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By: John Alexander Bartlett, MD

  • Professor of Medicine
  • Director of the AIDS Research and Treatment Center
  • Research Professor of Global Health
  • Professor in the School of Nursing
  • Affiliate of the Duke Initiative for Science & Society
  • Member of the Duke Cancer Institute


Later arteria ileocolica cheap telmisartan 40 mg on-line, when the ostium primum is obliterated by fusion of the septum primum with the endocardial cushions blood pressure medication olmetec purchase telmisartan 20 mg with mastercard, the ostium secundum is formed by cell death that creates an opening in the septum primum blood pressure chart for children cheap telmisartan 80 mg line. Finally heart attack video generic telmisartan 40 mg without a prescription, a septum secundum forms, but an interatrial opening, the oval foramen, persists. Only at birth, when pressure in the left atrium increases, do the two septa press against each other and close the communication between the two. Four endocardial cushions surround Chapter 13 Cardiovascular System 199 the atrioventricular canal. Cushion tissue then becomes fibrous and forms the mitral (bicuspid) valve on the left and the tricuspid valve on the right. The interventricular septum consists of a thick muscular part and a thin membranous portion. In many cases, these three components fail to fuse, resulting in an open interventricular foramen. Although this abnormality may be isolated, it is commonly combined with other compensatory defects. The bulbus is divided into (1) the truncus (aorta and pulmonary trunk), (2) the conus (outflow tract of the aorta and pulmonary trunk), and (3) the smooth-walled portion of the right ventricle. The truncus region is divided by the spiral aorticopulmonary septum into the two main arteries. The conus swellings divide the outflow tracts of the aortic and pulmonary channels and with tissue from the inferior endocardial cushion, close the interventricular foramen. Many vascular abnormalities, such as transposition of the great vessels and pulmonary valvular atresia, result from abnormal division of the conotruncal region; their origin may involve neural crest cells that contribute to septum formation in the conotruncal region. Four important derivatives of the original aortic arch system are (1) the carotid arteries (third arches); (2) the arch of the aorta (left fourth aortic arch); (3) the pulmonary artery (sixth aortic arch), which during fetal life is connected to the aorta through the ductus arteriosus; and (4) the right subclavian artery formed by the right fourth aortic arch, distal portion of the right dorsal aorta, and the seventh intersegmental artery. The most common vascular aortic arch abnormalities include (1) open ductus arteriosus and coarctation of the aorta. The vitelline arteries initially supply the yolk sac but later form the celiac and superior mesenteric arteries. After birth, the distal portions of these arteries are obliterated to form the medial umbilical ligaments, whereas the proximal portions persist as the internal iliac and vesicular arteries. Three systems can be recognized: (1) the vitelline system, which develops into the portal system; (2) the cardinal system, which forms the caval system; and (3) the umbilical system, which disappears after birth. The complicated caval system is characterized by many abnormalities, such as double inferior and superior vena cava and left superior vena cava. During prenatal life, the placental circulation provides the fetus with its oxygen, but after birth, the lungs take on gas exchange. In the circulatory system, the following changes take place at birth and in the first postnatal months: (1) the ductus arteriosus closes; (2) the oval foramen closes; (3) the umbilical vein and ductus venosus close and remain as the ligamentum teres hepatis and ligamentum venosum; and (4) the umbilical arteries form the medial umbilical ligaments. The lymphatic system develops later than the cardiovascular system, originating from the endothelium of veins as five sacs: two jugular, two iliac, one retroperitoneal, and one cisterna chyli. Numerous channels form to connect the sacs and provide drainage from other structures. Ultimately, the thoracic duct forms from anastomosis of the right and left thoracic ducts, the distal part of the right thoracic duct, and the cranial part of the left thoracic duct. The right lymphatic duct develops from the cranial part of the right thoracic duct. A prenatal ultrasound of a 35-year-old woman in her 12th week of gestation reveals an abnormal image of the fetal heart. Instead of a four-chambered view provided by the typical cross, a portion just below the crosspiece is missing. What structures constitute the cross, and what defect does this infant probably have A child is born with severe craniofacial defects and transposition of the great vessels. What cell population may play a role in both abnormalities, and what type of insult might have produced this effect What type of tissue is critical for dividing the heart into four chambers and the outflow tract into pulmonary and aortic channels

