Patho Exam 2 Review

Acute pain is a 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, and 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 and there is expectation of limited duration. Acute pain arises from cutaneous and deep somatic tissue, or from visceral organs and can be classified as (1) acute somatic, (2) acute visceral, and (3) referred. Somatic pain is superficial, arising from connective tissue, muscle or bone, and skin. Visceral pain refers to pain in internal organs and the lining of body cavities with an aching, gnawing, throbbing, or intermittent cramping quality. Referred pain is pain that 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.

Acute pain

. Delayed hypersensitivity. Allergic contact dermatitis is a common form of T-cell mediated or delayed hypersensitivity (type IV).

Allergic contact dermatitis is associated with:

Yes. In depressed individuals neurotransmitters are hypothesized to be reduced. Monoamine hypothesis of depression in which a deficit in the concentration of brain norepinepherine, dopamine, and or serotonin is the underlying cause of depression.

Are neurotransmitters associated with depression?

Peripheral nerve pathways are differentiated into afferent pathways (ascending pathways) that carry sensory impulses toward the CNS and efferent pathways (descending pathways) that innervate effector organs, such as skeletal, cardiac, and smooth muscle, as well as glands, by transmitting motor impulses away from the CNS. The somatic nervous system consists of motor and sensory pathways regulating voluntary motor control of skeletal muscle. The autonomic nervous system (ANS) also consists of motor and sensory components and 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. Sensory neurons carry impulses from peripheral sensory receptors to the CNS. Motor neurons transmit impulses away from the CNS to an effector organ.

Be familiar with how the brain gets information and how it responds. Think about it in terms of the ascending, descending, afferent, efferent, and somatic pathways and sensory versus motor.

Reflex is a Autonomic, subconscious response. A seizure is a sudden, transient disruption in brain electrical function caused by abnormal excessive hypersynchronous discharges of cortical neurons. Epilepsy is the recurrence of seizures and a type of seizure disorder for which no underlying correctable cause for the seizure can be found. The term convulsion is sometimes applied to seizures and refers to the tonic-clonic (jerky, contract-relax) movement associated with some seizures.

Briefly describe: Reflex, seizure, epilepsy, convulsion.

Nerve regeneration depends on many factors, such as location of the injury, the type of injury, the inflammatory responses, and the process of scarring. The closer the injury is 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 often form connective tissue scars that block or slow regenerating axonal branches.

Can nerves regenerate?

Chronic pain is usually defined as lasting at least 3 months and lasting well beyond the expected healing time following the initial onset of tissue damage or injury. Chronic or persistent pain serves no purpose and is poorly understood. It often appears to be out of proportion to any observable tissue injury. 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.

Chronic pain

In 95% of cases, delayed puberty is a physiologic (constitutional) delay in which hormonal levels are normal and the hypothalamic-pituitary-gonadal (HPG) axis is intact, but maturation is happening slowly. This physiologic delay tends to be familial, is not as common in girls as it is in boys, and is frequently diagnosed retrospectively once pubertal progression is complete. Many clinicians recommend intervention (i.e., exogenous sex steroid administration) in physiologic cases of delayed puberty to reduce the psychologic effects (e.g., self-esteem issues, embarrassment) often associated with delayed puberty. The other 5% of cases are caused by a disruption of the HPG axis of various etiologies, including any chronic condition that delays bone aging (i.e., celiac disease, anorexia, hypothyroidism). Hypergonadotropic Hypogonadism (Turner syndrome, gonadal dysgenesis, chemotherapy, or radiation therapy). Permanent Hypogonadotropic Hypogonadism (Tumors or infiltrative diseases of the central nervous system, GnRH deficiency (isolated hypogonadotropic hypogonadism, Kallmann syndrome), combined pituitary-hormone deficiency, chemotherapy, or radiation therapy). Functional Hypogonadotropic Hypogonadism (Systemic illness (inflammatory bowel disease, celiac disease, anorexia nervosa, or bulimia), hypothyroidism, excessive exercise

Delayed development of puberty is most often associated with what kinds of problems?

Eccrine sweat glands. These appendages are distributed over the body, with the greatest numbers in the palms of the hands, soles of the feet, and forehead. Secretions of the eccrine glands are important in thermoregulation and cooling of the body through evaporation.

Dermal appendages that are important in body temperature regulation are:

Cheyne-Stokes respiration is an abnormal rhythm of breathing (periodic breathing) with alternating periods of hyperventilation and apnea (crescendo-decrescendo pattern). The pathophysiology of Cheyne-Stokes respiration involves a hyperventilatory response to carbon dioxide stimulation. In the damaged brain, higher levels of Paco2 (hypercapnia) are required to stimulate ventilation, and the response is hyperventilation. As a result, the Paco2 level decreases to below normal and breathing stops (PHVA) until carbon dioxide reaccumulates and stimulates hyperventilation. In cases of opiate or sedative drug overdose, the respiratory center is depressed and the rate of breathing gradually decreases until respiratory failure occurs.

Describe Cheyne-Stokes respirations

If DNA damage is severe, the cell undergoes programmed cell death, or apoptosis, rather than simply dividing with damaged DNA. This self-destruct mechanism, called apoptosis, is triggered by diverse stimuli, including normal development and excessive growth. The pathway to apoptosis is disabled in advanced cancers. The most common mutations conferring resistance to apoptosis occur in the TP53 gene.

Describe apoptosis.

Erythrocytes (red blood cells [RBCs]) are the most abundant cells of the blood, occupying approximately 48% of the blood volume in men and about 42% in women. Erythrocytes are primarily responsible for tissue oxygenation. The erythrocyte contains hemoglobin, which carries the gases, and electrolytes, which regulate diffusion through a cell's plasma membrane. The mature erythrocyte lacks a nucleus and cytoplasmic organelles (e.g., mitochondria), so it cannot synthesize protein or carry out oxidative reactions. Because it cannot undergo mitotic division, the erythrocyte has a limited life span (approximately 100 to 120 days), ages, and is removed from the circulation to be replaced by new erythrocytes. The erythrocyte's size and shape are ideally suited to its function as a gas carrier. An RBC is a small disk with two unique properties: (1) a biconcave shape and (2) the capacity to be reversibly deformed (Figure 27-2 and Figure 27-6). The flattened, biconcave shape provides a surface area/volume ratio that is optimal for gas diffusion into and out of the cell and for deformity.2 During its life span, the erythrocyte, which is 6 to 8 μm in diameter, repeatedly circulates through sinusoids of the spleen and capillaries that are only 2 μm in diameter. Reversible deformity enables the erythrocyte to assume a more compact torpedo-like shape, squeeze through the microcirculation, and return to normal.

Describe the erythrocyte?

CLL involves malignant transformation and progressive accumulation of monoclonal B lymphocytes; rarely (less than 5%) are CLL malignancies of T-cell origin. The characteristic immunophenotype is expression of CD5, CD19, and CD23 molecules and low amounts of surface membrane Ig and CD20 molecules. CD5 is a signal transduction molecule linked to the B-cell receptor (BCR); CD19 is a low-affinity antigen receptor expressed on maturing B cells, but is lost in plasma cells; and CD23 is a low-affinity receptor for the Fc portion of IgE. CLL is derived from a transformation of a partially mature B cell that has not yet encountered antigen. The gene for the variable region of the antibody heavy chain (IGHV) is frequently mutated (30% to 40% of persons). Individuals with a mutated IGHV tend to have a more benign condition with a more slowly developing and less malignant disease. Significant numbers of this mutation are associated with a median survival in excess of 20 to 25 years, whereas the absence of mutations is associated with a poorer survival rate (median survival 8 to 10 years). The etiology of CLL is unknown. A familial tendency suggests a genetic linkage; first-degree relatives have a three times greater risk of developing the disease. It is rare in individuals younger than 45 years of age, and when diagnosed, 95% of individuals are older than age 50. Genetic anomalies occur in approximately 90% of cases, frequently as deletions, although none has been linked to the etiology of CLL. CLL cells that accumulate in the marrow do not interfere with normal blood cell production to the extent found in acute leukemias. This is a significant feature explaining the reduced severity in the beginning stage of disease. Accumulation of malignant B cells is the result of cell cycle arrest in the G0/G1 phase. CLL cells tend to express increased levels of anti-apoptotic proteins (e.g., BCL2) and suppress pro-apoptotic proteins (e.g., BAX), which reduces their sensitivity to apoptosis. Because the major pathophysiologic deficit in CLL is the failure of B cells to mature into plasma cells that synthesize immunoglobulin, this often results in hypogammaglobulinemia (60% of clients).

Describe the underlying pathophysiology of Chronic lymphocytic leukemia (CLL)?

During the late follicular phase, the preovulatory rise in progesterone facilitates the positive feedback of estrogen; estrogen levels begin to increase, stimulating a surge of LH secretion from the anterior pituitary. The midcycle surge of LH and FSH induces ovulation.Ovulation generally occurs 1 to 2 hours before the final progesterone surge, or about 12 to 36 hours after the onset of the FSH and LH surge. Progesterone, proteolytic enzymes, and prostaglandins (E and F series) trigger mechanisms controlling follicularrupture and release of the ovum.1 Possible mechanisms include thinning, stretching, degradation, and digestion of the follicular wall and contraction of smooth muscle cells of the follicle. The role of prostaglandins is essential to ovulation, and

Hormonally, what happens to cause ovulation?

Endogenous opioids are a family of morphine-like neuropeptides that inhibit transmission of pain impulses in the spinal cord, brain, and periphery. The best known and the most prevalent of these natural opioids are the enkephalins. Enkephalins, like the other endogenous opioids, can be identified immunohistochemically. They are found concentrated in the hypothalamus, the PAG matter, the nucleus raphe magnus of the medulla, and the dorsal horns of the spinal cord. The synthesis and activity of β-endorphin are concentrated in the hypothalamus and the pituitary gland. β-Endorphin is purported to produce a greater sense of exhilaration, or "high," than all of the other endorphin types. It is a strong μ-receptor agonist and is generally believed to provide substantial natural pain relief.

How are enkephalins and endorphins related to the pain response?

Amniocentesis and Analysis of fetal DNA in maternal circulation. Prenatally using ultrasound or evaluating maternal serum alpha fetoprotein (AFT)

How do we test for neural tube defects in the fetus?

HUS, CAT scan or MRI. If the tumor is located in the posterior fossa region, the fourth ventricle may become blocked, which leads to hydrocephalus and signs of increased ICP.

How do you diagnose hydrocephalus in children? How can a brain tumor cause this problem?

The posterior pituitary secretes polypeptide hormones ADH, also called arginine-vasopressin. The major homeostatic function of the posterior pituitary is the control of plasma osmolality, as regulated by ADH. At physiologic levels, ADH acts on the vasopressin 2 (V2) receptors of the renal tubular cells to increase their permeability. This increased permeability leads to an increase in water reabsorption into the blood and the production of more concentrated urine. These effects may be inhibited by hypercalcemia, prostaglandin E, and hypokalemia. At pathophysiologically high serum levels, ADH acts on vasopressin 1 (V1) receptors and causes vasoconstriction. The secretion of ADH is regulated primarily by the osmoreceptors of the hypothalamus, located near or in the supraoptic nuclei. As plasma osmolality increases, these osmoreceptors are stimulated, the rate of ADH secretion increases, more water is reabsorbed from the kidney, and the plasma is diluted to its set-point osmolality (approximately 280 mOsm/kg).15 ADH has no direct effect on electrolyte levels, but by increasing water reabsorption, serum electrolyte concentrations may decrease because of a dilutional effect. ADH secretion also is increased by changes in intravascular volume, which are monitored by mechanoreceptors in the left atrium and in the carotid and aortic arches. A volume loss of 7% to 25% acts through these receptors to stimulate ADH secretion. Stress, trauma, pain, exercise, nausea, nicotine, exposure to heat, and drugs such as morphine also increase ADH secretion. ADH secretion decreases with a decrease in plasma osmolality; an increase in intravascular volume; hypertension; an increase in estrogen, progesterone, and angiotensin II levels; and alcohol ingestion. ADH at high serum levels acts on the V1 receptors and causes vasoconstriction and a resulting increase in arterial blood pressure.

How does ADH work?

