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Lysosome: Cell organelles having powerful hydrolytic enzymes that destroy unwanted material within the cell order 50 mg losartan visa. Macrophage: large tissue bound phagocytic cells Mean arterial blood pressure: the pressure responsible for driving blood forward through the arteries in to the tissues throughout the cardiac cycle purchase losartan 50mg visa. Motor neurons: neurons that innervate skeletal muscles Motor unit: is motor nerve plus all of the muscle fibers innervated buy generic losartan 25mg. Multi-unit smooth muscle: muscle with multiple discrete cells independent of each other Myelinated fiber: neuronal axon covered at regular intervals with insulative myelin buy losartan 25mg with mastercard. Negative feed: a regulatory mechanism in which a change in the controlled variable triggers a response that opposes the change, thus maintaining a steady state of the variable. Paracrine: a local chemical messenger exerting effects only on nearby cells in the immediate vicinity of secretion. Phagocytosis: a type of endocytosis Plaque: a deposit of cholesterol and other lipids, perhaps calcified, in the thickened, abnormal smooth muscle with in blood vessels as a result of altherosclersis. Positive feedback: a regulatory mechanism in which the inputs and outputs in control system continue to enhance each other so that the variable moves further from steady state value. Purkinje fibers: Small terminal fibers that extend from the bundle of it is and rapidly transmit an action potential throughout the ventricular myocardium. Refractory period: Period when an activated membrane is refractory to further stimulation preventing action potential from spreading backward. Right atrium: the heart chamber that receive venous blood from the systemic circulation. Right Ventricle: the heart chamber that pumps blood in to the pulmonary circulation. Saltatory condition: propagation of action potential in a myelinated fiber with the impulse jumping from one node of Ranvier to another. Sarcoplasmic reticulum: reservoir of ionic calcium Second messenger: an intracellular chemical messenger activated by extracellular chemical that triggers preprogramed biochemical events, resulting in control of cellular activity. Signal transduction: The sequence of events, which carry signals from first chemical messenger conveyed to the cell. Vasoconstriction: the narrowing of a blood vessel lumen as a result of contraction of the vascular circular smooth muscle. Vasodilatation: the enlargement of a blood vessel lumen as a result of relaxation of the vascular circular smooth muscle. Venous return: the volume of blood returned to each atrium per minute from the veins. After this chapter the student is expected to: • relate the structural organization of the respiratory system to its function • describe the functional importance of the intraplueral fluid , the parietal and visceral pleura • know the structural and functional features that distinguish the respiratory zone of the airways from the conducting zone • define and describe the alveolar-capillary unit • know the definitions fractional concentrations (of dry gas) and partial pressure of gases • know the normal values of partial pressure of oxygen and carbondioxide in arterial and mixed venous blood • know how exchange of gases occur between the blood and tissues • know the control mechanisms involved in respiration Introduction The major functions of the respiratory system can be divided in two categories: respiratory and non-respiratory. The respiratory system must obtain oxygen from the environment and must eliminate carbondioxide produced by cellular metabolism. These processes must be coordinated so that the demand for oxygen is met and so that the carbondioxide that is produced is eliminated. The respiratory system is well designed to carry out gas exchange in an expeditious manner. It participates in + maintaining acid-base balance, since increase in Co2 in the body lead to increased H the lungs also metabolize naturally occurring compounds such as angiotensin I, 229 prostaglandins and epinephrine. Functional anatomy of the respiratory system Functionally, the respiratory air passages are divided into two zones: a conductive zone and a respiratory zone. The airway tree consists of a series of highly branched hollow tubes thatdecrease in diameter and become more numerous at each branching. Trachea, the main airwayin turn branches into two bronchi, one of which enters each lung. Within each lung, these bronchi branch many times into progressively smaller bronchi, which in turn branch into terminal bronchioles analogous to twigs of a tree. The terminal bronchioles redivide to form respiratory bronchioles, which end as alveoli, analogous to leaves on a tree. The conducting zone includes all of the anatomical structures through which air passes before reaching the respiratory zone. The conducting zone of the respiratory system, in summary consists of the following parts: Mouth→ nose→ pharynx→ larynx→ trachea→ primary bronchi→ all successive branches of bronchioles including terminal bronchioles. This ensures that a constant internal body temperature will be maintained and that delicate lung tissue will be protected from desiccation. Filtration and cleaning: Mucous secreted by the cells of the conducting zone serves to trap small particles in the inspired air and thereby performs a filtration function. This mucus is moved along at a rate of 1-2cm/min by cilia projecting from the tops of the epithelial cells that line the Conducting zone. There are about 300 cilia per cell that bend in a coordinated fashion to move mucus toward the pharynx, where it can either be swallowed or expectorated. As a result of this filtration function, particles larger than about 6μm do not enter the respiratory zone of the lungs.

