NR 507 Week 8 Final Exam Study Guide
Reproductive:
endometrial cycle and the occurrence of ovulation; During the midfollicular phase, increasing levels
... [Show More] of estrogen contribute to endometrial repair and proliferation, thus increasing endometrial thickness (luteal phase). 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) (see Fig. 24.9). Sloughing of tissue (menstrual bleeding) begins about 14 days after ovulation.
uterine prolapse; A uterine prolapse is when the uterus descends toward or into the vagina. Prevention of constipation and treatment of chronic cough may help prevent uterine prolapse, the uterus slips down into or protrudes out of the vagina.
1. Cause = pelvic floor muscles and ligaments stretch and weaken, providing inadequate support
2. Risks - aging/gravity, pregnancy/birthing, straining
3. Treatment - nothing to pessary to hysterectomy
polycystic ovarian syndrome excessive androgens that affect follicular decline by suppressing apoptosis, enabling follicles, which normally disintegrate to survive, infertility
testicular cancer and conditions that increase risk; Firm, nontender testicular mass cancer is a germ cell tumor arising from the male gamete
Most common cancer in men ages 15-34
Incidence higher in Caucasians
5:1 (Caucasian:African American)
- undescended testes
- first-born
- pre/perinatal estrogen exposure
- polyvinyl cholirde exposure
- advanced maternal age
- Down's syndrome
- Klinefelter's syndrome (XXY)
- CIS
- HIV/AIDS
symptoms that require evaluation for breast cancer; painless lump
signs of premenstrual dysphoric disorder; Premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD) are the cyclic recurrence (in the luteal phase of the menstrual cycle) of distressing physical, psychologic, or behavioral changes that impair interpersonal relationships or interfere with usual activities and resolve after menstruation. Emotional symptoms, particularly depression, anger, irritability, and fatigue, have been reported as the most prominent and the most distressing, whereas physical symptoms seem to be the least prevalent and problematic. Physical symptoms include breast tenderness, abdominal bloating, headache, and swelling of extremities. In addition, underlying physical or psychologic disease may be aggravated premenstrually and must be diagnosed and treated independently from PMS/PMDD.
dysfunctional uterine bleeding; The clinical manifestations of a woman include the following: irregular or heavy bleeding, passage of large clots, and depletion of iron stores. This person is experiencing:
pathophysiology of prostate cancer; normal prostate epithelium --> proliferative inflammatory atrophy --> prostatic intraepithelial neoplasia --> localized prostate cancer --> metastatic prostate cancer --> androgen-independent 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. Prostatic adenocarcinoma is a heterogeneous group of tumors with a diverse spectrum of molecular and pathologic characteristics, and therefore clinical behaviors and challenges.111 The biologic aggressiveness of the neoplasm appears to be related to the degree of differentiation rather than the size of the tumo
HPV and the development of cervical cancer
Endocrine:
body’s process for adapting to high hormone levels; D) down-regulation.
To adapt to high levels of hormones, some cells have the capacity to decrease the number of receptors for that hormone through the process of down-regulation.
Cushing’s Syndrome; B) ectopic production of ACTH from a lung tumor.
Cushing disease is excessive ACTH production most commonly caused by an adrenal adenoma or a non-pituitary adenoma as is often seen with lung cancer.
Autoimmune destruction of the adrenal cortex results in hypocortisolism or Addison disease.
Cushing syndrome occurs whenever there is an excessive level of cortisol regardless of cause.
Excessive production of aldosterone from a tumor in the adrenal cortex causes hyperaldosteronism. Cushing disease is excessive cortisol secondary to increased ACTH.
causes of hypoparathyroidism; Parathyroid gland injury or removal
Parathyroid gland injury or surgical removal of the gland is the most common cause of hypoparathyroidism.
lab results that point to primary hypothyroidism; Primary hypothyroidism
Low levels of T3 and T4 production caused by the destruction or removal of the thyroid gland (primary hypothyroidism) stimulate the anterior pituitary to increase the production of TSH. An endocrinologist orders a series of lab tests to assess thyroid function. Low levels of thyroid hormone (T3 and T4) and high levels of thyroid-stimulating hormone (TSH) are indicative of:
pathophysiology of thyroid storm; Fever and tachycardia leading to high-output heart failure
High levels of thyroid hormone in conjunction with high levels of stress hormones lead to fever, tachycardia, and eventually high-ouput heart failure if the condition is not treated.
