred vision occurs as water balance in eye fluctuates because of elevated blood glucose levels; diabetic retinopathy may ensue Paresthesias-Paresthesias are common manifestations of diabetic neuropathies Cardiovascular symptoms (e.g., chest pain, extremity pain, and neurologic deficits)- Diabetes contributes to formation of atherosclerotic plaques that involve coronary, peripheral, and cerebrovascular circulations and alterations in microvessels

Describe postconcussive syndrome, and list its symptoms and treatment

Postconcussion syndrome, including headache, dizziness, fatigue, nervousness or anxiety, irritability, insomnia, depression, inability to concentrate, and forgetfulness, may last for weeks to months after a concussion. Treatment entails reassurance and symptomatic relief in addition to 24 hours of close observation after the concussion in the event bleeding or swelling in the brain occurs. Symptoms requiring further evaluation and treatment include drowsiness or confusion, nausea or vomiting, severe headache, memory deficit, seizures, drainage of cerebrospinal fluid from the ear or nose, weakness or loss of feeling in the extremities, asymmetry of the pupils, and double vision. Guidelines for the management of pediatric and adult concussion are available

Identify the types of pneumothorax, including manifestations and causes.

Primary (spontaneous) pneumothorax occurs unexpectedly in healthy individuals (usually men) between 20 and 40 years of age and is caused by the spontaneous rupture of blebs (blister-like formations) on the visceral pleura. Bleb rupture can occur during sleep, rest, or exercise. The ruptured blebs are usually located in the apexes of the lungs. The cause of bleb formation is not known, although more than 80% of these individuals have been found to have emphysema-like changes in their lungs even if they have no history of smoking or no known genetic disorder. Approximately 10% of affected individuals have a significant family history of primary pneumothorax that has been linked to mutations in the folliculin gene. Secondary pneumothorax can be caused by chest trauma (such as a rib fracture or stab and bullet wounds that tear the pleura; rupture of a bleb or bulla [larger vesicle], as occurs in emphysema; or mechanical ventilation, particularly if it includes positive end-expiratory pressure [PEEP]). Iatrogenic pneumothorax is most commonly caused by transthoracic needle aspiration. Primary pneumothorax and secondary pneumothorax can present as either open or tension. In open (communicating) pneumothorax, air pressure in the pleural space equals barometric pressure because air that is drawn into the pleural space during inspiration (through the damaged chest wall and parietal pleura or through the lungs and damaged visceral pleura) is forced back out during expiration. In tension pneumothorax, however, the site of pleural rupture acts as a one-way valve, permitting air to enter on inspiration but preventing its escape by closing during expiration. As more and more air enters the pleural space, air pressure in the pneumothorax begins to exceed barometric pressure. Air pressure in the pleural space pushes against the already recoiled lung, causing compression atelectasis, and against the mediastinum, compressing and displacing the heart, great vessels, and trachea (mediastinal shift). The pathophysiologic effects of tension pneumothorax are life-threatening. Clinical manifestations of spontaneous or secondary pneumothorax begin with sudden pleural pain, tachypnea, and dyspnea. Depending on the size of the pneumothorax, physical examination may reveal absent or decreased breath sounds and hyperresonance to percussion on the affected side. Tension pneumothorax may be complicated by severe hypoxemia, tracheal deviation away from the affected lung, and hypotension (low blood pressure).

Describe the countercurrent exchange system of urine concentration.

Production of concentrated urine involves a countercurrent exchange system, in which fluid flows in opposite directions through the parallel tubes of the loop of Henle. A concentration gradient causes fluid to be exchanged across the parallel pathways. The longer the loop, the greater the concentration gradient; the concentration gradient increases from the cortex to the tip of the medulla. The loops of Henle multiply the concentration gradient, and the vasa recta blood vessels act as a countercurrent exchanger for maintaining the gradient. The process is initiated in the thick ascending limb of the loop of Henle with the active transport of chloride and sodium out of the tubular lumen and into the medullary interstitium (Figure 29- 13). Because the lumen of the ascending limb is impermeable to water, water cannot follow the sodium-chloride transport. This causes the ascending tubular fluid to become hypoosmotic and the medullary interstitium to become hyperosmotic. The descending limb of the loop, which receives fluid from the proximal tubule, is highly permeable to water but it is the only place in the nephron that does not actively transport either sodium or chloride. Sodium and chloride may, however, diffuse into the descending tubule from the interstitium. The hyperosmotic medullary interstitium causes water to move out of the descending limb, and the remaining fluid in the descending tubule becomes increasingly concentrated while it flows toward the tip of the medulla. While the tubular fluid rounds the loop and enters the ascending limb, sodium and chloride are removed and water is retained. The fluid then becomes more and more dilute as it encounters the distal tubule.

Describe the pathophysiology associated with pulmonary edema.

Pulmonary edema is excess water in the lung. The normal lung is kept dry by lymphatic draining and a balance among capillary hydrostatic pressure, capillary oncotic pressure, and capillary permeability. In addition, surfactant lining the alveoli repels water, keeping fluid from entering the alveoli. Predisposing factors for pulmonary edema include include heart disease, acute respiratory distress syndrome, and inhalation of toxic gasses. The most common cause of pulmonary edema is left-sided heart disease. When the left ventricle fails, filling pressures on the left side of the heart increase. Vascular volume redistributes into the lungs, causing an increase in pulmonary capillary hydrostatic pressure. When the hydrostatic pressure exceeds oncotic pressure (which holds fluid in the capillary), fluid moves out into the interstitial space (the space within the alveolar septum between alveolus and capillary). When the flow of fluid out of the capillaries exceeds the lymphatic system's ability to remove it, pulmonary edema develops. Another cause of pulmonary edema is capillary injury that increases capillary permeability, as in cases of acute respiratory distress syndrome or inhalation of toxic gases, such as ammonia. Capillary injury and inflammation causes water and plasma proteins to leak out of the capillary and move into interstitial space, increasing the interstitial oncotic pressure (which is usually very low). As the interstitial oncotic pressure begins to exceed capillary oncotic pressure, water moves out of the capillary and into the lungs. Pulmonary edema also can result from obstruction of the lymphatic system. Drainage can be blocked by compression of lymphatic vessels by edema, tumors, and fibrotic tissue and by increased systemic venous pressure.

Describe the cellular changes, clinical manifestations, treatments, outcomes, and complications of pulmonary embolus.

Pulmonary embolism (PE) is an occlusion within the pulmonary vascular bed by an embolus. PE's commonly are the result of a clot originating from the deep veins of the lower leg. The main risk factors for PE are termed Virchow's triad.....WHAT ARE THE 3 COMPONENTS??? 1) venous stasis, 2) hypercoagulability, and 3) trauma to the endothelium. As you may remember, a blood clot becomes an embolus when it detaches from the site of formation and begins to travel in the bloodstream. Patho: The impact or effect of the embolus depends on the extent of pulmonary blood flow obstruction, the size of the affected vessels, the nature of the embolus, and the secondary effects. Pulmonary emboli can occur as 1) an embolus with infarction (causes permanent lung injury, 2) an embolus without infarction (does not cause permanent lung injury, 3) a massive occlusion (occlusion within pulmonary circulation), and 4) multiple pulmonary emboli (significant obstxn within pulmonary vasculature). S/S: sudden onset of pleuritic chest pain, dyspnea, tachypnea, tachycardia, and unexplained anxiety. Occasionally syncope (fainting) or hemoptysis occurs. With large emboli, a pleural friction rub, pleural effusion, fever, and leukocytosis may be noted. Recurrent small emboli may not be detected until progressive incapacitation, precordial pain, anxiety, dyspnea, and right ventricular enlargement are exhibited. Massive occlusion causes severe pulmonary hypertension and shock.

Describe the two most common tumors of the renal and urologic systems: renal carcinoma and bladder tumors.

