Intrinsic factor is essential for the absorption of the small amounts of vitamin B12 normally present in the diet from the terminal ileum. The parietal cells of the stomach produce intrinsic factor, and following a gastrectomy, the absorption of vitamin B12 will be markedly reduced, and a deficiency state will exist.

Atracurium is a non-depolarizing neuromuscular blocker that is used to help with intubation and controlled ventilation by causing muscle relaxation and paralysis. At the neuromuscular junction’s post-synaptic membrane, atracurium competes with acetylcholine for nicotinic (N2) receptor binding sites. This prevents the receptors from being stimulated by acetylcholine. Muscle paralysis occurs gradually due to the competitive blockade.

Cholera has an incubation period of 12 hours to 6 days.Other infectious disease that have an incubation period of less than 1 week include:Staphylococcal enteritis (1-6 hours)Salmonella enteritis (12-24 hours)Botulism (18-36 hours)Gas gangrene (6 hours to 4 days)Scarlet fever (1-4 days)Diphtheria (2-5 days)Gonorrhoea (3-5 days)Yellow fever (3-6 days)Meningococcaemia (1-7 days)Brucellosis has an incubation period of 7-21 days.Measles has an incubation period of 14-18 days.Falciparum malaria usually has an incubation period of 7-14 days. The other forms of malaria have a longer incubation period of 12-40 days.Rubella has an incubation period of 14-21 days.

Ketamine is a non-competitive antagonist of the calcium-ion channel in the NMDA (N-methyl-D-aspartate) receptor. It further inhibits the NMDA-receptor by binding to its phencyclidine binding site. Ketamine also acts at other receptors as an opioid receptor agonist (analgesic effects), as an muscarinic anticholinergic receptor antagonist (antimuscarinic effects) and by blocking fast sodium channels (local anaesthetic effect).Overdose may lead to panic attacks and aggressive behaviour; rarely seizures, increased ICP, and cardiac arrestVery similar in chemical makeup to PCP (phencyclidine), but it is shorter acting and less toxic

Laboratory results often show that:PFA-100 test results are abnormal.Low levels of factor VIII (if a factor VIII/VWF binding assay is conducted)APTT is Prolonged (or normal)PT is normalVWF values are low.Defective Platelet aggregationThe platelet count is normal.

Osteoclasts are a type of bone cell that breaks down bone tissue. This is a critical function in the maintenance, repair and remodelling of bones. The osteoclast disassembles and digests the composite of hydrated protein and minerals at a molecular level by secreting acid and collagenase. This process is known as bone resorption and also helps to regulate the plasma calcium concentration.Osteoclastic activity is controlled by a number of hormones:1,25-dihydroxycholecalciferol increases osteoclastic activityParathyroid hormone increases osteoclastic activityCalcitonin inhibits osteoclastic activityBisphosphonates are a class of drug that slow down and prevent bone damage. They are osteoclast inhibitors.

Hepatitis B surface antigen (HBsAg) is a protein on the surface of the hepatitis B virus, that is the first serologic marker to appear in a new acute infection.It can be detected as early as 1 week and as late as 9 weeks. It can be detected in high levels in serum during acute or chronic hepatitis B virus infection. The presence of HBsAg indicates that the person is infectious. The body normally produces antibodies to HBsAg as part of the normal immune response to infection. HBsAg is the antigen used to make hepatitis B vaccine.Hepatitis B surface antibody (anti-HBs) indicates recovery and immunity from the hepatitis B virus infection. Anti-HBs also develops in a person who has been successfully vaccinated against hepatitis B.Total hepatitis B core antibody (anti-HBc): Appears at the onset of symptoms in acute hepatitis B and persists for life. The presence of anti-HBc indicates previous or ongoing infection with hepatitis B virus in an undefined time frame. It is not present following hepatitis B vaccination.IgM antibody to hepatitis B core antigen (IgM anti-HBc) indicates recent infection with hepatitis B virus (<6 months). Its presence indicates acute infection.The following table summarises the presence of hepatitis B markers according to each situation:Susceptible to infection:HBsAg = NegativeAnti-HBc = NegativeAnti-HBs = NegativeImmune due to natural infection:HBsAg = NegativeAnti-HBc = PositiveAnti-HBs = PositiveImmune due to vaccination:HBsAg = NegativeAnti-HBc = NegativeAnti-HBs = PositiveAcute infection:HBsAg = PositiveAnti-HBc = PositiveAnti-HBs = NegativeIgM anti-HBc = PositiveChronic infection:HBsAg = PositiveAnti-HBc = PositiveAnti-HBs = NegativeIgM anti-HBc = Negative

