NR507 PATH FINAL EXAM STUDY GUIDE

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2019 NR507 PATH FINAL EXAM STUDY GUIDE ** due Saturday REPRODUCTIVE Endometrial cycle and occurrence of ovulation Manifestation of female reproductive functioning is menstrual bleeding, which start... s with menarche (1stperiod) and ends with menopause (cessation of menstrual flow for 1 year). Average age of menarche is 12 with a range of 9-17. Appears to be r/t body weight, especially body fat ratio. At first cycles are anovulatory and vary from 10-60 days or >. Then in adulthood range form 25-35 days. Length varies considerably. Cycle and regular ovulation are dependent on • The activity of gonadostat • Initial pituitary secretion of gonadotropin FSH • Estrogen positive feedback for the preovulatory FSH and LH surge, oocyte maturation, andcorpus luteum formation and production of progesterone. The average menstrual cycle lasts 27 to 30 days and consists of three phases, which are named for ovarian and endometrial changes: the follicular/proliferative phase, the luteal/secretory phase, and the ischemic/menstrual phase. Phase 1-is the follicular phase in which begins on day one of one’s menstrual cycle. It lasts until aboutday 14. -In phase 1 the endometrium grows to form a lush lining inside of the uterus. Phase 2: Luteal phase-this is where the body secretes the hormones estrogen and progesterone. -These hormones work together to prepare the lining of the uterus for implantation. -This last for 12 days. Phase 3: Menstrual phase-The estrogen and progesterone start to decline and the endometrial liningbegins to shed. This lasts for 3-5 days and the process restarts. Ovulation -Release of ovum -Present at the beginning of the luteal/secretory phase. -The ovarian follicle begins to transform into the corpus luteum. -Pulsatile secretion of the LH from the anterior pituitary stimulates the corpus luteum to secreteprogesterone. -This will initiate the secretory phase of endometrial development.-Glands and blood vessels in the endometrium branch and curl through a functional layer, and the glandsbegin to secrete a thin glycogen-containing fluid= the secretory phase. *If conception occurs the nutrient-laden endometrium is ready for implantation. *The HCG hormone is secreted 3 days after fertilization by blastocytes and maintains the corpus luteumonce implantation occurs at day 6 or 7. *HCG can be detected in maternal blood or urine about 8-10 days after ovulation. *Production of estrogen and progesterone continue until placenta can adequately maintain hormonalproduction. *Ovulatory cycles have a length of 24-26.5 days. *The primary ovarian follicle requires 10-12.5 days to develop. *The luteal phase appears at 14 days. Ovarian events of the menstrual cycle are controlled by gonadotropins. High FSH levels stimulate follicle and ovum maturation (follicular phase), then a surge of LH causes ovulation, which is followed by development of the corpus luteum (luteal phase). Ovarian hormones control the uterine (endometrial) events of the menstrual cycle. During the follicular/proliferative phase of the ovarian cycle, estrogen produced by the follicle causes the endometrium toproliferate (proliferative phase) and induces the LH surge and progesterone production in the granulosa layer. During the luteal/secretory phase, estrogen maintainsthe thickened endometrium, and progesterone causes it to develop blood vessels and secretory glands (secretory phase). As the corpus luteum degenerates, production of both hormones drops sharply, and the “starved” endometrium degenerates and sloughs off, causing menstruation, the ischemic/menstrual phase. Cyclic changes in hormone levels also cause thinning and thickening of the vaginal epithelium, thinning and thickening of cervical secretions, and changes in basal body temperature. Uterine Prolapse descent of cervix or entire uterus into vaginal canal. In severe cases the uterus falls completely throughthe vagina and protrudes from the introitus. Symptoms of other pelvic floor disorders may also be present. Tx depends on severity of symptoms and physical condition of woman. First line treatment is often a pessary- removable mechanical device that holds uterus in position. The pelvic fascia may be strengthened through kegels or by estrogen therapy in menopausal women. Healthy BMI, preventing constipation, and treating chronic cough may also help. Surgical repair with or without hysterectomy is the last resort. Page-771 fig 25.11 -Dropping of the cervix or the entire uterus into the vaginal canal.-In severe cases the uterus completely through the vagina and protrudes from the introitus. -Symptoms of other pelvic floor disorders may also be present. Symptoms: urinary-sensation of incomplete emptying of bladder, incontinence,frequency,bladdersplinting to accomplish voiding. Bowel-constipation or feeling of rectal fullness, difficult defecation, stool or flatus incontinence. *Pain or bulging includes pelvic pressure, low back pain, and vagina, bladder or rectum bulging. *Sexual-decreased sensation, lubrication or arousal. -Dyspareunia Treatment: -Depends on age and severity. -Isometric exercise-strengthen the pubococcygeal muscle. KEGELS* -Estrogen-to improve tone and vascularity of fascial support POSTMENOPAUSAL* -Pessary—a removable device to hold pelvic organs in place. -Weight loss -Stool softeners to avoid constipation -tx of lung and cough conditions PCOS 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. Presenting s/s: obesity, menstrual disturbance, oligomenorrhea, amenorrhea, regular menstruation,hyperandrogenism, infertility or they could be asymptomatic. Diagnosis of PCOS is based on evidence of androgen excess, chronic anovulation, and inappropriate gonadotropin secretion. Tests for impaired glucose tolerance are recommended. As stated, polycystic ovaries do noT have to be present and, conversely, their presence alone does not establish the diagnosis. Goals of treatment include reversing signs and symptoms of androgen excess, instituting cyclic menstruation, restoring fertility, and ameliorating any associated metabolic or endocrine, or both, disturbances.*Most common cause of anovulation and ovulatory dysfunction in women. *Leading cause of infertility and most common endocrine disturbance. *Mostly common in younger women *Usually has two/three of the following: irregular ovulation, elevated levels of androgens (testosterone), and the appearance of polycystic ovaries on ultrasound. *Polycystic ovaries do not need to be present to dx POS. *Thyroid dysfunction, hyperprolactinemia, and congenital adrenal hyperplasia must be ruled out first. *Associated with metabolic dysfunction, dyslipidemia, insulin resistance, and obesity. *Strong genetic component and possibly differentially inherited. *Difficult to diagnose as symptoms may change over time. *80% of women have one or more of the symptoms with normal ovaries. *More prominent sx as we age. *May be associated with Cushing’s syndrome, acromegaly, premature ovarian failure, obesity, congenital adrenal hyperplasia, thyroid disease and androgen producing adrenal tumors. Pathophysiology: *Underlying cause is unknown *Genetic involvement suggested because ofsteroid and androgen biosynthesis. *No single factor accounts for abnormalities of pcos. ***A HYPERANDROGENIC STATE IS A CARDINAL GEATURE IN THE PATHOGENSIS OF PCOS*** -3 X LIKELY TO HAVE INSULIN RESISTENCE. *Insulin stimulates androgen secretion by the ovarian stroma and reduces the serum sex hormone-binding globulin. * Free testosterone levels increase *Excessive androgens affect follicular growth and insulin affects follicular decline by suppressing apoptosisDecreased intraovarian receptors for estrogen receptor -a- or insulin like growth factor 1, increased leptin levels, or direct infrared redaction select ovarian cells. *Intrauterine and early child enviroment contribute to childhood development. *Weight gain aggravates symptoms and women will have an increased leptin level. *Leptin levels are increased in thin women as well *Leptin influences the hypothalamic pulsatility of GNRH and interaction with HPO. *Dysfunction in ovarian follicle development results from inappropriate gondatropin secretes and triggersthe beginning ofanovulation. *FSH is low and LH are high. *Persistent LH elevation causes an increase in androgens *DHEA (in adrenal glands and testosterone). And Androstenedione and dhea in the ovary. *Characterized by excessive levels of androgen and estrogen. -increased androgen contributes to a premature follicular failure (anovulation). -Persistent anovulation causes the pearly white smooth capsules (polycystic ovaries). -Thickening of the tunica, increased cortical stromal thickening, and hyperplasia. -**Women with PCOS 3 x greater of developing uterine cancer.Clinical Manifestations: *Appear within 2 years of puberty. *May not present until normal menstrual function or pregnancy. *Obese *Anovulation, hyperandrogenism, insulin resistance *infertility, hirsutism, acne, dysfunctional bleeding. *More likely to experience sleep apnea. Evaluation and Treatment:*dx is made based on androgen excess, chronic anovulation, and sonographic evidence of polycystic ovaries. *Must have 2 -3 of these. *Impaired glucose tolerance test isrecommended *Goals are to suppress androgen, instituting menstruation, restore fertility, and reduce endocrine disturbance. **FIRST LINE TREATMENT= COMBINED ORAL CONTRACEPTIVES** -This helps to initiate regular menses. -Lifestyle modifications= exercise and weight loss. --Insulin resistance= metformin -If pregnancy is not desired- progesterone therapy is important to oppose estrogen effects on the endometrium to help monthly bleeding. **FOR OBESE WOMEN LIFESTYLE MODIFICATIONS ARE FIRST LINE** -CLOMIPHENE CITRATE CAN BE USED TO FACILITATE OVULATION* Testicular cancer & Risk factors Highly treatable, usually curable cancer most often develops in young and middle aged men. Rare, but most common form of cancer between young men 15-35. More common on R side than left. Germ cell tumors arising from male gametes: seminomans and nonseminomas. Seminomas are most common, least aggressive. Nonseminomas include embryonal carcinomas, teratomas, and choriocarcinomas, mostaggressive but rare. Neoplasm cause is unknown. Genetic predisposition is suggested d/t incidence in brothers, identical twins and close male relatives. Risk factors: cryptochordism- neoplasms develop more commonly in contralateral testis. Abnormaltesticular development, HIV and AIDS, Klinefelter syndrome, and hx of testicular cancer. Symptoms that require evaluation for Breast CancerClinical manifestation Pathophysiology Chest pain Metastasisto lung Dilated blood vessels Obstruction of venous return by fast growing tumor Dimpling of skin Can occur with invasion of dermal lymphatics because of retraction of cooper ligament Edeme of arm Local inflammation of lymphatic obstruction Hemorrhage Erosion of blood vessels Local pain Local obstruction by tumor Nipple/areolar eczema Paget disease Nipple discharge in a nonlactating woman Spontaneous and intermittent d/c caused by tumor obstruction Nipple retraction Shortening of mammary ducts Pitting of the skin Obstruction of subq lymphatics, resulting in fluid accumulation Reddened skin, local tenderness, warmth Inflammation Skin retraction Involvement of suspensory ligaments Ulceration Tumor necrosis Signs of premenstrual dysphoric disorder (PMDD) • The cyclic recurrence (in the luteal phase of the menstrual cycle) of distressing physical, physical, psychologic, or behavioral changes that impair interpersonal relationships or interfere with usualactivities. • Neurotransmitters, GABA, and noradrenaline may have mediating or moderating roles on symptom manifestation. These neurotransmitters have demonstrated interactions with estrogen and progesterone and all of these are neuroactive with known mood and behavior effects, including negative mood, irritability, aggression, and impulse control. • Symptoms usually appear a week before menstruation and end a few days after your period starts. When this happens, some women have trouble functioning at home, at work and in relationships during this time. • Women show symptoms of irritability, nervousness, anger, insomnia, anxiety, paranoia, trouble sleeping, N&V, headaches, fainting. Dysfunctional uterine bleeding • DUB is heavy or irregular bleeding in the absence of organic disease, such as submucous fibroids, endometrial polyps, blood dyscrasias, pregnancy, infection, or systemic disease. • This accounts for 70% of all hysterectomies and almost all endometrial ablation procedures. • Caused by the lack of ovulation. Normal periods result in the complex interplay of the hypothalamus, the pituitary, the ovary, and the uterine endometrium. Disruptions in this system can affect the amount and structure of the uterine endometrium causing it to shed irregularly orheavily. • Occurs more in women ages 40-50 because they are at the end of their reproductive years andare more likely to ovulate irregularly. • PCOS can lead to irregular heavy uterine bleeding• The formation of the follicle and its rupture release an ovum which is a very important part of the menstrual cycle. As the follicles forms it produces estrogen. Following ovulations, the remainportions of the follicle, known as the corpus luteum, releases progesterone. Progesterone acts on the endometrium to limit growth and causes, which helps limit bleeding during endometrial shedding. • If a follicle forms but never releases in the ovum, the follicle may continue to produce estrogen which causes thickening of the endometrium. This causes the endometrium to be able to shed ina predictable fashion. Pathophysiology of prostate cancer • More than 95% of prostatic neoplasms are adenocarcinomas and most occur in the periphery of the prostate.Prostatic adenocarcinoma is a heterogenous group of tumors. • Estrogen receptor -a has shown evidence to participate in the pathogenesis of prostate cancer. • This ER-a receptor leads to inflammation, proliferation and development of premalignant lesions. ER-B leads toantiproliferative, anti-inflammatory, and potentially anticarcinogenic effect that tries to balance ER-a and the androgens involved. • Increased expression of ER-a has been shown to increase prostate cancer progression, metastasis. • The prostate glandsrequire male hormones, known as androgens, to work properly. Androgensinclude testosterone,which is made in the testes, dehydroepiandrosterone, made in the adrenal glands; and dihydrotestosterone, which is converted from testosterone within the prostate itself. Androgens are also responsible for secondary sex characteristics such as facial hair and increased muscle mass. Prostate cancer is classified as an adenocarcinoma, or glandular cancer, that begins when normal semen- screening prostate gland cells mutate into cancer cells. The region of prostate gland where the adenocarcinoma is most common isthe peripheral zone. Initially, small clumps of cancer cells remain confined to otherwise normal prostate glands, a condition known as carcinoma in situ or prostate intraepithelial neoplasia (PIN). Although there is no proof that PIN is a precursor, it is closely associated with cancer. Overtime, these cancer cells begin to multiply and spread to the surrounding prostate tissue (the stroma) forming a tumor. Eventually, the tumor may grow large enough to invade nearby organs such as the seminal vesicles, or the rectum, or the tumor cells may develop the ability to travel in the blood stream and lymphatic system HPV and development of cervical cancer • Cervical cancer is almost exclusively caused by cervical human papillomavirus (HPV) infection. • Infection with “high-risk” (oncogenic) types of HPV (predominately 16 and 18) is necessary precursor to development of precancerous cell changes, known as dysplasia of the cervix thatleads to invasive cancer. • With these cell changes, they can be detected noninvasively through examination of the cervicalcells. The cells can be destroyed to prevent cancer development if dysplasia can be detected early. • The line where two cell types meet, known as the transformation zone, is very vulnerable to oncogenic effects of HPV. In girls and young woman, a large portion of the cervix is covered withcolumnar epithelium, a condition called squamous metaplasia. As women age the transformation zone moves as the squamous epithelium covers the surface of the cervix. The younger the woman is when she contracts HPV, the more sensitive cervical cells are exposed. • Vaccinating against HPV early before the initiate of sexual activity is important • Normally, women can clear most HPV infections by the immune system. But some cannot which contributes to the develop of cervical cancer. ENDOCRINE Body’s process for adapting to high hormone levels: Negative-feedback systems are important in maintaining hormoneconcentrations within physiologic ranges. The lack of negative-feedback inhibition on hormonal release often results inpathologic conditions. hormonal imbalances and related conditions are caused by excessive hormone production, which is the result of failure to “turn off” the system. High concentrations of hormone decrease the number of receptors, called down-regulation. Thus the cell can adjust its sensitivity to the concentration of the signaling hormone. The receptors on the plasma membrane are continuously synthesized and degraded, so that changes in receptor concentration may occur within hours. Various physiochemical conditions also can affect both the receptor number and the affinity of the hormone for its receptor. Some of these physiochemical conditions arethe fluidity and structure of the plasma membrane, pH, temperature, ion concentration, diet, and the presence of other Cushing’s Syndrome: overproduction of anterior pituitary ACTH by a pituitary adenoma; chronic excess cortisol (at any age) With ACTH-dependent hypercortisolism, the excess ACTH stimulates excess production of cortisol and there isloss of feedback control of ACTH secretion. Whatever the cause, two observations consistently apply to individuals with Cushing syndrome: (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. Exogenous result from administration of glucocorticoids. Endogenous either corticotropin dependent (most common & caused by ACTH-secreting pituitary tumor) or corticotropin independent (usually caused by an adrenal cortical tumor). Clinical features: weight gain in trunk, face, and cervical areas. “truncal obesity, moon face, buffalo hump”. Transient weight gain from sodium and water retention may be present because of the mineralocorticoid effects of cortisol, exhibited when cortisol is present in high levels. Glucose intolerance occurs because of cortisol-induced insulin resistance and increased gluconeogenesis and glycogen storage by the liver. Protein wasting is caused by the catabolic effects of cortisol on peripheral tissues. 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 the protein matrix and increases in bone resorption lead to osteoporosis and can result in pathologic fractures, vertebralcompression fractures, bone and back pain, kyphosis, and reduced height. Hypercalciuria may result in renal stones, which are experienced by approximately 20% of individuals with this disease. Loss of collagen also leads to thin, weakened integumentary tissues through which capillaries are more visible; the tissues are easily stretched by adipose deposits.Hypoparathyroidism CX: low PTH levels. Usually caused by damage to the PT glands during thyroid surgery & anatomic proximity of PT glands to thyroid. Assoc c genetic syndromes, including familial HX & DiGeorge syndrome (velocardiofacial syndrome) & idiopathic or autoimmune form of the disease. Low mag can cause a decrease of PTH secretion & function Lab results point to primary hypothyroidism: caused by a deficient production of TH by the thyroid gland. 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. Primary hypothyroidism DX: is made by documentation of the clinical symptoms of hypothyroidism, and by measurement of increased levels of TSH and decreased levels of TH (total T3 and both total and free T4). When hypothyroidism is caused by pituitary deficiencies, serum TSH levels are decreased or are inappropriately normal in the face of low levels of TH. Pathophysiology of thyroid storm: (Thyrotoxic Crisis) rare but dangerous worsening of thyrotoxic state. Death within 48hr without treatment. Occurs in individuals who have undiagnosed or partially treated severe hyperthyroidism & subjected to excessive stress. CX: infection, pulmonary/cardiac disorder, trauma, burns, seizures, SX (esp thyroid surgery), OB complications, emotional distress, or dialysis. Symptoms: ↑thyroxine action(T4) & triiodothyronine (T3) exceeding metabolic demands. Signs of thyrotoxicosis: Excessive concentrations of thyroid hormones. Symptoms: ↑metabolic rate, hyperthermia (heat intolerance), tachycardia (esp atrial tachydysrhythmias), high-output HF; agitation or delirium, goiter, reproductive disorders, excessive sweating, nausea, vomiting, diarrhea (n/v/d=fluid volume depletion) Dermatomes NEUROSpecific 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. Substance release at synapse The region between adjacent neurons is called a synapse. Impulses are transmitted across the synapse by chemical and electrical conduction. The conducting substance is called a neurotransmitter and it is often formed in the neuron, transported to the synaptic knobs (boutons) of the presynaptic neuron’s axon, and stored in synaptic vesicles within the knobs. Action potentials in the presynaptic neuron cause the synaptic vesicles to release their neurotransmitter(s) through the plasma membrane into the synaptic cleft (the space between the neurons), where they bind to specific neurotransmitter (protein) receptor sites on the plasma membrane of the postsynaptic neuron Spondylolysis Degenerative process of the vertebral column and associated with soft tissue. Characterized by a structural defect of spine involving lamina or neural arch of vertebra. Most common site affected is the lumbar spine. This defect occurs in the portion of the lamina between the superior and inferior articular facets called the pars interarticularis. Mechanical pressure may cause a forward displacement of the deficient vertebra called spondylolisthesis. Heredity plays a significant role, and spondylolysis is associated with an increased incidence of other congenital spinal defects. As a result of torsional and rotational stress, “microfractures” occur at the affected site and eventually cause dissolution of the pars interarticularis. Location of motor and sensory areas of the brain The special senses of vision, hearing, touch, smell, and taste are the means by which individuals perceive stimuli that are essential for interacting with the environment. Special sensory receptors are connected to specific areas of the brain through the afferent pathways of the peripheral and central nervous system (CNS). Each of the special senses thus involves a connected system of organs and tissues that receives stimuli and sends sensory messages to areas of the CNS, where they are processed and guide behavior. Patho of cerebral infarction and excitotoxins results when an area of the brain loses supply and becomes ischemic because of vascular occlusion embolic or thrombotic. 