Renal tumors account for 3.8% of new cancer cases and 13,040 deaths each year, and there are a number of different types of kidney tumors. Renal adenomas (benign tumors) are uncommon but increasing in number. The tumors are encapsulated and are usually located near the cortex of the kidney. Because they can become malignant, they are usually surgically removed. Renal cell carcinoma (RCC) is the most commont renal neoplasm and represents about 2% of cancer deaths. Renal transitional cell carcinoma (RTCC) is rare and primarily arises in the renal parenchyma and renal pelvis. Renal cell carcinoma usually occurs in men (2 time more often than in women) between ages 50-60. Risk factors include cigarette smoking, obesity, and uncontrolled hypertension. With surgical resection five-year survival rate is about 90% for stage 1 cancer. Bladder tumors are the fifth most common malignancy and represent about 1 % of all malignant tumors w/ 70,530 new cases each year and 14,680 deaths. The development of bladder cancer is most common in men older than 60 years. Transitional cell carcinoma is the most common bladder malignancy and tumors are usually superficial.

Define acute respiratory failure and identify risk factors.

Respiratory failure is defined as inadequate gas exchange such that PaO2 ≤60 mm Hg or PaCO2 ≥50 mm Hg, with pH ≤7.25.10 Respiratory failure can result from direct injury to the lungs, airways, or chest wall or indirectly because of disease or injury involving another body system, such as the brain, spinal cord, or heart. -It can occur in individuals who have an otherwise normal respiratory system or in those with underlying chronic pulmonary disease. Most pulmonary diseases can cause episodes of acute respiratory failure. If the respiratory failure is primarily hypercapnic, it is the result of inadequate alveolar ventilation and the individual must receive ventilatory support, such as with a big-valve mask or mechanical ventilator. If the respiratory failure is primarily hypoxemic, it is the result of inadequate exchange of oxygen between the alveoli and the capillaries and the individual must receive supplemental oxygen therapy. Many people will have combined hypercapnic and hypoxemic respiratory failure and will require both kinds of support. Respiratory failure is an important potential complication of any major surgical procedure, especially those that involve the central nervous system, thorax, or upper abdomen. The most common postoperative pulmonary problems are atelectasis, pneumonia, pulmonary edema, and pulmonary emboli. People who smoke are at risk, particularly if they have preexisting lung disease. Limited cardiac reserve, chronic renal failure, chronic hepatic disease, and infection also increase the tendency to develop postoperative respiratory failure.

Describe the significant differences between the pulmonary systems of infants, children, and normal adults.

Ribs are more horizontal Rib cartilage is more spongy which can allow the chest wall to retract during episodes of respiratory distress and decrease tidal volume intercoastal muscles aren't fully developed which can increase orthopnea children have a larger tongue the internal diameter of a child's airway is smaller. children have higher respiratory rates

Identify how acute respiratory distress syndrome in childhood differs from adulthood.

SAME AS ADULTS (CH.27)

Differentiate among the different types of seizures.

Seizures represent a sudden, chaotic discharge of cerebral neurons with transient alterations in brain function. Seizures may be generalized or focal and can result from cerebral lesions, biochemical disorders, trauma, or epilepsy. Generalized Seizure; (First clinical manifestations indicate that seizure activity starts in or involves both cerebral hemispheres; consciousness may be impaired; bilateral manifestations; may be preceded by an aura) *Tonic-clonic- Musculature stiffens, then intense jerking as trunk and extremities undergo rhythmic contraction and relaxation *Atonic -Sudden, momentary loss of muscle tone; drop attacks *Myoclonic-Sudden, brief contractures of a muscle or group of muscles *Absence seizure-Brief loss of consciousness with minimal or no loss of muscle tone; may experience 20 or more episodes a day lasting approximately 5 to 10 sec each; may have minor movement, such as lip smacking, twitching of eyelids ---------------------------------------- Partial (Focal) Seizure (Seizure activity that begins and usually is limited to one part of left or right hemisphere; an aura is common) Simple- Seizure activity that occurs without loss of consciousness Complex-Seizure activity that occurs with impairment of consciousness

Describe the progression from sepsis through septic shock and ultimately to multisystem organ dysfunction syndrome.

Septic shock begins when bacteria enter the bloodstream to produce bacteremia. These bacteria may directly stimulate an inflammatory response or release toxic substances into the bloodstream. Gram-negative bacteria release endotoxins, and gram-positive bacteria release exotoxins, lipoteichoic acids, and peptidoglycans. These substances trigger the septic syndrome by interacting with Toll-like receptors on macrophages and activate complement, coagulation, kinins, and inflammatory cells. The release of inflammatory mediators triggers intense cellular responses and the subsequent release of secondary mediators, including cytokines, complement fragments, prostaglandins, platelet-activating factor, oxygen free radicals, nitric oxide, and proteolytic enzymes. Chemotaxis, activation of granulocytes, and reactivation of the phagocytic cells and inflammatory cascades result. This systemic inflammation, especially through the action of nitric oxide, leads to widespread vasodilation with compensatory tachycardia and increased cardiac output in the early stages of septic shock (hyperdynamic phase). Later in the course of disease, inflammatory mediators, such as complement and interleukins, depress myocardial contractility such that cardiac output falls and tissue perfusion decreases. Tissue perfusion and cellular oxygen extraction also are affected by activation of the clotting cascade through the action of platelet-activating factor and depletion of the endogenous anticoagulant protein C. Furthermore, unresponsiveness to or depletion of vasoactive factors such as vasopressin contributes to hypotension and tissue hypoperfusion. The inflammatory response can become overwhelming, leading to the systemic inflammatory response syndrome (SIRS), which can progress to widespread tissue hypoxia, necrosis, and apoptosis, leading to septic shock and MODS.

Describe the four classifications of vertebral column injury.

Simple fractures: refer to a single break affecting the transverse or spinous processes Compressed (wedged) vertebral fractures: involve anterior compression of the vertebrae Comminuted (burst) fractures: involves affected vertebrae that shatter into fragments Dislocation: occurs when the ligaments or disc connections between two vertebra are stretched/torn

Identify and discuss the normal sleep cycle.

Sleep is an active multiphase process that provides restorative functions and promotes memory consolidation. Complex neural circuits, interacting hormones, and neurotransmitters involving the hypothalamus, thalamus, brainstem, and cortex control the timing of the sleep-wake cycle and coordinate this cycle with circadian rhythms (24-hour rhythm cycles). Normal sleep has two phases that can be documented by electroencephalogram (EEG): rapid eye movement (REM) sleep (20% to 25% of sleep time) and slow-wave (non-REM) sleep. Non-REM sleep is further divided into three stages (N1, N2, N3) from light to deep sleep followed by REM sleep. Four to six cycles of REM and non-REM sleep occur each night in an adult. The hypothalamus is a major sleep center and the hypocretins (orexins), acetylcholine, and glutamate are neuropeptides secreted by the hypothalamus that promote wakefulness. Prostaglandin D2, adenosine, melatonin, serotonin, L-tryptophan, gamma-aminobutyric acid (GABA), and growth factors promote sleep. The pontine reticular formation is primarily responsible for generating REM sleep, and projections from the thalamocortical network produce non-REM sleep. REM (rapid eye movement) sleep is initiated by REM-on and REM-off neurons in the pons and mesencephalon. REM sleep occurs about every 90 minutes beginning 1 to 2 hours after non-REM sleep begins. This sleep is known as paradoxical sleep because the EEG pattern is similar to that of the normal awake pattern and the brain is very active with dreaming. REM and non-REM sleep alternate throughout the night, with lengthening intervals of REM sleep and fewer intervals of deeper stages of non-REM sleep toward morning. The changes associated with REM sleep include increased parasympathetic activity and variable sympathetic activity associated with rapid eye movement; muscle relaxation; loss of temperature regulation; altered heart rate, blood pressure, and respiration; penile erection in men and clitoral engorgement in women; release of steroids; and many memorable dreams. Respiratory control appears largely independent of metabolic requirements and oxygen variation. Loss of normal voluntary muscle control in the tongue and upper pharynx may produce some respiratory obstruction. Cerebral blood flow increases. Non-REM sleep (NREM) accounts for 75% to 80% of sleep time in adults and is initiated when inhibitory signals are released from the hypothalamus. Sympathetic tone is decreased and parasympathetic activity is increased during NREM sleep, creating a state of reduced activity. The basal metabolic rate falls by 10% to 15%; temperature decreases 0.5° to 1.0° C (0.9° to 1.8° F); heart rate, respiration, blood pressure, and muscle tone decrease; and knee jerk reflexes are absent. Pupils are constricted. During the various stages, cerebral blood flow to the brain decreases and growth hormone is released, with corticosteroid and catecholamine levels depressed. *Sleep is an active process and is divided into REM and non-REM stages, each of which has its own series of stages. While asleep, an individual progresses through REM and non-REM (slow wave) sleep in a predictable cycle. * REM sleep is controlled by mechanisms in the pons and mesencephalon. Non- REM sleep is controlled by release of inhibitory signals from the hypothalamus and accounts for 75% to 80% of sleep time. *The restorative, reparative, and growth processes occur during slow-wave (non- REM) sleep. Sleep deprivation can cause profound changes in personality and functioning.