Aldosterone is the most potent of the naturally occurring mineralocorticoids and acts to conserve sodium by increasing the activity of the sodium pump of the epithelial cells in the nephron. Aldosterone synthesis and secretion are regulated primarily by the renin-angiotensinaldosterone system, although other factors also may be involved. The renin-angiotensin system is activated by sodium and water depletion, increased potassium levels, and a diminished effective blood volume. Angiotensin II is the primary stimulant of aldosterone synthesis and secretion; however, sodium and potassium levels also may directly affect aldosterone secretion. When sodium and potassium levels are within normal limits, approximately 50 to 250 mg of aldosterone is secreted daily. Of the secreted aldosterone, 50% to 75% binds to plasma proteins. Aldosterone is degraded in the liver and is excreted by the kidney. Aldosterone maintains extracellular volume by acting on distal nephron epithelial cells to increase sodium reabsorption and potassium and hydrogen excretion.52 This renal effect takes 90 minutes to 6 hours. Other effects of aldosterone include enhancement of cardiac muscle contraction, stimulation of ectopic ventricular activity through secondary cardiac pacemakers in the ventricles, stiffening of blood vessels with increased vascular resistance, and decreased fibrinolysis. Pathologically elevated levels of aldosterone have been implicated in the myocardial changes associated with heart failure.

How does Aldosterone work?

Local expansion of pituitary adenomas may cause both neurologic and secretory defects. Neurologically, the tumor may impinge on the optic chiasm if it extends upward from the sella turcica. This causes a variety of visual disturbances, depending on the area of the optic chiasm that is compressed.

How does a pituitary tumor contribute to visual problems?

Inflammatory and immune responses may create a local environment in which cells can develop into a malignant phenotype and may even benefit progression and spread of malignancies. Chronic inflammation increases the risk of cancer by increasing cell divisions in an effort to repair damaged tissues. Chronic inflammation is also associated with the release of potentially toxic substances such as oxygen radicals, prostaglandins, and some interleukins. Inhibition of inflammation by some anti-inflammatory medications (e.g., ibuprofen) has been associated with a decreased risk for certain cancers.

How does chronic inflammation lead to cancer?

Glaucoma is a leading cause of visual impairment and blindness. It is characterized by intraocular pressures greater than the normal pressures of 12 to 20 mmHg maintained by the aqueous fluid. Chronic increased intraocular pressure causes death of retinal ganglions and optic nerve degeneration with loss of peripheral vision, followed by central vision impairment and blindness. Extremely high pressures can cause blindness within days or hours. Loss of visual acuity results from pressure on the optic nerve, which is believed to block the flow of cytoplasm from neuronal bodies in the retina to peripheral optic nerve fibers entering the brain.

How does glaucoma cause blindness?

• Skin is first line of defense, regulates body temp, immune response • The epidermis provides a protective barrier between the host and the outside environment, and the linings of the internal body organs help absorb substances into the body, excrete waste products, and secrete substances into body cavities. • Epithelial tissue covers most internal and external surfaces of the body. The functions of epithelial tissue include protection, absorption, secretion, and excretion • Epithelial surfaces provide biochemical barriers by synthesizing and secreting substances meant to trap of destroy microorganisms. i.e. Mucus, earwax, goblet cells, saliva, tears.

How does the skin protect us against antigens in the environment? What kinds of cells play a role in this process?

Platelets circulate in the bloodstream for about 8 to 10 days before losing their ability to carry out thrombogenic activity. Senescent platelets are sequestered and destroyed in the spleen by mononuclear cell phagocytosis.

How long do platelets live in the circulation?

It receives approximately 15% to 20% of the total cardiac output.

How much of the cardiac output does the brain get?

• autosomal dominant hereditary degenerative disorder of basal ganglia of caudate and putamen nuclei & frontal cortex • short arm chromo #4 • loss of dopaminergic FX in substantia nigra • depletion of gamma aminobutyric (GABA) • S/S: abn mov't w/o conscious effort, emotional liability, and dementia • TX - no cure, dopamine receptor blocking meds may help

Huntington's Disease

. Allergic contact dermatitis is a common form of T-cell mediated or delayed hypersensitivity (type IV). • Allergan comes into contact with the skin bound to a carrier protein, forming a hapten-specific sensitizing antigen • Langerhans cells process antigen and carry it to T-Cells • T-Cells become sensitized to antigen, releasing cytokines and chemokine leading to leukocyte infiltration and inflammation

In allergic contact dermatitis, how does the body recognize the antigen? Think about how the immune response and the cells involved.

Severe degen of basal ganglia (corpus stratum) involving the dopaminergic nigrostriatal pathway • loss of dopaminergic pigmented neurons in the substantial nigra • S/S: rigidity, bradykinesia, akinesia, tremor, postural abnormalities, autonomic-neuro endocrine symptoms, cognitive-affective symptoms of dementia • TX: Levodopa, anticholinergic drugs, antihistamines, Amantadine

Parkinson's Disease

Premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD) are the cyclic recurrence (in the luteal phase of the menstrual cycle) of distressing physical, psychologic, or behavioral changes that impair interpersonal relationships or interfere with usual activities

Premenstrual syndrome

In primary hypothyroidism the loss of functional thyroid tissue leads to a decreased production of TH. Causes in adults include autoimmune thyroiditis (Hashimoto disease), iatrogenic loss of thyroid tissue after surgical or radioactive treatment for hyperthyroidism, head and neck radiation therapy, medications, and endemic iodine deficiency. Infants and children may present with hypothyroidism because of congenital defects in the pituitary or thyroid glands. Central (secondary) hypothyroidism is caused by the pituitary's failure to synthesize adequate amounts of TSH or a lack of TRH. Pituitary tumors that compress surrounding pituitary cells or the consequences of their treatment are the most common causes of secondary hypothyroidism. Other causes include traumatic brain injury, subarachnoid hemorrhage, or pituitary infarction. Hypothalamic dysfunction results in low levels of TRH, TSH, and TH. Primary hypothyroidism has several causes. Iodine deficiency (endemic goiter) is the most common cause worldwide, but is relatively rare in the United States because of the use of iodized table salt and fortified foods. The most common cause of hypothyroidism in the United States is autoimmune thyroiditis (Hashimoto disease, chronic lymphocytic thyroiditis), which results in gradual inflammatory destruction of thyroid tissue by infiltration of lymphocytes and circulating thyroid autoantibodies. Subacute thyroiditis (subacute granulomatous thyroiditis, or de Quervain thyroiditis) is an uncommon nonbacterial inflammation of the thyroid often preceded by a viral infection. It is accompanied by fever, tenderness, and enlargement of the thyroid. The inflammatory process initially results in elevated levels of TH caused by release of stored thyroglobulin, and then is associated with transient hypothyroidism before the gland recovers normal activity. Painless thyroiditis (silent or subacute lymphocytic thyroiditis) has a course similar to that of subacute thyroiditis but is pathologically identical to Hashimoto disease. Iatrogenic hypothyroidism results from radioiodine thyroid ablation, thyroidectomy, and medications (lithium and amiodarone). Postpartum thyroiditis generally occurs within 6 to 12 months of delivery, develops in up to 5.4% of all women, and has a course similar to that of painless thyroiditis. The individual develops a low basal metabolic rate, cold intolerance, lethargy, tiredness, and slightly lowered basal body temperature and also may have diastolic hypertension. The characteristic sign of severe or long-standing hypothyroidism is myxedema. Myxedema is also responsible for thickening of the tongue and the laryngeal and pharyngeal mucous membranes. This results in thick, slurred speech and hoarseness, both of which are common in hypothyroidism.

Review Causes and signs and symptoms of hypothyroidism.

Microvascular: retinopathy, nephropathy, and neuropath. Diabetic microvascular complications (disease in capillaries) are a leading cause of blindness, end-stage renal failure, and various neuropathies. Thickening of the capillary basement membrane, endothelial cell hyperplasia, thrombosis, and pericyte degeneration are characteristic of diabetic microangiopathy and emerge over a period of 1 to 2 years. The thickening eventually results in decreased tissue perfusion. Diabetic retinopathy results from relative hypoxemia, damage to retinal blood vessels and vasoconstriction, red blood cell (RBC) and platelet aggregation, influence of vascular endothelialgrowth factors and growth hormone, and angiogenesis. Diabetic neuropathy is the most common cause of neuropathy in the Western world and is probably the most common complication of diabetes. Nerves do not require insulin for glucose transport and are particularly vulnerable to the pathologic effects of chronic hyperglycemia. The underlying pathologic mechanism includes both metabolic and vascular factors related to chronic hyperglycemia. Inflammation, ischemia, oxidative stress, advanced glycation end products and increased formation of polyols contribute to demyelination, nerve degeneration, and delayed conduction. Both somatic and peripheral nerve cells show diffuse or focal damage resulting in polyneuropathy. Sensory deficits generally precede motor involvement. The extremities are involved first in a "stocking and glove" pattern. Macrovascular disease (lesions in large and medium sized arteries) increases morbidity and mortality and increases risk for accelerated atherosclerosis and myocardial infarction, stroke, and peripheral vascular disease, particularly among individuals with type 2 diabetes mellitus.

Review complications associated with diabetes: Microvascular versus Macrovascular, nephropathy, retinopathy.

Guillain-Barré syndrome (GBS) is an acquired acute inflammatory demyelinating or axonal polyneuropathy with four subtypes. GBS is considered to be an autoimmune disease triggered by a preceding bacterial or viral infection. Molecular mimicry (cross-activation of self-epitopes and pathogen-derived peptides by autoreactive T and B cells) is associated with the immune injury. It has been recognized that glycolipids, particularly gangliosides, are immune targets in the subtypes of GBS. Different gangliosides predominate in different locations in peripheral nerves and in different nerve fiber types. The muscle innervated by the damaged peripheral nerves undergoes denervation and atrophy. If the cell body survives, regeneration of the peripheral nerve takes place and recovery of function is likely. If the cell body dies from intense root involvement in the inflammatory degenerative process, no regeneration is possible. Collateral reinnervation from surviving axons and regenerating axons may take place. In this case, motor recovery is less complete and residual deficits persist. Typical first manifestations are numbness, pain, paresthesias, or weakness in the limbs. Motor signs manifest as an acute or subacute progressive paralysis.

Review pathophysiology and signs and symptoms of Guillian-Barre

Multiple sclerosis (MS) is a chronic inflammatory disease involving degeneration of CNS myelin, scarring or formation of plaque, and loss of axons. MS is caused by an autoimmune response to self-antigens in genetically susceptible individuals. MS is a diffuse and progressive CNS disease that affects white and gray matter. Autoreactive T and B cells recognize myelin autoantigens and trigger inflammation in the CNS, leading to the loss of myelin sheaths and nerve conductivity and subsequently to the death of neurons. MS is described as occurring when a previous infectious insult to the nervous system has occurred in a genetically susceptible individual with a subsequent abnormal CNS immune response. Various mechanisms cause irreversible tissue damage (inflammation, oligodendrocyte injury, demyelination, scarring or plaque formation, and axonal degeneration) that characterizes MS. These degenerative processes begin early in the course of the disease and continue to progress throughout a person's life. Demyelinated axons are more fragile and susceptible to further damage and, when degeneration exceeds self-repair ability (remyelination), permanent disability results. Myelin destruction and axonal damage begin before symptom onset (early inflammatory demyelination). Optic signs—optic neuritis Brainstem signs—internuclear ophthalmoplegia, diplopia, vertigo (vomiting), nystagmus, dysarthria. Spastic ataxia Deep sensory changes in the extremities Bladder and bowel symptoms. Motor ataxia Hypotonia Asthenia, Blindness

Review pathophysiology and signs and symptoms of Multiple Sclerosis

Myasthenia gravis is a chronic autoimmune disease mediated by acetylcholine receptor (AchR) antibodies that act at the neuromuscular junction. Myasthenia gravis results from a defect in nerve impulse transmission at the neuromuscular junction. The main defect is T-cell-dependent formation of autoantibodies (an IgG antibody) against receptors at the Ach-binding site on the postsynaptic membrane. The autoantibodies block the AchR or cause complement-mediated loss of AchRs from the neuromuscular junction The cause of this autosensitization is unknown. Destruction of receptor sites occurs, decreasing the number of receptors on the plasma membrane and causing diminished transmission of nerve impulses across the neuromuscular junction. Muscle depolarization is incomplete or unsuccessful. Clinical Manifestations. Myasthenia gravis typically has an insidious onset. Clinical manifestations may first appear during pregnancy, during the postpartum period, or in conjunction with the administration of certain anesthetic agents. Hallmark symptoms are exertional fatigue and weakness that worsens with activity, improves with rest, and recurs with resumption of activity. The individual often complains of fatigue after exercise and has a recent history of recurring upper respiratory tract infections. The muscles of the eyes, face, mouth, throat, and neck usually are affected first. The extraocular (eye) muscles and the levator muscles are most affected. Manifestations include diplopia, ptosis, and ocular palsies. The muscles of facial expression, mastication, swallowing, and speech are the next most involved. The results are facial droop and an expressionless face; difficulty chewing and swallowing associated with dietary changes and weight loss; drooling; episodes of choking and aspiration; and a nasal, low-volume but high-pitched monotonous speech pattern.

Review pathophysiology and signs and symptoms of Myasthenia Gravis.