signs of thyrotoxicosis; Weight loss and enlarged thyroid gland
Weight loss and enlarged thyroid gland are common signs of hyperthyroidism in thyrotoxicosis
Neurological:
dermatomes; Sensory innervation by a single spinal nerve in the skin is ___ A dermatome is the area of the skin of the human anatomy that is mainly supplied by branches of a single spinal sensory nerve root. These spinal sensory nerves enter the nerve root at the spinal cord, and their branches reach to the periphery of the body. The sensory nerves in the periphery of the body are a type of nerve that transmits signals from sensations (for example, pain symptoms, touch, temperature) to the spinal cord from specific areas of our anatomy.
substance release at the synapse; Chemicals, called neurotransmitters, are released from one neuron at the presynaptic nerve terminal.
Spondylolysis; structural defect either degenerative or developmental of the vertebra. heredity and associated with other malformations of the spine
location of the motor and sensory areas of the brain; motor: Location: Precentral gyrus of frontal lobe of each hemisphere sensory: Location: Postcentral gyrus of the parietal lobe
pathophysiology of cerebral infarction and excitotoxins;
In the pathophysiology of cerebral infarction, the release of which substance is associated with neuron hyperpolarization and seizure activity? excitotoxins
c. release of excitotoxins especially aspartate and glutamate - these are normal neurotransmitters that are released in toxic amounts during brain injury of any kind
agnosia; Agnosia is the inability to process sensory information. Often there is a loss of ability to recognize objects, persons, sounds, shapes, or smells while the specific sense is not defective nor is there any significant memory loss.
accumulation of blood in a subarachnoid hemorrhage; A) in the cerebrospinal fluid (CSF) between the brain and skull.
most common cause of meningitis; Viral infections are the most common cause of meningitis
Neisseria Meningitides (meningococcus)
and
Streptococcus pneumoniae (pnemococcus)
Genitourinary: diet and the prevention of prostate cancer; Epidemiologic studies have found total fat intake, animal and saturated fat, red meat, and dairy products are associated with an increase in prostate cancer risk. Healthy lifestyles
Diet low in red meats and high in vegetable and fruits
Exercise
Impact of Benign Prostatic Hypertrophy (BPH) on the urinary system -kidney disorders caused by pressure and back flow of urine - post renal
-recurrent UTI's
-pyelonephritis
-sepsis-infection gets in blood
-secondary renal insufficiency
Genetics:
the role of DNA in genetics; DNA stores, copies and transmits the genetic information in a cell.
transcription; RNA is formed from DNA in a process that is called transcription and requires the enzyme RNA polymerase.
RNA serves as the bridge between DNA and protein synthesis.
effects of genetic mutations; -Any type of mutation in DNA or RNA can result in a nonfunctional protein or one with reduced function -A silent point mutation does not change protein function, a missense point mutation usually reduces protein function, and a nonsense mutation often eliminates protein function
Trisomy; [BLANK_AUDIO] -Trisomy 21
-A person has 47 chromosomes with an extra chromosome in the 21 position
-Due to nondisjunction, or the failure of chromosome pairs to separate properly during meiosis
-This leads to a sperm or egg cell to have 24 chromosomes (instead of 23)
-After conception, the extra chromosome is replicated in each cell in the embryo
When we fertilize these abnormal gametes with normal gametes, what we will end up with is then a mixture of chromosomes. Extra amounts trisomy, cuz our gamete had two chromosomes instead of the one it should have. So we bring in the gamete with the matching chromosome. And now we have two plus one is a trisomy.
In this case, the gamete didn't get the chromosome it needed. And so, the normal gamete that fertilizes it will not have a mate. So, we have monosomy. And when we have nondisjunction, the overall effect in meiosis will always be significant. Because this results in aneuploidy. Gamete cells that do not contain 23 chromosomes, the resulting embryo will have fewer or extra chromosomes.