Such distinction involves the notion of out- groups (organisms that are closely related to the group but not part of it) buy losartan 50 mg fast delivery. The choice of an outgroup constitutes an essential step order losartan 25 mg, since it can profoundly change the topology of a tree order 25 mg losartan with mastercard. Similarly 50 mg losartan free shipping, much attention is needed to distinguish between characters and character states prior to such analysis (e. A character state of a determined clade which is also present in its outgroups and its ancestor is designated as plesiomorphy (meaning “close form”, also called ancestral state). The character state which occurs only in later descendants is called an apomorphy (meaning “separate form”, also called the “derived” state). As only synapomor- phies are used to characterize clades, the distinction between plesiomorphic and synapomorphic character states is made by considering one or more outgroups. A collective set of plesiomorphies is commonly referred to as a ground plan for the clade or clades they refer to; and one clade is considered basal to another if it 54 Molecular Evolution of the Mycobacterium tuberculosis Complex holds more plesiomorphic characters than the other clade. Thus, conservative (apomorphic) branches, defined as anagenetic branches represent species whose characteristics are closer to those of the ancestor than others. Possibly, the founder of the genus Mycobacterium was a free-living organism and today’s free-living mycobacterial species (and also some saprophytic species? The more distant organisms are probably the ones that live in association with various multicellular organisms. It has been suggested that the mycobacteria that created a long-lasting association with marine animals (probably placoderms) are at the root of this phy- logenetic branch. Thus, Mycobacterium marinum would stem from the conserva- tive branch, whereas other vertebrate-associated mycobacteria would build the anagenetic branch. Grmek speculates that the association of a mycobacterial spe- cies with a marine vertebrate may have occurred during the superior Devonian (300 million years ago) (Grmek 1994). Figure 2-1: Phylogenetic position of the tubercle bacilli within the genus Mycobacterium (re- produced with permission from Gutierrez et al. A basic evolutionary scheme of mycobacteria 55 In the past, mycobacterial systematics used to rely on phenotypic characters; more recently, however, genetic techniques have boosted taxonomic studies (Tortoli 2003). The first natural characters used to distinguish between mycobacterial spe- cies were growth rate and pigmentation. Rapid growers (< 7 days) are free, envi- ronmental, saprophytic species, whereas slow growers are usually obligate intra- cellular, pathogenic species. In the ’50s, the hypothesis of co-evolution, or parallel evolution, between hosts and mycobacteria looked no more likely than the alternative hypothesis of «multiple, casual (furtive) introductions» of various saprophytes into different hosts. For example, the sequencing of the Mycobacterium leprae genome, by its defective nature, confirmed the previous history-driven hypothesis that M. The association of hyperdisease and endemic stability may have promoted a smooth and long-term transition from zoonosis to anthropozoonosis (Coleman 2001, Rotschild 2006b). If confirmed, these findings are new evidence that strain differences affect human interferon-based T cell responses (de Jong 2006). Strain-related differences in lymphokine (including interferon- gamma) response in mice with experimental infection were also reported in 2003 (Lopez 2003). The advent of molecular methods, and their widespread use in population studies, introduced both new conceptual and new technological developments. Our research group bet that the highly diverse signature patterns observed by spoligotyping could indeed contain phylogenetical signals, and the construction of a diversity database was started de novo (Sola 1999). The concept of endemic stability, already mentioned above, suggests that an infec- tious disease may reach an epidemiological state in which the clinical disease is scarce, despite high levels of infection in the population (Coleman 2001). The question of how many isolated communities of between 180 to 440 persons may have experienced, sequentially or concomitantly, the introduction of one or more founding genotypes of M. To provide the initial conditions of a dynamic epidemic system we must understand how these early founding genotypes spread in low demographic conditions. Today, we can observe a phylogeographically structured global epidemic, built as a result of millennia of evolution. One recent success of the first strategy is exemplified by the finding of a peculiar highly genetically diverse “M. Figure 2-3 shows an ancient Egyptian clay arte- 60 Molecular Evolution of the Mycobacterium tuberculosis Complex fact with a traditional kyphosis suggestive of Pott’s disease. Taken together, these results may argue that the limited number of different genogroups that we observe today are likely to stem from those that were seeded in the past, have re- mained isolated by distance during millennia, and have had time to co-evolve inde- pendently before gaining reasonable statistical chances to meet. The term was introduced as a way to bridge population genetics and molecular ecology and to describe geographically structured signals within species. The geographic distribution of bacteriophage types was the only method to detect the geographic subdivision of the M. The im- portance of lateral genetic transfer in one species’ history is of primary importance to better understand its specificity.

