Endometrial Cycle and Occurrence of Ovulation, Exams of Nursing

Download Endometrial Cycle and Occurrence of Ovulation and more Exams Nursing in PDF only on Docsity! 1 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 14. -In phase 1 the endometrium grows to form a lush lining inside of the uterus. Phase 2: Luteal phase-this is where the body secretes the hormones estrogen and progesterone. -These hormones work together to prepare the lining of the uterus for implantation. -This last for 12 days. Phase 3: Menstrual phase-The estrogen and progesterone start to decline and the endometrial 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. NR507 IPATH IFINAL IEXAM ISTUDY IGUIDE 2 Uterine IProlapse -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 25.11 -Dropping of the cervix or the entire uterus into the vaginal canal. 5 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: 6 Testicular Icancer I& IRisk Ifactors Symptoms Ithat Irequire Ievaluation Ifor IBreast ICancer *dx is made based on androgen excess, chronic anovulation, and sonographic evidence of polycystic ovaries. *Must have 2 -3 of these. *Impaired glucose tolerance test is recommended *Goals are to suppress androgen, instituting menstruation, restore fertility, and reduce endocrine disturbance. **FIRST LINE TREATMENT= COMBINED ORAL CONTRACEPTIVES** -This helps to initiate regular menses. -Lifestyle modifications= exercise and weight loss. --Insulin resistance= metformin -If pregnancy is not desired- progesterone therapy is important to oppose estrogen effects on the endometrium to help monthly bleeding. **FOR OBESE WOMEN LIFESTYLE MODIFICATIONS ARE FIRST LINE** -CLOMIPHENE CITRATE CAN BE USED TO FACILITATE OVULATION* Highly treatable, usually curable cancer most often develops in young and middle aged men. Rare, but most common form of cancer between young men 15-35. More common on R side than left. Germ cell tumors arising from male gametes: seminomans and nonseminomas. Seminomas are most common, least aggressive. Nonseminomas include embryonal carcinomas, teratomas, and choriocarcinomas, most aggressive but rare. Neoplasm cause is unknown. Genetic predisposition is suggested d/t incidence in brothers, identical twins and close male relatives. Risk factors: cryptochordism- neoplasmsdevelop more commonly in contralateral testis. Abnormal testicular development, HIV and AIDS, Klinefelter syndrome, and hx of testicular cancer. 7 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. Women Ishow Isymptoms Iof Iirritability, 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 Symptoms Iusually Iappear Ia Iweek Ibefore Imenstruation Iand Iend Ia Ifew Idays Iafter Iyour Iperiod I Iincluding Inegative Imood, Iirritability, Iaggression, Iand Iimpulse Icontrol. I Iand Iprogesterone Iand Iall Iof Ithese Iare Ineuroactive Iwith Iknown Imood Iand Ibehavior Ieffects, symptom Imanifestation.IThese Ineurotransmitters Ihave Idemonstrated Iinteractions Iwith Iestrogen Neurotransmitters, IGABA, Iand Inoradrenaline Imay Ihave Imediating Ior Imoderating Iroles Ion I aI ctivities. 10 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 11 Substance Irelease Iat Isynapse Location Iof Imotor Iand Isensory Iareas Iof Ithe Ibrain 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 Isynapse. 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) 12 Diet Iand Iprevention Iof Iprostate Icancer Agnosia Impaired/defect of recognition and may be tactile, visual or auditory stimuli. Caused by dysfunction in the primary sensory area or the interpretive areas of the cerebral cortex Accumulation Iof Iblood Iin Ia Isubarachnoid Ihemorrhage I(SAH) Hemorrhage from a defective or injured vasculature into the subarachnoid space. The blood is extremely irritating to the meningeal and other neural tissues and so produces an Iinflammation I& Iimpairs Icirculation Iof Icerebrospinal Ifluid. Additionally, the blood coats nerve roots, clogs arachnoid granulations (impairing CSF reabsorption), and clogs foramina within the ventricular system (impairing CSF circulation). ICP immediately increases to almost diastolic levels within 10 mins. ICP returns to near baseline in about 10 minutes. Cerebral blood flow and cerebral perfusion pressure (CPP) decrease. The expanding hematoma acts like a space-occupying lesion, compressing and displacing brain tissue. Granulation tissue is formed and scarring of the meninges, with resulting impairment of CSF reabsorption and secondary hydrocephalus, often results. Most Icommon Icause Iof Imeningitis Meningitis is inflammation of the brain or spinal cord. Infectious meningitis may be caused by bacteria, viruses, fungi, parasites, or toxins. Bacterial I& Iviral meningitis is the most common. Bacterial infection may be due to Neisseria meningitis, Haemophilus influenza, streptococcus pneumoniae, or Escherichia coli. Sometimes, no causative organisms can be found. In most patients, the infections that cause meningitis is secondary to another bacterial infection, such as bacteremia. Respiratory infections increase the risk. It may follow a skull fracture, a penetrating head wound, lumbar puncture, ventricular shunting, or neuro procedure. Viral meningitis aka aseptic viral meningitis may result from a direct infection or secondary to disease such as mumps, herpes, measles, or leukemia. (Textbook) GENITOURINARY Evidence exists that dietary factors play a role in prostate cancer development. The lack of biomarkers for certain nutrients, difficulty measuring and quantifying diet, and limitation of clinical trials all make the understanding of the relationship difficult. 15 = short nt/protein segments on the ends of chromosome arms that protect DNA and prevent chromosome fusions during the cell division cycle. Telomeres gradually erode away with each cell division until DNA unravels and chromosome disintegrates. This is an important way to help eliminate chromosomes (and cells) carrying accumulated undesirable mutations! DNA is the genetic basis of life = the “blueprint of life" Transcription –Transcription is the process by which DNA specifies a sequence of mRNA. RNA is synthesized using DNA as the template via the process of transcription. However, unlike the replication process where an exact copy is made of all the DNA within the nucleus, only small portions of DNA are transcribed at a time to make RNA. Each transcribed segment of DNA corresponds to one of the 1000’s of genes that make up our chromosomes. Several 100-1000 DNA nt comprise a gene = information for synthesis of a specific protein. Effects Iof Igenetic Imutations – Changes in the DNA can also occur as the result of a mutation = inheritable alteration of genetic material. Mutations can occur either spontaneously or as a result of exposure to external mutagens such as radiation, chemicals, and even certain infectious agents (eg – viruses). Mutations in individual genes can also result in single gene disorders. (e.g. sickle cell anemia, cystic fibrosis, hemophilia) Depending on the location of the mutated gene, and whether or not it is a dominant or recessive allele, disorders are classified as: autosomal dominant, autosomal recessive, sex-linked Most diseases (including diabetes, dementia, cardiovascular conditions, cancer) have a genetic component and are classified as multi-factorial: mutations occur at multiple (polygenic) chromosomal sites that have a cumulative effect to cause disease. Down Isyndrome/ITrisomy: Trisomy is a type of aneuploidy in which one chromosome is present in three copies in somatic cells. A partial trisomy is one in which only part of a chromosome is present in three copies. Down Syndrome- pg. 146 – aneuploidy in an autosome is trisomy of the 21 chromosome, low nasal bridge, epicanthal folds, protruding tongue, flat low set ears. Down syndrome, a trisomy of chromosome 21, is the most well-known disease caused by a chromosome aberration. It affects 1 in 800 live births and is much more likely to occur in the offspring of women older than 35 years of age. • Failure of the homologous chromosome pairs to separate during meiosis is called nondisjunction and also results inaI bnormalities of chromosome number. • Aneuploidy: gamete cell that does not have 23 chromosomes so resulting embryo will have fewer or extra chromosome (not all abnormal chromosomes may even survive). Cells with fewer than normal chromosomes are less likely to survive than cells that have more than normal chromosomes. • Aneuoploidy of sex chromosomes results in conditions: o Klinefeiter symdrome (XXY) o Turner syndrome (XO) • Aneuoploidy of autosomal chromosomes results in conditions such as: o Down syndrome (trisomy 21) o Or Edwards syndrome (trisomy 18) Aneuploid cells are those that do not contain a multiple of 23 chromosomes. An aneuploid cell containing three copies of one chromosome is said to be trisomic (a condition termed trisomy) 16 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 17 - 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: NF1 and NF2, which are clinically and genetically distinct disorders. The gene products are neurofibromin and merlin (schwannomin), both of which are thought to be tumor suppressors - Inherited autosomal dominant disorder accounting for 5% of all neuromas and is divided into two types: NF1 and NF2 - NF1 is associated with cutaneous manifestations, iris hamartomas, and tumors primarily involving the peripheral nervous systems and occasionally the CNS - NF2 is associated with cataracts, hearing loss, and tumors primarily in the CNS; most commonly vestibular schwannoma and meningioma - The tumors most commonly affect people older than 50, women more than men - The tumor originates most commonly just distal to the junction between the nerve roots and the brainstem o As the tumor grows, it extends into he posterior fossa to occupy the cerebropontine angle and compressadjacent nerves o Eventually, the brainstem is displaced, and the CSF flow is obstructed - Clinical manifestations: headache, tinnitus, hearing loss, impaired balance, unsteady gait, facial pain, and loss of facial sensations o Later, vertigo with nausea, vomiting, a sense of pressure in the ear, and moderate to severe 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 20 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. —Axial Skeleton —Appendicular Skeleton Sternum Vertebral Column Sacrum Carpals ——, Uf Veg Metacarpais (if AN Phalanges © Buzzle.com Skull Clavicle Scapula Humerus UlIna Radius Metatarsals be <22n)-Phalanges Sketch by Abhishake Sharma DIAGRAM OF SKELETON 22 IMMUNITY How Ivaccines Iare Iperformed – A vaccine is a biological preparation that provides active acquired immunity to a particular disease. A vaccine typically contains an agent that resembles a disease-causing microorganism and is often made from weakened or killed forms of the microbe, its toxins, or one of its surface proteins. Vaccines are like a training course for the immune system. They prepare the body to fight disease without exposing it to disease symptoms. When foreign invaders such as bacteria or viruses enter the body, immune cells called lymphocytes respond by producing antibodies, which are protein molecules. Antigens are present in extremely small quantities to elicit an immune response through a vaccine. The most common routes of administration are intravenous, intraperitoneal, subcutaneous, intranasal, and oral. Each route stimulates a different set of lymphocyte-containing tissues and therefore results in the induction of different types of cell-mediated or humoral immune responses. Vaccines are considered nonimmunogenic. Populations Iare Irisk Ifor Igetting Isystematic Ifungal Iinfections Iand Iparasitic Iinfections- In immunocompromised individuals, particularly those with diminished levels of neutrophils (neutropenia), fungal infections may occur. Candida is the most common fungal infection in people with cancer (particularly acute leukemia and other hematologic cancers) transplantation (bone marrow and solid organ), and HIV/AIDS. Almost 90% of people with AIDS have candida at least one time (usually thrush or vaginitis) because of their decreased number of neutrophils. Invasive candidiasis may also be secondary to indwelling catheters, intravenous lines, or peritoneal dialysis which provided direct entrance into the blood. Disseminated candidiasis may involve several internal organs, including abscesses in the kidney, brain, liver, and heart. It is characterized by a persistent fever and gram-negative shock like symptoms (hypotension, tachycardia), DIC, and death. The