And not all of the abnormal embryos may even survive. [BLANK_AUDIO] When we have aneuploidy of the sex chromosome, during meiosis. This results in conditions such as Klinefelter syndrome, or Turner syndrome. Where we have an abnormal amount of the sex chromosomes, either too few or too many. Abnormalities are aneuploidy of sex chromosomes are always gender specific.
So an individual with Klinefelter syndrome, even though they have two X chromosomes, the normal genotype for a female, that Y chromosome will still cause development of male characteristics. So Klinefelter syndrome that individual is genetically male. In the case of Turner syndrome that individual is missing one of the sex chromosomes.
And so they have still one X chromosome. They will be typically female. But with a genetic abnormalities present. An employee of autosomal chromosomes results, it conditions such as Down syndrome trisomy 21 or Edwards syndrome Trisomy 18. Since these don't involve the sex chromosomes. These are not gender specific meaning that they can occur in either male or female.
Down Syndrome; 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 35 years of age.
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. also known as 47,XXY or XXY, is the set of symptoms that result from two or more X chromosomes in males. The primary features are infertility and small testicles. Often, symptoms may be subtle and many people do not realize they are affected. ... Klinefelter syndrome usually occurs randomly.
diseases that have multifactorial traits; They include isolated cleft lip and/or cleft palate (CL/P), neural tube defects (anencephaly, spina bifida), clubfoot (talipes), and some forms of congenital heart disease.
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
When the trait/disease is the consequence of the combined effect of mutations in multiple genes +/- environmental effects. Usually do not show a clear pattern of mendelian inheritance. The more genes that combine to produce the trait the more possible phenotypes there are resulting in a normal distribution within the population. low heritability (most affected progeny have unaffected parents), relationship by blood slightly increases the risk for an affected offspring, risk of affected relatives falls off very quickly with the degree of relationship, risk increases with the number of affected offspring in a family (indicated parents more likely to be closer to the threshold), a more severely affected parent is more likely to produce an affected offspring.
Duchenne muscular dystrophy; Duchenne muscular dystrophy (DMD) is a genetic disorder characterized by progressive muscle degeneration and weakness. It is one of nine types of muscular dystrophy. DMD is caused by an absence of dystrophin, a protein that helps keep muscle cells intact. first affecting the muscles of the hips, pelvic area, thighs and shoulders, and later the skeletal (voluntary) muscles in the arms, legs and trunk. The calves often are enlarged.
Neurofibromatosis Neurofibromatosis is a genetic disorder that causes tumors to form on nerve tissue. These tumors can develop anywhere in your nervous system, including your brain, spinal cord and nerves. Neurofibromatosis is usually diagnosed in childhood or early adulthood
Musculoskeletal: ions that initiate muscle contraction; Calcium
growth of long bones in children; takes place in the epiphyseal plate.
bones belonging to the appendicular skeleton; Ilium
Immunity/Inflammation:
how vaccines are formed; B) an attenuated antigen, a dead antigen, a detoxified toxin.
populations at risk for getting systemic fungal infections and parasitic infections; immunocompromised
systemic manifestations of infection; interleukin 1? Fever (pyrexia), Leukocytosis, & increase plasma protein synthesis wich are called acute phase reactants.
mechanisms responsible for the increase in antimicrobial resistance worldwide; the misuse and overuse of antimicrobials is accelerating this process
functions of normal flora in the body; The functions of the normal flora include digestion of substrates, production of vitamins, stimulation of cell maturation, stimulation of the immune system, aid in intestinal transit and colonization resistance
desensitization therapy; improves allergies by which of the following mechanisms? Producing antibodies that prevent the allergen from binding to IgE
cells involved in “left shift” in the WBC count differential; Bands and PMN's
forms of immunity; If a person has innate resistance to a disease, the person has _____ immunity.
A) natural
If a person has resistance to a disease from natural exposure to an antigen, the person has which form of immunity?D) Active naturally acquired
Humoral immunity is generated through the process of:C) producing antibodies.
What type of immunity is conferred when an individual is given a vaccine?