Hyoscine butylbromide is an antispasmodic drug that blocks muscarinic receptors and reduces intestinal motility. It is used for gastrointestinal and genitourinary smooth muscle spasms and symptomatic relief of IBS.It has the following contraindications: 1. Closed-angle glaucoma2. Gastrointestinal obstruction3. Intestinal atony4. Paralytic ileus5. Toxic megacolon6. Severe ulcerative colitis7. Significant bladder outflow obstruction8. Urinary retention9. Myasthenia gravisUse cautiously in the following conditions: 1. Acute myocardial infarction (in adults)2. Arrhythmias (may be worsened)3. Autonomic neuropathy4. Hypertension5. Cardiac insufficiency (due to association with tachycardia)6. Congestive cardiac failure (maybe worsened)7. Cardiac surgery (due to association with tachycardia)8. Gastro-oesophageal reflux disease9. Ulcerative colitis10. Prostatic hyperplasia11. Use in children (increased risk of side effects)

The NICE guidelines for pregnant women with lower UTIs are:1. Prescribe an antibiotic immediately, taking into account the previous urine culture and susceptibility results or avoiding past antibiotics that may have caused resistance2. Obtain a midstream urine sample before starting antibiotics and send for urine culture and susceptibility – Review the choice of antibiotic when the results are available – change the antibiotic according to susceptibility results if the bacteria are resistant, using a narrow-spectrum antibiotic wherever possibleThe first choice of antibiotics for pregnant women aged 12 years and over is:1. Nitrofurantoin100 mg modified-release PO BD for 3 days – if eGFR >45 ml/minuteThe second-choice (no improvement in lower UTI symptoms on first-choice for at least 48 hours, or when first-choice is not suitable) are:1. Amoxicillin 500 mg PO TDS for seven days (ONLY if culture results available and susceptible)2. Cefalexin500 mg BD for seven daysAlternative second-choices – consult local microbiologist, choose antibiotics based on culture and sensitivity results

The commonest implicated organisms in hospital-acquired bacteraemia following cannulation are Staphylococcus aureus and Staphylococcus epidermidis. The risk is directly proportional to the length of time in-situ. Peripheral cannula should be replaced after 48 hours.

Axons from the lateral geniculate nucleus (LGN) carry visual information, via the upper and lower optic radiations, to the visual cortex in the occipital lobe:The upper optic radiation carries fibres from the superior retinal quadrants (corresponding to the inferior visual field quadrants) and travels through the parietal lobe to reach the visual cortex. The lower optic radiation carries fibres from the inferior retinal quadrants (corresponding to the superior visual field quadrants) and travels through the temporal lobe to reach the visual cortex of the occipital lobe.

Impetigo is a highly contagious infection of the superficial epidermis that most commonly affects young children but can occur in any age group. In children it is the most common bacterial skin infection and it is the third most common skin disease overall, behind dermatitis and viral warts.The commonest causative organism is Staphylococcus aureus. Streptococcus pyogenesis the second commonest and causes fewer cases, either alone or in combination withS. aureus.The streptococcal form tends to be commoner in warmer, more humid climates. (Hirschmann JV. Impetigo: etiology and therapy. Curr Clin Top Infect Dis. 2002;22:42–51.)Impetigo is most commonly spread by direct person-to-person contact, and can spread rapidly through families and school classes. It can also, less commonly, be spread by indirect contact.There are two main forms of impetigo:Non-bullous impetigo – lesions usually start as tiny pustules or vesicles that evolve rapidly into honey-crusted plaques that tend to be under 2 cm in diameter. These can be itchy but are rarely painful.Bullous impetigo – lesions have a thin roof and tend to rupture spontaneously. This type is more likely to be painful and may be associated with systemic upset.

