NR507 Wk 8 study guide Already graded A
Week 8 Final Exam Study Guide
endometrial cycle and the occurrence of ovulation Ovulation is the release of an ovum from a mature follicle and marks the beginning of the luteal/secretory phase of the menstrual cycle. HCG can be detected in maternal blood and urine 8 to 10 days after ovulation. Ovulatory cycles appear to have a minimum length of 24 to 26.5 days. Once ovulation occurs and serum progesterone levels increase, the endometrial tissue develops secretory characteristics (secretory phase). If implantation of a fertilized ovum does not take place, endometrial tissue begins to break down approximately 11 days after ovulation (ischemic phase of menstruation) Determines whether ovulation has occurred by obtaining endometrial tissue on day 26 of 28-day menstrual cycle (or postovulatory day 12). Normal menstrual cycle 27-30 days. Ovulatory phase: estrogen levels dip; progesterone levels begin to rise, Corpus luteum begins to develop; endometrium enters secretory phase. Shift in temperature is related to ovulation.
uterine prolapse is descent of the cervix or entire uterus into the vaginal canal. Loss of support by pelvic muscles. Uterine prolapse descent or herniation of the uterus into or beyond the vagina because of weakness of the pelvic musculature, ligaments, and fascia or obstetric trauma and lacerations sustained during labor and delivery.
polycystic ovarian syndrome (PCOS) Strong genetic factor -A hyperandrogenic state is a cardinal feature in the pathogenesis of PCOS. Glucose intolerance/insulin resistance (IR) and hyperinsulinemia often run parallel to and markedly aggravate the hyperandrogenic state. Signs and symptoms of women with PCOS may change over time, with metabolic syndrome becoming more prominent with age. In addition, polycystic ovaries may be associated with Cushing syndrome, acromegaly, premature ovarian failure, simple obesity, congenital adrenal hyperplasia, thyroid disease, androgen-producing adrenal tumors or ovarian tumors. Anovulation results from metabolic abnormalities contributing to obesity include Cushing syndrome, Cushing disease, polycystic ovary syndrome.
testicular cancer and conditions that increase risk: Painless testicular enlargement is the first sign of testicular cancer. Signs of testicular cancer include abnormal consistency, induration, nodularity, or irregularity of the testis A firm, nontender testicular mass or diffuse enlargement is found in the majority of cases. Risk factor for men with undescended testicles, a factor in some studies correlated with DES exposure. The risk of testicular cancer is 35 to 50 times greater for men with cryptorchidism. In men between the ages of 15-35 y/o. Germ cell tumors constitute 90% of testicular cancer. Risk factors include history of cryptorchidism, abnormal testicular development, HIV, and AIDS, Klinefelter syndrome, and hx of testicular cancer. Scrotal incisions may increase risk or recurrence. Some affected men have persistent paresthesia, Raynaud phenomenon, or infertility. Cryptorchidism (one of the testes fails to descend into the scrotum) significantly increases the risk of testicular cancer
symptoms that require evaluation for breast cancer woman who carries a mutation in the BRCA1 or BRCA2 genes. First sign of breast cancer is a painless lump. Other presenting signs include palpable nodes in the axilla, retraction of tissue (dimpling) (Fig. 25.49), or bone pain caused by metastasis to the vertebrae. Benign breast disease (BBD) most common symptoms reported are pain, palpable mass, nipple discharge. Strong link between stress and breast cancer progression. shift-work and its disruptive effects on circadian rhythms and sleep deprivation at night have been suggested as a risk factor for breast cancer.
Clinical manifestation of breast Ca:
Chest pain			nipple discharge
Dilated blood vessel		nipple retraction
Dimpling of skin		pitting of the skin
Edema				reddened skin, local tenderness, warmth
Hemorrhage			skin retraction
Local pain			ulceration
signs of premenstrual dysphoric disorder Cyclic recurrence (in the luteal phase of the menstrual cycle) of distressing physical, psychologic, or behavioral changes that impair interpersonal relationships or interfere with usual activities and resolve after menstruation. It is linked to hormonal changes emotional symptoms of depression, anger, irritability, aggression, fatigue, and impulse control. Physical symptoms s/s breast tenderness, abdominal bloating, headache, and swelling of extremities, water retention, bloating, weight gain.