mortality rates of sepsis or disseminated candidiasis are in the range of 30-40%. Parasitic infections are uncommon in the United States, with significant mortality and morbidity of individuals in developing countries. Malaria is most common in Africa. Systematic Imanifestations Iof Iinfection – Systematic infection is the term used to describe an infection that is circulating in the blood. This means it affects the entire body. Signs/symptoms of this can be fever, tachycardia, hypotension, septic shock, toxic shock, hypovolemia, respiratory alkalosis, and hyperventilation, neutropenia, thrombocytopenia, and DIC. Alterations in sensorium may occur in severe infection and may cause anxiety, confusion, delirium, stupor, seizures, and coma. Mechanism Iresponsible Ifor Ithe Iincrease Iin Iantimicrobial Iresistance Iworldwide – Antimicrobial resistance occurs naturally overtime, usually through genetics. However, the misuse and overuse of antimicrobials is accelerating this process. In many places antibiotics are overused and misused. Example of misuse include they are taken by people with viral infections such as the flu. Poor infection control, inadequate sanitary conditions and inappropriate food handling encourage the spread of antimicrobial resistance. Functions Iof Inormal Ibody Iflora The normal microbiome provides protection by inhibiting colonization by pathogens and by releasing chemicals that prevent infection. Each surface including the skin, mucous membranes of the eyes, upper and lower GI, urethra and vagina are all colonized by combo of bacteria (mostly bacteria) and fungi that are unique to the particular location. The relationship betweenthis “good” bacteria and humans is both commensal (to the benefit of one organism without affecting the other) and mutualistic (to the benefit of both). Many of these microorganisms help digest fatty acids, large polysaccharides and other dietary substances. They also produce biotin and Vit K, assist in the absorption of various ions: such as calcium, iron and magnesium. These good bacteria compete with pathogens for nutrients and block attachment to the epithelium. They produceIchemicals (ammonia, phenols, and indoles). Treatment with broad spectrum abx can alter this normal flora, decreasing its protective activity, leading to overgrowth of yeast Candida Albicans or C Dif. The good flora trains the adaptive immune systemby growth of gut-associated lymphoid tissue (where cells of adaptive immunity reside). DesensitizationItherapy Also known as allergen Immunotherapy. This is where minute quantities of the allergen are injected in increasing doses over aprolonged period. The therapy may reduce the severity of the allergic reaction in the treated individual. This therapy is associated with a risk of systemic anaphylaxis, which can be life threatening. This approach works best for routine respiratory allergies and biting insect allergies (80-90% rate of desensitization over 5 years of treatment). The mechanisms by which desensitization occurs may be several, one of which is the production of large amounts os so called blocking antibodies, usually circulating IgG. A blocking antibody presumably competes in the tissues or in the circulation for binding with antigenic determinants on the allergen so the allergen is “neutralized” and is unable to bind with IgE on the mast cells. Desensitization 25 ACID/BASE Causes Iof Irespiratory Ialkalosis: hyperventilation, anxiety, panic, pain, altitude changes, hypermetabolic states (fever, sepsis, hyperthyroidism). Molecules Ithat Iact Ias Ibuffers Iin Ithe Iblood: Carbonic acid bicarbonate is the most important buffer system.to remove H+ or OH-. H+ reacts with HO3- (bicarbonate) presents in bloodstream. It forms a weak base HCO3-. Get rid of bicarbonate it can add with water and it can split HCO3- and water can be excreted in urine and can put our PH back to normal. 26 Most Icommon Icardiac Ivalve Idisease Iin Iwomen When Imyocardial Iischemia Imay Ibe Ireversible CARDIOVASCULAR Mitral valve prolapse is common in young women. Although not grossly abnormal, the mitral valve leaflets do not position themselves properly during systole. Mitral valve prolapse is a condition in which the anterior and posterior cusps of the mitral valve billow upward (prolapse) into the atrium during systole. It is often be asymptomatic and often have an excellent prognosis. Some at-risk individuals are at risk for complications such as cardioembolic stroke and endocarditis. Mitral valve prolapse is the most common cause of mitral regurgitation, which allows backflow of blood from the left ventricle into the left atrium during systole. This causes a murmur. The increased blood volume, causes the left atrium and ventricle to enlarge, causing associated a-fib and the left ventricle to become hypertrophied. Eventually, as the regurgitation progresses, the left ventricle will become impaired, causing failure, and eventually leading to pulmonary hypertension and right sided heart failure. Mitral valve prolapse is the most common valve disorder in the United States, and most prevalent among young women. Some studies suggest there to be an autosomal dominant and X-linked inheritance pattern. Because mitral valve prolapse often is associated with other inherited connective tissue disorders (Marfan syndrome, Ehlers-Danlos syndrome, osteogenesis imperfecta), it is thought to result from a genetic or environmental disruption of valvular development during the fifth or sixth week of gestation. There may also be a relationship between hyperthyroidism and mitral valve prolapse. Afflicted valves may be at greater risk for developing infective endocarditis. An acute obstruction in a coronary artery can cause myocardial cell death (infarction) within minutes if the blood supply is not restored, whereas the gradual onset of ischemia usually results in myocardial adaptation. Ischemic injury is often caused by gradual narrowing of arteries (arteriosclerosis) and complete blockage by blood clots (thrombosis). Individuals with coronary heart disease may develop myocardial ischemia during mental or acute emotional stress even though their exercise results are negative. Ischemia, a local state in which the cells are temporarily deprived of blood supply. They remain alive but cannot function normally. Persistent ischemia or the complete occlusion of a coronary artery causes acute coronary syndrome. Myocardial ischemia develops if the supply of coronary blood cannot meet the demand of the myocardium for oxygen and nutrients. Imbalances between myocardial demand and coronary blood supply can result from a number of conditions. Common causes of increased myocardial demand for blood include tachycardia, exercise, hypertension (hypertrophy), and valvular disease. The most common cause of decreased coronary blood flow and resultant myocardial ischemia is the formationof atherosclerotic plaques in the coronary circulation. As the plaque increases in size, it may partially occlude the vessel lumina,thus limiting coronary flow and causing ischemia especially during exercise. Thrombus formation can suddenly cut off blood supply to the heart muscle, resulting in acute myocardial ischemia, and if the vessel obstruction cannot be reversed rapidly, ischemia will progress to infarction. Myocardial ischemia also can result from other causes of decreased blood and oxygen delivery to the myocardium, such as coronary spasm, hypotension, dysrhythmias, and decreased oxygen- carrying capacity of the blood (anemia, hypoxemia). Myocardial cells become ischemic within 10 seconds of coronary occlusion. After several minutes the heart cells lose the ability to contract, and cardiac output decreases. Ischemia also causes conduction abnormalities that lead to changes in the electrocardiogram and may initiate dysrhythmias. Anaerobic processes take over, and lactic acid accumulates. Cardiac cells remain viable for approximately 20 minutes under ischemic conditions. If blood flow is restored, aerobic metabolism resumes, contractility is restored, and cellular repair begins. If the coronary artery occlusion persists beyond 20 minutes, MI occurs Symptoms Iof Istable Iangina I(angina pectoris) Caused by gradual luminal narrowing and hardening of the arterial walls, affected vessels cannot dilate in response to increased myocardial demand associated with physical exertion or emotional stress. If demand is decreased, no necrosis of myocardial cells results Symptoms: • Transient substernal chest discomfort- ranging in a sensation of heaviness or pressure to moderately severe pain (like a clenched fist over the left sternal border) • Often mistaken for indigestion 27 Orthostatic Ihypotension • Pain may radiate to the neck, lower jaw, left arm, and left shoulder or occasionally to the back or down the right arm.Pallor, diaphoresis, and dyspnea may be associated with the pain. The pain is usually relieved by rest and nitrates; lack of relief indicates an individual may be developing infarction • Myocardial ischemia in women may not present with typical anginal pain o Common symptoms in women include: atypical chest pain, palpitations, sense of unease, and severe fatigue and sometimes can be silent. Decrease in systolic and diastolic arterial blood pressure upon standing. The compensatory vasoconstriction response to standing is altered by a marked vasodilation and blood pooling in the muscle vasculature. Orthostatic hypotension may be acute or chronic. The acute form is caused by a delay in the normal regulatory mechanisms. The chronic forms are secondary to a specific disease or are idiopathic. The clinical manifestations of orthostatic hypotension include fainting and may involve cardiovascular symptoms, as well as impotence and bowel and bladder dysfunction. • Defined with a systolic blood pressure decrease of at least 20 mmHg or a diastolic blood pressure decrease of at least 10 mmHg within 3 minutes of standing up. • It can be categorized as arteriolar, venular, or mixed. • Compensatory changes during standing normally increase sympathetic activity mediated through stretch receptors (baroreceptors) in the carotid sinus and the aortic arch. This reflex response to shifts in volume caused by postural changes leads to a prompt increase in heart rate and constriction of the systemic arterioles, which maintains a stable blood pressure. These compensatory mechanisms are not effective in maintaining a stable blood pressure in individuals with orthostatic hypotension. • Orthostatic hypotension may be acute or chronic. o Acute orthostatic hypotension (temporary type) may result from: (1) altered body chemistry (2) drug action (e.g., antihypertensives or antidepressants) (3) prolonged immobility caused by illness (4) starvation (5) physical exhaustion (6) any condition that produces volume depletion (e.g., massive diuresis, potassium or sodium depletion) (7) venous pooling (e.g., pregnancy, extensive varicosities of the lower extremities). (8) Older adults are susceptible to this type of orthostatic hypotension, in which postural reflexes are slowed as part of the aging process. • Chronic orthostatic hypotension can be categorized as: (1) secondary to a specific disease (2) idiopathic or primary. • The diseases that cause secondary orthostatic hypotension are endocrine disorders (e.g., adrenal insufficiency, diabetes mellitus), metabolic disorders (e.g., porphyria), or diseases of the central or peripheral nervous system (e.g., intracranial tumors, cerebral infarcts, Wernicke encephalopathy, peripheral neuropathies). • Cardiovascular autonomic neuropathy is a common cause of orthostatic hypotension in diabetes. • Idiopathic, or primary, orthostatic hypotension is the term for hypotension in which there is no known initial cause. o It affects men more often than women and usually occurs between the ages of 40 and 70 years. o It is a significant risk factor for falls and associated injuries and has been associated with an increased risk for cardiovascular events. • Orthostatic hypotension often is accompanied by dizziness, blurring or loss of vision, and syncope or fainting. o To assess hypotensive episode frequency, severity, and correlation with symptoms, 24-hour blood pressure monitoring is recommended. o No curative treatment is available for idiopathic orthostatic hypertension. o In the secondary form, postural hypotension improves when the underlying disorder is corrected. 