The hormone-active metabolite of vitamin D is 1,25-dihydroxycholecalciferol (commonly known as calcitriol). Its activities raise calcium and phosphate levels in the bloodstream.In the presence of UVB light, 7-dehydrocholesterol is converted to cholecalciferol in the epidermal layer of the skin, resulting in 1,25-dihydroxycholecalciferol.Cholecalciferol is then converted to 25-hydroxycholecalciferol in the endoplasmic reticulum of liver hepatocytes by 25-hydroxylase (calcifediol).Finally, 1-alpha-hydroxylase converts 25-hydroxycholecalciferol to 1,25-dihydroxycholecalciferol in the kidney. The key regulatory point in the formation of 1,25-dihydroxycholecalciferol is 1-alpha-hydroxylase, which is induced by parathyroid hormone or hypophosphatemia.The following are the primary effects of 1,25-dihydroxycholecalciferol:Calcium and phosphate absorption in the small intestine is increased.Calcium reabsorption in the kidneys is increased.Increases phosphate reabsorption in the kidneys.Increases the action of osteoclastic bacteria (increasing calcium and phosphate resorption from bone)Inhibits the action of 1-alpha-hydroxylase in the kidneys (negative feedback)

Blood loss from the gastrointestinal (GI) tract is the most common cause of iron deficiency anaemia in adult men and postmenopausal women.

Campylobacter spp. are a common cause of acute infective gastroenteritis, particularly in children, with Campylobacter jejuni responsible for 90% of Campylobacter gastroenteritis. Infection typically follows ingestion of contaminated meat (most frequently undercooked poultry), unpasteurised milk or contaminated water, following which the microorganism invades and colonises the mucosa of the small intestine.

Continuous data is data where there is no limitation on the numerical value that the variable can take e.g. weight, height.

Acetaminophen is an acetanilide derivative and is a widely used non-prescription analgesic and antipyretic medication for mild-to-moderate pain and fever.The route of elimination: Metabolites are mainly excreted in the urine. 90% of the dose administered is excreted within 24 hours. It is thought to work by selectively inhibiting COX-1 receptors in the brain and spinal cord: It is categorized by the FDA as an NSAID as it is believed to selectively inhibit cyclo-oxygenase 3 (COX-3) receptors in the brain and spinal cord. COX-3 is a unique variant of the more known COX-1 and COX-2. It is responsible for the production of prostaglandins in central areas, which sensitizes free nerve endings to the chemical mediators of pain. Therefore, by selectively inhibiting COX-3, paracetamol effectively reduces pain sensation by increasing the pain threshold.Toxicity is primarily due to glutathione production: Acetaminophen metabolism by the CYP2E1 pathway releases a toxic metabolite known as N-acetyl-p-benzoquinoneimine (NAPQI). NAPQI primarily contributes to the toxic effects of acetaminophen. NAPQI is an intermediate metabolite that is further metabolized by fast conjugation with glutathione. The conjugated metabolite is then excreted in the urine as mercapturic acid. High doses of acetaminophen (overdoses) can lead to hepatic necrosis due to depleting glutathione and high binding levels of reactive metabolite (NAPQI) to important parts of liver cells.It has a half-life of 6-8 hours: Acetaminophen can be administered orally, rectally, or intravenously. It is predominantly metabolized in the liver, and the elimination half-life is 1-3 hours after a therapeutic dose. But maybe greater than 12 hours after an overdose.It is primarily metabolized via the cytochrome p450 enzyme system: It is predominantly metabolized in the liver by three main metabolic pathways:1. Glucuronidation (45-55%)2. Sulphate conjugation (30-35%)3. N-hydroxylation via the hepatic cytochrome p450 enzyme system (10-15%)

A botulism infection results in neuroparalysis caused by the neurotoxin generated by Clostridium botulinum. Food-borne botulism symptoms often appear 12-36 hours after ingestion of the toxin-containing food and may include nausea, vomiting, stomach discomfort, and diarrhoea at first. The most common neurological pattern is an acute onset of bilateral cranial neuropathies with symmetric declining weakening. Other distinguishing characteristics include the absence of fever, the absence of cognitive abnormalities, the presence of a normal heart rate and blood pressure, and the absence of sensory defects.

