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As this curtails synthesis of both prostaglandins and leukotrienes 160 mg valsartan fast delivery, glucocorticoids have a strong anti-inflammatory effect purchase genuine valsartan on line. The main bifurcation in arachidonic acid metabolism may result in hyperactivity of one pathway in case the other is blocked purchase valsartan 80 mg with mastercard. It has many pro-inflammatory effects, including platelet activation, increasing vascular permeability, bronchial constriction and neutrophil chemotaxis and activation. This works very well to kill phagocytized pathogens, but also kills the phagocyte and frequently damages surrounding tissue. It denotes a polypeptide signaling molecule produced primarily, but not exclusively, by cells of the immune system with the aim of coordinating the defense functions of many different cell types. Designated chemokines, these are small (8-10 kDa) proteins with a conserved structure of three β-sheets and a C-terminal α-helix. To improve on the bewildering chaos of traditional designations, a unified nomenclature was introduced. The guiding system of chemokine-gradient fields and chemokine receptors enables all cells of the immune system to arrive in the right place at the right time. Cortisol and other glucocorticoids at higher than physiologic concentrations are highly immunosuppressive. Recombinant proteins counteracting specific cytokines can be used to inhibit limited aspects of an immune reaction without exposing the patient to the danger of generalized immune suppression. Receptor activation results in expression of genes, the products of which contribute to defending the organism against infection. Purpose of the molecule: Coordination of a non-adaptive defense reaction on a local and a systemic level. Strategy: Local level: In case an epithelial barrier is breached, it is essential to confine the ensuing bacterial infection to this area. The most dangerous development possible would be the distribution of these pathogens via the blood over the entire organism, a life-threatening complication termed sepsis. This can be prevented by enhancing permeability of the small blood vessels and closing the draining venules by clotting. Driven by blood pressure, which is locally increased by vasodilatation, this creates a slow movement of tissue lymph toward the regional lymph node, taking some of the pathogens with it. At the same time, leukocytes are recruited from the blood to the primary infection area and endothelial cells are instructed to help them pass. Everywhere in the body, the coagulation cascade is kicked off, together with the fibrinolytic cascade, consuming all available clotting factors (disseminated intravascular coagulation) and causing profuse bleeding. This causes fever, the sensation of feeling sick with conservation of energy, but mobilization of energy to produce more defense equipment: plasma proteins and neutrophils. These two effects allow complement components and IgG to reach the source of infection, they facilitate the extravasation of leukocytes and increase the flow to local lymph nodes. Tissue lymph flow carries pathogen antigens --packaged in phagocytes and ohterwise-- into lymph nodes, helping to initiate an adaptive immune response. This process is already in full swing after one or two days, while it takes much longer to produce antibodies. Acute phase peptide hepcidin blocks iron export via ferroportin, a membrane protein expressed in many cell types including macrophages. Iron is a limiting factor for many pathogens (including staphylococci, streptococci, fungi); in fighting them, our organism may therefore gain an advantage by "locking iron away". In chronic inflammation, however, 12 continuing misallocation of iron may result in anemia, as iron remains unavailable not only for pathogens, but also for erythropoiesis. This is probably due to the fact that they are produced in human cells, making their appearance "less unfamiliar" than that of other pathogens. Three types of interferons were originally described, depending on the cell type used for purification: α, β and γ. Type-I-interferons are signaling molecules secreted by virus-infected cells with the aim of slowing or inhibiting virus replication in neighboring cells. This severely restricts replication opportunities for any virus infecting these cells, as it relies on the host cell machinery to produce virus proteins. Additional proteins induced by type I-interferons facilitate the initiation of an adaptive immune response to eventually eliminate the virus. Viral infections would seem like logical indications, but interferons are both expensive and have considerable adverse effects, e. Viruses using this trick have a selective advantage later on, as these cells cannot be identified as infected by cytotoxic T cells (explained in sections 2. The importance of this mechanism has been shown in the early defense