30 Events Ithat Iinitiate Ithe Iprocess Iof Iatherosclerosis: Type I Ib: combined hyperlipidemia; carbohydrate-induced hypertriglyceridemia Lab findings: LDL, VLDL increased Cholesterol increased Triglycerides increased Clinical features: Same as IIa Therapy: Same as IIa; plus carbohydrate restriction Clofibrate Gemfibrozil Lovastatin Type I II: dysbetalipoproteinemia Lab findings: IDL or chylomicron remnants increased Cholesterol increased Triglycerides increased Clinical Features: Premature vascular disease Xanthomas of tendons and bony prominences Uncommon Onset: adulthood Therapy: Weightcontrol Low-carbohydrate, low-saturated-fat, and low-cholesterol diet Alcoholrestriction Clofibrate Gemfibrozil Lovastatin Nicotinic Acid Estrogens Intestinal bypass Type I V: endogenoushyperlipidemia; carbohydrate-induced hypertriglyceridemia Lab findings: Glucose intolerance Hyperuricemia Cholesterol normal or increased VLDL increased Triglycerides increased Clinical features: Premature vascular disease Skin lipid deposits Obesity Hepatomegaly Common onset: adulthood Therapy: Weightcontrol Low-carbohydratediet Alcoholrestriction Clofibrate Nicotinic acid Intestinal bypass Type IV: mixedhyperlipidemia; carbohydrate and fat-induced hypertriglyceridemia Lab findings: Glucose intolerance Hyperuricemia Chylomicrons increased VLDL increased LDL increased Cholesterol increased Triglycerides increased three times Clinical features: Abdominal pain Hepatosplenomegaly Skin lipid deposits Retinal lipid deposits Onset: childhood Therapy: Weightcontrol Low-carbohydrate and low-fat diet Clofibrate Lovastatin Nicotinic acid Progesterone Intestinal bypass High serum LDL is a risk factor for atherosclerosis. LDL adheres to the injured endothelium and is oxidized by macrophages to form the fatty streak. The macrophages in the tunica media of the vessel wall accumulate and form the fatty streak. Endothelial inquiry and release of cytokines initiates atherosclerosis. The most common consequence of atherosclerosis is obstruction of the blood vessel lumen. Smooth muscle proliferations, fibrosis, and calcification in atherosclerosis all reduce the size of the blood vessel lumen. 31 Difference Ibetween IL I& IR Isided I Ifailure • result of pulmonary vascular congestion & inadequate perfusion of systemic circulation o dyspnea, orthopnea, frothy sputum cough, fatigue, urine output, edema o pulmonary edema ▪ cyanosis, inspiratory crackles, pleuraleffusions ▪ hypo/hypertension, S3 gallop, evidence of underlying CAD or HTN Cardiac dysfunction caused by inability of the heart to provide adequate cardiac output, resulting in inadequate tissue perfusion ▪ Left HF (CHF) o Inability of LV to provide enough adequate blood flow into systemic circulation o Cause: Systemic HTN (most common), LVMI, LV hypertrophy, Aortic SLV or Bicuspid valve damage, 2ndary to Rt HF ▪ LV MI- results in weakening of muscle d/t damage ▪ LV hypertrophy - 2ndary to cardiac damage, resulting in enlarged but weaker structure holding more blood ▪ Aortic SLV- causes backflow of blood into Lt atrium or ventricle after eject ▪ RT HF- from buildup of pressure of damaged Rt ventricle o Disease Process ▪ High systemic vascular pressure ⟶ 𝖳LV contraction force (𝖳 afterload) ⟶ LV unable to eject normal amount of blood ⟶ 𝖳 LV preload (amount of blood remaining) ⟶ LA unable to eject normal amount of blood ⟶ 𝖳 LA preload (amount of blood remaining in LA) ⟶ 𝖳 blood volume + pressure in pulmonary veins ⟶ fluid forced out into pulmonary tissues ⟶ pulmonary edema + dyspnea ⟶ Rt HF= biventricular HF ▪ Right HF (Cor Pulmonale) o Inability of RV to provide enough adequate blood flow into pulmonary circulation o Cause: Pulmonary disease, Pulmonary HTN (most common), RV MI, RV hypertrophy, Pulmonary SLV or tricuspid valve damage, 2ndary to Lt HF ▪ RV MI- results in weakening of muscle S&S Iof I𝖳Left IAtrial I&Pulmonary Ivenous Ipressures Iin ILeft ISided IHF 32 InfectiveIEndocarditis ▪ RV hypertrophy- 2ndary to cardiac damage ▪ Pulmonary SLV or tricuspid valve damage- causing backflow of blood into RA or RV after ejection ▪ 2ndary to Lt HF- from buildup of pressure in damaged left ventricle o Disease Process ▪ High Pulmonary vascular resistance ⟶ 𝖳RV contraction force (𝖳 afterload) ⟶ RV unable to empty completely ⟶ 𝖳 RV preload (amount of blood remaining in RV) ⟶ RA unable to empty completely ⟶ 𝖳 RA preload (amount of blood remaining in RA) ⟶ 𝖳 vena cava + systemic venous volume + pressure ⟶ fluid forced out into peripheral tissues ⟶ JVD, Liver & Spleen become engorged (hepatosplenomegalia) 𝖳 pressure forced fluid from systemic capillaries into peripheral tissues, flooding areas, resulting in peripheral edema ⟶ Lt HF= biventricular HF ▪ Infection & Inflammation of the endocardium, esp. cardiac valves ▪ Bacteria most common cause (strep, staph, enterococci) o Endocardial damage ▪ Trauma, congenital heart disease, valvular heart disease, prosthetic valves ▪ turbulent blood caused by these affects atrial surface of AV valves or ventricular surface of SL valves ▪ endocardial damage exposes membrane (contains collagen that attracts platelets, stimulating thrombus formation on membrane) ▪ causes inflammatory reaction (nonbacterial thrombotic endocarditis) ▪ Blood borne microorganism adherence to damaged endocardial surface oenter bloodstream during injection drug use, trauma, dental procedures, cardiac surgery, genitourinary procedures, indwelling cath in presence of infection, may spread from upper resp infect or skin infect obacteria damage endocardium using adhesins ▪ Infective endocardialvegetations form obacteria infiltrate thrombi and accelerate fibrin formation, activating clottingcI ascade ovegetative lesions can form anywhere in endocardium, usually on heart valves and surrounding structures obacterial colonies are inaccessible to antibody containing blood due to being embedded in protective fibrin clots 35 HEMATOLOGY Physiological Iresponse ItoIhypoxia Iin Ianemia Hypoxemia, reduced oxygen levels in the blood, further contributes to cardiovascular dysfunction by causing dilations of arterioles, capillaries, and venules, thus leading to decreased vascular resistance and increased flow. Increased peripheral blood flow and venous return further contribute to an increase in heart rate and stroke volume in a continuing effort to meet normal oxygen demand and prevent cardiopulmonary congestion. These compensatory mechanisms may lead to heart failure. Populations Iat Ihighest Irisk Ifor Ideveloping Ifolate Ideficiency Ianemia Humans are totally dependent on dietary intake meet the daily requirement of 50-200mcg/day. Increased amounts are required for pregnancy and lactating females. Folate deficiency is more common than B12 deficiency, particularly in alcoholics and individuals with chronic malnourishment. Alcohol interferes with folate metabolism in the liver, causing a profound depletion of folate stores. Fad diets and diets low in vegetables also may cause folate deficiency because of the absence of plant sources of folate. Cause Iof IIron IDeficiency IAnemia Iron deficiency Anemia can arise from one of two different etiologies or a combination of both- inadequate dietary intake or excessive blood loss. In both instances there is no intrinsic dysfunction in iron metabolism; however, both deplete iron stores and reduce hemoglobin synthesis. A second category is a metabolic or functional iron deficiency in which various metabolic disorders lead to either insufficient iron delivery to bone marrow or impaired iron use within the marrow. Paradoxically, iron stores may be sufficiency but delivery is inadequate to maintain heme synthesis, thus producing a functional or relative iron deficiency. The most common cause of IDA in developed countries is pregnancy and chronic blood loss. Blood loss of 2-4 ml/day(1-2 mg of iron) is sufficient to cause iron deficiency and may results in erosive esophagitis, gastric and duodenal ulcers, colon adenomas, or cancers. H. pylori infections also have been found to cause IDA of unknown origin, although H. pylori impairs iron uptake. In females, menorrhagia is a common cause of primary IDA. Other causes of IDA for both genders are 1. Use of medication that cause GI bleeding such as aspirin or NSAIDS 2. Surgical procedures that decrease stomach 36 acidity, intestinal 37 transit time, and absorptions such as with gastric bypass 3. Insufficient dietary intake of iron 4. Eating disorders, such as pica, which is the craving and eating of non-nutritional substances, such as dirt, chalk, and paper. Expected Ilab Itest Iresults Ifound Iin Ilong Istanding IIron IDeficiency IAnemia Symptoms of IDA begin gradually, and individuals usually do not seek medical attention until hemoglobin level have decrease to 7-8 g/dl. Other lab values include: Hemoglobin – low, Hematocrit – low, Reticulocyte – Normal or slightly high or low, Mean corpuscular volume – low, Plasma iron – low, Total iron-binding capacity – high, Ferritin – low, Serum B12 – Normal, Folate – Normal, Bilirubin – Normal, Free erythrocyte protoporphyrin – High, Transferrin - Low Sickle ICell IAnemia -Sickle cell anemia is an inherited (autosomal recessive) disorder of erythrocytes -300 million people are affected by a hemoglobinopathies (sickle cell or Thalassemia) -genes involved: Alpha=chromosome 16 Beta= chromosome 11 -Inherited autosomal recessive=inheritance of 2 abnormal genes from each parent -Inheritance of 1 normal gene/1 abnormal gene=sickle cell trait carrier = asymptomatic -Most common in certain geographic areas *African America *Mediterranean *South Eastern Descent -Cells that contain more abnormal types of hemoglobin (sickle cell) are more resistant to parasites that cause malaria -Also, the decrease in lifespan/circulation of these cells do not give the parasite enough time to allow production cycle. -Individuals who are affected by sickle cell happen to be from same geographic location that malaria is an endemic. Pathophysiology-Single amino acid changes occur on beta chain of hemoglobin. -Amino acid valine replaces glutamine acid resulting in elongated sickle cells -Distortion (elongated) of RBC’s causes cells to weaken and rupture-this is why the cells only circulate in blood for 10-15 days. -Abnormal shape cell=occlusion of blood vessels/spleen ------- risk of CVA, splenic or kidney damage *Splenic damage most prevalent, so most sickle cell people are asplenic (without spleen) by adulthood. Factors -oxidative stress (hypoxia)--------------------- * All of these factors further decrease o2 -anxiety---------------------------------------------- from binding to hemoglobin and -fever----------------------------------------------- increases sickling tendencies of -Temp-cold--------------------------------------- hemoglobin. 40 ConditionsIthatIresult IinIpure Iwater Ideficit I(hypertonic Ivolume Idepleted) Hypertonic alterations develop when the osmolality of the ECF is elevated above normal, usually because of an increased concentration of ECF sodium or a deficit of ECF water. The ECF osmolality is greater than the ICF osmolality so water moves out of the cell which causes cellular shrinkage and increased plasma volume. Water deficit, or hypertonic dehydration, can be caused by lack of access to water, pure water losses, hyperventilation, arid climates, or increased renal clearance. Other mechanisms include loss of thirst, water diarrhea, diabetes insipidus, excessive diuresis and excessive diaphoresis. A hypertonic state causes signs and symptoms of hypovolemia. OsmoreceptorsIthatIstimulate IthirstIand ItheIreleaseIof IADH Thirst is experience when water loss equals 2% of an individual’s body water or when there is an increase in osmolality. Dry mouth, hyperosmolality and plasma volume depletion activate hypothalamic osmoreceptors. The action of the osmoreceptors than cause thirst. Drinking water restores plasma volume and dilutes the ECF osmolarity. Water balance is regulated by the sensation of thirst and by the level of antidiuretic hormone, which is initiated by an increase in plasma osmolality or a decrease in circulating blood volume. The hypothalamic osmoreceptors signal the posterior pituitary gland to release antidiuretic hormone (ADH). ADH alters the collecting tubules permeability to water, increased ADH causes increased permeability to water resulting in more water to be absorbed. This allows for restoration of plasma volume and blood pressure. The release of ADH is regulated by a feedback mechanism so when there is restoration of the plasma osmolality, blood volume and blood pressure then ADH secretion is inhibited. FLUIDS I& IELECTROLYTES 41 With fluid loss there is a blood volume and blood