Parkinson disease (PD) is a complex motor disorder accompanied by systemic nonmotor and neurologic symptoms. The main disease feature is degeneration of the basal ganglia (corpus striatum, globus pallidus, subthalamic nucleus, and substantia nigra) involving the dopaminergic (dopamine-secreting) nigrostriatal pathway. The hallmark pathologic features of PD are loss of dopaminergic pigmented neurons in the substantia nigra (SN) pars compacta with dopaminergic deficiency in the putamen portion of the striatum. Dopamine loss in other brain areas including the brainstem, thalamus, and cortex also occurs.81 Degeneration of the dopaminergic nigrostriatal pathway to the basal ganglia results in underactivity of the direct motor pathway (normally facilitates movement) and overactivity of the indirect motor loop (normally inhibits movement). This results in inhibition of the motor cortex manifested with bradykinesia and rigidity. The classic motor manifestations of PD are resting tremor, bradykinesia/akinesia (poverty of movement), rigidity (muscle stiffness), and postural abnormalities. These manifestations may develop alone or in combination; however, as the disease progresses, all four are usually present to at least some degree. There is no true paralysis.

Review pathophysiology and signs and symptoms of Parkinson's.

Schizophrenic symptoms are classified into positive, negative, and cognitive categories. Positive symptoms include hallucinations, delusions, formal thought disorder, and bizarre behavior. Negative symptoms include flattened affect, alogia, anhedonia, attention deficits, and apathy. Cognitive symptoms are the inability to perform daily tasks requiring attention and planning. Schizophrenia has a strong genetic predisposition and environmental factors (e.g., viral infection, nutritional deficiencies, prenatal birth complications, urban upbringing) may interfere with genetically programmed neural development to alter brain structure and function. Brain imaging studies reveal structural brain abnormalities, including an enlargement of the cerebroventricles and widening of the fissures and sulci in the frontal cortex. In addition, there is a reduction in the volumes of both the thalamus, which may disrupt communication among cortical brain regions, and the temporal lobe, which may be responsible for the manifestations of positive symptoms.

Review pathophysiology and signs and symptoms of Schizophrenia.

Earlyonset familial Alzheimer disease (FAD) is autosomal dominant and has been linked to three gene defects. Lateonset AD may be associated with chromosome 19 involved withthe apolipoprotein E gene-allele 4 (apoE4).37 Sporadic AD is the most common and does not have a specific genetic association. Pathologic alterations in the brain include the formation of neuritic plaques containing a core of amyloid beta protein, the formation of neurofibrillary tangles, and the 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. Amyloid also is deposited in cerebral arteries, causing an amyloid angiopathy and disturbance in blood flow. The tau protein, a microtubulebinding protein, in neurons detaches and forms an insoluble filament called a neurofibrillary tangle, which contributes to neuronal death. The loss of neurons results in brain atrophy with decreases in weight and volume. The sulci widen and the gyri thin, especially in the frontal and temporal lobes, and the ventricles enlarge to fill the space. Loss of acetylcholine and other neurotransmitters contributes to the decline of memory and attention and the decline of other cognitive functions associated with AD. Neuroinflammation is evident in the pathophysiology of AD but the exact mechanisms are still being determined

Review pathophysiology of Alzheimer's disease.

Hypertension is the single greatest risk factor for stroke.48 Risk factors for stroke include the following: 1. Arterial hypertension 2. Intracranial atherosclerosis 3. Insulin resistance and diabetes mellitus 4. High total cholesterol or low high-density lipoprotein (HDL) cholesterol level, elevated lipoprotein-A level 5. Hyperhomocysteinemia 6. Congestive heart disease and peripheral vascular disease 7. Asymptomatic carotid stenosis 8. Polycythemia and thrombocythemia 9. Atrial fibrillation and patent ductus arteriosus 10. Chlamydia pneumoniae infection promotes atherosclerosis50 11. Sickle cell disease 12. Postmenopausal hormone therapy 13. High sodium intake, >2300 mg; low potassium intake, <4700 mg 14. Smoking 15. Physical inactivity 16. Obesity 17. Chronic sleep deprivation 18. Depression Most common is ischemic (thrombotic or embolic) stroke. Thrombotic strokes (cerebral thrombosis) arise from arterial occlusions caused by thrombi formed in the arteries supplying the brain or in the intracranial vessels. The development of a cerebral thrombosis most frequently is attributed to atherosclerosis and inflammatory disease processes (arteritis) that damage arterial walls. Embolic stroke involves fragments that break from a thrombus formed outside the brain or in the heart, aorta, or common carotid artery. Other sources of embolism include fat, air, tumor, bacterial clumps, and foreign bodies. The embolus usually involves small vessels and obstructs at a bifurcation or other point of stenosis, thus causing ischemia. An embolus may obstruct the lumen entirely and remain in place or shatter into fragments and become part of the vessel's blood flow. A lacunar stroke (lacunar infarct) is microinfarct smaller than 1 cm in diameter and involves occlusion of the small perforating arteries, predominantly in the basal ganglia, internal capsules, and pons. Lacunar infarcts are caused by lipohyalinosis, subintimal lipid-loading foam cells, and fibrinoid materials that thicken the arterial walls. The small arterioles lengthen, become tortuous, and develop subintimal dissections and microaneurysms. They are associated with hyperlipidemia, smoking, hypertension, and diabetes mellitus. Because of the subcortical location and small area of infarction, these strokes may have pure motor and sensory deficits. Hemorrhagic stroke is spontaneous bleeding into the brain. It is the third most common cause of CVA. Risk factors for hemorrhagic stroke include hypertension, previous cerebral infarct, coronary artery disease, and diabetes mellitus. The most common causes of spontaneous primary hemorrhagic strokes are hypertension (56% to 81%), ruptured aneurysms, arteriovenous malformation and fistula, amyloid angiopathy, and cavernous angioma. ICH can occur secondary to traumatic brain injury, bleeding into ischemic brain infarction or tumor, or bleeding disorder or anticoagulation therapy.

Review risk factors for cerebral vascular accident. What is the difference between hemorrhagic and ischemic, Thrombotic, embolic, and lacunar.

The anterior pituitary is composed of two main cell types: (1) the chromophobes, which appear to be nonsecretory; and (2) the chromophils, which are considered the secretory cells of the adenohypophysis. The chromophils are subdivided into seven secretory cell types, each type secreting one or more specific hormones. In general, the regulation of the anterior pituitary hormones is achieved by (1) feedback of hypothalamic releasing-inhibitory hormones and factors, (2) feedback from target gland hormones (i.e., cortisol, estrogen), and (3) direct effects of neurotransmitters. The major tropic hormones secreted by the anterior pituitary include ACTH, melanocyte-stimulating hormone (MSH), luteinizing hormone (LH), growth hormone (GH), prolactin, follicle-stimulating hormone (FSH), and TSH. These major hormones can be grouped into three categories: corticotropin-related hormones (ACTH and MSH), glycoproteins (LH, FSH, and TSH), and somatomammotropins (GH and prolactin). The corticotropin-related hormones are all derived from the precursor pro-opiomelanocortin (POMC). The role of ACTH is discussed later in this chapter. MSH promotes the secretion of melanin, which makes the skin darker. β-Lipotropin and β-endorphins are minor corticotropic hormones also released from the anterior pituitary. β-Lipotropin plays a role in fat catabolism and β-endorphins impact pain perception, body temperature, and food and water intake. The glycoprotein gonadotropins FSH and LH control reproductive processes in men and women

Review the function of the anterior pituitary.

The parathyroid glands produce parathyroid hormone (PTH), which works in concert with vitamin D to increase serum calcium concentration. The overall effect of PTH secretion is to increase serum calcium concentration and decrease serum phosphate level. Magnesium and phosphate levels also affect PTH secretion. Hypomagnesemia in persons with normal calcium levels acts as a mild stimulant to PTH secretion, whereas in hypocalcemic individuals, hypomagnesemia decreases PTH secretion. Hyperphosphatemia leads to hypocalcemia because of calcium phosphate precipitation in soft tissue and bone. Alterations in serum phosphate levels therefore may indirectly influence PTH secretion by affecting serum calcium levels.

Review the function of the parathyroid gland

The posterior pituitary secretes two polypeptide hormones: (1) ADH, also called arginine-vasopressin; and (2) oxytocin. The posterior pituitary thus can be seen as a storage and releasing site for hormones synthesized in the hypothalamus.The major homeostatic function of the posterior pituitary is the control of plasma osmolality, as regulated by ADH. Oxytocin is responsible for contraction of the uterus and milk ejection in lactating women and may affect sperm motility in men.

Review the function of the posterior pituitary.

The characteristic sign of severe or long-standing hypothyroidism is myxedema, which is histologically similar to the pretibial myxedema deposits that often occur with Graves disease. Myxedema is a result of an alteration in the composition of the dermis and other tissues. The connective fibers are separated by an increased amount of protein and mucopolysaccharides. This protein-mucopolysaccharide complex binds water, producing nonpitting, boggy edema, especially around the eyes, hands, and feet and in the supraclavicular fossae. Myxedema is also responsible for thickening of the tongue and the laryngeal and pharyngeal mucous membranes. This results in thick, slurred speech and hoarseness, both of which are common in hypothyroidism.

Review the pathophysiology and signs and symptoms of , myxedema

Diabetes insipidus (DI) is an insufficiency of ADH, leading to polyuria (frequent urination) and polydipsia (frequent drinking). There are three forms: neurogenic (hypothalamic), nephrogenic (renal), and polydipsic (polydipsia-polyuria syndrome). Neurogenic DI is the form encountered most often in clinical practice and is caused by insufficient amounts of ADH. It occurs when any organic lesion of the hypothalamus, pituitary stalk, or posterior pituitary interferes with ADH synthesis, transport, or release. Causative lesions include primary or secondary brain tumors, aneurysms, thrombosis, infections, and immunologic disorders. Nephrogenic DI is associated with an insensitivity of the renal collecting tubules to ADH. The nephrogenic form of DI can be genetic or acquired. Dipsogenic DI occurs when excessive fluid intake lowers the plasma osmolarity to the point that it falls below the threshold for ADH secretion. This condition may be associated with psychiatric disorders but also has been found in individuals who have a low osmotic threshold for inducing thirst. Neurogenic, nephrogenic, and dipsogenic DI are all characterized by the inability of the kidney to increase permeability to water. This causes excretion of large volumes of dilute urine and an increase in plasma osmolality. In conscious individuals, the thirst mechanism is stimulated and induces polydipsia. For unknown reasons the person usually craves cold drinks. The urine output is varied but can increase from the normal output of 1 to 2 L/day to as much as 8 to 12 L/day. The urine specific gravity is low, from 1.00 to 1.005, which is consistent with the failure to reabsorb water. Dehydration develops rapidly without ongoing fluid replacement. If the individual with DI cannot maintain balance with the urinary loss of water,serum hypernatremia and hyperosmolality occur. Other serum electrolytes generally are not affected. Clinical Manifestations. The signs and symptoms of DI include polyuria, nocturia, continuous thirst, and polydipsia.

Review the pathophysiology and signs and symptoms of Diabetes Insipidus.

