Aayesha

Endocrinology

PBL - Day 1
1. Causes of Skin Hyperpigmentation
In dermatology, hyperpigmentation is the darkening of an area of skin or nails caused by increased melanin. Hyperpigmentation may be caused by sun damage, inflammation, or other skin injuries, including those related to acne vulgaris.[1] People with darker Asian, Mediterranean, or African skin tones are also more prone to hyperpigmentation, especially if they have excess sun exposure. Many forms of hyperpigmentation are caused by an excess production of melanin. Hyperpigmentation can be diffuse or focal, affecting such areas as the face and the back of the hands. Melanin is produced by melanocytes at the lower layer of the epidermis. Melanin is a class of pigment responsible for producing color in the body in places such as the eyes, skin, and hair. As the body ages, melanocyte distribution becomes less diffuse and its regulation less controlled by the body. UV light stimulates melanocyte activity, and where concentrations of the cells are denser than surrounding areas, hyperpigmentation is effected.[2] Can also be caused by using skin lightening lotions. Another form of hyperpigmentation is Post inflammatory hyperpigmentation. These are dark and discolored spots that appear on your skin following acne that has healed.[3] Hyperpigmentation is associated with a number of diseases or conditions, including but not limited to the following: Addison's disease and other sources of adrenal insufficiency, in which hormones that stimulate melanin synthesis, such as melanocyte-stimulating hormone (MSH), are frequently elevated. Cushing's disease or other excessive adrenocorticotropic hormone (ACTH) production, because MSH production is a byproduct of ACTH synthesis from proopiomelanocortin (POMC). Acanthosis nigricans hyperpigmentation of intertriginous areas associated with insulin resistance. Melasma, also known as chloasma patchy hyperpigmentation often found in pregnant women. Linea nigra a hyperpigmented line found on the abdomen during pregnancy. Peutz-Jeghers syndrome an autosomal dominant disorder characterized by hyperpigmented macules on the lips and oral mucosa and gastrointestinal polyps. Exposure to certain chemicals such as salicylic acid, bleomycin, and cisplatin. Smoker's melanosis Celiac disease Cronkite-Canada syndrome Porphyria Tinea fungal infections such as ringworm Haemochromatosis - a common but debilitating genetic disorder characterized by the chronic accumulation of iron in the body. Mercury poisoning - particularly cases of cutaneous exposure resulting from the topical application of mercurial ointments or skin-whitening creams. Aromatase deficiency Nelson's syndrome Hyperpigmentation can sometimes be induced by dermatological laser procedures.

2. Causes of Syncope
Central nervous system ischaemia The central ischaemic response is triggered by an inadequate supply of oxygenated blood in the brain.
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The respiratory system may contribute to oxygen levels through hyperventilation, though a sudden ischaemic episode may also proceed faster than the respiratory system can respond. These processes cause the typical symptoms of fainting: pale skin, rapid breathing, nausea and weakness of the limbs, particularly of the legs. If the ischaemia is intense or prolonged, limb weakness progresses to collapse. An individual with very little skin pigmentation may appear to have all color drained from his or her face at the onset of an episode. This effect combined with the following collapse can make a strong and dramatic impression on bystanders. The weakness of the legs causes most sufferers to sit or lie down if there is time to do so. This may avert a complete collapse, but whether the sufferer sits down or falls down, the result of an ischaemic episode is a posture in which less blood pressure is required to achieve adequate blood flow. It is unclear whether this is a mechanism evolved in response to the circulatory difficulties of human bipedalism or merely a serendipitous result of a pre-existing circulatory response. Vertebro-basilar arterial disease Arterial disease in the upper spinal cord, or lower brain, causes syncope if there is a reduction in blood supply, which may occur with extending the neck or after drugs to lower blood pressure. Vasovagal Vasovagal (situational) syncope, one of the most common types, may occur in scary, embarrassing or uneasy situations, or during blood drawing, coughing, urination or defecation. Other types include postural syncope (caused by a change in body posture), cardiac syncope (due to heart-related conditions), and neurological syncope (due to neurological conditions). There are many other causes of syncope, including low blood-sugar levels and lung disease such as emphysema and a pulmonary embolus. The cause of the fainting can be determined by a doctor using a complete history, physical, and various diagnostic tests. The vasovagal type can be considered in two forms: Isolated episodes of loss of consciousness, unheralded by any warning symptoms for more than a few moments. These tend to occur in the adolescent age group, and may be associated with fasting, exercise, abdominal straining, or circumstances promoting vaso-dilation (e.g., heat, alcohol). The subject is invariably upright. The tilt-table test, if performed, is generally negative. Recurrent syncope with complex associated symptoms. This is so-called Neurally Mediated Syncope (NMS). It is associated with any of the following: preceding or succeeding sleepiness, preceding visual disturbance ("spots before the eyes"), sweating, light-headedness. The subject is usually but not always upright. The tilt-table test, if performed, is generally positive. A pattern of background factors contributes to the attacks. There is typically an unsuspected relatively low blood volume, for instance, from taking a low-salt diet in the absence of any salt-retaining tendency. Heat causes vaso-dilation and worsens the effect of the relatively insufficient blood volume. That sets the scene, but the next stage is the adrenergic response. If there is underlying fear or anxiety (e.g., social circumstances), or acute fear (e.g., acute threat, needle phobia), the vaso-motor centre demands an increased pumping action by the heart (flight or fight response). This is set in motion via the adrenergic (sympathetic) outflow from the brain, but the heart is unable to meet requirement because of the low blood volume, or decreased return. The high (ineffective) sympathetic activity is always modulated by vagal outflow, in these cases leading to excessive slowing of heart rate. The abnormality lies in this excessive vagal response. The tilt-table test typically evokes the attack. Much of this pathway was discovered in animal experiments by Bezold (Vienna) in the 1860s. In animals, it may represent a defence mechanism when confronted by danger ("playing possum"). This reflex occurs in only some people and may be similar to that described in other animals.