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The patient is positioned in such a way that the organ to be examined remains at the centre of the machine order 50mg losartan with amex. Here the X-Rays are not used buy discount losartan 50mg on line, instead radio frequency waves and strong magnetic field are used discount 25mg losartan visa, this eliminates the fear of harmful radiation 50mg losartan with amex. Each cell has a different number of protons and with the help of radio signals and advanced computers one can accurately calculate the various numbers of protons and thus differentiate each and every type of cell which can be photographed from every angle, with the help of a laser camera on a 14" x 17" photo film. Thus, in 30 to 45 minutes, 80 to 100 photographs of the brain from the different angles (X, Y, Z, axis) can be taken, which an expert radiologist analyzes and a report is given. In some diseases, a special drug (contrast) has to be used to specify some defects; this drug has very few side effects. This makes the diagnosis of hampered blood circulation in any part of the brain in minutes, so prompt treatment can prevent disease like paralysis. The important centers in the brain can be avoided during surgery and the patient can be saved from permanent disability. Angiography is the examination of the arteries and veins that carry blood to the various parts of the body. With the help of X-Ray and the computer monitor, the catheter is made to enter the vessels of the brain. As the drug enters the bloodstream, its progression in the blood vessels is seen live on a monitor and if necessary, with the help of X-Rays the blood vessels are also visualized from various angles. Another X- Ray is taken after the introduction of the contrast medium and the differences in the vessels and brain seen in both the X-Rays are used for diagnosis. If the Lumen of the carotid artery, which passes across the neck and supplies blood to the brain, becomes narrow due to arteriosclerosis, it can be widened with the help of a balloon. The investigation of the blood vessels is possible by totally non-risky methods too, but the information gained by them is 5-10% less accurate. The diameter of the Artery, the pressure flow of the blood and the deposits in the wall can be determined easily using simple Sonography. Science, technology and the modern computers have brought innovative advancements in the field of radiology at a very fast pace. The invention of the radiation and the X-rays is not only important in the field of health, but is useful in other sectors too. Stupor, partial loss of consciousness, or long deep sleep, all these words signify varying state of the altered consciousness of the brain and body. In medical science, Coma is defined as a state in which the brain loses its alertness and the body stops responding to any inner or external stimuli and stops experiencing even the basic necessities. If this state continues for a long period of time or till death, the patient can be termed a Coma-patient. The fear psychosis that has been created by this word is not really justified as coma is not always so dangerous, but at the same time it is not to be taken too lightly either. It is more common now, due to high blood pressure caused by the modern day lifestyle, habits and stress, diabetes, and road accidents etc. Diseases related to blood circulation of the brain : Thrombosis (clotting of blood in the vessels), Embolism, Hemorrhage, and Sub-arachnoid Hemorrhage. Brain Tumor: Cancerous tumors (primary or secondary) like Glioma or Metastasis, simple tumors like meningioma. In all these tumors, symptoms like headaches, vertigo, convulsions, vomiting, and paralysis of one or both the sides are seen. Oxygen deficiency, fluctuation in the blood sugar level, liver diseases, kidney diseases, respiratory disorders etc. Hormonal Imbalance: Imbalance in the hormones of thyroid, parathyroid, adrenal, pituitary glands can also lead to coma. Poison: Organophospherous poisoning or heavy metals like arsenic or lead used for murder or suicide, overdose of sleeping pills, can also lead to coma. Psychogenic Coma: (the patient is not actually in coma) The treatment of coma should be done systematically. Usually, the patient is thoroughly examined and his/her history, pulse, temperature, respiration are noted. Before a coma patient is considered brain dead, the brain death has to be ascertained very carefully and the rules and regulations made specifically for this purpose are to be followed before declaring it. In this situation, the brain never regains consciousness, so such a patient can donate his/her kidney and other parts to save the life of another patient before his/her heart stops functioning. Immediate treatment is initiated to normalise important functions like respiration, blood circulation, blood pressure. If the cause is unknown, immediate glucose, vitamin B1 and injection Nalorphine are administered as the first line of treatment: 4.

