NR 507 Final Examinations Study Guide

NR 507 Final Examinations Study Guide NR 507 Final Study Guide  Reproductive: o Endometrial cycle (menstrual cycle) and the occurrence of ovulation  During menstruation (menses), the functional layer if endometriu ...

NR 507 Final Examinations Study Guide NR 507 Final Study Guide  Reproductive: o Endometrial cycle (menstrual cycle) and the occurrence of ovulation  During menstruation (menses), the functional layer if endometrium disintegrates and is discharges through the vagina.  Follicular/proliferative phase - GnRH and a balance between activin and inhibin from the granulosa cells contribute to the rise of FSH levels, which stimulates a number of follicles. The pulsatile secretion of FSH from the anterior pituitary gland rescues a dominant ovarian follicle from apoptosis by days 5 to 7 days of the cycle. Together estrogen and FSH increase FSH receptors in the granulosa cells of the primary follicle, making them more sensitive to FSH. FSH and estrogen combine to induce production of LH receptors on the granulosa cells of the primary follicle, thus promoting LH stimulation to combine with FSH stimulation, causing more rapid secretion of follicular estrogen. As estrogen levels increase, FSH levels drop because of an increase in inhibin-B secreted by the granulosa cells in the dominant follicle. This drop in FSH level decreases the growth of the less-developed follicles. Estrogen causes cells of the endometrium to proliferate and stimulates production of LH.  Luteal/secretory phase – ovulation marks the beginning of this phase. The ovarian follicle begins its transformation into a corpus luteum. Pulsatile secretion of LH from the anterior pituitary stimulates the corpus luteum to secrete progesterone, which in turn initiates the secretory phase of endometrial development. Glands and blood vessels in the endometrium branch and curl throughout the functional layer, and the glands begin to secrete a thin glycogen-containing fluid, the secretory phase. If conception occurs, the nutrient-laden endometrium is ready for implantation. Human chorionic gonadotropin (HCG) is secreted 3 days after fertilization by blastocytes and maintains the corpus luteum once implantation occurs at about day 6 or 7. HCG can be detected in maternal blood and urine 8 to 10 days after ovulation.  Ischemic/menstrual phase  The production of estrogen and progesterone continues until the placenta can adequately maintain hormonal production. If conception and implantation do not occur, the corpus luteum degenerates and ceases production of progesterone and estrogen. Without progesterone or estrogen to maintain it, the endometrium becomes ischemic and disintegrates. Menstruation then occurs marking the beginning of another cycle. Ovulatory cycles appear to have a minimum length of 24 to 26.5 days: the primary ovarian follicle requires 10 to 12.5 days to develop, and the luteal phase appears relatively fixed at 14 days (+/- 3 days). Menstrual blood flow usually lasts 3-7 days, but it may last as long as 8 days or stop after 1 to 2 days and still be considered within normal limits.  Ovulation – the release of an ovum from a mature follicle and marks the beginning of the luteal/secretory phase. o Uterine prolapse  Descent of the cervix or entire uterus into the vaginal canal.  In severe cases, the uterus falls completely through the vagina and protrudes from the introitus.  Symptoms of other pelvic floor disorders also may be present.  Urinary: sensation of incomplete emptying of the bladder, urinary incontinence, urinary frequency/urgency, bladder “splinting” to accomplish voiding  Bowel: constipation or feeling of rectal fullness or blockage, difficult defecation, stool or flatus incontinence  Urgency: manual “splinting” of posterior vaginal wall to accomplish defecation  Pain & Bulging: vaginal, bladder, rectum; pelvic pressure, bulging, pain, lower back pain  Sexual: dyspareunia, decreased sensation, lubrication, arousal  Tx:  Kegel exercises  Estrogen to improve tone and vascularity of fascial support  Pessary  Weight loss  Avoidance of constipation o Polycystic ovarian syndrome  Most common cause of anovulation and ovulatory dysfunction in women.  Defined as having at least two of the following three features: irregular ovulation, elevated levels of androgens (testosterone), and the appearance of polycystic ovaries on ultrasound.  Polycystic ovaries do not have to be present to diagnose PCOS, and conversely their presence alone does not establish the diagnosis.  Initial identification of genes involved in steroid biosynthesis, androgen biosynthesis, and insulin receptors within the ovary indicates genetic involvement.  A hyperandrogenic state is a cardinal feature in the pathogenesis of PCOS. However, glucose intolerance/insulin resistance and hyperinsulinemia often run parallel to and markedly aggravate the hyperandrogenic state, thus contributing to the severity of signs and symptoms of PCOS.  Excessive androgens affect follicular growth, and insulin affects follicular decline by suppressing apoptosis and enabling follicles to persist.  Weight gain tends to aggravate symptoms, whereas weight loss may ameliorate some of the endocrine and metabolic events and thus decrease symptoms.  Women with PCOS tend to have increased leptin levels. Leptin influences the hypothalamic pulsatility of GnRH and consequent interaction along the entire HPO axis.  In PCOS there is dysfunction in ovarian follicle development. Inappropriate gonadotropin secretion triggers the beginning of a vicious cycle that perpetuates anovulation.  Typically, levels of FSH are low or below normal and LH levels and LH bioactivity are elevated. An increased frequency of GnRH pulses appears to cause increased frequency of LH pulses. Persistent LH elevation causes a increase in the levels of androgens. Androgens are converted to estrogen in peripheral tissues, and increased testosterone levels cause a significant reduction in SHBG, which in turn causes increased levels of free estradiol.  Elevated estrogen levels trigger a positive-feedback response in LH and a negative-feedback response in FSH.  The accumulation of follicular tissue is various stages of development allows an increased and relatively constant production of steroids in response to gonadotropin stimulation. Thus PCOS is characterized by excessive production of both androgen and estrogen.  In turn, persistent anovulation causes enlarged polycystic ovaries characterized by a smooth, pearly white capsule. This characteristic appearance is caused by an increase of surface area and increased volume of up to 2.8 times, doubling of growing and atretic follicles, thickening of the tunica by 50%, increasing cortical stromal thickening by one-third and a fivefold increase in subcortical stroma, and escalating hyperplasia.  Manifestations:  Usually appear within 2 years of puberty but may present after a variable period of normal menstrual function and possibly pregnancy.  Symptoms are related to anovulation, hyperandrogenism, and insulin resistance and include dysfunctional bleeding or amenorrhea, hirsutism, acne, acanthosis nigricans, and infertility. Eval & Treatment:  Diagnosis is based on evidence of androgen excess, chronic anovulation, and sonographic evidence of polycystic ovaries with at least 2 of the 3 criteria present.  Tests for impaired glucose tolerance are recommended.  Evidence of hyperandrogenism must be present before PCOS is diagnosed in an adolescent female.  Goals of tx: reversing signs and symptoms of androgen excess, instituting cyclin menstruation, restoring fertility, and ameliorating any associated metabolic or endocrine, or both, disturbances.  First line: combined oral contraceptives for management of symptoms and to establish regular menses.  For those women with PCOS who are overweight or obese, lifestyle modifications including regular exercise and weight loss, also are considered first-line treatment. o Testicular cancer and conditions that increase risk  Highly treatable, usually curable cancer that most often develops in young and middle-aged men  90% of testicular cancers are germ cell tumors arising from the male gametes.  