pressure decrease. Baroreceptors (volume/pressure sensitiveIreceptors) located in the R/L atria, large veins, aorta, pulmonary arteries and carotid sinus also stimulate the release of ADH. When the arterial and atrial pressure drops baroreceptors signal the hypothalamus to releaseADH. ADH also stimulates arterial vasoconstriction. CausesIof Ihypernatremia Hypernatremia (sodium levels >147 mEq/L) may be caused by an acute increase in sodium level or a loss of water (most common cause). Some specific causes of hypernatremia from water loss include fever, respiratory tract infections (that increase respiratory rate and enhance water loss from the lungs), diabetes insipidus (deficiency of ADH), polyuria, profuse sweating, diarrhea. Insufficient water intake causes include individuals who are comatose or receiving gastric feedings and infants who can’t communicate thirst. Other causes of increased sodium retention are inappropriate administration of hypertonic saline solution, over secretion of aldosterone (hyperaldosteronism) and Cushing syndrome (excess secretion of adrenocorticotropic hormone (ACTH) which increases secretion of aldosterone). High amounts of dietary sodium rarely cause hypernatremia because healthy kidneys will eliminate excess sodium. Hypernatremia can cause thirst, dry mucous membranes, hypotension or hypertension (depending on cause of hypernatremia), tachycardia, pulmonary edema, confusion and convulsions. Treatment of hypernatremia is with an isotonic salt-free fluid (5% dextrose in water) and must be given slowly to prevent cerebral edema. EffectsIofIincreasedIaldosterone Aldosterone is produced by the adrenal cortex. Sodium balance is regulated by aldosterone, which increases reabsorption of sodium by the distal tubule of the kidney. Renin and angiotensin are enzymes that promote or inhibit secretion of aldosterone and thus regulate sodium and water balance. Aldosterone promotes sodium and water reabsorption to conserve sodium, blood volume and blood pressure. Potassium balance is regulated by the kidney, by aldosterone and insulin secretion, and by changes in pH. Increased aldosterone secretion can lead to hypokalemia by increasing the secretion of potassium. Dependent Iedema Edema is the excessive accumulation of fluid within the interstitial spaces. Dependent edema, in which fluid accumulates in gravity-dependent areas of the body, might appear in the feet and legs when standing and in the sacral area and buttocks when supine. Dependent edema can be identified by using fingers to press away edematous fluid in tissues overlying bony prominences. A pit will be left in the skin (pitting edema). Edema may be treated symptomatically until the underlying disorderis corrected. Supportive measures include elevating edematous limbs, using compression stockings or devices, avoiding prolonged standing, restricting salt intake, and taking diuretics. Definition Iof Iisotonic -Isotonic conditions occur when the osmolality in the ICF and ECF are equal. -Normal fluid movement favors isotonic conditions. -Examples of isotonic solutions: 5% dextrose in water and normal (0.9%) saline solution Principle Iof Icapillary Ioncotic Ipressure -Capillary (plasma) oncotic pressure osmotically attracts water from the interstitial space back into the capillary. -Oncotic (colloid) pressure (OCP) - chemical force exerted by large molecules (e.g. – proteins/albumin) to pull fluid in = reabsorption 42 -The movement of fluid back and forth across the capillary wall is called net filtration and is best described by the Starling hypothesis: -Net filtration= (Forces favoring filtration)- (Forces opposing filtration) -Forces favoring filtration= Capillary hydrostatic pressure and interstitial oncotic pressure -Forces opposing filtration= Capillary oncotic pressure and interstitial hydrostatic pressure Types Iof Ifluid Icompartments Iin Ithe Ibody -Fluids are in two distinct locations in the body: intracellular fluid (ICF) and extracellular fluid (ECF). -Two thirds of the body’s water is ICF and one-third is in the ECF compartments. - The ICF is the fluid within cells and is 40% of body weight. -The ECF is the fluid outside of the cells and makes up 20% of body weight. It can be found in three separate locations. It can be in the intravascular fluid (IV), the interstitial fluid (IF), and other fluids (3rd spaces). -Intravascular (IV)= blood plasma (<5% body weight) -Interstitial fluid (IF)= fluid between cells and outside of blood vessels (<15%) -Other fluids (3rd spaces) = lymph, synovial, CSF, intestinal, sweat, urine, intraocular, and body cavity fluids PULMONARY most Ieffective Imeasure ItoIprevent Ipulmonary Iembolus Ifrom Ideveloping Iin Ipatients Pulmonary Embolism = occlusion or partial occlusion of pulmonary artery or its branches by an embolism • RISKIFACTORIRECOGNITIONIandIELIMINATIONIOFIPREDISPOSINGIFACTORS: IIncreased risk for thrombosis associated with hemodynamic stasis, hypercoagulability, and endothelial injury is known as Virchow’s triad ▪ Risk Factors include: • Venous Stasis: immobilization, heart failure • Hypercoagulability:Iinherited coagulation disorders, malignancy, hormone replacement, oral contraceptives, pregnancy • Endothelial injury: trauma, caustic intravenous infusion Prevention measures: • Venous stasis in hospitalized individuals is minimized by Ibed Iexercises, Ifrequent Iposition Ichanges, Iearly Iambulation, Iand Ipneumatic Icalf Icompression. • prophylactic anticoagulation with unfractionated heparin, low-molecular-weight heparin, warfarin, or fondaparinux. • In individuals who have contraindications to anticoagulation, the placement of a filter in the inferior vena cava can prevent emboli from reaching the lungs. Risk factor recognition and elimination of predisposing factors. Most at-risk individuals also will receive prophylactic anticoagulation with unfractionated heparin, low-molecular-weight heparin, warfarin, or fondaparinux. In individuals who have contraindications to anticoagulation, the placement of a filter in the inferior vena cava can prevent emboli from reaching the lungs. Increased risk for thrombosis associated with hemodynamic stasis, hypercoagulability, and endothelial injury is known as Virchow’s triad144 (see Chapter 32). The ideal treatment of PE is prevention through risk factor recognition and elimination of predisposing factors. Venous stasis in hospitalized individuals is minimized by bed exercises, frequent position changes, early ambulation, and pneumatic calf compression.155 Most at-risk individuals also will receive prophylactic anticoagulation with 45 Approximately 15 percent of adults with alpha-1 antitrypsin deficiency develop liver damage (cirrhosis) due to the formation of scar tissue in the liver. Signs of cirrhosis include a swollen abdomen, swollen feet or legs, and jaundice. Individuals with alpha- 1 46 antitrypsin deficiency are also at risk of developing a type of liver cancer called hepatocellular carcinoma. In rare cases, people with alpha-1 antitrypsin deficiency develop a skin condition called panniculitis, which is characterized by hardened skin with painful lumps or patches. Panniculitis varies in severity and can occur at any age. Symptoms related to the lung: • Shortness of breath. • Wheezing. • Chronic bronchitis, which is cough and sputum (phlegm) production that lasts for a long time. • Recurring chest colds. • Less exercise tolerance. • Year-round allergies. • Bronchiectasis. The Iresult Iof Iloss Iof Isurfactant Iin IARDS Surfactant impairment results from decreased production or inactivation of surfactant, which is necessary to reduce surface tension in the alveoli and thus prevent lung collapse during expiration. Surfactant impairment can occur because of premature birth, acute respiratory distress syndrome, anesthesia, or mechanical ventilation. As the alveoli increase in size, the surfactant becomes more spread out over the surface of the liquid. This increases surface tension effectively slowing the rate of expansion of the alveoli. Surfactant reduces surface tension more readily when the alveoli are smaller because the surfactant is more concentrated. When there is not enough surfactant the tiny Ialveoli Icollapse with each breath, and as they collapse damaged cells collect in the airway causing further affect in Ibreathing. Characteristics IofICheyne-Stokes Irespirations Alternating periods of deep and shallow breathing. Apnea lasting 15 to 60 seconds is followed by ventilations that increase involume until a peak is reached, after which ventilation (tidal volume) decreases again to apnea. Cheyne-Stokes respirations result from any condition that slows the blood flow to the brainstem, which in turn slows impulses sending information to the respiratory centers of the brainstem. Neurologic impairment above the brainstem is also a contributing factor. Usually seen in comatose individuals having disease nervous centers respirations. 47 SHOCK (7th Edition, pg. 1672-3) Hypovolemic shock is caused by loss of whole blood (hemorrhage), plasma (burns), or interstitial fluid (diaphoresis, diabetes mellitus, diabetes insipidus, emesis, or diuresis) in large amounts. Loss of whole blood or plasma causes hypovolemia directly. Loss of interstitial fluid causes an indirect “relative” hypovolemia by promoting diffusion of plasma from the intravascular to the extravascular space. Hypovolemic shock begins to develop when intravascular volume has decreased by about 15%. (7th Edition, pg. 1670) In shock, glucose metabolism may be increased or disrupted because of fever or bacteria, and glucose uptake can be prevented by the presence of vasoactive toxins, endotoxins, histamine, and kinins. Some of the compensatory mechanisms activated by shock contribute to decreased glucose uptake and use by the cells. High serum levels of cortisol, growth hormone, and catecholamines account for hyperglycemia and insulin resistance, tachycardia, increased SVR, and increased cardiac contractility. Cells shift to glycogenesis, gluconeogenesis, and lipolysis to generate fuel for survival. Except in the liver, kidneys, and muscles, the body’s cells have extremely limited stores of glycogen. In fact, total body stores can fuel the metabolism for only about 10 hours. When gluconeogenesis causes proteins to be used for fuel, these proteins are no longer available to maintain cellular structure, function, repair, and replication. Causes Iof Ihypovolemic Ishock How Ithe Ibody Imaintains Iglucose Ilevels Iduring Ishock 50 Alveolar Iventilation/perfusion- Humoral = antibody mediated! Antibody circulates in the blood and binds to antigens. Antibody is primarily responsible for protection against many viruses/bacteria. When theantibody/antigen bind it can result in a direct activation of the microorganism or an activation of inflammatory mediators that will destroy the pathogen. Cell-Mediated = in an immune response, T-cells undergo differentiation so they develop into several subpopulations of cells that react directly with antigens. Some react directly with antigens while others develop into T cells that stimulate the activities of other leukocytes via cell-to-cell contact or through secretion of cytokines. Others will develop into Tc (T-cytotoxic cells) that attack/kill targets directly. ** Both the humoral and cell-mediated arms are interdependent and the success of an acquired immune response depends on the function of both. Both arms produce specialized “memory cells” that are long-lived *** Active Immunity vs Passive Immunity Active = produced by individual either after natural exposure to antigen or after immunization – long-lived! Passive – does not require host’s immune system at all. Preformed antibodies or T- lymphocytes are transferred from donor to recipient. I.e. maternal, immunotherapy. Temporary! 