C) Active acquired immunity
major histocompatibility class I antigens; are found in All body cells except for red blood cells
inflammatory chemicals blocked by anti-inflammatory drugs; prostaglandins
characteristics of acute phase reactant C-reactive protein A) Produced by the liver, B) Plasma indicator of inflammation, C) Significant risk factor for heart disease
Dermatology:
process by which a deep pressure ulcer heals; Secondary intention
Successful healing requires continued adequate relief of pressure; débridement of dead tissue; opening of deep pockets for drainage; and repair of damaged tissue by construction of skin flaps for large, deep ulcers. Negative-pressure wound healing is used in the treatment of advanced-stage pressure injuries, but clinical trials are lacking.13 Infection requires treatment with topical and/or systemic agents, but there are no clear guidelines.14 Pain must be controlled. Randomized controlled trials are needed to determine the best methods for treating pressure injuries. Deep injuries develop closer to the bone as a result of tissue distortion and vascular occlusion from pressure that is perpendicular to the tissue (over the heels, trochanter, and ischia). Bacteria colonize the dead tissue, and infection is usually localized and self-limiting. Proteolytic enzymes from bacteria and macrophages dissolve necrotic tissues and cause a foul-smelling discharge that resembles, but is not, pus. The necrotic tissue initiates an inflammatory response with potential pain, fever, and leukocytosis. If the ulceration is large, toxicity and pain lead to a host of possible complications, including loss of appetite, debility, local/systemic infections, and renal insufficiency
complications of the development of contractures during wound healing Excessive wound contraction may result in a deformity or contracture. Burn wounds are especially susceptible to the development of contractures. Internal contractures may occur as well, and are common in cirrhosis of the liver. Internally, scar tissue that becomes contracted constricts blood flow that may contribute to the development of portal hypertension and esophageal varices. Other types of internal contraction deformity include duodenal strictures caused by dysfunctional healing of an ulcer and esophageal strictures caused by chemical burns.
Proper positioning and range-of-motion exercises, as well as surgery, are among the physical means used to overcome the excessive myofibroblast-derived tension that results in contractures. Clinical use of pharmacologic methods for control of wound contracture is still largely experimental, but includes control of myofibroblast contraction by the administration of smooth muscle cell inhibitors such as colchicine and inhibition of proper collagen matrix assembly with drugs that prevent either collagen cross-linking or MMP activity. These latter treatments are based on the knowledge that myofibroblast binding to collagen can “lock” contracted cells into position.
Acid/Base:
• causes of respiratory alkalosis; hyperventilation (anxiety, aspirin overdose)
• Respiratory alkalosis occurs when there is alveolar hyperventilation and decreased concentration of plasma carbon dioxide (termed hypocapnia), thus increasing the ratio of HcO3 to PCO2 (H2CO3). Stimulation of ventilation is precipitated by hypoxemia (i.e., high altitudes); hypermetabolic states such as fever, anemia, and thyrotoxicosis; early salicylate intoxication; or anxiety or panic disorder. Improper use of mechanical ventilators can cause iatrogenic respiratory alkalosis. Secondary respiratory alkalosis may develop from hyperventilation stimulated by metabolic acidosis, causing a mixed acid-base disorder. Stress[1]
• Pulmonary disorder[2]
• Thermal insult[5]
• High altitude areas[6]
• Salicylate poisoning (aspirin overdose)[6]
• Fever[1]
• Hyperventilation (due to heart disorder or other, including improper mechanical ventilation)[1][7]
• Vocal cord paralysis (compensation for loss of vocal volume results in over-breathing/breathlessness).[8]
• Liver disease[6]
molecules that act as buffers in the blood; Buffering occurs in response to changes in acid-base status. Buffers can absorb excessive H+ (acid) or hydroxyl ion (OH−) (base) to minimize fluctuations in pH. The buffer systems are located in both the ICF and the ECF compartments, and they function at different rates. Buffer systems exist as buffer pairs, consisting of a weak acid and its conjugate base (Table 3.11). The most important plasma buffer systems are bicarbonate–carbonic acid and hemoglobin. Phosphate and protein are the most important intracellular buffers and provide a first line of defense. Ammonia and phosphate can attach hydrogen ion and are important renal buffers. The carbonic acid–bicarbonate buffer pair operates in both the lung and the kidney. The greater the carbon dioxide partial pressure (PCO2), the more carbonic acid is formed. The buffer systems of the body also act to stabilize the acid-base balance (pH). There are three major buffer systems, with the plasma buffer system being the quickest to act (within seconds), whereas the respiratory system responds in minutes. The renal system is more powerful but responds over a period of hours to days. Each buffer system has a differing ability to compensate or correct acid-base disturbances. For example, respiratory compensation for a primary metabolic acid-base disorder can be initiated within minutes. However, the respiratory system can compensate for a metabolic disorder but requires the kidneys to fully correct the imbalance. Chronic respiratory acid-base disturbances can be fully compensated by renal activity, but the ultimate correction occurs through the regulation of carbon dioxide.