Diagnostic Criteria for Premenstrual Dysphoric Disorder
•	A. ≥5 symptoms below: occur in most cycles during the week before menses onset, improve within a few days after menses onset, and diminish in the week postmenses
•	B. One (or more) of the following symptoms must be present:
o	a. Marked affective lability
o	b. Marked irritability or anger or increased interpersonal conflicts
o	c. Marked anxiety, tension
•	C. One (or more) of the following symptoms must also be present:
o	a. Decreased interest
o	b. Difficulty concentrating
o	c. Easy fatigability, low energy
o	d. Increase or decrease in sleep
o	e. Feelings of being overwhelmed
o	f. Physical symptoms such as breast tenderness, muscle or joint aches, “bloating” or weight gain
NOTE: Criteria A–C must be present for most menstrual cycles in the preceding year
•	D. Symptoms are associated with significant distress or interferences with work, school, relationships
•	E. The disturbance is not merely an exacerbation of another disorder such as major depression, panic disorder, persistent depressive disorder, or a personality disorder
•	F. Criterion A should be confirmed by prospective daily ratings in at least two symptomatic cycles
•	G. The symptoms are not due to physiological effects of a substance or another medical condition
dysfunctional uterine bleeding (DUB) Heavy or irregular bleeding in the absence of organic disease, such as submucous fibroids, endometrial polyps, blood dyscrasias, pregnancy, infection, or systemic disease. Increased endometrial bleeding is correlated with a change from ovulatory to anovulatory cycles due to high estrogen levels. Heavy & unpredictable flow bleeding (clot & flooding)
pathophysiology of prostate cancer More than 95% of prostatic neoplasms are histologically similar to adenocarcinomas and rely on androgen-dependent signaling for their development and progression.108-110 Most of these neoplasms occur in the periphery of the prostate. Heterogenous group of tumors. Testicular testosterone provides the main source of androgens in the prostate and is the major circulating androgen, whereas DHT predominates in prostate tissue and binds to the AR (androgen receptors) with greater affinity than does T (hormone testosterone). Androgen production outside of the testes, or extra testicular sources. Testosterone is converted to dihydrotestosterone. DHT is the most potent intraprostatic androgen
HPV and the development of cervical cancer Virtually all cervical cancer is caused by infection with specific types of HPV, which infects basal skin cells and commonly causes warts. HPV-16, -18, -31, and -45) are associated with the highest risk for developing cervical. viral DNA becomes integrated into the genomic DNA of the infected basal cell of the cervix and directs the persistent production of viral oncogenes. HPV is mainly transmitted through sexual contact. Persistence of infection with high-risk HPV is a prerequisite for the development of cervical intraepithelial neoplasia (CIN) (see Fig. 25.19), lesions, and invasive cervical cancers
body’s process for adapting to high hormone levels Hormones operate within feedback systems, either positive or negative, to maintain an optimal internal environment. Feedback systems provide precise monitoring and control of the cellular environment. Both negative and positive feedback systems are important for maintaining hormone levels within physiologic ranges. Negative feedback is the most common and occurs when a changing chemical, neural, or endocrine response decreases the subsequent synthesis and secretion of a hormone. Positive feedback occurs when a neural, chemical, or endocrine response increases the synthesis and secretion of a hormone. Positive feedback also occurs when an increased hormone level further increases the synthesis and secretion of that same hormone. The sensitivity or affinity of the target cell to a particular hormone is related to the concentration of receptors per cell: the more receptors, the higher the affinity or the more sensitive the cell is to the stimulating effects of the hormone. Thus the cell can adjust its sensitivity to the concentration of the signaling hormone. hormone is distributed throughout the body, only target cells with specific receptors for that hormone are affected. Target cell response depends on blood levels of the hormone, the concentration of target cell receptors, and affinity of the receptor for the hormone. Hormone receptors of the target cell have two main functions: (1) to recognize and bind with high affinity to their particular hormones and (2) to initiate a signal to appropriate intracellular effectors. See Chapter 1 for cell signaling pathways, particularly
Cushing’s Syndrome Hyperfunction. Excess endogenous secretion of ACTH (corticotropin). Oversecretion of adrenocorticotropic hormone (ACTH) or aldosterone. Excess ACTH stimulates excess production of cortisol. Two observations apply to individuals with Cushing’s Syndrome 1. They don’t have diurnal or circadian secretion patterns of ACTH and cortisol. 2. They don’t increase ACTH and cortisol secretion in response to stressor. Weight gain is the most common feature; “moon face” due to excess sodium and water retention, truncal obesity.
causes of hypoparathyroidism Hypoparathyroidism (abnormally low PTH levels) most commonly is caused by damage to or removal of the parathyroid glands during thyroid. Hypomagnesemia also can cause a decrease in PTH secretion and function. Causes low sodium and high phosphorous level
lab results that point to primary hypothyroidism Increased levels of TSH and decreased levels of TH (total T3 and both total and free T4)
pathophysiology of thyroid storm Thyrotoxic crisis (thyroid storm) is a severe form of hyperthyroidism that often is associated with physiologic stress. Pathophysiology: Acute confusional states arise from disruption of a widely distributed neural network involving the reticular activating system of the upper brainstem and its projections into the thalamus, basal ganglion, and specific association areas of the cortex and limbic areas. Delirium is associated with autonomic nervous system hyperactivity. The effect of dangerous high levels of thyroid hormone with high fever, extreme tachycardia, and potential death from heart failure or cardiac dysrhythmia
signs of thyrotoxicosis Thyrotoxicosis (Hyperthyroidism) is a condition that results from any cause of increased amounts of TH levels -Grave’s disease. Individuals with thyrotoxicosis may have signs of proximal weakness, paresis of the extraocular muscles (exhibited as exophthalmic ophthalmoplegia), or hypokalemic periodic paralysis, Thyrotoxicosis excessive concentrations of thyroid hormones in the body that are marked by increased metabolic rate, heat intolerance, goiter, reproductive disorders, excessive sweating, and other alterations in systemic function. The effect of having too much thyroid hormone or seen in hyperthyroidism.
Dermatomes Specific areas of cutaneous (skin) innervation at these spinal cord segments are called dermatomes. The sensation of pain corresponds to skin dermatomes T6 and L1. Sensory nerve distribution of skin dermatomes. Referred pain is usually well localized and is felt in the skin dermatomes or deeper tissues because visceral afferent neurons and regional somatic neurons converge on second-order neurons at the same level of the spinal cord. Referred pain
substance release at the synapse Chemical messengers called neurotransmitters are released
Spondylolysis Is a structural defect (Degeneration, fracture, or developmental defect) in the pars interarticularis of the vertebral arch (the joining of the vertebral body to the posterior structures). The lumbar spine at L5 is affected most often. Heredity plays a significant role and spondylolysis is associated with an increased incidence of other congenital spinal defects. Symptoms include lower back pain and lower limb pain.
location of the motor and sensory areas of the brain Cerebral Cortex The peripheral nervous system is divided int somatic nervous system and autonomic nervous system. The somatic nervous system consist of motor and sensory pathways regulating voluntary motor control of skeletal system. The autonomic nervous system consists of motor and sensory components involved in regulating the body’s internal environment (viscera) through involuntary control of organ systems. Primary motor cortex (M1) lies along the precentral gyrus in frontal lobe, Sensory is postcentral gyrus in the cortex.
pathophysiology of cerebral infarction and excitotoxins Pathophysiology- Cerebral infarction results when an area of the brain loses its blood supply because of vascular occlusion. IV tPA is used to treat acute strokes due to its thrombolytic activity but can also cause neurotoxic outcomes during stroke. Intracerebral injection of excitotoxins such as glutamate causes neuronal damage. Neuronal injury following focal cerebral ischemia is attributed to excitotoxic effects of glutamate injury causing hypoxia from depolarization.