The type of diarrhea caused by an inflammatory disorder of the intestine is

Small volume

Compare childhood systemic hypertension to adulthood primary hypertension.

Systemic hypertension in children differs from HTN in adults in etiology and presentation. When significant hypertension is found in a young child, the examiner should evaluate for the presence of secondary hypertension, most commonly renal disease or Coarctation of the aorta (COA) .

Discuss the role of the sympathetic nervous system in the regulation of renal blood flow.

The blood vessels of the kidney are innervated by sympathetic nerve fibers located primarily on afferent arterioles. When systemic arterial pressure decreases, increased renal sympathetic nerve activity is mediated reflexively through the carotid sinus and the baroreceptors of the aortic arch. The sympathetic nerves release catecholamines. This stimulates afferent renal arteriolar vasoconstriction and decreases RBF and GFR, increases renal tubular sodium and water reabsorption, and increases blood pressure. Decreased afferent renal sympathetic nerve activity produces the opposite effects. The integrated response regulates water and sodium balance. Renalase is a hormone released by the kidney and heart that promotes the metabolism of catecholamines and in this way participates in blood pressure regulation.The sympathetic nervous system also participates in hormonal (i.e., angiotensin II) regulation of renal blood flow. There is no significant parasympathetic innervation. The innervation of the kidney arises primarily from the celiac ganglion and greater splanchnic nerve.

Discuss the purpose of the blood-brain barrier, and how (and by what cells) the barrier is formed and maintained.

The blood-brain barrier (BBB) describes cellular structures that selectively inhibit certain potentially harmful substances in the blood from entering the interstitial spaces of the brain or CSF allowing neurons to function normally. Endothelial cells in brain capillaries with their intracellular tight junctions are the site of the BBB. Supporting cells include astrocytes, pericytes, and microglia. The exact nature of this mechanism is controversial, but it appears that certain metabolites, electrolytes, and chemicals can cross into and out of the brain to varying degrees. This has substantial implications for drug therapy because certain types of antibiotics and chemotherapeutic drugs show a greater propensity than others for crossing this barrier. Breakdown of the BBB can contribute to neuroinflammation and neurodegeneration.

Describe the significance of the circle of Willis.

The circle of Willis provides an alternative route for blood flow when one of the contributing arteries is obstructed (collateral blood flow). The circle of Willis is formed by the posterior cerebral arteries, posterior communicating arteries, internal carotid arteries, anterior cerebral arteries, and anterior communicating artery. The anterior cerebral, middle cerebral, and posterior cerebral arteries leave the circle of Willis and extend to various brain structures. The border zone is the area between the major arterial territories.

Discuss the pathophysiology of tetralogy of Fallot.

The classic form of tetralogy of Fallot (TOF) includes four defects: (1) VSD, (2) PS, (3) overriding aorta, and (4) right ventricular hypertrophy . The pathophysiology varies widely, depending not only on the degree of PS but also on the pulmonary and systemic vascular resistance to flow. If total resistance to pulmonary flow is greater than systemic resistance, the shunt is from right to left. If systemic resistance is more than pulmonary resistance, the shunt is from left to right. PS decreases blood flow to the lungs and, consequently, the amount of oxygenated blood that returns to the left heart. Physiologic compensation to chronic, severe hypoxia includes production of more red blood cells (polycythemia), development of collateral bronchial vessels, and enlargement of the nail beds (clubbing).

Discuss the clinical significance of blood urea nitrogen and creatinine measurements.

The concentration of urea nitrogen in the blood reflects glomerular filtration and urine-concentrating capacity. Because urea is filtered at the glomerulus, blood urea nitrogen (BUN) levels increase as glomerular filtration drops. Because urea is reabsorbed by the blood through the permeable tubules, the BUN value rises in states of dehydration and with acute and chronic renal failure when passage of fluid through the tubules slows. BUN values also change as a result of altered protein intake and protein catabolism. The normal range for BUN level in the adult is 10 to 20 mg/dl of blood. Creatinine, a substance produced by muscle, is measured in both plasma and urine to calculate a commonly used clinical measurement of GFR.

Describe the pathophysiology of Alzheimer disease.

The exact cause of Alzheimer disease is unknown. Early-onset FAD has been linked to three genes with mutations on chromosome 21 (abnormal amyloid precursor protein 14 [APP14], abnormal presenilin 1 [PSEN1], and abnormal presenilin 2 [PSEN2]). Late-onset AD may be related to the involvement of chromosome 19 with the apolipoprotein E gene-allele 4 (APOE4). Studies are ongoing to classify the genetic variations of AD. DNA methylation is an epigenetic marker for Alzheimer disease. Sporadic late-onset AD is the most common, and does not have a specific genetic association; however, the cellular pathology is the same as that for gene- associated early- and late-onset AD. Pathologic alterations in the brain include accumulation of extracellular neuritic plaques containing a core of amyloid beta protein, intraneuronal neurofibrillary tangles, and degeneration of basal forebrain cholinergic neurons with loss of acetylcholine. Failure to process and clear amyloid precursor protein results in the accumulation of toxic fragments of amyloid beta protein that leads to formation of diffuse neuritic plaques, disruption of nerve impulse transmission, and death of neurons. The tau protein, a microtubule-binding protein, in neurons detaches and forms an insoluble filament called a neurofibrillary tangle, contributing to neuronal death (Figure 15-8). Neuritic plaques and neurofibrillary tangles are more concentrated in the cerebral cortex and hippocampus. The loss of neurons results in brain atrophy with widening of sulci and shrinkage of gyri (see Figure 15-8). Loss of synapses, acetylcholine and other neurotransmitters contributes to the decline of memory and attention and the loss of other cognitive functions associated with AD.

Explain the relationship between cell types and function of the exocrine pancreas.

The exocrine pancreas secretes an alkaline solution and the enzymes (trypsin, chymotrypsin, carboxypeptidase, α-amylase, lipase) that digest proteins, carbohydrates, and fats. Acinar cells: grouped together. Produce digestive enzymes Pancreatic ductal epithelial cells: Secrete H2O and HCO3- (bicarb)

List several factors that affect glomerular filtration rate.

The factors determining the GFR are directly related to the pressures that favor or oppose filtration Obstruction to the outflow of urine (caused by strictures, stones, or tumors along the urinary tract) can cause a retrograde increase in hydrostatic pressure at Bowman space and a decrease in GFR. Low levels of plasma protein in the blood can result in a decrease in glomerular capillary oncotic pressure, which increases GFR. Excessive loss of protein-free fluid from vomiting, diarrhea, use of diuretics, or excessive sweating can increase glomerular capillary oncotic pressure and decrease the GFR. Renal disease also can cause changes in pressure relationships by altering capillary permeability and the surface area available for filtration

Describe the large intestine and identify normal intestinal flora and their activities.

The large intestine consists of the cecum, appendix, colon (ascending, transverse, descending, and sigmoid), rectum, and anal canal. The teniae coli are three bands of longitudinal muscle that extend the length of the colon. Haustra are pouches of colon formed with alternating contraction and relaxation of the circular muscles. The mucosa of the large intestine contains mucus-secreting cells and mucosal folds, but no villi. The large intestine massages the fecal mass and absorbs water and electrolytes. The largest number of intestinal bacteria (intestinal microbiome) is in the colon. The most numerous anaerobes are Bacteroides and Firmicutes. Intestinal bacteria are important for metabolism of bile salts, metabolism of selected drugs and hormones, and prevention of pathogen colonization.