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Intrinsic Pathway The intrinsic pathway (also known as the contact activation pathway) is longer and more complex purchase losartan 50mg free shipping. Common Pathway Both the intrinsic and extrinsic pathways lead to the common pathway order losartan 25mg mastercard, in which fibrin is produced to seal off the vessel buy discount losartan 50mg online. As these proteins contract order losartan 50 mg fast delivery, they pull on the fibrin threads, bringing the edges of the clot more tightly together, somewhat as we do when tightening loose shoelaces (see Figure 18. This process also wrings out of the clot a small amount of fluid called serum, which is blood plasma without its clotting factors. During this process, the inactive protein plasminogen is converted into the active plasmin, which gradually breaks down the fibrin of the clot. Additionally, bradykinin, a vasodilator, is released, reversing the effects of the serotonin and prostaglandins from the platelets. This allows the smooth muscle in the walls of the vessels to relax and helps to restore the circulation. Several circulating plasma anticoagulants play a role in limiting the coagulation process to the region of injury and restoring a normal, clot-free condition of blood. For instance, a cluster of proteins collectively referred to as the protein C system inactivates clotting factors involved in the intrinsic pathway. And as noted earlier, basophils release heparin, a short-acting anticoagulant that also opposes prothrombin. A pharmaceutical form of heparin is often administered therapeutically, for example, in surgical patients at risk for blood clots. The coagulation cascade restores hemostasis by activating coagulation factors in the presence of an injury. How does the endothelium of the blood vessel walls prevent the blood from coagulating as it flows through the blood vessels? Disorders of Clotting Either an insufficient or an excessive production of platelets can lead to severe disease or death. As discussed earlier, an insufficient number of platelets, called thrombocytopenia, typically results in the inability of blood to form clots. Another reason for failure of the blood to clot is the inadequate production of functional amounts of one or more clotting factors. This is the case in the genetic disorder hemophilia, which is actually a group of related disorders, the most common of which is hemophilia A, accounting for approximately 80 percent of cases. Patients with hemophilia bleed from even minor internal and external wounds, and leak blood into joint spaces after exercise and into urine and stool. It is not a true recessive condition, since even individuals with a single copy of the mutant gene show a tendency to bleed. Regular infusions of clotting factors isolated from healthy donors can help prevent bleeding in hemophiliac patients. In contrast to the disorders characterized by coagulation failure is thrombocytosis, also mentioned earlier, a condition characterized by excessive numbers of platelets that increases the risk for excessive clot formation, a condition known as thrombosis. While the formation of a clot is normal following the hemostatic mechanism just described, thrombi can form within an intact or only slightly damaged blood vessel. In a large vessel, a thrombus will adhere to the vessel wall and decrease the flow of blood, and is referred to as a mural thrombus. In a small vessel, it may actually totally block the flow of blood and is termed an occlusive thrombus. Thrombi are most commonly caused by vessel damage to the endothelial lining, which activates the clotting mechanism. These may include venous stasis, when blood in the veins, particularly in the legs, remains stationary for long periods. This is one of the dangers of long airplane flights in crowded conditions and may lead to deep vein thrombosis or atherosclerosis, an accumulation of debris in arteries. Thrombophilia, also called hypercoagulation, is a condition in which there is a tendency to form thrombosis. Acquired forms include the autoimmune disease lupus, immune reactions to heparin, polycythemia vera, thrombocytosis, sickle cell disease, pregnancy, and even obesity. A thrombus can seriously impede blood flow to or from a region and will cause a local increase in blood pressure. If flow is to be maintained, the heart will need to generate a greater pressure to overcome the resistance. When a portion of a thrombus breaks free from the vessel wall and enters the circulation, it is referred to as an embolus. An embolus that is carried through the bloodstream can be large enough to block a vessel critical to a major organ. In the heart, brain, or lungs, an embolism may accordingly cause a heart attack, a stroke, or a pulmonary embolism. Physicians sometimes recommend that patients at risk for cardiovascular disease take a low dose of aspirin 810 Chapter 18 | The Cardiovascular System: Blood on a daily basis as a preventive measure. A class of drugs collectively known as thrombolytic agents can help speed up the degradation of an abnormal clot. If a thrombolytic agent is administered to a patient within 3 hours following a thrombotic stroke, the patient’s prognosis improves significantly.