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Normal ras protein (p21) flips back and forth between an activated blood pressure medication exercise buy telmisartan 40 mg on-line, signal-transmitting form and an inactive state blood pressure testing discount telmisartan 40mg without prescription. Normal cellular genes (proto-oncogenes) may become oncogenic by being 140 Pathology incorporated into the viral genome (forming v-oncs) blood pressure medication benicar generic 80 mg telmisartan amex, or they may be activated by other processes to heart attack 6 days collections telmisartan 80 mg low cost form cellular oncogenes (c-oncs). These other processes include gene mutations, chromosomal translocations, and gene amplifications. Gene mutations, such as point mutations, are associated with the formation of cancers by mutant c-ras oncogenes. The former involves the proto-oncogene c-abl, which is rearranged in proximity to a break point cluster region (bcr) on chromosome 22. The resultant chimeric c-abl/bcr gene encodes a protein with tyrosine kinase activity. Expression of the oncogene bcl-2 is associated with the prevention of apoptosis in germinal centers. Examples of associations that involve gene amplification include N-myc and neuroblastoma, c-neu and breast cancer, and erb-B and breast and ovarian cancer. Gene amplifications can be demonstrated by finding doublet minutes or homogenous staining regions. In general, these tumor suppressor genes encode proteins that can function as cell surface molecules, regulators of signal transduction, or regulators of nuclear transcription. Products of these genes are found within the nucleus and are involved in regulation of the cell cycle. The product of the Rb gene is a nuclear phosphoprotein that reg- General Pathology Answers 141 ulates the cell cycle at several points. It exists as an active unphosphorylated form (pRb) and an inactive phosphorylated form (pRb-P). The active unphosphorylated form (pRb) normally stops the cell cycle at G1 going to S. It does this by binding to transcription factors such as the product of c-myc and the E2F protein. Inactivation of the pRb stop signal causes the cell to continually cycle and undergo repeated mitosis. The p53 gene, located on chromosome 17, is the single most common target for genetic alterations in human cancers. These patients have an increased incidence of skin cancers, including basal cell carcinoma, squamous cell carcinoma, and malignant melanoma. Wiskott-Aldrich syndrome, characterized by thrombocytopenia and eczema, is an immunodeficiency disease associated with an increased incidence of lymphomas and acute leukemias. Familial polyposis is characterized by the formation of numerous neoplastic adenomatous colon polyps. These individuals have a 100% risk of developing colorectal carcinoma unless surgery is performed. Sturge-Weber syndrome is a rare congenital disorder associated with venous angiomatous masses in the leptomeninges and ipsilateral port-wine nevi of the face. The highest rates for gastric carcinoma are found in Japan, Chile, China, and Russia, while it is much less common in the United States, the United Kingdom, Canada, and France. The high rates for gastric cancer in Japan might be related to dietary factors, such as eating smoked and salted foods. Other examples of geographic variations in the incidence of neoplasms include nasopharyngeal carcinoma, liver cancer, and trophoblastic disease. Nasopharyngeal carcinoma, associated with the Epstein-Barr virus, is rare in most parts of the world, except for parts of the Far East, especially China. Liver cancer is associated with both hepatitis B infection and high levels of aflatoxin B1. Trophoblastic diseases, including choriocarcinoma, have high rates of occurrence in the Pacific rim areas of Asia.

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Laboratory examination reveals increased serum uric acid and cholesterol with decreased serum glucose levels fitbit prehypertension buy cheap telmisartan 80mg on line. Following oral administration of fructose blood pressure quick reduction telmisartan 80mg otc, there is no increase in blood glucose levels heart attack or stroke telmisartan 80mg line. A liver biopsy specimen reveals increased amounts of glycogen in hepatocytes blood pressure tracking chart excel buy 80 mg telmisartan mastercard, which also have decreased levels of glucose-6-phosphatase. In tissues affected by the predominant form of Niemann-Pick disease, which one of the following is found at abnormally high levels Physical examination reveals a child with short stature, coarse facial features (low, flat nose, thick lips, widely spaced teeth, facial fullness), a large tongue, and clear corneas. Laboratory examination reveals increased urinary levels of heparan sulfate and dermatan sulfate. Metachromatic granules (Reilly bodies) are found in leukocytes from a bone marrow biopsy. Hyperphenylalaninemia Tyrosinemia Tyrosinase-positive oculocutaneous albinism Alkaptonuria Maple syrup urine disease 62. Which one of the listed processes is the most likely cause of an aneuploid karyotype A reciprocal translocation between two acrocentric chromosomes Deletion of both ends of a chromosome with fusion of the damaged ends Division of the centromere along a transverse plane Failure of homologous chromosomes or paired chromatids to separate Two breaks within a single chromosome with reincorporating of the inverted segment 63. Gross examination at the time of autopsy reveals polydactyly, a cleft lip and palate, and a single, central eye ("cyclops"). Further examination reveals holoprosencephaly, consisting of fused frontal lobes with a single ventricle. Which of the listed chromosomal abnormalities is most consistent with these findings A 2-month-old girl presents with a soft, high-pitched, mewing cry and is found to have microcephaly, low-set ears and hypertelorism, and several congenital heart defects. A 6-year-old female with a fair complexion is being evaluated for severe mental retardation and seizures. A 19-year-old female of average intelligence and short stature is being evaluated for amenorrhea. Physical examination reveals that she has a shield-shaped chest and her elbows turn outward when her arms are at her sides. She has a "thick neck" and you notice the absence of secondary female characteristics. Which immunoglobulins are characteristically present on mature (virgin) B cells, which are B lymphocytes that have not yet been exposed to the appropriate antigen What type of antibody is produced first against a bacterial infection, is very effective at activating complement, and is too large to cross the placenta Which one of the following sequences correctly describes the usual temporal sequence of T-lymphocyte maturation within the cortex and medulla of the thymus Double negative double positive single positive Double negative single positive double positive Double positive double negative single positive Double positive single positive double negative Single positive double positive double negative 72. In antigen recognition by cytotoxic T lymphocytes, the T cell receptor recognizes antigens bound to a. Ten minutes after being stung by a wasp, a 30-year-old male develops multiple patches of red, irregular skin lesions over his entire body. This response is primarily the result of liberation of specific vasoactive substances by the action of a. Activated T lymphocytes on smooth muscle cells IgA on basophils and mast cells IgA on lymphocytes and eosinophils IgE on basophils and mast cells IgE on lymphocytes and eosinophils 76. After receiving incompatible blood, a patient develops a transfusion reaction in the form of back pain, fever, shortness of breath, and hematuria. Which one of the following histologic or immunofluorescent findings is most indicative of a delayed type hypersensitivity reaction