1. Abrupt vascular occlusion (embolus) 2. Gradual vessel occlusion (atheroma) 3. Vessels thats are stenosed but not completely occluded (atherosclerosis/hypotension) are the dominant underlying processes (Textbook)Release of excitatory neurotransmitters after brain injury causes secondary neural injury known as excitotocity. (Workbook pg. 86)Agnosia Impaired/defect of recognition and may be tactile, visual or auditory stimuli. Caused by dysfunction in the primary sensory area or the interpretive areas of the cerebral cortex Accumulation of blood in a subarachnoid hemorrhage (SAH) Hemorrhage from a defective or injured vasculature into the subarachnoid space. The blood is extremely irritating to the meningeal and other neural tissues and so produces an inflammation & impairs circulation of cerebrospinal fluid. Additionally, the blood coats nerve roots, clogs arachnoid granulations (impairing CSF reabsorption), and clogs foramina within the ventricular system (impairing CSF circulation). ICP immediately increases to almost diastolic levels within 10 mins. ICP returns to near baseline in about 10 minutes. Cerebral blood flow and cerebral perfusion pressure (CPP) decrease. The expanding hematoma acts like a space-occupying lesion, compressing and displacing brain tissue. Granulation tissue is formed and scarring of the meninges, with resulting impairment of CSF reabsorption and secondary hydrocephalus, often results. Most common cause of meningitis Meningitis is inflammation of the brain or spinal cord. Infectious meningitis may be caused by bacteria, viruses, fungi, parasites, or toxins. Bacterial & viral meningitis is the most common. Bacterial infection may be due to Neisseria meningitis, Haemophilus influenza, streptococcus pneumoniae, or Escherichia coli. Sometimes, no causative organisms can be found. In most patients, the infections that cause meningitis is secondary to another bacterial infection, such as bacteremia. Respiratory infections increase the risk. It may follow a skull fracture, a penetrating head wound, lumbar puncture, ventricular shunting, or neuro procedure. Viral meningitis aka aseptic viral meningitis may result from a direct infection or secondary to disease such as mumps, herpes, measles, or leukemia. (Textbook) GENITOURINARY Diet and prevention of prostate cancer Evidence exists that dietary factors play a role in prostate cancer development. The lack of biomarkers for certain nutrients, difficulty measuring and quantifying diet, and limitation of clinical trials all make the understanding of the relationship difficult.Dietary intake effects the signaling pathways, hormones, oxidative stress, and reactive oxygen species (RDS). Nutrients most associated with cancer are carotenoids, fat, vit E, vit D/calcium, and selenium. Less studied are isoflavones, curcumin, lycopene, zinc, green tea, omega 3 polyunsaturated fats, and sulforaphane. The hypothesis for MEAL is that a change in diet of higher intake of animal products to vegetables and fruits will slow the progression of the indolent to the aggressive form of prostate cancer. As adipose tissue is increasingly being regarded as hormonally active tissue, high body fat and obesity need in-depth exploration to understand the associated risk of prostate problems Obesity has a positive association with aggressive prostate cancer and worse outcomes but a negative association with indolent (slow growing) prostate cancer. Adipose tissue is considered hormonally active tissue. It effects circulating bio-active messengers therefore influences the risk of developing prostate problems. - Consumption of excess calories increases the need for insulin and IGF-1 which is a powerful carcinogenic. Total fat intake, animal and saturated fat, red meat and dairy all increase the risk for prostate cancerHigh calorie and high carb diet increase the risk for prostate cancer Monosaturated fats decrease the risk for prostate cancer. Linoteic acid and high ratios of omega 6/omega 3 are all proinflammatories - This promotes cell proliferation and angiogenesis (new flood vessel formation) but inhibits apoptosis (cell death). Cooking meat at high temperatures produces heterocyclic amines and aromatic hydrocarbons. Both are carcinogenic. Vitamin E is a fat-soluble vitamin found in vegetable oils, nuts, and egg yolks. It is a intracellular antioxidant which inhibits peroxidation and DNA change. Studies have shown it reduces incidence of prostate CA in smokers, kills cancer cells, and inhibits androgen receptors. Selenium is a trace mineral found in food. Essential for functioning of antioxidant enzymes and proteins in body. It inhibits cellproliferation, kills prostate cells, stops angiogenesis, and sensitizes cells for radiation-induced killing. It is capable of activating intrinsic and extrinsic pathways for apoptosis. Vitamin E in combination with selenium does not reduce cancer incidence or provide any type of defense. Separately theydecrease the risk but together they do not. Vitamin D/Zinc/Tomatoes/Tomato products- may be important but lack data Soy will inhibit cell proliferation and angiogenesis but can also reduce the PSA and androgen receptor level Vegetablesincluding broccoli, cabbage, cauliflower, brussel sprouts, and turnips all protect against prostate cancer. However, broccoli will decrease the growth of cancer cells. Green tea contains polyphenols and has been associated with decrease incidence of several cancers including prostate cancer.It helps improve antioxidant potential, binds directly to carcinogens, inhibits IGF-1 which results in decreased development and progression of prostate cancer. Black tea also decreases the risk for prostate cancer. As you can see multiple signaling pathways such as proliferation, angiogenesis, and apoptosis, are all involved in the development and progression of prostate cancer and closely related to dietary factors. Impact of BPH on the Urinary System Benign Prostate Hyperplasia is an enlargement of the prostate gland. As the prostatic tissue enlarges is compresses the urethra, where it passes through the prostate, causing lower urinary tract symptoms. At birth the gland is pea sized and growth is gradual until puberty. Development continues until 3rd decade of life. Benignhyperplasia begins around age 40-45 and continues until death.Bladder outflow obstruction occurs as the hypertrophy continues and the urethra is compressed. - Symptoms sometimes called spectrum of lower urinary tract symptoms (LUTS) are: urge to urinate often, delay instarting urination, decrease in force of stream. As this progresses over years the bladder cannot empty leading to long term urinary retention. The overload of volume may cause “overflow incontinence” if intra-abdominal pressure occurs. The stream force is significantly reduced and much moretime is required to initiate and complete urination at this stage. Hematuria, bladder or kidney infection, bladder calculi, acute urinary retention hydroureter, hydronephrosis, and renalinsufficiency are other common complication of BPH. Sometimes the initial signs may be uremia and renal failure. The palpated prostate does not always reflect the degree of BPH because a large portion of enlargement is intravesicular. On digital rectal exam the prostate may be soft or firm enlargement with smooth muscle surface. Asymmetry is common. Digital exam and PSA are used to determine BPH. Cannot use PSA only because it is also elevated in prostate cancer. If enlargement is noted and symptoms are severe a transrectal ultrasound is performed to determine residual urine. BPH can be treated successfully with drugs that relax the smooth muscle of the bladder and prostate (adrenergic blockers). Other medications can block androgens at the cellular level and cause the prostate gland to shrink (antiandrogen agents). Surgical removal of the hyperplastic tissue to prevent the serious consequences of urethral obstruction is an option if medication is ineffective. If medication is ineffective and an individual cannot tolerate surgery a permanent indwelling catheter is placed. GENETICS The role of DNA in genetics – Genes are composed of DNA Chromosomes are composed of many genes = basic units of inheritance, carrying information for synthesis of specific proteins. Genes are composed of the chemical deoxyribonucleic acid (DNA). the replication of DNA occurs a finite number of times per chromosome due to the presence of telomeres= short nt/protein segments on the ends of chromosome arms that protect DNA and prevent chromosome fusionsduring the cell division cycle. Telomeres gradually erode away with each cell division until DNA unravels and chromosome disintegrates. This is an important way to help eliminate chromosomes (and cells) carrying accumulated undesirable mutations! DNA is the genetic basis of life = the “blueprint of life" Transcription –Transcription is the process by which DNA specifies a sequence of mRNA.RNA is synthesized using DNA as the template via the process of transcription. However, unlike the replication process where an exact copy is made of all the DNA within the nucleus, 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 genes that make up our chromosomes.Several 100-1000 DNA nt comprise a gene = information for synthesis of a specific protein. Effects of genetic mutations – Changes in the DNA can also occur as the result of a mutation = inheritable alteration of genetic material. Mutations can occur either spontaneously or as a result of exposure to external mutagens such as radiation, chemicals, and even certain infectious agents (eg – viruses). Mutations in individual genes can also result in single gene disorders. (e.g. sickle cell anemia, cystic fibrosis, hemophilia) Depending on the location of the mutated gene, and whether or not it is a dominant or recessive allele, disorders are classified as: autosomal dominant, autosomal recessive, sex-linked 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. Down syndrome/ Trisomy: Trisomy is a type of aneuploidy in which one chromosome is present in three copies in somatic cells. A partial trisomy is one in which only part of a chromosome is present in three copies. Down Syndrome- pg. 146 – aneuploidy in an autosome is trisomy of the 21 chromosome, low nasal bridge, epicanthal folds, protruding tongue, flat low set ears. Down syndrome, a trisomy of chromosome 21, is the most well-known disease caused by a chromosome aberration. It affects 1 in 800 live births and is much more likely to occur in the offspring of women older than 35years of age. • Failure of the homologous chromosome pairs to separate during meiosis is called nondisjunction and also results inabnormalities of chromosome number. • Aneuploidy: gamete cell that does not have 23 chromosomes so resulting embryo will have fewer or extra chromosome (not all abnormal chromosomes may even survive). Cells with fewer than normal chromosomes are lesslikely to survive than cells that have more than normal chromosomes. • Aneuoploidy of sex chromosomes results in conditions: o Klinefeiter symdrome (XXY) o Turner syndrome (XO) • Aneuoploidy of autosomal chromosomes results in conditions such as: o Down syndrome (trisomy 21) o Or Edwards syndrome (trisomy 18)Aneuploid cells are those that do not contain a multiple of 23 chromosomes. An aneuploid cell containing three copies of one chromosome is said to be trisomic (a condition termed trisomy)o The only trisomies frequent in live births are trisomy 13, 18 and 21. Fetuses with other trisomies do not survive to term, trisomy 16 most common trisomy among abortuses. o Partial trisomy: extra portion of a chromosome is present in each cell. o Most well-known example of aneuploidy in an autosome is trisomy 21= Down Syndrome o IQs between 25-70 Facial appearance: low nasal bridge, epicanthal folds, protruding tongue, flat low-set ears, poor muscle tone. Congenital heart defects are common with inability to fight off respiratory tract infections and increased susceptibility to leukemia. o After age of 40, develop symptoms similar to Alzheimer disease because gene of Alzheimer disease is located on chromosome 21. o 97% of Down Syndrome cases are caused by nondisjunction during the formation of one of the parents games or earlyembryonic development. Remaining 3% is translocation. 90-95%, nondisjunction occurs in formation of mothers egg cell. o 1% of individuals with ds are known to be mosaics, the effects of the trisomic cells are attenuated and symptoms areless severe. Klinefelter syndrome: smallness of testes with fibrosis and hyalinization of seminiferous tubules, variable degrees of masculinization, azoospermia, infertility, and increased levels of urinary gonadotropins; associatedtypically with an XXY chromosome complement although variants include XXYY, XXXY, and XXXXY - Diagnosed in individuals with at least 2 X chromosomes and a Y chromosome - Individuals have a male appearance - Usually sterile - About half develop female-like breasts (condition called gynecomastia_ - Testes are small, body hair is sparse, voice is often high pitched, stature is elevated, and a moderate degree of mental impairment is present - 1 in 1000 male births - About 2/3rd are caused by nondisjunction of the x chromosomes in the mother and frequency rises with increasedmaternal age - XXXY and XXXXY karyotypes are also considered to have Klinefelter syndrome, the degree of physical and mentalimpairment increases with each additional X chromosome - Those with an extra Y chromosome produce the 47,XYY karyotype: these individuals are taller than average, and have a 10-15 point reduction in IQ; condition causes few serious physical problems but evidence shows increased behavioral disorders Duchenne muscular dystrophy Duchenne muscular dystrophy, is the most common of the muscular dystrophies. The X-linked inherited type of Duchenne muscular dystrophy is thought to be caused by deletion of a segment of deoxyribonucleic acid (DNA) or a single-gene defect on the short arm of the X chromosome. A protein encoded by the Duchenne muscular dystrophy gene, called dystrophin, has been identified. Dystrophin is present in normal muscle cells and absent in Duchenne muscular dystrophy (it is present in reduced amounts in Becker dystrophy). Dystrophin mediates anchorage of the actin cytoskeleton of skeletal muscle fibers to the basement membrane through a membrane glycoprotein complex. The complete lack of dystrophin in severe Duchenne dystrophy means that poorly anchored fibers tear themselves apart under the repeated stress of contraction. Free calcium then enters the muscle cells, causing cell death and fiber necrosis. An X-linked genetic disorder in which fat and fibrous tissue infiltrate and weaken muscle tissues such as in the legs and pelvis, lungs, and heart; usually results in death before adulthood. - X-linked recessive disorder - 1 in 3500 males - Progressive muscle degeneration; affected individuals are unable to walk by the age 10 to 12 - Disease affects the heart and respiratory muscles, and death caused by respiratory or cardiac failure usually occurs before the age of 20- Dystrophin: muscle protein o Dystrophin plays an important role in maintaining the structural integrity of muscle cells: one end of the protein binds to actin filaments in the cytoplasm of the cell, and other end binds to a group of membrane-spanning proteins known as dystrophin-associated glycoproteins o When Dystrophin is absent, as in individuals with DMD, the muscle cell cannot survive, and muscledeterioration ensues - Most cases of DMD is caused by deletions of portions of the DMD genes Neurofibromatosis Neurofibromatosis (NF) is an inherited autosomal dominant disorder accounting for 5% of allneuromas and is divided into two types: NF1 and NF2, which are clinically and genetically distinct disorders. The gene products are neurofibromin and merlin (schwannomin), both of which are thought to be tumor suppressors - Inherited autosomal dominant disorder accounting for 5% of all neuromas and is divided into two types: NF1 and NF2 - NF1 is associated with cutaneous manifestations, iris hamartomas, and tumors primarily involving the peripheral nervous systems and occasionally the CNS - NF2 is associated with cataracts, hearing loss, and tumors primarily in the CNS; most commonly vestibular schwannoma and meningioma - The tumors most commonly affect people older than 50, women more than men - The tumor originates most commonly just distal to the junction between the nerve roots and the brainstem o As the tumor grows, it extends into he posterior fossa to occupy the cerebropontine angle and compressadjacent nerves o Eventually, the brainstem is displaced, and the CSF flow is obstructed - Clinical manifestations: headache, tinnitus, hearing loss, impaired balance, unsteady gait, facial pain, and loss of facial sensations o Later, vertigo with nausea, vomiting, a sense of pressure in the ear, and moderate to severe unsteadinesswith rapid position changes may appear - CT or MRI help diagnose o Posterior fossa dye studies maybe required - Treatment o Surgical excision o Radiotherapy of the neuroma diseases that have multifactorial traits/multifactorial inheritance - When environmental factors are also believed to cause variation in the trait, which is usually the case, the term multifactorial trait is used. Blood pressure is another example of a multifactorial trait. A correlation exists between parents’ blood pressures (systolic and diastolic) and those of their children. The evidence is good that this correlation is partially caused by genes, but blood pressure is also influenced by environmental factors, such as diet, exercise, and stress. Two goalsof genetic research are the identification and measurement of the relative roles of genes and environment in the causation of multifactorial diseases. - Hypertension, dementia, coronary heart disease, stroke, diabetes mellitus (1 and 2), and some cancers - Autism, pyloric stenosis, cleft lip, cleft palate, neural tube defects, clubfoot, and congenital heart disease - Definition: when genes +environmental factors cause a disease - Read pages 165-168 - Criteria used to define multifactorial inheritance o The recurrence risk becomes higher if more than one family member is affected o If the expression of the disease in a proband is more severe, the recurrence risk is higher o The recurrence risk is higher if the proband is of the less commonly affected sex o The recurrence risk for the disease usually decreases rapidly in more remotely related relativeso If the prevalence of the disease in a population is f, the risk for offspring and siblings of probands is approx.square root of f What is multifactorial inheritance? • Multifactorial inheritance means that "many factors" are involved in causing a birth defect. The factors are usually both genetic and environmental, where a combination of genes from both parents, in addition to unknown environmental factors, produce the trait or condition. Often one gender is affected more frequently than the other inmultifactorial traits. There appears to be a different "threshold of expression", which means that one gender is more likely to show the problem over the other gender. For example, hip dysplasia is nine times more common in females than males. Multifactorial traits do recur in families, because they are partly caused by genes. The chance for a multifactorial trait or condition to happen again depends upon how closely the family member with the trait isrelated to you. • Some disorders, such as sickle cell disease and cystic fibrosis, are caused by mutations in a single gene. The causes of many other disorders, however, are much more complex. Common medical problems such as heart disease, type 2 diabetes, and obesity do not have a single genetic cause—they are likely associated with the effects of multiple genes (polygenic) in combination with lifestyle and environmental factors. Conditions caused by many contributing factors are called complex or multifactorial disorders. MUSCULOSKELETAL Ions that initiate muscle contraction: (page 1533) Calcium is the main ion that initiates muscle contraction, 4-step process: excitation, coupling, contraction, and relaxation. Initial contraction process is the excitation-contraction coupling (ECC) series involving the electrical properties of all cells and the movement of ions across the plasma membrane.Specific intracellular receptors with skeletal muscle sarcoplasmic reticulum, called ryanodine receptors (RyRs) are primary ion channels that control calcium release. RyRs are the largest known channels, allowing rapid movement of calcium. RyRs1 is predominantly found in skeletal muscle. Excitation – the first step of muscle contraction, begins with the spread of an action potential from the nerve terminal to the neuromuscular junction. The rapid depolarization of the membrane initiates an electrical impulse in the muscle fiber membrane called the muscle fiber action potential. The action potential spreads to the T-tubules. An action potential triggers receptors in the T-tubule wall, opening the RyR channels, releasing calcium from the sarcoplasmic reticulum. The second stage, Coupling, consists of the migration of calcium ions to the myofilaments. Calcium affects troponin and tropomyosin, muscle proteins that bind with actin when the muscle is at rest. In the presence of calcium, both of these proteins are attracted to calcium ions, leaving actin free to bind with myosin. Contraction begins as the calcium ions combine with troponin, a reaction that overcomes the inhibitory function of the troponin-tropomyosin system (troponin is attached to the protein tropomyosin and lies within the groove between actin filaments in muscle tissue. In a relaxed muscle, tropomyosin blocks the attachment site for the myosin crossbridge, preventing contraction). The thin filament actin then slides toward the thick filament myosin. The two ends of the myofibril shorten after contraction when the myosin heads attach to the actin molecules, forming a crossbridge that constitutes an actin-myosin complex. ATP, located on the actin-myosin complex, is released when the cross-bridges attach. *the useful distance of contraction of a skeletal muscle is approximately 25-35% of the muscles length. The last step, Relaxation, begins as the sarcoplasmic reticulum absorbs the calcium molecules, removing them from interaction with troponin. Calcium is pumped back into the sarcoplasmic reticulum by means of an active transport process. The cross-bridges detach, andthe sarcomere lengthens. Growth of long bones in children: 1592 Long bones of the body include: clavicles, humeri, radii, ulnae, metacarpals, femurs, tibiae, fibulae, metatarsals, and phalanges. Endochondral formation of bone is the development of new bone from cartilage. First, mesenchymal tissue forms a cartilage anlage, which defines the shape of the bone by 6 weeks of gestation. Blood vessel invasion to inside the anlage brings osteoprogenitor cells leading to primary centers of calcification by 8 weeks. Endochondral bone formation begins in the outer layer of the cartilage model, which consists of a layer of dense connective tissue called perichondrium. The perichondrium contains cells that develop into osteoblasts, forming a collar of bone, termed the periosteal collar, around the cartilage model. Cartilage enclosed within the periosteal collar degenerates, and capillaries from outside the perichondrium invade the degenerating cartilage cells, carrying with them osteoblast precursors from the inner layer of the perichondrium and osteoclast precursors from the blood itself. Endochondral bone formation progresses at the primary center of ossification in the middle of the cartilage model and extends toward either end of the developing bone. At the same time, the periosteal collar thickens and becomes wider toward the epiphyses. By the end of gestation secondary centers of ossification begin to lay down bone at both ends of the cartilage model. Here, too, cartilage within the periosteal collar degenerates, and blood vessels grow inward, delivering bone cell precursors. Once the osteoblasts begin to secrete osteoid, ossification spreads from the secondary centers in all directions until all the cartilage within the model is replaced by bone. Two regions of cartilage remain at the ends of long bones: (1) articular cartilage over the free ends of the bone, and (2) the physeal plate, a layer of cartilage between the metaphysis and epiphysis. The physeal plate retains the ability to form and calcify new cartilage and deposit bone until the skeleton matures approximately 1 year after sexual maturity (11-15 yrs. in females, 15-18 yrs. in males). Bones belonging to the appendicular skeleton: pg. 1519 Appendicular skeleton has 126 bones and supports the appendages of the body. Pectoral Girdle – total of 4 bones Clavicle (2) - braces the shoulder joint against the sternum, it articulates with the scapula Scapula (2) - flat, triangular bones, lateral angle articulates with the head of the humerus and forms the shoulder joint Upper Extremities – total of 60 bonesHumerus (2)- only long bone of the arm, articulates at the proximal end with the glenoid cavity of the scapulaRadius (2) – the lateral forearm bone. Proximal end articulates with the capitulum of the humerus, distal end widens and forms primary articulation with proximal carpal bones. Ulna (2) – medial bone of the forearm. Proximal end forms the olecranon process (the point of the elbow) Carpals (16) – (wrist) each bone has a unique shape and name. Metacarpals (10) – (palm) associated with a number starting with the thumb on lateral side Phalanges (28) – (fingers) thumb has two phalanges and each finger has three Pelvic Girdle– total of 2 bones Coxal (hip) bone (2) – results from the fusion of three bones Ilium, Ischium, and Pubis Ilium – large flaring bone that forms the superior part of hip. Upper edge is the iliac crest, crest ends anteriorly in the anterior superior iliac spine (can be felt easily in thin people). Ischium – inferior part of coxal bone. Inferior surface hasroughened part called the ischial tuberosity, they are the parts of the hip bones that press against objects you sit on. Pubis – (pubic bone) most anterior part of hip. **the ilium, ischium and pubis together form a deep socket called acetabulum which articulates with the head of the femur Lower Extremities – total of 60 bones Femur (2) – only long bone of the thigh, heaviest and strongest bone in the body. Proximal end has ball like head (greater trochanter) that fits into the acetabulum of the coxal (hip) bone. Patella (2) – (kneecap) small, freestanding bone that rests between the femur and tibia. Femur has a dedicated groove which the kneecap slides. Tibia (2) – (shinbone) is the larger, medial bone of lower leg. Anterior surface forms an anterior border that can be easily felt, distally there is a process called the medial malleolus that forms the inner bulge of the ankle. Fibula (2) – long, slender bone lateral to the tibia. Distal part forms the lateral malleolus (outer part of ankle) Tarsals (14) – 2 notable tarsal bones are the calcaneus (heel bone), and the talus which articulates with the tibia to form hinge- like ankle joint Metatarsals (10) - form the sole of the foot Phalanges (28) – similar to phalanges of hand, great toe, like thumb, has only two phalanges.IMMUNITY How vaccines are performed – A vaccine is a biological preparation that provides active acquired immunity to a particular disease. A vaccine typically contains an agent that resembles a disease-causing microorganism and is often made from weakened or killed forms of the microbe, its toxins, or one of its surface proteins. Vaccines are like a training course for the immune system. They prepare the body to fight disease without exposing it to disease symptoms. When foreign invaders such as bacteria or viruses enter the body, immune cells called lymphocytes respond by producing antibodies, which are protein molecules. Antigens are present in extremely small quantities to elicit an immune response through a vaccine. The most common routes of administration are intravenous, intraperitoneal, subcutaneous, intranasal, and oral. Each route stimulates a different set of lymphocyte-containing tissues and therefore results in the induction of different types of cell-mediated or humoral immune responses. Vaccines are considered nonimmunogenic. Populations are risk for getting systematic fungal infections and parasitic infections- In immunocompromised individuals, particularly those with diminished levels of neutrophils (neutropenia), fungal infections may occur. Candida isthe most common fungal infection in people with cancer (particularly acute leukemia and other hematologic cancers) transplantation (bone marrow and solid organ), and HIV/AIDS. Almost 90% of people with AIDS have candida at least one time (usually thrush or vaginitis) because of their decreased number of neutrophils. Invasive candidiasis may also be secondary to indwelling catheters, intravenous lines, or peritoneal dialysis which provided direct entrance into the blood. Disseminated candidiasis may involve several internal organs, including abscesses in the kidney, brain, liver, and heart. It is characterized by a persistent fever and gram-negative