Distribution of data is usually unimodal (one peak) but may be bimodal (two peaks) or uniform (no peaks, each value equally likely). The normal distribution is a symmetrical bell-shaped curve. The mean, median, and mode of a normal distribution are equal. In a positive skew, the right tail is longer and the mass of distribution is concentrated on the left; mean > median > mode. In a negative skew, the left tail is longer and the mass of distribution is concentrated on the right; mean < median < mode.

The LDH level is usually markedly increased in severe megaloblastic anaemia. Reticulocyte counts are inappropriately low, representing a lack of production of RBCs due to massive intramedullary haemolysis. These findings are characteristics of ineffective haematopoiesis that occurs in megaloblastic anaemia as well as in other disorders such as thalassemia major.The common feature in megaloblastosis is a defect in DNA synthesis in rapidly dividing cells. To a lesser extent, RNA and protein synthesis are impaired. Unbalanced cell growth and impaired cell division occur since nuclear maturation is arrested. More mature RBC precursors are destroyed in the bone marrow prior to entering the bloodstream (intramedullary haemolysis).

Penicillins and the other ß-lactam antibiotics are bactericidal. They produce their antimicrobial action by preventing cross-linkage between the linear peptidoglycan polymer chains that make up the bacterial cell wall. They, therefore, inhibit cell wall synthesis.The integrity of the ß-lactam ring is essential for antimicrobial activity. Many bacteria (including most Staphylococci) are resistant to benzylpenicillin and phenoxymethylpenicillin because they produce enzymes (penicillinases, ß-lactamases) that open the ß-lactam ring.

Neutrophils are the most numerous peripheral blood leukocytes, accounting for 50-70 percent of all circulating white cells. Neutrophils have a compact nucleus with two to five lobes and a pale cytoplasm with an irregular shape containing numerous fine pink-blue or grey-blue granules. The granules are classified as primary, which emerges during the promyelocyte stage, and secondary, which develop at the myelocyte stage and predominate in the mature nucleus.The lifespan of neutrophils in the blood is only 6 – 10 hours. In response to tissue damage, cytokines and complement proteins, neutrophils migrate from the bloodstream to the site of insult within minutes, where they destroy pathogens by phagocytosis.

Clostridium difficile causes pseudomembranous colitis, an acute inflammatory diarrhoeal disease and an important cause of morbidity and mortality in hospitals. Gas gangrene is primarily caused by Clostridium perfringens. Tetanus is caused by Clostridium tetani. Toxic shock syndrome may be caused by Staphylococcus aureus or Streptococcus pyogenes. Necrotising fasciitis is most commonly caused by Streptococcus pyogenes but has a multitude of causes.

Bupivacaine has a longer duration of action than the other local anaesthetics, up to 8 hours when used for nerve blocks. It has a slow onset, taking up to 30 minutes for full effect. It is often used in lumbar epidural blockade and is particularly suitable for continuous epidural analgesia in labour, or for postoperative pain relief. It is the principal drug used for spinal anaesthesia.

Majority of carbohydrates are broken down into monosaccharides (glucose, fructose galactose) and are absorbed by the small intestine. Enzymes released from the brush border break down carbohydrate. Some carbohydrates, such as cellulose, are not digested at all, despite being made of multiple glucose units. This is because the cellulose is made out of beta-glucose that makes the inter-monosaccharide bindings different from the ones present in starch, which consists of alpha-glucose. Humans lack the enzyme for splitting the beta-glucose-bond.The principal brush border enzymes are dextranase and glucoamylase. Other brush border enzymes are maltase, sucrase, and lactase.Pancreatic amylase breaks down some carbohydrates (notably starch) into oligosaccharides. Dextranase and glucoamylase, then further break down oligosaccharides.Trypsin aids in digestion of protein.Chymotrypsin is a proteolytic enzyme that digests proteinCarboxypeptidase hydrolyses the first peptide or amide bond at the carboxyl or C-terminal end of proteins and peptides