Graves disease is the underlying cause of 50% to 80% of cases of hyperthyroidism. Although the cause of Graves disease is not known, genetic factors interacting with environmental triggers play an important role in the pathogenesis of this autoimmune thyroid disease. Graves disease results from a form of type II hypersensitivity in which there is stimulation of the thyroid by autoantibodies directed against the TSH receptor. These autoantibodies, called thyroidstimulating immunoglobulins (TSIs; also called thyroidstimulating antibodies [TSAbs] or thyroid receptor antibodies [TRAbs]), override normal regulatory mechanisms. The TSI stimulation of TSH receptors in the gland results in hyperplasia of the gland (goiter) and increased synthesis of TH, especially of triiodothyronine (T3). Increased levels of TH affect every physiologic system and result in the classic signs and symptoms of hyperthyroidism. TSH production by the pituitary is inhibited through the usual negative feedback loop. TSIs also contribute to two major distinguishing clinical manifestations of Graves disease: ophthalmopathy and pretibial myxedema (Graves dermopathy). Graves ophthalmopathy affects more than half of individuals with Graves disease. Increased secretion of hyaluronic acid, orbital fat accumulation, inflammation, and edema of the orbital contents result in exophthalmos (protrusion of the eyeball). Periorbital edema and extraocular muscle weakness lead to diplopia (double vision). The individual may experience irritation, pain, lacrimation, photophobia, blurred vision, decreased visual acuity, papilledema, visual field impairment, exposure keratosis, and corneal ulceration. A small number of individuals with Graves disease and very high levels of TSI experience pretibial myxedema (Graves dermopathy), characterized by subcutaneous swelling on the anterior portions of the legs and by indurated and erythematous skin

Review the pathophysiology and signs and symptoms of Graves disease

Syndrome of inappropriate antidiuretic hormone (SIADH) secretion is characterized by high levels of ADH in the absence of normal physiologic stimuli for its release. SIADH can complicate malignancies, pulmonary disorders, central nervous system disorders, surgical procedures, and the use of certain medications. SIADH is associated with ectopic secretion of ADH by several types of tumor cells. Tumors that have been reported in association with SIADH include small cell carcinoma of the lung, duodenum, stomach, and pancreas; cancers of the bladder, prostate, and endometrium; lymphomas; and sarcomas. Pulmonary disorders associated with SIADH include pneumonia (e.g., tuberculosis), asthma, cystic fibrosis, and respiratory failure requiring mechanical ventilation. Central nervous system disorders that may cause SIADH include encephalitis, meningitis, intracranial hemorrhage, tumors, and trauma. A nephrogenic form of SIADH has recently been described. In these individuals, mutations in arginine vasopressin (AVP) genes lead to chronic activation of tubular V2 receptor and resulting excessive free water reabsorption. Any surgery can result in postoperative fluid volume shifts and transient SIADH for as long as 5 to 7 days after surgery. The pathophysiologic features of SIADH are the result of enhanced renal water retention. Water retention results from the action of ADH on renal collecting ducts, where it increases their permeability to water, thus increasing water reabsorption by the kidneys. This results in an expansion of extracellular fluid volume that leads to dilutional hyponatremia (low serum sodium concentration), hypoosmolarity, and urine that is inappropriately concentrated with respect to serum osmolarity. Clinical Manifestations. The symptoms of SIADH result from hypotonic (dilutional) hyponatremia and are associated with hypervolemia and weight gain. The severity and rapidity of onset of the hyponatremia determine the extent of the symptoms. Thirst, impaired taste, anorexia, dyspnea on exertion, fatigue, and dulled sensorium occur when the serum sodium level decreases rapidly from 140 to 130 mEq/L. Peripheral edema is usually absent. Severe gastrointestinal symptoms, including vomiting and abdominal cramps, occur with a drop in sodium concentration from 130 to 120 mEq/L. With a serum sodium level below 115 mEq/L, confusion, lethargy, muscle twitching, and seizures may occur. Even if hyponatremia develops slowly, serum sodium levels below 110 to 115 mEq/L are likely to cause severe and sometimes irreversible neurologic damage. Symptoms resolve with correction of hyponatremia.

Review the pathophysiology and signs and symptoms of SIADH

Two distinct types of type 1 diabetes have been identified: autoimmune and nonimmune. In autoimmune- mediated diabetes mellitus, environmental-genetic factors are thought to trigger cell-mediated destruction of pancreatic beta cells. Autoimmune type 1 diabetes is called type 1A. Nonimmune type 1 diabetes is far less common than autoimmune. It occurs secondary to other diseases, such as pancreatitis, or to a more fulminant disorder termed idiopathic (type 1B) diabetes. Type 1B diabetes occurs mostly in people of Asian or African descent and affected individuals have varying degrees of insulin deficiency. A disequilibrium of hormones produced by the islets of Langerhans occurs in diabetes mellitus. Alpha-cell and beta-cell functions are abnormal. Lack of insulin and amylin (produced by beta cells) and a relative excess of glucagon (produced by alpha cells) exist in type 1 diabetes. The ratio of insulin to glucagon in the portal vein controls hepatic glucose and fat metabolism. The paracrine action of insulin and amylin normally suppresses secretion of glucagon. Considerable data have documented that high levels of glucagon relative to insulin levels contribute to the generation of hyperglycemia and hyperketonemia. Thus, both alpha-cell and beta-cell functions are abnormal and both a lack of insulin and amylin and a relative excess of glucagon contribute to hyperglycemia in type 1 diabetes. Polydipsia Because of elevated blood glucose levels, water is osmotically attracted from body cells, resulting in intracellular dehydration and hypothalamic stimulation of thirst Polyuria Hyperglycemia acts as an osmotic diuretic; the amount of glucose filtered by the glomeruli of the kidneys exceeds the amount that can be reabsorbed by the renal tubules; glycosuria results, accompanied by large amounts of water lost in the 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 the loss of body tissue as fat and proteins are used for energy as a result of the effects of insulin deficiency Fatigue Metabolic changes result in poor use of food products, contributing to lethargy and fatigue; sleep loss from severe nocturia also contributes to fatigue

Review the pathophysiology and signs and symptoms of Type I Diabetes.

Many organs contribute to the insulin resistance and chronic hyperglycemia associated with type 2 diabetes mellitus. Additionally, genes have been identified that are associated with type 2 diabetes, including those that code for beta-cell mass, beta-cell function (ability to sense blood glucose levels, insulin synthesis, and insulin secretion), proinsulin and insulin molecular structure, insulin receptors, hepatic synthesis of glucose, glucagon synthesis, and cellular responsiveness to insulin stimulation. Genetic abnormalities also are the result of epigenetic changes that occur in response to environmental influences that span generations. The combination of genetic, epigenetic, and environmental influences results in the basic pathophysiologic mechanisms of type 2 diabetes: insulin resistance and decreased insulin secretion by beta cells. All of these mechanisms are essential to the development of type 2 diabetes. Although many individuals with risk factors for type 2 diabetes (including obesity, metabolic syndrome, and hypertension) are insulin resistant, only those individuals who are genetically predisposed to beta cell dysfunction (and therefore a relative deficiency in insulin) will develop type 2 diabetes. Clinical manifestations of type 2 diabetes are nonspecific. The affected individual often is overweight, dyslipidemic, hyperinsulinemic, and hypertensive. Classic symptoms of polyuria and polydipsia may present, but more often individuals will complain of nonspecific symptoms such as fatigue, pruritus, recurrent infections, visual changes, or symptoms of neuropathy (paresthesias or weakness). In those whose diabetes has progressed without treatment, symptoms related to coronary artery, peripheral artery, and cerebrovascular disease may develop

Review the pathophysiology and signs and symptoms of Type II Diabetes.

Ketoacidosis, a serious complication of diabetes mellitus, is a common cause for hospital admissions. Diabetic ketoacidosis (DKA) develops when there is an absolute or relative deficiency of insulin and an increase in the levels of insulin counterregulatory hormones. The most common precipitating factor for DKA is intercurrent illness, such as infection, trauma, surgery, or myocardial infarction. Interruption of insulin administration also may result in DKA. In a state of relative insulin deficiency there is an increase in the concentrations of insulin counterregulatory hormones including catecholamines, cortisol, glucagon, and GH. These counterregulatory hormones antagonize insulin by increasing glucose production and decreasing tissue use of glucose. Profound insulin deficiency results in decreased glucose uptake, increased fat mobilization with release of fatty acids, and accelerated gluconeogenesis and ketogenesis Relatively increased glucagon levels also contribute to activation of the gluconeogenic (glucose-forming) and ketogenic (ketone-forming) pathways in the liver. Because of the insulin deficiency, hepatic overproduction of β-hydroxybutyrate and acetoacetic acids causes increased ketone concentrations. Ordinarily ketones are used by tissues as an energy source to regenerate bicarbonate. This balances the loss of bicarbonate, which occurs when the ketone is formed. Hyperketonemia (increased blood ketone levels) may be a result of impairment in the use of ketones by peripheral tissue, which permits strong organic acids to circulate freely. Bicarbonate buffering then does not occur, and the individual develops a metabolic acidosis. The signs and symptoms of DKA are nonspecific. Polyuria and dehydration result from the osmotic diuresis associated with hyperglycemia. In this case, the plasma glucose level is higher than the individual's renal threshold, allowing significant amounts of glucose to be lost in the urine. Deficits of sodium, phosphorus, and magnesium are common. The most important electrolyte disturbance, however, is a marked deficiency in the level of total body potassium. Although the serum potassium concentration may appear normal or elevated because of volume contraction and a shift of potassium out of the cell and into the blood caused by metabolic acidosis, the total body deficiency of potassium may reach 3 to 5 mEq/kg. Symptoms of diabetic ketoacidosis include Kussmaul respirations (hyperventilation in an attempt to compensate for the acidosis), postural dizziness, central nervous system depression, ketonuria, anorexia, nausea, abdominal pain, thirst, and polyuria

Review the pathophysiology and signs and symptoms of diabetic ketoacidosis

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. It is caused by the increased permeability of the capillary endothelium of the brain after injury to the vascular structure. The result is a disruption in the blood-brain barrier (selective permeability of brain capillaries). Plasma proteins leak into the extracellular spaces, drawing water to them, and the water content of the brain parenchyma increases. Vasogenic edema begins in the area of injury and spreads with preferential accumulation in the white matter of the ipsilateral side because the parallel myelinated fibers separate more easily. Edema then promotes more edema because of ischemia from increasing pressure. Clinical manifestations of vasogenic edema include focal neurologic deficits, disturbances of consciousness, and a severe increase in intracranial pressure. 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 blood-brain barrier is not disrupted. The cells lose their potassium and gain larger amounts of sodium. Water follows by osmosis into the cell 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 oncommunicating 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 thus is increased predominantly around the ventricles. The hydrostatic pressure within the white matter increases, and the size of the white matter is reduced because of the rapid disappearance of myelin lipids.

Understand the types of cerebral edema: vasogenic, ischemic, cytotoxic, interstitial.

The most common feedback system, negative feedback, occurs because the changing chemical, neural, or endocrine response to a stimulus negates the initiating change that triggered the release of the hormone. An example of hormone negative feedback is shown in a Thyroid- stimulating hormone (TSH) secretion from the anterior pituitary is stimulated by thyrotropin-releasing hormone (TRH) from the hypothalamus. Secretion of TSH stimulates the synthesis and secretion of thyroid hormones. Increasing levels of T4 (thyroxine) and T3 (triiodothyronine) then generate negative feedback on the pituitary and hypothalamus to inhibit TRH and TSH synthesis.

Understand what is meant by negative feedback system in hormonal control.

Severe pruritus, eczematoid appearance with redness, edema, and scaling. The skin becomes increasingly dry, sensitive, itchy, and easily irritated because the barrier is impaired. Is associated with a family history of allergies, hay fever, elevated immunoglobulin E (IgE) levels, and increased histamine sensitivity. • A chronic hereditary skin disease characterized by intense itching inflamed skin which causes redness swelling cracking crusting and scaling. Aka Atopic Eczema. Severe Puritis • Lichenification - thickening of the epidermis from constant itching and scar tissue formation

What are signs and symptoms of atopic dermatitis

-Heat cramps are severe spasmodic cramps in the abdomen and extremities that follow prolonged sweating and associated sodium loss. Heat cramps usually appear in individuals who are not accustomed to heat or in those who are performing strenuous work in very warm climates. Fever, rapid pulse rate, and increased blood pressure often accompany the cramps. Treatment involves administration of dilute salt solutions through oral or parenteral routes. -Heat exhaustion, or collapse, is a result of prolonged high core or environmental temperatures. These high temperatures cause the appropriate hypothalamic response of profound vasodilation and profuse sweating. Over a prolonged period the hypothalamic responses produce dehydration, decreased plasma volumes, hypotension, decreased cardiac output, and tachycardia. The individual feels weak, dizzy, nauseated, and faint. The symptoms of heat exhaustion cause the individual to stop work, lie down, and rest. Ceasing activity decreases muscle work, causing decreased heat production. Lying down redistributes vascular volume. The individual should be encouraged to drink warm fluids to replace fluid lost through sweating. -Heat stroke is a potentially lethal result of a breakdown in control of an overstressed thermoregulatory center. The brain cannot tolerate temperatures greater than 40.5° C (104.9° F). In instances of very high core temperatures (40° to 43° C [104° to 109.4° F]), the cardiovascular and thermoregulatory centers may cease to function appropriately. Sweating ceases, and the skin becomes dry and flushed. The individual may be irritable, confused, stuporous, or comatose. Visual disturbances may occur. As heat loss through the evaporation of sweat ceases, core temperatures increase rapidly. High core temperatures and vascular collapse produce cerebral edema, degeneration of the CNS, swollen dendrites, renal tubular necrosis, and multiple organ failure. Death results unless immediate, effective treatment is initiated. Individuals who recover from heat stroke may have permanent damage to the thermoregulatory center and thus may have difficulty tolerating environmental temperature changes. -Malignant hyperthermia is a potentially lethal hypermetabolic complication of a rare inherited muscle disorder. The condition is precipitated by the administration of volatile anesthetics and neuromuscularblocking agents. Malignant hyperthermia is caused by either increased myoplasmic calcium release or decreased calcium uptake with muscle contraction. This allows intracellular calcium levels to rise, producing sustained, uncoordinated muscle contractions, which in turn increase muscle work, oxygen consumption, and lactic acid production. As a result of these contractions, acidosis develops and temperature rises (body temperature may rise 1° C [1.8° F] every 5 minutes); approximately 5% of those who develop malignant hyperthermia do not survive.