51 Folliculitis Infection of hair follicle caused by bacteria, viruses or fungi. Lesions = pustules with surrounding erythema Most prominent: scalp and extremities. Prolonged skin moisture, occlusive clothing, topical agents, skin trauma, poor hygiene Tx: clean with soap/water and possibly antibiotics Furuncles Boil. Inflammation of hair follicles develops from folliculitis that spreads through follicular wall into surrounding dermis. Lesion = deep, firm, red, painful nodule 1-5 cm The initial erythematous nodule changes to a large fluctuant/tender cystic nodule that may be accompanied by cellulitis. No systemic symptoms. Lesion may drain large amounts of pus and necrotic tissue Erysipelas Acute, superficial infection of upper dermis most often Strep pyogenes, beta-hemolytic strep and Staph aureus. Face, ears, lower legs most common and site of initial infections may not be ID’d Chills, fevers, malaise precede onset of lesions by 4-20 days Initial lesions: firm, red spots that enlarge/coalesce into clearly circumscribed, advancing edge, bright red, hot lesion with raised border. Vesicles may appear over lesion and at the border, producing a bullous form of the disease. Itching, burning and tenderness. Tx: Cold compresses, systemic antibiotics Croup Croup illnesses can be divided into 2 categories: all characterized by infection and upper airway obstruction: 1) acute laryngotracheobronchitis 2) spasmodic Laryngotracheobronchitis: Most common in children 6month-3years (peak 2 years) 85% cases caused by virus: parainfluenza most common, but also influenza A, RSV, rhinovirus, adenovirus and rubella (measles) as well as atypical bacterium (Mycoplasma pneumonia). Dermatologic Iconditions Ie.g. Ipityriasis Irosea 52 Types Iof Ianemia Spasmodic croup: characterized by hoarseness, barking cough/stridor with sudden onset @ night Etiology unknown but often associated w/ viruses, allergies, asthma, GERD Patho: subglottic edema from the infection. The subglottic mucous membranes are looser than those of the larynx, which allows for mucosal and submucosal edema between the membranes and underlying cartilage. OF NOTE: the cricoid cartilage is the narrowest point of the airway so swelling inthis area is critical. Increased airflow resistance leads to increased work of breathing, which generates more negative intrathoracic pressure, which can exacerbate dynamic upper airway collapse! Prodrome of rhinorrhea, sore throat, low-grade fever. After a few days, the characteristic seal-like cough, hoarse voice, and inspiratory stridor. Usually resolves on it’s own but occasionally UAO requires urgent management! Treatment depends on symptoms. Usually viral, so no intervention just symptom management. Stridor, retractions and/or agitation suggest advanced illness. The Westley croup score: provides cumulative score for the degree of stridor, retractions, air entry, cyanosis, dyspnea and LOC. Inhalation of humidified air does NOT improve symptoms. Glucocorticoids (injected/oral/nebulized) may improve symptoms within 6 hours but they do let the child sleep and decrease parent anxiety Moderate-Severe croup can be helped with nebulized racemic epinephrine, which stimulates the alpha and beta-adrenergic receptors, which decreases airway secretions and mucosal edema. This is a temporary fix until steroids kick in. Heliox (helium-oxygen mixture of 80:20 or 70:30) may be used for severe cases butevidence remains lacking. Commonly result from: 1) Impaired erythrocyte production 2) Blood loss (acute or chronic) 3) Increased erythrocyte destruction 4) Combination of the above 3 55 GI Isymptoms Iresulting Iin Iheart Iburn Pulmonary Iterminology Isuch Ias Idyspnea, Iorthopnea, Ietc Complications Iof Igastric Iresection Isurgery Mast cells release other chemotactic factors that act as signals to recruit other types ofWBCs to area to amplify inflammatory response. Mast cells have enzymes that allow them to synthesize other mediators, such as leukotrienes and prostaglandins Dyspnea = difficult or labored breathing. AKA breathless, air hunger, SOB, increased work of breathing, chest tightness. Orthopnea = discomfort in breathing when lying down flat. Basically dyspnea that occurs when patient lies flat. Common in heart failure, lung disease, pulmonary edema, sleep apnea, COPD and valvular disease. Caused by changes in motor and control functions of the stomach and upper small intestine after gastric resection. Malabsorption Syndromes Interfere w/ nutrient absorption Classified as: maldigestion – failure of the chemical process of digestion to take place in the intestinal lumenor at the brush border of the intestinal mucosa of the small intestine. Usually caused by deficiencies of enzymes such as pancreatic lipase or intestinal lactase. Also, inadequate secretion of bile salts and inadequate reabsorption of bile in ileum. Malabsorption – failure of the mucosa to absorb (transport) the digested nutrients. As a result of mucosal disruption caused by gastric/intestinal resection, vascular disorders or intestinal disease. Dumping Syndrome The rapid emptying of hypertonic chyme into small intestine 10-20 minutes after eating. Factors that influence: loss of gastric capacity, loss of emptying control when pylorus removed and lossoI f feedback control by duodenum when removed. The rapid gastric emptying and creation of a nonphysiologic, high osmotic gradient within smallintestines = sudden shift of fluid from vascular compartment to intestinal lumen. 56 Macule I= Dermatology Iterminology-macules, Inevi, Ietc Plasmavolume decreases =vasomotor response like tachycardia, hypotension, weakness, pallor,sweating and dizziness. Rapid intestinal distention = epigastric fullness, cramping, N/V. Diarrhea can either be frequent andpersistent or intermittent, precipitous and unpredictable. Late dumping syndrome = 1-3 hours after meal. High carb meal causes hypoglycemia 2/2 increase in insulin secretion stimulated by hyperglycemia that follows large meal. Frequent, small meals that are high protein and low carb. Drink fluid between meals instead of with meals. Recline on left side after eating. Lesions: Primary (freckles, flat moles, petechiae, measles) flat, circumscribed area that is a change in color of skin. Papule = (wart, lichen planus, fibroma, insect bite) elevated, firm circumscribed area Patch = (vitiligo, port-wine stain, mongolion spot)- flat, non-palpable, irregular Plaque = (psoriasis, seborrheic/actinic keratosis)- elevated, firm, rough, flat top surface IWheal = (uritcaria, allergic reaction)- elevated, irregular shaped area of cutaneous edema, solid, transient Nodule = (erythema nodosum, lipomas)- elevated, firm circumscribed deeper lesion. ITumor = (neoplasms, lipoma, neurofibroma, hemangioma)- elevated, solid lesion, may be clearly demarcated, deeper. Vesicle = (chickenpox, shingles, herpes simplex)- elevated, circumscribed, superficial and does not extend into dermis Bulla = (blister, pemphigus vulgaris) IPustule = (impetigo, acne) Cyst = (sebaceous cyst, cystic acne) Telangiectasia = 2/2 capillary dilation (acne rosacea, venous HTN, systemic sclerosis or birthmarks) Nevi- mole are benign, pigmented lesions that form melanocytes beginning at age three. Secondary Scale = seborrheic dermatitis post-scarlet fever or drug reaction, dry skin ILichenification = chronic dermatitis Keloid IScar 57 Excoriation = abrasion/scratch, scabies- loss of epidermis, linear, hollowed out, crusted area. Fissure = athlete’s foot, cracks @ corner of mouth, anal fissure, dermatitis- linear crack or break from epidermis to dermis-may be moist or dry Erosion = chemical injury- partial loss of epidermis; depressed, moist, flistening, follows rupure of a vesicle or bulla or chemical injury Ulcer = pressure ulcer, stasis ulcer- concave loss of epidermis and dermis AI trophy = ages skin, striae- Thinning of skin surface. Cutaneous Vasculitis Inflammation of blood vessels of the skin. Immune complexes, which initiate an uncontrolled inflammatory response, are often the cause of damage and the lesions are often polymorphic. Develops from the deposit of immune complexes in small vessels as a toxic response to drugs or allergens, as a response to strep/viral infections or as a component of systemic vasculitic syndromes Urticaria Hives! Most commonly associated w/ type-1 hypersensitivity reactions to drugs, foods, systemic diseases, physical agents or complement mediated reactions. Scleroderma Sclerosis of the skin. The skin is hard, hypopigmented, taut, shiny and tightly attached to the underlying tissue. Seborrheic Keratosis Benign proliferation of cutaneous basal cells. Tan to waxy yellow, flesh colored or dark brown/black lesions. Looks greasy hyperkeratotic stuck-on scaly. Keratoacanthoma Benign self-limiting tumor of squamous cell differentiation arising from hair follicles. Look like squamous cell carcinoma. Actinic Keratosis Premalignant, composed of aberrant proliferations of epidermal keratinocytes 2/2 prolonged UV radiation exposure. Lesions are rough, scaly and poorly defined pink to reddish or reddish brown papules that are felt more than seen. Considered an early in situsquamous cell carcinoma. Nevi Moles! Benign. Pigmented or non-pigmented. Form from melanocytes. May undergo transition to malignant melanomas. Junctional nevus = rarely develop into melanoma Compound nevus = rarely develop into melanoma Intradermal nevus = slight likelihood of developing into melanoma 60 Hypochromi c 61 Antibodies, I gG, IIgA, Ietc Normochromic An antibody (or immunoglobulin) is a serum glycoprotein produced by plasma cells in response to challenge by an immunogen. The term immunoglobulin is used to denote all molecules that are known to have specificity for antigen. The term antibody is used to denote one particular set of immunoglobulins with specificity against a known antigen. There are 5 molecular classes of immunoglobulins: IgG – most abundant = 80-85% Account for most of the protective activity against infections. Placental transfer = so it’s the major class of Ab found in fetal/newborn bloodProduced by plasma B cells Has 4 subclasses. Monomer structure / circulates 30-45 days IgA – secretory – has 2 subclasses! Plays crucial role in the immune function of mucous membranes. Found in high concentrations in mucosa (especially GI and respiratory), saliva, tears, and breast milk/colostrum. Dimer structure / circulates 12 days IgM – largest. Synthesized early in neonatal life and is the 1st Ab produced during initial response to antigen. Pentameter structure – it’s the first to respond but the large structure is unstable so it only circulates for 2 days IgE – the lease concentrated of all classes. It appears to have very specialized function as a mediator of many common allergic responses and in the defense against parasitic infections. Circulates 4 days IgD – information/role is limited and found in very low quantities in blood. They are primarily located on surface of developing B-lymphocytes and function as 1 type of B-cell antigen receptor. Circulates 6 days. 62 Skin Icancer Skin Cancer Basal cell carcinoma and squamous cell carcinoma most prevalent Malignant melanoma most deadly Chronic UV exposure causes most skin cancers. Less common in darker skinned people b/c the basal cells contain the pigment melanin, which is a protective factor against sun exposure. Basal Cell Carcinoma Most common in whites. Surface epithelial tumor from undifferentiated basal or germinative cells. They grow upward and laterally or downward to dermal-epidermal junction. Usually depressed center with rolled borders. As lesion grows, it ulcerates and develops crusting and becomes firm to the touch. If not treated they invade surrounding tissue and can destroy a nose, eyelid or ear. Metastatic spread is rare b/c they don’t invade vessels or lymph. From UV exposure, arsenic from groundwater wells and autosomal dominant nevoid basal cell carcinoma syndrome. 