In addition, testicular tumors can arise from specialized calls of the gonadal stroma. These tumors, which are named for their cellular origins are Leydig cell, Sertoli cell, granulosa cell, and theca cell tumors and constitute less than 10% of all testicular cancer.  Risk factors: history of cryptorchidism, abnormal testicular development, human immunodeficiency virus (HIV) and AIDS, Klinefelter syndrome, and history of testicular cancer.  Manifestations:  Painless testicular enlargement is usually the first sign.  Enlargement is usually gradual and may be accompanied by a sensation of testicular heaviness or dull ache in the lower abdomen.  Lumbar pain may be present and usually is caused by retroperitoneal node metastasis.  Signs of metastasis to the lungs: cough, dyspnea, hemoptysis  Supraclavicular node involvement: dysphagia, neck swelling  Metastasis to CNS: alterations in vision, mental status, papilledema, and seizures o Symptoms that require evaluation for breast cancer  The first sign of breast cancer is usually a painless lump. Lumps caused by breast tumors do not have any classic characteristics.  Chest pain (lung metastasis) Dilated blood vessels  Dimpling of the skin  Edema  Edema of the arm  Hemorrhage  Local pain  Nipple/areolar eczema  Nipple discharge in nonlactating woman  Nipple retraction  Pitting of the skin (peaud’orange)  Reddened skin, local tenderness, and warmth  Skin retraction  Ulceration o Signs of premenstrual dysphoric disorder  >/= 5 symptoms below: occur in most cycles during the week before menses onset, improve within a few days after menses onset, and diminish in the week postmenses  Marked affective lability  Marked irritability or anger or increased interpersonal conflicts  Marked anxiety, tension  Decreased interest  Difficulty concentrating  Easy fatigability, low energy  Increase or decrease in sleep  Feelings of being overwhelmed  Physical symptoms: breast tenderness, muscle or joint aches, “bloating” or weight gain o Dysfunctional uterine bleeding (Abnormal uterine bleeding)  Bleeding that is abnormal in duration, volume, frequency, or regularity and has been present for the majority of the previous 6 months.  May be acute or chronic and is classified by PALM-COEIN system:  Polp  Adenomyosis  Leiomyoma  Malignancy  Hyperplasia  Coagulopathy  Ovulatory dysfunction  Endometrial  Iatrogenic  Not-yet classified  In premenstrual or menopausal women, any bleeding is considered abnormal. Therefore bleeding more frequently than every 21 daysor less frequently than every 35 days, is considered to be abnormal. Menstrual bleeding for longer than 7 days also is considered abnormal.  AUB is the leading reason for hysterectomy.  Perimenopausal women are most commonly affected.  The majority of AUB is due to lack of ovulation. Normal, regular periods are the result of complex interplay between the hypothalamus, pituitary, ovary, and the uterine endometrium. Disruptions in this system can affect the amount and structure of the uterine endometrium, causing it to shed irregularly or heavily.  If a follicle forms but never releases the ovum, the follicle may continue to produce estrogen, encouraging endometrial proliferation beyond the normal 14-day time window. In addition, the lack of progesterone causes the thickened endometrium to be unable to shed in a predictable fashion without excessive blood loss. Women who fail to ovulate experience irregularities in their menstrual bleeding related to the lack of progesterone and, in some cases, an excess of estrogen.  Without ovulation, menstrual flow may become irregular, excessive, or both, resulting from the large quantity of tissue available for bleeding and the random breakdown of tissue that results in exposure of vascular channels. In the absence of adequate progesterone levels, usual endometrial control mechanisms are missing, such as vasoconstrictive rhythmicity, tight coiling of spiral vessels, and orderly collapse, and stasis does not occur.  AUB also can result from defects of the corpus luteum, resulting in progesterone deficiencies, or from abnormalities of the uterus or cervix, such as endometrial polyps, uterine fibroids, or even uterine or cervical cancers.  Coagulation defects also can cause heavy and abnormal uterine bleeding and should be suspected in younger women with a history of extensive bruising or bleeding during dental procedures. Iatrogenic AUB can be caused by intrauterine devices or longacting contraceptive implants or medications, such as anticoagulants, steroids, digitalis, phenytoin, or hypothalamic depressants.  Manifestations:  Unpredictable and variable bleeding  Increased menstrual flow and the passage of large clots, leading to excessive blood loss  Pain, decreased productivity, and sexual dysfunction  Eval & Tx:  1st step in assessing AUB is determining the cause of the bleeding. Treatment goals include preventing or controlling abnormal bleeding, identifying underlying disease, and inducing regular menstrual cycles.  NSAIDs, such as ibuprofen and naproxen, are often 1st-line treatment for excessive menstrual bleeding because they reduce prostaglandin synthesis within the endometrial tissues, which causes vasoconstriction and decreased menstrual blood loss. NSAIDs can reduce menstrual bleeding significantly with minimal side effects. For the best effect, they should be taken in the few days preceding the beginning of the menstrual period and be continued through the days of heaviest bleeding. NSAIDs are not as effective in controlling menstrual blood loss as hormonal therapies.  Young women and those of childbearing age with abnormal bleeding are often treated with hormonal therapies to override the HPG axis and mimic normal menstrual bleeding or suppress it entirely. Common treatments include oral contraceptive pills that contain both estrogen and progesterone, long-term treatment with medroxyprogesterone and the levonorgestrel intrauterine device.  Women who do not wish to have future pregnancies can opt for treatments that permanently suppress their uterine lining. These treatments include ablation, where the lining is burned to prevent future proliferation of the endometrial cells, and complete removal of the uterus in hysterectomy.  If a woman is menopausal, and has not had a menstrual period for more than 1 year, all vaginal bleeding should be investigated to rule out uterine and other cancers.  Women with coagulation disorders may have excessive menstrual bleeding because they have a predisposition to bleeding or because they are taking anticoagulant medications to overcome a genetic predisposition to excessive clotting. To control their menstrual bleeding, these women can opt for cycle suppression. o Pathophysiology of prostate cancer  One of the most common forms of cancer occurring in the male.  Prostatic cancer occurs in older men, is slow growing, and is not highly invasive.  Individuals experiencing this cancer typically have high levels of prostatic-specific antigen in their blood.  Most occur in the periphery of the prostate. o HPV and the development of cervical cancer  Cervical cancer is almost exclusively caused by cervical human papillomavirus (HPV) infection. Infection with high-risk types ofHPV is a necessary precursor to development of cervical dysplasia, otherwise known as the precancerous cell changes that lead to invasive cancer.  Precancerous dysplasia, also called cervical intraepithelial carcinoma (CIN) and cervical carcinoma in situ (CIS), is a more advanced form of these cell changes. Importantly, cervical dysplasia can be detected noninvasively through examination of the cervical cells. If dysplasia is detected early, treatment is available to prevent invasive cancer.  High-risk HPV may persist and cause abnormal cellular changes that can become cancerous. Most HPV infections are cleared by the immune system; the vast majority of infections do not cause cervical cancer. For this reason, screening for cervical cancer before age 21 is not recommended.  Women with multiple sexual partners are more likely to be exposed to high-risk HPV, but women with only one lifetime sexual partner also can become infected. Smoking has been shown to increase the risks of persistent infection and later development of cervical cancer; in addition, women who have many children, have a long history of oral contraceptive use, and are immunocompromised also are at higher risk of cervical cancer. Women who use vaginal douches also seem to be at increased risk of HPV infection.  