against the protozoon Leishmania, which is spread by sand flies. Five alternative types of heavy chains exist (μ, γ, δ, α, ε), giving rise to respectively IgM, IgG, IgD, IgA or IgE. A few technical terms used in immunology: Functionally, an antibody has a variable and a constant region. Antigens include, but are not limited to, polypeptides, carbohydrates, fats, nucleic acids and (less frequently than commonly perceived) synthetic materials. Any non-covalent binding force can be used to establish this contact: electrostatic attraction, hydrogen bonds, Van der Waals- and hydrophobic forces. In most cases, a biological macromolecule contains several independent structures able to elicit an antibody response, so-called antigenic determinants or epitopes. Conversely, two very different macromolecules which by chance share a certain three-dimensional structure may be bound by the same antibody, a phenomenon known as cross-reaction. Antigens recognized by T-lymphocytes are more narrowly restricted: epitopes sensed by T-lymphocytes are linear peptides from 8 to 20 amino acids. If a certain protease is used to digest the Y-formed antibody, three fragments result: two identical fragments termed Fab (fraction antigen binding) and one fragment representing the other end, containing a large part of the constant region. In early experiments, this fraction was successfully crystallized, giving the fragment the name Fc (fraction crystallizable). As this is the "back" end of an antibody, many cells of the immune system have receptors binding 16 to it: so-called Fc-receptors, named for the heavy chain they recognize: Fcγ-R (for IgG), Fcα- R (for IgA), Fcα/µ-R (for IgA and IgM), Fcε-R (for IgE). The affinity of most of these receptors is too low to bind single, free antibodies for longer periods of time. Only after antigen-binding, resulting in larger immune complexes, cooperative binding between several Fc ends and their receptors leads to rapid internalization by phagocytosis, providing a mechanism for rapid antigen clearance. An exception to this rule are mast cells and eosinophils, which also bind free (meaning non-antigen-complexed) IgE via their high- affinity Fc-ε-receptors. After a lag phase of at least five days, which we must survive with the help of innate immunity, B-lymphocyte-derived plasma cells will produce specific antibodies.

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Observation period between two examination Depends on the age of the patient buy valsartan 80mg with mastercard;  7 days to 2 month old minimum 48 hr interval cheap 40 mg valsartan with visa. Communication with family and further decision making After the clinical criteria of brain death have been met discount 80mg valsartan otc, the physician should inform the next of kin, who can be approached about organ donation. Counseling  The family should be counseled that the patient cannot recover  Family should be counseled for organ donation  If the patient cannot become an organ donor, withholding or withdrawing of life support may be discussed with the family. Referral Criteria  If the patient is a potential organ donor, he should be transferred to a tertiary level centre that is certified by the competent authority and is capable of supporting the brain dead organ donor  If in some cases further diagnostic studies are required to confirm brain death o Difficulty to determine coma. Supportive treatment should start early as soon as brain death has been recognized irrespective of the consent. Switch the focus of the management for elevated intracranial pressure and brain protection, to preservation of organ function and optimization of tissue oxygen delivery. Hemodynamic support Hypertension  Hypertension and bradycardia preceding brain death characterize the Cushing’s response. Thyroid hormone replacement  Thyroid hormone administration typically with T3 (triiodothyronine) which is the active form of thyroid hormone. Coagulopathy  If clinically significant mucocutaneous bleeding, treatment with appropriate blood components is required. Absolute Contraindications to organ donation  Malignancy (except primary brain tumors, low grade skin malignancies and carcinoma in situ of the cervix). Conclusion A severe shortage of organs the world over has led to increased pressure on the intensive care staff for early identification of the brain dead donor and optimum management of this condition. The diagnosis of brain death as per the Transplantation Human Organ Act 1994 is based on simple clinical bedside tests,no need of routine confirmatory test. This Act has made it possible in India to use this pool of patients for organ retrieval and transplantation. The process of organ donation and transplantation requires co-ordination between multidisciplinary teams operating almost simultaneously and sometimes in different locations like getting surgeons from different specialties together for both donor and recipient