65 Tetralogy of Fallot: the most common cyanotic defect and accounts for 10% or all. Consists of 4 defects: 1) Large VSD high in the septum 2) An overriding aorta that straddles the VSD 3) Pulmonary stenosis 4) RV hypertrophy The embryologic error that causes TOF is unknown. There are 2 trains of thought: 1) The truncus arteriosus divides unevenly, resulting in great vessels of unequal size. 2) The infundibular overgrowth in the RV is the major developmental anomaly. The patho depends on the degree of pulmonary stenosis, the size of the VSD and the pulmonary/systemic resistance to flow. Because the VSD is usually large, pressures are equal in the RV and LV so the major determinant of shunt direction through the VSD is the difference b/t pulmonary and systemic resistance. Infants who have little to no R-L shunting are acyanotic and are known as “pink tets” PS decreases blood flow to the lungs so the amount of oxygenated blood that returns to the left heart is also decreased. If blood also shunts from R to L through the VSD, deoxygenated and oxygenated blood mix before returning to the lungs = hypoxemia which leads to polycythemia to compensate. Infants with decreased pulmonary flow through the RV outflow tract while the ductus arteriosus remains open will become more cyanotic as the ductus closes. Chronic hypoxemia causes clubbing of fingers/toes. Hypercyanotic or “tet” spell = rare manifestation of TOF = sudden onset of dyspnea, cyanosis and restlessness that usually occurs w/ crying/exertion. These spells are often what initiates surgical intervention. Infants with TOF have trouble feeding b/c the exertion increases hypoxia. Squatting is a spontaneous compensatory mechanism. It increases systemic resistance and decreases venous return to the heart from the IVC so more oxygenated blood is available to the body. The increase of systemic resistance also reverses the shunt through the VSD to a L-R shunt, which increases pulmonary blood flow. Typical murmur in TOF is a pulmonary systolic ejection murmur that is caused by obstruction in the outflow tract. More obstruction to flow produces louder murmur, which explains why the murmur often disappears during hypoxic spell since the pulmonary blood flow decreases to a minimum amount. Dx: ECG shows RV hypertrophy, X-Ray shows heart shaped like a boot with decreased pulmonary vasculature markings. Tx: current standard to repair before 1 yo. 66 Urinary Itract Iobstruction, Coarctation of the Aorta: Often seen in Turner’s syndrome A narrowing of lumen that impedes blood flow. About half of those with COA have a bicuspid aortic valve. COA causes higher pressures proximal to the site of stenosis and lower pressures distally. In preductal COA the RV acts as a systemic pump, sending oxygenated blood through theductus into descending aorta below the coarctation In postductal COA the RV cannot pump enough blood through the ductus to the descending aorta b/c of pressure caused by narrowed aorta. Over time LV hypertrophy develops 2/2 increased afterload and obstruction to flow. HF may also develop. S/Sx: newborns usually present with CHF and once the ductus closes they will deteriorate rapidly from the development of hypotension, acidosis and shock. Older children may not be diagnosed until HTN noted in upper extremities w/ weak/absent pulses in lower. May have cool, mottled skin and occasionally leg cramps w/ exercise. Tx: symptom stabilization first (i.e. prostaglandin admin. mech. Vent, inotropic support for CO maintenance) then surgical repair. Anatomical or functional interference with the flow of urine at any site along the urinary tract. Impedes flow proximal toobstruction and dilates structures distal tothe obstruction which increases risk for infection and compromises renal function. Severity determined by 1. Location of lesion 2. Involvement of one or both upper urinary tracts (ureters and renal pelvis) 3. Completeness of obstruction 4. Duration of obstruction 5. Nature of obstruction Causes: UPPER- stones, ureteral compression from aberrant vessel, tumor or abdominal inflammation and scarring LOWER- neurogenic bladder, overactive bladder syndrome, urethral stricture, prostate enlargement, pelvic organ prolapse 67 Hiatal Hernia Herniation of upper stomach through diaphragm into thorax. 4 types: 1) Type I = sliding, most common, exacerbated by things that increase abdominal pressure. Associated w/ GERD b/c the hernia diminishes LES resting pressure. In pregnant women, progesterone/estrogen diminishes pressure of LES even further. 2) Type II = paraesophageal, “rolling”. Stomach pushes up into thorax alongside esophagus through a second hole in diaphragm. Reflux is uncommon BUT with partof the stomach above the diaphragm = congestion of mucosal blood flow leading to gastritis and ulcers. One major complication = strangulation that occludes vessels and results in vascular engorgement, edema, ischemia and hemorrhage. 3) Type III = mixed type 4) Type IV = entire stomach/other abdominal organs slide into thorax S/Sx: Hiatal hernias are often asymptomatic. The symptoms that do develop are associated with other GI disorders like GERD. Some symptoms may include heartburn, regurgitation, dysphagia, and epigastric pain. Ischemia from hernia strangulation causes acute, severe chest/epigastric pain, N/V and GI bleeding Pyloric Stenosis: READ WEEK 5 PART 2 DISCUSSION Per Quizlet: A condition in which the opening b/t the stomach/small intestine blocks food from entering. Symptoms usually appear 3-5 weeks after birth. S/SX are projectile vomiting after feeding, persistent hunger, stomach contractions, dehydration, changes in bowel movements and weight problems. Ulcerative Colitis Chronic, inflammatory and causes ulceration of the colonic mucosa and extends proximally from rectum into the colon. Risk factors: 20-40 years old, family history, Jewish descent, more prevalent in whites and Northern Europeans. Less common in smokers! Cause unknown but possibly r/t diet, infection, genetic and immunologic factors. The primary lesions are continuous with no skip lesions, limited to the mucosa and are not transmural. Rectum almost always involved. The disease is most severe in rectum and sigmoid colon. Mild inflammation = mucosa is hyperemic and edematous, dark red/velvety Severe inflammation = mucosa hemorrhagic, small erosions coalesce into ulcers – then abscess formation then necrosis and ragged ulceration of the mucosa. Course = intermittent periods of remission and exacerbation. Affects innermost lining of large intestine (colon). S/Sx: usually develop over time rather than suddenly. Depending on severity of disease you may see: large volume watery diarrhea, cramping, urge to defecate but unable to, purulent GI Isymptoms Iof Iconditions Isuch Ias Ipyloric Istenosis, Ihiatal Ihernia, Iulcerative Icolitis 70 Congenital Iintrinsic Ifactor Ideficiency Acid Ibase Iimbalance Acute Iepiglottitis *** Allergy, autoimmunity and alloimmunity are collectively known as hypersensitivity reactions *** Type I – IgE-mediated Hypersensitivity Reactions – IgE, mast cells, basophils Most common allergies. I.e. seasonal allergies / rhinitis Immediate development Principle effector cells: Mast Cells Type II – Tissue-specific Hypersensitivity Reactions – IgG and IgM i.e. autoimmune thrombocytopenic purpura, Graves disease, AI hemolytic anemiaImmediate reaction Principle effector cells: Macrophages in tissues Type III – Immune-Complex Mediated Hypersensitivity Reactions – IgG/IgM i.e. SLE (systemic lupus erythematous), serum sickness, Raynaud’s Immediate development Principle effector cells: Neutrophils Most are caused by antigen-antibody complexes that are formed in circulation anddeposited later in vessels/tissue. Primary difference b/t types II and III are that: II = the Ab binds to the antigen on the cell surface III – the Ab binds to soluble antigen that was released into the blood/body fluids and the complex is then deposited into tissue. Type IV – Cell-Mediated Hypersensitivity Reactions – non Ab involvement i.e. Contact sensitivity to poison ivy and metals (jewelry), graft rejection, RA, Hashimoto disease, Type-1 diabetes. Delayed development is either a genetic disorder that is autosomal recessive or an autoimmune disorder directed against gastric parietal cells. It is characterized by pernicious anemia and neurological abnormalities that are permanent. Patients will exhibit signs of anemia (PA, specifically, so think red-beefy tongue). Tx = B12 injections 71 Types Iof Igastric Iulcers-signs Iand Isymptoms, Icharacteristics Caused by: Haemophilus influenza type B caused 25%, Group A streptococci, also trauma, thermal injuries, posttransplant lymphoproliferative disorder. Infants < 1 yr old at highest risk. Pathophysiology- Bacterial invasion of mucosa with associated inflammation leads to rapid development of edema causing severe, life-threatening obstruction of upper airway. S+S- Children aged 2-6, sudden high fever, irritability, hot potato voice, inspiratory stridor and severe respiratory distress with drooling and dysphagia, looks very ill. Exam may cause laryngospasm and cause respiratory collapse. Death may occurwithin a few hours. Treatment: early recognition is key, avoiding disturbance of child and airway management. No exam of the throat!! Tracheal intubation should be consideredwith culture of trachea. Corticosteroids. Resolution is typically rapid. Can affect those outside the age range Gastric Ulcers: Peptic Ulcer Disease: break/ulceration in mucosa of lower esophagus, stomach or duodenum. Risk: genetic predisposition, H.Pylori, NSAID overuse, ETOH, smoking, acute pancreatitis, COPD, obesity, cirrhosis, age > 65. Can be acute or chronic, superficial or deep. Duodenal Ulcers: Most common type of peptic ulcer. Acid/pepsin concentrations in the duodenum penetrate the mucosal barrier leading to ulceration. S/Sx: chronic, intermittent epigastric pain, 30 minutes-2hours after eating, when stomach is empty (ex… middle of the night is common). Pain is relieved by either ingesting food or antacids = “pain-food-relief pattern”. May be asymptomatic with first manifestation beingperforation or hemorrhage. May cause hematemesis/melena. Gastric Ulcers: Stomach ulcers. Most common b/t 55-65 years and only about ¼ as common as duodenal ulcers. Typically in antral region and frequently caused by H.pylori. The primary defect is an abnormality that increases the mucosal barrier’s permeability to hydrogen ions. S/Sx: similar to duodenal ulcers BUT pain is immediate after eating. GU’s tend to be chronic rather than alternating b/t periods of remission and exacerbation. They cause more anorexia, vomiting and weight loss than duodenal ulcers. Stress Ulcers: 72 Acute for of peptic ulcer that tends to accompany the physiologic stress of severe illness, multisystem organ failure, major trauma (severe burns/head injury). Characteristic is bleeding. Usually includes multiple sites of ulceration within stomach and duodenum. Classifieds as: Ischemic = develop within hours of event that causes ischemia of stomach/duodenal mucosa (i.e.… hemorrhage, heart failure, sepsis, burns, trauma) Cushing = associated with severe head trauma or brain surgery as a result of decreased mucosal blood flow and hypersecretion of acid caused by overstimulation of the vagal nuclei. Curling = as a result of burn injury *** Stress ulcers rarely become chronic *** Zollinger-Ellison Syndrome: Associated with peptic ulcers r/t increased secretion of gastrin, which causes excess secretion of gastric acid, which leads to gastric and duodenal ulcers, GERD, abdominal pain and diarrhea. Caused by a gastrinoma of the pancreas or duodenum. Lupus A chronic, multisystem, inflammatory disease that is 1 of the most common, complex and serious AI disorders. Characterized by a large variety of autoantibodies against nucleic acids, erythrocytes, coagulation proteins, phospholipids, lymphocytes, platelets and many other self- components. ***The most characteristic autoantibodies produced in SLA are against nucleic acids (DNA), histones, ribonucleoproteins and other nucleic materials DNA and DNA-containing immune complexes have a high affinity for glomerular basement membranes so may be selectively deposited in glomerulus. The presence of DNA in circulation increases from cellular damage in response to trauma, drugs or infections and is usually removed by the liver HOWEVER the removal of circulating DNA is slowed in the presence of immune complexes so the potential for kidney deposition is increased. Deposition of immune complexes that are made up of DNA/antibody also causes inflammatory lesions in renal tubular basement membranes, brain, heart, spleen lung, GI tract, skin and peritoneum. More common in women 20-40 years old. Blacks more than whites. Genetic predisposition is implicated S/Sx: Arthralgias or arthritis (90%) Vasculitis/rash (70-80%) Renal disease (40-50%) Hematologic abnormalities (50% - anemia is the most common complication) Cardiovascular disease (30-50%) 75 Obstructive Isleep Iapnea Large Ibowel Iobstruction represent millions of foreign antigens. This process is called the generation of clonal diversity and happens in primary lymphoid organs --- thymus for T cells and bone marrow for B cells! These organs release lymphocytes as immature cells that have the capacity to react with antigens and they migrate to secondary lymphoid organs to prepare for antigen exposure. The lymphocytes remain dormant until an antigen initiates the 2nd phase of the immune response, clonal selection. Clonal selection involves a complex interaction among cells. Inorder to initiate an effective immune response, antigens must be “presented” to the immune cells in a very specific manner, which is the job of antigen-processing cells (antigen-presenting or APC’s). There are 3 groups of cells that must cooperate to make an immune response: APC’s interact with subpopulation of T-cells (Th cells) and immunocompetent B or T