A thyroid function test is used in the diagnosis of hyperthyroidism.Serum TSH should be the first-line investigation for patients with suspected hyperthyroidism as it has the highest sensitivity and specificity for hyperthyroidism. A normal TSH level almost always excludes the diagnosis, though there are rare exceptions to this.Antithyroglobulin antibodies are commonly present in Graves’ disease, but the test has a sensitivity of 98% and specificity of 99, and is not widely available.Radioactive iodine uptake scan using iodine-123 – shows low uptake in thyroiditis but high in Graves’ disease and toxic multinodular goitre. It is however, not first-line investigation in this caseThyroid ultrasound scan – is a cost-effective and safe alternative to the radioactive iodine uptake scan.

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.

Amoxicillin and Ampicillin are more hydrophilic (broad-spectrum) penicillins than benzylpenicillin and phenoxymethylpenicillin. Because they may penetrate through gaps in the outer phospholipid membrane, they are effective against Gram-negative bacteria. Amoxicillin and Ampicillin are resistant to penicillinase-producing microbes.Community-acquired pneumonia, otitis media, sinusitis, oral infections, and urinary tract infections are among the most prevalent conditions for which they are prescribed. The normal adult oral dose of Amoxicillin is 500 mg three times/day, which can be increased to 1 g three times/day if necessary. Ampicillin is given to adults in doses of 0.5-1 g every 6 hours.

Neutrophil polymorphs are the predominant type of white cells in an acute reaction. They pass between endothelial cell junctions to invade damaged tissue so that the effects of injury can be combated. Extravasation occurs with the movement of leukocytes out of the vessel lumen, and is achieved in five phases which are margination, ‘rolling’, adhesion, transmigration and chemotaxis.

Tendinopathy and spontaneous tendon rupture are caused by fluoroquinolones, which are an uncommon but well-known cause. Tendon problems caused by fluoroquinolones are expected to affect 15 to 20 people per 100,000. Patients over the age of 60 are most likely to develop them.It usually affects the Achilles tendon, but it has also been described in cases involving the quadriceps, peroneus brevis, extensor pollicis longus, long head of biceps brachii, and rotator cuff tendons. The exact aetiology is uncertain, although the fluoroquinolone medication is thought to obstruct collagen activity and/or cut off blood supply to the tendon.Other factors linked to tendon rupture spontaneously include:GoutTreatment with corticosteroidsHypercholesterolaemiaLong-term dialysisKidney transplantRheumatoid arthritis 

Calcium is stored in bones for nearly all of the body’s calcium, but it is also found in some cells (most notably muscle cells) and the blood. The average adult diet comprises roughly 25 mmol of calcium per day, of which the body absorbs only about 5 mmol.

CML is a myeloproliferative disorder characterised by an abnormal pluripotent haemopoietic stem cell. A cytogenetic abnormality known as the Philadelphia chromosome, which results from a reciprocal translocation between the long arms of chromosomes 9 and 22, causes more than 80% of cases of CML.CML is a disease that develops slowly over several years. This is known as the ‘chronic stage.’ This stage is usually asymptomatic, and 90 percent of patients are diagnosed at this point, with the disease being discovered frequently as a result of a routine blood test. During this stage, the bone marrow contains less than 10% immature white cells (blasts).When CML cells expand, symptoms typically begin to appear. The ‘accelerated stage’ is what it’s called. Approximately 10% of people are diagnosed at this point. During this stage, between 10% and 30% of blood cells in the bone marrow are blasts. During this stage, common clinical features include:Fatigue and exhaustionNight sweats and feverDistension of the abdomenPain in the left upper quadrant (splenic infarction)Splenomegaly (commonest examination finding)HepatomegalyBruising is simple.Gout is a type of arthritis that affects (rapid cell turnover)Hyperviscosity is a condition in which the viscosity of (CVA, priapism)A small percentage of patients experience a ‘blast crisis’ (blast stage). More than 30% of the blood cells in the bone marrow are immature blast cells at this stage. Patients with severe constitutional symptoms (fever, weight loss, bone pain), infections, and bleeding diathesis typically present at this stage.In CML, laboratory findings include:White cell count is abnormally high (often greater than 100 x 109/l).Increased number of immature leukocytes causes a left shift.Anaemia that is mild to moderately normochromic and normocytic.Platelets can be low, normal, or elevated, and the Philadelphia chromosome can be found in > 80% of patients. Serum uric acid and ALP levels are frequently elevated. Tyrosine kinase inhibitors (TKIs), such as imatinib and dasatinib, are the current mainstay of CML treatment. Allogenic bone marrow transplantation is now only used in cases where TKIs have failed to work.