What are the defining factors for heat cramps, heat stroke, heat exhaustion, malignant hypothermia?

They are associated with cerebral dysfunction secondary to drug intoxication, alcohol or drug withdrawal, metabolic disorders (hypoglycemia, thyroid storm), nervous system disease, trauma or surgery (following anesthesia), febrile illnesses or heat stroke, and electrolyte imbalance; in addition, ACSs may be associated with systemic diseases (such as heart, kidney, or liver failure), head injury, anesthesia administration, or the presence of certain focal cerebral lesions.

What are the risk factors for delirium?

The symptoms of thyroid crisis are caused by the increased action of thyroxine (T4) and triiodothyronine (T3) exceeding metabolic demands. The systemic symptoms of thyrotoxic crisis include hyperthermia; tachycardia, especially atrial tachydysrhythmias; high-output heart failure; agitation or delirium; and nausea, vomiting, or diarrhea, contributing to fluid volume depletion

What are the signs and symptoms of a thyrotoxic crisis?

Painless testicular enlargement commonly is the first sign of testicular cancer. Enlargement is usually gradual and may be accompanied by a sensation of testicular heaviness or dull ache in the lower abdomen.40 Occasionally, acute pain occurs because of rapid growth, resulting in hemorrhage and necrosis. Ten percent of affected men have epididymitis, 10% have hydroceles,35 and 5% have gynecomastia or hydrocele. Incidence of gynecomastia increases considerably (30% to 45%) in men with Sertoli or Leydig tumors. Approximately 10% of individuals already have symptoms related to metastases at the time of initial diagnosis, which correlates with the typical delay of 3 to 6 months from initial recognition to definitive treatment. Lumbar pain may be present and usually is caused by retroperitoneal node metastasis.

What are the signs and symptoms of testicular cancer?

The basal ganglia system is believed to exert a fine-tuning effect on motor movements. Parkinson disease and Huntington disease are conditions associated with defects of the basal ganglia.

What areas of the brain are affected by Parkinson's and Huntington disease?

During this transition period the ovaries produce erratic and high levels of estrogen that contribute to such symptoms as hot flashes. The physiology of vasomotor flushes is poorly understood. One theory proposes that rapid changes in estrogen may result in loss of negative feedback over hypothalamic noradrenaline synthesis, the primary neurotransmitter involved in thermoregulation.56 Estrogen modulates adrenergic receptors. The decrease in estrogen in menopause is thought to decrease the number of receptors leading to increased noradrenaline levels and hot flushes. Interestingly, emerging evidence shows that the intensity of vasomotor flushes may be associated with increased risk for cardiovascular disease

What causes "hot flashes" in menopausal women?

Astrocytomas are a type of glioma and the most common primary CNS tumor (50% of all brain and spinal cord tumors). Astrocytomas develop from astrocytes and grow by expansion and infiltration into the normal surrounding brain tissues. These tumor cells are believed to have lost normal growth restraint, and thus they proliferate uncontrollably. Nerve Sheath Tumors either neurofibromas or neuroma. Gliomas comprise 50% to 60% of all adult primary brain tumors and include astrocytomas, oligodendrogliomas, mixed oligoastrocytomas, and glioblastoma multiforme. A brain neoplasm derived from microglial cells that is structurally similar to reticulum cell sarcoma.

What do these tumors affect: microglioma, astrocytoma, neuroblastoma, neuroma. What is the most common that we see?

GH deficiency in children is manifested by growth failure. Another feature of GH deficiency in children is fasting hypoglycemia, likely attributable to impaired substrate mobilization for gluconeogenesis and enhanced insulin sensitivity. In both children and adults, acute GH and IGF-1 deficiency has been implicated in significant metabolic perturbations seen with critical illness. Symptoms of chronic adult GH deficiency syndrome include increased body fat, decreased muscle bulk and strength, reduced sweating, dry skin, and psychologic problems, including depression, social withdrawal, fatigue, loss of motivation, and a diminished feeling of well-being. Several studies also have documented increased mortality in adults who are GH deficient. Osteoporosis and alterations in body composition (i.e., reduced lean body mass) are common concomitants of adult GH deficiency. A decline in GH production is an inevitable consequence of aging.

What happens if you have too little of the growth hormone?

Hypersecretion of Growth Hormone: Acromegaly Acromegaly occurs in adults who are exposed to continuously excessive levels of GH and concomitant elevation of IGF-1. The most common cause of acromegaly is a primary autonomous GH-secreting pituitary adenoma. Acromegaly occurs more often in women than men and is diagnosed most often in adults in their forties and fifties, although the disease is usually present for years preceding the diagnosis. Acromegaly is a slowly progressive disease that, if untreated, is associated with a decreased life expectancy. In children and adolescents whose epiphyseal plates have not yet closed, the effect of increased GH levels causes excessive skeletal growth, with some individuals becoming 8 or 9 feet tall. In the adult, epiphyseal closure has occurred and increased amounts of GH and IGF-1 cause connective tissue proliferation and increased cytoplasmic matrix, as well as bony proliferation that results in the characteristic appearance of acromegaly. GH also has significant effects on glucose, lipid, and protein metabolism.31 Hyperglycemia results from GH's inhibition of peripheral glucose uptake and increased hepatic glucose production, followed by compensatory hyperinsulinism and, finally, insulin resistance.32 Excessive levels of GH and IGF-1 also affect the cardiovascular system. GH also acts on the renal tubules to increase phosphate reabsorption, leading to mild hyperphosphatemia. The adenoma increasingly becomes a space-occupying lesion and hypopituitarism may occur because of compression of surrounding hormone-secreting cells.As a result of connective tissue proliferation, individuals with acromegaly have enlarged tongues, interstitial edema, increase in the size and function of sebaceous and sweat glands (leading to increased body odor), and coarse skin and body hair. The coarse skin condition becomes very apparent when procedures such as inserting an intravenous needle are performed; the skin is very thick and difficult to penetrate. Bony proliferation results in large joint arthropathy with swelling and decreased range of motion and periosteal vertebral growth, which causes kyphosis. Enlargement of the facial bones and the bones of the hands and feet result in protrusion of the lower jaw and forehead and a need for increasingly larger sizes of shoes, hats, rings, and gloves

What happens if you have too much of the growth hormone?

Diffuse axonal injury (DAI) results from the effects of head rotation. The brain experiences shearing stresses resulting in axonal damage ranging from concussion to a severe DAI state. Categories of diffuse brain injury include mild concussion; classic cerebral concussion; and mild, moderate, and severe DAI. Axonal damage reduces the speed of information processing and response and disrupts the individual's attention span. CSF pressure rises, and ECG and EEG changes occur without loss of consciousness. The Glasgow Coma Scale score is 13 to 15. The initial confusional state lasts from 1 to several minutes, possibly with amnesia for events preceding the trauma (retrograde amnesia). Anterograde amnesia also may exist transiently. Persons may experience head pain and complain of nervousness and "not being themselves" for up to a few days.

What happens in diffuse axonal injuries? What signs and symptoms would you look for?

Multiple myeloma (MM) is a clonal plasma cell cancer characterized by the slow proliferation of malignant cells as tumor cell masses in the bone marrow that usually results in destruction of the bone. Most MMs secrete large amounts of monoclonal proteins that resemble intact immunoglobulins.Multiple myeloma occurs in all races, but the incidence in blacks is about twice that of whites. It rarely occurs before the age of 40 years—peak age of incidence is about 70 years. It is slightly more common in men than in women. Neoplastic cells of multiple myeloma reside in the bone marrow and are usually not found in the peripheral blood. Occasionally it may spread to other tissues, especially in very advanced disease. Many myelomas are aneuploidy, with chromosomal numbers ranging from 44 chromosomes to near tetraploid. Chromosomal translocations (breakpoints) are responsible for development of myeloma in most individuals. Malignant plasma cells arise from one clone of B cells that produce abnormally large amounts of one class of immunoglobulin (usually IgG, occasionally IgA, and rarely IgD or IgE). The malignant transformation may begin early in B-cell development, possibly before encountering antigen in the secondary lymphoid organs. The myeloma cells returneither to the bone marrow or to other soft tissue sites. Their return is aided by cell adhesion molecules that help them target favorable sites that promote continued expansion and maturation. Myeloma cells in the bone marrow directly secrete hepatocyte growth factor and parathyroid hormone-related peptide and adhere to stromal cells, inducing their production of several cytokines. These factors, particularly IL-6, act as an osteoclast-activating factor and stimulate osteoclasts to reabsorb bone. This process results in bone lesions and hypercalcemia (high calcium levels in the blood) resulting fromrelease of calcium from the breakdown of bone.The antibody produced by the transformed plasma cell is usually defective, containing truncations, deletions, and other abnormalities, and is frequently referred to as a paraprotein (abnormal protein in the blood). Because of the large number of malignant plasma cells, the abnormal antibody, called the M protein, becomes the most prominent protein in the blood in 80% of myeloma clients. Suppression of normal plasma cells by the myeloma results in diminished or absent normal antibodies. The excessive amount of M protein also may contribute to many of the clinical manifestations of the disease. The myeloma may produce free immunoglobulin light chain (Bence Jones protein) that is present in the blood and urine in approximately 80% of clients and contributes to damage of renal tubular cells.

What happens in multiple myeloma (MM)?

Most CNS disorders produce nausea and vomiting. Vomiting without nausea indicates direct involvement of the central neural mechanism (or pyloric obstruction). Vomiting often accompanies CNS injuries that (1) involve the vestibular nuclei or its immediate projections, particularly when double vision (diplopia) also is present; (2) impinge directly on the floor of the fourth ventricle; or (3) produce brainstem compression secondary to increased intracranial pressure.

What happens in the CNS that can induce vomiting?

This 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.

What happens in uncal herniation?

Phenylketonuria is an an inborn error in the metabolism of amino acids, an autosomal recessive that is a mutation of the phenylalanie hydroxylase gene (PAH). Loss of PAH activity reults in inability to convert the essential amino acd phenylalanine to tyrosine, leading to accumulation of phenylalanine in the serum causing damage to the CNS.

What is PKU?

• A condition known as RINGWORM that is a fungal infection of the skin caused by Trichophyton or mircosporum, classified according to the location. • results in a circular, clearly circumscribed, mildly erythematous (pink to red) scaly patches with a slightly elevated "ring-like" boarder, rash and itching or areas no covered by hair • Commonly found on scalp, feet, face, hands and groin • Source: kittens, puppies, lesion to lesion contact

What is Tinea Corpis?

Nociceptors are free nerve endings in the afferent peripheral nervous system that selectively respond to different chemical, mechanical, and thermal stimuli. Nociceptors are located throughout the body but are not evenly distributed so the relative sensitivity to pain differs according to their location. For example, fingertips have more nociceptors than the skin of the back, and all skin has many more nociceptors than the internal organs.

What is a nociceptor?

Thyroid hormone (TH) is regulated through a negative-feedback loop involving the hypothalamus, the anterior pituitary, and the thyroid gland. Thyrotropin-releasing hormone (TRH), which is synthesized and stored within the hypothalamus, initiates this loop. TRH is released into the hypothalamicpituitary portal system and circulates to the anterior pituitary, where it stimulates the release of TSH . • TSH, which is synthesized and stored in the anterior pituitary, stimulates secretion of TH by activating intracellular, including uptake of iodine necessary for the synthesis of TH • Synthesis of TH depends on the glycoprotein thyroglobulin, which contains a precursor of TH, tyrosine. Tyrosine then combines with iodide to form precursor molecules of the thyroid hormones T4 and T3 processes, including uptake of iodine necessary for the synthesis of TH.

What is an important substance that is needed for thyroid stimulating hormone to work effectively?

Radiation sources, such as small I-labeled capsules (also called seeds), can also be temporarily placed into body cavities, a delivery method termed brachytherapy. Brachytherapy is useful in the treatment of cervical, prostate, and head and neck cancers.

What is brachytherapy? When would it be used?

caretaker genes, genes that are responsible for the maintenance of genomic integrity. Caretaker genes encode proteins that are involved in repairing damaged DNA, such as occurs with errors in DNA replication, mutations caused by ultraviolet or ionizing radiation, and mutations caused by chemicals and drugs. Loss of function of caretaker genes leads to increased mutation rates. If DNA damage is severe, the cell undergoes programmed cell death, or apoptosis, rather than simply dividing with damaged DNA. Inherited mutations can disrupt the caretaker genes that protect the integrity of the genome.

What is meant by "caretaker genes?"