During the AP plateau, Ca2+enters the cell and activates Ca2+sensitive Ca2+release channels in the sarcoplasmic reticulum allowing stored Ca2+to flood into the cytosol; this is called Ca2+-induced Ca2+release. In relaxation, about 80% of Ca2+is rapidly pumped back into the SR (sequestered) by Ca2+ATPase pumps. The Ca2+that entered the cell during the AP is transported out of the cell primarily by the Na+/Ca2+exchanger in the membrane which pumps one Ca2+ion out in exchange for three Na+ions in, using the Na+electrochemical gradient as an energy source. Increased heart rate increases the force of contraction in a stepwise fashion as intracellular [Ca2+] increases cumulatively over several beats; this is the Treppe effect. Factors that affect intracellular [Ca2+] and hence cardiac contractility are called inotropes.

Antiepileptic medications such as carbamazepine (Tegretol), topiramate (Topamax), and phenytoin (Dilantin) are widely known for reducing the contraceptive effectiveness of OCPs.

The oculomotor nerve is the third cranial nerve. It is the main source of innervation to the extraocular muscles and also contains parasympathetic fibres which relay in the ciliary ganglion. Damage to the third cranial nerve may cause diplopia, pupil mydriasis, and/or upper eyelid ptosis. The clinical manifestations of third cranial nerve dysfunction reflect its constituent parts.

Cushing’s syndrome is a group of symptoms and signs brought on by long-term exposure to high amounts of endogenous or exogenous glucocorticoids. Cushing’s syndrome affects about 10-15 persons per million, and it is more common in those who have had a history of obesity, hypertension, or diabetes.Iatrogenic corticosteroid injection is the most prevalent cause of Cushing’s syndrome. Cushing’s illness is the second most prevalent cause of Cushing’s syndrome. Cushing’s disease is distinct from Cushing’s syndrome in that it refers to a single cause of the illness, a pituitary adenoma that secretes high quantities of ACTH, which raises cortisol levels.Cushing’s syndrome has several endogenous sources, including:Cushing’s disease is caused by a pituitary adenoma.Adrenal adenoma Ectopic corticotropin syndrome, e.g. small cell cancer of the lungAdrenal carcinoma is a cancer of the adrenal gland.Hyperplasia of the adrenal glands

Digoxin is most useful for controlling the ventricular response in persistent and permanent atrial fibrillation and atrial flutter. Digoxin is usually only effective for controlling the ventricular rate at rest, and should therefore only be used as monotherapy in predominantly sedentary patients with non-paroxysmal atrial fibrillation. It is now rarely used for rapid control of heart rate, as even with intravenous administration, response may take many hours. Digoxin is reserved for patients with worsening or severe heart failure due to left ventricular systolic dysfunction refractory to combination therapy with first-line agents. Digoxin is contraindicated in supraventricular arrhythmias associated with accessory conduction pathways e.g. Wolff-Parkinson-White syndrome.

The glomerular filtration membrane is composed of fenestrated capillary endothelium, basement membrane, and filtration slits. It is an organized, semipermeable membrane preventing the passage of most of the proteins into the urine. The anatomical arrangement of the glomerular filtration membrane maximizes the surface area available for filtration. The arrangement of its arterioles results in high hydrostatic pressures and facilitates filtration. Fenestrated capillary endothelium of the glomerular filtration membrane is with relatively large pores. It allows the free movement of plasma proteins and solutes but still restricts the movement of blood cells. Filtration slits are the smallest filters and restrict the movement of plasma proteins but still allow free movement of ions and nutrients. The glomerular basement membrane (GBM) is a critical component of the glomerular filtration membrane. Thus, it is not true that its absence will reduce the resistance of flow. The basement membrane is true to be more selective and contains negatively charged glycoproteins. However, it still allows free passage of water, nutrients, and ions. Severe structural abnormalities of the GBM can result in protein (albumin) leakage.