Agnosia A defect of pattern recognition—a failure to recognize the form and nature of objects. Agnosia can be tactile, visual, or auditory, but only one sense is generally affected. For example, an individual may be unable to identify a safety pin by touching it with a hand but able to name it when looking at it. Agnosia may be as minimal as a finger agnosia (failure to identify by name the fingers of one's hand) or more extensive, such as a color agnosia. Agnosia most commonly is associated with cerebrovascular accidents (CVA), it may arise from any pathologic process that injures these specific areas of the brain. Ex. Spatial, object, visual, color, auditory, finger, tactile
accumulation of blood in a subarachnoid hemorrhage Subarachnoid hemorrhage is when a vessel is leaking, blood oozes into the subarachnoid space. When a vessel tears, blood under pressure is pumped into the subarachnoid space. Subarachnoid hemorrhage (SAH) is the escape of blood from a defective or injured vasculature into the subarachnoid space. The blood increases the intracranial volume, (Increased ICP, headache). Chronic subdural hematomas develop over weeks to months. The existing subdural space contains the liquefied clot from the acute bleed and/or accumulation of blood from a leaking vein. 80% have chronic headaches and tenderness over the hematoma on palpation. They may have confusion, memory loss, or coma, difficulty speaking or swallowing, and weakness with difficulty walking, loss of sensation, or seizures. Chronic subdural hematomas require a craniotomy to evacuate the gelatinous blood and to prevent brain herniation. Percutaneous drainage for chronic subdural hematomas has proven successful
most common cause of meningitis Infectious meningitis may be caused by bacteria, viruses, fungi, parasites, or toxins. Viral meningitis is the most common cause. Streptococcus pneumoniae bacteria is the most common cause of bacterial meningitis. Bacterial: Meningococcus (Neisseria meningitidis) and pneumococcus (Streptococcus pneumoniae) are the most common pathogens.
diet and the prevention of prostate cancer Nongenetic risk factors for prostate cancer may include a high-fat diet. Change in diet from high intake of animal products to more fruits and vegetables is beneficial. Mediterranean Diet reduces mortality rate of Prostate Ca (increase fruit and vegetable, fish oil, whole grain, olive oil, and tomatoes, green tea, & curcumin, alcohol and red wine in moderation, reduce saturated fats, red & processed meats and dairy product), increase Vitamins D & E & selenium. The Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study showed supplementation with vitamin E could reduce the incidence of prostate cancer, Vitamin D may play an important role in prostate cancer prevention.
Impact of Benign Prostatic Hypertrophy (BPH) on the urinary system Benign prostatic hyperplasia (BPH) is enlargement of the prostate gland. Postrenal-caused by UT obstruction, BPH is problematic as prostatic tissue compresses the urethra resulting in frequent lower urinary tract symptoms such as urge to urinate often, a delay in starting urination, decreased force of the urinary stream, long-term urinary retention. Obstruction to urine flow in the lower urinary tract includes enlargement of prostate in men.
the role of DNA in genetics Genes are composed of DNA, and the most important constituent of DNA is four types of nitrogenous bases (Fig. 4.1). The four bases, adenine, cytosine, guanine, and thymine, are commonly represented by their first letters: A, C, G, and T, respectively. DNA to serve as the basis of genetic inheritance, DNA must be able to provide a code for all the body's proteins. In addition to having the ability to specify amino acid sequences, DNA must be able to replicate itself accurately during cell division so that the genetic code can be preserved in subsequent cell generations
transcription transcription of the information stored in DNA. Transcription is the process by which RNA is synthesized from a DNA template. The result is the formation of messenger RNA (mRNA) from the base sequence specified by the DNA molecule. Transcription of a gene begins when an enzyme called RNA polymerase binds to a promoter site on the DNA. The flow of genetic information from DNA to mRNA so the proteins are specified by DNA, ex. Specifies a sequence of mRNA.