Tumor markers are substances produced by both benign and malignant cells that either are present in or on tumor cells. Tumor markers are substances (i.e., hormones, enzymes, genes, antigens, antibodies) found in cancer cells and in blood, spinal fluid, or urine. They are used to screen and identify individuals at high risk for cancer, to help diagnose specific types of tumors, and to follow the clinical course of cancer. If the tumor marker itself has biologic activity, then it can cause symptoms, a phenomenon known as a paraneoplastic syndrome.

What is meant by tumor cell markers?

Obstructive sleep apnea syndrome (OSAS) is a disorder of breathing during sleep related to upper airway obstruction that is associated with reduced blood oxygen saturation and hypercapnia. The typical classification of the severity of this disease uses the Apnea Hypopnea Index (AHI). This index represents how many apnea (total airway closure) or hypopnea (partial airway closure) episodes occur per night—the number of which is then divided by the night's total sleep time to give an average number of apnea or hypopnea episodes per hour. The AHI severity scale is as follows: • Normal: fewer than 5 episodes of abnormal sleep episodes per hour • Mild: between 5 and 15 episodes of abnormal sleep episodes per hour • Moderate: between 15 and 30 episodes of abnormal sleep episodes per hour • Severe: more than 30 episodes of abnormal sleep episodes per hour Risk factors include obesity, male gender, menopause, and age.

What is obstructive sleep apnea?

Polycythemia vera (PV) (also known as primary polycythemia) is one of several disorders collectively known as chronic myeloproliferative disorders (CMPDs).52 Others in this group include essential thrombocytosis, chronic idiopathic myelofibrosis, chronic myeloid leukemia, chronic neutrophilic leukemia, and chronic eosinophilic leukemia. All result from abnormal regulation of the multipotent hematopoietic stem cells. The major characteristics shared by these disorders are: (1) involvement of a multipotent hematopoietic progenitor cell; (2) overproduction of one or more of the formed elements of the blood in the absence of a defined stimulus; (3) dominance of a transformed progenitor cell over the nontransformed progenitor cells; (4) marrow hypercellularity or fibrosis; (5) cytogenetic abnormalities; (6) predisposition to thrombus formation and hemorrhage; and (7) spontaneous transformation to acute leukemia. Determining a precise distinction between the CMPDs is difficult if not impossible because of overlapping clinical features and a lack of specific molecular markers. As a result, diagnosis is quite challenging. Polycythemia vera (PV) is a chronic neoplastic, nonmalignant condition characterized by overproduction of red blood cells (frequently with increased levels of white blood cells [leukocytosis] and platelets [thrombocytosis]) and splenomegaly. Erythrocytosis is the essential component of PV. Clonal proliferation of erythroid progenitors occurs in thebone marrow independent of erythropoietin, although the cells express a normal erythropoietin receptor. However, more than 95% of individuals with PV possess an acquired mutation in Janus kinase 2 (JAK2).53 JAK2 increases the activity of the erythropoietin receptor and is self-regulatory so that JAK2 activity diminishes over time. The mutation associated with PV negates the self-regulatory activity of JAK2 so that the erythropoietin receptor is constitutively active regardless of the level of erythropoietin. These red blood cell precursors also demonstrate sensitivity to other growth factors, such as interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), or insulin-like growth factor. A unique feature of PV, one helpful in diagnosis, is the development of intense, painful itching that is intensified by heat or exposure to water (aquagenic pruritus), particularly warm water when bathing or showering. The intensity of the itching is related to the concentration of mast cells in the skin and is generally not responsive to antihistamines or topical lotions.

What is polycythemia vera?

Tardive (slow onset) dyskinesia is the involuntary movement of the face, trunk, and extremities. Although the condition occurs occasionally in individuals with Parkinson disease, it usually occurs as a side effect of prolonged use of first- or second- generation antipsychotic drugs.70 The antipsychotic drugs cause denervation hypersensitivity, thereby mimicking the effect of excessive dopamine. The most common symptom of tardive dyskinesia is rapid, repetitive, stereotypic movements. The most characteristic movements of tardive dyskinesia include continual chewing with intermittent protrusions of the tongue, lip smacking, and facial grimacing. Stereotypic movements are believed to be a form of excessive dopaminergic activity

What is tardive dyskinesia, what causes it?

Early oncogenic HPV infection is readily detected by the Papanicolaou (Pap) test, an examination of cervical epithelial scrapings.

What is the Pap test used for?

Decorticate posture is characterized by upper extremities that are flexed at the elbows and held close to the body and by lower extremities that are externally rotated and extended Decorticate posture is believed to occur when the brainstem, which facilitates the antigravity position, is not inhibited by the motor function of the cerebral cortex. Decerebrate posture refers to increased tone in extensor muscles and trunk muscles, with active tonic neck reflexes. When the head is in a neutral position, all four limbs are rigidly extended. The decerebrate posture is caused by severe injury to the brain and brainstem, resulting in overstimulation of the postural righting and vestibular reflexes.

What is the difference between decerebrate and decorticate posturing?

The arachnoid villi protrude from the arachnoid space, through the dura mater, and lie within the blood flow of the venous sinuses. CSF is reabsorbed by means of a pressure gradient between the arachnoid villi and the cerebral venous sinuses. The villi function as one-way valves directing CSF outflow into the blood but preventing blood flow into the subarachnoid space. Thus CSF is derived from the blood, and after circulating throughout the CNS, it returns to the blood.

What is the function of the arachnoid villi?

a) The Pons - transmits information from the cerebellum to the brainstem nuclei and relays motor information from the cerebral cortex to the contralateral cerebellar hemisphere -controls respiration (rate and relationship of inspiration to expiration) b) Medulla oblongata (myelin cephalon) - lowest portion of the brainstem • Reflex activites: Controls HR, RR, B/P • coughing, sneezing, swallowing, and vomiting • contralateral control c) Reticular activating system (RAS) • nerve cell bodies w/in brain stem that works w/ c.cortex • maintains wakefulness d) Midbrain - -conscious and unconscious muscle synergy and for maintaining balance and posture • voluntary and involuntary visual motor movements • movements affecting the auditory system • motor output center • synthesis of Dopamine • carries cerebrospinal fluid (CSF)

What is the function, in general, associated with the Pons, Medulla oblongata, Reticular activating system, Midbrain.

Benign prostatic hyperplasia (BPH), also called benign prostatic hypertrophy, is the enlargement of the prostate gland. Because the major prostatic changes are caused by hyperplasia, not hypertrophy, benign prostatic hyperplasia is the preferred term. This condition becomes problematic as prostatic tissue compresses the urethra, where it passes through the prostate, resulting in frequency of lower urinary tract symptoms. The prevalence among U.S. men 60 years and older is about 50% and among men 70 years or older 90%.44 BPH is common and involves a complex pathophysiology with several endocrine and local factors and remodeled microenvironment. Its relationship to aging is well documented. At birth the prostate is pea sized, and growth of the gland is gradual until puberty. A period of rapid development continues until the third decade of life, when the prostate reaches adult size. Around 40 to 45 years of age, benign hyperplasia begins and continues slowly until death. Although dihydrotestosterone (DHT) is necessary for normal prostatic development, its role in BPH remains unclear. Among all androgen-metabolizing enzymes within the human prostate, 5α-reductase is the most powerful. This reductase corresponds to an age-dependent DHT level. Therefore, although 5α-reductase and DHT decrease with age in the epithelium, they remain relatively constant in the stroma of the prostate gland.Current causative theories of BPH focus on levels and ratios of endocrine factors such as androgens, estrogens, gonadotropins, and prolactin and changes in the balance between autocrine/paracrine growth-stimulatory and growth inhibitory factors. These factors include insulin-like growth factors (IGFs), epidermal growth factor, nerve growth factor, fibroblast factors, IGF binding proteins, and transforming growth factor-beta (TGF-β).45 Aging and circulating androgens are associated with BPH and enlargement. These factors are predisposed as disrupting the balance of growth factor signaling pathways and stromal/ epithelial interactions creating a growth-promoting and tissue remodeling microenvironment. However, BPH is a multifactorial disease, and not all men respond well to available treatments, suggesting factors other than androgens are involved. BPH begins in the periurethral glands, which are the inner glands or layers of the prostate. The prostate enlarges as nodules form and grow (nodular hyperplasia) and glandular cells enlarge (hypertrophy). The development of BPH occurs over a prolonged period, and changes within the urinary tract are slow and insidious. As nodular hyperplasia and cellular hypertrophy progress, tissues that surround the prostatic urethra usually compress it but not always cause bladder outflow obstruction. These symptoms are sometimes called the spectrum of lower urinary tract symptoms (LUTS). Symptoms include the urge to urinate often, some delay in starting urination, and decreased force of the urinary stream. As the obstruction progresses, often over several years, the bladder cannot empty all the urine and the increasing volume leads to long-term urine retention. The volume of urine retained may be great enough to produce uncontrolled "overflow incontinence" with any increase in intra-abdominal pressure. At this stage the force of the urinary stream is significantly reduced, and much more time is required to initiate and complete voiding. Hematuria, bladder or kidney infection, bladder calculi, acute urinary retention hydroureter, hydronephrosis, and renal insufficiency are common complications.

What is the pathophysiology and signs and symptoms of BPH?

IDA is the most common microcytic-hypochromic anemias. IDA can arise from one of two different etiologies or a combination of both—inadequate dietary intake or excessive blood loss. In both instances there is no intrinsic dysfunction in iron metabolism; however, both deplete iron stores and reduce hemoglobin synthesis. A second category is a metabolic or functional iron deficiency in which various metabolic disorders lead to either insufficient iron delivery to bone marrow or impaired iron use within the marrow. Paradoxically, iron stores may be sufficient but delivery is inadequate to maintain heme synthesis, thus producing a functional or relative iron deficiency. The most common cause of IDA in developed countries is pregnancy and chronic blood loss. In females, menorrhagia (excessive bleeding during menstruation) is a common cause of primary IDA. Other causes of IDA for both genders are (1) use of medications that cause gastrointestinal bleeding (such as aspirin or nonsteroidal anti-inflammatory drugs [NSAIDs]); (2) surgical procedures that decrease stomach acidity, intestinal transit time, and absorption (e.g., gastric bypass); (3) insufficient dietary intake of iron; and (4) eating disorders, such as pica, which is the craving and eating of nonnutritional substances, such as dirt, chalk, and paper. Symptoms of IDA begin gradually, and individuals usually do not seek medical attention until hemoglobin levels have decreased to about 7 to 8 g/dl. Early symptoms are nonspecific and include fatigue, weakness, shortness of breath, and pale earlobes, palms, and conjunctivae. As the condition progresses and becomes more severe, structural and functional changes occur in epithelial tissue. The fingernails become brittle, thin, coarsely ridged, and "spoon-shaped" or concave (koilonychia) as a result of impaired capillary circulation. IDA also is associated with unexplained burning mouth syndrome. Tongue papillae atrophy and cause soreness along with redness and burning (glossitis). Individuals also experience dryness and soreness in the epithelium at the corners of the mouth, known as angular stomatitis. Difficulty in swallowing is associated with an esophageal "web," a thin, concentric, smooth extension of normal esophageal tissue consisting of mucosa and submucosa at the juncture between the hypopharynx and esophagus. The duration of iron deficiency required for web formation is uncertain. Dysphagia also is exacerbated by hyposalivation. The pathophysiology associated with these epithelial lesions is not well understood, but the lesions have the potential to become cancerous.

What is the pathophysiology and signs and symptoms of Iron deficiency anemia?

