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.

Isoniazid, a first-line agent for the treatment of tuberculosis, has the commonest side effect of peripheral neuropathy. It occurs in up to 20% of patients taking the drug at a dose > 6 mg/kg daily. Isoniazid combines with pyridoxine (vitamin B6) to form hydrazone, which is excreted in the urine. This causes a deficiency of biologically active pyridoxine leading to peripheral neuropathy.Peripheral neuropathy of isoniazid is prevented by the co-administration of pyridoxine at a dose of 10 mg for each 100 mg of isoniazid given.

Penicillins and cephalosporins are the major antibiotics that inhibit bacterial cell wall synthesis. They inactivate transpeptidases that help cross-link peptidoglycans in cell walls. Isoniazid decreases the synthesis of mycolic acids in mycobacterium.Clarithromycin binds to the 50S subunit of ribosomes and inhibits protein synthesis. Metronidazole and the other 5-nitroimidazole agents inhibit nucleic acid synthesis by forming toxic free radical metabolites in the bacterial cell that damage DNA. Tetracycline bind to 30S and prevent attachment of aminoacyl-tRNA.

The Likelihood Ratio (LR) is the likelihood that a given test result would be expected in a patient with the target disorder compared to the likelihood that that same result would be expected in a patient without the target disorder.The LR is used to assess how good a diagnostic test is and to help in selecting an appropriate diagnostic tests or sequence of tests. They have advantages over sensitivity and specificity because they are less likely to change with the prevalence of the disorder, they can be calculated for several levels of the symptom/sign or test, they can be used to combine the results of multiple diagnostic test and they can be used to calculate post-test probability for a target disorder.A LR greater than 1 produces a post-test probability which is higher than the pre-test probability. An LR less than 1 produces a post-test probability which is lower than the pre-test probability. When the pre-test probability lies between 30 and 70 per cent, test results with a very high LR (say, above 10) rule in disease. An LR below 1 produces a post-test probability les than the pre-test probability. A very low LR (say, below 0.1) virtually rules out the chance that the patient has the disease.

The endocervix is the most common site of Neisseria gonorrhoeae infection in women. Symptoms of infection, when present, include dysuria, cervical discharge, and lower abdominal pain. However, 50% of cases in women may be asymptomatic leading to complications such as pelvic inflammatory disease (PID), which may cause sterility, ectopic pregnancy, or perihepatitis.PID is also known as Fitz-Hugh-Curtis syndrome is defined as an inflammation of the upper genital tract due to an infection in women. The disease affects the uterus, fallopian tubes, and ovaries. It is typically an ascending infection, spreading from the lower genital tract. The recommended intramuscular or oral regimens for PID are as follows:Ceftriaxone at 500 mg IM in a single dose (for persons weighing ≥150 kg, administer 1 g of ceftriaxone); plus doxycycline at 100 mg PO BID for 14 days with metronidazole at 500 mg PO BID for 14 days.

Bacillus cereus = Gram-positive bacillusNeisseria meningitidis = Gram-negative coccusSalmonella enterica & Escherichia coli = Gram-negative bacilliIn Gram staining, crystal violet is a purple stain that is used to stain the bacteria first. The stained bacteria are decolorized and then stained with a red stain, which is safranin. Bacteria with thick cell walls keep the purple stain and are called Gram-positive. Thin-walled bacteria are easily decolorized so when safranin, the red stain, is placed on the organisms, they become red or Gram-negative. The Staphylococci that are associated with infections in humans are colonizers of various skin and mucosal surfaces. Because the carrier state is common among the human population, infections are frequently acquired when the colonizing strain gains entrance to a normally sterile site as a result of trauma or abrasion to the skin or mucosal surface.