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The mechanism described here suggests that a practical way to prevent attacks might seem to be counterintuitive, specifically to block the adrenergic signal with a beta-blocker. A simpler plan might be to explain the mechanism, discuss causes of fear, and optimise salt as well as water intake.[citation needed] Psychological factors also have been found to mediate syncope. It is important for general practitioners and the psychologist in their primary care team to work closely together, and to help patients identify how they might be avoiding activities of daily living due to anticipatory anxiety in relation to a possible faint and the feared physical damage it may cause. Fainting in response to a blood stimulus, needle or a dead body are common and patients can quickly develop safety behaviours to avoid any recurrences of a fainting response. See link for a good description of psychological interventions and theories.[4] An evolutionary psychology view is that some forms of fainting are non-verbal signals that developed in response to increased inter-group aggression during the paleolithic. A non-combatant who has fainted signals that she or he is not a threat. This would explain the association between fainting and stimuli such as bloodletting and injuries seen in blood-injection-injury type phobias such as trypanophobia as well as the gender differences. Deglutition (Swallowing) syncope Syncope may occur during deglutition. Manisty et al. note: "Deglutition syncope is characterised by loss of consciousness on swallowing; it has been associated not only with ingestion of solid food, but also with carbonated and ice-cold beverages, and even belching." Cardiac Cardiac arrhythmias Most common cause of cardiac syncope. Two major groups of arrhythmias are bradycardia and tachycardia. Bradycardia can be caused by heart blocks. Tachycardias include SVT (supraventricular tachycardia) and VT (ventricular tachycardia). SVT does not cause syncope except in Wolff-ParkinsonWhite syndrome. Ventricular tachycardia originate in the ventricles. VT causes syncope and can result in sudden death. Ventricular tachycardia, which describes a heart rate of over 100 beats per minute with at least three irregular heartbeats as a sequence of consecutive premature beats, can degenerate into ventricular fibrillation, which requires DC cardioversion.[citation needed] Typically, tachycardic generated syncope is caused by a cessation of beats following a tachycardic episode. This condition, called tachycardia-bradycardia syndrome, is usually caused by sinoatrial node dysfunction or block or atrioventricular block. Obstructive cardiac lesion Aortic stenosis and mitral stenosis are the most common examples. Aortic stenosis presents with repeated episodes of syncope. A pulmonary embolism can cause obstructed blood vessels. High blood pressure in the arteries supplying the lungs (pulmonary artery hypertension) can occur during pulmonary embolism. Rarely, cardiac tumors such as atrial myxomas can also lead to syncope. Structural cardiopulmonary disease These are relatively infrequent causes of faints. The most common cause in this category is fainting associated with an acute myocardial infarction or ischemic event. The faint in this case is primarily caused by an abnormal nervous system reaction similar to the reflex faints. In general, faints caused by structural disease of the heart or blood vessels are particularly important to recognize, as they are warning of potentially life-threatening conditions. Among other conditions prone to trigger syncope (by either hemodynamic compromise or by a neural reflex mechanism, or both), some of the most important are hypertrophic cardiomyopathy, acute aortic dissection, pericardial tamponade, pulmonary embolism, aortic stenosis, and pulmonary hypertension.