HIV infection greatly increases the risk that women infected with HPV will develop cervical cancer, and women with HIV should be screened for cervical cancer more frequently more women without HIV. In addition, high-risk HPV is found more frequently in women who are coinfected with chlamydia or gonorrhea, suggesting that those infectious processes may support the persistence of HPV in those women.  There are two main cell types: squamous epithelium cells and columnal epithelial cells. The line where the two cell types meet, known as the transformation zone, is very vulnerable to the oncogenic effects of HPV, and this is where carcinoma in situ is most likely to develop.  Because metaplastic cells are at increased risk of incorporating foreign or abnormal genetic material, neoplastic changes are most common in the transformation zone.  In girls and young women, a large portion of their cervix is covered with columnar epithelium, a condition known as squamous metaplasia. Therefore the younger a woman is when she contacts HPV, the more sensitive cervical cells are exposed.  Manifestations:  Asymptomatic  PAP test necessary for early detection  If symptoms exist: vaginal bleeding or abnormal discharge.o Vaginal bleeding may occur after intercourse or between menstrual periods. o Vaginal discharge is a less common presenting symptom and may be serosanguineous or yellowish with a foul odor.  Eval & Tx:  For women aged 30-65, HPV testing is now recommended at the same time as the Pap test because it is noninvasive and identifies women at later risk for cellular abnormalities leading to cancer; indeed, HPV is often detectable for more than a decade before any noticed cellular changes. For women aged 21-29, HPV testing is only indicated if a PAP test is abnormal, which is known as reflex HPV testing.  Cervical cytologic exam is most accurate if cells are obtained from both the endocervix and ectocervix, which involves placing the collection device into the cervical os.  When dysplasia is detected, further testing is indicated for diagnosis.  Endocrine: o Body’s process for adapting to high hormone levels  Negative feedback is the most common and occurs when a changing chemical, neural, or endocrine response decreases the subsequent synthesis and secretion of a hormone.  High concentrations of hormone decrease the number or affinity of receptors called downregulation. o Cushing’s Syndrome  Clinical manifestations resulting from chronic exposure to excess endogenous cortisol and is more common to women.  Whatever the cause, 2 observations apply: (1) they do not have diurnal or circadian secretion patterns of ACTH and cortisol, and (2) they do not increase ACTH and cortisol secretion in response to a stressor.  In individuals with ACTH-dependent hypercortisolism, secretion of both cortisol and adrenal androgens is increased, and corticotropin-releasing hormone (CRH) secretion is inhibited.  Elevated cortisol levels suppress CRH and ACTH secretion from the hypothalamus and anterior pituitary, respectively, which leads to low levels of ACTH. Low levels of ACTH cause atrophy of the remaining normal portions of the adrenal cortex, which over time will alter the cortisol-secreting activity of normal cells. When the secretion of cortisol by the tumor exceeds normal cortisol levels, symptoms of hypercortisolism develop.  Manifestations:  Weight gain is the most common feature and results from the accumulation of adipose tissue in the truck, facial, and cervical areas. These characteristic patterns of fatdeposition have been described as “truncal (central) obesity,” “moon face,” and “buffalo hump”  Polyuria is a manifestation of hyperglycemia and resultant glycosuria.  Muscle wasting leads to muscle weakness and is especially obvious in the muscles of the extremities, with thinning of the limbs.  In bone, loss of protein matrix and increases in bone resorption lead to osteoporosis and can result in pathologic fractures, vertebral compression fractures, bone and back pain, kyphosis, and reduced height.  Hypercalciuria may result in renal stones.  With elevated cortisol levels, vascular sensitivity to catecholamines is increased significantly, leading to vasoconstriction and hypertension.  Metabolic syndrome with abdominal obesity, hypertension, glucose intolerance, and dyslipidemias is a common complication.  Chronically elevated cortisol levels also cause suppression of the immune system, increased susceptibility to infections, and poor wound healing.  Females may experience symptoms of increased adrenal androgen levels, increased hair growth (facial hair), acne, and oligomenorrhea.  Infertility is common among women.  Eval & Treatment:  Tests: urine and serum cortisol and serum ACTH concentration  Treatment is specific for the cause of hypercorticoadrenalism and includes medication, radiation, and surgery. o Causes of hypoparathyroidism  Most commonly is caused by damage to or removal of the parathyroid glands during thyroid surgery and occurs because of the anatomic proximity of the parathyroid glands to the thyroid.  Also associated with genetic syndromes including familial hypoparathyroidism and DiGeorge syndrome (velocardiofacial syndrome), and an idiopathic or autoimmune form of the disease.  Hypomagnesemia also can cause a decrease in PTH secretion and function.  There is an inherited condition associated with hypocalcemia with normal to elevated levels of PTH called pseudohypoparathyroidism. o Lab results that point to primary hypothyroidism  Increased levels of TSH Decreased levels of total T3 and total and free T4 o Pathophysiology of thyroid storm  Thyrotoxic crisis (thyroid storm) is a rare but dangerous worsening of the thyrotoxic state, in which death can occur within 48 hours without treatment.  The condition may develop spontaneously, but it usually occurs in individuals who have undiagnosed or partially treated severe hyperthyroidism and who are subjected to excessive stress from other causes.  These causes may include infection, pulmonary or cardiovascular disorders, trauma, burns, seizures, surgery (thyroid), obstetric complications, emotional distress, or dialysis.  The symptoms of thyroid crisis are caused by the sudden release and increased action of thyroxine (T4) and tri-iodothyronine (T3) exceeding metabolic demands. o Signs of thyrotoxicosis  Enlarged thyroid gland (goiter)  Oligomenorrhea or amenorrhea/erectile dysfunction and decreased libido  Weight loss  Increased peristalsis leading to less formed and more frequent stools  Nausea, vomiting  Anorexia  Abdominal pain  Excessive sweating, flushing, and warm skin  Heat intolerance  Fine, soft, straight hair  Temporary hair loss  Nails that grow away from the nail beds  Palmar erythema  Exophthalmos  Tachycardia  Supraventricular dysrhythmias  Restlessness  Short attention span  Compulsive movement  Fatigue  Tremor  Insomnia  Increased appetite  Emotional lability  Dyspnea  Neurological: o Dermatomes Specific areas of cutaneous (skin) innervation at these spinal cord segments  The dermatomes of various spinal nerves are distributed in a fairly regular pattern, although adjacent regions between dermatomes can be innervated by more than one spinal nerve. o Substance release at the synapse  The narrow gap that separates the presynaptic neuron from the postsynaptic cell o Spondylolysis  A structure defect (degeneration, fracture, or developmental defect) in the pars interarticularis of the vertebral arch (the joining of the vertebral body to the posterior structures).  The lumbar spine at L5 is affected most often.  Mechanical pressure may cause an anterior displacement of the deficient vertebra (spondylolisthesis). This defect occurs in the portion of the lamina between the superior and inferior articular facets called the pars interarticularis.  Heredity plays a significant role, and spondylolysis is associated with an increased incidence of other congenital spinal defects.  