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Endometrial Icycle Iand Ioccurrence Iof Iovulation
REPRODUCTIVE
Manifestation of female reproductive functioning is menstrual bleeding, which starts with menarche (1st
period) 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, and
corpus 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 aboutIday
- 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 lining
begins 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 secrete
progesterone.
- This will initiate the secretory phase of endometrial development.
NR 507 IPATHIFINALIEXAMISTUDYIGUIDE
UterineIProlapse
- Glands and blood vessels in the endometrium branch and curl through a functional layer, and the glands
begin to secrete a thin glycogen-containing fluid= the secretory phase.
*If conception occurs the nutrient-laden endometrium is ready for implantation.
*The HCG hormone is secreted 3 days after fertilization by blastocytes and maintains the corpus luteum
once 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 hormonal
production.
*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 to
proliferate (proliferative phase) and induces the LH surge and progesterone production in the granulosa layer.
During the luteal/secretory phase, estrogen maintains the 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.
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.
- Dropping of the cervix or the entire uterus into the vaginal canal.
*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 of steroid 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 apoptosis
Decreased 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 triggers the beginning of anovulation.
- 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:
Signs Iof Ipremenstrual Idysphoric Idisorder I(PMDD)
Dysfunctional I uterine I bleeding
Clinical manifestation Pathophysiology
Chest pain Metastasis to 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
• 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 or
heavily.
• Occurs more in women ages 40 - 50 because they are at the end of their reproductive years and
are more likely to ovulate irregularly.
• PCOS can lead to irregular heavy uterine bleeding
The cyclic recurrence (in the luteal phase of the menstrual cycle) of distressing physical, Iphysical,
pI sychologic, Ior Ibehavioral Ichanges Ithat Iimpair Iinterpersonal Irelationships Ior Iinterfere Iwith Iusual
sleeping,IN&V,Iheadaches,Ifainting.
WomenIshowIsymptomsIofIirritability,Inervousness,Ianger,Iinsomnia,Ianxiety,Iparanoia,Itrouble I
rI elationships Iduring Ithis Itime.
starts. IWhen Ithis Ihappens, Isome Iwomen Ihave Itrouble Ifunctioning Iat Ihome, Iat Iwork Iand Iin
SymptomsIusuallyIappearIaIweekIbeforeImenstruationIandIendIaIfewIdaysIafterIyourIperiod I
IincludingInegative Imood, Iirritability, Iaggression, Iand Iimpulse Icontrol. I
Iand Iprogesterone Iand Iall Iof Ithese Iare Ineuroactive Iwith Iknown Imood Iand Ibehavior Ieffects,
symptomImanifestation.ITheseIneurotransmittersIhaveIdemonstratedIinteractionsIwithIestrogen
Neurotransmitters,IGABA,IandInoradrenalineImayIhaveImediatingIorImoderatingIrolesIon I
aI ctivities.
Pathophysiology I of I prostate I cancer
HPVIand Idevelopment Iof Icervical Icancer
• 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 remain
portions 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.
- 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 to antiproliferative, 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 glands require male hormones, known as androgens, to work properly. Androgens include 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 is the 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
• 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 that
leads to invasive cancer.
• With these cell changes, they can be detected noninvasively through examination of the cervical
cells. The cells can be destroyed to prevent cancer development if dysplasia can be detectedearly.
• 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 with
columnar 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 Iprocess Ifor Iadapting ItoIhigh Ihormone Ilevels: Negative-feedback systems are important in maintaining hormone concentrations within physiologic ranges. The lack of negative-feedback inhibition on hormonal release often results in
Hypoparathyroidism ICX: 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 Iresults Ipoint Ito Iprimary Ihypothyroidism: 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 Ihypothyroidism IDX: 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 Iof Ithyroid Istorm: (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 Iof Ithyrotoxicosis : 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
NEURO
Substance Irelease Iat Isynapse
LocationIofImotorIandIsensory IareasIofItheIbrain
Specific areas of cutaneous (skin) innervation at these spinal cord segments. The dermatomes of various spinal nerves are distributed in a fairly regular pattern, although adjacent regions between dermatomes can be innervated by more than one spinal nerve. The region between adjacent neurons is called a I 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. 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 Iareas 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 Iareas of the CNS, where they are processed and guide behavior. PathoIof IcerebralIinfarction IandIexcitotoxins 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 completelyoccluded (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)
ImpactIofIBPHIonItheIUrinaryISystem
Dietary intake effects the signaling pathways, hormones, oxidative stress, and reactive oxygen species (RDS). INutrients Imost IassociatedIwithIcancer IareIcarotenoids, Ifat, Ivit IE, Ivit ID/calcium, Iand Iselenium. 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 cancer High 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 cell proliferation, 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 Vegetables including 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. 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 3 rd^ 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 in starting 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 moreItime is required to initiate and complete urination at this stage. Hematuria, bladder or kidney infection, bladder calculi, acute urinary retention hydroureter, hydronephrosis, and renal insufficiency 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 Irole Iof IDNAIin Igenetics – 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
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. KlinefelterIsyndrome:
smallness of testes with fibrosis and hyalinization of seminiferous tubules, variable degrees of
masculinization, azoospermia, infertility, and increased levelsof urinary gonadotropins; associated
typically 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 mental impairment 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 Imuscular Idystrophy
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 all
neuromas and is divided into two types: NF 1 and NF 2 , 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 NF
- 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 unsteadiness with 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 IthatIhaveImultifactorialItraits/multifactorial Iinheritance
- 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 goals
of 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 relatives
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 cross- bridge 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 Iof Ilong Ibones Iin Ichildren : 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 Ibelonging Ito Ithe Iappendicular Iskeleton : 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 bones Humerus (2)- only long bone of the arm, articulates at the proximal end with the glenoid cavity of the scapula
Radius (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 has roughened 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.