Discuss the normal structure and function of the lymphatic system.

The lymphatic system is a one-way network of lymphatic vessels and the lymph nodes that is important for immune function, fluid balance, and transport of lipids, hormones, and cytokines. Fluid from plasma flowing through the capillaries moves into interstitial spaces. Although most of this interstitial fluid is either absorbed by tissue cells or reabsorbed by blood capillaries, some of the fluid tends to accumulate in the interstitial spaces. This lymph then diffuses into the lymphatic vessels that carry it to the lymph nodes and then into the systemic venous blood. 1. The vessels of the lymphatic system run in the same sheaths as the arteries and veins. 2. Lymph (interstitial fluid) is absorbed by lymphatic venules in the capillary beds and travels through ever larger lymphatic veins until it empties through the right lymphatic duct or thoracic duct into the right or left subclavian veins, respectively. 3. As lymph travels toward the thoracic ducts, it passes through thousands of lymph nodes clustered around the lymphatic veins. The lymph nodes are sites of immune function and are ideally placed to sample antigens and cells carried by the lymph from the periphery of the body into the central circulation.

Describe the mechanics of breathing.

The mechanical aspects of inspiration and expiration are known collectively as the mechanics of breathing and involve (1)Major and accessory muscles of inspiration and expiration The major muscles of inspiration are the diaphragm and the external intercostal muscles (muscles between the ribs). The diaphragm is a dome-shaped muscle that separates the abdominal and thoracic cavities. When it contracts and flattens downward, it increases the volume of the thoracic cavity, creating a negative pressure that draws gas into the lungs through the upper airways and trachea. Contraction of the external intercostal muscles elevates the anterior portion of the ribs and increases the volume of the thoracic cavity by increasing its front-to-back (anterior-posterior [AP]) diameter. Although the external intercostals may contract during quiet breathing, inspiration at rest is usually assisted by the diaphragm only. The accessory muscles of inspiration are the sternocleidomastoid and scalene muscles. Like the external intercostals, these muscles enlarge the thorax by increasing its AP diameter. The accessory muscles assist inspiration when the minute volume (volume of air inspired and expired per minute) is high, as during strenuous exercise, or when the work of breathing is increased because of disease. The accessory muscles do not increase the volume of the thorax as efficiently as the diaphragm does. There are no major muscles of expiration because normal, relaxed expiration is passive and requires no muscular effort. The accessory muscles of expiration, the abdominal and internal intercostal muscles, assist expiration when minute volume is high, during coughing, or when airway obstruction is present. When the abdominal muscles contract, intra-abdominal pressure increases, pushing up the diaphragm and decreasing the volume of the thorax. The internal intercostal muscles pull down the anterior ribs, decreasing the AP diameter of the thorax. (2) elastic properties of the lungs and chest wall The lung and chest wall have elastic properties that permit expansion during inspiration and return to resting volume during expiration. The elasticity of the lung is caused both by elastin fibers in the alveolar walls and surrounding the small airways and pulmonary capillaries, and by surface tension at the alveolar air-liquid interface. The elasticity of the chest wall is the result of the configuration of its bones and musculature. Elastic recoil is the tendency of the lungs to return to the resting state after inspiration. Normal elastic recoil permits passive expiration, eliminating the need for major muscles of expiration. Passive elastic recoil may be insufficient during labored breathing (high minute volume), when the accessory muscles of expiration may be needed. The accessory muscles are used also if disease compromises elastic recoil (e.g., in emphysema) or blocks the conducting airways. Compliance is the measure of lung and chest wall distensibility and is defined as volume change per unit of pressure change. It represents the relative ease with which these structures can be stretched and is, therefore, the opposite of elasticity. Compliance is determined by the alveolar surface tension and the elastic recoil of the lung and chest wall. Increased compliance indicates that the lungs or chest wall is abnormally easy to inflate and has lost some elastic recoil. A decrease in compliance indicates that the lungs or chest wall is abnormally stiff or difficult to inflate. Compliance increases with normal aging and with disorders such as emphysema; it decreases in individuals with acute respiratory distress syndrome, pneumonia, pulmonary edema, and fibrosis. (3) resistance to airflow through the conducting airways. Airway resistance, which is similar to resistance to blood flow, is determined by the length, radius, and cross-sectional area of the airways and by the density, viscosity, and velocity of the gas (Poiseuille law). Resistance (R) is computed by dividing change in pressure (P) by rate of flow (F), or R = P/F (Ohm law). Airway resistance is normally very low. One half to two thirds of total airway resistance occurs in the nose. The next highest resistance is in the oropharynx and larynx. There is very little resistance in the conducting airways of the lungs because of their large cross-sectional area. Airway resistance is affected by the diameter of the airways. Bronchodilation, which decreases resistance to airflow, is caused by β2-adrenergic receptor stimulation. Bronchoconstriction, which increases airway resistance, can be caused by stimulation of parasympathetic receptors in the bronchial smooth muscle and by numerous irritants and inflammatory mediators.Airway resistance can also be increased by edema of the bronchial mucosa and by airway obstructions such as mucus, tumors, or foreign bodies. Pulmonary function tests (PFTs) measure lung volumes and flow rates and can be used to diagnose lung disease. Alterations in any of these properties increase the work of breathing or the metabolic energy needed to achieve adequate ventilation and oxygenation of the blood.

Describe the structural alterations that result in vesicoureteral reflex.

The normal distal ureter enters the bladder through the detrusor muscle and passes through a submucosal tunnel before opening into the bladder lumen via the ureteral orifice. As the bladder fills with urine the ureter is compressed within the bladder wall, preventing reflux. Primary VUR results from a congenital abnormally short submucosal tunnel and ureter that permits reflux by the rising pressure of the filling bladder (Figure 31-4). Urine sweeps up into the ureter and then flows back into the empty bladder. The reflux perpetuates infection by preventing complete emptying of the bladder and providing a reservoir for infection. With bladder filling, the maximal intravesical pressure can be transmitted up the ureter to the renal pelvis and calyces. The combination of reflux and infection is an important cause of pyelonephritis. Renal parenchymal injury, scarring, hypertension, and chronic renal insufficiency can occur many years later, making early diagnosis and treatment important. Secondary reflux develops in association with acquired conditions (e.g., neurogenic bladder dysfunction, ureteral obstruction, voiding disorders, or surgery on the ureterovesical [UV] junction). Reflux may be unilateral or bilateral, and is graded using the International Reflux Grading System.

Describe the process of normal thermoregulation.

The normal range of body temperature is considered to be 36.2° to 37.7° C (96.2° to 99.4° F) Temperature regulation (thermoregulation) is mediated primarily by the hypothalamus and endocrine system. Peripheral thermoreceptors in the skin and abdominal organs (unmyelinated C fibers and thinly myelinated A-delta fibers) and central thermoreceptors in the hypothalamus, spinal cord, abdominal organs, and other central locations provide the hypothalamus with information about skin and core temperatures. If these temperatures are low or high, the hypothalamus triggers heat production and heat conservation or heat loss mechanisms. Body heat is produced by the chemical reactions of metabolism and skeletal muscle tone and contraction. The heat-producing mechanism (chemical or nonshivering thermogenesis) begins with hypothalamic thyrotropin-stimulating hormone-releasing hormone (TSH-RH); it stimulates the anterior pituitary to release thyroid-stimulating hormone (TSH), which acts on the thyroid gland and stimulates the release of thyroxine. Thyroxine then acts on the adrenal medulla, causing the release of epinephrine into the bloodstream. Epinephrine causes vasoconstriction, stimulates glycolysis, and increases metabolic rate, thus increasing body heat. Norepinephrine and thyroxine activate brown fat thermogenesis where energy is released as heat instead of as adenosine triphosphate (ATP). Heat is distributed by the circulatory system. The hypothalamus also triggers heat conservation by stimulating the sympathetic nervous system, which stimulates the adrenal cortex and results in increased skeletal muscle tone, initiating the shivering response and producing vasoconstriction. By constricting peripheral blood vessels, centrally warmed blood is shunted away from the periphery to the core of the body where heat can be retained. This involuntary mechanism takes advantage of the insulating layers of the skin and subcutaneous fat to protect core temperature. The hypothalamus relays information to the cerebral cortex about cold and voluntary responses result. Individuals typically bundle up, keep moving, or curl up in a ball. These types of voluntary physical activities respectively provide insulation, increase skeletal muscle activity, and decrease the amount of skin surface available for heat loss through radiation, convection, and conduction.