Flexor carpi ulnaris is a fusiform muscle located in the anterior compartment of the forearm. It belongs to the superficial flexors of the forearm, along with pronator teres, palmaris longus, flexor digitorum superficialis and flexor carpi radialis. Flexor carpi ulnaris is the most medial of the superficial flexors.Innervation of the flexor carpi ulnaris muscle is from the brachial plexus via the ulnar nerve (C7-T1).Flexor carpi ulnaris receives its arterial blood supply via three different routes. Proximally, a branch of the posterior ulnar recurrent artery supplies the muscle as it passes between the humeral and ulnar heads. Branches of the ulnar artery supply the middle and distal parts of the muscle, with an accessory supply also present distally via the inferior ulnar collateral artery.Due to its position and direction in the forearm, flexor carpi ulnaris can move the hand sideways as well as flexing it. Contracting with flexor carpi radialis and palmaris longus, flexor carpi ulnaris produces flexion of the hand at the wrist joint. However, when it contracts alongside the extensor carpi ulnaris muscle in the posterior compartment, their counteracting forces produce adduction of the hand at the wrist, otherwise known as ulnar deviation or ulnar flexion

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)

Prochlorperazine is a phenothiazine drug as it is categorized as a first-generation antipsychotic. It mainly blocks the D2 (dopamine 2) receptors in the brain. Along with dopamine, it also blocks histaminergic, cholinergic, and noradrenergic receptors.It exerts its antiemetic effect via dopamine (D2) receptor antagonist. It is used to treat nausea and vomiting of various causes, including labyrinthine disorders.

Gallbladder inflammation can cause pain in the right upper quadrant and right shoulder, which is caused by irritation of the diaphragmatic peritoneum. Pain from areas supplied by the phrenic nerve is often referred to other somatic regions served by spinal nerves C3-C5.

A low anion gap is frequently caused by hypoalbuminemia. Albumin is a negatively charged protein and its loss from the serum results in the retention of other negatively charged ions such as chloride and bicarbonate. As bicarbonate and chloride anions are used to calculate the anion gap, there is a subsequent decrease in the gap. The anion gap is sometimes reduced in multiple myeloma, where there is an increase in plasma IgG (paraproteinaemia).

Although Ca2+entry during the action potential (AP) is essential for contraction, it only accounts for about 25% of the rise in intracellular Ca2+. The rest is released from Ca2+stores in the sarcoplasmic reticulum (SR). APs travel down invaginations of the sarcolemma called T-tubules, which are close to, but do not touch, the terminal cisternae of the SR. 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. The amount of Ca2+released is dependent on how much is stored, and on the size of the initial Ca2+influx during the AP.

Insulin is an anabolic hormone. Its actions can be broadly divided into:Lipid metabolismProtein metabolism andCarbohydrate metabolismFor lipid metabolism, insulin:Stimulates lipogenesisInhibits lipolysis by lipaseFor carbohydrate metabolism, insulin:Decreases gluconeogenesisStimulates glycolysisPromotes glucose uptake in muscle and adipose tissuePromotes glycogen storageIncreases glycogenesisDecreases glycogenolysisProtein metabolism:Stimulates protein synthesisAccelerates net formation of proteinStimulates amino acid uptakeInhibits protein degradationInhibits amino acid conversion to glucose

There is a lifelong susceptibility to increased risk of infection from a variety of organisms in patients with hyposplenism, especially in children under 5 years and those with sickle cell anaemia. Patients are most susceptible is to the encapsulated bacteria Streptococcus pneumoniae, Haemophilus influenzae type B and Neisseria meningitidis. Streptococcus pneumoniae is particular concerning as it can cause rapid and fulminant disease, which can be fatal. Malaria and animal bites that become infected also tend to be more severe.

Adverse effects include:Common: NauseaUncommon: VomitingRare: Abdominal pain, hypertension, hypotension, tachycardia

Newborn babies have a higher concentration of red blood cells with shorter lifespan leading to higher bilirubin levels than in adults. This condition is short-lived and harmless but with potential serious causes that need to be assessed for if present. The most obvious physical sign of jaundice is a yellow discolouration of the sclera, skin and mucous membranes. At a bilirubin level of 35 μmol/L or higher, the eye is affected. The bilirubin level will need to be higher than 255 μmol/L for the feet and extremities to be affected.

Phenytoin Contraindications include:HypersensitivitySinus bradycardiaSinoatrial blockSecond and third degree A-V blockAdams-Stokes syndromeConcurrent use with delavirdineHistory of prior acute hepatotoxicity attributable to phenytoin

Lysosomes are formed by the Golgi apparatus or the endoplasmic reticulum. Lysosome releases its enzymes and digests the cell when the cell dies.