As a result of torsional and rotation stress, “microfractures” occur at the affected site and eventually cause dissolution of the pars interarticularis.  Symptoms include lower back and lower limb pain. o Location of the motor and sensory areas of the brain  Precentral gyrus - strip of frontal cortex just in front of the central sulcus, that is crucial for motor control.  Postcentral gyrus – strip of parietal cortex, just behind the central sulcus, that receives somatosensory information from the entire body. o Pathophysiology of cerebral infarction  Results when an area of the brain loses its blood supply because of vascular occlusion.  Causes include (1) abrupt vascular occlusion (embolus or thrombi), (2) gradual vessel occlusion (atheroma), and (3) vessels that are stenosed but not completely occluded.  Cerebral thrombi and cerebral emboli most commonly produce occlusion, but atherosclerosis and hypotension are the dominant underlying processes.  Cerebral infarctions are ischemic or hemorrhagic. In ischemic infarcts, the affected area becomes pale and softens 6-12 hours after the occlusion (white infarct).  Necrosis, swelling around the insult, and mushy disintegration appear by 48 to 72 hours after infarction.  There is infiltration of macrophages and phagocytosis of necrotic tissue. The necrosis resolves by about the second week, ultimately leaving a cavity surrounded by glial scarring. In hemorrhagic infarcts, bleeding occurs into the infarcted area through leaking vessels when the embolic fragments resolve and reperfusion begins to occur. Hemorrhagic transformation of ischemic infarct (red infarct) may be exacerbated by thrombolytic therapy.  Unfortunately, reperfusion can compromise recovery by accelerating the sequence of metabolically damaging events, including oxidative stress (reperfusion injury). o Excitotoxins  Toxins that overstimulate glutamate release and cause neuron suicide. Excessive activation (kalinic acid, oxidopamine) o Agnosia  A defect of pattern recognition – a failure to recognize the form and nature of objects.  Can be tactile, visual, or auditory, but only one sense is generally affected.  May be minimal as a finger (failure to identify by name the fingers of one’s hand) or more extensive such as color agosia.  Agnosia is produced by dysfunction in the primary sensory area or in the interpretive areas of the cerebral cortex (temporo-occipital area)  Although agnosia moat commonly is associated with cerebrovascular accidents, it may arise from any pathologic process that injures these specific areas of the brain.  Table 17.9 pg 518 Types of Agnosia o Accumulation of blood in a subarachnoid hemorrhage  Subarachnoid hemorrhage – the escape of blood from a defective or injured vasculature into the subarachnoid space.  When a vessel is leaking, blood oozes into the subarachnoid space. When a vessel tears, blood under pressure is pumped into the subarachnoid space. The blood increases the intracranial volume, is extremely irritating to the meningeal and other neural tissues, and produces an inflammatory reaction.  Additionally, the blood coats nerve roots, clogs arachnoid granulations and clogs foramina within the ventricular system.  ICP immediately increases to almost diastolic levels. o Most common cause of meningitis  Bacterial: Neisseria meningitis, streptococcus pneumoniae, haemophilus influenzae  Genitourinary: o Diet and the prevention of prostate cancer  Epidemiologic studies have found total fat intake, animal and saturated fat, red meat, and dairy products are associated with an increase in prostate cancer risk. Calorie- dense or excessive carbohydrate intake and obesity, independent of dietary fat intake, may increase the risk of developing prostate cancer.  Dietary fat may increase androgens, increase oxidative stress, and increase reactive oxygen species.  Cooking meat at high temperatures produces heterocyclic amines and aromatic hydrocarbons that are carcinogenic.  Vitamin E has long been considered a candidate for prostate cancer.  Vitamin D may play an important role in prostate cancer prevention.  Tomatoes or tomato products ingested daily seem to reduce prostate cancer risk.  Vegetables including broccoli, cabbage, cauliflower, brussel sprouts, Chinese cabbage, and turnips may be protective against prostate cancer.  Green tea consumption has been associated with a reduced incidence of several cancers including prostate cancer. o Impact of Benign Prostatic Hypertrophy (BPH) on the urinary system  Enlargement 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.  Aging and circulating androgens are associated with BPH and enlargement.  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, tissue that surround the prostatic urethra usually compress it, but do not always cause bladder outflow obstruction. These symptoms are sometimes called the spectrum of lower urinary tract symptoms.  Symptoms include the urge to urinate often, a delay in starting urination, and decreased force of 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 intraabdominal pressure. At this stage the force of the urinarystream 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.  Some men initially have signs of uremia and renal failure.  On digital exam, the prostate is a soft and firm enlargement with a smooth mucosal surface.  Genetics: o The role of DNA in genetics  DNA contains the genetic information, the programming for our cells.  Genetic basis of life = “the blueprint of life” o Transcription  RNA is synthesized using DNA as the template via the process of transcription.  Only small portions of DNA are transcribed at a time to make RNA.  Each transcribed segment of DNA corresponds to one of the 1000’s of chromosomes.  Several 100-1000 DNA comprise a gene  Which genes are transcribed and when is based on which proteins the cells needs at any given time.  Some proteins are in “high demand” in our cells so those genes are transcribed continually; other proteins may be needed very rarely so those genes are not transcribed frequently. o Effects of genetic mutations  Mutations can occur either spontaneously or as a result of exposure to external mutagens such as radiation, chemicals, and even certain infectious agents (viruses).  A base pair substitution is the simplest type of mutation, it represents the simplest typo.  Frame shift mutations are a little bit more complex and more serious.  Every cell of our body is “hit” once every 10 seconds by a potential mutagen.  Junk/Spacer DNA is part of controlling, regulating, and protecting our DNA. If it gets zapped or hit, it’s not so critical because its not part of the DNA coding.  Things that prevent mutation:  Compartmentalization of DNA within the nucleus (any potential mutagen has to get through the cell membrane, through the cytoplasm, actually into the nucleus to do damage.)  Presence of natural antioxidant molecules that help inactivate potential mutagens (help neutralize or deactivate some of these mutagenic substances.) Presence of repair enzymes within nucleus that are able to correct mistakes on DNA.  Failure of homologous chromosome pairs to separate during meiosis is called nondisjunction and also results in the abnormalities of chromosome number.  Aneuploidy – somatic cells that do not contain the appropriate number of chromosomes. o Trisomy  Result of aneuploidy of autosomal chromosomes  An aneuploid cell containing three copies of one chromosome is said to be trisomic.  Can occur for any chromosome at conception, but the only forms seen with an appreciable frequency in live births are trisomies of the 13th, 18th, or 21st chromosome.  Fetuses with most other chromosomal trisomies do not survive to term.  Trisomy 16 is the most commonly known trisomy among abortuses, but it is not seen in live birth.  Partial trisomy, in which only an extra portion of a chromosome is present in each cell, also can occur. The consequences are not as severe as those of complete trisomies.  Trisomies can occur in only some cells in the body.  Individuals affected are said to be chromosomal mosaics, meaning that the body has two or more different cell lines each of which has a different karyotype.  