Macrocytic-Normochromic Anemias Pernicious anemia (PA), the most common type of megaloblastic anemia, is caused by vitamin B12 deficiency, which is often associated with the end stage of type A chronic atrophic (congenital or autoimmune) gastritis. The principal disorder in PA is an absence of intrinsic factor (IF), a transporter required for absorption of dietary vitamin B12, which is essential for nuclear maturation and DNA synthesis in erythrocytes. IF is secreted by gastric parietal cells and complexes with dietary vitamin B12 in the small intestine. The B12-IF complex binds to cell surface receptors in the ileum and is transported across the intestinal mucosa. Deficiency in IF secretion may be congenital or, more often, an autoimmune process directed against gastric parietal cells. Congenital IF deficiency is a genetic disorder that demonstrates an autosomal recessive inheritance pattern. The autoimmune form of the disease also has a genetic component, as do most autoimmune diseases. Family clusters have been identified; 20% to 30% of individuals related to persons with PA also have PA. These relatives, particularly first-degree female relatives, also demonstrate a higher frequency of the presence of gastric autoantibodies. Most cases of PA result from an autoimmune gastritis (type A chronic gastritis) in which gastric atrophy results from destruction of parietal and zymogenic cells. Individuals with PA commonly have autoantibodies against the gastric H+-K+ ATPase, which is the major protein constituent of parietal cell membranes. Early in the disease process the gastric submucosa becomes infiltrated with inflammatory cells, including CD4 lymphocytes, eventually extending into the lamina propria and causing degeneration of the parietal and zymogenic cells. The parietal and zymogenic cells are destroyed and replaced by mucous-containing cells (intestinal metaplasia). Gastric mucosal atrophy, in which gastric parietal cells are destroyed, results in a deficiency of all secretions of the stomach—hydrochloric acid, pepsin, and IF. A direct correlation exists between the severity of the gastric lesion and the degree of malabsorption of vitamin B12. Additionally, autoantibodies against IF prevent the formation of the B12-IF complex. Thus, PA is secondary to autoimmune destruction of parietal cells, thus diminishing the production of IF, and the presence of autoantibodies that neutralize the capacity of remaining IF to transport vitamin B12. Initiation of the autoimmune process may be secondary to a past infection with Helicobacter pylori.7 Although active infection with H. pylori is rare in individuals with PA, more than half of these individuals possess circulating antibodies against this microorganism, suggesting a history of infection. The current opinion is that in genetically prone individuals, antigens expressed by H. pylori mimic the parietal cell H+-K+ ATPase, resulting in production of an antibody that binds and damages the parietal cell. Early symptoms are often ignored because they are nonspecific and vague and include infections, mood swings, and gastrointestinal, cardiac, or kidney ailments. When the hemoglobin level has decreased significantly (7 to 8 g/dl), the individual experiences the classic symptoms of anemia—weakness, fatigue, paresthesias of the feet and fingers, difficulty in walking, loss of appetite, abdominal pains, weight loss, and a sore tongue that is smooth and beefy red secondary to atrophic glossitis. The skin may become "lemon yellow" (sallow) as a result of a combination of pallor and icterus. Hepatomegaly, indicating right-sided heart failure, may be present in the elderly along with splenomegaly, which is nonpalpable. Neurologic manifestations result from nerve demyelination that may produce neuronal death. The posterior and lateral columns of the spinal cord also may be affected, causing a loss of position and vibration sense, ataxia, and spasticity. These complications pose a serious threat because they are not reversible, even with appropriate treatment. The cerebrum also may be involved with manifestations of affective disorders, most commonly of the depressive types.

What is the pathophysiology and signs and symptoms of Pernicious anemia?

Normocytic-Normochromic Anemias Aplastic anemia (AA) is a critical condition characterized by pancytopenia, a reduction or absence of all three blood cell types, resulting from failure or suppression of bone marrow to produce adequate amounts of blood cells. The rate or decline in the quantity of blood cells is related to their respective life span; thus erythrocytes (life span about 120 days) are last to demonstrate a reduction in numbers. The characteristic lesion of AA is a hypocellular bone marrow that has been replaced with fat. Most cases of idiopathic AA result from an autoimmune disease directed against hematopoietic stem cells.23 As with most autoimmune diseases, a genetic predisposition is apparent and has been attributed to polymorphisms in human leukocyte antigens (HLAs) and inhibitory cytokines (e.g., tumor necrosis factoralpha [TNF-α], transforming growth factor-beta [TGF-β], and interferon-gamma [IFN-γ]).24 The evidence supporting an autoimmune process includes the response of AA to immunosuppressive therapy including depletion of T cells by antithymocyte antibodies. Cytotoxic T cells (Tc cells) appear to be the main culprits, although the causative antigen has yet to be identified. Th1 cytokines (involved in the differentiation of Tc cells), such as IFN-γ and TNF-α, as well as cellular contact with Tc cells through FasL, induce apoptosis of CD34+ target cells, which includes most of the hematopoietic progenitors. Clinical Manifestations. The onset of symptoms is insidious and related to the rapidity with which the bone marrow is destroyed and replaced. Approximately 50% of AA cases progress rapidly, with a high risk of death from overwhelming infection or bleeding. In some cases the rate of decline is slow and the individual may adapt progressively to a new level of hematologic function. This condition is referred to as hypoplastic anemia rather than aplastic anemia. Initial symptoms depend on which cell line is affected. Rapidly progressing disease is usually associated with hypoxemia, pallor (occasionally with a brownish pigmentation of the skin), and weakness along with fever and dyspnea with rapidly developing signs of hemorrhaging if platelets are affected (e.g., unexplained bruising, nosebleeds, bleeding gums, bleeding in the GI tract, prolonged bleeding at sites of minor injury). A slower onset over weeks or months is characterized by progressive weakness and fatigue with developing signs of hemorrhaging. Major hemorrhage may occur from any organ; however, it is generally observed in the late stages and is often secondary to other events. Menorrhagia and purpura also may be evident; however, purpura is not necessarily a classic indication of AA and may not be representative of the degree of thrombocytopenia. In both rapid and slow onset AA, diminished leukocyte production may result in a progressive frequency and prolongation of infections. Late manifestations of the condition include ulcerations of the mouth and pharynx or a low-grade cellulitis in the neck. Splenomegaly is extremely rare, and if present, other conditions that may imitate AA should be ruled out. Neurologic changes are only evident when hemorrhages have occurred within the system; however, some individuals have complained of paresthesias.

What is the pathophysiology and signs and symptoms of aplastic anemia?

Macrocytic-Normochromic Anemias Folate (folic acid) is an essential vitamin for RNA and DNA synthesis within the maturing erythrocyte. Folates are coenzymes required for the synthesis of thymine and purines (adenine and guanine) and the conversion of homocysteine to methionine. Deficient production of thymine, in particular, affects cells undergoing rapid division (e.g., bone marrow cells undergoing erythropoiesis). Humans are totally dependent on dietary intake to meet the daily requirement of 50 to 200 mcg/ day. Impaired DNA synthesis secondary to a folate deficiency results in megaloblastic cells with clumped nuclear chromatin. Anemia may result from apoptosis of erythroblasts in the late stages of erythropoiesis. In addition to anemia, folate deficiency in pregnant women is associated with neural tube defects of the fetus. Folate is necessary for the reduction of circulating levels of homocysteine, a risk factor for the development of atherosclerosis; thus a folate deficiency increases the risk for developing coronary artery disease. A deficiency of folate also is implicated in the development of cancers, specifically colorectal cancers. Clinical manifestations are similar to the cachectic, malnourished appearance of individuals with PA. Specific symptoms include severe cheilosis (scales and fissures of the lips and corners of the mouth), stomatitis (inflammation of the mouth), and painful ulcerations of the buccal mucosa and tongue, characteristic of burning mouth syndrome. Burning mouth syndrome may be secondary to a large number of disorders (e.g., extremely dry mouth, infection, autoimmune disease, nutritional deficiencies, and other conditions). The mechanisms underlying folate deficiency as a cause remain unknown. Gastrointestinal symptoms may be present and include dysphagia (difficulty swallowing), flatulence, and watery diarrhea, as well as histologic and roentgenographic changes of the GI tract suggestive of sprue (a chronic malabsorption syndrome). Undiagnosed inflammatory bowel disease (e.g., Crohn disease, ulcerative colitis) may be the underlying cause of folate malabsorption in some individuals, and folate deficiency may suppress proliferation of the intestinal mucosa, leading to exacerbation of gastrointestinal damage. Neurologic manifestations, such as those that occur in PA, are generally not seen in folate deficiency anemia. Any neurologic symptoms are usually caused by a thiamine deficiency, which often accompanies folate deficiency.

What is the pathophysiology and signs and symptoms of folic acid deficiency anemia?

Normocytic-Normochromic Anemias The predominant event in hemolytic anemias is premature accelerated destruction of erythrocytes, either episodically or continuously. The consequences of the anemia are elevated levels of erythropoietin to induce accelerated production of erythrocytes and an increase in the products of hemoglobin catabolism. Hemolytic anemias may be either congenital or acquired. Congenital hemolytic anemias result from intrinsic defects in erythrocytes, including the red cell membrane (e.g., hereditary spherocytosis, paroxysmal nocturnal hemoglobinuria), enzymatic pathways (e.g., glucose-6-phosphate dehydrogenase deficiency), and hemoglobin synthesis (e.g., the thalassemia syndromes, sickle cell anemia). Acquired hemolytic anemias are usually immunologic (immune hemolytic anemias), such as erythrocyte destruction caused by autoantibodies against erythrocyte antigens (e.g., autoimmune hemolytic anemia), isohemagglutinins (e.g., mismatched erythrocyte transfusions), or allergic reactions against drug antigens adsorbed onto the erythrocyte surface (drug-induced hemolytic anemia). Acquired hemolytic anemia may also be secondary to erythrocyte damage caused by cardiac valve prostheses or by increased shear stresses in narrowed small vessels (e.g., during disseminated intravascular coagulation). Jaundice (icterus) is present when heme destruction exceeds the liver's ability to conjugate and excrete bilirubin. Jaundice is first noticed in the neonatal period. Children and adults with congenital hemolytic anemia may not have icterus, or it may be mild enough that it remains unnoticed. In some individuals, faint scleral icterus may be the only indication of hemolytic disease. Commonly, individuals with congenital hemolytic disorders demonstrate splenomegaly, which is often only mild in nature. In some cases the spleen may become quite enlarged and may cause discovery of the underlying hemolytic disorder. Another underlying condition that may be the cause of inadvertently determining the presence of the anemic disorder is the development of gallstones. Children who have hemolytic anemia often demonstrate skeletal abnormalities caused by expansion of erythroid bone marrow during the active phase of growth and development. These alterations are more pronounced in the bony structures of the face and skull and may result in pathologic fractures. Cardiovascular and respiratory manifestations vary with the degree of anemia. In spite of the disorder being characterized as hemolytic in nature, thromboembolism may occur. Pulmonary embolism is a common finding during autopsies of individuals with immune hemolytic anemia.

What is the pathophysiology and signs and symptoms of hemolytic anemia?

Primary dysmenorrhea is attributed to excessive endometrial prostaglandin production.20,21 Women with painful periods produce 10 times as much prostaglandin F (PGF2α), a potent myometrial stimulant and vasoconstrictor as asymptomatic women. Elevated levels of prostaglandins (especially PGF2α and PGE2α) cause uterine hypercontractility, decreased blood flow to the uterus, and increased nerve hypersensitivity, thus resulting in pain.20 Women with dysmenorrhea may have up-regulated cyclo-oxygenase (COX) enzyme activity, which contributes to increased synthesis of prostaglandins. Furthermore, leukotriene production is elevated further contributing to increased levels of pain.20 Prostaglandins are primarily released during the first 48 hours of menstruation, when symptoms are the most intense. Women who are anovulatory because they use oral contraceptives rarely have primary dysmenorrhea.

What is the pathophysiology associated with primary dysmenorrhea?

Epidermis: • Keratinocytes - produce keratin (scleroprotein - protection from stress) • Melanocyte - produces melanin, shields UV radiation, determines skin color • Langerhans Cells - migrate from bone marrow, initiates immune response with dendrites • Merkel Cells - "touch receptors" slowly adapting mechanoreceptors Dermis: • Fibroblasts - generate connective tissue, for wound healing • Mast Cells - release histamine, hypersensitivity and immune FX • Magrophanges - Phagocytotic, partial role in immune response, wound healing • Histocytes - in loose connective tissue, Machrophange, phagocytes pigments and debris of inflammation Nails: protective keratinized plates Sebaceous Glands: secrete sebum, oils skin/hair, prevents drying Eccrine Sweat Glands: thermoregulate/ cool the body, evaporation

What kinds of cells play a role in this process?

Childhood cancers are most often diagnosed during peak times of physical growth.

When is cancer in children most likely to be identified?

Bone- Osteogenic sarcoma (Tumors of Mesenchymal Origin) Basal cells — Basal cell carcinoma (Tumors of Epithelial Origin) Plasma cells - Multiple myeloma (Tumors of Mesenchymal Origin) Glandular or ductal epithelium -Adenocarcinoma (Tumors of Epithelial Origin)

Where do these cancers originate osteogenic sarcoma , basal cell carcinoma, multiple myeloma, adenocarcinoma?

Spermatogenesis takes place within the seminiferous tubules of the testes

Where does spermatogenesis occur?

Sleep is an active, multiphase, complex brain process that provides restorative functions and promotes memory consolidation. Several areas of the brain are associated with sleep and sleep-wake cycles. The pineal body (a component of the epithalamus) secretes melatonin, which maintains circadian rhythms and the sleep-wake cycle

Which part of the brain is involved with sleep?

AIDS (HIV, herpesvirus type 8) Non-Hodgkin lymphoma, squamous cell carcinomas, Kaposi sarcoma. (HPV, gonorrhea, chlamydia) Ovarian carcinoma, cervical/anal carcinoma Recently, HPV infections have been found to cause cancer of the oropharynx (soft palate, base of the tongue, tonsils).

Which sexually transmitted disease is associated with cancer?

The B-lymphocyte proliferation in response to a great deal of antigen (e.g., during infection) may result in lymph node enlargement and tenderness (reactive lymph node)

Why do lymph nodes become enlarged when we develop an infection?