The Focused Assessment with Sonography in Trauma (FAST) is an ultrasound protocol developed to assess for hemoperitoneum and hemopericardium. Numerous studies have demonstrated sensitivities between 85% to 96% and specificities exceeding 98%.The FAST exam evaluates four regions for pathologic fluid: (1) the right upper quadrant, (2) the subxiphoid (or subcostal) view, (3) the left upper quadrant, and (4) the suprapubic region.The right upper quadrant (RUQ) visualizes the hepatorenal recess, also known as Morrison’s pouch, the right paracolic gutter, the hepato-diaphragmatic area, and the caudal edge of the left liver lobe. The probe is positioned in the sagittal orientation along the patient’s flank at the level of the 8 to 11 rib spaces. The hand is placed against the bed to ensure visualization of the retroperitoneal kidney. The RUQ view is the most likely to detect free fluid with an overall sensitivity of 66%. Recent retrospective evidence suggests the area along the caudal edge of the left lobe of the liver has the highest sensitivity, exceeding 93%.

Clostridium tetani (causing tetanus) produces the exotoxin tetanospasmin which causes its neurotoxic effects.

Local currents propagate action potentials down the axons of neurons. Following depolarization, this local current flow depolarizes the next axonal membrane, and when this region crosses the threshold, more action potentials are formed, and so on. Due to the refractory period, portions of the membrane that have recently depolarized will not depolarize again, resulting in the action potential only being able to go in one direction.The square root of axonal diameter determines the velocity of the action potential; the axons with the biggest diameter have the quickest conduction velocities. When a neuron is myelinated, the speed of the action potential rises as well.The myelin sheath is an insulating coating that surrounds certain neural axons. By increasing membrane resistance and decreasing membrane capacitance, the myelin coating increases conduction. This enables faster electrical signal transmission via a neuron, making them more energy-efficient than non-myelinated neuronal axons.Nodes of Ranvier are periodic holes in a myelinate axon when there is no myelin and the axonal membrane is exposed. There are no gated ion channels in the portion of the axon covered by the myelin sheath, but there is a high density of ion channels in the Nodes of Ranvier. Action potentials can only arise at the nodes as a result of this.Electrical impulses are quickly transmitted from one node to the next, causing depolarization of the membrane above the threshold and triggering another action potential, which is then transmitted to the next node. An action potential is rapidly conducted down a neuron in this manner. Saltatory conduction is the term for this.

Fat necrosis typically occurs following either direct trauma or from enzymatic lipolysis in acute pancreatitis, where release of triglyceride elicits a rapid inflammatory response and fat is phagocytosed by neutrophils and macrophages with subsequent fibrosis.

Immunodeficiency is present in all patients with chronic lymphocytic leukaemia (CLL), though it is often mild and not clinically significant. Infections are the leading cause of death in 25-50 percent of CLL patients, with respiratory tract, skin, and urinary tract infections being the most common.Hypogammaglobulinemia is the most common cause of immunodeficiency in CLL patients, accounting for about 85 percent of all cases.

Gaussian distribution, also known as normal distribution, is the most important probability distribution in statistics because it fits many natural phenomena. The normal distribution is a probability function that describes how the values of a variable are distributed. Below are its characteristics:(1) Bell-shaped and symmetrical about the mean(2) The mean, median, mode are all equal(3) The total area under the curve and above the x-axis is equal to 1(4) It has long tapering tails extending infinitely but never touching the x-axis(5) It is determined by its parameters: its mean and standard deviation(6) The standard deviation becomes a more meaningful quality than merely being a measure of dispersionThe mean is the most common measure of central tendency. It is the sum of all observed values divided by the number of observation, and is also known as the ‘average’.The median is the value that falls in the middle position when the observations are ranked in order from the smallest to the largest. If the number of observations is odd, the median is the middle number. If it is even, the median is the average of the two middle numbers.The mode is the value that occurs with the greatest frequency in a set of observations, and is commonly used in public health statistics, such as the top 10 causes of mortality.