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The usual cause is detrusor instability arrhythmia when lying down 80 mg telmisartan visa, which occurs most often in women hypertension obesity generic telmisartan 80mg visa, and the aetiology is not known blood pressure 80 60 buy telmisartan 20 mg without a prescription. Mild cases may respond to hypertension table telmisartan 20 mg discount bladder retraining (gradually increasing the time interval between voids). Less commonly, urge incontinence is caused by bladder hypersensitivity from local pathology. Overflow incontinence Overflow incontinence is most often seen in men with prostatic hypertrophy causing outflow obstruction. There is leakage of small amounts of urine, and on abdominal examination the distended bladder is felt rising out of the pelvis. If the obstruction is not relieved with urethral or suprapubic catheterization, renal damage will develop. Neurological causes these are usually apparent from the history and examination, which reveal accompanying neurological deficits. The aim of treatment is to reduce outflow pressure, either with -adrenergic blockers or by sphincterotomy. In elderly people, incontinence may be the result of a combination of factors: diuretic treatment, dementia (antisocial incontinence) and difficulty in getting to the toilet because of immobility. Chest pain or discomfort is a common presenting symptom of cardiovascular disease and must be differentiated from non-cardiac causes. The site of pain, its character, radiation and associated symptoms will often point to the cause (Table 10. Left heart failure is the most common cardiac cause of exertional dyspnoea and may also cause orthopnoea and paroxysmal nocturnal dyspnoea. The normal heartbeat is sensed when the patient is anxious, excited, exercising or lying on the left side. In other circumstances it usually indicates a cardiac arrhythmia, commonly ectopic beats or a paroxysmal tachycardia (p. Syncope this is a temporary impairment of consciousness due to inadequate cerebral blood flow. There are many causes and the most common is a simple faint or vasovagal attack (Table 17. They last only 1 or 2 minutes, with complete recovery in seconds (compare with epilepsy, where complete recovery may be delayed for some hours). May radiate to jaw or arms Similar in character to angina but more severe, occurs at rest, lasts longer Sharp pain aggravated by movement, respiration and changes in posture Severe tearing chest pain radiating through to the back With dyspnoea, tachycardia and hypotension Tender to palpate over affected area May be exacerbated by bending or lying down (at night). The electrocardiogram 411 Other symptoms Tiredness and lethargy occur with heart failure and result from poor perfusion of brain and skeletal muscle, poor sleep, side effects of medication, particularly -blockers, and electrolyte imbalance due to diuretic therapy. Heart failure also causes salt and water retention, leading to oedema, which in ambulant patients is most prominent over the ankles. Each cardiac cell generates an action potential as it becomes depolarized and then repolarized during a normal cycle. The right and left bundle branches continue down the right and left side of the interventricular septum and supply the Purkinje network which spreads through the subendocardial surface of the right ventricle and left ventricle, respectively. The main left bundle divides into an anterior superior division (the anterior hemi-bundle) and a posterior inferior division (the posterior hemi-bundle). This chest X-ray demonstrates cardiomegaly, hilar haziness, Kerley B lines, upper lobe venous blood engorgement and fluid in the right horizontal fissure. Hilar haziness and Kerley B lines (thin linear horizontal pulmonary opacities at the base of the lung periphery) indicate interstitial pulmonary oedema. The heart rate (if the rhythm is regular) is calculated by counting the number of big squares between two consecutive R waves and dividing into 300. In normal circumstances only the specialized conducting tissues of the heart undergo spontaneous depolarization (automaticity), which initiates an action potential. Ventricular depolarization starts in the septum and spreads from left to right. Thus in the right ventricular leads (V1 and V2) the first deflection is upwards (R wave) as the septal depolarization wave spreads towards those leads. The second deflection is downwards (S wave) as the bigger left ventricle (in which depolarization is spreading away) outweighs the effect of the right ventricle. The opposite pattern is seen in the left ventricular leads (V5 and V6), with an initial downwards deflection (small Q wave reflecting septal depolarization) followed by a large R wave caused by left ventricular depolarization. The R wave in the chest (precordial) leads steadily increases in amplitude from lead V1 to V6 with a corresponding decrease in S wave depth, culminating in a predominantly positive complex in V6.


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