Describe the partial pressure of oxygen and its measurement.

The partial pressure of oxygen is equal to the percentage of oxygen in the air (20.9%) times the total barometric pressure (760 mm Hg at sea level), or 159 mm Hg (760 × 0.209 = 158.84 mm Hg).

Identify how an allergic response can trigger childhood asthma attacks.

The pathophysiology of asthma in children is similar to that for adults and is described in Chapter 27. Asthma is initiated by a type I hypersensitivity reaction primarily mediated by Th2 lymphocytes whose cytokines activate mast cells, eosinophilia, leukocytosis, and enhanced B-cell IgE production . As in adults, inflammation, bronchospasm, and mucus production in the airways lead to ventilation and perfusion mismatch with hypoxemia and expiratory airway obstruction with air trapping and increased work of breathing. In young children, airway obstruction can be more severe because of the smaller diameter of their airways.

Define cerebral perfusion pressure.

The pressure required to perfuse the cells of the brain (70-90mmHg)

Identify the gallbladder-liver relationship.

The relationship between the liver and gallbladder is their structure and location. The gallbladder is located just underneath the liver.

Describe the small intestine, noting specific structures, function and secretions.

The small intestine is 5 meters long and has three segments: the duodenum, jejunum, and ileum. The duodenum receives chyme from the stomach through the pyloric valve. The presence of chyme stimulates the liver and gallbladder to deliver bile and the pancreas to deliver digestive enzymes. Bile and enzymes flow through an opening guarded by the sphincter of Oddi. Enzymes secreted by the small intestine (maltase, sucrase, lactase), pancreatic enzymes, and bile salts act in the small intestine to digest proteins, carbohydrates, and fats. Digested substances are absorbed across the intestinal wall and then transported to the liver, where they are metabolized further. The ileocecal valve connects the small and large intestines and prevents reflux into the small intestine. Villi are small fingerlike projections that extend from the small intestinal mucosa and increase its absorptive surface area. Carbohydrates, amino acids, and fats are absorbed primarily by the duodenum and jejunum; bile salts and vitamin B12 are absorbed by the ileum. Vitamin B12 absorption requires the presence of intrinsic factor.

Note the significance of splanchnic blood flow.

The splanchnic blood flow provides blood to the esophagus, stomach, small and large intestines, liver, gallbladder, pancreas, and spleen.

Describe the stomach, noting specific structures, function and secretions.

The stomach is a hollow, muscular organ just below the diaphragm that stores food during eating, secretes digestive juices, mixes food with these juices, and propels partially digested food, called chyme, into the duodenum of the small intestine. Functional areas are the fundus (upper portion), body (middle portion), and antrum (lower portion). The vagus nerve stimulates gastric (stomach) secretion and motility. Gastric glands in the fundus and body of the stomach secrete intrinsic factor, which is needed for vitamin B12 absorption; and hydrochloric acid, which dissolves food fibers, kills microorganisms, and activates the enzyme pepsin. Chief cells in the stomach secrete pepsinogen, which is converted to pepsin in the acidic environment created by hydrochloric acid. Acid secretion is stimulated by the vagus nerve, gastrin, and histamine and is inhibited by sympathetic stimulation and cholecystokinin. The three phases of acid secretion by the stomach are the cephalic phase (anticipation and swallowing), the gastric phase (food in the stomach), and the intestinal phase (chyme in the intestine).

Identify the electrolytes reabsorbed and secreted by the proximal and distal tubes.

Things that are reabsorbed in the proximal convoluted tubule - Sodium ions: moved by active transport - Chloride ions: move from a charge gradient - Glucose: co-transported - Water: move from concentration gradient - Hydrogen ions and bicarbonate ions Substances secreted in proximal tubule H, NH3 and urea Substances reabsorbed in distal and collecting tubules Na, Cl, and water Substances secreted in distal and collecting tubules H and K

Describe the clinical symptoms and underlying pathophysiology of postural and idiopathic hypotension.

The term orthostatic (postural) hypotension (OH) refers to a decrease in systolic blood pressure of at least 20 mm Hg or a decrease in diastolic blood pressure of at least 10 mm Hg within 3 minutes of moving to a standing position. Orthostatic hypotension is often accompanied by dizziness, blurring or loss of vision, and syncope or fainting caused by insufficient vasomotor compensation and reduction of blood flow through the brain. Normally when an individual stands, the gravitational changes on the circulation are compensated by such mechanisms as baroreceptor-mediated reflex arteriolar and venous constriction and increased heart rate. Other compensatory mechanisms include mechanical factors, such as the closure of valves in the venous system, contraction of the leg muscles, and a decrease in intrathoracic pressure.The normally increased sympathetic activity during upright posture is mediated through a stretch receptor (baroreceptor) reflex that responds to shifts in volume caused by postural changes. This reflex promptly increases heart rate and constricts the systemic arterioles. Thus, arterial blood pressure is maintained. These mechanisms are dysfunctional or inadequate in individuals with orthostatic hypotension; Idiopathic, or primary, orthostatic hypotension implies no known initial cause. This kind of OH is often called "neurogenic" and is usually the result of primary neurologic disorders or secondary to conditions that affect autonomic function

Describe the critical role of the endothelium for vascular function.

The vascular endothelium is important to several body functions and is sometimes considered a separate endocrine organ. All tissues depend on a blood supply and the blood supply depends on endothelial cells, which form the lining, or endothelium, of the blood vessel. In addition to substance transport, the vascular endothelium has important roles in coagulation, antithrombogenesis, and fibrinolysis; immune system function; tissue and vessel growth and wound healing; and vasomotion, the contraction and relaxation of vessels -Filtration and permeability- Facilitates transport of large molecules via vesicular transport movement through intercellular junctions Facilitates transport of small molecules via movement of vesicles, through opening of tight junctions, and across cytoplasm. -Vasomotion Stimulates vascular relaxation through production of nitric oxide, prostacyclin, and other vasodilators-Stimulates vascular constriction through production of endothelin-1 and of angiotensin II by the action of endothelial angiotensin- converting enzyme on angiotensin I

Compare gastric, duodenal and stress ulcers; identify complications of surgical treatment of ulcers.