surgery. Further reading  Evidence-based guideline update: Determining brain death in adults : Report of the Quality Standards Subcommittee of the American Academy of Neurology Eelco F. N Engl J Med 2008; 359:674-675  Transcranial Doppler Ultrasonography to confirm brain death: a meta-analysis Louisa M. Simini Intensive Care Med (1995) 21:657-662  Brain death: timing of apnea testing in primary brain stem lesion, G. In non-immunosuppressed patient two consecutive temperature (core) of more than 101° F warrants further investigation. New onset of fever below this range, in a hemodynamically stable patient requires a bedside assessment to look for a source of infection and non infectious fever and sending investigation appropriately. Genitourinary: Bacterial or fungal cystitis, Pyelonephritis, Perinephric abscess, Tubo-ovarian mass, Endometritis, Prostatitis vii. Cutaneous: Cellulitis, Suppurative wound infection, Necrotizing fasciitis, Bacterial myositis, Herpes zoster ix. Strict asepsis, hand hygiene measures & universal precautions can bring down the infection related fevers. Regular surveillance can help in identifying non-compliant staff, which can be appropriately counseled. Optimal Diagnostic Criteria, Investigations, treatment & referral criteria *Situation1: At secondary Hospital/ Non-Metro situations: Optimal standards of treatment in situations where technology & resources are limited. Symptoms and signs in the absence of fever, which mandate a comprehensive search for infection and aggressive, immediate empirical therapy: Unexplained hypotension, tachycardia, tachypnea, confusion, rigors, skin lesions, respiratory manifestations, oliguria, lactic acidosis, leukocytosis, leukopenia, immature neutrophils (i. A detailed medication history, line manipulation, blood transfusion, appearance of new rash, diarrhea, or any new procedure performed should be enquired b. Focused physical examination should be performed looking for any source of sepsis or non-infectious cause of fever. New fever, purulent secretion, bronchial breathing Central line sepsis-Line in place for more than 48 hours Erythema, purulent discharge at central line site. Urinary catheter related infection – Catheter more than 48 hours in place,suprapubic tenderness cloudy urine Surgical site infection – purulent discharge from wound site Sinusitis- Nasogastric or nasotracheal tube, purulent nasal discharge 59 Parotitis- poor oral hygiene, unilateral tender parotid swelling A calculus cholecystitis- abdominal tenderness, intolerance of feed d. Non specific treatment with antipyretic should be instituted in patients with central nervous system disorder, extremes of age, poor cardiac reserve. Referral Criteria: If higher diagnostic tests and imaging techniques are not available and the patient is not improving, transfer to well equipped centres should be undertaken. Guidelines for evaluation of new fever in critically ill adult patients: 2008 update from the American College of Critical Care Medicine and the Infectious Diseases Society of America. Clinical practice guidelines for the diagnosis and management of intravascular catheter- related infection: 2009 Update by the Infectious Diseases Society of America. Attention to technical details correct interpretation of data, and its application in selecting therapy should be individualized within the clinical context. In addition, presence of arterial catheter enables frequent sampling of arterial blood without arterial punctures in critically ill patients. Set up of the pressure tranducing system o The pressure transducing assembly consists of a coupling system, pressure transducer, amplifier and signal conditioner, analog to digital converter, microprocessor which convert the signal received from the vein or artery into a waveform on the a bedside monitor o The flushing system – is set up using a 500 ml saline bottle encased in a bag 65 pressurized to 300 mm Hg. At this pressure the catheter will be flushed with 3 ml saline per hour and help keep the catheter patent. Heparinised saline is no longer routinely used  The reference point is usually at the level of the heart where the transducer is zeroed. Other veins that may be used are the arm veins (basilic, cephalic), external jugular and femoral veins. The fluid challenge is performed in 4 steps: o Select the type of fluid: usually normal saline or a colloid o Infuse rapidly. Rate of infusion: 500ml of crystalloid or 200 ml of colloid over 20-30 minutes o Target the Desired therapeutic response: the parameters are set empirically by the physician. This brought the catheter out of the domain of radiologists and at the bedside of the patients in intensive care. An SvO2 below 65% implies low oxygen delivery, while a value below 60% indicates that there is a serious risk of tissue hypoxia if corrective measures are not taken. In some disease states, cells in some tissues are unable to assimilate and/or process the needed oxygen.