Fick’s law tells us that the rate of diffusion of a gas increases: the larger the surface area involved in gas exchangethe greater the partial pressure gradient across the membranethe thinner the membranethe more soluble the gas in the membranethe lower the molecular weight of the gas

Fluid accumulates most often in the hepatorenal pouch (of Morrison) in a supine patient. The hepatorenal pouch is located behind the liver and anterior to the right kidney and is the lowest space in the peritoneal cavity in the supine position.Although the vesicouterine and rectouterine spaces are also potential spaces for fluid accumulation, fluid accumulation in them occur in the erect position.

When you take too much aspirin, you have a mix of respiratory alkalosis and metabolic acidosis. Respiratory centre stimulation produces hyperventilation and respiratory alkalosis in the early phases. The direct acid actions of aspirin tend to create a higher anion gap metabolic acidosis in the latter phases.Below summarizes some of the most common reasons of acid-base abnormalities:Respiratory alkalosis: – Hyperventilation (e.g. anxiety, pain, fever)- Pulmonary embolism- Pneumothorax- CNS disorders (e.g. CVA, SAH, encephalitis)- High altitude- Pregnancy- Early stages of aspirin overdoseRespiratory acidosis:- COPD- Life-threatening asthma- Pulmonary oedema- Respiratory depression (e.g. opiates, benzodiazepines)- Neuromuscular disease (e.g. Guillain-Barré syndrome, muscular dystrophy- Incorrect ventilator settings (hypoventilation)- ObesityMetabolic alkalosis:- Vomiting- Cardiac arrest- Multi-organ failure- Cystic fibrosis- Potassium depletion (e.g. diuretic usage)- Cushing’s syndrome- Conn’s syndromeMetabolic acidosis (with raised anion gap):- Lactic acidosis (e.g. hypoxaemia, shock, sepsis, infarction)- Ketoacidosis (e.g. diabetes, starvation, alcohol excess)- Renal failure- Poisoning (e.g. late stages of aspirin overdose, methanol, ethylene glycol)Metabolic acidosis (with normal anion gap):- Renal tubular acidosis- Diarrhoea- Ammonium chloride ingestion- Adrenal insufficiency

GFR can be estimated by:GFR = UCr x V / PCrWhere:UCr = urine concentration of creatininePCr = plasma concentration of creatinineV = rate of urine flowIn this case GFR = (18 x 2) / 0.25 = 144 ml/minNote: Creatinine is used to estimate GFR because it is an organic base naturally produced by muscle breakdown, it is freely filtered at the glomerulus, it is not reabsorbed from the nephron, it is not produced by the kidney, it is not toxic, and it doesn’t alter GFR.

The NICE guidelines for women with lower UTIs who are not pregnant are:1. Consider prescribing a different antibiotic if symptoms do not improve within 48 hours or worsen at any time 2. If the urine culture and susceptibility test results are available, review the choice of antibiotic according to the results and change the antibiotic accordingly if symptoms are not improving or bacteria is resistant to the prescribed antibioticThe first choice of antibiotics for non-pregnant women aged 16 years and over is:1. Nitrofurantoin100 mg modified-release PO BD for 3 days – if eGFR >45 ml/minute2. Trimethoprim 200 mg PO BD for three daysThe 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. Nitrofurantoin100 mg modified-release PO BD for three days – if eGFR >45 ml/minute2. Pivmecillinam400 mg PO initial dose, then 200 mg PO TDS for three days3. Fosfomycin 3 g single sachet dose