Mosaics are usually formed by early mitotic nondisjunction occurring in one embryonic cell but not in other. o Down Syndrome  Trisomy 21  Result of aneuploidy of autosomal chromosomes  Most well-known example of aneuploidy in an autosome is trisomy of the 21st chromosome  The facial appearance is distinctive, with a low nasal bridge, epicanthal folds, protruding tongue, and flat, low-set ears.  Poor muscle tone (hypotonia) and short stature are both characteristic.  Congenital heart defects affect about 1/3 to ½ of live-born children with Down syndrome; a reduced ability to fight respiratory tract infections and an increased susceptibility to leukemia also contribute to reduced survival.  The risk of having a child with Down syndrome increases greatly with maternal age.  This dramatic increase in risk is a consequence of the age of maternal egg cells, which are held in an arrested state of prophase I from the time they are formed in the female embryo until they are shed in ovulation. Thus, an egg cell formed by a 45-year-old woman is itself 45 years old. This long suspended state may allow for the accumulation of errors leading to nondisjunction. o Klinefelter syndrome  Result of aneuploidy of sex chromosomes  Individuals with at least 2 X chromosomes and a Y chromosome in each cell (47, XXY karyotype)  Because of the presence of a Y chromosome, these individuals have a male appearance, but they are usually sterile, and about half develop female-like breasts (gynecomastia).  The tests are small, body hair is sparse, the voice is often somewhat high pitched, stature is elevated, and a moderate degree of mental impairment may be present.  Individuals with the 48, XXXY and 49, XXXXY karyotypes also are considered to have Klinefelter syndrome, and the degree of physical and mental impairment increases with each additional X chromosome.  Regardless of the number of X chromosomes, these individuals have a male appearance. The presence of a single Y-chromosome, which causes the undifferentiated gonads to become testes, always produces a male.  Mosaicism is sometimes seen in Klinefelter syndrome and results in less severe disease; the most prevalent combination is XXY and XY cells.  Individuals with 47, XYY tend to be taller than average and they have a 10-15 point reduction in average IQ. This condition, which causes few serious physical problems, achieved notoriety when it was found that its incidence was significantly elevated in prison populations. o Diseases that have multifactorial traits  Diabetes, dementia, cardiovascular conditions, cancer o Multifactorial inheritance  Most diseases (including diabetes, dementia, cardiovascular conditions, cancer) have a genetic component and are classified as multi-factorial: mutations occur at multiple (polygenic) chromosomal sites that have a cumulative effect to cause disease. o Duchenne muscular dystrophy  Progressive weakness associated with large calf muscles, said to be pseudohypertropic, because they consisted of fat and connective tissue rather than muscle.  DMD is the most common of the muscular dystrophies.  Primarily occurs in boys because of an X-linked inheritance  Caused by deletion of one or more exons of the DMD gene on the X chromosome or, more rarely, by a nonsense mutation resulting in premature termination of translation. DMD is the largest gene in the human genome and encodes dystrophin, a large, membrane-stabilizing protein.  Dystrophin is present in normal muscle cells and absent in DMD.  Milder mutations with residual dystrophin expression result in Becker muscular dystrophy, a milder syndrome.  Marked elevations of CK levels (100-1000 times or more) are easily identified in children suspected to have DMD and are an important diagnostic screen.  As muscle degenerates, there is an increased endomysial connective tissue and fat; loss of striations; and concomitant hyaline, granular, and fatty degeneration of fibers.  Disorganization of tendinous insertions is associated with fat accumulation in these areas. Although fibers regenerate in the younger child, regeneration is not able to keep up with muscle cell death, resulting in progressive weakness.  Manifestations:  Identified in children at approximately 3-4 years of age, when the parents first notice gait abnormalities, including toe walking, difficulty getting up from the ground, and frequent falls  Muscular weakness begins in the pelvic girdle, causing a “waddling” gait.  The method of rising from the floor by “climbing up the legs” (Gower sign) is characteristic and is caused by weakness of the lumbar and gluteal muscles.  Within 3-5 years, muscles of the shoulder girdle become involved.  Progressive weakness results in loss of ambulation between 12-15 years. Subsequent progression includes slowly progressive respiratory insufficiency, cardiomyopathy, and orthopedic complications including scoliosis.  Treatment with oral corticosteroids early in disease has become the standard of care and has dramatically improved outcomes.  Complications such as compromised pulmonary function and kyphoscoliosis are delayed.  Cognitive dysfunction is a common and often overlooked aspect of DMD.  As the condition progresses, constipation and incontinence of urine and stool may develop, possibly because of smooth muscle involvement.  Genetic counseling is recommended for all families who have children with DMD.  Children with DMD require a multidisciplinary approach to care, including attention to heart and breathing problems, weightloss/gain, constipation, rehabilitative/developmental problems, psychosocial needs, neurologic issues, and orthopedic problems.  Maintaining function in unaffected muscle groups for as long as possible is the primary goal of treatment. o Neurofibromatosis  Neurofibromatosis type 1 – most prevalent type  Causes multiple cutaneous neurofibromas; cutaneous macular lesions (café-au-lait spots and freckles); and less commonly, bone and soft tissue tumors.  Inactivation of the NF1 gene results in loss of function of neurofibromin in schwann cells and promotes tumorigenesis.  Diagnosis: o 6 or more safe-au-lait macules greater than 5 mm in greatest diameter in prepubertal individuals and greater than 15mm in greatest diameter in postpubertal individuals. o Multiple axillary or inguinal freckles o One plexiform neurofibroma or two or more neurofibromas of any type o Optic glioma o Two or more Lisch nodules o A distinctive osseous lesion such as sphenoid dysplasia or thinning of the cortex of long bones with or without pseudoarthrosis. o A first degree relative with NF1  Neurofibromatosis type 2 – rare  The NF2 gene product is neurofibromin 2, a tumorsuppressor protein.  Mutations promote development of central nervous system tumors, particularly schwannomas, although other tumor types can occur.  Benign bilateral schwannomas of the vestibular nerves present with hearing loss progressing to deafness, dizziness, and balance problems, tinnitus, and facial nerve paralysis. Other symptoms may include loss of balance and dizziness.  Schwannomas also may develop in other cranial, spinal, and peripheral nerves, and cutaneous signs are less prominent. Intracranial meningiomas can involve the optic nerve with loss of visual acuity and cataracts or can be intraspinal with formation of ependymomas.  Diagnosis: o Bilateral masses of the 8th cranial nerve seen with appropriate imaging o First degree relative with NF2o 2 of the following: neurofibroma, meningioma, glioma, schwannoma, juvenile posterior subcapsular lenticular opacity  Diagnosis is based on clinical manifestations and neuroimaging studies.  Musculoskeletal: o Ions that initiate muscle contraction  Acetylcholine – neurotransmitter that enables learning and memory and also triggers muscle contraction; a chemical released at the end of nerve cells  Tropomycin – a protein of muscle that forms a complex with troponin regulating the interaction of actin and myosin in muscle contraction  Myocin and actin – contractile and motor proteins o Growth of long bones in children  Long bones are longer than they are wide and consist of a narrow tubular midportion (diaphysis) that merges into a broader neck (metaphysis) and a broad end (epiphysis).  