shock like symptoms (hypotension, tachycardia), DIC, and death. The mortality rates of sepsis or disseminated candidiasis are in the range of 30-40%. Parasitic infections are uncommon in the United States, with significant mortality and morbidity of individuals in developing countries. Malaria is most common in Africa. Systematic manifestations of infection – Systematic infection is the term used to describe an infection that is circulating in the blood. This means it affects the entire body. Signs/symptoms of this can be fever, tachycardia, hypotension, septic shock, toxic shock, hypovolemia, respiratory alkalosis, and hyperventilation, neutropenia, thrombocytopenia, and DIC. Alterations in sensorium may occur in severe infection and may cause anxiety, confusion, delirium, stupor, seizures, and coma. Mechanism responsible for the increase in antimicrobial resistance worldwide – Antimicrobial resistance occurs naturally overtime, usually through genetics. However, the misuse and overuse of antimicrobials is accelerating this process. In many places antibiotics are overused and misused. Example of misuse include they are taken by people with viral infections such as the flu. Poor infection control, inadequate sanitary conditions and inappropriate food handling encourage the spread of antimicrobial resistance. Functions of normal body flora The normal microbiome provides protection by inhibiting colonization by pathogens and by releasing chemicals that prevent infection. Each surface including the skin, mucous membranes of the eyes, upper and lower GI, urethra and vagina are all colonized by combo of bacteria (mostly bacteria) and fungi that are unique to the particular location. The relationship betweenthis “good” bacteria and humans is both commensal (to the benefit of one organism without affecting the other) and mutualistic (to the benefit of both). Many of these microorganisms help digest fatty acids, large polysaccharides and other dietary substances. They also produce biotin and Vit K, assist in the absorption of various ions: such as calcium, iron and magnesium. These good bacteria compete with pathogens for nutrients and block attachment to the epithelium. They producechemicals (ammonia, phenols, and indoles). Treatment with broad spectrum abx can alter this normal flora, decreasing its protective activity, leading to overgrowth of yeast Candida Albicans or C Dif. The good flora trains the adaptive immune systemby growth of gutassociated lymphoid tissue (where cells of adaptive immunity reside). Desensitization therapy Also known as allergen Immunotherapy. This is where minute quantities of the allergen are injected in increasing doses over aprolonged period. The therapy may reduce the severity of the allergic reaction in the treated individual. This therapy is associated with a risk of systemic anaphylaxis, which can be life threatening. This approach works best for routine respiratory allergies and biting insect allergies (80-90% rate of desensitization over 5 years of treatment). The mechanisms by which desensitization occurs may be several, one of which isthe production of largeamounts os 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 the allergen is “neutralized” and is unable to bind with IgE on the mast cells. Desensitizationinjections may also stimulate the generation of clones of T- regulatory lymphocytes which inhibit hypersensitivity by suppressing the production of IgE and anti-inflammatory cytokines. Cells involved in the “left shift” in the WBC count differential -Neutrophil left shift and white blood cell (WBC) count are routine laboratory tests used to assess neutrophil state, which depends on supply from the bone marrow and consumption in the tissues Early in the response to infection or inflammation, immature forms of neutrophils will be seen. These are call Stab or Band cells. The presence of these immature cells is called a "shift to the left" and can be the earliest sign of a WBC response, even before the WBC becomes elevated. Forms of Immunity -Innate, native- natural immunity (non-specific)- First line - physical, mechanical and biochemical barriers. Epithelial barrier and inflammation confer innate resistance and protection. Skin, mucous membranes, stomach acid, oils on skin (Barriers). Second line - The inflammatory response (redness, swelling, heat and pain). Cells involved in the inflammatory response are Phagocytes (WBC-Leukocytes) and chemical mediators (leukotrienes and prostaglandins). -Adaptive, acquired immunity (specific)- Inflammation associated with infection initiates an adaptive response. Provides backup to second line of defense. Relatively slow to develop but has memory and more rapidly targets and eradicates a second infection with a disease-causing microorganism. Specialized WBCs- Lymphocytes B (humoral response) and T (cell-mediated response) cells. Long term memory response. Major histocompatibility class (MHC) I antigens (7th Edition, pg. 233-235, 244) Major histocompatibility class (MHC) I antigens are heterodimers composed of a large α-chain along with a smaller chain called β2-microglobulin. • Structure: single transmembrane chain (α) and β2-microglobulin. • Distribution: All nucleated cells and platelets • Presents: “Endogenous” antigens (8-10 amino acids) derived from intracellular proteins • Reacts with: CD8 on Tc cells Because class I MHC molecules are expressed on all cells, except red blood cells, any change in that cell attributable to viral infection or malignancy may result in foreign antigen being presented by MCH class I on the cell’s surface. Inflammatory chemicals blocked by anti-inflammatory drugs (7th Edition, pg. 207) Aspirin and some other nonsteroidal anti-inflammatory drugs (NSAIDs) block the synthesis of prostaglandins of the E series and other arachidonic acid derivatives, thereby inhibiting inflammation. Characteristics of acute phase reactant C-reactive protein (CRP) (7th Edition, pg. 214) C-reactive protein is increased in acute phase during inflammation. CRP is a product of liver that reaches maximal circulating levels within 10-40 hours of initial infection. Administration of IL-1 into animals leads to fever and elevation of most acute-phase reactants, including C-reactive protein.DERMATOLOGY Process by which a deep pressure ulcer heals: Most significant cause is constant pressure that interrupts arterial and venous blood flow to and from the skin or deeper tissue. Healing requires continued relief of pressure, debridement of dead tissue, wound care products (dressings…), and repair with skin flaps for large/deep ulcers. Antibiotic treatment for infection. Stage I & II pressure ulcers and partial thickness wounds heal by tissue regeneration. Stage III & IV pressure ulcers and full thickness wounds heal by scar formation and contraction Phases of wound healing: Inflammatory-Proliferation-Maturation Inflammatory phase: 0 – 3 days • Hemostasis (bleeding stops) • Inflammation (redness, swelling, warmth and pain maybe present) • Phagocytosis (WBC’s engulf bacteria and foreign debris) • Growth factor stimulation stimulation Proliferation Phase: 3 – 21 days • Angiogenesis (new blood vessels develop) • Collagen synthesis (protein fibers) • Granulation formation • Epithelialization • Contraction Maturation Phase: 21 days – 2 years • Reorganization of collagen • Tensile strength improves (up to 80% of original) Complications of the development of contractures during wound healing: Contractures can form during wound healing due to an exaggeration of normal wound edge contraction forming deformities(more common after burn injuries). Excess of wound contraction, a normal healing process, leads to physical deformity characterized by skin constriction and functional limitations. Myofibroblasts exert their contractile forces by focal adhesion contacts that link the intracellular cytoskeleton to the ECM. Wound contraction must be distinguished from contracture. Clinically, contracture is defined as tissue shortening or distortion that causes decreased joint mobility and function. Scar contracture commonly refers to decreased function in the area, whereas scar contraction refers to shortening of the scar length compared with theoriginal wound.ACID/BASE Causes of respiratory alkalosis: hyperventilation, anxiety, panic, pain, altitude changes,hypermetabolic states (fever, sepsis, hyperthyroidism). Molecules that act as buffers in the blood: Carbonic acid bicarbonate is the most important buffer system.to remove H+ or OH-. H+ reacts with HO3- (bicarbonate) presents in bloodstream. It forms a weak base HCO3-. Get rid of bicarbonate it can add with water and itcan split HCO3- and water can be excreted in urine and can put our PH back to normal.CARDIOVASCULAR Most common cardiac valve disease in women Mitral valve prolapse is common in young women. Although not grossly abnormal, the mitral valve leaflets do not position themselves properly during systole. Mitral valve prolapse is a condition in which the anterior and posterior cusps of the mitral valve billow upward (prolapse) into the atrium during systole. It is often be asymptomatic and often have an excellent prognosis. Some at-risk individuals are at risk for complications such as cardioembolic stroke and endocarditis. Mitral valve prolapse is the most common cause of mitral regurgitation, which allows backflow of blood from the left ventricle into the left atrium during systole. This causes a murmur. The increased blood volume, causes the left atrium and ventricle to enlarge, causing associated a-fib and the left ventricle to become hypertrophied. Eventually, as the regurgitation progresses, the left ventricle will become impaired, causing failure, and eventually leading to pulmonary hypertension and right sided heart failure. Mitral valve prolapse is the most common valve disorder in the United States, and most prevalent among young women. Some studies suggest there to be an autosomal dominant and X-linked inheritance pattern. Because mitral valve prolapse often is associated with other inherited connective tissue disorders (Marfan syndrome, Ehlers-Danlos syndrome, osteogenesis imperfecta), it is thought to result from a genetic or environmental disruption of valvular development during the fifth or sixth week of gestation. There may also be a relationship between hyperthyroidism and mitral valve prolapse. Afflicted valves may be at greater risk for developing infective endocarditis. When myocardial ischemia may be reversible An acute obstruction in a coronary artery can cause myocardial cell death (infarction) within minutes if the blood supply is not restored, whereas the gradual onset of ischemia usually results in myocardial adaptation. Ischemic injury is often caused by gradual narrowing of arteries (arteriosclerosis) and complete blockage by blood clots (thrombosis). Individuals with coronary heart disease may develop myocardial ischemia during mental or acute emotional stress even though their exercise results are negative. Ischemia, a local state in which the cells are temporarily deprived of blood supply. They remain alive but cannot function normally. Persistent ischemia or the complete occlusion of a coronary artery causes acute coronary syndrome. Myocardial ischemia develops if the supply of coronary blood cannot meet the demand of the myocardium for oxygen and nutrients. Imbalances between myocardial demand and coronary blood supply can result from a number of conditions. Common causes of increased myocardial demand for blood include tachycardia, exercise, hypertension (hypertrophy), and valvular disease. The most common cause of decreased coronary blood flow and resultant myocardial ischemia is the formationof atherosclerotic plaques in the coronary circulation. As the plaque increases in size, it may partially occlude the vessel lumina,thus limiting coronary flow and causing ischemia especially during exercise. 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. Myocardial ischemia also can result from other causes of decreased blood and oxygen delivery to the myocardium, such as coronary spasm, hypotension, dysrhythmias, and decreased oxygen-carrying capacity of the blood (anemia, hypoxemia). Myocardial cells become ischemic within 10 seconds of coronary occlusion. After several minutes the heart cells lose the ability to contract, and cardiac output decreases. Ischemia also causes conduction abnormalities that lead to changes in the electrocardiogram and may initiate dysrhythmias. Anaerobic processes take over, and lactic acid accumulates. Cardiac cells remain viable for approximately 20 minutes under ischemic conditions. If blood flow is restored, aerobic metabolism resumes, contractility is restored, and cellular repair begins. If the coronary artery occlusion persists beyond 20 minutes, MI occurs Symptoms ofstable angina (angina pectoris) Caused by gradual luminal narrowing and hardening of the arterial walls, affected vessels cannot dilate in response to increased myocardial demand associated with physical exertion or emotional stress. If demand is decreased, no necrosis of myocardial cells results Symptoms: • Transient substernal chest discomfort- ranging in a sensation of heaviness or pressure to moderately severe pain (like aclenched fist over the left sternal border)• Often mistaken for indigestion• 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. The pain is usually relieved by rest and nitrates; lack of relief indicates an individual may be developing infarction • Myocardial ischemia in women may not present with typical anginal pain o Common symptoms in women include: atypical chest pain, palpitations, sense of unease, and severe fatigueand sometimes can be silent. Orthostatic hypotension Decrease in systolic and diastolic arterial blood pressure upon standing. The compensatory vasoconstriction response to standing is altered by a marked vasodilation and blood pooling in the muscle vasculature. Orthostatic hypotension may be acute or chronic. The acute form is caused by a delay in the normal regulatory mechanisms. The chronic forms are secondary to a specific disease or are idiopathic. The clinical manifestations of orthostatic hypotension include fainting and may involve cardiovascular symptoms, as well as impotence and bowel and bladder dysfunction. • Defined with a systolic blood pressure decrease of at least 20 mmHg or a diastolic blood pressure decrease of at least 10 mmHg within 3 minutes of standing up. • It can be categorized as arteriolar, venular, or mixed. • Compensatory changes during standing normally increase sympathetic activity mediated through stretch receptors (baroreceptors) 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 a stable blood pressure. These compensatory mechanisms are not effective in maintaining a stable blood pressure in individuals with orthostatic hypotension. • Orthostatic hypotension may be acute or chronic. o Acute orthostatic hypotension (temporary type) may result from: (1) altered body chemistry (2) drug action (e.g., antihypertensives or antidepressants) (3) prolonged immobility caused by illness (4) starvation (5) physical exhaustion (6) any condition that produces volume depletion (e.g., massive diuresis, potassium or sodiumdepletion) (7) venous pooling (e.g., pregnancy, extensive varicosities of the lower extremities). • Older adults are susceptible to this type of orthostatic hypotension, in which postural reflexes are slowed as part of the aging process. • Chronic orthostatic hypotension can be categorized as: (1) secondary to a specific disease (2) idiopathic or primary. • The diseases that cause secondary orthostatic hypotension are endocrine disorders (e.g., adrenal insufficiency, diabetes mellitus), metabolic disorders (e.g., porphyria), or diseases of the central or peripheral nervous system (e.g., intracranial tumors, cerebral infarcts, Wernicke encephalopathy, peripheral neuropathies). • Cardiovascular autonomic neuropathy is a common cause of orthostatic hypotension in diabetes. • Idiopathic, or primary, orthostatic hypotension is the term for hypotension in which there is no known initial cause. o It affects men more often than women and usually occurs between the ages of 40 and 70 years. o It is a significant risk factor for falls and associated injuries and has been associated with an increased risk for cardiovascular events. • Orthostatic hypotension often is accompanied by dizziness, blurring or loss of vision, and syncope or fainting. o To assess hypotensive episode frequency, severity, and correlation with symptoms, 24-hour blood pressuremonitoring is recommended. o No curative treatment is available for idiopathic orthostatic hypertension. o In the secondary form, postural hypotension improves when the underlying disorder is corrected.o Several treatments can help acute and chronic orthostatic hypotension, including liberalization of salt intake, raising the head of the bed, thigh-high stockings, volume expansion with mineralocorticoids, and vasoconstrictors such as midodrine. Isolated systolic HTN elevated systolic blood pressure accompanied by normal diastolic blood pressure (less than 90 mmHg). ISH is becoming more prevalent in all age groups and is strongly associated withcardiovascular and cerebrovascular events Sustained controlled HTN • Increased peripheral resistance and increased blood volume are two primary causes of sustainedHTN. Sustained HTN and the neurohumoral perturbations, especially an increase in activity of the RAA, contribute to remodeling of vessels, resulting in the changes known as hyaline sclerosis and atherosclerosis. • Target organs of HTN include the eyes (retinal changes), kidneys (nephrosclerosis), heart (CAD/CHF), and brain / neurologic disease (stroke, encephalopathy, dementia). Relationship of insulin resistance on the development of primary hypertension; pg 1136. • Genetic predisposition to HTN. Inherited defects associated with renal Na excretion,insulin & insulin sensitivity, activity of SNS & RAAS, & cell membrane Na or Ca transport. • Primary hypertension is the result of a complicated interaction b/t genetics and the environmentthat increase vascular tone (increased peripheral resistance) and blood volume leading to increases in BP. • Insulin resistance is common in hypertension, even individuals without clinical diabetes. Insulin resistance is associated with decreased endothelial release of nitric oxide and other vasodilators.(Nitric oxide dilates blood vessels, raising blood supply and lowering BP – so a decrease in this is going to constrict blood vessels and raise BP) • It also affects renal function and causes renal salt and water retention leading to increased bloodvolume and hypertension. Insulin resistance is associated with overactivity of the SNS and the RAAS. Defects in normal secretion of natriuretic hormones & impact on renal system; pg 1134 • Natriuretic hormones modulate renal sodium (Na+) excretion and require adequate potassium,calcium, and magnesium to function properly. • Natriuretic hormones include atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), C-type natriuretic peptide (CNP), and urodilatin. • These hormones induce diuresis; enhancement of renal blood flow and glomerular filtrationrate, systemic vasodilation, and suppression of aldosterone, and inhibition of SNS. • Dysfunction of these hormones, along with alterations in the RAA system and the SNS cause anincrease in vascular tone and a shift in the pressure natriuresis relationship. • When there is inadequate natriuretic function, serum levels of natriuretic peptides are increased. In hypertension, increased ANP and BNP levels are linked to an increased risk forventricular hypertrophy, atherosclerosis, and heart failure. Salt retention leads to waterretention and increased blood volume which leads to increased BP. Effects of increased sympathetic nervous system activity due to primary HTN; pg 1133 • The SNS contributes to the pathogenesis of hypertension in many people. • In a healthy individual, the SNS contributes to the maintenance of adequate blood pressure andtissue prefusion by promoting cardiac contractility and heart rate (maintenance of adequate cardiac output) and by inducing arteriolar vasoconstriction (maintenance of adequate peripheralresistance) • in patients with hypertension, overactivity of SNS can result from increased production of catecholamines (epi and norepi) or from increased receptor reactivity involving these neurotransmitters. • Increased SNS activity cause increased HR and systemic vasoconstriction thusraising BP. Complications of unstable plaque in the coronary arteries: CAD (buildup of plaque), leads to stable angina (on exertion and then resolves on rest) angina pectoris (strangling/tightening of heart muscle when there’s a lack of o2), acute coronary syndrome (unstable angina and MI). Unstable angina causes chest pain at rest. MI is the death of a part of the heart muscle.An MI or unstable angina are caused by rupture or erosion of a plaque with subsequent thrombus formation and occlusion of the artery. The most common cause of obstruction is atherosclerosis (ACS) Forms of dyslipidemia associated with the development of the fatty streak inatherosclerosis: Type I: exogenous hyperlipidemia; fat-induced hypertriglyceridemia Lab findings: Cholesterol normal Triglycerides increased three times Chylomicronsincreased Clinical features: Abdominal pain Hepatosplenomegaly Skin and retinal lipid deposits Usual onset:childhood Therapy: Low-fat diet Type IIa: hypercholesterolemia Lab findings: Triglycerides normal LDL increased Cholesterol increased Clinical findings: Premature vascular disease Xanthomas of tendons and bony prominences CommonOnset: all ages Therapy: Low-saturated-fat and low-cholesterol diet Cholestyramine Colestipol Lovastatin Nicotinic acidNeomycin Intestinal bypassType IIb: combined hyperlipidemia; carbohydrate-induced hypertriglyceridemia Lab findings: LDL, VLDL increased Cholesterol increased Triglycerides increasedClinical features: Same as IIa Therapy: Same asIIa; plus carbohydrate restriction Clofibrate Gemfibrozil Lovastatin Type III: dysbetalipoproteinemia Lab findings: IDL or chylomicron remnantsincreased Cholesterol increased Triglycerides increased Clinical Features: Premature vascular disease Xanthomas of tendons and bony prominences UncommonOnset: adulthood Therapy: Weight control Low-carbohydrate, low-saturated-fat, and low-cholesterol diet Alcoholrestriction Clofibrate Gemfibrozil Lovastatin Nicotinic Acid Estrogens Intestinal bypass Type IV: endogenous hyperlipidemia; carbohydrate-induced hypertriglyceridemia Lab findings: Glucose intolerance Hyperuricemia Cholesterol normal or increased VLDL increasedTriglycerides increased Clinical features: Premature vascular disease Skin lipid deposits Obesity Hepatomegaly Common onset:adulthood Therapy: Weight control Low-carbohydrate diet Alcohol restriction Clofibrate Nicotinic acid Intestinalbypass Type V: mixed hyperlipidemia; carbohydrate and fat-induced hypertriglyceridemia Lab findings: Glucose intolerance Hyperuricemia Chylomicrons increased VLDL increased LDL increasedCholesterol increased Triglycerides increased three times Clinical features: Abdominal pain Hepatosplenomegaly Skin lipid deposits Retinal lipid deposits Onset:childhood Therapy: Weight control Low-carbohydrate and low-fat diet Clofibrate Lovastatin Nicotinic acidProgesterone Intestinal bypass High serum LDL is a risk factor for atherosclerosis. LDL adheres to the injured endothelium and is oxidized by macrophages to form the fatty streak. The macrophages in the tunica media of the vesselwall accumulate and form the fatty streak. Events that initiate the process of atherosclerosis: Endothelial inquiry and release of cytokines initiates atherosclerosis. The most common consequence ofatherosclerosis is obstruction of the blood vessel lumen. Smooth muscle proliferations, fibrosis, and calcification in atherosclerosis all reduce the size of the blood vessel lumen.S&S of ?Left Atrial &Pulmonary venous pressures in Left Sided HF • result of pulmonary vascular congestion & inadequate perfusion of systemic circulation o dyspnea, orthopnea, frothy sputum cough, fatigue, urine output, edema o pulmonary edema ▪ cyanosis, inspiratory crackles, pleural effusions ▪ hypo/hypertension, S3 gallop, evidence of underlying CAD or HTN Difference betweenL & R sided failure Cardiac dysfunction caused by inability of the heart to provide adequate cardiac output,resulting in inadequate tissue perfusion ▪ Left HF (CHF) o Inability of LV to provide enough adequate blood flow into systemic circulation o Cause: Systemic HTN (most common), LV MI, LV hypertrophy, Aortic SLV or Bicuspid valve damage, 2ndary to Rt HF ▪ LV MI- results in weakening of muscle d/t damage ▪ LV hypertrophy - 2ndary to cardiac damage, resulting in enlarged but weaker structure holding more blood ▪ Aortic SLV- causes backflow of blood into Lt atrium or ventricle after eject ▪ RT HF- from buildup of pressure of damaged Rt ventricle o Disease Process ▪ High systemic vascular pressure ⟶ ?LV contraction force (? afterload) ⟶ LV unable to eject normal amount of blood ⟶ ? LV preload (amount of blood remaining) ⟶ LA unable to eject normal amount of blood ⟶ ? LA preload (amount of blood remaining in LA) ⟶ ? blood volume + pressure in pulmonary veins ⟶ fluid forced out into pulmonary tissues ⟶ pulmonary edema + dyspnea ⟶ Rt HF= biventricular HF ▪ Right HF (Cor Pulmonale) o Inability of RV to provide enough adequate blood flow into pulmonary circulation o Cause: Pulmonary disease, Pulmonary HTN (most common), RV MI, RV hypertrophy, Pulmonary SLV or tricuspid valve damage, 2ndary to Lt HF ▪ RV MI- resultsin weakening of muscle▪ RV hypertrophy- 2ndary to cardiac damage ▪ Pulmonary SLV or tricuspid valve damage- causing backflow of blood into RA orRV after ejection ▪ 2ndary to Lt HF- from buildup of pressure in damaged left ventricle o Disease Process ▪ High Pulmonary vascular resistance ⟶ ?RV contraction force (? afterload) ⟶ RV unable to empty completely ⟶ ? RV preload (amount of blood remaining in RV) ⟶ RA unable to empty completely ⟶ ? RA preload (amount of blood remaining in RA) ⟶? vena cava + systemic venous volume + pressure ⟶ fluid forced out into peripheral tissues ⟶ JVD, Liver & Spleen become engorged (hepatosplenomegalia) ? pressure forced fluid from systemic capillaries into peripheral tissues,flooding areas, resulting in peripheral edema ⟶ Lt HF= biventricular HF Infective Endocarditis ▪ Infection & Inflammation of the endocardium, esp. cardiac valves ▪ Bacteria most common cause (strep, staph, enterococci) o Endocardial damage ▪ Trauma, congenital heart disease, valvular heart disease, prosthetic valves ▪ turbulent blood caused by these affects atrial surface of AV valves or ventricularsurface of SL valves ▪ endocardial damage exposes membrane (contains collagen that attractsplatelets, stimulating thrombus formation on membrane) ▪ causes inflammatory reaction (nonbacterial thrombotic endocarditis) ▪ Blood borne microorganism adherence to damaged endocardial surface oenter bloodstream during injection drug use, trauma, dental procedures, cardiacsurgery, genitourinary procedures, indwelling cath in presence of infection, may spread from upper resp infect or skin infect obacteria damage endocardium using adhesins ▪ Infective endocardial vegetationsform obacteria infiltrate thrombi and accelerate fibrin formation, activating clottingcascade ovegetative lesions can form anywhere in endocardium, usually on heart valvesand surrounding structures obacterial colonies are inaccessible to antibody containing blood due to beingembedded in protective fibrin clots5P’s PVD PAD oembolization of vegetations can lead to abscesses and skin changes such aspetechiae, splinter hemorrhages, osler nodes, janeway lesions ▪ acute, subacute, or chronic, may associate with several organ systems ▪ S&S caused by infection and inflammation, systemic spread of microemboli, immune complex deposition oclassic finding: fever; new or changed cardiac murmur; petechial lesions of theskin, conjunctiva, oral mucosa ophysical findings: osler nodes (painful erythematous nodules on pads of fingersand toes) and janaway lesions (nonpainful hemorrhagic lesions on palms and soles), night sweats, weight loss, back pain, HF ▪ Dx: persistent bacteremia, new heart murmurs, vascular complications ▪ ATB therapy ▪ Ex. prosthetic heart valve pt receiving prophylactic ATB before gingival dental procedure PERIPHERAL VASCULAR DISEASE Peripheral vascular disease: Narrowing, blockage or spasming of veins and arteries. It can be difficult to differentiate PVD from Peripheral Arterial Disease (PAD). Consider what symptoms and problems areexperienced as a result of an arterial occlusion as opposed to a venous occlusion. It is helpful to consider the five P’s when assessing these types of disorders: 1) Pallor (pale skin) 2) pain 3) pulselessness 4) paresthesia’s (pins and needles) 5) paralysis Pallor browning discoloration (stasis dermatitis) discoloration, paleness, bluish, darkening of thetoes. Elevated pallor Pain dull, constant achy pain Intermittent claudication(pain w/ambulation) Pain in the legs is provoked by walking, relievedwith rest Pulse regular pulse, warm extremities Absent pulse, weak pulse, unequal pulses. Cold/coolextremities Paresthesia None Present: numbing, tingling Paralysis None unable to move limb Other Edema present No Edema Types of PVD: Thromboangiitis obliterans (Buerger disease) is an inflammatory disease of the peripheral arteries. Raynaud phenomenon and Raynaud disease are characterized by attacks of vasospasm in the small arteries and arterioles of the fingers and, less commonly, the toes. Atherosclerosis is a form of arteriosclerosis in which thickening and hardening of the vessel are caused by the accumulation of lipid-laden macrophages within the arterial wall, which leads to the formation of a lesion called a plaque. Deep Vein Thrombosis pathophysiology DVTs are formed when platelets, fibrin mesh and RBCs clump together in the veins (most often near a valve) via the coagulation cascade to form a thrombus. Inflammation around the thrombus promotes further platelet aggregation and the thrombus propagates or grows proximally. Blood clot or thrombus in a deep vein, usually of the leg. 