effects of genetic mutations A mutation is an inherited alteration of genetic material (ex. DNA) caused by mutagens. They cause many of the serious genetic diseases, disease causing mutations. Mutation generally means an alteration in the DNA sequence affecting expression or function of a gene, affecting expression or function of a gene ( the activity of the protein) ex. Cancer & Hemophilia
Trisomy An aneuploid cell containing three copies of one chromosome is said to be trisomic (a condition termed trisomy. Chromosome disorders, such as trisomy 21, are routinely detected using karyotypes. Chromosomes 13, 18, or 21. The most well-known example of aneuploidy in an autosome is trisomy of the twenty-first chromosome, which causes Down syndrome. females, is trisomy X. Instead of two X chromosomes, these females have three X chromosomes in each cell. Trisomy 13- cleft lip palate
Trisomy 13 syndrome (Patau Syndrome) VSD ((ventricular septal defect)), PDA (patent ductus arteriosus), dextrocardia
Trisomy 18 syndrome (Turners Syndrome) VSD, PDA, PS (pulmonary stenosis)
Trisomy 21 (Down syndrome) AVSD (atrioventricular septal defect), VSD
Down Syndrome Trisomy 21 chromosome, 47 chromosomes with an extra on #21. The facial appearance is distinctive (Fig. 4.14), with a low nasal bridge, epicanthal folds, protruding tongue, and flat, low-set ears. Poor muscle tone (hypotonia) and short stature are both characteristic. Approximately 97% of Down syndrome cases are caused by nondisjunction during the formation of one of the parent's gametes or during early embryonic development. Risk increases with maternal age >35. . It affects 1 in 800 live births and is much more likely to occur in the offspring of women older than 35 years of age. Associated with acute leukemia
Klinefelter syndrome Individuals with at least two X chromosomes and a Y chromosome in each cell (47,XXY karyotype) have a disorder known as Klinefelter syndrome, have a male appearance b/c of Y chromosome, sterile, female-like breasts (gynecomastia), testes are small, body hair is sparse, the voice is often somewhat high pitched, stature is elevated, and a moderate degree of mental impairment may be present. Klinefelter syndrome is found in about 1 in 1000 male births. Individuals with the 48,XXXY and 49,XXXXY karyotypes also are considered to have Klinefelter syndrome. Klinefelter syndrome smallness of testes with fibrosis and hyalinization of seminiferous tubules, variable degrees of masculinization, azoospermia, infertility, and increased levels of urinary gonadotropins; associated typically with an XXY chromosome complement although variants include XXYY, XXXY, and XXXXY.
diseases that have multifactorial traits Hypertension, coronary heart disease, stroke, diabetes mellitus (types 1 and 2), and some cancers
multifactorial inheritance Principles of Multifactorial Inheritance Basic Model- Traits in which variation is thought to be caused by the combined effects of multiple genes are polygenic (“many genes”). When environmental factors are also believed to cause variation in the trait, which is usually the case, the term multifactorial trait is used.2 Many quantitative traits (those, such as blood pressure, that are measured on a continuous numeric scale) are multifactorial. Because they are caused by the additive effects of many genetic and environmental factors, these traits tend to follow a normal, or bell-shaped, distribution in populations. Principles of Multifactorial Inheritance 1. Traits in which variation is thought to be caused by the combined effects of multiple genes are polygenic. 2. The term multifactorial is used when environmental factors also are believed to cause variation in the trait. 3. Many quantitative traits (e.g., blood pressure) are multifactorial. 4. Because traits are caused by the additive effects of many genetic and environmental factors, they tend to follow a normal or bell-shaped distribution in populations. 5. Those diseases, however, that do not follow a bell-shaped distribution appear to be either present or absent in individuals. They do not follow the inheritance patterns of single-gene disease. Instead, such diseases may follow an underlying liability distribution. It is thought that a threshold of liability must be crossed before the disease is expressed. 6. Examples of diseases that correspond to the liability model include pyloric stenosis, neural tube defects, CL/P, and some forms of congenital heart disease. 7. Many of the common adult diseases, such as hypertension, coronary heart disease, stroke, diabetes mellitus (types 1 and 2), and some cancers, are caused by complex genetic and environmental factors and are thus multifactorial diseases. 8. For most multifactorial diseases, empirical risks (risks based on direct observation of data) have been derived. 9. In contrast to most single-gene diseases, recurrence risks for multifactorial diseases can change significantly from one population to another because gene frequencies, as well as environmental factors, can differ among populations. 10. Several criteria are used to define multifactorial inheritance: (a) the recurrence risk becomes higher if more than one family member is affected; (b) if the expression of the disease in a proband is more severe, the recurrence risk is higher; (c) the recurrence risk is higher if the proband is of the less commonly affected sex; (d) the recurrence risk for the disease usually decreases rapidly in more remotely related relatives; and (e) if the prevalence of the disease in a population is f, the risk for offspring and siblings of probands is approximately .