There are three types of peptic ulcers: duodenal, gastric, and stress ulcers. *Duodenal ulcers, the most common peptic ulcers, are associated with H. pylori infection, chronic use of NSAIDs, increased numbers of parietal (acid-secreting) cells in the stomach, elevated gastrin levels, and rapid gastric emptying. Pain occurs when the stomach is empty, and it is relieved with food or antacids. Duodenal ulcers tend to heal spontaneously and recur frequently. * Gastric ulcers develop near parietal cells, generally in the antrum, and tend to become chronic. Gastric secretions may be normal or decreased, and pain may occur after eating. *Stress ulcers develop suddenly after severe illness, systemic trauma, or neural injury. Ulceration follows mucosal damage caused by ischemia (decreased blood flow to the gastric mucosa). Complications from surgery: Postgastrectomy syndromes are a group of signs and symptoms that occur after gastric resection for the treatment of peptic ulcer, gastric carcinoma, or bariatric surgery for extreme obesity. They are caused by anatomic and functional changes in the stomach and upper small intestine and include the following: 1. Dumping syndrome. Rapid emptying of hypertonic chyme from the surgically residual stomach (the stomach component remaining after surgical resection following gastric or bariatric surgery) into the small intestine 10 to 20 minutes after eating; promoted by loss of gastric capacity, loss of emptying control when pylorus is removed, and loss of feedback control by duodenum when it is removed; responds to dietary management. Symptoms include cramping pain, nausea, vomiting, osmotic diarrhea, weakness, pallor, and hypotension. 2. Alkaline reflux gastritis. Stomach inflammation caused by reflux of bile and alkaline pancreatic secretions containing proteolytic enzymes that disrupt the mucosal barrier in the remnant stomach. Symptoms include nausea, bilious vomiting, and sustained epigastric pain that worsens after eating and is not relieved by antacids; responds somewhat to avoidance of aspirin and alcohol, but surgical correction may be required. 3. Afferent loop obstruction. Intermittent severe pain and epigastric fullness after eating as a result of volvulus, hernia, adhesion, or stenosis of the duodenal stump on the proximal side of the gastrojejunostomy; vomiting relieves symptoms; management includes low-fat diet, but decompression or surgery revision is required for complete obstruction. 4. Diarrhea. Either frequent, persistent elimination of loose stools or intermittent, precipitous, and unpredictable elimination of a large volume of stool; related to rapid gastric emptying and osmotic attraction of water into the gut, especially after large intake of high-carbohydrate liquids; small, dry meals and anticholinergic drugs are effective control measures (see p. 907). 5. Weight loss. Commonly caused by inadequate caloric intake because individual cannot tolerate carbohydrates or a normal-size meal; stomach is also less able to mix, churn, and break down food. In the case of bariatric surgery for extreme obesity, weight loss is the intended outcome but nutrient deficiencies, including vitamins and minerals, must be supplemented. 6. Anemia. Iron malabsorption may result from decreased acid secretion or lack of duodenum after Billroth II procedure (gastrojejunostomy); deficiencies of iron and vitamin B12 or folate may result. 7. Bone and mineral disorders. Related to altered calcium absorption and metabolism with increased risk for fractures and deformity and malabsorption of vitamins and nutrients, such as vitamin D.

Describe how thrombus formation and the triad of Virchow lead to deep venous thrombosis (DVT) and how this increases the risk for pulmonary embolism. (p. 599)

Three factors (triad of Virchow) promote venous thrombosis: (1) venous stasis (e.g., immobility, age, congestive heart failure), (2) venous endothelial damage (e.g., trauma, intravenous medications), and (3) hypercoagulable states (e.g., inherited disorders, malignancy, pregnancy, use of oral contraceptives or hormone replacement therapy).

Discuss the importance of surfactant.

Type II alveolar cells secrete surfactant, a lipoprotein that coats the inner surface of the alveolus and lowers alveolar surface tension at end-expiration, thereby preventing lung collapse.

Compare ulcerative colitis and Crohn's disease

Ulcerative colitis is a chronic inflammatory bowel disease that causes ulceration, abscess formation, and necrosis of the colonic and rectal mucosa. Cramping pain, bleeding, frequent diarrhea, dehydration, and weight loss accompany severe forms of the disease. A course of frequent remissions and exacerbations is common. Crohn disease is similar to ulcerative colitis but it affects the GI tract from the mouth to the anus and tends to involve all the layers of the intestinal lumen. "Skip lesion" fissures and granulomata are characteristic of Crohn disease. Abdominal tenderness, diarrhea, and weight loss are the usual symptoms.

Compare and contrast the acute coronary syndromes.

Unstable angina is the result of reversible myocardial ischemia and is a harbinger of impending infarction. 1. Rest angina—Angina occurring at rest and prolonged, usually >20 minutes 2. New-onset angina—New-onset angina of at least CCS Class III severity 3. Increasing angina—Previously diagnosed angina that has become distinctly more frequent, longer in duration, or lower in threshold (i.e., increased by ≥1 CCS class to at least CCS Class III severity) Myocardial infarction (MI) results when there is prolonged ischemia causing irreversible damage to the heart muscle. MI can be further subdivided into non-ST elevation MI (non-STEMI) and ST elevation MI (STEMI). In this case, however, the thrombus is less labile and occludes the vessel for a prolonged period, such that myocardial ischemia progresses to myocyte necrosis and death. Pathologically, there are two major types of myocardial infarction: subendocardial infarction and transmural infarction. Clinically, however, myocardial infarction is categorized as non-ST segment elevation myocardial infarction (non-STEMI) or ST segment elevation MI (STEMI). he infarction will involve only the myocardium directly beneath the endocardium (subendocardial MI). This infarction will usually present with ST segment depression and T wave inversion without Q waves; therefore it is termed non-STEMI. It is especially important to recognize this form of acute coronary syndrome because recurrent clot formation on the disrupted atherosclerotic plaque is likely. If the thrombus lodges permanently in the vessel, the infarction will extend through the myocardium all the way from endocardium to epicardium, resulting in severe cardiac dysfunction (transmural MI). Transmural myocardial infarction will usually result in marked elevations in the ST segments on ECG, and these individuals are categorized as having ST segment elevation MI, or STEMI. Clinically, it is important to identify those individuals with STEMI because they are at highest risk for serious complications and should receive definitive intervention without delay.

Compare and contrast urinary tract infections, cystitis, acute pyelonephritis, and chronic pyelonephritis.

Urinary tract infections (UTIs) are rare in newborns, and children with congenital renal abnormalities and noncircumcised males are at increased risk. UTIs in children are most common in 7- to 11-year-old girls as a result of perineal bacteria, especially E. coli, ascending the urethra. Susceptibility, bacterial virulence, and, perhaps, genetics affect the severity of the disease. An abnormal urinary tract (presence of reflux, obstruction, stasis, or stones) is particularly susceptible to infection. Sexually active female adolescents are at increased risk to have a UTI. Cystitis, or infection of the bladder, results in mucosal inflammation and congestion. This causes detrusor muscle hyperactivity and a resulting decrease in bladder capacity, resulting in urgency and frequency. It may also cause distortion of the ureterovesical (UV) junction leading to transient reflux of infected urine up the ureters, causing acute or chronic pyelonephritis. Differentiating whether an infection is in the bladder or in the kidneys is difficult based on symptoms alone. Infants may be asymptomatic or develop fever, lethargy, abdominal pain, vomiting, diarrhea, or asymptomatic jaundice. Children may present with fever of undetermined origin, frequency, urgency, dysuria, enuresis or incontinence in a previously dry child, flank or back pain, and sometimes hematuria. Acute pyelonephritis usually causes chills, high fever, and flank or abdominal pain, along with enlarged kidney(s) caused by inflammatory edema. Chronic pyelonephritis may be asymptomatic.

Discuss the causes and effects of obstruction in various locations within the urinary tract.