Cardiovascular:
most common cardiac valve disease in women; Mitral valve prolapse
when myocardial ischemia may be reversible;
Anaerobic metabolism maintains basic cellular integrity for approximately 20 minutes, although cardiac output during this time can be dramatically reduced.
Individuals with reversible myocardial ischemia present clinically in several ways. Chronic atherosclerotic coronary obstruction usually results in recurrent predictable chest pain called stable angina. Abnormal vasospasm of coronary vessels results in unpredictable chest pain called Prinzmetal angina. Myocardial ischemia that does not cause detectable symptoms is called silent ischemia. . Reversible myocardial ischemia presents clinically in several ways. Chronic coronary obstruction results in recurrent predictable chest pain called stable angina. Abnormal vasospasm of coronary vessels results in unpredictable chest pain called Prinzmetal angina. Myocardial ischemia that does not cause detectable symptoms is called silent ischemia. Unstable angina causes reversible myocardial ischemia and is a harbinger of impending infarction. MI results when prolonged ischemia causes irreversible damage to the heart muscle. Sudden cardiac death can occur in any of the acute coronary syndromes. Reversibility of damage to ischemic myocardium after reperfusion may mainly occur within 60-min ischemia
symptoms of stable angina;
Severe substernal pain that lasts more than a few hours
Severe substernal pain lasting more than a few hours is a symptom of a myocardial infarctioin. Stable angina manifests with chest tightness or discomfort that goes away with rest.
Angina pectoris is chest pain caused by myocardial ischemia. Stable angina is caused by gradual luminal narrowing and hardening of the arterial walls, so that affected vessels cannot dilate in response to increased myocardial demand associated with physical exertion or emotional stress. With rest, blood flow is restored and no necrosis of myocardial cells results. 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. The pain is caused by the buildup of lactic acid or abnormal stretching of the ischemic myocardium that irritates myocardial nerve fibers. These afferent sympathetic fibers enter the spinal cord from levels C3 to T4, accounting for the variety of locations and radiation patterns of anginal pain. 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.
Myocardial ischemia in women may not present with typical angina. Common symptoms in women include atypical chest pain, palpitations, sense of unease, and severe fatigue. In addition, it is estimated that half of women with stable angina do not have obstructive coronary artery disease, but rather have microvascular angina that results from vasoconstriction of small coronary arterioles deep in the myocardium116 (see What's New? Women and Microvascular Angina). Similarly, in individuals who have autonomic nervous system dysfunction, such as older adults or those with diabetes, angina may be mild, atypical, or even silent (see the following).
orthostatic hypotension;
Stands up
Orthostatic hypotension refers to a decrease in blood pressure upon standing and is caused by the gravitational changes on the circulation that are inadequately compensated for.
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.55 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 (see Chapter 32). 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. Primary OH is often chronic. Older adults are susceptible to this type of OH because of slowing of postural reflexes as part of the aging process. It also occurs in neurologic diseases, such as Parkinson disease, multiple system atrophy, and inherited neurologic disorders. Multiple system atrophy is a severe form of chronic autonomic failure in which there are multiple central nervous system degenerative changes, and Parkinson disease. Individuals with this disorder also may exhibit supine hypertension, altered drug sensitivity, hyperresponsiveness of blood pressure to hypo/hyperventilation, sleep apnea, and other neurologic disturbances.56Primary 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.57
Secondary OH is often acute and associated with (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 sodium depletion), and (7) any condition that results in venous pooling (e.g., pregnancy, extensive varicosities of the lower extremities). Other more chronic forms of secondary OH are seen with adrenal insufficiency, diabetes mellitus, cardiovascular diseases, and paraneoplastic syndromes.57
Orthostatic hypotension often is accompanied by dizziness, blurring or loss of vision, and syncope or fainting. To assess hypotensive episode frequency, severity, and correlation with symptoms, 24-hour blood pressure monitoring is recommended. Basic diagnostic tests include ECG and blood electrolyte measurements. Other tests in selected individuals may include autonomic testing, serum catecholamine measurements, and heart rate variability testing.