Criteria are commonly used to define multifactorial inheritance
1.The recurrence risk becomes higher if more than one family member is affected
2. If the expression of the disease in the proband is more severe, the recurrence risk is higher.
3.The recurrence risk is higher if the proband is of the less commonly affected sex
4. The recurrence risk for the disease usually decreases rapidly in more remotely related relatives
Duchenne muscular dystrophy Most common and most severe X-linked recessive disorders, males. characterized by progressive muscle degeneration. Can’t walk by 10-12 years of age. The disease affects the heart and respiratory muscles, and death caused by respiratory or cardiac failure usually occurs before 20 years. DMD gene is the largest gene known in the human. It encodes a previously undiscovered muscle protein, termed dystrophin. When dystrophin is absent, as in individuals with DMD, the muscle cell cannot survive, and muscle deterioration ensues. Deletions of portions of DMD. They usually involve frameshift deletions in which all the amino acids following the deletion are altered and a premature stop codon occurs. Duchenne muscular dystrophy (DMD) is caused by deletion of one or more exons of the DMD gene on the X chromosome or, more rarely, by a nonsense mutation resulting in premature termination of translation.40 DMD is the largest gene in the human genome and encodes dystrophin, a large, membrane-stabilizing protein. “climbing up the legs” (Gower sign) is characteristic. Treatment with oral corticosteroids
MAJOR NEUROMUSCULAR DISORDERS IN CHILDRN -Duchenne muscular dystrophy (DMD) X-linked recessive onset- About 3 years, Hips and shoulders, quadriceps femoris, gastrocnemius (pseudohypertrophy) Rapid
Neurofibromatosis variable expressivity in an autosomal dominant disease is type 1 neurofibromatosis. neurofibromatosis gene normally encodes a tumor suppressor. The expression of this condition can vary from a few harmless café-au-lait spots (“coffee with milk,” describing the light brown color) on the skin to malignant tumors, scoliosis, seizures, gliomas, hypertension, learning disabilities, and neuromas. Tumor-suppressor gene. Wilms tumor also is associated with neurofibromatosis. Neurofibromas (benign nerve sheath tumors) are a group of autosomal dominant disorders of the nervous system. Neurofibromatosis (NF) Autosomal dominant Variable expressivity Multiple café-au-lait spots, neurofibromas, learning disability, seizure disorder
Neurofibromatosis type 1 – more prevalent. Brain tumors, sarcomas, neuroblastomas, Wilms tumor, nonlymphocytic leukemia
Neurofibromatosis type 2 – rare. Meningioma (malignant or benign), acoustic neuroma/schwannoma, gliomas, ependymomas
Box 18.3 Nih Diagnostic Criteria for Neurofibromatosis Criteria for the Diagnosis of NF1 Two of the following seven criteria: • Six or more café-au-lait macules greater than 5 mm in greatest diameter in prepubertal individuals and greater than 15 mm in greatest diameter in postpubertal individuals (adults) • Multiple axillary or inguinal freckles • One plexiform neurofibroma or two or more neurofibromas of any type • Optic glioma • Two or more Lisch nodules (iris hamartomas) • A distinctive osseous lesion such as sphenoid dysplasia or thinning of the cortex of long bones with or without pseudarthrosis • A first-degree relative with NF1 by the above criteria
Criteria for the Diagnosis of NF2 Either one of the following criteria: • Bilateral masses of the eighth cranial nerve seen with appropriate imaging techniques (e.g., CT or MRI) • A first-degree relative with NF2 and either: a. Unilateral mass of the eighth cranial nerve or b. Two of the following: 1. Neurofibroma 2. Meningioma 3. Glioma 4. Schwannoma 5. Juvenile posterior subcapsular lenticular opacity
ions that initiate muscle contraction Ca ions active transport system that regulates the Ca levels in the cell's cytoplasm, which in turn regulates muscle contraction
growth of long bones in children long bones of the extremities (tibia, femur, radius, ulna). growth in the length of long bones occurs at the physeal plate (growth plate) through endochondral ossification. With growth the femur assumes its normal alignment (by 12 years of age) and tibial rotation neutralizes at 8 years of age.5. Long bones have a broad end (epiphysis), broad neck (metaphysis), and narrow midportion (diaphysis) that contains the medullary cavity. Rickets occurs in the growing bones of children, deficient Vit. D or calcium.
bones belonging to the appendicular skeleton The appendicular skeleton consists of 126 bones that make up the upper and lower extremities, the shoulder girdle (pectoral girdle), and the pelvic girdle (os coxae)
how vaccines are formed prophylactic or therapeutic procedures have been developed to prevent pathogens from initiating disease (vaccines). Contracting and surviving an infectious disease is the most effective means of developing lifelong immunity against particular pathogens. The purpose of vaccination is to induce active immunologic protection before exposure to the risks of debilitating or fatal infection. For each vaccine an initial immunization. For each vaccine an initial immunization protocol is developed to produce large numbers of memory cells and a sustained protective secondary immune response in the greatest number of individuals. Development of a successful vaccine depends on many factors. These include characterizing the desired protective immune response (e.g., antibody, T cell), identifying the appropriate antigen to induce that response (i.e., immune responses against some antigens on an infectious agent are ineffective or even increase the risk for infection), determining the most effective route of administration (e.g., injected, oral, inhaled), optimizing the number and timing of vaccine doses to induce protective immunity in a large proportion of the at-risk population, and deciding the most effective, yet safe, form in which to administer the vaccine. For instance, most vaccines against viral infections (e.g., measles, mumps, rubella, Varicella zoster [chickenpox], yellow fever) contain live viruses that are weakened (attenuated) to continue expressing the appropriate antigens but are unable to establish more than a limited and easily controlled infection. Some common bacterial vaccines are killed microorganisms or extracts of bacterial antigens. he existence of a prolonged and protective secondary immune response explains how vaccinations provide protection against certain pathogenic microorganisms. Edward Jenner, an English physician of the late eighteenth century, performed the first well-documented vaccine trial with smallpox. “vacca”=cow (cowpox) Edward Jenner- smallpox. Active immune response- 3rd line of defense used when immunizing against disease. The immunization contains Ag in small amounts. The body’s lymph system sees it as a foreign material. The lymph system tells T cell specific to Ag. Clones it to B cells forming antibodies to fight the antigen for when you get exposed. Now body can fight the antigen.
populations at risk for getting systemic fungal infections and parasitic infections people with weakened immune systems, genetic defects, infections such as HIV, cancer, and drugs used to prevent transplant rejection. ppl on broad spectrum antibiotics. Poor hygiene & sanitation, developing countries, children. Immune deficiencies may allow invasive systemic infections (e.g., systemic fungal infections)
systemic manifestations of infection fever, leukocytosis, plasma protein synthesis. Systemic manifestations of cellular injury include fever, leukocytosis, increased heart rate, pain, and serum elevations of enzymes in the plasma
mechanisms responsible for the increase in antimicrobial resistance worldwide overuse or misuse of antimicrobials (antibiotics). Antimicrobial resistance occurs naturally through genetic changes.
functions of normal flora in the body 1st line of defense used to sweep flush, or peristaltic action such as mucous, urine, tears, and bile. Our most important immune defense is intact skin and mucous membrane used as impermeable barriers to anything that tries to invade our body from the outside. Physical and mechanical barriers are the first lines of defense that prevent damage to the individual and prevent invasion by pathogens; these include the skin and mucous membranes. Antibacterial peptides in mucous secretions, perspiration, saliva, tears, and other secretions provide a biochemical barrier against pathogenic microorganisms. The normal bacterial flora provides protection by releasing chemicals that prevent colonization by pathogens.