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 propagates or grows proximally. This inflammation may cause local symptoms, but because the vein is deep in the leg it is usually not accompanied by clinical symptoms or signs. If the thrombus creates significant obstruction to venous blood flow, increased pressure in the vein behind the clot may lead to edema of the extremity. Vichow’s traid: The etiology of a blood clot (venous thrombus) 1) Vessel endothelial injury: trauma, medications 2) Venous stasis: immobility, obesity, prolonged leg dependency, age, heart failure 3) Hypercoagulability: inherited disorders, malignancy, pregnancy, oral contraceptives, hormone replacement,hyperhomocysteinemia, antiphospholipid syndrome S/Sx of DVT: Asymmetrical edema, asymmetrical calf swelling, localized pain most notably in the calf area. Diagnosis: is most often made by combining measurement of serum d-dimer concentration with lower extremity ultrasonography. d-dimer is an indirect measure of the presence of thrombosis that is very sensitive but is not specific. If the d- dimer is negative, DVT is ruled out. If it is positive, the diagnosis must be confirmed with ultrasonography. In selected individuals, computed tomography (CT) or magnetic resonance imaging (MRI) may be needed to make the diagnosis. Treatment: DVT is treated with low-molecular-weight heparin, unfractionated intravenous heparin, antithrombin agents, or adjusted- dose subcutaneous heparin. Thrombolytic therapy may be used to dissolve the clot more quickly and reduce the risk of postphlebotic syndrome, especially when a large clot is located in a proximal vein.HEMATOLOGY Physiological response to hypoxia in anemia Hypoxemia, reduced oxygen levels in the blood, further contributes to cardiovascular dysfunction by causing dilations of arterioles, capillaries, and venules, thus leading to decreased vascular resistance and increased flow. Increased peripheral blood flow and venous return further contribute to an increase in heart rate and stroke volume in a continuing effort to meet normal oxygen demand and prevent cardiopulmonary congestion. These compensatory mechanisms may lead to heart failure. Populations at highest risk for developing folate deficiency anemia Humans are totally dependent on dietary intake meet the daily requirement of 50-200mcg/day. Increased amountsare required for pregnancy and lactating females. Folate deficiency is more common than B12 deficiency, particularly in alcoholics and individuals with chronic malnourishment. Alcohol interferes with folate metabolism in the liver, causing a profound depletion of folate stores. Fad diets and diets low in vegetables also may cause folate deficiency because of the absence of plant sources of folate. Cause of Iron Deficiency Anemia Iron deficiency Anemia 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 sufficiency 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. Blood loss of 2-4 ml/day(1-2 mg of iron) is sufficient to cause iron deficiency and may results in erosive esophagitis, gastric and duodenal ulcers, colon adenomas, or cancers. H. pylori infections also have been found to cause IDA of unknown origin, although H. pylori impairs iron uptake. In females, menorrhagia is a common cause of primary IDA. Other causes of IDA for both genders are 1. Use of medication that cause GI bleeding such as aspirin or NSAIDS 2. Surgical procedures that decrease stomach acidity, intestinaltransit time, and absorptions such as with gastric bypass 3. Insufficient dietary intake of iron 4. Eating disorders, such as pica, which is the craving and eating of non-nutritional substances, such as dirt, chalk, and paper. Expected lab test results found in long standing Iron Deficiency Anemia Symptoms of IDA begin gradually, and individuals usually do not seek medical attention until hemoglobin level have decrease to 7-8 g/dl. Other lab values include: Hemoglobin – low, Hematocrit – low, Reticulocyte – Normal or slightly high or low, Mean corpuscular volume – low, Plasma iron – low, Total iron-binding capacity – high, Ferritin – low, Serum B12 – Normal, Folate – Normal, Bilirubin – Normal, Freeerythrocyte protoporphyrin – High, Transferrin - Low Sickle Cell Anemia -Sickle cell anemia is an inherited (autosomal recessive) disorder of erythrocytes -300 million people are affected by a hemoglobinopathies (sickle cell or Thalassemia) -genes involved: Alpha=chromosome 16Beta= chromosome 11 -Inherited autosomal recessive=inheritance of 2 abnormal genes from each parent -Inheritance of 1 normal gene/1 abnormal gene=sickle cell trait carrier = asymptomatic -Most common in certain geographic areas *African America *Mediterranean *South Eastern Descent -Cells that contain more abnormal types of hemoglobin (sickle cell) are more resistant to parasites that cause malaria -Also, the decrease in lifespan/circulation of these cells do not give the parasite enough time to allow production cycle. -Individuals who are affected by sickle cell happen to be from same geographic location that malaria is an endemic. Pathophysiology-Single amino acid changes occur on beta chain of hemoglobin. -Amino acid valine replaces glutamine acid resulting in elongated sickle cells -Distortion (elongated) of RBC’s causes cells to weaken and rupture-this is why the cells only circulate in blood for 10- 15 days. -Abnormal shape cell=occlusion of blood vessels/spleen risk of CVA, splenic or kidney damage *Splenic damage most prevalent, so most sickle cell people are asplenic (without spleen) by adulthood. Factors-oxidative stress (hypoxia)--------------------- * All of these factors further decrease o2 -anxiety---------------------------------------------- from binding to hemoglobin and -fever----------------------------------------------- increases sickling tendencies of -Temp-cold--------------------------------------- hemoglobin.-dehydration Aplastic Anemia -Aplastic= without plasia/cell growth -Impaired RBC production -Considered a Normocytic-Normochromic Anemia Normocytic=normal cell size, Normochromic=Normal color (hgb) -Since the size and color (hgb) are normal in aplastic anemia, the problem is the decrease in the number of cells. Causes: -chemical/radiation exposure=cancer treatment -viral induced=hepatitis, Epstein barr, CMV virus -tumors=in bone marrow-multiple myeloma -antibiotics/meds=Penicillin, Phenytoin, diuretics, antidiabetic meds, sulfa meds -congenital defects=fanconi’s anemia *rare, 1/5000 births Pathophysiology The agent (causes listed above) destroys the red marrow and replaces it with fatty yellow marrow which does not produce blood cells pancytopenia=decrease in all blood cell types. • Hemolytic anemia -Hemolytic=lysis of blood cells (cell destruction) -Same type of anemia as aplastic anemia; normal cell size, normal color (hgb). The problem is thedecrease number of cells -Considered a Normocytic-Normochromic Anemia Normocytic=normal cell size, Normochromic=normal color (hgb) Causes-infection*E.coli -transfusion reaction -hemolytic disease of newborn *RH compatibility -autoimmune reaction *congenital, idiopathic -drug induced *drugs auto oxidize (self-destruct) Pathophysiology Premature destruction of RBC’s due to enzymes/toxins produced by infectious agents, mediated by own immune system or the effects of certain chemicals/drugs. *Circulating blood has vit.C and RBC’s that contains glutathione=natural antioxidant to help protect cells. Pathophysiology of Autoimmune Hemolytic Anemia -Hemolytic anemia can be caused by intrinsic/extrinsic factors -Autoimmune hemolytic anemia=extrinsic factor -The immune system mistakes its own RBC’s as a foreign substance and responds by producing antibodies. This causes the antigen to prematurely destroy the RBC’s (the RBC’S are destroyed faster than they are replaced) leading to hemolytic anemia. -Cause of hemolytic anemia is unknown Secondary polycythemia Vera Chronic Bronchitis leads to chronic pulmonary hypoxia (from right to left shunting-RV to lungs to LV without gas exchange [perfusion] occurring)-then in response to the hypoxia... erythropoietin secretion increases resulting in an elevated hct (increased red blood cells made from the bone marrow in response to circulating erythropoietin) —- secondary polycythemia Vera occurs.Anemia of chronic renal failure: Anemia of chronic renal failure Kidneys are important for production of the hormones erythropoietin and renin. When the kidneys are damaged (glomerulonephritis etc which leads to chronic renal failure) erythropoietin production decrease resulting in decreasedproduction of red blood cells from bone marrow = anemia of chronic renal failureFLUIDS & ELECTROLYTES Conditions that result in pure water deficit (hypertonic volume depleted) Hypertonic alterations develop when the osmolality of the ECF is elevated above normal, usually because of an increased concentration of ECF sodium or a deficit of ECF water. The ECF osmolality is greater than the ICF osmolality so water moves out of the cell which causes cellular shrinkage and increased plasma volume. Water deficit, or hypertonic dehydration, can be caused by lack of access to water, pure water losses, hyperventilation,arid climates, or increased renal clearance. Other mechanisms include loss of thirst, water diarrhea, diabetes insipidus, excessive diuresis and excessive diaphoresis. A hypertonic state causes signs and symptoms of hypovolemia. Osmoreceptors that stimulate thirst and the release of ADH Thirst is experience when water loss equals 2% of an individual’s body water or when there is an increase in osmolality. Dry mouth, hyperosmolality and plasma volume depletion activate hypothalamic osmoreceptors. The action of the osmoreceptors than cause thirst. Drinking water restores plasma volume and dilutes the ECF osmolarity. Water balance isregulated by the sensation of thirst and by the level of antidiuretic hormone, which is initiated by an increase in plasma osmolality or a decrease in circulating blood volume. The hypothalamic osmoreceptors signal the posterior pituitary gland to release antidiuretic hormone (ADH). ADH alters the collecting tubules permeability to water, increased ADH causes increased permeability to water resulting in more water to be absorbed. This allows for restoration of plasma volume and blood pressure. The release of ADH is regulated by a feedback mechanism so when there is restoration of the plasma osmolality, blood volume and blood pressure then ADH secretion is inhibited.With fluid loss there is a blood volume and blood pressure decrease. Baroreceptors (volume/pressure sensitive receptors) located in the R/L atria, large veins, aorta, pulmonary arteries and carotid sinus also stimulate the release of ADH. When the arterial and atrial pressure drops baroreceptors signal the hypothalamus to releaseADH. ADH also stimulates arterial vasoconstriction. Causes of hypernatremia Hypernatremia (sodium levels >147 mEq/L) may be caused by an acute increase in sodium level or a loss of water (most common cause). Some specific causes of hypernatremia from water loss include fever, respiratory tract infections (that increase respiratory rate and enhance water loss from the lungs), diabetes insipidus (deficiency of ADH), polyuria, profuse sweating, diarrhea. Insufficient water intake causes include individuals who are comatose or receiving gastric feedings and infants who can’t communicate thirst. Other causes of increased sodium retention are inappropriate administration of hypertonic saline solution, over secretion of aldosterone (hyperaldosteronism) and Cushing syndrome (excess secretion of adrenocorticotropic hormone (ACTH) which increases secretion of aldosterone). High amounts of dietary sodium rarely cause hypernatremia because healthy kidneys will eliminate excess sodium. Hypernatremia can cause thirst, dry mucous membranes, hypotension or hypertension (depending on cause of hypernatremia), tachycardia, pulmonary edema, confusion and convulsions. Treatment of hypernatremia is with an isotonic salt-free fluid (5% dextrose in water) and must be given slowly toprevent cerebral edema. Effects of increased aldosterone Aldosterone is produced by the adrenal cortex. Sodium balance is regulated by aldosterone, which increases reabsorption of sodium by the distal tubule of the kidney. Renin and angiotensin are enzymes that promote or inhibit secretion of aldosterone and thus regulate sodium and water balance. Aldosterone promotes sodium and water reabsorption to conserve sodium, blood volume and blood pressure. Potassium balance is regulated by the kidney, by aldosterone and insulin secretion, and by changes in pH. Increased aldosterone secretion can lead to hypokalemia by increasing the secretion of potassium. Dependent edema Edema is the excessive accumulation of fluid within the interstitial spaces. Dependent edema, in which fluid accumulates in gravity-dependent areas of the body, might appear in the feet and legs when standing and in the sacral area and buttocks when supine. Dependent edema can be identified by using fingers to press away edematous fluid in tissues overlying bony prominences. A pit will be left in the skin (pitting edema). Edema may be treated symptomatically until the underlying disorderis corrected. Supportive measures include elevating edematous limbs, using compression stockings or devices, avoiding prolonged standing, restricting salt intake, and taking diuretics. Definition of isotonic -Isotonic conditions occur when the osmolality in the ICF and ECF are equal. -Normal fluid movement favors isotonic conditions. -Examples of isotonic solutions: 5% dextrose in water and normal (0.9%) saline solution Principle of capillary oncotic pressure -Capillary (plasma) oncotic pressure osmotically attracts water from the interstitial space back into the capillary. -Oncotic (colloid) pressure (OCP) - chemical force exerted by large molecules (e.g. – proteins/albumin) to pull fluid in = reabsorption-The movement of fluid back and forth across the capillary wall is called net filtration and is best described by the Starling hypothesis: -Net filtration= (Forces favoring filtration)- (Forces opposing filtration) -Forces favoring filtration= Capillary hydrostatic pressure and interstitial oncotic pressure -Forces opposing filtration= Capillary oncotic pressure and interstitial hydrostatic pressure Types of fluid compartments in the body -Fluids are in two distinct locations in the body: intracellular fluid (ICF) and extracellular fluid (ECF). -Two thirds of the body’s water is ICF and one-third is in the ECF compartments. - The ICF is the fluid within cells and is 40% of body weight. -The ECF is the fluid outside of the cells and makes up 20% of body weight. It can be found in three separate locations. It can be in the intravascular fluid (IV), the interstitial fluid (IF), and other fluids (3rd spaces). -Intravascular (IV)= blood plasma (<5% body weight) -Interstitial fluid (IF)= fluid between cells and outside of blood vessels (<15%) -Other fluids (3rd spaces) = lymph, synovial, CSF, intestinal, sweat, urine, intraocular, and body cavity fluids PULMONARY most effective measure to prevent pulmonary embolus from developing in patients Pulmonary Embolism = occlusion or partial occlusion of pulmonary artery or its branches by an embolism • RISK FACTOR RECOGNITION and ELIMINATION OF PREDISPOSING FACTORS: Increased risk for thrombosis associatedwith hemodynamic stasis, hypercoagulability, and endothelial injury is known as Virchow’s triad Prevention measures: ▪ Risk Factors include: • Venous Stasis: immobilization, heart failure • Hypercoagulability: inherited coagulation disorders, malignancy, hormone replacement,oral contraceptives, pregnancy • Endothelial injury: trauma, caustic intravenous infusion • Venous stasis in hospitalized individuals is minimized by bed exercises, frequent position changes, early ambulation, and pneumatic calf compression. • prophylactic anticoagulation with unfractionated heparin, low-molecular-weight heparin, warfarin, or fondaparinux. • In individuals who have contraindications to anticoagulation, the placement of a filter in the inferior vena cava can prevent emboli from reaching the lungs. Risk factor recognition and elimination of predisposing factors. Most at-risk individuals also will receive prophylactic anticoagulation with unfractionated heparin, low-molecular-weight heparin, warfarin, or fondaparinux. In individuals who have contraindications to anticoagulation, the placement of a filter in the inferior vena cava can prevent emboli from reaching the lungs. Increased risk for thrombosis associated with hemodynamic stasis, hypercoagulability, and endothelial injury is known as Virchow’s triad144 (see Chapter 32). The ideal treatment of PE is prevention through risk factor recognition and elimination ofpredisposing factors. Venous stasis in hospitalized individualsis minimized by bed exercises, frequent position changes, early ambulation, and pneumatic calf compression.155 Most at-risk individuals also will receive prophylactic anticoagulation withunfractionated heparin, low-molecular-weight heparin, warfarin, or fondaparinux.156 In individuals who have contraindicationsto anticoagulation, the placement of a filter in the inferior vena cava can prevent emboli from reaching the lungs.157 when the practitioner will note tactile fremitus * increased with pneumonia because of the density o Tactile Fremitus: ▪ Normal lung transmits a palpable vibratory sensation to the chest wall = fremitus ▪ Detected by placing the ulnar aspects of both hangs firmly against either side of the chest whilethe patient says “Ninety-Nine” ▪ Repeated until the entire posterior thorax is covered o Pathologic Conditions will alter fremitus ▪ Lung Consolidation: Consolidation occurs when the normally air-filled lung parenchyma becomesengorged with fluid or tissue (pneumonia). This alters the transmission of air and sound ▪ FREMITUS MORE PRONOUNCED o Pleural Fluid ▪ Pleural Effusion • Collection of fluid in the space between lung and chest wall displaces lung upwards • FREMITUS OVER AN EFFUSION WILL BE DECREASED After checking for symmetrical chest expansion, feel for tactile fremitus. Fremitus refers to vibratory tremors that can be feltthrough the chest by palpation. To assess for tactile fremitus, ask the patient to say “99” or “blue moon”. While the patient is speaking, palpate the chest from one side to the other. Tactile fremitus may be decreased or absent when vibrations from the larynx to the chest surface are impeded by chronic obstructive pulmonary disease, obstruction, pleural effusion, or pneumothorax. cause of acute airway obstruction in the patient with chronic bronchitis o Inspired irritantsresult in airway inflammation with infiltration of neutrophils, macrophages, andlymphocytes into the bronchial wall o The thick mucus and hypertrophied bronchial smooth muscle narrow the airways and lead to obstruction,particularly during expiration when the airways are restricted. o Airway s collapse early in expiration, trapping gas in the distal portions of the lung The thick mucus and hypertrophied bronchial smooth muscle narrow the airways and lead to obstruction, particularly during expiration when the airways are constricted. Obstruction eventually leads to ventilation-perfusion mismatch with hypoxemia The thick mucus and hypertrophied bronchial smooth muscle narrow the airways and lead to obstruction, particularly during expiration when the airways are constricted. Obstruction eventually leads to ventilationperfusion mismatch with hypoxemia. The airways collapse early in expiration, trapping gas in the distal portions of the lung (Figure 35-15). Air trapping expands the thorax, putting the respiratory muscles at a mechanical disadvantage. Thisleads to decreased tidal volume, hypoventilation, and hypercapnia. TYPES OF PNEUMOTHORAX o Pneumothorax- presence of air or gas in the pleural space caused by a rupture in the visceral pleura orthe parietal pleura and chest wall o Diagnosed with chest radiographs, ultrasound, and CT. o Types ▪ Primary (Spontaneous) Pneumothorax • Often caused by spontaneous rupture of blebs ▪ Secondary (Traumatic) Pneumothorax • Caused by chest trauma (rib fracture, stab, bullet) ▪ Iatrogenic Pneumothorax• Commonly caused by transthoracic needle aspirationo Spontaneous or Traumatic and present as open or tension ▪ Open Pneumothorax (Communicating pneumothorax) • Air pressure in the pleural space equals barometric pressure because air that is drawn into the pleural space during inspiration is forced back out during expiration ▪ Tension Pneumothorax • Site of pleural rupture acts as a one-way valve, permitting air to enter oninspiration, but prevents air escape by closing during expiration Pneumothorax is the presence of air or gas in the pleural space caused by a rupture in the visceral pleura (which surrounds the of the pleural space. This disrupts the state of equilibrium that normally exists between elastic recoil forces of the lung and chest wall. No longer held in check by the recoil forces of the chest wall, the lung fulfills its tendency to recoil by collapsingtoward the hilum. Primary Pneumothorax: occurs unexpectedly in healthy individuals (usually men) between ages 20 and 40 years, is most often caused by the spontaneous rupture of blebs (blister-like formations) on the visceral pleura, although there may be underlying pleural disease with emphysema-like changes. Secondary (traumatic) pneumothorax: can be 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 vesicle) as occurs in COPD; or mechanical ventilation, particularly if it includes positive end-expiratory pressure (PEEP). Clinical manifestations of spontaneous or secondary pneumothorax begin with sudden pleural pain, tachypnea, and possibly mild dyspnea. Iatrogenic pneumothorax: most commonly caused by transthoracic needle aspiration. Open pneumothorax (communicating pneumothorax): air pressure in the pleural space equals barometric pressure because airthat 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 pneumothorax: the site of pleural rupture acts as a one-way valve, permitting air to enter on inspiration, but preventing its escape by closing during expiration. As more and more air enters the pleural space, air pressure in the pneumothorax begins to exceed barometric pressure. The pathophysiologic effects of tension pneumothorax are life threatening. Air pressure in the pleural space pushes