Epiphysis – bone ends  Metaphysis – region between diaphysis and epiphysis  Diaphysis – center portion of the thick compact bone (shaft of the long bone)  The two phases of the long bone often have varying activity rates. The more active of 2 has more power to remodel deformity but also can be more sensitive to injury. The architecture of the physis also dictates its sensitivity to injury. o Bones belonging to the appendicular skeleton  Consists of 126 bones that make up the:  Upper and lower extremities  The shoulder girdle (pectoral girdle)  Pelvic girdle (os coxae)  Contributes about 14% of the weight of the adult body  Immunity/Inflammation: o How vaccines are formed  Development of a successful vaccine depends on many factors. These include characterizing the desired protective immune response (antibody, T cell), identifying the appropriate antigen to induce that response (immune responses against some antigens on an infectious agent are ineffective or even increase the risk for infection), determining the most effective route of administration (injected, oral, inhaled), optimizing the number and the timing of vaccine doses to induce protective immunity in a large proportion of the at-risk population, and deciding the most effective, yet safe, form in which to administer the vaccine. o Populations at risk for getting systemic fungal infections and parasitic infectionso Systemic manifestations of infection  Fever o Mechanisms responsible for the increase in antimicrobial resistance worldwide o Functions of normal flora in the body  Respiratory flora: streptococcus pneumoniae, haemophilus influenzae, staph aureus, klebsiella  Gut flora: the billions of normal bacteria present in the large intestine to protect against infection and help maintain the immune system.  Skin flora: gram + cocci (staph/propio) gram – rods (enteric bacilli) o Desensitization therapy  To allergens can be achieved to some individuals.  Minute quantities of the allergen are injected in increasing doses over a prolonged period. The procedure may reduce the severity of the allergic reaction in the treated individual and works best for routine respiratory tract allergens and biting insect allergies.  However, this form of therapy is associated with a risk of systemic anaphylaxis, which can be severe and life threatening.  Food allergies have been very difficult to suppress, but some promising trials are underway to evaluate desensitization by oral or sublingual administration of increasing amounts of allergen.  The mechanisms by which desensitization occurs may be several, one of which is the production of large amounts of so-called blocking antibodies, usually circulating IgG. A blocking antibody presumably competes in the tissues or in the circulation for binding with antigenic determinants on the allergen so that the allergen is “neutralized” and is unable to bind with IgE on mast cells. o Cells involved in “left shift” in the WBC count differential  Neutrophils o Forms of immunity  Innate  The immunity we are born with  Present before exposure and effective from birth  Responds to a broad range of pathogens  Nonspecific, immediate, localized protection mediated by barrier systems, phagocytic WBCs, chemical components  Adaptive/Acquired  Provides specific slower-acting, systemic protection mediated by specialized WBCs = lymphocytes, chemical components  Vaccination  Passive An individual does not produce his/her own antibodies but rather receives them directly from another source, such as mother to infant through breast milk  Active  A form of acquired immunity in which the body produces its own antibodies against disease-causing antigens involving T-cells and B-cells. o Major histocompatibility class I antigens o Inflammatory chemicals blocked by anti-inflammatory drugs  Prostaglandins – a group of bioactive, hormone-like chemicals derived from fatty acids that have a wide variety of biological effects including roles in inflammation, platelet aggregation, vascular smooth muscle dilation and constriction, cell growth, protection of from acid in the stomach, and many more. Intensify histamine and kinin effect.  Histamine – chemical stored in mast cells that triggers dilation and increased permeability of capillaries.  Kinin system – functions to activate and assist inflammatory cells. Primary kinin is bradykinin. Causes dilation of blood vessels, pain, smooth muscle contraction, vascular permeability, and leukocyte chemotaxis. o Characteristics of acute phase reactant C-reactive protein  An acute phase reactant C-reactive protein mostly synthesized in the liver and in an indirect measure of atherosclerotic plaquerelated inflammation and plaqure progression.  Risk factors for high CRP: smoking, obesity, diabetes  Dermatology: o Process by which a deep pressure ulcer heals  Deep injuries develop closer to the bone as a result of tissue distortion and vascular occlusion from pressure that is perpendicular to the tissue (over the heels, trochanter, and ischia).  Bacteria colonize the dead tissue, and infection is usually localized and self-limiting. Proteolytic enzymes from bacteria and macrophages dissolve necrotic tissues and cause a foul-smelling discharge that resembles, but is not, pus.  The necrotic tissue initiates an inflammatory response with potential pain, fever, and leukocytosis. If the ulceration is large, toxicity and pain lead to a host of possible complications, including loss of appetite, debility, local/systemic infections, and renal insufficiency. o Complications of the development of contractures during wound healing  Excessive wound contraction may result in a deformity or contracture. Burn wounds are especially susceptible to the development of contractures.  Internal contractures may occur as well and are common in cirrhosis of the liver. Internally, scar tissue that becomes contracted constricts blood flow that may contribute to the development of portal hypertension and esophageal varices.  Duodenal strictures caused by dysfunctional healing of an ulcer and esophageal strictures caused by chemical burns are other types of internal contraction deformity.  Acid/Base: o Causes of respiratory alkalosis  Hyperventilation  Extreme anxiety/panic/pain  Altitude change  Hypermetabolic states (fever, sepsis, hyperthyroidism) o Molecules that act as buffers in the blood  H+ or OH-  The carbonic acid-bicarbonate buffer system is the most important plasma buffering system to remove excess body acids (H+) or bases (OH-)  Cardiovascular: o Most common cardiac valve disease in women  Mitral valve stenosis occurs mostly in women: 70% o When myocardial ischemia may be reversible o Symptoms of stable angina  Transient substernal chest discomfort ranging from a sensation of heaviness or pressure to moderately severe pain.  Described as sensation by clenching fist over the left sternal border  Discomfort may be mistaken for indigestion  Pain is caused by the buildup lactic acid or abnormal stretching of the ischemic myocardium that irritates myocardial nerve fibers  Pain may radiate to the neck, lower jaw, left arm, and left shoulder or occasionally to the back or down the right arm.  Pallor, diaphoresis, and dyspnea may be associated with the pain.  Pain is relieved by rest and nitrates. o Orthostatic hypotension  Refers to a decrease in systolic BP of at least 20 mmHg or a decrease in diastolic BP of at least 10 mmHg within 3 minutes of moving to a standing position.  Primary/neurogenic: result of neurologic disorders that affect autonomic function  Secondary: acute and associated with (1) altered body chemistry (2) drug action (3) prolonged immobility caused by illness (4) starvation (5) physical exhaustion (6) any condition that produces volume depletion (massive diuresis, potassium or sodiumdepletion) (7) any condition that results in venous pooling (pregnancy, extensive varicosities of the lower extremities)  Compensatory changes during standing normally increase sympathetic activity mediated through stretch receptors in the carotid sinus and the aortic arch. This reflex response to shifts in volume caused by postural changes leads to a prompt increase in heart rate and constriction of the systemic arterioles, which maintains stable blood pressure.  