desensitization therapy Clinical desensitization to allergens can be achieved in some individuals. Minute quantities of the allergen are injected in increasing doses over a prolonged period. The procedure may reduce the severity of the allergic reaction in the treated individual. mechanisms by which desensitization occurs may be several, one of which is the production of large amounts of so-called blocking antibodies, usually circulating IgG. Suppressing the allergic response
cells involved in “left shift” in the WBC count differential During many infections, leukocytosis may be accompanied by a left shift in the ratio of immature to mature neutrophils, so that the more immature forms of neutrophils, such as band cells, metamyelocytes, and occasionally myelocytes, are present in relatively greater than normal proportions. Premature release of the immature white cells (leukocytes) is responsible for the phenomenon known as a shift-to-the-left or leukemoid reaction. Increased number of immature neutrophils
forms of immunity Innate- 1st-line of defense against a pathogen skin barrier. Innate-2nd line of defense- inflammatory (WBC). 3rd line of defense-Adaptive immunity-acquired (active and passive) Lymphocytes- B & T cells, NK cells. Passive immunity occurs when antibiotics are passed from one person to another ex. Transfusion). Active immunity involves T & B cells lymphocytes & WBCs. Autoimmunity- immune system responds to self-antigens, responds to antigens within your own body. IgM appears first but rapidly disintegrates, followed by IgG persists longer. Adaptive immunity – primary response within 5 days of Ag exposure, increased IgM, secondary response- after re-exposure to same Ag, IgG rises faster and higher due to memory cells B & T cells.
major histocompatibility class I antigens On Chromosome #6. Intracellular Proteins are expressed on the surface of all cells except RBCs. Referred to as human leukocyte antigens (HLA), each person inherits 2 sets of MHC genes, it acts as the unique barcode on the surface of each of our cells. It also displays present foreign material to the immune system for B & T cell activation. Class 1 MHC (HLA A, B, C) expressed on all nucleated cells and platelets, presents ENDOGENOUS antigens, recruits CD8 & Tc-Cells. MHC class I molecules are heterodimers composed of a large alpha (α) chain and a smaller chain called β2-microglobulin. Endogenous antigens are “non-self” (foreign) intracellular proteins
inflammatory chemicals blocked by anti-inflammatory drug Prostaglandin blocked by anti-inflammatory drugs
characteristics of acute phase reactant C-reactive protein markers of inflammation that have been linked to an increase in CAD risk, highly sensitive C-reactive protein (hs-CRP) has been explored in the greatest depth. hs-CRP is an acute phase reactant or protein mostly synthesized in the liver and is an indirect measure of atherosclerotic plaque-related inflammation and plaque progression. C-reactive protein (CRP) is an acute phase reactant protein produced by the liver, mainly in response to interleukin-6 produced by inflammation of any type. CRP is most sensitive to acute phase reactants; consequently, its level rises rapidly during inflammation
process by which a deep pressure ulcer heals Negative pressure wound therapy. Requires adequate relief of pressure, debridement of dead tissue, opening of deep pockets for drainage, and repair of damage tissue by construction of skin flaps for large, deep ulcers.
complications of the development of contractures during wound healing Scar formation with contractures is often a consequence of healing in burns. development of portal hypertension and esophageal varices and esophageal strictures
causes of respiratory alkalosis high blood pH and low PaCO2. Causes: Hyperventilation, extreme anxiety/panic, pain, altitude changes, hypermetabolic states (fever, sepsis, hyperthyroidism). In general, alkalosis increases CNS responsiveness => dizziness, cramping, agitation, seizure
molecules that act as buffers in the blood carbonic acid-bicarbonate buffer system (H2CO3) removes excess body acids (H ) or bases (OH-).
most common cardiac valve disease in women Mitral valve stenosis from rheumatic heart disease. Mitral stenosis is the most common form of rheumatic heart disease
when myocardial ischemia may be reversible Many individuals with reversible myocardial ischemia exhibit a normal physical examination between episodes. Individuals with reversible myocardial ischemia present clinically in several ways. Chronic atherosclerotic coronary obstruction usually results in recurrent predictable chest pain called stable angina. Unstable angina is the result of reversible myocardial ischemia and is a harbinger of impending infarction. Unstable angina is a form of acute coronary syndrome that results in reversible myocardial ischemia. It is important to recognize this syndrome because it signals that the atherosclerotic plaque has ruptured, and infarction may soon follow. When an MI happens anaerobic metabolism maintains basic cellular integrity for approximately 20 minutes, although the cardiac output during this time can be dramatically reduced
symptoms of stable angina (Angina pectoris) chest pain or discomfort described as heartburn, pressure, fullness, squeezing in center of chest, may radiate to neck, jaw, shoulder, back, or arm, lasts a short time (less than 5 min), relieved by rest or medication. Angina pectoris is typically experienced as transient substernal chest discomfort, ranging from a sensation of heaviness or pressure to moderately severe pain. Individuals often describe the sensation by clenching a fist over the left sternal border. The discomfort may be 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. Women with myocardial ischemia often have either no or atypical symptoms, such as palpitations, anxiety, weakness, and fatigue
orthostatic hypotension The term orthostatic (postural) hypotension (OH) refers to a decrease in systolic blood pressure of at least 20 mmHg or a decrease in diastolic blood pressure of at least 10 mmHg within 3 minutes of moving to a standing position. The compensatory vasoconstriction response to standing is altered by a marked vasodilation and blood pooling in the muscle vasculature. Primary OH is often called neurogenic and is usually the result of neurologic disorders that affect autonomic function. Compensatory changes during standing normally increase sympathetic activity mediated through stretch receptors (baroreceptors) in the carotid sinus and the aortic arch. Primary OH is a significant risk factor for falls and associated injury. It also is associated with an increased risk of death, coronary artery disease, heart failure, and stroke. Causes decrease in BP and increase in Heart rate. Orthostatic hypotension often is accompanied by dizziness, blurring or loss of vision, and syncope or fainting.