against the already recoiled lung, causing compression atelectasis, and against the mediastinum, compressing and displacing the heart and great vessels. Tension pneumothorax may be complicated by severe hypoxemia, tracheal deviation away from the affected lung, and hypotension (low blood pressure) Results of the loss of alph-1- antitrypsin in emphysema Primary emphysema, which accounts for 1% to 3% of all cases of emphysema, is commonly linked to an inherited deficiency of the enzyme α1-antitrypsin.94 Normally α1-antitrypsin inhibits the action of many proteolytic enzymes (enzymes that break downproteins). Individuals who have α1-antitrypsin deficiency (an autosomal recessive trait) have an increased likelihood of developing emphysema, because proteolysis in lung tissues is not inhibited. Homozygous individuals have a 70% to 80% likelihood of developing lung disease. (Mechanisms of genetic inheritance are described in Chapter 4.) Persons with α1- antitrypsin deficiency who smoke are even more susceptible to emphysema than those with the deficiency alone. α1-Antitrypsin deficiency is suggested in nonsmokers and individuals who develop emphysema before age 40 years (or in their early forties). Alpha-1 antitrypsin deficiency is an inherited disorder that may cause lung disease and liver disease. The signs and symptoms of the condition and the age at which they appear vary among individuals. People with alpha-1 antitrypsin deficiency usually develop the first signs and symptoms of lung disease between ages 20 and 50. The earliest symptoms are shortness of breath following mild activity, reduced ability to exercise, and wheezing. Other signs and symptoms can include unintentional weight loss, recurring respiratory infections, fatigue, and rapid heartbeat upon standing. Affected individuals often develop emphysema, which is a lung disease caused by damage to the small air sacs in the lungs (alveoli). Characteristic features of emphysema include difficulty breathing, a lungs) or the parietal pleura and chest wall. As air separatesthe visceral and parietal pleurae, it destroysthe negative pressurehacking cough, and a barrel-shaped chest. Smoking or exposure to tobacco smoke accelerates the appearance of emphysema symptoms and damage to the lungs. About 10 percent of infants with alpha-1 antitrypsin deficiency develop liver disease, which often causes yellowing of the skin and whites of the eyes (jaundice). Approximately 15 percent of adults with alpha-1 antitrypsin deficiency develop liver damage (cirrhosis) due to the formation of scar tissue in the liver. Signs of cirrhosis include a swollen abdomen, swollen feet or legs, and jaundice. Individuals with alpha-1antitrypsin deficiency are also at risk of developing a type of liver cancer called hepatocellular carcinoma. In rare cases, people with alpha-1 antitrypsin deficiency develop a skin condition called panniculitis, which is characterized by hardened skin with painful lumps or patches. Panniculitis varies in severity and can occur at any age. Symptoms related to the lung: • Shortness of breath. • Wheezing. • Chronic bronchitis, which is cough and sputum (phlegm) production that lasts for a long time. • Recurring chest colds. • Less exercise tolerance. • Year-round allergies. • Bronchiectasis. The result of loss of surfactant in ARDS Surfactant impairment results from decreased production or inactivation of surfactant, which is necessary to reduce surface tension in the alveoli and thus prevent lung collapse during expiration. Surfactant impairment can occur because of premature birth, acute respiratory distress syndrome, anesthesia, or mechanical ventilation. As the alveoli increase in size, the surfactant becomes more spread out over the surface of the liquid. This increases surface tension effectively slowing the rate of expansion of the alveoli. Surfactant reduces surface tension more readily when the alveoli are smaller because the surfactant is more concentrated. When there is not enough surfactant the tiny alveoli collapse with each breath, and as they collapse damaged cells collect in the airway causing further affect in breathing. Characteristics of Cheyne-Stokes respirations Alternating periods of deep and shallow breathing. Apnea lasting 15 to 60 seconds is followed by ventilations that increase involume until a peak is reached, after which ventilation (tidal volume) decreases again to apnea. Cheyne-Stokes respirations 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. Usually seen in comatose individuals having disease nervous centers respirations.SHOCK Causes of hypovolemic shock (7th Edition, pg. 1672-3) Hypovolemic shock is caused by loss of whole blood (hemorrhage), plasma (burns), or interstitial fluid(diaphoresis, diabetes mellitus, diabetes insipidus, emesis, or diuresis) in large amounts. Loss of wholeblood or plasma causes hypovolemia directly. Loss of interstitial fluid causes an indirect “relative” hypovolemia by promoting diffusion of plasma from the intravascular to the extravascular space. Hypovolemic shock begins to develop when intravascular volume has decreased by about 15%. How the body maintains glucose levels during shock (7th Edition, pg. 1670) In shock, glucose metabolism may be increased or disrupted because of fever or bacteria, and glucose uptake can be prevented by the presence of vasoactive toxins, endotoxins, histamine, and kinins. Some of the compensatory mechanisms activated by shock contribute to decreased glucose uptake and use bythe cells. High serum levels of cortisol, growth hormone, and catecholamines account for hyperglycemia and insulin resistance, tachycardia, increased SVR, and increased cardiac contractility. Cells shift to glycogenesis, gluconeogenesis, and lipolysis to generate fuel for survival. Except in the liver, kidneys, andmuscles, the body’s cells have extremely limited stores of glycogen. In fact, total body stores can fuel themetabolism for only about 10 hours. When gluconeogenesis causes proteins to be used for fuel, these proteins are no longer available to maintain cellular structure, function, repair, and replication.NR 507 Week Five Quiz Study Guide 1. What controls the direct stimulation of the insulin-secreting cells? Neural; Direct stimulation ofthe insulin-secreting cells of the pancreas by the autonomic nervous system is a form of neural control. 2. Types of protein hormones --Which of the following is an example of the protein hormone? Insulin 3. Assessing patients for elevated thyroxine production --A patient who has elevated thyroxine production should be assessed for which accompanyingcondition? Decreased thyroid-stimulating hormone (TSH) 4. Direct effect of insulin binding to receptors --What type of effect occurs when insulin binds to its receptors on muscle cells, resulting in an increase in glucose uptake by those muscle cells? Direct; Direct effects are the obvious changes in cell function that result specifically from stimulation by a particular hormoneas is true with insulin. 5. Lipid-soluble hormone receptors crossing plasma membrane --How do lipid-soluble hormone receptors cross the plasma membrane? Diffusion 6. Effects of the removal of the posterior pituitary --How do the releasing hormones that are made in the hypothalamus travel to the anteriorpituitary? Hypophyseal portal system --If a patient's posterior pituitary is removed, which hormone would the nurse expect to decrease? ADH; The hormones ADH and oxytocin are released from the posterior pituitary gland. 7. Insulin regulation --Insulin is primarily regulated by: Serum Glucose Levels; Insulin secretion is promoted whenblood levels of glucose rise. 8. Hormone-secreting tumor of the pancreas—what would increase? --A patient is diagnosed with a hormone-secreting tumor of the pancreas alpha cells. Which ofthe following would the nurse expect to be most likely increased in this patient? Glucagon; Glucagon is produced by the alpha cells of the pancreas. 9. The effect of insulin on electrolytes --A nurse recalls insulin has an effect on which of the following groups of electrolytes? Potassium, Magnesium, Phosphate; Insulin facilitatesthe intracellular transport of potassium(K+), phosphate, and magnesium.10. Hormonal regulation involved in child birth and stopping uterine bleeding? --A 39-year-old female isrecovering from the birth of her third child. Which hormone would helpprevent uterine bleeding? Oxytocin; Oxytocin functions near the end of labor to enhance effectiveness of contractions, promote delivery of the placenta, and stimulate postpartum uterine contractions, thereby preventing excessive bleeding. Types of immunity-e.g. innate, active, etc Innate: Includes 2 lines of defense = natural barriers and inflammation!!AKA T-cell immunity Natural barriers: 1 st Line!!! 1) Physical = skin, mucous membranes 2) Mechanical = flushing, sweeping cilia, peristaltic actions 3) Biochemical = mucus, tears, urine, bile Inflammation: 2 nd Line Activated when 1 st line of defense is breached by bacteria, fungi, protozoa, viruses, etc.Immediate response Localized Nonspecific Includes macrophages and cytokinesDecreased by cortisol and stress Adaptive: 3 rd line of defense! Slower acting Specific Long-lived “memory” Designed to provide long-term specific protection (immunity) against particular microorganisms, unlike inflammation (innate immunity), which provides the same fastreaction no matter the cause of injury. Triggers of Adaptive Immunity: Antigens – foreign or “non-self”. Immunogens – result in activation of B and T cells. FYI – all immunogens are antigens butnot the other way around! With ONE EXCEPTION, Haptens: they are too small to be immunogens but can become immunogenic by combining w/ larger carrier molecules. Haptens are common triggers of allergic reactions!Humoral = antibody mediated! Antibody circulates in the blood and binds to antigens. Antibody is primarily responsible for protection against many viruses/bacteria. When theantibody/antigen bind it can result in a direct activation of the microorganism or an activation of inflammatory mediators that will destroy the pathogen. Cell-Mediated = in an immune response, T-cells undergo differentiation so they developinto several subpopulations of cells that react directly with antigens. Some react directlywith antigens while others develop into T cells that stimulate the activities of other leukocytes via cell-to-cell contact or through secretion of cytokines. Others will develop into Tc (T-cytotoxic cells) that attack/kill targets directly. ** Both the humoral and cell-mediated arms are interdependent and the success ofan acquired immune response depends on the function of both. Both arms produce specialized “memory cells” that are long-lived *** Active Immunity vs Passive Immunity Active = produced by individual either after natural exposure to antigen or afterimmunization – long-lived! Passive – does not require host’s immune system at all. Preformed antibodies or T- lymphocytes are transferred from donor to recipient. I.e. maternal, immunotherapy.Temporary! Alveolar ventilation/perfusion-Dermatologic conditions e.g. pityriasis rosea Folliculitis Infection of hair follicle caused by bacteria, viruses or fungi.Lesions = pustules with surrounding erythema Most prominent: scalp and extremities. Prolonged skin moisture, occlusive clothing, topical agents, skin trauma, poor hygieneTx: clean with soap/water and possibly antibiotics Furuncles Boil. Inflammation of hair follicles develops from folliculitis that spreads through follicularwall into surrounding dermis. Lesion = deep, firm, red, painful nodule 1-5 cm The initial erythematous nodule changes to a large fluctuant/tender cystic nodule that maybe accompanied by cellulitis. No systemic symptoms. Lesion may drain large amounts of pus and necrotic tissue Erysipelas Acute, superficial infection of upper dermis most often Strep pyogenes, beta-hemolyticstrep and Staph aureus. Face, ears, lower legs most common and site of initial infections may not be ID’dChills, fevers, malaise precede onset of lesions by 4-20 days Initial lesions: firm, red spots that enlarge/coalesce into clearly circumscribed, advancingedge, bright red, hot lesion with raised border. Vesicles may appear over lesion and at the border, producing a bullous form of the disease. Itching, burning and tenderness. Tx: Cold compresses, systemic antibiotics Croup Croup illnesses can be divided into 2 categories: all characterized by infection and upperairway obstruction: 1) acute laryngotracheobronchitis 2) spasmodic Laryngotracheobronchitis: Most common in children 6month-3years (peak 2 years) 85% cases caused by virus: parainfluenza most common, but also influenza A, RSV, rhinovirus, adenovirus and rubella (measles) as well as atypical bacterium (Mycoplasmapneumonia).Spasmodic croup: characterized by hoarseness, barking cough/stridor with sudden onset @ nightEtiology unknown but often associated w/ viruses, allergies, asthma, GERD Patho: subglottic edema from the infection. The subglottic mucous membranes are looserthan those of the larynx, which allows for mucosal and submucosal edema between the membranes and underlying cartilage. OF NOTE: the cricoid cartilage is the narrowest point of the airway so swelling inthis area is critical. Increased airflow resistance leads to increased work of breathing, which generates morenegative intrathoracic pressure, which can exacerbate dynamic upper airway collapse! Prodrome of rhinorrhea, sore throat, low-grade fever. After a few days, the characteristicseal-like cough, hoarse voice, and inspiratory stridor. Usually resolves on it’s own but occasionally UAO requires urgent management! Treatment depends on symptoms. Usually viral, so no intervention just symptommanagement. Stridor, retractions and/or agitation suggest advanced illness. The Westley croup score: provides cumulative score for the degree ofstridor, retractions,air entry, cyanosis, dyspnea and LOC. Inhalation of humidified air does NOT improve symptoms. Glucocorticoids (injected/oral/nebulized) may improve symptoms within 6 hours but theydo let the child sleep and decrease parent anxiety Moderate-Severe croup can be helped with nebulized racemic epinephrine, which stimulates the alpha and betaadrenergic receptors, which decreases airway secretions andmucosal edema. This is a temporary fix until steroids kick in. Heliox (helium-oxygen mixture of 80:20 or 70:30) may be used for severe cases butevidence remains lacking. Types of anemia Commonly result from: 1) Impaired erythrocyte production 2) Blood loss (acute or chronic) 3) Increased erythrocyte destruction 4) Combination of the above 3Macrocytic-normochromic anemias: Large, abnormally shaped erythrocytes BUT normal hemoglobin concentrations Pernicious Anemia: Lack of B12 for erythropoiesis, abnormal DNA/RNA synthesis in erythroblast = premature cell death. Cause: congenital or acquired deficiency of intrinsicfactor (IF), genetic disorder of DNA synthesis) S/Sx: early symptoms often vague (infection, mood swings, GI/cardiac/kidney ailments),later symptoms: nerve damage, confusion, dementia, memory loss, depression, nausea, heartburn, weight loss, smooth beefy tongue. Folate Deficiency Anemia: lack of folate for erythropoiesis premature cell death. Cause:dietary folate deficiency. S/SX: irritability, diarrhea and smooth tongue Microcytic-hypochromic anemias: Causes: Small, abnormally shaped erythrocytes AND reduced hemoglobin concentrations Iron Deficiency Anemia: lack of iron for hemoglobin production. Cause: chronic bloodloss, dietary iron deficiency, disruption of iron metabolism or iron cycle. S/Sx: unusual cravings (ice, dirt), brittle nails, swollen/sore tongue, tiny cracks on side ofmouth, frequent infections Sideroblastic Anemia: dysfunctional iron uptake by erythroblasts and defective porphyrinand heme synthesis. Cause: congenital dysfunction of iron metabolism in erythroblasts, acquired dysfunction of iron metabolism 2/2 drugs/toxins Thalassemia: impaired synthesis of (alpha/beta) chain of hemoglobin A, phagocytosis ofabnormal erythroblasts in the marrow. Cause: congenital defect of globin synthesis Normocytic-normochromic Anemias: Normal size and normal hemoglobin concentrations Aplastic anemia: insufficient erythropoiesis. Cause: depressed stem cell proliferationresulting in bone marrow aplasia. S/SX: nausea and skin rashes Posthemorrhagic anemia: blood loss. Cause: acute/chronic hemorrhage that stimulatesincreased erythropoiesis, which depletes body iron. Hemolytic anemia: premature lysis of mature erythrocytes in circulation. Cause: increasedfragility of erythrocytes. S/Sx: jaundice, leg ulcers and abdominal pain Anemia of chronic disease: abnormal increase in demand for new erythrocytes. Cause:chronic infection/inflammation or malignancy. Sickle cell anemia: abnormal hemoglobin synthesis, abnormal cell shape with susceptibility to damage, lysis and phagocytosis. Cause: congenital dysfunction ofhemoglobin synthesis. S/Sx: Edema in hands/feet, damage to spleen Mnemonic for different types of anemiaMicrocytic Anemia = TICS- Thalassemia, iron deficiency, chronic disease, sideroblastic anemia Normocytic Anemia = ABBRA - Anemia of chronic disease, bone marrow infiltration, bone marrow failure, renal failure, acute hemorrhage Macrocytic Anemia = BALD HAIR - B12/B9 deficiency, alcohol, liver disease, drugs (eg. phenytoin), hypothyroidism, aplastic anemia & myelodysplasia, increased reticulocytes The inflammatory process upon injury https://www.khanacademy.org/science/biology/human-biology/immunology/v/inflammatory-response Inflammation occurs in vascularized tissue and when activated results in: redness, heat,swelling and pain. The purpose of the inflammatory process is: 1) To wall off intruder / prevent further infection 2) Acts to destroy and remove intruder 3) Stimulates/enhances further immune response 4) Promotes healing/repair Influx of fluid to dilute toxins produced by bacteria and dying cells, influx/activation of plasma protein systems (i.e. complement system, clotting system) and influx of cells (i.e. neutrophils, macrophages) that destroy cellular debris/infectious agents. The byproductsof cellular debris/infectious agents are removed vie channels through the epithelium or drainage by lymphatic vessels. On injury, acute inflammation has 2 parts: 1) Vascular response 2) WBC response Immediately one of the PRR’s (pattern-recognition receptors) recognizes a PAMP or DAMPand release inflammatory mediators, which is what causes the classic signs of inflammation. Redness / Heat: vasodilation of local arterioles, etc. Edema: increased permeability of vessels that cause plasma proteins/fluids to leak intotissue Pain: some of the released mediators (i.e. bradykinin) increase sensitivity to painHow does all this happen? Injury/Infection triggers mast cells to degranulate and release histamine, which causesimmediate vascular response. Large vessels constrict which increases flow to capillaries Small vessels dilate and epithelial cellsretract which increases permeability.Mast cells release other chemotactic factors that act as signals to recruit other types ofWBCs to area to amplify inflammatory response. Mast cells have enzymes that allow them to synthesize other mediators, such asleukotrienes and prostaglandins GI symptoms resulting in heart burn Pulmonary terminology such as dyspnea, orthopnea, etc Dyspnea = difficult or labored breathing. AKA breathless, air hunger, SOB, increased work of breathing,chest tightness. Orthopnea = discomfort in breathing when lying down flat. Basically dyspnea that occurs when patientlies flat. Common in heart failure, lung disease, pulmonary edema, sleep apnea, COPD and valvular disease. Complications of gastric resection surgery Caused by changes in motor and control functions of the stomach and upper small intestine after gastricresection. Malabsorption Syndromes Interfere w/ nutrient absorption Classified as: maldigestion – failure of the chemical process of digestion to take place in the intestinal lumenor at the brush border of the intestinal mucosa of the small intestine. Usually caused by deficiencies of enzymes such as pancreatic lipase or intestinal lactase. Also, inadequate secretion of bile salts and inadequate reabsorption of bile in ileum. Malabsorption – failure of the mucosa to absorb (transport) the digested nutrients. As a resultof mucosal disruption caused by gastric/intestinal resection, vascular disorders or intestinal disease. Dumping Syndrome The rapid emptying of hypertonic chyme into small intestine 10-20 minutes after eating. Factors that influence: loss of gastric capacity, loss of emptying control when pylorusremoved and lossof feedback control by duodenum when removed. The rapid gastric emptying and creation of a nonphysiologic, high osmotic gradient within smallintestines = sudden shift of fluid from vascular compartment to intestinal lumen.Plasma volume decreases = vasomotor response like tachycardia, hypotension, weakness, pallor,sweating and dizziness. Rapid intestinal distention = epigastric fullness, cramping, N/V. Diarrhea can either be frequent andpersistent or intermittent, precipitous and unpredictable. Late dumping syndrome = 1-3 hours after meal. High carb meal causes hypoglycemia 2/2 increase ininsulin secretion stimulated by hyperglycemia that follows large meal. Frequent, small meals that are high protein and low carb.Drink fluid between meals instead of with meals. Recline on left side after eating. Dermatology terminology-macules, nevi, etc Lesions: Primary Macule = (freckles, flat moles, petechiae, measles) flat, circumscribed area that is a changein color of skin. Papule = (wart, lichen planus, fibroma, insect bite) elevated, firm circumscribed areaPatch = (vitiligo, port-wine stain, mongolion spot)- flat, non-palpable, irregular Plaque = (psoriasis, seborrheic/actinic keratosis)- elevated, firm, rough, flat top surface Wheal = (uritcaria, allergic reaction)- elevated, irregular shaped area of cutaneous edema,solid, transient Nodule = (erythema nodosum, lipomas)- elevated, firm circumscribed deeper lesion. Tumor = (neoplasms, lipoma, neurofibroma, hemangioma)- elevated, solid lesion, may beclearly demarcated, deeper. Vesicle = (chickenpox, shingles, herpes simplex)- elevated, circumscribed, superficial anddoes not extend into dermis Bulla = (blister, pemphigus vulgaris)Pustule = (impetigo, acne) Cyst = (sebaceous cyst, cystic acne) Telangiectasia = 2/2 capillary dilation (acne rosacea, venous HTN, systemic sclerosis orbirthmarks) Nevi- mole are benign, pigmented lesions that form melanocytes beginning at age three. Secondary Scale = seborrheic dermatitis post-scarlet fever or drug reaction, dry skinLichenification = chronic dermatitis Keloid ScarExcoriation = abrasion/scratch, scabies- loss of epidermis, linear, hollowed out, crustedarea. Fissure = athlete’s foot, cracks @ corner of mouth, anal fissure, dermatitis- linear crack orbreak from epidermis to dermis-may be moist or dry Erosion = chemical injury- partial loss of epidermis; depressed, moist, flistening, followsrupure of a vesicle or bulla or chemical injury Ulcer = pressure ulcer, stasis ulcer- concave loss of epidermis and dermisAtrophy = ages skin, striae- Thinning of skin surface. Cutaneous Vasculitis Inflammation of blood vessels of the skin. Immune complexes, which initiate an uncontrolled inflammatory response, are often the cause of damage and the lesions areoften polymorphic. Develops from the deposit of immune complexes in small vessels as a toxic response to drugs or allergens, as a response to strep/viral infections or as a component of systemicvasculitic syndromes Urticaria Hives! Most commonly associated w/ type-1 hypersensitivity reactions to drugs, foods,systemic diseases, physical agents or complement mediated reactions. Scleroderma Sclerosis of the skin. The skin is hard, hypopigmented, taut, shiny and tightly attached tothe underlying tissue. Seborrheic Keratosis Benign proliferation of cutaneous basal cells. Tan to waxy yellow, flesh colored or darkbrown/black lesions. Looks greasy hyperkeratotic stuck-on scaly. Keratoacanthoma Benign self-limiting tumor of squamous cell differentiation arising from hair follicles. Looklike squamous cell carcinoma. Actinic Keratosis Premalignant, composed of aberrant proliferations of epidermal keratinocytes 2/2 prolonged UV radiation exposure. Lesions are rough, scaly and poorly defined pink to reddish or reddish brown papules that are felt more than seen. Considered an early in situsquamous cell carcinoma. Nevi Moles! Benign. Pigmented or non-pigmented. Form from melanocytes. May undergotransition to malignant melanomas. Junctional nevus = rarely develop into melanoma Compound nevus = rarely develop into melanoma Intradermal nevus = slight likelihood of developing into melanomaChicken pox T-cell immune response Highly contagious and spread by contact and airborne droplets.Incubation 10-27 days (average 14). Children are contagious at least 1 day before rash and transmission can occur until 5-6 days after 1 st lesion appears. In immunocompromised children must be considered contagious for 7-10 days. Uncommon but ulcerative lesions can pop up in mouth, conjunctiva and pharynx. Fever for 2-3 daysbetween 101.3-104. Complications more common in adults. Transient hematuria, epistaxis, laryngeal edema, varicella PNA.1 case of pox provides almost all needed immunity. If acquired during 1 st trimester may cause fetal malformation (congenital varicella syndrome). If mom gets pox at any point during pregnancy, baby has higher risk of developing herpes zoster duringfirst few years of life. Maternal varicella-zoster immunoglobulin before rash development (with or without antiviral medication can modify disease progression). Tx: symptom management. Baths/wet dressings/antihistamines. If secondary bacterial infection (fromruptured vesicles) then oral antistaphylococcal drugs. Zoster immune globulin for immunodeficient ptsbut must be given within 72 hours after exposure. Oral antivirals may relieve symptoms. Vaccine will prevent!! Maternal immune system At about 32 weeks gestation the placenta transports maternal Ab into fetal blood thatprotects child during it’s first few months of life. The maternal immune system changes during pregnancy in order to tolerate the semiallogenic fetus, but most pregnant women experience healthy pregnancies, which suggests