Treatment for secondary OH is focused on correcting the underlying disorder. No curative treatment is available for primary orthostatic hypertension. Management includes liberalizing salt intake; raising the head of the bed; wearing thigh-high stockings; and administering erythropoietin, somatostatin, volume expansion with mineralocorticoids, and vasoconstrictors, such as midodrine and pyridostigmine
isolated systolic hypertension; Isolated systolic hypertension (ISH) is 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 with cardiovascular and cerebrovascular events.5loss of elasticity of the arteries resulting in an increase in cardiac output or stroke volume, a systolic blood pressure consistently greater than 160 mmHg, and a diastolic pressure less than 90 mmHg.
results of sustained controlled hypertension;
Vascular remodeling
Over time, prolonged vasoconstriction can result in permanent remodeling of blood vessel walls.
Renal disease, stroke and retinal damage
High pressures in the vasculature cause damage to many organs, including the eye (retinal injury), kidneys (nephrosclerosis), and brain (aneurysm resulting in stroke).
In the healthy individual, the RAAS provides an important homeostatic mechanism for maintaining adequate blood pressure and therefore tissue perfusion (see Chapter 32). In hypertensive individuals, overactivity of the RAAS contributes to salt and water retention and increased vascular resistance. In the brain, angiotensin (ang) II enhances sympathetic neural outflow and alters the release of hormones that contribute to endothelial dysfunction, insulin resistance, dyslipidemia, and platelet aggregation.23 Further, ang II mediates arteriolar remodeling, which is a structural change in the vessel wall that results in permanent increases in peripheral resistance24 (see Figs. 33.5 and 32.28). Ang II is associated with end-organ effects of hypertension, including atherosclerosis, renal disease, and cardiac hypertrophy. Decreased renal salt excretion. (shift in pressure-natriuresis relationship)
the relationship of insulin resistance on the development of primary hypertension;
Insulin resistance activates the sympathetic nervous system, contributes to the development of diabetes, dyslipidemia, and eventually atherosclerosis, and promotes thrombus formation
Insulin resistance contributes to increases in SNS activity, peripheral resistance, endothelial injury and thrombus formation.
Finally, insulin resistance is common in hypertension, even in individuals without clinical diabetes. Insulin resistance is associated with endothelial injury and affects renal function, causing renal salt and water retention.37 Insulin resistance is associated with overactivity of the SNS and the RAAS. It is interesting to note that in many individuals with diabetes treated with drugs that increase insulin sensitivity, blood pressure often declines, even in the absence of antihypertensive drugs. The interactions between obesity, hypertension, insulin resistance, and lipid disorders in the metabolic syndrome result in a high risk of cardiovascular disease
defects in the normal secretion of natriuretic hormones and the impact on renal system;
Sodium
Natriuretic hormones affect renal reabsorption of sodium.
The natriuretic hormones modulate renal sodium (Na+) excretion and require adequate potassium, calcium, and magnesium to function properly. The natriuretic hormones include atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP), C-type natriuretic peptide (CNP), and urodilatin. These hormones induce diuresis; enhancement of renal blood flow and glomerular filtration rate, systemic vasodilatation, and suppression of aldosterone; and inhibition of the SNS. Dysfunction of these hormones, along with alterations in the RAAS and the SNS, cause an increase in vascular tone and a shift in the pressure-natriuresis relationship. When there is inadequate natriuretic function, serum levels of the natriuretic peptides rise in an attempt to compensate. In hypertension, increased ANP and BNP levels are linked to an increased risk for ventricular hypertrophy, atherosclerosis, and heart failure.28 Salt retention leads to water retention and increased blood volume, which contributes to an increase in blood pressure. Subtle renal injury results, with renal vasoconstriction and tissue ischemia. Tissue ischemia causes inflammation of the kidney and contributes to dysfunction of the glomeruli and tubules and promotes additional sodium retention. Increasing dietary intake of potassium, calcium, and magnesium can enhance natriuretic peptide function. New natriuretic peptide agonists are being studied.
effects of increased sympathetic nervous system activity due to primary hypertension;
Peripheral vasoconstriction
A major factor in the development of primary hypertension is vasoconstriction and increased peripheral resistance caused by abnormal SNS activity.