isolated systolic hypertension Isolated systolic hypertension (ISH) is elevated systolic blood pressure accompanied by normal diastolic blood pressure (less than 90 mmHg). strongly associated with cardiovascular and cerebrovascular events.
results of sustained controlled hypertension Sustained HTN => Vascular remodeling (Hyaline sclerosis & Atherosclerosis) leading to either (Heart)-Cardiac disease, Coronary artery disease (CAD), Congestive heart failure, (Kidney)-Renal disease (Nephrosclerosis), (Eye)-Retinal changes; sustained HTN => Neurologic disease (stroke, dementia, encephalopathy)
the relationship of insulin resistance on the development of primary hypertension Genetic and Environmental => Insulin resistance- Adipokines => vasoconstriction => increase peripheral resistance => Sustained hypertension
defects in the normal secretion of natriuretic hormones and the impact on renal system Genetic & Environmental => Natriuretic hormones => Vasoconstriction => Increased peripheral resistance => Sustained HTN => Vascular remodeling, Hyaline sclerosis, & Atherosclerosis => Renal Disease (Nephrosclerosis)
effects of increased sympathetic nervous system activity due to primary hypertension Fight or flight response: Genetic & Environmental => SNS => Vasoconstriction => Increased peripheral resistance => Sustained HTN => Vascular remodeling (Hyaline sclerosis, & atherosclerosis) => Retinal Changes OR Renal disease (Nephrosclerosis) OR Cardiac Disease (CAD, CHF); Sustained HTN => Neurological disease (stroke, dementia, encephalopathy). Epi/NE dominates under stress/pathological conditions
complications of unstable plaque in the coronary arteries Prone to rupture and thrombosis so platelets begin sticking to the exposed underlying tissue and form a clot that completely occlude the vessels. This results in acute coronary syndrome known as unstable angina and indicates a higher risk for subsequent MI.
forms of dyslipidemia associated with the development of the fatty streak in atherosclerosis Macrophages that are filled with lipoproteins are called foam cells. These migrate into the vessel wall and accumulate, forming fatty streaks. Smooth muscle cells migrate over the fatty streaks & Fibrous tissue is synthesized. This form of plague which can partially obstruct the lumen of the vessel.
events that initiate the process of atherosclerosis Atherosclerosis begins with endothelial injury. Macrophages that are filled with lipoproteins are called foam cells. These migrate into the vessel wall and accumulate, forming fatty streaks.
signs and symptoms of increased left atrial and pulmonary venous pressures in left sided heart failure High pressure in the pulmonary system b/c fluid that is not ejected into the central circulation by the left ventricle will back up through the pulmonary vein and creates pulmonary congestion. This causes the right ventricle to hypertrophy. Right heart failure secondary to left heart failure is called Cor Pulmonale.
differences between left and right sided heart failure
Left sided heart failure- CHF. Inability of LV to provide adequate blood flow into systemic circulation. Causes: Systemic hypertension (most common), LV MI, LV hypertrophy, aortic SLV or bicuspid valve damage secondary to right heart failure. Most common cause of LHF is high systemic vascular pressure. Process of Systemic vascular pressure: Increase LV afterload, Increase LV preload, Increase LA preload, Increase blood volume and pressure in pulmonary veins, fluid forced out into pulmonary tissues. Results in Pulmonary edema, dyspnea, and secondary right heart failure (Cor Pulmonale) = Biventricular heart failure (R & L heart)
Right sided heart failure- Cor Pulmonale. Inability of RV to provide adequate blood flow into pulmonary circulation. Causes: Pulmonary disease such as Pulmonary HTN most common right heart failure, RV MI, RV hypertrophy, pulmonary SLV or tricuspid valve damage secondary to left heart failure. Process of pulmonary vascular pressure: increased RV afterload, Increased RV preload, increased RA preload, Increased vena cava, fluid forced out into peripheral tissues. Results in jugular vein distension (JVD), hepatosplenomegaly, peripheral edema, left heart failure = biventricular heart failure.
infective endocarditis Infective endocarditis (IE) is a general term used to describe infection and inflammation of the endocardium, especially the cardiac valves. Most common cause of aortic regurgitations (mitral valve regurgitations) due to implantation of prosthetic valves. Pathogen enters the nervous system by hematogenous spread. Trauma, congenital heart disease, valvular heart disease, and the presence of prosthetic valves are the most common risk factors for endocardial damage that leads to IE. Blood-borne microorganism adherence to the damaged endocardial surface. Bacteria may enter the bloodstream during injection drug use, trauma, dental procedures. Formation of infective endocardial vegetations (Fig. 33.36). Bacteria infiltrate the sterile thrombi and accelerate fibrin formation by activating the clotting cascade. The “classic” findings are fever, new or changed cardiac murmur, and petechial lesions of the skin, conjunctiva, and oral mucosa. Characteristic physical findings include Osler nodes (painful erythematous nodules on the pads of the fingers and toes) and Janeway lesions. Other manifestations include weight loss, back pain, night sweats, and heart failure. CNS, splenic, renal, pulmonary peripheral arterial, coronary, and ocular emboli may lead to a wide variety of signs and symptoms. The widely accepted Duke criteria for the diagnosis of IE include the two major criteria of positive blood cultures (at least 2 positive cultures drawn >12 hours apart) and evidence for endocardial involvement (echocardiographic findings of vegetations and valvular dysfunction or damage), plus minor criteria including predisposing conditions, fever, evidence of emboli (e.g., Janeway lesions), and immunologic phenomena (e.g., Osler nodes).