that the immunological changes do not dramatically affect the integrity of themother. IgG major class of Ab found in blood of fetus/newborn! Hemolytic Disease of the Newborn (this isr/t to immunity b/c it’s a alloimmunecondition! This happens if antigens on fetal erythrocytes differ from antigens on maternal erythrocytes. Maternal-fetal incompatibility exists if mother and fetus differ in ABO bloodtype or if the fetus is Rh-positive and the mother is Rh-negative. Usually erythrocytes from 1 st incompatible baby (offers no reaction) cause the mother’simmune system to produce Ab’s that affect the fetuses of subsequent incompatible pregnancies. Most cases of HDN are caused by ABO incompatibility than Rh reaction though.Candidiasis exacerbation Yeastlike fungus Candida albicans is normal on mucosa, skin, GI tract and vagina but canchange to a pathogen in critically ill or immunosuppressed. Predisposition: moist, warm, macerated or occluded areasystemic antibiotics pregnancy DM Cushing’s Debilitated states < 6 months old 2/2 decreased immune reactivity immunosuppression neoplastic disease of blood and monocyte-macrophage system Carbuncles Collection of infected hair follicles. Most often on back of neck, upper back and lateralthighs. Lesion begins in SQ tissue and lower dermis as a firm mass that evolves into an erythematous, painful, swollen mass that drains through many openings. Abscesses maydevelop. Chills, fever and malaise are systemic symptoms that can occur. Furuncles and carbuncles are treated with warm compresses. Abscess requires I&D.Recurrent infections, extensive lesions or those associated with cellulitis or systemicsymptoms are treated with systemic Abx. Terms such as hypochromic, macrocytic, microcytic, etc Anisocytosis = assuming various sizes Poikilocytosis = assuming various shapes Eryptosis = premature death of damaged erythrocytes Macrocytic-normochromic anemias: Large, abnormally shaped erythrocytes BUT normal hemoglobin concentrations Microcytic-hypochromic anemias: Causes: Small, abnormally shaped erythrocytes AND reduced hemoglobin concentrationsMicrocytic Macrocytic HypochromicNormochromic Antibodies, IgG, IgA, etc An antibody (or immunoglobulin) is a serum glycoprotein produced by plasma cells in response to challenge by an immunogen. The term immunoglobulin is used to denote allmolecules that are known to have specificity for antigen. The term antibody is used to denote one particular set of immunoglobulins with specificity against a known antigen. There are 5 molecular classes of immunoglobulins: IgG – most abundant = 80-85% Account for most of the protective activity against infections. Placental transfer = so it’s the major class of Ab found in fetal/newborn bloodProduced by plasma B cells Has 4 subclasses. Monomer structure / circulates 30-45 days IgA – secretory – has 2 subclasses! Plays crucial role in the immune function of mucous membranes. Found in high concentrations in mucosa (especially GI and respiratory), saliva,tears, and breast milk/colostrum. Dimer structure / circulates 12 days IgM – largest. Synthesized early in neonatal life and is the 1 st Ab produced during initialresponse to antigen. Pentameter structure – it’s the first to respond but the large structure is unstable so it onlycirculates for 2 days IgE – the lease concentrated of all classes. It appears to have very specialized function as amediator of many common allergic responses and in the defense against parasitic infections. Circulates 4 days IgD – information/role is limited and found in very low quantities in blood. They are primarily located on surface of developing B-lymphocytes and function as 1 type of B-cellantigen receptor. Circulates 6 days.Skin cancer Skin Cancer Basal cell carcinoma and squamous cell carcinoma most prevalentMalignant melanoma most deadly Chronic UV exposure causes most skin cancers. Less common in darker skinned people b/c the basal cells contain the pigment melanin,which is a protective factor against sun exposure. Basal Cell Carcinoma Most common in whites. Surface epithelial tumor from undifferentiated basal or germinative cells. They grow upward and laterally or downward to dermal-epidermal junction. Usually depressed centerwith rolled borders. As lesion grows, it ulcerates and develops crusting and becomes firm to the touch. If not treated they invade surrounding tissue and can destroy a nose, eyelid or ear. Metastatic spread is rare b/c they don’t invade vessels or lymph. From UV exposure, arsenic from groundwater wells and autosomal dominant nevoid basal cell carcinoma syndrome.Squamous Cell Carcinoma 2 nd most common tumor of epidermis.2 types: in situ and invasive 75% head/neck, 15% hands, 10% elsewhere Arsenic in drinking water, UV light exposure, Gamma rays and X-raysImmunosuppressed patients have higher risk Invasive SCC can arise from premalignant lesions ie… sun-damaged skin, actinic keratosis, leukoplakia, scars, radiation-induced keratosis, tar and oil keratosis and chronic ulcers andsinuses. Grows rapidly and can spread to regional lymph. In situ SCC confined to epidermis but may extend into dermis. Mohs micrographic surgery (MMS) is a tissue sparing surgical technique. It is indicated for non-melanoma skin cancers (NMSC’s) that have a high risk of recurrence, lesions involving the face, ears, genitalia or when wider excision may risk functional impairment. Parts of the heart in terms of function, such as pericardium The Heart: (parts of the heart in terms of function): Heart structures are categorized by function Structures that direct circulation through the heart: Heart wall = epicardium (outer layer), myocardium (thickest layer) and endocardium(inner layer) Pericardium – prevents displacement, physical barrier against infection/inflammation from lungs and pleural space and contains pain receptors and mechanoreceptors that elicitreflex changes in BP and HR. Pericardial fluid = lubrication (about 20mL) Heart Chambers: There are 4 and they form 2 pumps: Atria (R/L) and Ventricles (R/L)The right heart – lowpressure and pumps blood through lungs The left heart – high-pressure and pumps blood systemically Blood: from lung into LA then LV then out to body via Aorta Back up through body via SVC into RA then RV then back to lungs Heart Valves: AV valves (atrioventricular) = tricuspid valve (right) and mitral valve (left) = control bloodflow from atria to ventricles. Semilunar valves = aortic valve and pulmonary valve = control blood flow out of theventricles.Great Vessels: SVC – superior vena cava and IVC – inferior vena cava = deoxygenated blood flows in RAfrom SVC/IVC R and L pulmonary arteries = carries unoxygenated blood from the R heart to both lungs.These arteries branch further into pulmonary capillary bed. Pulmonary veins (there are 4) – carry oxygenated blood from lungs to the left heart.Aorta = delivers oxygenated blood systemically Congenital heart defects Leading cause of death (excluding prematurity) during 1 st year of life.Develops before birth. Fewer than 200K cases/year Cause only known in about 10% but several factors increase risk: maternal rubella, maternal insulin-dependent diabetes, maternal ETOH, maternal age (>40), maternalphenylketonuria and maternal hypercalcemia and some drugs during pregnancy (i.e.thalidomide, lithium, phenytoin (Dilantin) and warfarin). There are >35 different types and they are classified into 4 categories: 1) Lesions increasing pulmonary blood flow = pulmonary congestion. Ex: PDA, ASD,VSD, complete AV canal defect 2) Lesions decreasing pulmonary blood flow = cyanosis. Ex: Tetralogy of Fallot,tricuspid atresia 3) Obstructive lesions – blood flow out of heart is obstructed. Ex: coarctation of theaorta, hypoplastic left heart, aortic stenosis, pulmonary stenosis 4) Mixing lesions – oxygenated/deoxygenated blood mix. Ex: transposition of the greatarteries, total anomalous pulmonary venous connection, truncus arteriousus. PDA – patent ductus arteriosus = usually closes b/t 15 hours-2 weeks after birth. Vessel located b/t the junction of the main and left pulmonary arteries and the descending aorta.Only 5-10% of all defects. ASD – atrial septal defect = abnormal communication b/t atria. Only 5-10% of all defects. VSD – ventricular septal defect = abnormal communication b/t ventricles. Most common –25-33% of all defects. There are 4 types based on location in septum.Tetralogy of Fallot: the most common cyanotic defect and accounts for 10% or all.Consists of 4 defects: 1) Large VSD high in the septum 2) An overriding aorta that straddles the VSD 3) Pulmonary stenosis 4) RV hypertrophy The embryologic error that causes TOF is unknown. There are 2 trains of thought: 1) The truncus arteriosus divides unevenly, resulting in great vessels of unequal size. 2) The infundibular overgrowth in the RV isthe major developmental anomaly. The patho depends on the degree of pulmonary stenosis, the size of the VSD and thepulmonary/systemic resistance to flow. Because the VSD is usually large, pressures are equal in the RV and LV so the major determinant of shunt direction through the VSD is the difference b/t pulmonary andsystemic resistance. Infants who have little to no R-L shunting are acyanotic and are known as “pink tets” PS decreases blood flow to the lungs so the amount of oxygenated blood that returns to theleft heart is also decreased. If blood also shunts from R to L through the VSD, deoxygenatedand oxygenated blood mix before returning to the lungs = hypoxemia which leads to polycythemia to compensate. Infants with decreased pulmonary flow through the RV outflow tract while the ductusarteriosus remains open will become more cyanotic as the ductus closes. Chronic hypoxemia causes clubbing of fingers/toes. Hypercyanotic or “tet” spell = rare manifestation of TOF = sudden onset of dyspnea, cyanosis and restlessness that usually occurs w/ crying/exertion. These spells are oftenwhat initiates surgical intervention. Infants with TOF have trouble feeding b/c the exertion increases hypoxia. Squatting is a spontaneous compensatory mechanism. It increases systemic resistance anddecreases venous return to the heart from the IVC so more oxygenated blood is available to the body. The increase of systemic resistance also reverses the shunt through the VSD to a L-R shunt, which increases pulmonary blood flow. Typical murmur in TOF is a pulmonary systolic ejection murmur that is caused by obstruction in the outflow tract. More obstruction to flow produces louder murmur, which explains why the murmur often disappears during hypoxic spell since the pulmonary bloodflow decreases to a minimum amount. Dx: ECG shows RV hypertrophy, X-Ray shows heart shaped like a boot with decreasedpulmonary vasculature markings. Tx: current standard to repair before 1 yo.Coarctation of the Aorta: Often seen in Turner’s syndrome A narrowing of lumen that impedes blood flow. About half of those with COA have abicuspid aortic valve. COA causes higher pressures proximal to the site ofstenosis and lower pressures distally. In preductal COA the RV acts as a systemic pump, sending oxygenated blood through theductus into descending aorta below the coarctation In postductal COA the RV cannot pump enough blood through the ductus to the descendingaorta b/c of pressure caused by narrowed aorta. Over time LV hypertrophy develops 2/2 increased afterload and obstruction to flow. HFmay also develop. S/Sx: newborns usually present with CHF and once the ductus closes they will deterioraterapidly from the development of hypotension, acidosis and shock. Older children may not be diagnosed until HTN noted in upper extremities w/ weak/absentpulses in lower. May have cool, mottled skin and occasionally leg cramps w/ exercise. Tx: symptom stabilization first (i.e. prostaglandin admin. mech. Vent, inotropic support forCO maintenance) then surgical repair. Urinary tract obstruction, Anatomical or functional interference with the flow of urine at any site along the urinary tract. Impedes flow proximal to obstruction and dilates structures distal tothe obstruction which increases risk for infection and compromises renal function. Severity determined by 1. Location of lesion 2. Involvement of one or both upper urinary tracts (ureters and renal pelvis) 3. Completeness of obstruction 4. Duration of obstruction 5. Nature of obstruction Causes: UPPER- stones, ureteral compression from aberrant vessel, tumor or abdominalinflammation and scarring LOWER- neurogenic bladder, overactive bladder syndrome, urethral stricture,prostate enlargement, pelvic organ prolapseGI symptoms of conditions such as pyloric stenosis, hiatal hernia, ulcerative colitis Hiatal Hernia Herniation of upper stomach through diaphragm into thorax.4 types: 1) Type I = sliding, most common, exacerbated by things that increase abdominal pressure. Associated w/ GERD b/c the hernia diminishes LES resting pressure. In pregnant women, progesterone/estrogen diminishes pressure of LES even further. 2) Type II = paraesophageal, “rolling”. Stomach pushes up into thorax alongside esophagus through a second hole in diaphragm. Reflux is uncommon BUT with partof the stomach above the diaphragm = congestion of mucosal blood flow leading to gastritis and ulcers. One major complication = strangulation that occludes vessels and results in vascular engorgement, edema, ischemia and hemorrhage. 3) Type III = mixed type 4) Type IV = entire stomach/other abdominal organs slide into thorax S/Sx: Hiatal hernias are often asymptomatic. The symptoms that do develop are associatedwith other GI disorders like GERD. Some symptoms may include heartburn, regurgitation, dysphagia, and epigastric pain. Ischemia from hernia strangulation causes acute, severe chest/epigastric pain, N/V and GI bleeding Pyloric Stenosis: READ WEEK 5 PART 2 DISCUSSIONPer Quizlet: A condition in which the opening b/t the stomach/small intestine blocks food from entering. Symptoms usually appear 3-5 weeks after birth. S/SX are projectile vomitingafter feeding, persistent hunger, stomach contractions, dehydration, changes in bowel movements and weight problems. Ulcerative Colitis Chronic, inflammatory and causes ulceration of the colonic mucosa and extends proximallyfrom rectum into the colon. Risk factors: 20-40 years old, family history, Jewish descent, more prevalent in whites andNorthern Europeans. Less common in smokers! Cause unknown but possibly r/t diet, infection, genetic and immunologic factors. The primary lesions are continuous with no skip lesions, limited to the mucosa and are nottransmural. Rectum almost always involved. The disease is most severe in rectum and sigmoid colon.Mild inflammation = mucosa is hyperemic and edematous, dark red/velvety Severe inflammation = mucosa hemorrhagic, small erosions coalesce into ulcers – thenabscess formation then necrosis and ragged ulceration of the mucosa. Course = intermittent periods of remission and exacerbation.Affects innermost lining of large intestine (colon). S/Sx: usually develop over time rather than suddenly. Depending on severity of disease youmay see: large volume watery diarrhea, cramping, urge to defecate but unable to, purulentmucus/bloody diarrhea, fever, tachycardia, dehydration, weight loss, anemia, rectalpain/bleeding. In about 30% of patients, extraintestinal manifestations occur. Cutaneous lesions, migratory polyarthritis and sacroiliitis, osteopenia/osteoporosis, mouth ulcers, gallstones(common), alterations in coagulation 2/2 the chronic inflammation which leads to DVTs etc. *** The risk of left-sided colon cancer increases after years of UC *** Tx: First line = mesalazine (5-aminosalicylic acid). Corticosteroids and salicylates suppress the inflammatory response to help alleviatecramping pain. Immunosuppressive agents(i.e.… 6-mercaptopurine or azathioprine), cyclosporine,tacrolimus and infliximab). Broad-spectrum antibiotics may induce remission Nicotine may have protective effect in UC BUT NOT Crohn’s disease.If all else fails = surgical resection! Skin cancer lesions Cutaneous Melanoma Malignant tumor from melanocytes. Risk factors: genetic predisposition, UV exposure, acquired melanocytic nevi, family history,fair hair/skin, and presence of susceptibility genes. The relationship b/t nevi and melanoma makes it important to understand the various neval forms. Most nevi never become suspicious BUT suspicious ones should always beevaluated/removed. Biopsy indications: color/size change, irregular notched margin, itching, bleeding/oozing,nodularity, scab formation, ulceration or unusual pattern of presentation. ABCDE: Assymetry, Border irregularity, Color variation, Diameter > 6mm, Elevation (raisedor rapid enlargement). Melanomas arise as a result of malignant degeneration of melanocytes located either alongthe basal layer of the epidermis or in a benign melanocytic nevus. Clinical types of melanoma: Lentigo Malignant Melanoma = 4-15%, 50-80 years old (mean 65) head/neck/handsSuperficial spreading melanoma (SSM) = most common 57-70%, 20-60 years old, females/legs and upper back of both genders Primary nodular melanoma (PNM) = 12-21%, 20-60 years (53 mean), trunk/head/neck Acral-lentiginous melanoma = 2-8% whites, 30-75% blacks/Hispanics/Asians, 20-60 years,palms/soles of feet/mucosa Surveillance: total body exam with pictures, dermoscopy, self-skin examsStaged using TMN criteria Prognostic factors: thickness of lesion, mitotic index, immunohistochemical assessment,ulceration and metastasis.Gastroesophageal reflux disease GERD The reflux of acid/pepsin from stomach to esophagus causing esophagitis. Risk factors: obesity, hiatal hernia and drugs/chemicalsthat relax the LES (anticholinergics,nitrates, calcium channel blockers, nicotine). ** May be a trigger for asthma or chronic cough ** Asymptomatic GERD is known as physiologic reflux Nonerosive reflux disease (NERD) = symptoms of reflux but no esophageal mucosa injury.Vomiting, coughing, lifting, bending or obesity increase abdominal pressure leading to development of reflux esophagitis. Delayed gastric emptying also contributes to reflux esophagitis by 1) lengthening period which reflux is possible 2) increasing acid content of chyme. Disorders that delay emptyinginclude gastric/duodenal ulcers that can cause pyloric edema, strictures that narrow the pylorus, and hiatal hernia, which weakens the LES. Precancerous lesions (Barrett esophagus) with progression to adenocarcinoma can be along-term consequence. S/Sx: heartburn, chronic cough, asthma attacks, laryngitis. Upper abdominal pain 1 hourpost prandial especially if lying down or doing anything that will increase abdominal pressure (vomiting, straining to poop!) Edema, fibrosis (strictures), esophageal spasm, or decreased esophageal motility can =dysphagia. ETOH or acidic foods can hurt when swallowing Tx: PPI (Prilosec, protonix …) most effective monotherapy. Histamine-2 (H2) receptor antagonists (famotidine, zantac…)Prokinetics (metoclopramide …) Antacids (tums…) Hypersensitivity reaction An altered response to an antigen that results in disease/damage to host. Hypersensitivityreactions can be classified in 2 ways: 1) By the source of the antigen that the immune system is attacking (allergy,autoimmunity, alloimmunity) 2) By the mechanism that causes disease (Types I-IV) Hypersensitivity reactions require sensitization against a particular antigen. After sensitization the reactions can be immediate or delayed. The most immediate is anaphylaxis. Some become sensitized rapidly and some take multiple exposures over years.Allergy = exaggerated responses against environmental antigens Autoimmunity = misdirected response against host’s own tissues Alloimmunity = misdirected response against beneficial foreign tissues (i.e. transfusionsor transplants)*** Allergy, autoimmunity and alloimmunity are collectively known ashypersensitivity reactions *** Type I – IgE-mediated Hypersensitivity Reactions – IgE, mast cells, basophils Most common allergies. I.e. seasonal allergies / rhinitisImmediate development Principle effector cells: Mast Cells Type II – Tissue-specific Hypersensitivity Reactions – IgG and IgM i.e. autoimmune thrombocytopenic purpura, Graves disease, AI hemolytic anemiaImmediate reaction Principle effector cells: Macrophages in tissues Type III – Immune-Complex Mediated Hypersensitivity Reactions – IgG/IgM i.e. SLE (systemic lupus erythematous), serum sickness, Raynaud’sImmediate development Principle effector cells: Neutrophils Most are caused by antigen-antibody complexes that are formed in circulation anddeposited later in vessels/tissue. Primary difference b/t types II and III are that: II = the Ab binds to the antigen on the cell surface III – the Ab binds to soluble antigen that was released into the blood/body fluids and thecomplex is then deposited into tissue. Type IV – Cell-Mediated Hypersensitivity Reactions – non Ab involvement i.e. Contact sensitivity to poison ivy and metals (jewelry), graft rejection, RA, Hashimotodisease, Type-1 diabetes. Delayed development Congenital intrinsic factor deficiency is either a genetic disorder that is autosomal recessive or an autoimmune disorder directedagainst gastric parietal cells. It is characterized by pernicious anemia and neurological abnormalities that arepermanent. Patients will exhibit signs of anemia (PA, specifically, so think red-beefy tongue). Tx = B12injections Acid base imbalance Acute epiglottitisCaused by: Haemophilus influenza type B caused 25%, Group A streptococci, also trauma, thermal injuries, posttransplant lymphoproliferative disorder. Infants < 1 yrold at highest risk. Pathophysiology- Bacterial invasion of mucosa with associated inflammation leads to rapid development of edema causing severe, life-threatening obstruction ofupper airway. S+S- Children aged 2-6, sudden high fever, irritability, hot potato voice, inspiratorystridor and severe respiratory distress with drooling and dysphagia, looks very ill. Exam may cause laryngospasm and cause respiratory collapse. Death may occurwithin a few hours. Treatment: early recognition is key, avoiding disturbance of child and airway management. No exam of the throat!! Tracheal intubation should be consideredwith culture of trachea. Corticosteroids. Resolution is typically rapid. Can affect those outside the age range Types of gastric ulcers-signs and symptoms, characteristics Gastric Ulcers: Peptic Ulcer Disease: break/ulceration in mucosa of lower esophagus, stomach or duodenum. Risk: genetic predisposition, H.Pylori, NSAID overuse, ETOH, smoking, acute pancreatitis, COPD, obesity, cirrhosis, age > 65. Can be acute or chronic, superficial or deep. Duodenal Ulcers: Most common type of peptic ulcer. Acid/pepsin concentrations in the duodenum penetratethe mucosal barrier leading to ulceration. S/Sx: chronic, intermittent epigastric pain, 30 minutes-2hours after eating, when stomachis empty (ex… middle of the night is common). Pain is relieved by either ingesting food or antacids = “pain-food-relief pattern”. May be asymptomatic with first manifestation beingperforation or hemorrhage. May cause hematemesis/melena. Gastric Ulcers: Stomach ulcers. Most common b/t 55-65 years and only about ¼ as common as duodenalulcers. Typically in antral region and frequently caused by H.pylori. The primary defect is an abnormality that increases the mucosal barrier’s permeability tohydrogen ions. S/Sx: similar to duodenal ulcers BUT pain is immediate after eating. GU’s tend to bechronic rather than alternating b/t periods of remission and exacerbation. They cause more anorexia, vomiting and weight loss than duodenal ulcers. Stress Ulcers:Acute for of peptic ulcer that tends to accompany the physiologic stress of severe illness,multisystem organ failure, major trauma (severe burns/head injury). Characteristic is bleeding. Usually includes multiple sites of ulceration within stomach and duodenum.Classifieds as: Ischemic = develop within hours of event that causes ischemia of stomach/duodenalmucosa (i.e.