Urinary tract obstruction is an interference with the flow of urine at any site along the urinary tract (Figure 30-1). An obstruction may be anatomic or functional. The obstruction impedes flow proximal to the blockage, dilates structures distal to the obstruction, increases the risk for infection, and compromises renal function. Anatomic changes in the urinary system caused by obstruction are referred to as obstructive uropathy. The severity of an obstructive uropathy is determined by (1) the location of the obstructive lesion, (2) the involvement of ureters and kidneys, (3) the severity (completeness) of the blockage, (4) the duration of the blockage, and (5) the nature of the obstructive lesion. Obstructions may be relieved or partially alleviated by correction of the obstruction, although permanent impairments occur if a complete or partial obstruction persists over a period of weeks to months or longer. Upper Urinary tract obstruction: (Before bladder) Common causes of upper urinary tract obstruction include stricture (an abnormal narrowing of a bodily passage) or congenital compression of a calyx or the ureteropelvic or ureterovesical junction (e.g. stones [calculi]); compression from an aberrant vessel (deviates from normal course), tumor, or abdominal inflammation and scarring (retroperitoneal fibrosis); or ureteral blockage from stones or a malignancy of the renal pelvis or ureter. Obstruction of the upper urinary tract causes dilation of the ureter, renal pelvis, calyces, and renal parenchyma proximal to the site of urinary blockage. Dilation of the ureter (the duct by which urine passes from the kidney to the bladder) is referred to as hydroureter (accumulation of urine in the ureter), and dilation of the renal pelvis (point of convergance for 2-3 major calyces, acts as a funnel for urine flowing to the ureter) and calyces proximal to a blockage leads to hydronephrosis (enlargement of the renal pelvis and calyces) or ureterohydronephrosis (fig 29-2). Dilation of the upper urinary tract is an early response to obstruction. It reflects smooth muscle hypertrophy and accumulation of urine above the level of blockage (urinary stasis). Unless the obstruction is relieved, this dilation leads to enlargement and tubulointerstitial fibrosis affecting the distal nephron and renal function within approximately 7 days. By 14 days, obstruction has adversely affected both distal and proximal aspects of the nephron. Within 28 days, the glomeruli of the kidney have been damaged and the renal cortex and medulla are reduced in size (thinned). Tubular damage initially decreases the kidney's ability to concentrate urine, causing an increase in urine volume despite a decrease in glomerular filtration rate (GFR). The affected kidney is unable to conserve sodium, bicarbonate, and water or excrete hydrogen or potassium, leading to metabolic acidosis and dehydration. The magnitude of this damage, and the kidney's ability to recover normal homeostatic function, is affected by the severity and duration of the obstruction. With complete obstruction and compression of the renal vasculature, damage to the renal tubules occurs in a matter of hours, and irreversible damage occurs within 4 weeks. Nevertheless, even in the face of complete obstruction, the human kidney may recover at-least partial homeostatic function provided the blockage is removed within 56 to 69 days. This recovery requires a period of approximately 4 months. Partial obstruction, in the absence of renal infection, leads to subtler but ultimately permanent impairments including loss of the kidney's ability to concentrate urine, reabsorb bicarbonate, excrete ammonia, or regulate metabolic acid-base balance. Lower Urinary Tract Obstruction: Obstructive disorders of the lower urinary tract (LUT) are primarily related to storage of urine in the bladder or emptying of urine through the bladder outlet. The causes of obstruction include both neurogenic and anatomic alterations or, in some instances, a combination of both. Incontinence is a common symptom and types of incontinence are reviewed on table 29-1. Neurogenic bladder is a general term for bladder dysfunction caused by neurologic disorders (table 29-2). The types of dysfunction are related to the sites in the nervous system that control sensory and motor bladder function. Anatomic causes of resistance to urine flow include urethral stricture (narrowing of its lumen), prostatic enlargement in men (caused by acute inflammation, benign prostatic hyperplasia, or prostate cancer), and pelvic organ prolapse in women. Symptoms of obstruction are more common in men and include (1) frequent daytime voiding (urination more than every 2 hrs while awake); (2) nocturia (awakening more than once each night to urinate for adults less than 65 years of age or more than twice for older adults); (3) poor force of stream; (4) intermittency of urinary stream; (5) bothersome urinary urgency, often combined with hesitancy; and (6) feelings of incomplete bladder emptying despite micturition. Renal tumors account for 3.8% of new cancer cases and 13,040 deaths each year, and there are a number of different types of kidney tumors. Renal adenomas (benign tumors) are uncommon but increasing in number. The tumors are encapsulated and are usually located near the cortex of the kidney. Because they can become malignant, they are usually surgically removed. Renal cell carcinoma (RCC) is the most commont renal neoplasm and represents about 2% of cancer deaths. Renal transitional cell carcinoma (RTCC) is rare and primarily arises in the renal parenchyma and renal pelvis. Renal cell carcinoma usually occurs in men (2 time more often than in women) between ages 50-60. Risk factors include cigarette smoking, obesity, and uncontrolled hypertension. With surgical resection five-year survival rate is about 90% for stage 1 cancer. The classical manifestations of renal tumors are hematuria, dull and aching flank pain, palpable flank mass, and weight loss, but all of these symptoms occur in fewer than 10% of cases. Bladder tumors are the fifth most common malignancy and represent about 1 % of all malignant tumors w/ 70,530 new cases each year and 14,680 deaths. The development of bladder cancer is most common in men older than 60 years. Transitional cell carcinoma is the most common bladder malignancy and tumors are usually superficial. Gross painless hematuria is the archetypal clinical manifestation of bladder cancer. Episodes of hematuria tend to recur, and they are often accompanied by bothersome lower urinary tract symptoms including daytime voiding frequency, nocturia, urgency, and urge urinary incontinence, particularly for carcinoma in situ. Flank pain may occur if tumor growth obstructs one or both ureterovesical junctions.

Describe the differences between viral, bacterial, atypical, and aspiration pneumonia.

Viral pneumonia is two to three times more likely to occur in children than in adults, and incidence generally follows a seasonal pattern. Bacterial coinfections are common. RSV (respiratory syncytial virus) is the most common viral pneumonia in young children. A number of other viruses are important, including parainfluenza, influenza, human rhinovirus, human metapneumovirus, adenoviruses, and Mycoplasma pneumoniae. Acquisition of these viruses is by direct contact, droplet transmission, or aerosol exposure. There is initial destruction of the ciliated epithelium of the distal airway with sloughing of cellular material. A mononuclear- predominant inflammatory response occurs, in the interstitium initially, and later may involve the alveoli as well. Early in the course of the disease, it is often difficult to determine whether the pneumonia is viral or bacterial. Viral pneumonia often presents with cough and no fever. Differences in the clinical presentation can help to determine origin, such as degree of elevation of temperature, absolute neutrophil counts, and percentage of bands. Ultimately, diagnosis requires laboratory confirmation using immunofluorescence tests. Development of safe agents to treat and prevent viral pneumonia continues to be a focus of much research. Bacterial pneumonia beyond the neonatal period is most commonly the result of infection with streptococci and staphylococci microorganisms. Pneumococcal (Streptococcus pneumoniae) pneumonia is the most common cause of community- acquired bacterial pneumonia and presents acutely and with variable severity. Childhood immunization with polyvariant pneumococcal conjugate vaccine appears to decrease the incidence of pneumococcal pneumonia in children younger than 2 years of age.50 Staphylococcal pneumonia and group A streptococcal pneumonia can be particularly fulminant (sudden, severe) and necrotizing (causing cell death) with a high incidence of accompanying empyema, pneumatocele (a lung lesion filled with air), and sepsis. H. influenzae pneumonia has become rare because of widespread immunization. Bacterial pneumonia usually begins with aspiration of nasopharyngeal bacteria. A preceding viral infection sometimes sets the stage for bacterial infection by causing epithelial damage, reduced mucociliary clearance in the trachea and major bronchi, and a reduced immune response. Once in the alveolar region, bacteria encounter local host defenses, such as antibodies, complement, and cytokines, which prepare bacteria for ingestion by alveolar macrophages. Alveolar macrophages recognize bacteria with their surface receptors and phagocytose them. If these mechanisms fail, macrophages release numerous inflammatory cytokines and neutrophils will be recruited into the lung. An intense, cytokine-mediated inflammation will ensue. Vascular engorgement, edema, and a fibrinopurulent exudate occur. Alveolar filling precludes gas exchange and, if extensive, can lead to respiratory failure. If sepsis occurs at the same time, shock and end-organ hypoperfusion will cause metabolic acidosis. The clinical presentation of bacterial pneumonia, particularly pneumococcal, may include a preceding viral illness followed by fever with chills and rigors, shortness of breath, and an increasingly productive cough. Occasionally, there is blood streaking of the sputum. Respiratory rate and oxygen saturation also are important clinical indicators. Auscultation usually shows such abnormalities as crackles or decreased breath sounds. Other, less specific findings may include malaise, emesis, abdominal pain, and chest pain. Chest films will usually present with a lobar pattern in older children and adolescents but may appear patchier with a bronchopneumonic pattern in younger children. Atypical pneumonia (Mycoplasma pneumoniae, Chlamydophila pneumoniae) is the most common cause of community-acquired pneumonia for school-age children and young adults. Chlamydophila pneumonia is clinically indistinguishable from and is typically grouped with Mycoplasma as "atypical pneumonia." Transmission is from person-to-person with a 2- to 3-week incubation period.Mycoplasmic microorganisms lack cell walls but have a limiting membrane and a specialized receptor for attaching to ciliated respiratory epithelial cells. Local sloughing of cells occurs. Peribronchial lymphocytic infiltration develops, along with neutrophil recruitment to the airway lumen. The pattern resembles bronchitis or bronchopneumonia. Onset is usually gradual, resembling a typical upper respiratory tract infection but with low-grade fever, cough, and chest pain.Mycoplasma can cause a wide spectrum of disease and is more extensive as a cause of complications than previously noted. It also is occurring more frequently in infants and younger children. Most cases are not clinically severe and full recovery should be expected. Complications, when they do occur, can include bronchopneumonia, parapneumonic effusions, and necrotizing pneumonitis. Aspiration pneumonitis is caused by a foreign substance, such as food, meconium, secretions (saliva or gastric), or environmental compounds, entering the lung and resulting in inflammation of the lung tissue. The aspiration of meconium from amniotic fluid can occur at birth.Neurologically compromised children or children with chronic lung disease may have chronic pulmonary aspiration (CPA), which can cause progressive lung disease, bronchiectasis, and respiratory failure. This is the leading cause of death in children who are neurologically compromised because of failure of protective reflexes and difficulty swallowing. Children undergoing sedation or anesthesia also may aspirate oral secretions contaminated with anaerobic bacteria or acidic stomach contents. The severity of lung injury after an aspiration incident is determined by the volume and pH of the material aspirated and the presence of pathogenic bacteria. Very low pH or extremely high pH will cause a significant inflammatory response. With hydrocarbon ingestions, lung injury is determined by the volatility and viscosity of the aspirated substance. A low- viscosity substance, such as gasoline or lighter fluid, is the most toxic, and high- viscosity hydrocarbons, such as petroleum jelly or mineral oil, are much less likely to cause a pneumonitis. Treatment for aspiration pneumonitis depends on the material aspirated but can include broad-spectrum antibiotics with failure to improve after 48 hours. Children with CPA and a large amount of upper respiratory