The Renin-Angiotensin-Aldosterone System (RAAS) is a hormone system composed of renin, angiotensin, and aldosterone. Those hormones are essential for the regulation of blood pressure and fluid balance. Cases of hypotension, sympathetic stimulation, or hyponatremia can activate the Renin-angiotensin-aldosterone system (RAAS). The following process will then increase the blood volume and blood pressure as a response. When renin is released it will convert the circulating angiotensinogen to angiotensin I. The ACE or angiotensin-converting enzyme will then catalyst its conversion to angiotensin II, which is a potent vasoconstrictor. Angiotensin II can constrict the vascular smooth muscles and the efferent arteriole of the glomerulus. The efferent arteriole is a blood vessel that delivers blood away from the capillaries of the kidney. The angiotensin II-mediated constriction of efferent arterioles increases GFR, reduces renal blood flow and peritubular capillary hydrostatic pressure, and increases peritubular colloid osmotic pressure, as a response to its action of increasing the filtration fraction.

Mannitol is a low molecular weight compound and is therefore freely filtered at the glomerulus and is not reabsorbed. It, therefore, increases the osmolality of the glomerular filtrate and tubular fluid, increasing urinary volume by an osmotic effect. It also does not cross the blood-brain barrier (BBB).Mannitol is primarily used to reduce the pressure and volume of cerebrospinal fluid (CSF). It decreases the volume of CSF by:Decreasing the rate of CSF formation,and;Withdrawing extracellular fluid from the brain across the BBBOther uses of mannitol include:Short-term management of glaucomaTreatment of rhabdomyolysisPreserve renal function in peri-operative jaundiced patientsTo initiate diuresis in transplanted kidneysBowel preparation prior to colorectal proceduresThe recommended dose of mannitol for the reduction of CSF pressure/cerebral oedema is 0.25-2g/kg as an intravenous infusion over 30-60 minutes. This can be repeated 1-2 times after 4-8 hours if needed.Circulatory overload and rebound increases in intracranial pressure may occur following the use of mannitol. It is irritant to tissues and veins and can cause inflammation and phlebitis.Mannitol causes an expansion of the extracellular fluid space, which may worsen congestive cardiac failure. Contraindications to the use of mannitol include:AnuriaIntracranial bleeding (except during craniotomy)Severe cardiac failureSevere dehydrationSevere pulmonary oedema

Anatomical barriers to infection include:tight junctions between cells of the skin and mucosal membranesthe flushing action of tears, saliva and urinethe mucociliary escalator in the respiratory tract (together with the actions of coughing and sneezing)the acidic pH of gastric and vaginal secretionsthe acidic pH of the skin (maintained by lactic acid and fatty acids in sebum)enzymes such as lysozyme found in saliva, sweat and tearspepsin present in the stomachbiological commensal flora formed on the skin and the respiratory, gastrointestinal and genitourinary tracts which protect the host by competing with pathogenic bacteria for nutrients and attachment sites and by producing antibacterial substances

Inguinal hernias can present with an array of different symptoms. Most patients present with a bulge in the groin area, or pain in the groin. Some will describe the pain or bulge that gets worse with physical activity or coughing. Symptoms may include a burning or pinching sensation in the groin. These sensations can radiate into the scrotum or down the leg. It is important to perform a thorough physical and history to rule out other causes of groin pain. At times an inguinal hernia can present with severe pain or obstructive symptoms caused by incarceration or strangulation of the hernia sac contents. A proper physical exam is essential in the diagnosis of an inguinal hernia. Physical examination is the best way to diagnose a hernia. The exam is best performed with the patient standing. Visual inspection of the inguinal area is conducted first to rule out obvious bulges or asymmetry in groin or scrotum. Next, the examiner palpates over the groin and scrotum to detect the presence of a hernia. The palpation of the inguinal canal is completed last. The examiner palpates through the scrotum and towards the external inguinal ring. The patient is then instructed to cough or perform a Valsalva manoeuvre. If a hernia is present, the examiner will be able to palpate a bulge that moves in and out as the patient increases intra abdominal pressure through coughing or Valsalva.Groin hernias are categorized into 2 main categories: inguinal and femoral.Inguinal hernias are further subdivided into direct and indirect. An indirect hernia occurs when abdominal contents protrude through the internal inguinal ring and into the inguinal canal. This occurs lateral to the inferior epigastric vessels. The hernia contents may extend into the scrotum, and can be reduced superiorly then superolaterally. A direct inguinal hernia is protrusion of abdominal contents through the transversalis fascia within Hesselbach’s triangle. The borders of Hesselbach’s triangle are the inferior epigastric vessels superolaterally, the rectus sheath medially, and inguinal ligament inferiorly.A femoral hernia is a protrusion into the femoral ring. The borders of the femoral ring are the femoral vein laterally, Cooper’s ligament posteriorly, the iliopubic tract/inguinal ligament anteriorly and lacunar ligament medially.