… hemorrhage, heart failure, sepsis, burns, trauma) Cushing = associated with severe head trauma or brain surgery as a result of decreasedmucosal blood flow and hypersecretion of acid caused by overstimulation of the vagal nuclei. Curling = as a result of burn injury *** Stress ulcersrarely become chronic *** Zollinger-Ellison Syndrome: Associated with peptic ulcers r/t increased secretion of gastrin, which causes excess secretion of gastric acid, which leads to gastric and duodenal ulcers, GERD, abdominal painand diarrhea. Caused by a gastrinoma of the pancreas or duodenum. Lupus A chronic, multisystem, inflammatory disease that is 1 of the most common, complex andserious AI disorders. Characterized by a large variety of autoantibodies against nucleic acids, erythrocytes,coagulation proteins, phospholipids, lymphocytes, platelets and many other self- components. ***The most characteristic autoantibodies produced in SLA are against nucleicacids (DNA), histones, ribonucleoproteins and other nucleic materials DNA and DNA-containing immune complexes have a high affinity for glomerular basement membranes so may be selectively deposited in glomerulus. The presence of DNA in circulation increases from cellular damage in response to trauma, drugs or infections and isusually removed by the liver HOWEVER the removal of circulating DNA is slowed in the presence of immune complexes so the potential for kidney deposition is increased. Deposition of immune complexes that are made up of DNA/antibody also causes inflammatory lesions in renal tubular basement membranes, brain, heart, spleen lung, GItract, skin and peritoneum. More common in women 20-40 years old. Blacks more than whites.Genetic predisposition is implicated S/Sx: Arthralgias or arthritis (90%) Vasculitis/rash (70-80%) Renal disease (40-50%) Hematologic abnormalities (50% - anemia is the most common complication)Cardiovascular disease (30-50%)The disease process develops slowly and characterized by frequentremissions/exacerbations. Extremely difficult to diagnose because the s/sx affect almost every body system and tendsto be intermittent. The list of 11 most common findings was developed and the serial or simultaneouspresence of at least 4 is a good indicator of SLE in a patient: 1) Facial rash confined to cheeks (malar rash) most distinctive sign (butterfly rash) 2) Discoid rash (raised patches, scaling) 3) Photosensitivity (rash develops from exposure to sunlight) 4) Oral or nasopharyngeal ulcers 5) Nonerosive arthritis of at least 2 peripheral joints 6) Serositis(pleurisy, pericarditis) 7) Renal disorder (proteinuria of 0.5g/day or cellular casts) 8) Neurologic disorders (seizures or psychosis) 9) Hematologic disorders(hemolytic anemia, leukopenia or thrombocytopenia) 10)Immunologic disorders (+ lupus erythematosus (LE) cell preparation, anti-doublestranded DNA, antiSmith (Sm) antigen, false + serologic test for syphilis or antiphospholipid antibodies (anticadiolipin antibody or lupus anticoagulant) 11)Presence of antinuclear antibody (ANA) There is NO cure. Tx: goal is symptom management and prevention of further damage by suppressing the AIresponse. NSAIDS (ASA, ibuprofen, naproxen) reduce inflammation and relieve painCorticosteroids – for more serious disease Immunosuppressive drugs –(methotrexate, azathioprine, cyclophosphamide) for severesymptoms that involve internal organs. UV light can WORSEN symptoms so protection from sun is helpful to prevent “flares” Prolonged use of some drugs can cause transient SLE-like symptoms so medication historyis important for diagnostic evaluation. IVIg is currently being used to treat a variety of AI diseases including SLE! It results in arebound of platelets when thrombocytopenia is present. More recently, monoclonal antibodies and other reagents have specifically targeted/suppressed B and T cells that are participating in AI responses – this has beensomewhat successful in SLE, RA and other AI diseases. General adaptation syndrome STRESS!!!!GAS is a triad or syndrome of manifestations that represent a nonspecific response to noxious stimuli such as cold, surgical injury and restraint. The 3 most common structuralchanges (the triad) found when lab rats were exposed to noxious stimuli are: 1) adrenal cortex enlargement 2) atrophy of thymus and other lymphoid structures 3) bleeding ulcers in stomach and duodenal lining.There are 3 successive stages of the GAS: 1) Alarm or reaction – the CNS is aroused and “fight or flight” immobilized 2) Resistance or adaptation –fight or flight in action 3) Exhaustion – this is where the continuous stress causes progressive breakdown ofcompensatory mechanisms/homeostasis. Exhaustion marks the onset of certain diseases (diseases of adaptation) The stressresponse is holistic and complex and involves biochemical relationships of theCNS, ANS, endocrine system and immune system, which all together cause the stress response. Also, commonly referred to as the HPA axis (hypothalamic-pituitary-adrenal! The hypothalamus secretes CRH (corticotropin-releasing hormone) that bindstoreceptors on pituitary cells. The pituitary cells produce ACTH (adrenocorticotropic hormone) that travel to theadrenal glands The adrenal glandsthen release glucocorticoid hormones, mainly cortisol. *** Glucocorticoids (cortisol) enhance immunity during acute stress but suppressimmunity during chronic stress b/c of prolonged exposure and increased concentration *** Ventilation/perfusion ratio normal is 0.8 and this is the amount by which perfusion exceeds ventilation under normal conditions. This ratio is used to assess the efficiency/adequacy of the matching of 2 variables: Ventilation (air thatreaches the alveoli) and Perfusion (blood that reaches alveoli via capillary). V: Q ratio can be defined asthe amount of air reaching the alveoli per minute. Bile salt deficiencies Bile salts needed to digest/absorb fat. Bile enters duodenum, then bile salts aggregate with fatty acidsand monoglycerides to form micelles. Micelle formation makes fat molecules more soluble and minimum concentration of bile salts is needed to form micelles (critical micelle concentration). So decreased micelle formation = fat malabsorption. Clonal selection Before birth we produce a large number of T and B-lymphocytes that have the capacity to recognized almost any foreign antigen. Each individual T or B cell specifically recognizes ONLY one particular antigen but the sum of the population of lymphocyte specificities mayrepresent millions of foreign antigens. This process is called the generation of clonal diversity and happens in primary lymphoid organs --- thymus for T cells and bone marrowfor B cells! These organs release lymphocytes as immature cells that have the capacity to react with antigens and they migrate to secondary lymphoid organs to prepare for antigenexposure. The lymphocytes remain dormant until an antigen initiates the 2nd phase of the immune response, clonal selection. Clonal selection involves a complex interaction among cells. Inorder to initiate an effective immune response, antigens must be “presented” to the immune cells in a very specific manner, which is the job of antigen-processing cells (antigen-presenting or APC’s). There are 3 groups of cells that must cooperate to make an immune response: APC’s interact with subpopulation of T-cells (Th cells) and immunocompetent B or T cells. This results in differentiation of B cells into active antibody-producing cells (plasma cells) and T cells in effector cells (i.e. Tc cells). Obstructive sleep apnea A breathing disorder defined by prolonged partial and/or intermittent complete UAO while sleeping. Repetitive increases in resistance to airflow in upper airway w/ loud snoring, gasping, intervals of apnea10-30 seconds long Associated w/ reduced blood O2 saturation and hypercapnia. Common in children. R/T adenotonsillar inflammation or obesity. Severity of disease determined by AHI(apnea hypopnea index). The index represents how many apnea or hypopnea (partial airway closure) occur/night. Risk factors: obesity, male gender, menopause and age Excessive daytime sleepiness most common sign. Dx: polysomnography Tx: CPAP, dental devices that modify position of tongue/jaw, surgical reconstruction of upper airway,weight reduction Tx in children: 1 st = tonsillectomy/adenoidectomy, then CPAP Large bowel obstruction Any condition that prevents normal flow of chyme through intestinal lumen.Small bowel more commonly obstructed 2/2 narrow lumen Criteria for classification: Onset Acute – sudden, usually 2/2 torsion, intussusception, herniation Chronic – protracted onset, usually tumor growth or progressive stricturesExtent of Obstruction Partial – incomplete obstruction of lumen Complete – complete obstruction of lumen Location of Obstruction Intrinsic – obstruction develops within lumen (i.e. luminal edema, gallstones, tumors,intraluminal fibrosis) Extrinsic – obstruction originates outside lumen (i.e. tumors, torsion, fibrosis, hernia,intussusception) Effects of Intestinal Wall Simple – obstruction without impairment of blood supplyStrangulated – occlusion of blood supply Closed Loop – obstruction at each end of a segment of the intestine Causal Factors Mechanical – intrinsic or extrinsic lesions (usually treated surgically) Functional – paralysis of intestinal musculature 2/2 accidental or surgical trauma,peritonitis, electrolyte imbalance, spasmolytic agents (usually treated medically). Common causes of obstructions: Herniation Intussusception – more common in childrenTorsion Diverticulosis Tumor Paralytic Ileus – post-op ileusFibrous adhesions Most common obstruction is simple obstruction of the small intestine from fibrousadhesions. Most common large bowel obstructions: colorectal cancer, volvulus (torsion) and stricturesr/t diverticulitis. Large Bowel Obstructions consequences are r/t to competence of the ileocecal valve, which normally prevents reflux of colonic contents into small intestine. When valve is competent the cecum can’t decompress = distention. Ischemia occurs when the intraluminal pressure exceeds the capillary pressurein the lumen. S/Sx: hypogastric pain and abdominal distention. Pain can vary from vague to excruciating. Vaginal candidiasisYeastlike fungus Candida albicans is normal on mucosa, skin, GI tract and vagina but canchange to a pathogen in critically ill or immunosuppressed. Predisposition: moist, warm, macerated or occluded areasystemic antibiotics pregnancy DM Cushing’s Debilitated states < 6 months old 2/2 decreased immune reactivity immunosuppression neoplastic disease of blood and monocyte-macrophage system Folate deficiency Folate essential for RNA/DNA synthesis within maturing erythrocytes. Common in alcoholics and chronically malnourished. ETOH interferes with folate metabolism in liver.Fad diets and diets that lack vegetables are also common dietary causes. Impaired DNA synthesis results in megaloblastic cells with clumped nuclear chromatin andanemia result s from apoptosis of erythroblasts in the late stages of erythropoiesis. Also cause neural tube defects of fetus! Increases risk of CAD and cancers, especially colorectal! S/Sx: Cachectic, malnourished, scales/fissures at corners of mouth, stomatitis, ulcerations of buccal mucosa/tongue (burning mouth syndrome), dysphagia, flatulence, watery diarrhea,sprue (chronic malabsorption syndrome). Thiamine deficiency often accompanies folate deficiency! Tx: Daily oral administration of folate supplement until adequate blood levels reached.Long-term treatment not indicated if patient is able to make dietary adjustments. Pancreatic insufficiency Causes: chronic pancreatitis, pancreatic carcinoma, pancreatic resection, CF. There has to be significant damage or loss of tissue before enzyme levels decrease enoughto cause maldigestion. Fat digestion is chief problem of pancreatic insufficiency even though all nutrients are affected. The reason that fat is most affected is because salivary amylase/enzymes secretedby the intestinal brush border assist in carb and protein digestion but not in fats.The absence of pancreatic HCO3- in duodenum/jejunum causes acidic pH that worsensmaldigestion by preventing activation of pancreatic enzymes that are present. The most common signs: steatorrhea (fat in stool), weight loss.Lipase supplementation is most successful treatment. Types of fractures Oblique: Fracture at an oblique angle from one side of bone to other caused by pressure/compression atan angle Occult: Hidden fracture that’s not readily visible caused by minor force Open: skin broken over fracture with poss. Soft tissue trauma Pathologic: transverse, oblique or spiral fracture of bone weakened by tumor pressure or presence. Segmented: two or more pieces/segments of bone resulting from fracture. Spiral: fracture that curves around cortices and may become displaced by a twist. Transverse: Perpendicular straight line fracture from one side of bone to the other Greenstick: break in one side of bone that does not go fully through to other side Impacted: One end of fracture wedged into opposite end of inside fractured fragment. Closed: Skin over fracture intact Open: Skin is broken over fracture Comminuted: Multiple bone fragments Linear: Fracture line parallel with long axis of bone Impacted: Fragments of fracture are pushed into each other Pathologic: Fracture occurs at point of bone which is weakened by disease Avulsion: Broken fragment of bone connected to ligament or tendon Compression: Fracture is wedged or squeezed together on one side of bone Displaced: Fracture with one or more bone fragments out of alignment Extracapsular: Bone fragment close to joint but not in joint capsule Intracapsular: Bone fragment extends into or is within joint capsule Fragility: Caused by low level trauma Torus: buckling of cortex (edge of bone)Bowing: Bending of the bone Stress: Microfracture Transchondral: Separation of cartilaginous joint surface from main shaft of bone Genetic disorders such as Down Syndrome, Turner Syndrome, etc Down syndrome- Trisomy of 21st chromosome-- 75% are inherited from mother Characterized by: Decreased IQ, low nasal bridge, epicanthal folds, protruding tongue, flat/low set ears,hypotonia, short stature. Many end up with similar symptoms to Alzheimer’s (both affect the 21st chromosome). Many are stillborn or will not live past the age of 10. Those who survive have a life expectancy no greaterthan 60. Caused by a nondisjunction during one parent’s formation of gamettes.Maternal age > 35 has more significant risk, paternal age has no effect.1/3-1/2 have congenital heart defects Decreased ability to fight infections and a higher susceptibility to leukemia. Turner syndrome- Chromosome 45 and has a single X with no Y therefore it only affects females Manifestations- gonadal streaks instead of ovaries, short stature, webbing of neck, widely spaced nipples, narrowing aorta, pedal edema in infants, sparce body hair, normal IQ (spacial and mathematicalabilities can be decreased). Treatment: Teenagersreceive estrogen treatment and often human growth hormones Klinefelter syndrome- 2 X chromosomes and at least one Y chromosome affecting males. Manifestations: usually sterile, gynomastia, small testes, sparce body hair, high pitched voice, elevatedstature, moderate mental impairment. Cause: nondisjunction of X chromosome in mother and each additional X chromosome increases themental impairment significantly. Risks- increasing maternal age. Cri du chat syndrome “cry of the cat”- Manifestations- low birth weight, severe mental retardation, microcephaly, heart defects and acharacteristic facial appearance. Fragile X syndrome- High level of cognitive impairment and is second most common cause of mentalretardation after Down syndrome Vitamin B-12 therapy Treatment of Pernicuous Anemia (megoblastic) and for vitamin B12 deficiency. Benefits- to help alleviatesymptoms and complications of deficiency (mood disorders, fatigue, memory failure, anemia and hypotension. Vit B12 is needed for erythrocyte production. Treatment of choice- Weekly injections until corrected followed by monthly injections for life.Effectiveness of treatment is determined by rising reticulocyte count. Within 5-6 weeks, blood count returns to normal. Glaucoma Leading cause of visual impairment and blindness. Caused by increased intraocular pressure (>12-20mmHg). Open angle is the most common subtype Chronic high intraocular pressures death of retinal ganglions and optic nerve degeneration 1) loss ofperipheral vision. 2) central vision impairment. 3) blindnessExtreme increase in pressures cause blindness within hours hour days Loss of visual acuity is caused by pressure on the optic nerve (causes acute pain). Treatmenteye drops which reduce secretion or increase absorption of aqueous humor.Surgery to open spaces of trabeculae and reduce intraocular pressure Cervical immunoglobulin Purpose- to protect body against antigens that have not yet penetrated the sin or mucous membranes. Itis an initial defense to keep bacteria levels within a normal range. The secretory response occurs locally and externally. Concept of pain **See pgs 485-495 • Pain is one of the body’s most important adaptive and protective mechanisms and all definitionssuggest it is a complex phenomenon and cannot be characterized as only a response to injury https://www.youtube.com/watch?v=fUKlpuz2VTs Nocioception has 4 phases: 1) Transduction (tissue exposed to chemical, mechanical or thermal stimulation by nocioceptors.2) Transmission 3) Perception 4) Transduction Autosomal dominant diseases (ADD) pg 152-154 ADDs are rare due to the fact that it is so uncommon for 2 people who both have a disease to produceoffspring.Necessary characteristics1) males and females have an equal chance to transmit disease to offspring 2) heterozygous individuals must transmit to at least ½ of their children 3) Cannot skip generations A child diagnosed with an ADD with no family history is due to a new mutation (more common)Reoccurance risk refers to the probability of a family member having disease. Age dependent penetrance- when symptoms are not seen until after 40 yrs of age. If one parent is affected and other is not then ½ of children will be affected as well. The odds continue tobe ½ with each new pregnancy. ADDs--- retinoblastoma (dysfunction of tumor suppressor gene), Huntington disease (progressive dementia and uncontrolled limb movements), Marfans, neurofibromatosis (von Recklinghausen disease)and hemophilia A. Congenital murmurs Murmur caused by a congenital heart condition. Symptoms include cyanosis and symptoms of CHF Conditions includePatent ductus arteriosis (PDA)—machine like continuous murmurAtrial septal defect (ASD) systolic ejection murmur Ventricular septal defect (VSD) initially no murmur. Once pulmonary vascular resistance decreases leftto right shunting occurs (loud harsh holosystolic murmur) Atrioventricular canal defect – holosystolic regurgant murmur Tetralogy of Fallot- Pulmonary systolic ejection murmur which often disappears during hypoxic spellsTricuspid atresiamurmur Lactose intolerance The inability to digest lactose (milk sugar) from an inadequate production of lactase.Common cause of diarrhea in children under the age of 7. Malabsorption of lactose osmotic diarrhea (fluids->via osmosis to vascular compartment intointestinal lumen. Undigested sugar is processed by colonic bacteria forming gas. Signs and symptoms are diarrhea, abdominal pain, bloating and gas. Diagnosis- elimination of dietary lactose or hydrogen breath testing. Treatment- lactase treated dairy products or lactase supplements, and decreased dairy intake Angiotensin-renin systemRenin is released by Juxtaglomerular cells (JG cells) and inactive angiotensin is released by liver cells. Renin activates angiotensin thus forming angiotensin II. This activation causes ADH to be released from the pituitary gland (constricting smooth muscle cells, and stimulates kidneys to hold water increasing blood volume, stroke volume, blood pressure), and the adrenal glands to release aldosterone (increasingblood volume). Triggersto release renin are hypotension, sympathetic nerve activation (nerve endings are located in JGcells) and low salt (sensors in macula densa send messengers-prostaglandins- to JG cells AIDS Viral acquired immune deficiency caused by HIV. HIV/AIDS depletes a person’simmune system(specifically Th cells) making a person extremely susceptible to malignancies and infections. Most new infections are in gay/bisexual men. Women continue to have the highest riskHIV is a blood borne pathogen present in body fluids and transmitted by IV drug use, sexual activity, andmaternal child transmission in utero or at birth. HIV is a retrovirus- uses reverse transcriptase (a viral enzyme) to convert RNA into double stranded DNA.This new DNA is inserted into infected cell’s genetic material by integrase (a second enzyme). Cell can remain dormant (can be dormant for years) or become activated. When activated the cell translation ofviral information can be activated resulting in new virions, lysis and death of infected cell and shedding of infections HIV particles. The CD4 molecule on surface of helper T cells binds with gp120 (primary surface receptor on HIV-theenvelope glycoprotein). The shedding of gp120 induces apoptotic cell death of uninfected T lymphocytes, neurons and monocytes Primary cellular targets of HIVCD4 positive Th cells, dendritic cells, macrophages, CD8 positive Tc cells, NK cells, some neural cells. **Brain, Thymus, lymp nodes, lung, bone marrow, colon, duodenum, rectum, skin** Major manifestation is striking decrease in number of CD4+ Th cells thus leading to a reversal in thenormal CD4/CD8 ratio People can be infected but remain seronegative for 6-14 months. Antiretroviral Therapy for treatment. This is a great video! https://www.khanacademy.org/science/health-and-medicine/infectious-diseases/hivand-aids/v/what-is-hiv-and-aids And this video gets a little more in depth with the pathophys of infectionhttps://www.khanacademy.org/science/health-and-medicine/infectious-diseases/hiv-and-aids/v/how-hiv-infectsus-cd4-t-helper-lymphocyte-infection Carcinoma BENIGN TUMORS MALIGNANT TUMORS Grow slowly Grow rapidly Have a well-defined capsule Are not encapsulated Are not invasive Invade local structures and tissues Are well differentiated; look like the tissue from which they arose Are poorly differentiated; may not be able to determine tissue of origin Have a low mitotic index; dividing cells are rare High mitotic index; many dividing cells Do not metastasize Can spread distantly, often through blood vessels and lymphatics Hormonal regulation of calciumBlood calcium levels are regulated by parathyroid hormone (PTH), which is produced by the parathyroidglands. PTH is released in response to low blood calcium levels. It increases calcium levels by targeting the skeleton, the kidneys, and the intestine. Calcium homeostasis refers to the regulation of the concentration of calcium ions in the extracellular fluid [Ca++]ECF. This parameter is tightly controlled because the calcium ions have a stabilizing effect on voltage-gated ion channels. For instance, when [Ca++]ECF is too low (hypocalcemia), voltage-gated ion channels start opening spontaneously, causing nerve and muscle cells to become hyperactive. The syndrome of involuntary muscle spasms due to low [Ca++]ECF is called hypocalcemic tetany. Conversely,when [Ca++]ECF istoo high (hypercalcemia), voltage-gated ion channels don't open as easily, and there isdepressed nervous system function. Another problem of hypercalcemia is that calcium can combine withphosphate ions, forming deposits of calcium phosphate (calcification and stones) in blood vessels and in the kidneys. The figure above illustrates the physiological influences on [Ca++]ECF.[Ca++]ECF is influenced by dietary intake, Ca++ absorption in the small intestine, and by excretion of Ca+ + in the urine. Importantly, the bones contain 99% of the Ca++ in the body, so bones provide a reservoirof Ca++ that can be used to maintain [Ca++]ECF. The two most important hormones for maintaining calcium levels in the body are parathyroid hormone(PTH) and 1,25(OH)2D (the active form of vitamin D). The major regulator is PTH, which is part of a negative feedback loop to maintain [Ca++]ECF (see Humoral regulation). PTH secretion is stimulated by hypocalcemia, and it works through three mechanisms to increase Ca++ levels: 1) PTH stimulates the release of Ca++ from bone, in part by stimulating bone resorption. 2) PTH decreases urinary loss of Ca++ by stimulating Ca++ reabsorption. 3) PTH indirectly stimulates Ca++ absorption in the small intestine by stimulating synthesis of 1,25(OH)2Din the kidney. PTH Effects on BonePTH has a rapid effect (occurring within minutes), whereby it stimulates osteoblasts to pump Ca++ ionsout of the fluid surrounding the bone (which has a higher Ca++ concentration) and into the ECF. Over a longer time course, PTH stimulates bone resorption by stimulating osteoclastogenesis. Although PTH stimulates bone resorption, it is actually the osteoblasts that express PTH receptors. PTH stimulation ofosteoblasts causes them to express the signaling molecule RANKL that activates the RANK receptor onosteoclast precursors. Neural tube defect NTD’s are formed within the first month of embryonic development when normal formation of spinalcord and brain during this time are stopped. Maternal folate deficiency is connected with NTD- reasonunknown. *Lack of closure of the neural groove caused by an arrest of the normal development of thebrain and spinal cord during the first month of embryonic development. Defects in lack of neural tube closure are divided into 2 categories- posterior defects (most common) andanterior midline defects. Birth defect related to NTD spinal bifida where there is a protrusion of meninges but the spinal cordremains in the spinal canal. Anencephaly- soft bony component of skull and much of brain are missing. Encephalocele- hernia or protrusion of various amounts of brain and meninges through a defect in theskill resulting in saclike structure. Meningocele- cystlike dilation of meninges protruding through a defect in posterior arch of the vertebra. Myelomeningocele- cystic dilation of meninges and protuberance of various amounts of spinal cordthrough vertebral defect—more severe than Meningocele. Types of hormones- (By gland/hormone) Endocrine gland Hormone Main tissues acted on by hormone Main function of hormones Hypothalamus Thyrotrophin releasing hormone (TRH) Anterior pituitary Stimulates release of thyroid stimulating hormone (TSH) from the anterior pituitary Somatostatin Anterior pituitary Inhibitory hormone that prevents release of hormones such as growth hormone from the anterior pituitary Gonadotrophin releasing hormone (GnRH) Anterior pituitary Stimulates release of follicle stimulating hormone (FSH) and luteinising hormone (LH) from the anterior pituitary Corticotrophin releasing hormone (CRH) Anterior pituitary Stimulates adrenocorticotrophic hormone (ACTH) release from the anterior pituitary Growth Hormone Anterior Stimulates release of growth hormone (GH)Releasing Hormone (GHRH) pituitary form the anterior pituitary Anterior pituitary Thyroid stimulating hormone (TSH) Thyroid gland Stimulates release of thyroxine and triiodothyronine from the thyroid gland Luteinising hormone (LH) Ovary/Testis Females: promotes ovulation of the egg and stimulates oestrogen and progesterone production Males: promotes testosterone release from the testis Follicle stimulating hormone (FSH) Ovary/Testis Females: promotes development of eggs and follicles in the ovary prior to ovulation Males: promotes production of testosterone from testis Growth Hormone (GH) Bones, cartilage, muscle, fat, liver, heart Acts to promote growth of bones and organs Prolactin (PRL) Breasts, brain Stimulates milk production in the breasts and plays a role in sexual behavior Adrenocorticotrophic hormone (ACTH) Adrenal glands Stimulates the adrenal glands to produce mainly cortisol Posterior pituitary Vasopressin (antidiuretic hormone, ADH) Kidney, blood vessels, blood components Acts to maintain blood pressure by causing the kidney to retain fluid and by constricting blood vessels Oxytocin Uterus, milk ducts of breasts Causes ejection of milk from the milk ducts and causes constriction of the uterus during labour Thyroid gland Thyroxine (T4) Most tissues Acts to regulate the body’s metabolic rate Tri-iodothyronine (T3) Most tissues Acts to regulate the body’s metabolic rate Parathyroid glands Parathyroid hormone (PTH) Kidney, Bone cells Increases blood calcium levels in the blood when they are low Calcitonin Kidney, Bone cells Decreases blood calcium levels when they are high Adrenal cortex Cortisol Most tissues Involved in a huge array of physiological functions including blood pressure