cells. This results in differentiation of B cells into active antibody-producing cells (plasma cells) and T cells in effector cells (i.e. Tc cells). A breathing disorder defined by prolonged partial and/or intermittent complete UAO while sleeping. Repetitive increases in resistance to airflow in upper airway w/ loud snoring, gasping, intervals of apnea 10-30 seconds long Associated w/ reduced blood O2 saturation and hypercapnia. Common in children. R/T adenotonsillar inflammation or obesity. Severity of disease determined by AHI (apnea hypopnea index). The index represents how many apnea or hypopnea (partial airway closure) occur/night. Risk factors: obesity, male gender, menopause and age Excessive daytime sleepiness most common sign. Dx: polysomnography Tx: CPAP, dental devices that modify position of tongue/jaw, surgical reconstruction of upper airway,Iweight reduction Tx in children: 1st = tonsillectomy/adenoidectomy, then CPAP Any condition that prevents normal flow of chyme through intestinal lumen.Small bowel more commonly obstructed 2/2 narrow lumen Criteria for classification: Onset Acute – sudden, usually 2/2 torsion, intussusception, herniation Chronic – protracted onset, usually tumor growth or progressive strictures 76 Vaginal Icandidiasis Extent of Obstruction Partial – incomplete obstruction of lumen Complete – complete obstruction of lumen Location of Obstruction Intrinsic – obstruction develops within lumen (i.e. luminal edema, gallstones, tumors, intraluminal fibrosis) Extrinsic – obstruction originates outside lumen (i.e. tumors, torsion, fibrosis, hernia, intussusception) Effects of Intestinal Wall Simple – obstruction without impairment of blood supply Strangulated – occlusion of blood supply Closed Loop – obstruction at each end of a segment of the intestine Causal Factors Mechanical – intrinsic or extrinsic lesions (usually treated surgically) Functional – paralysis of intestinal musculature 2/2 accidental or surgical trauma, peritonitis, electrolyte imbalance, spasmolytic agents (usually treated medically). Common causes of obstructions: Herniation Intussusception – more common in children Torsion Diverticulosis Tumor Paralytic Ileus – post-op ileus Fibrous adhesions Most common obstruction is simple obstruction of the small intestine from fibrous adhesions. Most common large bowel obstructions: colorectal cancer, volvulus (torsion) and strictures r/t diverticulitis. Large Bowel Obstructions consequences are r/t to competence of the ileocecal valve, which normally prevents reflux of colonic contents into small intestine. When valve is competent the cecum can’t decompress = distention. Ischemia occurs when the intraluminal pressure exceeds the capillary pressure in the lumen. S/Sx: hypogastric pain and abdominal distention. Pain can vary from vague to excruciating. 77 Folate Ideficiency Pancreatic Iinsufficiency Yeastlike fungus Candida albicans is normal on mucosa, skin, GI tract and vagina but canchange to a pathogen in critically ill or immunosuppressed. Predisposition: moist, warm, macerated or occluded area systemic antibiotics pregnancy DM Cushing’s Debilitated states < 6 months old 2/2 decreased immune reactivity immunosuppression neoplastic disease of blood and monocyte-macrophage system Folate essential for RNA/DNA synthesis within maturing erythrocytes. Common in alcoholics and chronically malnourished. ETOH interferes with folate metabolism in liver. Fad diets and diets that lack vegetables are also common dietary causes. Impaired DNA synthesis results in megaloblastic cells with clumped nuclear chromatin and anemia result s from apoptosis of erythroblasts in the late stages of erythropoiesis. Also cause neural tube defects of fetus! Increases risk of CAD and cancers, especially colorectal! S/Sx: Cachectic, malnourished, scales/fissures at corners of mouth, stomatitis, ulcerations of buccal mucosa/tongue (burning mouth syndrome), dysphagia, flatulence, watery diarrhea, sprue (chronic malabsorption syndrome). Thiamine deficiency often accompanies folate deficiency! Tx: Daily oral administration of folate supplement until adequate blood levels reached. Long-term treatment not indicated if patient is able to make dietary adjustments. Causes: chronic pancreatitis, pancreatic carcinoma, pancreatic resection, CF. There has to be significant damage or loss of tissue before enzyme levels decrease enoughto cause maldigestion. Fat digestion is chief problem of pancreatic insufficiency even though all nutrients are affected. The reason that fat is most affected is because salivary amylase/enzymes secreted by the intestinal brush border assist in carb and protein digestion but not in fats. 80 Vitamin IB-12 Itherapy Maternal age > 35 has more significant risk, paternal age has no effect. 1/3-1/2 have congenital heart defects Decreased ability to fight infections and a higher susceptibility to leukemia. Turner Isyndrome- Chromosome 45 and has a single X with no Y therefore it only affects females Manifestations- gonadal streaks instead of ovaries, short stature, webbing of neck, widely spaced nipples, narrowing aorta, pedal edema in infants, sparce body hair, normal IQ (spacial and mathematical abilities can be decreased). Treatment: Teenagers receive estrogentreatment and often human growthhormones Klinefelter Isyndrome- 2 X chromosomes and at least one Y chromosome affecting males. Manifestations: usually sterile, gynomastia, small testes, sparce body hair, high pitched voice, elevated stature, moderate mental impairment. Cause: nondisjunction of X chromosome in mother and each additional X chromosome increases the mental impairment significantly. Risks- increasing maternal age. “cry of the cat”- Manifestations- low birth weight, severe mental retardation, microcephaly, heart defects and acharacteristic facial appearance. Fragile IX Isyndrome- High level of cognitive impairment and is second most common cause of mental retardation after Down syndrome Treatment of Pernicuous Anemia (megoblastic) and for vitamin B12 deficiency. Benefits- to help alleviate symptoms and complications of deficiency (mood disorders, fatigue, memory failure, anemia and hypotension. Vit B12 is needed for erythrocyte production. Treatment of choice- Weekly injections until corrected followed by monthly injections for life.Effectiveness of treatment is determined by rising reticulocyte count. Within 5-6 weeks, blood count returns to normal. Glaucoma Leading cause of visual impairment and blindness. Caused by increased intraocular pressure (>12-20 mmHg). Open angle is the most common subtype Chronic high intraocular pressures death of retinal ganglions and optic nerve degeneration 1) lossoI peripheral vision. 2) central vision impairment. 3) blindness Cri Idu Ichat Isyndrome 81 Concept Iof Ipain I **See Ipgs I485-495 Autosomal Idominant Idiseases I (ADD) Ipg I152-154 Extreme increase in pressures cause blindness within hours hour days Loss of visual acuity is caused by pressure on the optic nerve (causes acute pain). Treatment- eye drops which reduce secretion or increase absorption of aqueous humor. Surgery to open spaces of trabeculae and reduce intraocular pressure Purpose- to protect body against antigens that have not yet penetrated the sin or mucous membranes. Itis an initial defense to keep bacteria levels within a normal range. The secretory response occurs locally and externally. • Pain is one of the body’s most important adaptive and protective mechanisms and all definitions suggest it is a complex phenomenon and cannot be characterized as only a response to injury https://www.youtube.com/watch?v=fUKlpuz2VTs Nocioception has 4 phases: 1) Transduction (tissue exposed to chemical, mechanical or thermal stimulation by nocioceptors.2) Transmission 3) Perception 4) Transduction ADDs are rare due to the fact that it is so uncommon for 2 people who both have a disease to produce offspring. Cervical Iimmunoglobulin 82 Congenital Imurmurs Necessary characteristics- 1) males and females have an equal chance to transmit disease to offspring 2) heterozygous individuals must transmit to at least ½ of their children 3) Cannot skip generations A child diagnosed with an ADD with no family history is due to a new mutation (more common) Reoccurance risk refers to the probability of a family member having disease. Age dependent penetrance- when symptoms are not seen until after 40 yrs of age. If one parent is affected and other is not then ½ of children will be affected as well. The odds continue to be ½ with each new pregnancy. ADDs--- retinoblastoma (dysfunction of tumor suppressor gene), Huntington disease (progressive dementia and uncontrolledlimb movements), Marfans, neurofibromatosis (von Recklinghausen disease) and hemophilia A. Murmur caused by a congenital heart condition. Symptoms include cyanosis and symptoms of CHF Conditions include- Patent ductus arteriosis (PDA)—machine like continuous murmur 85 Hormonal Iregulation Iof Icalcium HIV is a blood borne pathogen present in body fluids and transmitted by IV drug use, sexual activity, and maternal child transmission in utero or at birth. HIV is a retrovirus- uses reverse transcriptase (a viral enzyme) to convert RNA into double stranded DNA. This new DNA is inserted into infected cell’s genetic material by integrase (a second enzyme). Cell can remain dormant (can be dormant for years) or become activated. When activated the cell translation of viral information can be activated resulting in new virions, lysis and death of infected cell and shedding of infections HIV particles. The CD4 molecule on surface of helper T cells binds with gp120 (primary surface receptor on HIV-the envelope glycoprotein). The shedding of gp120 induces apoptotic cell death of uninfected T lymphocytes, neurons and monocytes Primary cellular targets of HIV- CD4 positive Th cells, dendritic cells, macrophages, CD8 positive Tc cells, NK cells, some neural cells. **Brain, Thymus, lymp nodes, lung, bone marrow, colon, duodenum, rectum, skin** Major manifestation is striking decrease in number of CD4+ Th cells thus leading to a reversal in the normal CD4/CD8 ratio People can be infected but remain seronegative for 6-14 months. Antiretroviral Therapy for treatment. This is a great video! https://www.khanacademy.org/science/health-and-medicine/infectious- diseases/hiv-and-aids/v/what-is-hiv-and-aids And this video gets a little more in depth with the pathophys of infection- https://www.khanacademy.org/science/health-and-medicine/infectious-diseases/hiv-and-aids/v/how- hiv-infects-us-cd4-t-helper-lymphocyte-infection Carcinoma BENIGN TUMORS MALIGNANT TUMORS Grow slowly Grow rapidly Have a well-defined capsule Are not encapsulated Are not invasive Invade local structures and tissues Are well differentiated; look like the tissue from which they arose Are poorly differentiated; may not be able to determine tissue of origin Have a low mitotic index; dividing cells are rare High mitotic index; many dividing cells Do not metastasize Can spread distantly, often through blood vessels and lymphatics 86 Blood calcium levels are regulated by parathyroid hormone (PTH), which is produced by the parathyroid glands. PTH is released in response to low blood calcium levels. It increases calcium levels by targeting the skeleton, the kidneys, and the intestine. Calcium homeostasis refers to the regulation of the concentration of calcium ions in the extracellular fluid [Ca++]ECF. This parameter is tightly controlled because the calcium ions have a stabilizing effect on voltage-gated ion channels. For instance, when [Ca++]ECF is too low (hypocalcemia), voltage-gated ion channels start opening spontaneously, causing nerve and muscle cells to become hyperactive. The syndrome of involuntary muscle spasms due to low [Ca++]ECF is called hypocalcemic tetany. Conversely, when [Ca++]ECF is too high (hypercalcemia), voltage-gated ion channels don't open as easily, and there is depressed nervous system function. Another problem of hypercalcemia is that calcium can combine with phosphate ions, forming deposits of calcium phosphate (calcification and stones) in blood vessels and in the kidneys. The figure above illustrates the physiological influences on [Ca++]ECF. 87 [Ca++]ECF is influenced by dietary intake, Ca++ absorption in the small intestine, and by excretion of Ca+ + in the urine. Importantly, the bones contain 99% of the Ca++ in the body, so bones provide a reservoir of Ca++ that can be used to maintain [Ca++]ECF. The two most important hormones for maintaining calcium levels in the body are parathyroid hormone (PTH) and 1,25(OH)2D (the active form of vitamin D). The major regulator is PTH, which is part of a negative feedback loop to maintain [Ca++]ECF (see Humoral regulation). PTH secretion is stimulated by hypocalcemia, and it works through three mechanisms to increase Ca++ levels: 1) PTH stimulates the release of Ca++ from bone, in part by stimulating bone resorption. 