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Other cardiac causes Sick sinus syndrome, a sinus node dysfunction, causing alternating bradycardia and tachycardia. Often there is a long pause asystole between heartbeat. Adams-Stokes syndrome is a cardiac syncope which may occur with seizures caused by complete or incomplete heart block. Symptoms include deep and fast respiration, weak and slow pulse and respiratory pauses that may last for 60 seconds. Aortic dissection (a tear in the aorta) and cardiomyopathy can also result in syncope.[7] Various medications, such as -blockers, may cause bradycardia induced syncope.[1] Blood pressure Orthostatic (postural) hypotensive faints are as common or perhaps even more common than vasovagal syncope. Orthostatic faints are most often associated with movement from lying or sitting to a standing position. Apparently healthy individuals may experience minor symptoms ("lightheadedness", "greying-out") as they stand up if blood pressure is slow to respond to the stress of upright posture. If the blood pressure is not adequately maintained during standing, faints may develop. However, the resulting "transient orthostatic hypotension" does not necessarily signal any serious underlying disease. The most susceptible individuals are elderly frail individuals, or persons who are dehydrated from hot environments or inadequate fluid intake. More serious orthostatic hypotension is often the result of certain commonly prescribed medications such as diuretics, -adrenergic blockers, other anti-hypertensives (including vasodilators), and nitroglycerin. In a small percentage of cases, the cause of orthostatic hypotensive faints is structural damage to the autonomic nervous system due to systemic diseases (e.g., amyloidosis or diabetes) or in neurological diseases (e.g., Parkinson's disease). Other causes Factors that influence fainting are fasting long hours, taking in too little food and fluids, low blood pressure, hypoglycemia, high g-force, emotional distress, and lack of sleep. Orthostatic hypotension caused by standing up too quickly or being in a very hot room can also cause fainting. The classic example of a combination of these is seen in the frequent fainting by medical students in the operating theatre during observation of surgery.[8] More serious causes of fainting include cardiac (heart-related) conditions such as an abnormal heart rhythm (an arrhythmia), wherein the heart beats too slowly, too rapidly, or too irregularly to pump enough blood to the brain. Some arrhythmias can be life-threatening. Other important cardio-vascular conditions that can be manifested by syncope include subclavian steal syndrome and aortic stenosis.

3. Lines of Anti-TB Therapy

With appropriate antibiotic treatment, TB can be cured in most people. Successful treatment of TB depends on close cooperation between patients and healthcare providers. Treatment usually involves taking several antibiotic drugs for at least 6 months and sometimes for as long as 12 months. Antibiotic Resistance and the Importance of Finishing the TB Medicine People who do not take all the required medicines can become sick again and spread TB to others. Additionally, when people do not take all the prescribed medicines or skip times when they are supposed to take them, the TB bacteria evolve to outwit the TB antibiotics. Soon those medicines no longer work against the disease. If this happens, the person now has drug-resistant TB. Additionally, some people with

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TB do not get better with treatment because their disease is caused by a strain of the TB bacterium that is already resistant to one or more of the standard TB drugs. Multidrug-resistant TB (MDR TB) is TB that is resistant to at least two of the best Food and Drug Administration-approved anti-TB drugs, isoniazid and rifampicin. These antibiotics are considered firstline drugs and are the first medicines used to treat all persons with TB disease. Extensively drug-resistant TB (XDR TB) is a relatively rare type of TB that is resistant to isoniazid and rifampin, plus any fluoroquinolone and at least one of three injectable second-line drugs (such as amikacin, kanamycin, or capreomycin). Worldwide, TB drug resistance is on the rise. In 2010, the World Health Organization estimated that more than 650,000 people have MDR TB. Treatment for Drug Resistant TB Treatment for drug-resistant TB often requires the use of special TB drugs, all of which can produce serious side effects. People with MDR TB may have to take several antibiotics, at least three to which the bacteria still respond, every day for up to two years. Even with this treatment, however, between 4 and 6 out of 10 patients with MDR TB will die, which is the same rate seen with TB patients who are not treated. Because XDR TB is resistant to first-line and second-line drugs, patients are left with limited treatment options that are much less effective. Infection Control Hospitals and clinics take precautions to prevent the spread of TB, which include identifying patients with suspected TB and using ultraviolet light to sterilize the air, special filters, and special respirators and masks. In hospitals, people with TB are isolated in special rooms with controlled ventilation and airflow until they can no longer spread TB bacteria. By having an infection control plan in place, healthcare settings can ensure the prompt detection and treatment of persons who have suspected or confirmed TB disease.