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To maintain the proper osmotic concentration of the extra cellular fluid to excrete wastes and to maintain proper kidney function the body must excrete at least 450ml of urine per day buy 160 mg valsartan visa. The volume and concentration of urine is controlled by: - Antidiuretic hormone - Aldestrone - The Renin – angiotensin mechanism 349 Human Anatomy and Physiology 12 cheap valsartan 40 mg with mastercard. Steps of urination are: Conscious desire to urinate Pelvic diaphram muscle relax Smooth muscle of Urinary bladder neck Moves Urinary bladder down purchase valsartan visa, outlet Opens, wall Contracts & urine stretch, and wall stretch ejects Receptors are stimulated 350 Human Anatomy and Physiology Study Questions 1. The apex of each renal pyramid end in the a) Cortical region b) Papilla c) Juxta medullary region d) Capsule e) Tubule 2. The inner most layer of the ureters is the a) Mucosa b) Muscularis c) Adventitia d) Longitudinal layer e) Circular layer 3. The kidney function in all of the following except a) Acid – base balance b) An endocrine organ c) By removing metabolic waste d) By removing excess carbon dioxide e) By maintaining osmotic concentration 4. An increased volume of urine formation would follow:- a) Inhibition of tubular sodium re-absorption b) A fall in plasma osmolarity c) A fall in plasma volume d) a and b e) a, b and c 5. The volume or chemical makeup of these fluids whenever deviates even slightly from normal, disease results. The correct proportion of water and electrolytes in the water and proper acid base balance are necessary for life to exist. Loss of 10% of total body water usually produce lethargy, fever and dryness on mucous membrane and a 20% loss is fatal. Extra cellular fluids found as interstitial fluid (the immediate environment of body cells), blood plasma and lymph, cerebrospinal, synovial, fluids of the eye & ear, pleural, pericardial, peritoneal, gastrointestinal and glomerular filtrate of the kidney. The concentration of water in the interstitial fluid is slightly higher than the concentration of water in plasma. The plasma proteins are responsible for this difference 354 Human Anatomy and Physiology A B Figure: 13. Hydrostatic pressure: it is the force exerted by a fluid against the surface of the compartment containing fluid. Osmotic pressure: Is the pressure that must be applied to a solution on one side of a selectively permeable membrane to prevent the Osmotic flow of water across the membrane from a compartment of pure water. When there is shift in the pressure of water to wards the interstitial space, accumulation of fluid in the space occur. Such accumulation of water produces distention of the tissue which appears as puffiness on the surface of the body. Causes of edema may be plasma protean leakage decreased protein synthesis, increased capillary or venous hydrostatic pressure, obstructed lymphatic vessels and inflammatory reaction. Under normal condition water is taken in to and excreted from the body, so it matches to maintain homeostasis. Drinking of water is regulated by nervous mechanism (thirst center in the brain) together with hormonal mechanism (Antidiuretic hormone). Kidneys are the organs regulated by homeostatic feed back response they are responsible for excreting most of the water from the body. These three electrolytes are particularly important in maintaining body function and normal water distribution among the fluid compartment. Enzymes, hormones and the distribution 360 Human Anatomy and Physiology of ions can all be affected by the concentration of hydrogen H ion. H Homeostatic maintenance of an acceptable P range in the extra cellular fluid is accomplished by three mechanisms: 1. This task is accomplished in renal tubules, where + hydrogen & ammonium ions are secreted in to urine, when H is excreted sodium is exchanged. Movement of water from one body compartment to another is controlled by a) Atmospheric pressure b) Hydrostatic pressure c) Osmotic pressure d) a & c only e) b & c only 364 Human Anatomy and Physiology 4. The function of electrolytes in the body include a) Contributing to body structure b) Facilitating the movement of water between body compartments c) Maintaining acid – base balance d) a and b only e) a, b, & c 5. Reproduction by means of sexual intercourse produces new human beings and hereditary traits to be passed from both parents to their children’s. The sex hormones play an important role both in the development and function of the reproductive organ and in sexual behavior & drives. By third fetal month it stats is to descend and by the seventh month of fetal life it passes through the inguinal canal. Because the tests hang in scrotum out side the body their temperature is of cooler than the body temperature by 3 Degree Fahrenheit. Next to tunica albuginea is Tunica Vaginals, which is a continuation of membrane of abdomino-pelvic cavity. Each test contain 800 lightly coiled Semniferous Tubules which produce thousands of sperm each second. The germinal tissue contains two types of cells: spermatogenetic cell producing or developing the sperm cell and the sustentacular cell, which provide nourishment for the germinal sperm. Between the semniferous tubules clusters of endocrine cells called interstitial endocrinocytes (Leydig cell) secret male sex hormone (Androgens) where testosterone is the most important. Epididymis: - The semniferous tubules merge in the central posterior portion of the testes as epydidimis. It is located easily over the spermatic cord; hence male permanent (surgical) contraceptive method (vasectomy) is usually performed over it. As it passes from tail of epididymis it is covered by spermatic cord containing testicular artery, vein, autonomic nerves, lymphatic and connective tissue. After the ducts deferens pass through the inguinal canal it free from spermatic cord and pass behind the urinary bladder, where it 372 Human Anatomy and Physiology travels along side an accessory gland, the seminal vesicle and becomes ejaculatory duct. They receive secretion from the seminal vesicles and pass through the prostate where they receive additional secretion. Seminal vesicles Seminal vesicles are paired; secretary sacs lie next to the Ampulla of the ducts deference. Bulbo urethral glands secrets clearly alkaline 374 Human Anatomy and Physiology fluid to neutralize the acidity of urine during the onset of sexual excitement and it also act as a lubricant. Has two main function, It caries urine through urethra to the out side during urination and it transports semen through the urethra during ejaculation. The loosely fitting skin of the penis is folded forward over the glans to form the prepuce or foreskin, which usually excised during circumcision.