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Teratogenicity means congenital malformation i) Drugs known to produce teratogenicity e cheap losartan 50 mg on line. Therefore the drugs buy losartan 50mg without prescription, which are excreted in the milk and harm the infant health should be cheap losartan 25 mg otc, avoided by breast-feeding mothers e losartan 25 mg mastercard. Body Weight: The average dose is mentioned either in terms of mg per kg body weight or as the total single dose for an adult weighing between 50-100kg. However, dose expressed in this fashion may not apply in cases of excessively obese individuals or those suffering from edema, or dehydration nutritional factors can sometimes alter drug metabolizing capacity and this should be kept in mind in malnourished patients. Thus gastric emptying is prolonged and the gastric pH fluctuates in neonates and infant, further the liver capacity to metabolize drugs is low, renal function is less developed and the proportion of body water is higher in the newborn and the neonates. With a few exceptions, drugs are more active and more toxic in the new born than the adults. Like children, old people also present problems in dosage adjustment and this may vary widely with different people. The metabolism of drugs may diminish in the elderly and the renal function declines with age. Elderly are sensitive to the drugs like hypnotics, tranquilizers, phenylbutazone, diazepam, pethidine, etc. So a) Using age of the child the dose will be 3 x 10 = 3 x100 = 20mg 3+12 15 b) Using body weight of the child it will be 30 x 100 = 1 x 100 = 20mg 150 5 5. Disease state: Some antimicrobial agents penetrate the cerebrospinal fluid well across the normal meninges while other antimicrobials penetrate well only when the meninges are inflammed (meningitis) e. Acute or chronic liver diseases markedly modify the rate and extent of biotransformation of drugs. The t1/2 of chlordiazepoxide and diazepam in patients with liver cirrhosis is greatly increased with corresponding prolongation of their effects. Cardiac disease by limiting blood flow to the liver may impair disposition of those drugs whose biotransformation is flow limited e. Pharmacogenetics: The science pharmacogenetics is concerned with the genetically- mediated variations in drug responses. It is a phenomenon which occurs when the effects of one drug are modified by the prior or concurrent administration of another drug(s). A drug interaction may result in beneficial or harmful effects and may be classified into: a) Pharmaceutical drug interactions: Serious loss of potency can occur from incompatibility between an infusion fluid and a drug that is added to it. For example diazepam if added to infusion fluid there will be a precipitate formation → loss of therapeutic effect. If the drug A is metabolized by the microsomal enzymes, then concurrent administration with a microsomal inducer (drug B) will result in enhanced metabolism of drug A. Warfarin (anticoagulant) + Barbiturate (enzyme inducer) → decreased anticoagulation. Penicillin (antibiotic) + Probenecid (antigout drug) → Increases the duration of action of penicillin (Both drugs excreted through tubular secretion). Pharmacodynamic interactions: (i) Drug Synergism: When the therapeutic effect of two drugs are greater than the effect of individual drugs, it is said to be drug synergism. Trimethoprim+sulfamethoxazole 23 (iii) Drug Antagonism: The phenomenon of opposing actions of two drugs on the same physiological system is called drug antagonism. Competitive antagonism can be overcome by increasing the concentration of the agonist at the receptor site. Acetyl choline causes constriction where as adrenaline causes dilatation of pupil. Importance of drug antagonism (i) Correcting adverse effects of drugs (ii) Treating drug poisoning. Tachyphylaxis: Rapid development of tolerance on repeated administration is called tachyphylaxis e. Ephedrine, amphetamine and nitroglycerine which produce tachyphylaxis on repeated administration. Placebo: It is a Latin word meaning” I shall please” and it is a tablet looking exactly like the active treatment but containing no active component. It refers originally to substances merely to please the patient when no specific treatment was available. Adverse drug reactions: The drugs that produce useful therapeutic effect may also produce unwanted or toxic effects. If is always an exaggeration of its pharmacological actions and some times it is predictable. The adverse effects are 1)Side effects 2)untoward effects 3)allergic reactions 4)idiosyncratic reactions and 5)teratogenic effects.

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