Box 33.3 Risk Factors for Infective Endocarditis • Implantation of prosthetic heart valves • Congenital lesions associated with highly turbulent flow (e.g., ventricular septal defect) • Acquired valvular heart disease (especially mitral valve prolapse) • Previous attack of infective endocarditis • Intravenous drug use • Long-term indwelling intravenous catheterization (e.g., for pressure monitoring, feeding, hemodialysis) • Implantable cardiac pacemakers • Heart transplant with defective valve.
Pathology of unstable angina:
1.	Unstable angina results form rupture of an atherosclerotic plaque with subsequent thrombosis or obstruction of flow through a coronary artery.
2.	Atherosclerosis begins with endothelial injury. Macrophages that are filled with lipoproteins are called foam cells. These migrate into the vessel wall and accumulate, forming fatty streaks.
3.	Smooth muscle cells migrate over the fatty streak & fibrous tissue is synthesized. This forms a plaque which can partially obstruct the lumen of the vessel.
4.	Unstable plaque are those with a thin fibrous cap and a rich lipid core. When those plaque rupture, platelets begin sticking to the exposed underlying tissue and form a clot that can completely occlude the vessels.
5.	If the clot dissolves within 10-20 minutes, tissue perfusion is restored before infarction can occur. This results in acute coronary syndrome known as unstable angina & indicates a higher risk for subsequent MI.
Peripheral vascular disease:
pathophysiology of deep vein thrombosis
physiological response to hypoxia in anemia The growth factor ERYTHROPOIETIN (EPO) is made by the kidney and liver in response to tissue hypoxia.
populations at the highest risk for developing folate deficiency anemia Alcoholics, malnutrition (poor diet), taking anticonvulsant prescription (seizure), pregnant women, those who can’t produce folate in their bodies (some babies), poor, elderly
causes of iron deficiency anemia Inadequate dietary intake, chronic and or occult blood, (hemorrhage, colitis, cirrhosis, GI ulcers, esophageal lesions, or menorrhagia) decreased ability to utilize Fe for heme synthesis (transferrin deficiencies, mitochondrial defects)
expected lab test results found in long standing iron deficiency anemia Microcytic-hypochromic anemia- small cells and low Hb level, paler cells
Sickle Cell Anemia Inherited Disorder of Erythrocytes: Hemoglobinopathies. Autosomal recessive genetic disorder. Inheritance of 2 abnormal genes (one from each parent). Inheritance of one normal Hb gene one abnormal Hb gene = sickle cell trait (carrier). Pathophysiology: Single amino acid change on beta-chain forms elongated Hb molecules (HbS). Oxidative stress (hypoxia), anxiety, fever, cold, dehydration, decreased oxygen binding to Hb and increases sickling tendencies. (Normochromic, normocytic) Hemolytic anemia, abnormal shape of hemoglobin. Occlude blood vessels and spleen => high risk for CVA and splenic damaged
causes of aplastic anemia Chemical or radiation exposure (SE or cancer tx), viral-induced (Hepatitis, Epstein-Barr, CMV), tumors (Multiple Myeloma), antibiotics and other prescriptions (PCN, chloramphenicol, phenytoin, diuretics, antidiabetic & Sulfa Rx), congenital defects (Fanconi’s anemia)
underlying pathophysiologic mechanisms leading to autoimmune hemolytic anemia Premature destruction of RBC due to enzymes/toxins produced by infectious agent, mediated by own immune system, or the effects of certain chemicals/drugs. Autoimmune reaction- congenital or idiopathic
secondary polycythemia Increased erythropoietin (RBCs) secretion in response to chronic hypoxia.
anemia of chronic renal failure Due to erythropoietin deficiency therefore, Recombinant human erythropoietin (r-HuEPO) is used in individuals with anemia secondary to decreased erythropoietin production from chronic renal failure. An immediate effect of increased endogenous or exogenous erythropoietin is an increase in the blood reticulocyte count, followed by increasing levels of erythrocytes.
Fluid and Electrolytes:
conditions that result in pure water deficit (hypertonic volume depletion) Hypertonic- ECF is increased more than ICF. Therefore, water draws out of cell resulting in cell shrinkage and increased plasma volume = hypervolemia
osmoreceptors that stimulate thirst and the release of ADH
causes of hypernatremia
effects of increased aldosterone
definition of isotonic Same and – charges in ECF and ICF (equal osmolality)
principle of capillary oncotic pressure Chemical force such as protein (albumin) to pull fluid in = Reabsorption
types of fluid compartments in the body Intracellular fluid, extracellular fluid, other
ICF- K , HPO4
ECF- 1. Intravascular fluid (IV)- blood pressure
2. Interstitial fluid (IF)- between cells - EDEMA
3. Other fluids- 3rd spaces- lymph, synovial fluid, CSF, intestinal fluid, sweat, urine, intraocular, and body cavity fluid
most effective measure to prevent pulmonary embolus from developing in patients
when the practitioner will note tactile fremitus
cause of acute airway obstruction in the patient with chronic bronchitis Long-term exposure to environmental irritants, repeated episodes of acute bronchitis (infection), factors affecting gestational or childhood lung development???
types of pneumothorax
results of the loss of alph-1-antitrypsin in emphysema
the result of loss of surfactant in ARDS
Characteristics of Cheyne-Stokes respirations
causes of hypovolemic shock
how the body maintains glucose levels during shock