The SNS contributes to the pathogenesis of hypertension in many people. In the healthy individual, the SNS contributes to the maintenance of adequate blood pressure and tissue perfusion by promoting cardiac contractility and heart rate (maintenance of adequate cardiac output) and by inducing arteriolar vasoconstriction (maintenance of adequate peripheral resistance). In individuals with hypertension, overactivity of the SNS can result from increased production of catecholamines (epinephrine and norepinephrine) or from increased receptor reactivity involving these neurotransmitters.22 Increased SNS activity causes increased heart rate and systemic vasoconstriction, thus raising the blood pressure. Efferent sympathetic outflow stimulates renin release, increases tubular sodium reabsorption, and reduces renal blood flow. Additional mechanisms of SNS-induced hypertension include structural changes in blood vessels (vascular remodeling), insulin resistance, increased renin and angiotensin levels, and procoagulant effects.22 The SNS is implicated in the cardiovascular and renal complications of hypertension. Beta-blocking medications oppose the effects of the SNS and have been used for decades in the treatment of hypertension. However, because of their side effects, these medications are no longer considered first-line treatment. The role of the SNS in the pathogenesis of cardiovascular disease is summarized in
complications of unstable plaque in the coronary arteries; Myocardial infarction
An unstable plaque can rupture, and the resulting thrombus can obstruct the lumen, causing an abrupt halt to myocardial blood flow. This event is called a myocardial infarction
Many plaques, however, are “unstable,” meaning they are prone to rupture even before they affect blood flow and are clinically silent until they rupture. Plaque rupture occurs because of the inflammatory activation of proteinases (matrix metalloproteinases and cathepsins), apoptosis of cells within the plaque, and bleeding within the lesion (plaque hemorrhage).76,77 Plaques that have ruptured are called complicated plaques (see Fig. 33.12). Once rupture occurs, exposure of underlying tissue results in platelet adhesion, initiation of the clotting cascade, and rapid thrombus formation that may suddenly occlude the affected vessel, resulting in ischemia and infarction. Aspirin or other antithrombotic agents are used to prevent this complication of atherosclerotic disease.
forms of dyslipidemia associated with the development of the fatty streak in atherosclerosis; High LDL
In atherosclerosis, LDL adheres to the injured endothelium and is oxidized by macrophages to form the fatty streak. High serum LDL is a risk factor for atherosclerosis.
Injured endothelial cells become inflamed and cannot make normal amounts of antithrombotic and vasodilating cytokines. The adventitia also plays an important role through production of reactive oxygen species and activation of endothelial inflammation.72 Low-density lipoprotein (LDL) penetrates into the subintima of arterial walls, where it is trapped by proteoglycans (Fig. 33.13). Inflammation, oxidative stress, and activation of macrophages cause the aggregated LDL to become oxidized. Hypertension, increased levels of LDL, oxidative stress, and activation of the renin-angiotensin-aldosterone system all contribute to an acceleration of this step in atherogenesis.73 Inflammation and oxidized LDL cause endothelial cells to express adhesion molecules that bind monocytes and other inflammatory and immune cells. Monocytes penetrate the vessel wall becoming macrophages. Several types of receptors on these macrophages (toll-like receptors [TLRs] and LDL receptor-related protein [LRP]) enable detection and engulfment of the oxidized LDL.74 These lipid-laden macrophages are now called foam cells, and when they accumulate in significant amounts, they form a lesion called a fatty streak and numerous inflammatory cytokines are released (e.g., tumor necrosis factor-alpha [TNF-α], interferons, interleukins, and C-reactive protein), as well as enzymes that further injure the vessel wall.75 Growth factors also are released, including ang II, fibroblast growth factor, TGF-β, and platelet- [Show Less]