Patients who suffer from ulcerative colitis and Crohn disease have abdominal pain, which is the result of distention and inflammation. This type of pain is known as

Visceral (organ pain)

Discuss the occurrence, patterns, and probable etiologies of enuresis

Wetness that occurs during the day is called daytime incontinence. Nighttime wetting is called enuresis. Primary incontinence (enuresis) means the child has never been continent, whereas secondary incontinence (enuresis) means the child has been continent for at least 6 months before wetting recurs. A child may have daytime incontinence, enuresis, or a combination of both. The incidence of incontinence (enuresis) is difficult to determine because it is not a problem parents often discuss. Enuresis occurs in as many as 10% of 7-year-old males and resolves at a rate of 15% per year. Daytime incontinence occurs in up to 9% of early school age children. Pathogenesis A combination of factors is likely to be responsible for incontinence or enuresis. Organic causes account for a minority of cases and include UTIs; neurologic disturbances; congenital defects of the meatus, urethra, or bladder neck; and allergies. Disorders that increase the normal output of urine, such as diabetes mellitus and diabetes insipidus, or disorders that impair the concentrating ability of the kidney, such as chronic renal failure or sickle cell disease, should be considered during evaluation. Other conditions that may be associated with incontinence include perinatal anoxia, CNS trauma, seizures, attention-deficit/hyperactivity disorder, developmental delay, imperforate anus, bladder trauma or surgery, obesity, and occult spinal dysraphism. Altered sleep arousal or obstructive sleep apnea may be associated with enuresis. Stressful psychologic situations, such as a new sibling, may cause incontinence or enuresis to develop. Constipation is frequently present in children with urinary incontinence.Incontinence or enuresis in which no structural or neurologic abnormality is identified is common in children. Genetic factors contribute to some types of incontinence. At least four gene loci associated with enuresis have been identified. Enuresis occurs with high frequency among parents, siblings, and other near relatives of symptomatic children. There is a high concordance rate in monozygotic twins with enuresis.

Discuss the importance of the oxyhemoglobin dissociation curve for evaluating effective gas exchange.

When hemoglobin saturation and desaturation are plotted on a graph, the result is a distinctive S-shaped curve known as the oxyhemoglobin dissociation curve. The oxyhemoglobin dissociation curve relates oxygen saturation (O2 saturation) and partial pressure of oxygen in the blood (PO2), and is determined by how readily hemoglobin acquires and releases oxygen molecules from its surrounding tissue.

Describe the typical blood gas abnormalities found during an acute asthma attack.

With an acute asthmatic attack, even though the alveoli are functioning normally, there may be enough upper and middle airway obstruction to block alveolar ventilation, leading to CO2 retention --> respiratory acidosis

Describe the cellular findings, manifestations, risk factors, and outcomes in Reye syndrome.

a life-threatening disease that leads to multisystem failure...primarily affects the liver and the brain -Extremely rare but serious illness that can affect the brain and liver. -Affects kids 4 to 14 years old -Almost always follow the start of a viral illness, -Requent vomiting -tiredness or sleepiness in babies, diarrhea and rapid breathing irritability or aggressive behavior -changes in vision, difficulty hearing, and abnormal speech. -In the later stages, a child may behave irrationally; be confused; or have severe muscle weakness, seizures, and loss of consciousness. -There usually is no fever. Risk Factors: -Using aspirin to treat a viral infection, such as flu, chickenpox or an upper respiratory infection -Having an underlying fatty acid oxidation disorder Outcome: Most children and teenagers who have Reye's syndrome survive, although varying degrees of permanent brain damage are possible. Without proper diagnosis and treatment, Reye's syndrome can be fatal within a few days.

Discuss how factors influencing cardiac output reflect cardiac performance; include ejection fraction, preload, afterload, stroke volume, heart rate, and the neurological and hormonal regulation of the heart rate.

a. Cardiac output is the volume of blood flowing through either the systemic or the pulmonary circuit per minute. Cardiac output=heart rate (beats per minute) is multiplied by stroke volume (liters per beat). b. Ejection fraction: With each heartbeat, the ventricles eject much of their blood volume, and the amount ejected per beat is called ejection fraction. The ejection fraction is increased by factors that increase contractility, such as increased sympathetic nervous system activity. A decrease in ejection fraction may indicate ventricular failure c. Preload is the volume and associated pressure generated in the ventricle at the end of diastole (ventricular end-diastolic volume [VEDV] and pressure [VEDP]. Preload is determined by two primary factors: (1) the amount of venous blood returning to the ventricle during diastole and (2) the amount of blood left in the ventricle after systole (end-systolic volume). d. Afterload: Left ventricular afterload is the resistance to ejection of blood from the left ventricle. Afterload depends on pressure in the aorta. e. Stroke volume: the volume of blood ejected per beat during systole, also depends on the force of contraction, which depends on myocardial contractility or the degree of myocardial fiber shortening. Preload, afterload, and contractility all affect stroke volume. f. Heart Rate- Heart rate is determined by the sinoatrial node and by components of the autonomic nervous system, including cardiovascular control centers in the brain, receptors in the aorta and carotid arteries, and hormones, including catecholamines (epinephrine, norepinephrine).

Identify the areas of the brain in which alterations in emotions and behaviors occur when damaged.

hippocampus, amygdala, and prefrontal cortex

Describe the role of the renin-angiotensin system as it relates to renal blood flow.

major hormonal regulator of renal blood flow is the renin-angiotensin-aldosterone system (RAAS), which can increase systemic arterial pressure and change RBF. Renin is an enzyme formed and stored in the cells of the arterioles of the juxtaglomerular apparatus. Renin release is triggered by decreased blood pressure in the afferent arterioles, decreased sodium chloride concentration in the distal convoluted tubule, sympathetic nerve stimulation of β-adrenergic receptors on the juxtaglomerular cells, and the release of prostaglandins.Numerous physiologic effects of the RAAS stabilize systemic blood pressure and preserve the extracellular fluid volume during hypotension or hypovolemia. Actions include sodium reabsorption, systemic vasoconstriction, sympathetic nerve stimulation, and thirst stimulation with increased fluid intake.

List the parts of the alimentary canal sequentially from mouth to anus.

mouth,esophagus,stomach,small intestine,large intestine, rectum, anus`

Briefly explain the process of urine formation.

three processes: plasma filtration at the glomerulus followed by reabsorption and secretion of selective components by the renal tubules