regulation, immune system functioning and blood glucose regulation Aldosterone Kidney Acts to maintain blood pressure by causing salt and water retention Androgens Most tissues Steroid hormones that promote developmentof male characteristics. Physiological function unclear Adrenal medulla Adrenaline and noradrenaline (the catecholamines) Most tissues Involved in many physiological systems including blood pressure regulation, gastrointestinal movement and patency of the airwaysPancreas Insulin Muscle, fat tissue Acts to lower blood glucose levels Glucagon Liver Acts to raise blood glucose levels Somatostatin Pancreas Acts to inhibit glucagon and insulin release Ovary Oestrogens Breast, Uterus, Internal and external genitalia Acts to promote development of female primary and secondary sexual characteristics.Important role in preparing the uterus for implantation of embryo Progesterone BreastUterus Affects female sexual characteristics and important in the maintenance of pregnancy Testis Testosterone Sexual organs Promotes the development of male sexual characteristicsincluding sperm development Stomach Gastrin Stomach Promotes acid secretion in the stomach Serotonin (5-HT) Stomach Causes constriction of the stomach muscles Duodenum and jejunum Secretin Stomach, Liver Inhibits secretions from the stomach and increases bile production Cholecystokinin (CCK) Liver, Pancreas Stimulates release of bile from the gall bladder and causes the pancreas to release digestive enzymes Kidney Erythropoietin Bone marrow Stimulates red blood cell development in the bone marrow Heart Atrial natiuretic factor (ANF) Kidney Lowers blood pressure by promoting salt and water loss Skin Vitamin D Small intestine, Kidney, Bone cells Stimulates the uptake of calcium in the small intestine, retention of calcium and release of calcium from bone stores Types of hormones by structureGlycoprotein Proteins attached to carbohydrates for the purpose of identification. Glycoproteins serve a number of important functions in the human body including providing structural support, lubrication, assisting withthe immune system and have a role in every other biological function studied thus far. Glycoproteins are produced in three types: N-linked, O-linked and nonenzymatic. The N-linked glycoproteins have the saccharide molecule attached to the nitrogen atoms of the aminoacid asparagine. The sugar molecules of N-linked glycoproteins are added as complex multi-chained molecules. O-linked glycoproteins add their saccharides as single sugars and are attached to the hydroxyl side chainof amino acids serine or threonine. These glycoproteins are usually secreted out of the cell into the extracellular matrix Nonenzymatic glycoproteins are polypeptides that have over time simply had sugar molecules added tothem as they became available. In patients with excess blood glucose levels, the nonenzymatic glycoprotein production can be quite high. A diagnostic test for diabetes, the A1C blood test, measuresthis excess production. Kidney stonesCalculi, or urinary stones (urolithiasis), are masses of crystals, protein, or other substances that are a common cause of urinary tract obstruction in adults. They can be located in the kidneys, ureters, andurinary bladder. Classified by primary minerals that they consist of. ***Most common type are calcium oxalate orphosphate*** (70%- 80%), struvite (15%) and uric acid (7%). Calcium stones- genetic and environmental factors, most are idiopathic. Some caused byhyperparathyroidism and prolonged immobilization (causing bone demineralization). Clinical manifestations- Renal colic (moderate to severe pain radiating from flank to groin (stone in renalpelvis or proximal ureter), colic radiating to lateral flank or lower abdomen (stone in mid ureter), urgency, frequent voiding, urge incontinence) obstruction in lower ureter or reterovesical junction. **Pain can be severe/incapacitating and may be accompanied by nausea and vomiting with either grossor microscopic hematuria. Diagnosis made by clinical presentation, history, imaging (ultrasound, CT, pyelogram and MRI) realpelvic/urethral pressures and UA (with pH) and 24 urine. Also, if possible, the stone is collected andanalyzed after passing to determine what stone consists of. Treatment: Manage pain (analgesics), promote stone passage (alpha agonists or calcium channel blocker), reduce size of stones already formed (increase fluid intake) and prevent new formation (changing diet) and removing stones (Percutaneous nephrolithotomy, uteroscopy, ultrasonic or laserlithotripsy). Type 2 diabetes Most common type due to an environmental-genetic interaction. Risk factors are age, obesity, HTN,physical inactivity, and family history. Metabolic syndrome (central obesity, dyslipidemia, prehypertension, and elevated fasting blood glucose level) is risk factor. Combination of genetic, epigenetic and environmental influences. ***Risk factors cause insulin resistance but only those predisposed to beta cell dysfunction will developtype II diabetes*** • 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 synthesisof glucose, glucagon synthesis, and cellular responsiveness to insulin stimulation. Pituitary hormone secretion Anterior pituitary • Growth hormone Targets Bone and muscle growth and liver glycogenolysis/increased fat mobilization. • ACTH (Adrenocorticotropic hormone) Stimulates adrenal cortex to release cortisol and aldosterone• TSH (Thyroid stimulating hormone) Stimulates thyroid to release Thyroxine- increased production and secretion of thyroid hormone. • Gonadotropic hormones (FSH, LH) Testesrelease Testosterone and ovaries to release Estrogen/progesterone. • MSH (Melanocyte stimulating hormone) Skin- promotes secretion of melanin and lipotropinto make skin darker. • Prolactin Mammary glands for milk production Posterior pituitary • ADH (Antidiuretic hormone) Kidney tubules/collecting ducts to hold onto water to increasestroke volume and blood pressure and smooth muscle cells in body to contract. • Oxytocin Mammary glands and smooth muscle of uterus to contract. Signs of breast cancerThe first sign of breast cancer is usually a painless lump. Other signs include-palpable nodes in the axilla,dimpling of the sin or nipple, bone pain (caused by metastatic spread), abnormal nipple discharge, orange peel like pitting of the skin, skin discoloration/abnormalities/ulcerations, localized pain and edema. Alzheimer’s diseaseAlzheimer’s is the leading cause of dementia and one of the most common causes of severe cognitivedysfunction in older adults. ****The greatest risk factors are age and family history**** ***Pictured is risk factors and Pathogenesis of early and late onset Alzheimer’s****There is a long preclinical and prodromal course and pathophysiological changes can take decades to become evident. It is progressive starting with mild short term memory loss progressing to total loss of cognition and executive functions. Pts suffer from increasing forgetfulness, and decreasing- ability to concentrate, ability for abstract/critical thinking, appropriate judgement and mathematical calculation. Mental status changes (anxious, depressed, hostile, emotionally labile, prone to mood swings and weightloss (wt loss can be significant)). Diagnosis- most definitive in post mortem exam of brain. Is diagnosed otherwise by clinical history,cognitive testing, course of illness, and brain imaging (blood flow changes). Treatments include cholinesterase inhibitors, glutamate block, NMDA receptor agonists. It is also important to work to maintain any preserved cognitive function and to maximize hygiene, nutrition andhealth. Guillain-Barre Syndrome Acquired acute inflammatory demyelinating or axonal polyneuropathy with 4 subtypes. GBS-autoimmune disease triggered by a preceding bacterial or viral infection. Molecular mimicry associated with immune injury and glycolipids are the immune targets. Muscleinnervated by damaged peripheral nerve undergoes denervation and atrophy. *If cell body survives regeneration recovery of function *If cell body dies no regeneration Typical 1 st manifestations- numbness, pain, paresthesia, weakness in limbs Acute/subacute progressive paralysis in proximal muscles, distal muscle paresis and paralysi present inascending pattern involving limbs, respiratory muscles and bulbar muscles (Chewing, swallowing, dysphagia, dysarthria). Other manifestations- tingling/burning, shock like sensations in limbs, respiratory weakness leading to ventilation, facial and bulbar weakness, autonomic dysfunction (tachycardia, bradycardia-less common, hypotension, HTN), hyponatremia-caused by SIADH, respiratory arrest and cardiovascular collapse. Improvement of weakness generally plateaus or improves by the 4 th week and strength takes days toweeks to return. Diagnosis- clinical history, CSF (high protein), nerve conduction studies (determines subtype), and EMG. Treatment- Ventilatory support and management of autonomic nervous system dysfunction. IVimmunoglobulins, plasmaphoresis, and rehab once condition is improvement. Sympathetic/parasympathetic nervous system *See pg 471-476 • The parasympathetic system balances the sympathetic nervous system and, thus, also influencesadaptation or maladaptation to stressful events. The parasympathetic system also has anti- inflammatory effects. • The parasympathetic system opposes the sympathetic (catecholamine) responses, for example, by slowing the heart rate. Researchers evaluate the relative balance of the parasympathetic andsympathetic nervous systems using a technique known as heart rate variability (themeasurement of R wave variability from heartbeat to heartbeat). • Under conditions of allostatic overload, the parasympathetic system may decrease itsrestraint ofthe sympathetic system, resulting in increased or prolonged inflammatory responses ANS promotes a steady state among visceral organs (regulation of cardiac muscle and glands of the bodyInvoluntary system divided into sympathetic and parasympathetic Sympathetic (fight or flight) which is widespread through whole symptom Uses epinephrine and norepinephrine Increase BP, pupil dilation, bronchodilation, goosebumps, increased sweat glands, arteriole smooth muscle contraction, increased force/rate of cardiac contractionand increased cardiac output, increased glycogen synthesis and decreased insulin production. Parasympathetic-(rest and relaxation) works with specific fibers with particular target areasDecreased HR, and innervations to enhance digestion. https://www.youtube.com/watch?v=jA1NyCE4M2g&feature=youtu.be ACTH Secretion of adrenocorticotropic hormone is controlled by three inter-communicating regions of the body, the hypothalamus, the pituitary gland and the adrenal glands. This is called the hypothalamic– pituitary–adrenal axis. When adrenocorticotropic hormone levels in the blood are low, a group of cells inthe hypothalamus release a hormone called corticotrophin-releasing hormone which stimulates the pituitary gland to secrete adrenocorticotropic hormone into the bloodstream. High levels of adrenocorticotropic hormone are detected by the adrenal glands which stimulate the secretion of cortisol, causing blood levels of cortisol to rise. As the cortisol levels rise, they start to slow down the release of corticotrophin-releasing hormone from the hypothalamus and adrenocorticotropic hormone from the pituitary gland. As a result, the adrenocorticotropic hormone levels start to fall. This is called a negative feedback loop. Stress, both physical and psychological, also stimulates adrenocorticotropic hormone production andhence increases cortisol levels. **The effects of too much adrenocorticotropic hormone are mainly due to the increase in cortisol levelswhich result. Higher than normal levels of adrenocorticotropic hormone may be due to: Cushing's disease – this is the most common cause of increased adrenocorticotropic hormone. It is caused by a noncancerous tumour called an adenoma located in the pituitary gland, which producesexcess amounts of adrenocorticotropic hormone. (Please note, Cushing’s disease is just one of the numerous causes of Cushing’s syndrome). A tumour, outside the pituitary gland, producing adrenocorticotropic hormone (also called ectopicadrenocorticotropic hormone tumour).Addison's disease (although cortisol levels are low, adrenocorticotropic hormone levels are raised). Congenital adrenal hyperplasia (a genetic disorder with inadequate production of cortisol, aldosteroneor both). Bartholin glands (pg 772) Also called greater vestibular or vulvovaginal glands. In response to sexual stimulation Bartholin glandssecrete mucus to lubricate inner labial surfaces and enhance viability and motility of sperm. It also facilitates coitus (sexual intercourse). Gonococcal disease (pg 920-922) Gonorrhea is caused by gonococci (species of Neisseria gonorrhoeae) Risk factors include: Transient or urban residence, sexual activity at a young age, drug use, prostitution,and previous case of gonorrheal or concurrent STI. Females have a higher risk of contracting than men Transmitted through sexual, oral or anal intercourse. Pregnant women can transmit to fetus. Glomerulonephritis- Inflammation of the glomerular filtration membrane (epithelium, podocytes, endothelium and basement membrane). Messangelial expansion leads to leaking and loss of negativecharge thus causing hematuria (casts and proteinuria). Severe glomerulonephritis -> edema, hypertension, impaired renal function causing decreased glomerular filtration (due to decreased blood flow)-> decreased GFR ultimately causing renal failure. Small patent ductus arteriosus (PDA)- ***Picture--PDA with left to right shunt*** In fetal circulation a PDA allows blood to shunt from PA to aorta. Then at birth when the placenta is removed and lungs expand, the PDA constricts within the first few hours of life. Full closure occurs within15hrs to 2 weeks after birth.Defect of the PDA accounts for 5-10% of all congenital cardiac defects and is most prevalent in preemies.Failure of PDA closure=persistent patency of ductus arteriosus. IN PDA: At birth pulmonary circulation = systemic circulation (minimal shunting) Later Pulmonary vascular resistance decreases and reverse fetal shunting occurs (left to right or aortato PA) pulmonary blood flow increases increasing pulmonary venous return to the LA and LV increased work of Left heart leading to increased Right heart ventricular pressure increased pulmonary vascular pressure. Clinical manifestations- Infant has an audible continuous machine like murmur best heard at the leftupper sternal border throughout systole and diastole. Small PDA is generally asymptomatic. Diagnosis through CXR, Echo and presence of machine like continuous murmur. Asymptomatic PDA or small PDA with no murmur- closure of PDA by 2 yrs old isrecommended viasurgical ligation and division or a prostaglandin inhibitor if unable to undergo surgery. Risk factors for hypertension- (HTN= >120/>80) Primary HTN= no known cause (95%) Secondary HTN= cause r/t underlying disease Risk factors are both genetic and environmental in primary HTN: Family history, advancing age, gender(men < 55, women >70), black, high Na+ intake, glucose intolerance, smoking, obesity, high alcohol use,low dietary intake of K+, Ca+ and Mag. Loss of language and/or comprehension-such as terms-aphasia, etc. –(Data Processing Deficits) Agnosia- Deficit of pattern recognition- one sense fails to recognize form/nature of objects but the others may maintain ability to recognize. Agnosia may be auditory, visual or tactile. Example: Person maybe able to look at a pin and say “pin” but is unable to do the same when touching it. Agnosia is most common in CVA but can also be found in other neurological issues. Dysphagia- Impairment of comprehension or production of language, comprehension or use of symbolsin either written or verbal language is impaired. Aphasia- Complete loss of comprehension or production of language. Chronic inflammatory joint disease Commonly called arthritis Characterized by damage/destruction ofsynovial membrane/articular cartilage and systemic signs ofinflammation (fever, leukocytosis, malaise, anorexia, hyperfibrinogenemia.Can be infectious or non-infectious. Noninfectious – Gout, rheumatoid arthritis (RA) and ankylosing spondylitis (AS) Infectious- caused by bacteria, virus and fungi (Lymes, TB, ), gonococcus, staph, strep, haemophilusinfluenza, parovirus B19, rubella, hep C, HIV • Rheumatoid arthritis (RA) is a chronic, systemic inflammatory autoimmune disease distinguishedby joint swelling and tenderness and destruction of synovial joints, leading to disability and premature death. Cytokines (interleukins, B Cells and matrix metalloproteinases) contribute to joint damage. Attack begins at synovial membrane and spreads to cartilage, joints, ligaments, and tendons causing pain, joint deformity and loss of function. Most common joints are fingers, feet, wrists, elbows, ankles and knees. Other symptoms include fever, malaise, rash, lymph node/spleen enlargement and Raynaud’s phenomenon. *Risk factors include: age, genetic factors and inflammatory mediator **Chemokines are thought to be responsible for inflammation by attracting T cells. DiagnosisPresence of serum RF (rheumatoid factor) in addition to physical findings.** Pathophysiology- In inflammation--Arginine (amino acid) modified by enzymes to become citrulline (Citrullination) to change structure and function. T and B cells attack the Citrullinatedproteins because they are seen as antigens, causing bony erosion, interlueukins breakdown cartilage and bone and a pannus (thick abnormal layer of granulation tissue) is formed. Synovial swelling and hyperplastic thickening (due to abnormal proliferation and increase in cellsize) contribute to damage. Treatment—early aggressive treatment of RA can prevent disability and joint destruction. Treated with disease modifying antirheumatic drugs (DMARDs) (methotrexate, cyclosporine, hydroxychloroquine), NSAIDs, glucocorticoids, steroid injections, PT, OT, assistive devices andsurgery to treat deformities. • Ankylosing spondylitis (AS) is the most common of a group of inflammatory arthropathies knownas spondyloarthropathies. It is a chronic inflammatory joint disease characterized by stiffening and fusion (ankylosis) of the spine and sacroiliac joints. Exact cause is unknown but strong association with: HLA-B27 in the endoplasmic reticulum (ER) causing misfolded proteins to accumulate stressresponsein ER increased interleukins and inflammatory cytokines. Most common signs and symptoms: Early- low back pain and stiffness typically in early 20s. Later- pain progresses, often worse after prolonged rest, and alleviated by physical activity. Early morning stiffness, and difficulty sitting up and twisting spine. Pain and loss of motion due to inflammation and reflex muscle spasm. Causes lumbar lordosis and kyphosis- thus Tspine isrounded andhead and neck are bent forward. Other manifestations- peripheral joint involvement, uveitis, fibrotic changes in lungs, cardiomegaly, aortic incompetence, amyloidosis, and Achillestendonitis. Symptoms: fatigue, wt loss, low grade fever,hypochromic anemia and increased sed rate. Diagnosis- by clinical findings (back pain > 3 months improving with exercise and not by rest) andradiologic findings (changes to sacroiliac joint and lab findings of presence of HLA-B27). Treatment- PT, OT, NSAIDs, DMARDs and surgery. • Gout is caused by an inflammatory response to uric acid production or excretion causing highlevels of uric acid in blood and other bodily fluids which is linked to purine metabolism and kidney function.Risk factors: age > 30 years, genetics, excessive alcohol, obesity, certain drugs (thiazides) and leadtoxicity. Pathophysiology- Uric acid crystalizes in connective tissues and joints causing painful inflammation triggering inflammatory response by macrophages, activating interleukinsresulting in joint damage. Primary gout- etiology unknown Secondary gout- etiology known Three stages1) Asymptomatic hyperuricemia- serum urate level elevated with no other symptoms 2) Acute gouty arthritis- attacks develop with increased serum urate triggered by increases in hyperuricemia or by trauma, drugs and alcohol. 3) Tophaceous gout- Chronic stage. Progressive inability to excrete uric acid until urate crystal deposits (tophi) appear in cartilage, synovial membranes and soft tissue Renal stones are 1000 times more prevalent in patients with primary gout. Treatment- Drugs (colchicine and NSAIDs, hydrocortisone injections), ice, reduce body weight, avoidalcohol, increase intake of low fat dairy, cherries, soybeans and vegetable protein. Male and female sex hormone production *See pgs 789-791 and 795-6 (male) and 776-78 (female) • The male sex hormones are androgens and testosterone is the primary male sex hormone. Leydig cells of the testes and, to a lesser degree, the adrenal glands produce testosterone andother androgens. In men, sex hormone production is relatively constant with some diurnal variation • The sex hormones are all steroid hormones and are synthesized from cholesterol Male and female sex hormones are present in all adults. However, the female body contains low levels of testosterone and other androgens, and the male body containslow levels of estrogen. Individualeffects of sex hormones depend on their amount and concentration in the blood. • The dominant female sex hormones, estrogen and progesterone, are produced primarily by theovaries. During fetal development, infancy, and childhood, sex hormone production is low. Endogenous antigenThere are two main types of antigens- exogenous and endogenous. Endogenous antigens are linked withMHC I molecules. Endogenous antigens are synthesized within a cell. This includes viruses due the fact that a virus infects a cell and uses the normal cellular protein synthesis mechanisms in order to translate viral genes into viral proteins. Cancer is an example also. When cells undergo malignant changes and begin producing unique proteinswhich are specific to the cancer cells, these are presented as foreign materials as a result of foreign antigens on the cell’s surface.Genital wartsThere are 120 types of HPV- stereotypes 6 and 11 are the cause for 90% of genital warts (GW). GW are very contagious and the level of contagion depends on HPV type, lesion location, and cellular immune response. Pregnant moms can pass GW to the fetus in utero. Children with HPV/GW are often victims ofsexual abuse. Epithelial cellsinfected with HPV undergo transformations and proliferate the growth of cells forming awarty type growth (called condylomata acuminate) which are soft skin colored growths. These growthscan be single lesions or groups of lesions forming a cauliflower like mass. Locations include; male- frenulum, glans, foreskin, urinary meatus, shaft, scrotum or anus and female- labia, clitoris, perineum,vagina or anus. **Lesions are not painful but can cause painful intercourse and may also bleed easily. **Urethral condylomata can become cancerous. **Laryngeal papillomas can occur in infants contracted from mom at birth causing stridor,hoarse/abnormal cry, and respiratory distress. Treatment in adults of GW is considered cosmetic not curative. Treatmentsinclude trichloroacetic acid(TCA) and bichloroacetic acid (BCA), cryotherapy and surgical excision. Pancreatic enzymesThe secretion of pancreatic enzymes are controlled by both hormonal and vagal stimulation. Theirpurpose is to break down/hydrolyze protiens (proteases), carbs (amylases) and fats (lipases). Proteases= trypsin, chymotrysinogen, procarboxypeptidase and elastase- also carries the primaryfunction of protecting the pancreas from its’ own juices. In the duodenum inactive proactins are activated by enerokinase. All proteases also reduce polypeptides to peptides. Pancreatic α amylase breaks the bonds of carbs to form glucose and maltosePancreatic lipase hydrolyzes fats to form free fatty acids. Process of muscle contractionCalcium Ions combine with troponin thus activating the inhibitory function of the troponin-tropomysincomplex. Actin (a thin filament) slides towards then over myosin (a thick filament)---------------------------Myosin heads attach to actin molecules (actin-myosin complex) and ATP is released. Actin slides onto myosin (causing shortening or contraction). The maximum usefulness of contraction is when the muscle is at 25%-35% orwhen actin and myosin have maximum potential interaction with one another thus equaling maximum force. Myosin heads connect with actin ATP released myosin releases from actin myosin is hydrolyzedenergizing it to allow myosin to crawl along actin (grab-release-grab-release)Here is a short video with a simple explanation- https://www.youtube.com/watch?v=e3Nq-P1ww5E Cervical dysplasiaDysplasia=abnormal shape, size and organization of mature cells. Not a “true” adaptive process and is said to be related to hyperplasia. Is strongly associated with neoplastic growths found adjacent to cancercells but does not necessarily indicate cancer. Dysplasia is categorized as mild, moderate and severe. Persistence of HPV virus (particularly subtypes 16 and 18), immune response, smoking and hormonebased contraceptives) illicit prime conditions for abnormal cervical cell growth. Consanguinity- Marriage between two people who are related. Proven to be a factor in producing children with recessive diseases related to the fact that families generally carry the same recessive genes- often when rare recessive diseases (ie. Cystic fibrosis) are present, consanguinity is considered. Nephrotic syndrome- More common in children 1) 3 or more grams of protein in the urine per day 2) Less than 3 g/dl serum albumin 3) Peripheral edema https://www.youtube.com/watch?v=fUKlpuz2VTs https://www.youtube.com/watch?v=jA1NyCE4M2g&feature=youtu.be https://www.khanacademy.org/science/health-and-medicine/infectious-diseases/hiv-and-aids/v/what-is-hiv-andaids https://www.khanacademy.org/science/biology/human-biology/immunology/v/inflammatory-response https://video.search.yahoo.com/yhs/search;_ylt=AwrJ56s_O4NbwxUAVcMPxQt.;_ylu=X3oDMTByMjB0a G5zBGNvbG8DYmYxBHBvcwMxBHZ0aWQDBHNlYwNzYw--? p=central+nervous+system+khan+academy&fr=yhs-pty-pty_converter&hspart=pty&hsimp=yhspty_converter#id=1&vid=1981577583d26a4533ed4df79759ab54&action=vie [Show More]

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