Often accompanied by dizziness, blurring or loss of vision and syncope or fainting  To assess hypotensive episode frequency, severity, and correlation with symptoms, 24-hour blood pressure monitoring is recommended.  Treatment for secondary OH is focused on correcting the underlying disorder. o Isolated systolic hypertension  A condition most commonly seen in the older adult in which the systolic blood pressure is greater than 140 mmHg and the diastolic pressure is within normal limits <90 mmHg o Results of sustained controlled hypertension o The relationship of insulin resistance on the development of primary hypertension  Insulin resistance is associated with endothelial injury and affects renal function, causing renal salt and water retention.  Insulin resistance is associated with overactivity of the SNS and the RAAS. It is interesting to note that in many individuals with diabetes treated with drugs that increase insulin sensitivity, blood pressure often declines, even in the absence of antihypertensive drugs.  The interaction between obesity, hypertension, insulin resistance, and the lipid disorders in the metabolic syndrome result in a high risk of cardiovascular disease. o Defects in the normal secretion of natriuretic hormones and the impact on renal system  Affect sodium o Effects of increased sympathetic nervous system activity due to primary hypertension  Increased SNS activity causes increased HR and systemic vasoconstriction, thus raising the blood pressure.  Efferent sympathetic outflow stimulates renin release, increases tubular sodium reabsorption, and reduces renal blood flow.  Additional mechanisms of SNS-induced hypertension include structural changes in blood vessels, insulin resistance, increased renin angiotensin levels, and procoagulant effects. o Complications of unstable plaque in the coronary arteries Unstable plaques are prone to ulceration or rupture even if there has been no significant impairment of coronary blood flow before the event.  When this ulceration or rupture occurs, underlying tissues of the vessel wall are exposed, resulting in platelet adhesion and thrombus formation.  Thrombus formation can suddenly cut off blood supply to the heart muscle, resulting in acute myocardial ischemia, and if the vessel obstruction cannot be reversed rapidly, ischemia will progress to infarction. o Forms of dyslipidemia associated with the development of the fatty streak in atherosclerosis  Inflammation and oxidized LDL cause endothelial cells to express adhesion molecules that bind monocytes and other inflammatory and immune cells. Monocytes penetrate the vessel wall becoming macrophages.  Several types of receptors on these macrophages enable detection and engulfment of the oxidized LDL. These lipid-laden macrophages are now called foam cells, and when they accumulate in significant amounts, they form a lesion called a fatty streak and numerous inflammatory cytokines are released as well as enzymes that further injure the vessel.  Growth factors are also released which stimulate smooth muscle cell proliferation in the affected vessel. These smooth muscle cells produce collagen and migrate over the fatty streak forming a fibrous plaque.  The fibrous plaque may calcify, protrude into the vessel lumen, and obstruct blood flow to distal tissues, especially during exercise, which may cause symptoms (angina or intermittent claudication) o Events that initiate the process of atherosclerosis  Atherosclerosis begins with injury to the endothelial cells that line artery walls.  There are many possible causes of endothelial injury such as aging, smoking, hypertension, and diabetes.  The risk factors for atherosclerosis are discussed in more detail in the following section on coronary artery disease. Injured endothelial cells become inflamed and cannot make normal amounts of antithrombic and vasodilating cytokines.  The adventitia also plays an important role through production of reaction oxygen species and activation of endothelial inflammation. o Signs and symptoms of increased left atrial and pulmonary venous pressures in left sided heart failure  Result of pulmonary vascular congestion and inadequate perfusion of the systemic circulation Individuals experience dyspnea, orthopnea, cough of frothy sputum, fatigue, decreased urine output, and edema.  Physical exam often reveals pulmonary edema (cyanosis, inspiratory crackles, pleural effusions), hypotension or hypertension, an S3 gallop, and evidence of underlying CAD or hypertension. o Differences between left and right sided heart failure  Left:  Inability of the left ventricle to provide adequate blood flow into systemic circulation  Causes: systemic hypertension, LV MI, LV hypertrophy, aortic SLV or bicuspid valve damage, secondary to right HF  Symptoms: pulmonary edema, dyspnea  Right:  Inability of the right ventricle to provide adequate blood flow into pulmonary circulation  Causes: pulmonary disease, RV MI, RV hypertrophy, pulmonary SLV or tricuspid valve damage, secondary to left HF.  Symptoms: JVD, hepatosplenomegaly, peripheral edema o Infective endocarditis  General term used to describe infection and inflammation of the endocardium, especially the cardiac valve.  Patho:  (1) trauma, congenital heart disease, valvular heart disease, and the presence of prosthetic valves are the most common risk factors for endocardial damage that leads to IE.  (2) blood-borne microorganism adherence to the damaged endocardial surface  (3) formation of infective endocardial vegetations  The classic findings are fever, new or changed cardiac murmur, and petechial lesions of the skin, conjunctiva, and oral mucosa.  Characteristic physical findings include Osler nodes (painful erythematous nodules on the pads of the fingers and toes) and Janeway lesions.  Other manifestations include weight loss, back pain, night sweats, and heart failure.  CBS, splenic, renal, pulmonary, peripheral, arterial, coronary, and ocular emboli may lead to a wide variety of signs and symptoms.  Peripheral vascular disease: o Pathophysiology of deep vein thrombosis  DVT is a blood clot that remains attached to a vessel wall, usually in a single side of a lower extremity. Accumulation of clotting factors and platelets leads to thrombus formation in the vein, often near a venous valve.  Inflammation around the thrombus promotes further platelet aggregation, and the thrombus grows proximally.  Most thrombi eventually dissolve without treatment, but untreated DVT is associated with a high risk of thromboembolization of a part of the clot from the leg traveling to the lung resulting in pulmonary embolism. o Virchow’s triad  (1) injury to the blood vessel endothelium (trauma, venipuncture, IV meds)  (2) abnormalities of blood flow (immobility, obesity, prolonged leg dependency, age, CHF)  (3) hypercoagulability of the blood (inherited disorders, smoking, malignancy, liver disease, pregnancy, oral contraceptives, hormone replacement, hyperhomocysteinemia, antiphospholipid syndrome)  Hematology: o Physiological response to hypoxia in anemia  Tissue vasodilation and vasoconstriction in the lungs  Weakness, fatigue, dyspnea on exertion, rarely angina, pallor/cyanosis of the skin, mucous membranes, nail bed, jaundice due to increased bilirubin in hemolytic anemias, damage to the myocardium, liver, and kidney o Populations at the highest risk for developing folate deficiency anemia  Alcoholics and individuals with chronic malnourishment  Pregnant and lactating women o Causes of iron deficiency anemia  Inadequate dietary intake, chronic or occult bleeding (hemorrhage, colitis, cirrhosis, GI ulcers, esophageal lesions, or menorrhagia), decreased ability to utilized iron for heme synthesis (transferrin deficiencies, mitochondrial defects) o Expected lab test results found in long standing iron deficiency anemia  Decreased hemoglobin and hematocrit  Lower than normal serum iron, ferritin, and transferring saturation levels. o Sickle Cell Anemia  Caused by inherited autosomal recessive genetic disorder (inheritance of two abnormal genes, one from each parent)  Single amino acid change on beta-chain -> elongated hemoglobin molecules  Oxidative stress, anxiety, fever, cold, dehydration  Decrease oxygen binding to hemoglobin and increases sickling tendencies Causes the distortion of RBCs  RBCs rupture after 10-15 days in circulation  Occlude blood vessels and spleen  High risk for CVA and splenic damage o Causes of aplastic anemia  Chemical or radiation exposure (SE of cancer treatment)  Viral-induced (hepatitis, Epstein-Barr, CMV)  Tumors (multiple myeloma)  Antibiotics & other RX (PCN, chloramphenicol, phenytoin, diuretics, antidiabetic, and sulfa)  Congenital defects (Fanconi’s anemia) o Underlying pathophysiologic mechanisms leading to autoimmune hemolytic anemia  The lysis of blood cells  Caused by infection, transfusion reaction, hemolytic disease of the newborn (Rh incompatibility), autoimmune reaction, druginduced.  