First line All first-line anti-tuberculous drug names have a standard three-letter and a single-letter abbreviation: Ethambutol is EMB or E, isoniazid is INH or H, pyrazinamide is PZA or Z, rifampicin is RMP or R, Streptomycin is no longer considered as a first line drug by ATS/IDSA/CDC because of high rates of resistance.[1] The US uses abbreviations and names that are not internationally recognised: rifampicin is called rifampin and abbreviated RIF; streptomycin is abbreviated STM. Drug regimens are similarly abbreviated in a standardised manner. The drugs are listed using their single letter abbreviations (in the order given above, which is roughly the order of introduction into clinical practice). A prefix denotes the number of months the treatment should be given for; a subscript denotes intermittent dosing (so 3 means three times a week) and no subscript means daily dosing. Most regimens have an initial high-intensity phase, followed by a continuation phase (also called a consolidation phase or eradication phase): the high-intensity phase is given first, then the continuation phase, the two phases divided by a slash. So, 2HREZ/4HR3

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means isoniazid, rifampicin, ethambutol, pyrazinamide daily for two months, followed by four months of isoniazid and rifampicin given three times a week. These standard abbreviations are used in the rest of this article. Second line The second line drugs are considered as the reserved therapy for tuberculosis treatment. These drugs are often used in special conditions. When situations like resistance to first line therapy, extensively drugresistant tuberculosis (XDR-TB) or multidrug-resistant tuberculosis (MDR-TB) arise, the second-line drugs are implemented for the treatment of tuberculosis.[2] There are six classes of second-line drugs (SLDs) used for the treatment of TB. A drug may be classed as second-line instead of first-line for one of three possible reasons: it may be less effective than the first-line drugs (e.g., p-aminosalicylic acid); or, it may have toxic side-effects (e.g., cycloserine); or it may be unavailable in many developing countries (e.g., fluoroquinolones): aminoglycosides: e.g., amikacin (AMK), kanamycin (KM); polypeptides: e.g., capreomycin, viomycin, enviomycin; Fluoroquinolones: e.g., ciprofloxacin (CIP), levofloxacin, moxifloxacin (MXF); thioamides: e.g. ethionamide, prothionamide cycloserine: e.g., closerin Terizidone: Third line Other drugs that may be useful, but are not on the WHO list of SLDs: rifabutin macrolides: e.g., clarithromycin (CLR); linezolid (LZD); thioacetazone (T); thioridazine; arginine; vitamin D; R207910. These drugs may be considered "third-line drugs" and are listed here either because they are not very effective (e.g., clarithromycin) or because their efficacy has not been proven (e.g., linezolid, R207910). Rifabutin is effective, but is not included on the WHO list because for most developing countries, it is impractically expensive.

4. Control of Blood Pressure (Physiology)

5. Causes of Hypotension
Conditions that can cause low blood pressure Some medical conditions can cause low blood pressure. These include: Pregnancy. Because a woman's circulatory system expands rapidly during pregnancy, blood pressure is likely to drop. During the first 24 weeks of pregnancy, systolic pressure commonly drops by five to 10 mm Hg and diastolic pressure by as much as 10 to 15 mm Hg. This is normal, and blood pressure usually returns to your pre-pregnancy level after you've given birth.
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Heart problems. Some heart conditions that can lead to low blood pressure include extremely low heart rate (bradycardia), heart valve problems, heart attack and heart failure. These conditions may cause low blood pressure because they prevent your body from being able to circulate enough blood. Endocrine problems. An underactive thyroid (hypothyroidism) or overactive thyroid (hyperthyroidism) can cause low blood pressure. In addition, other conditions, such as adrenal insufficiency (Addison's disease), low blood sugar (hypoglycemia) and, in some cases, diabetes, can trigger low blood pressure. Dehydration. When you become dehydrated, your body loses more water than it takes in. Even mild dehydration can cause weakness, dizziness and fatigue. Fever, vomiting, severe diarrhea, overuse of diuretics and strenuous exercise can all lead to dehydration. Far more serious is hypovolemic shock, a life-threatening complication of dehydration. It occurs when low blood volume causes a sudden drop in blood pressure and a reduction in the amount of oxygen reaching your tissues. If untreated, severe hypovolemic shock can cause death within a few minutes or hours. Blood loss. Losing a lot of blood from a major injury or internal bleeding reduces the amount of blood in your body, leading to a severe drop in blood pressure. Severe infection (septicemia). Septicemia can happen when an infection in the body enters the bloodstream. These conditions can lead to a life-threatening drop in blood pressure called septic shock. Severe allergic reaction (anaphylaxis). Anaphylaxis is a severe and potentially life-threatening allergic reaction. Common triggers of anaphylaxis include foods, certain medications, insect venoms and latex. Anaphylaxis can cause breathing problems, hives, itching, a swollen throat and a drop in blood pressure. Lack of nutrients in your diet. A lack of the vitamins B-12 and folate can cause anemia, a condition in which your body doesn't produce enough red blood cells, causing low blood pressure.

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