2) PTH decreases urinary loss of Ca++ by stimulating Ca++ reabsorption. 3) PTH indirectly stimulates Ca++ absorption in the small intestine by stimulating synthesis of 1,25(OH)2D in the kidney. PTH Effects on Bone 90 Types Iof Ihormones Iby Istructure Pancreas Insulin Muscle, fat tissue Acts to lower blood glucose levels Glucagon Liver Acts to raise blood glucose levels Somatostatin Pancreas Acts to inhibit glucagon and insulin release Ovary Oestrogens Breast, Uterus, Internal and external genitalia Acts to promote development of female primary and secondary sexual characteristics. Important role in preparing the uterus for implantation of embryo Progesterone BreastUterus Affects female sexual characteristics and important in the maintenance of pregnancy Testis Testosterone Sexual organs Promotes the development of male sexual characteristics including sperm development Stomach Gastrin Stomach Promotes acid secretion in the stomach Serotonin (5-HT) Stomach Causes constriction of the stomach muscles Duodenum and jejunum Secretin Stomach, Liver Inhibits secretions from the stomach and increases bile production Cholecystokinin (CCK) Liver, Pancreas Stimulates release of bile from the gall bladder and causes the pancreas to release digestive enzymes Kidney Erythropoietin Bone marrow Stimulates red blood cell development in the bone marrow Heart Atrial natiuretic factor (ANF) Kidney Lowers blood pressure by promoting salt and water loss Skin Vitamin D Small intestine, Kidney, Bone cells Stimulates the uptake of calcium in the small intestine, retention of calcium and release of calcium from bone stores 91 Kidney Istones Glycoprotein Proteins attached to carbohydrates for the purpose of identification. Glycoproteins serve a number of important functions in the human body including providing structural support, lubrication, assisting with the immune system and have a role in every other biological function studied thus far. Glycoproteins are produced in three types: N-linked, O-linked and nonenzymatic. The N-linked glycoproteins have the saccharide molecule attached to the nitrogen atoms of the amino acid asparagine. The sugar molecules of N-linked glycoproteins are added as complex multi-chained molecules. O-linked glycoproteins add their saccharides as single sugars and are attached to the hydroxyl side chainof amino acids serine or threonine. These glycoproteins are usually secreted out of the cell into the extracellular matrix Nonenzymatic glycoproteins are polypeptides that have over time simply had sugar molecules added to them as they became available. In patients with excess blood glucose levels, the nonenzymatic glycoprotein production can be quite high. A diagnostic test for diabetes, the A1C blood test, measures this excess production. 92 Type I2 Idiabetes Pituitary Ihormone Isecretion Calculi, or urinary stones (urolithiasis), are masses of crystals, protein, or other substances that are a common cause of urinary tract obstruction in adults. They can be located in the kidneys, ureters, and urinary bladder. Classified by primary minerals that they consist of. ***Most Icommon Itype Iare Icalcium Ioxalate Ior Iphosphate*** (70%-80%), struvite (15%) and uric acid (7%). Calcium stones- genetic and environmental factors, most are idiopathic. Some caused by hyperparathyroidism and prolonged immobilization (causing bone demineralization). Clinical manifestations- Renal colic (moderate to severe pain radiating from flank to groin (stone in renal pelvis or proximal ureter), colic radiating to lateral flank or lower abdomen (stone in mid ureter), urgency, frequent voiding, urge incontinence) obstruction in lower ureter or reterovesical junction. **Pain can be severe/incapacitating and may be accompanied by nausea and vomiting with either grossor microscopic hematuria. Diagnosis made by clinical presentation, history, imaging (ultrasound, CT, pyelogram and MRI) real pelvic/urethral pressures and UA (with pH) and 24 urine. Also, if possible, the stone is collected and analyzed after passing to determine what stone consists of. Treatment: Manage pain (analgesics), promote stone passage (alpha agonists or calcium channel blocker), reduce size of stones already formed (increase fluid intake) and prevent new formation (changing diet) and removing stones(Percutaneous nephrolithotomy, uteroscopy, ultrasonicor laser lithotripsy). Most common type due to an environmental-genetic interaction. Risk factors are age, obesity, HTN, physical inactivity, and family history. Metabolic syndrome (central obesity, dyslipidemia, prehypertension, and elevated fasting blood glucose level) is risk factor. Combination of genetic, epigenetic and environmental influences. ***Risk factors cause insulin resistance but only those predisposed to beta cell dysfunction will develop type II diabetes*** • genes have been identified that are associated with type 2 diabetes, including those that code for beta-cell mass, beta-cell function (ability to sense blood glucose levels, insulin synthesis, and insulin secretion), proinsulin and insulin molecular structure, insulin receptors, hepatic synthesis of glucose, glucagon synthesis, and cellular responsiveness to insulin stimulation. Anterior pituitary • Growth hormone Targets Bone and muscle growth and liver glycogenolysis/increased fat mobilization. • ACTH (Adrenocorticotropic hormone) Stimulates adrenal cortex to release cortisol and aldosterone 95 Cushing's Idisease sympathetic nervous systems using a technique known as heart rate variability (the measurement of R wave variability from heartbeat to heartbeat). • Under conditions of allostatic overload, the parasympathetic system may decrease its restraint of the sympathetic system, resulting in increased or prolonged inflammatory responses ANS promotes a steady state among visceral organs (regulation of cardiac muscle and glands of the body Involuntary system divided into sympathetic and parasympathetic Sympathetic I(fight or flight) which is widespread through whole symptom Uses epinephrine and norepinephrine Increase BP, pupil dilation, bronchodilation, goosebumps, increased sweat glands, arteriole smoothmuscle contraction, increased force/rate ofcardiac contraction and increased cardiac output, increased glycogen synthesis and decreased insulin production. Parasympathetic-(rest and relaxation) workswith specific fibers withparticular target areas Decreased HR, and innervations to enhance digestion. https://www.youtube.com/watch?v=jA1NyCE4M2g&feature=youtu.be ACTH Secretion of adrenocorticotropic hormone is controlled by three inter-communicating regions of the body, the hypothalamus, the pituitary gland and the adrenal glands. This is called the hypothalamic– pituitary–adrenal axis. When adrenocorticotropic hormone levels in the blood are low, a group of cells in the hypothalamus release a hormone called corticotrophin-releasing hormone which stimulates the pituitary gland to secrete adrenocorticotropic hormone into the bloodstream. High levels of adrenocorticotropic hormone are detected by the adrenal glands which stimulate the secretion of cortisol, causing blood levels of cortisol to rise. As the cortisol levels rise, they start to slow down the release of corticotrophin-releasing hormone from the hypothalamus and adrenocorticotropic hormone from the pituitary gland. As a result, the adrenocorticotropic hormone levels start to fall. This is called a negative feedback loop. Stress, both physical and psychological, also stimulates adrenocorticotropic hormone production and hence increases cortisol levels. **The effects of too much adrenocorticotropic hormone are mainly due to the increase in cortisol levels which result. Higher than normal levels of adrenocorticotropic hormone may be due to: – this is the most common cause of increased adrenocorticotropic hormone. It is caused by a non-cancerous tumour called an adenoma located in the pituitary gland, which produces excess amounts of adrenocorticotropic hormone. (Please note, Cushing’s disease is just one of the numerous causes of Cushing’s syndrome). (also called ectopic adrenocorticotropic hormone tumour). A Itumour, Ioutside Ithe Ipituitary Igland, Iproducing Iadrenocorticotropic Ihormone 96 Bartholin Iglands I(pg I772) Gonococcal Idisease I(pg I920-922) Small Ipatent Iductus Iarteriosus I(PDA)- Addison's Idisease (although cortisol levels are low, adrenocorticotropic hormone levels are raised). (a genetic disorder with inadequate production of cortisol, aldosteroneor both). Also called greater vestibular or vulvovaginal glands. In response to sexual stimulation Bartholin glands secrete mucus to lubricate inner labial surfaces and enhance viability and motility of sperm. It also facilitates coitus (sexual intercourse). Gonorrhea is caused by gonococci (species of Neisseria gonorrhoeae) Risk factors include: Transient or urban residence, sexual activity at a young age, drug use, prostitution,and previous case of gonorrheal or concurrent STI. Females have a higher risk of contracting than men Transmitted through sexual, oralor anal intercourse. Pregnant women cantransmit to fetus. Glomerulonephritis- Inflammation of the glomerular filtration membrane (epithelium, podocytes, endothelium and basement membrane). Messangelial expansion leads to leaking and loss of negative charge thus causing hematuria (casts and proteinuria). Severe glomerulonephritis -> edema, hypertension, impaired renal function causing decreased glomerular filtration (due to decreased blood flow)-> decreased GFR ultimately causing renal failure. ***Picture--PDA with left to right shunt*** In fetal circulation a PDA allows blood to shunt from PA to aorta. Then at birth when the placenta is removed and lungs expand, the PDA constricts within the first few hours of life. Full closure occurs within 15hrs to 2 weeks after birth. Congenital Iadrenal Ihyperplasia 97 Loss Iof Ilanguage Iand/or Icomprehension-such Ias Iterms-aphasia, Ietc. I–(Data IProcessing IDeficits) Chronic Iinflammatory Ijoint Idisease Defect of the PDA accounts for 5-10% of all congenital cardiac defects and is most prevalent in preemies. Failure of PDA closure=persistent patency of ductus arteriosus. IN PDA: At birth pulmonary circulation = systemic circulation (minimal shunting) Later Pulmonary vascular resistance decreases and reverse fetal shunting occurs (left to right or aortato PA) pulmonary blood flow increases increasing pulmonary venous return to the LA and LV increased work of Left heart leading to increased Right heart ventricular pressure increased pulmonary vascular pressure. Clinical manifestations- Infant has an audible continuous machine like murmur best heard at the leftupper sternal border throughout systole and diastole. Small PDA is generally asymptomatic. Diagnosis through CXR, Echo and presenceof machine like continuous murmur. Asymptomatic PDA or small PDA with no murmur- closure of PDA by 2 yrs old is recommended viasurgical ligation and division or a prostaglandin inhibitor if unable to undergo surgery. 80) Primary HTN= no known cause (95%) Secondary HTN= cause r/t underlying disease Risk factors are both genetic and environmental in primary HTN: Family history, advancing age, gender (men < 55, women >70), black, high Na+ intake, glucose intolerance, smoking, obesity, high alcohol use, low dietary intake of K+, Ca+ and Mag. Agnosia- Deficit of pattern recognition- one sense fails to recognize form/nature of objects but the others may maintain ability to recognize. Agnosia may be auditory, visual or tactile. Example: Person may be able to look at a pin and say “pin” but is unable to do the same when touching it. Agnosia is most common in CVA but can also be found in other neurological issues. Dysphagia- Impairment of comprehension or production of language, comprehension or use of symbolsIin either written or verbal language is impaired. Aphasia- Complete loss of comprehension or production of language. Commonly called arthritis Characterized by damage/destruction of synovial membrane/articular cartilage and systemic signs of inflammation (fever, leukocytosis, malaise, anorexia, hyperfibrinogenemia. Risk Ifactors Ifor Ihypertension- I(HTN= I>120/>