Premature destruction of RBC due to enzymes/toxins produced by infectious agent, mediated by own immune system, or the effects of certain chemicals/drugs. o Secondary polycythemia  More common type  Physiological response resulting from increased erythropoietin secretion in response to chronic hypoxia.  This hypoxia is noted in individuals that live at higher altitudes (greater than 10,000 feet), smokers with increased levels of carbon monoxide, and individuals with COPD or CHF, or both.  Abnormal types of hemoglobin (hemoglobin San Diego or hemoglobin Chesapeake), which have a greater affinity for oxygen, also can cause secondary polycythemia, as does secretion of erythropoietin by certain tumors (renal cell carcinoma, hepatoma, and cerebral hemangioblastoma. o Anemia of chronic renal failure  Anemia associated with CRF may result from variety of simultaneous mechanisms.  Damage to the kidney affects the secretion of erythropoietin, a necessary hormone for production of erythrocytes in the bone marrow, thus resulting in diminished bone marrow erythropoiesis.  Uremic toxins (uric acid, sulfates, phosphates) that increase in the blood secondarily to renal failure may suppress bone marrow function and damage erythrocytes, which undergo eryptosis.  Platelet function also may be defective in these individuals, which results in chronic bleeding and loss of erythrocytes.  Fluid and Electrolytes: o Conditions that result in pure water deficit (hypertonic volume depletion) Hypernatremia o Osmoreceptors that stimulate thirst and the release of ADH  The increase osmolality of the plasma stimulates hypothalamic osmoreceptors. In addition to causing thirst and water drinking, the stimulated osmoreceptors signal the posterior pituitary to release ADH. The action of ADH is to increase the permeability of distal renal tubular cells to water, increasing water absorption and promoting the restoration of plasma volume and blood pressure. o Causes of hypernatremia  Hypovolemic hypernatremia  Use of loop diuretics, osmotic diuresis (from hyperglycemia related to uncontrolled diabetes mellitus or use of mannitol), GI losses, or failure of the kidneys to concentrate urine.  Euvolemic hypernatremia  Inadequate water intake; excessive sweating, fever from hyperventilation and increased water loss from lungs, burns, vomiting, diarrhea, and central or nephrogenic diabetes insipidus.  Infants with severe diarrhea are vulnerable and have increased risk because they cannot communicate thirst.  Hypervolemic hypernatremia  Infusion of hypertonic saline solution (because sodium replacement for treatment of salt depletion can occur with renal impairment, heart failure, or GI losses or oversecretion of ACTH or aldosterone (cushing syndrome, adrenal hyperplasia), and near-salt water drowning. o Effects of increased aldosterone  High blood pressure  Low potassium levels  Abnormal increase in blood volume  Primary adrenal insufficiency o Dependent edema  Accumulates in gravity dependent areas of the body, might appear in the feet and legs when standing and in the sacral areas and buttocks when supine.  4 most common mechanisms:  Increased capillary hydrostatic pressure  Decreased capillary oncotic pressure  Increased capillary permeability  Lymphatic obstruction  Can occur from heart failure, renal failure, cirrhosis of the liver, hemorrhage, serous drainage from wounds or burns, crushing injuries, allergic reactions, infection, tumor o Definition of isotonic Describes a solution whose solute concentration is equal to the solute concentration inside the cell o Principle of capillary oncotic pressure  Osmotically attracts water from the interstitial space back into the capillary o Types of fluid compartments in the body  Intracellular – fluid within cells; 40% body weight  Extracellular – fluid outside cells; 20% body weight  Intravascular – blood plasma (<5%)  Interstitial – fluid between cells and outside of blood vessels (<15%)  Other fluids – lymph, synovial, CSF, intestinal, sweat, urine, intraocular, and body cavity fluids  Pulmonary: o Most effective measure to prevent pulmonary embolus from developing in patients  Bed exercises, frequent position changes, early ambulation, and pneumatic calf compression o When the practitioner will note tactile fremitus  In lung tissue disease – COPD, obstruction, pneumothorax, pleural effusion asthma, pneumonia o Cause of acute airway obstruction in the patient with chronic bronchitis  The thick mucus and hypertrophied bronchial smooth muscle narrow the airways and lead to obstruction, particularly during expiration when the airways are constricted. Obstruction also leads to ventilation-perfusion mismatch with hypoxemia. o Types of pneumothorax  Primary/Spontaneous – occurs unexpectedly in health individuals between 20-40 years and is caused by the spontaneous rupture of blebs (blister-like formations) on the visceral pleura.  Secondary/Traumatic – caused by chest trauma such as a rib fracture, stab, or bullet wounds, or a surgical procedure that tears the pleura; rupture of a bleb or bulla (larger vessel) as occurs in COPD; or mechanical ventilation, particularly if it includes positive end-expiratory pressure (PEEP)  Iatrogenic – caused by a transthoracic needle aspiration  Open/Communicating – air pressure into the pleural space equals barometric pressure because air that is drawn into the pleural space during inspiration (through the damaged chest wall and parietal pleura or through the lungs and damaged visceral pleura) is forced back out during expiration.  Tension – the site of pleural rupture acts as a one-way valve, permitting air to enter on inspiration but preventing its escape by closing during expiration. May be complicated with hypoxemia, tracheal deviation away from the affected lung, and hypotension o Results of the loss of alph-1-antitrypsin in emphysema  Inhibits the action of many proteolytic enzymes; therefore individuals who have deficiency increase their likelihood of developing emphysema because proteolysis in lung tissues is not inhibited. o The result of loss of surfactant in ARDS  Surfactant is inactivated and its production by type II alveolar cells is impaired as alveoli and respiratory bronchioles fill with fluid or collapse.  The intraalveolar hemorrhagic exudate becomes a cellular granulation tissue appearing as hyaline membranes and there is progressive hypoxemia.  The lungs become less complaint, the work of breathing increases, ventilation of alveoli decreases, hypercapnia develops. o Characteristics of Cheyne-Stokes respirations  Alternating periods of deep and shallow breathing  Apnea lasting 15 to 60 seconds is followed by ventilations that increase in volume until a peak is reaches, after which ventilation (tidal volume) decreases again to apnea.  Result from any condition that slows the blood flow to the brainstem, which in turn slows impulses sending information to the respiratory centers of the brainstem.  Neurologic impairment above the brainstem is also a contributing factor.  Shock: o Causes of hypovolemic shock  Loss of whole blood (hemorrhage)  Plasma (burns)  Interstitial fluid (diaphoresis, diabetes mellitus, diabetes insipidus, emesis, or diuresis)  All in large amounts o How the body maintains glucose levels during shock  Glucose uptake can be prevented by the presence of vasoactive toxins, endotoxins, histamine, and kinins.  Cells shift to glycogenolysis, gluconeogenesis, and lipolysis to generate fuel for survival.  Except for the liver, kidneys, and muscles, the body’s cells have extremely limited stores of glycogen.