A papule is a solid, well circumscribed, skin elevation measuring less than 0.5 cm in diameter. A nodule is a solid, well circumscribed, raised area that lies in or under the skin and measures greater than 0.5 cm in diameter. They are usually painless. A bulla is a visible collection of clear fluid measuring greater than 0.5 cm in diameter. A furuncle, or boil, is a pyogenic infection of the hair follicle commonly caused by infection with Staphylococcus aureus. A pustule is a small visible skin elevation containing an accumulation of pus.

About one third of patients with allergy to natural latex rubber (NRL) have an associated allergy to some plant-derived foods. It is known as the latex-fruit syndrome and occurs commonly with consumption of fresh fruits. Banana and avocado are the most implicated fruits but it can also be seen with tomato, kiwi and chestnut.

Magnesium carbonate is an over the counter antacid commonly used to relieve symptoms in ulcer dyspepsia and non-erosive gastro-oesophageal reflux.Antacids containing magnesium also tend to work as a laxative, while the antacids with aluminium may cause constipation. There is no significant increased risk of anaphylaxis, hepatotoxicity or renal impairment.

Chlorhexidine is an anti-staphylococcal agent. Cleaning is the removal of foreign material from areas or objects to a point at which they are visually free from debris.  Disinfection is the reduction in the number of infectious particles. Isopropyl alcohol is not effective against C. difficile spores. Autoclaving is a method of sterilisation.

C. diphtheriae, which is the causative agent of diphtheria, is carried in the upper respiratory tract and spread by droplet infection or hand-to-mouth contact. The incubation period averages 2 to 5 days.Infectious mononucleosis is caused by Epstein-Barr virus (EBV). The incubation period for EBV varies from 2 weeks to 2 months.The incubation for Hepatitis A virus is approximately 1 month.The incubation period for Hepatitis C ranges from 2 weeks to 6 months.The period from infection to development of anti-HIV antibodies is usually less than 1 month but may be up to 3 months.

An audit assesses if a certain aspect of health care is attaining a recognized standard. This lets care providers and patients know where their service is doing well, and where there could be improvements. The aim is to achieve quality improvement and improve outcomes for patients.Audits are a quality improvement measure and one of the 7 pillars of clinical governance. It allows organizations to continually work toward improving quality of care by showing them where they are falling short, allows them to implement improvements, and reaudit or close the audit cycle to see if beneficial change has taken place.Clinical audits are a cycle with several steps:1. Identification of the problem2. Definition of criteria and setting of standards3. Observation of practice and collection of data4. Analysis of data and comparison of performance with the criteria and standards5. Implementation of change

Lung compliance is defined as change in volume per unit change in distending pressure. Lung compliance is calculated using the equation:Lung compliance = ΔV / ΔPWhere:ΔV is the change in volumeΔP is the change in pleural pressure.Static compliance is lung compliance in periods without gas flow, and is calculated using the equation:Static compliance = VT / Pplat − PEEPWhere:VT = tidal volumePplat = plateau pressurePEEP = positive end-expiratory pressure

Haemorrhage occurs into the fracture site from the ruptured vessels in the bone marrow and those supplying the periosteum immediately after fracture. This hematoma formation is the first phase of bone healing.The 4 stages of bone healing are:Haematoma at the fracture site (provides a framework for healing)Callus formationLamellar bone formationRemodelling