Hormone release is regulated by one or more of the following mechanisms: (1) chemical factors (such as blood glucose or calcium levels). In addition to being an important ion that participates in a multitude of cellular actions, Ca++ is considered an important second messenger. For cells that have calcium as their second messenger, an increase in intracellular calcium concentration causes calcium to bind with calmodulin, a regulatory protein. This step then initiates other intracellular processes.Calcium signaling systems are crucial to healthy functioning of virtually every tissue system in the body including heart, brain, bone, smooth muscle, and many others. The four parathyroid glands are located near the posterior side of the thyroid and function to control serum calcium levels. Calcitonin, also called thyrocalcitonin, acts to lower serum calcium levels by inhibition of bone-resorbing osteoclasts. The overall effect of PTH secretion is to increase serum calcium concentration and decrease serum phosphate level.

Why is the control of calcium important as it relates to the endocrine system?

CHARACTERISTIC/ACUTE PAIN/ CHRONIC PAIN Experience /An event /A situation; state of existence Source/ External agent or internal disease usually known/ Unknown; if known, treatment is prolonged or ineffective Onset /Usually sudden/ May be sudden or develop insidiously Duration /Transient (up to 6 months) /Prolonged and persistent (months to years) Pain identification /Painful and nonpainful areas generally well identified /Painful and nonpainful areas less easily differentiated: change in sensations becomes more difficult to evaluate Clinical signs/ Increased pulse rate, elevated blood pressure, increased respiratory rate, diaphoresis, dilated pupils /Response patterns vary; fewer overt signs (adaptation) Significance Significant/ (informs person something is wrong) /Person looks for significance Pattern/ Self-limiting or readily corrected /Continuous or intermittent; intensity may vary or remain constant Course /Suffering usually decreases over time /Suffering usually increases over time Actions/ Leads to actions to relieve pain/ Leads to actions to modify pain experience Prognosis /Likelihood of eventual complete relief/ Complete relief usually not possible

difference between acute and chronic pain

Dysfunctional uterine bleeding (DUB) is heavy or irregular bleeding in the absence of organic disease. The majority of abnormal uterine bleeding, commonly known as dysfunctional bleeding, is due to lack of ovulation

dysfunctional uterine bleeding

The sympathetic nervous system functions to mobilize energy stores in times of need (e.g., in the fight-or-flight response). Epinephrine and norepinephrine are mediators of the fight-or-flight response. The parasympathetic nervous system functions to conserve and restore energy. The action of catecholamines (epinephrine, norepinephrine, dopamine) varies with the type of neuroreceptor stimulated. It should be remembered that catecholamines also are released by the adrenal medulla gland that physiologically and biochemically resembles the sympathetic nervous system. Many body organs are innervated by the sympathetic and parasympathetic nervous systems. The two divisions frequently cause opposite responses; for example, sympathetic stimulation of the gastrointestinal (GI) tract causes decreased peristalsis, whereas parasympathetic stimulation of the GI tract increases peristalsis. In general, sympathetic stimulation promotes responses that are concerned with the protection of the individual. For example, sympathetic activity increases blood glucose levels and temperature and raises blood pressure. In emergency situations a generalized and widespread discharge of the sympathetic system occurs. This is accomplished by an increased firing frequency of sympathetic fibers and by activation of sympathetic fibers normally silent and at rest (fibers to the sweat glands, pilomotor muscles, and the adrenal medulla, as well as vasodilator fibers to muscle). Regulation of vasomotor tone is considered the single most important function of the sympathetic nervous system. Increased parasympathetic activity promotes rest and tranquility and is characterized by reduced heart rate and enhanced visceral functions leading to digestion. Stimulation of the vagus nerve in the GI tract increases peristalsis and secretion, as well as relaxation of sphincters. Activation of parasympathetic fibers in the head, provided by cranial nerves III, VII, and IX, causes pupillary constriction, tear secretion, and increased salivary secretion. Stimulation of the sacral division of the parasympathetic system contracts the urinary bladder and facilitates the process of genital erection. The parasympathetic system lacks the generalized and widespread response of the sympathetic system. Specific parasympathetic fibers are activated to regulate particular functions.

function of the sympathetic and parasympathetic nervous system and neurotransmitters involved. It helps to think about the sympathetic system and what we see happen in terms of the stress response...same neurotransmitters.

The common presentation of MM is characterized by elevated levels of calcium in the blood (hypercalcemia) (13%), renal failure (19%), anemia (72% of persons), and bone lesions (80% of persons). The hypercalcemia and bone lesions result from infiltration of the bone by malignant plasma cells and stimulation of osteoclasts to reabsorb bone. This process results in the release of calcium (hypercalcemia) and the development of "lytic lesions" (round, "punched-out" regions of bone). Destruction of bone tissue causes pain, the most common presenting symptom, and pathologic fractures. The pain may be felt in a single bone of the entire skeleton, and the bones most commonly involved, in decreasing order of frequency, are the vertebrae, ribs, skull, pelvis, femur, clavicle, and scapula. Spinal cord compression, because of the weakened vertebrae, occurs in about 10% of individuals. The pain is initially aching, intermittent, and aggravated by weightbearing. As the disease progresses, pain becomes severe and prolonged. It is common for the individual with myeloma to be treated for a slipped disk or arthritis before the correct diagnosis of myeloma is established. The individual may complain of weakness, fatigue, weight loss, and anorexia in addition to pain. Proteinuria is observed in 90% of individuals. Renal failure may be either acute or chronic and is usually secondary to the hypercalcemia. Bence Jones protein may lead to damage of the proximal tubules. Anemia is usually normocytic and normochromic and results from inhibited erythropoiesis caused by tumor cell infiltration of the bone marrow. The high concentration of paraprotein in the blood may lead to hyperviscosity syndrome. The increased viscosity interferes with blood circulation to various sites (brain, kidneys, extremities). Hyperviscosity syndrome is observed in up to 20% of individuals with MM. Additional neurologic symptoms (e.g., confusion, headaches, blurred vision) may occur secondary to hypercalcemia or hyperviscosity. Suppression of the humoral (antibody-mediated) immune response results in repeated infections, primarily pneumonias and pyelonephritis. The most commonly involved organisms are encapsulated bacteria that are particularly sensitive to the effects of antibody: pneumonia caused by Streptococcus pneumoniae, Staphylococcus aureus, or Klebsiella pneumoniae or pyelonephritis caused by Escherichia coli or other gram-negative organisms. Cell-mediated (T-cell) function is relatively normal. Overwhelming infection is the leading cause of death from MM.

multiple myeloma (MM) signs and symptoms that result?

Pathophysiology of Disseminated Intravascular Coagulation (DIC). DIC is initiated by a variety of factors (endothelial injury, tissue injury, inflammation, and others), most of which either directly or indirectly result in release of large amounts of tissue factor. Many cytokines create a procoagulant environment by concurrently (1) suppressing normal control of homeostasis and (2) inducing tissue factor release by endothelium or monocytes. Tissue factor initiates the coagulation cascade (3) leading to the activation of thrombin, production of fibrin, and polymerization into a fibrin clot. Fibrinolysis normally digests clots (4) through the activity of plasmin, resulting in the production of various fibrin degradation products. However, during DIC, factors, such as TNF-α, induce (5) inhibitors of plasmin generation, thus leading to diminished fibrinolysis. Fibrin split products possess several biologic activities that affect DIC, including (6) the induction of further cytokine release by monocytes. Enzymatically active products of the coagulation cascade, including thrombin, activate (7) other inflammatory systems, including platelets and the kinin and complement systems. Activation of platelets and monocytes continues the procoagulant cycle by inducing additional tissue factor and cytokines. Mediators produced from the kinin and complement system (8) affect vascular endothelium, leading to increased vascular permeability that contributes to hypotension and potential shock. The uncontrolled consumption of platelets and clotting factors (9) compromises the normal hemostatic mechanisms, resulting in potential systemic hemorrhages. Excess activation of the coagulation cascade and platelets, with decreased fibrinolysis, leads to systemic microvascular thrombosis (10) and blockage of the vessels with progressive ischemia. Uncontrolled DIC will eventually lead to multiple end-organ failure.

pathophysiology and signs and symptoms of DIC

HL is characterized by its progression from one group of lymph nodes to another, the development of systemic symptoms, and the presence of Reed-Sternberg (RS) cells. It is widely accepted that the RS cell represents the malignant transformed lymphocyte. The RS cells are often large and binucleate, with occasional mononuclear variants. RS cells are the hallmark of HL. RS cells are necessary for the diagnosis of HL. The triggering mechanism for the malignant transformation of cells remains unknown. Classic HL appears to be derived from a B cell in the germinal center that has not undergone successful immunoglobulin gene rearrangement and would normally be induced to undergo apoptosis. Survival of this cell may be linked to infection with EBV. Laboratory and epidemiologic studies have linked HL with EBV infections and EBV DNA. RNA and proteins are frequently observed in HL cells. The RS cells secrete and release cytokines (e.g., IL-10, transforming growth factor-beta [TGF-β]) that result in the accumulation of inflammatory cells that produces the local and systemic effects.

pathophysiology of Hodgkins lymphoma.

Polycystic ovary syndrome (PCOS) is a difficult syndrome to diagnose because several factors are involved. It is a syndrome in which at least two of the following are present: oligo-ovulation or anovulation, elevated levels of androgens, or clinical signs of hyperandrogenism and polycystic ovaries. Prolonged anovulation leads to infertility, menstrual bleeding disorders, hirsutism, acne, endometrial hyperplasia, cardiovascular disease, and diabetes mellitus in women with hyperinsulinemia.

polycystic ovary syndrome

Primary dysmenorrhea is painful menstruation not associated with pelvic disease. It often results from excessive synthesis of prostaglandins (or sensitivity to prostaglandins), which cause the myometrium to contract and constrict blood vessels, resulting in ischemic pain.

primary dysmenorrhea

Most symptoms are the result of either hemorrhage or thrombosis. Acute DIC presents with rapid development of hemorrhaging, such as oozing from venipuncture sites, arterial lines, and surgical wounds, or development of ecchymotic lesions (purpura, petechiae) and hematomas. Other sites of bleeding include the eyes (sclera and conjunctiva), the nose (epistaxis), and the gums. Most individuals with DIC demonstrate bleeding at three or more unrelated sites, and any combination may be observed. Shock of variable intensity, out of proportion to the amount of apparent blood loss, also may be observed. Hemorrhaging into closed compartments of the body also can occur and may precede the development of shock. Symptoms of thrombosis are not always as evident, even though it is often the first pathologic alteration to occur and ultimately determines the degree of morbidity and risk for death. A large amount of microvascular and macrovascular occlusion may occur that is not clinically obvious. Several organ systems are susceptible to microvascular thrombosis that affects their function; these include the cardiovascular, pulmonary, central nervous, renal, and hepatic systems. Quick and accurate clinical diagnosis is critical to preventing further progression of DIC that may lead to multisystem organ dysfunction or failure. Indicators of multisystem failure include changes in level of consciousness, behavior, and mentation; confusion; seizure activity; oliguria; hematuria; hypoxia; hypotension; hemoptysis; chest pain; and tachycardia. Symmetric cyanosis of the fingers and toes ("blue finger/toe syndrome") and, in some instances, of the nose and breasts may be present. Symmetric parts are often affected and are indicative of microvascular thrombosis. This may progress to infarction and gangrene, requiring amputation. Jaundice also may be present and is believed to result from red blood cell destruction rather than hepatic dysfunction. Integumentary System: Widespread hemorrhage and vascular lesions Oozing from puncture sites, incisions, mucous membranes Acrocyanosis (irregularly shaped cyanotic patches) Gangrene Central Nervous System: Subarachnoid hemorrhage Altered state of consciousness (slight confusion to convulsions and coma) Gastrointestinal System: Occult bleeding to massive gastrointestinal bleeding Abdominal distention Malaise Weakness Pulmonary System: Pulmonary infarctions ARDS Cyanosis Tachypnea Hypoxemia Renal System: Hematuria Oliguria Renal failure

signs and symptoms of DIC

Many of the characteristic clinical features of HL can be explained by the complex action of cytokines and other growth factors that are secreted by the malignant cells. These substances induce infiltration and proliferation of inflammatory cells, resulting in an enlarged, painless lymph node in the neck (often the first sign of HL) Physical Findings: Adenopathy Mediastinal mass Splenomegaly Abdominal mass Symptoms: Fever, weight loss, night sweats Pruritus (itching) Laboratory Findings: Thrombocytosis Leukocytosis Eosinophilia Elevated erythrocyte sedimentation rate (ESR) Elevated alkaline phosphatase Paraneoplastic syndromes

signs and symptoms of Hodgkins lymphoma.