Glomerular filtration is a passive process. It depends on the net hydrostatic pressure across the glomerular capillaries, the oncotic pressure, and the intrinsic permeability of the glomerulus.The mean values for glomerular filtration rate (GFR) in young adults are 130 ml/min/1.73m2 in males and 120 ml/min/1.73m2in females.The GFR declines with age after the age of 40 at a rate of approximately 1 ml/min/year.The Cockcroft and Gault formula overestimates creatinine in obese patients. This is because their endogenous creatinine production is less than that predicted by overall body weight.Creatinine is used in the estimation of GFR because it is naturally produced by muscle breakdown, not toxic, not produced by the kidney, freely filtered at the glomerulus, not reabsorbed from the nephron, and does not alter GFR.

Aciclovir is active against herpesviruses but does not eradicate latent virus.

Arterial baroreceptors are located in the carotid sinus and aortic arch, and detect the mean arterial pressure (MAP). A decrease in MAP (such as in postural hypotension, or haemorrhage) reduces arterial stretch and decreases baroreceptor activity, resulting in decreased firing in afferent nerves travelling via the glossopharyngeal nerve (carotid sinus) and vagus nerve (aortic arch) to the medulla where the activity of the autonomic nervous system is coordinated. Sympathetic nerve activity consequently increases, causing an increase in heart rate and cardiac contractility, peripheral vasoconstriction with an increase in TPR, and venoconstriction with an increase in CVP and thus an increase in cardiac output and blood pressure. Parasympathetic activity (vagal tone) decreases, contributing to the rise in heart rate.

Granulomatous inflammation is typically seen when an infective agent with a digestion-resistance capsule (e.g. Mycobacterium tuberculosis) or a piece of inert foreign material (such as suture or glass) is introduced into the tissue. A transient acute inflammatory response occurs and when this is ineffective in eradicating the stimulus, chronic inflammation occurs.Tuberculosis is the prototype of the granulomatous diseases, but sarcoidosis, cat-scratch disease, lymphogranuloma inguinale, leprosy, brucellosis, syphilis, some mycotic infections, berylliosis, reactions of irritant lipids, and some autoimmune diseases are also included

Legionella pneumophilais a Gram negative bacterium that is found in natural water supplies and in the soil, transmitted predominantly via inhalation of aerosols generated from contaminated water (direct person-to-person spread of infected patients does not occur). It is the cause of Legionnaires’ disease. Outbreaks of Legionnaires’ disease have been linked to poorly maintained air conditioning systems, whirlpool spas and hot tubs.The clinical features of the pneumonic form of Legionnaires’ disease include:Mild flu-like prodrome for 1-3 daysCough (usually non-productive and occurs in approximately 90%)Pleuritic chest painHaemoptysisHeadacheNausea, vomiting and diarrhoeaAnorexiaLegionella pneumophilainfections can be successfully treated with macrolide antibiotics, such as erythromycin, or quinolones, such as ciprofloxacin. Tetracyclines, such as doxycycline, can also be used.The syndrome of inappropriate antidiuretic hormone secretion (SIADH) can occur with Legionnaires’ disease and will result in hyponatraemia as is seen in this case.Legionella pneumophilainfections are resistant to amoxicillin but can be successfully treated with macrolide antibiotics, such as erythromycin, or quinolones, such as ciprofloxacin. Tetracyclines, such as doxycycline, can also be used. The majority of cases of Legionnaires’ disease are caused by Legionella pneumophila, however many other species of Legionella have been identified.Legionella longbeachae is another less commonly encountered species that has also been implicated in outbreaks. It is predominantly found in soil and potting compost, and has caused outbreaks of Pontiac fever, the non-respiratory and less severe variant of Legionnaires’ disease.

The p value is statistically significant when it is less than 0.05 (5% or 1 in 20).Statistical significance is not the same as clinical significance. The null hypothesis states that there is no difference between the groups.The power of a study is the probability of correctly rejecting the null hypothesis when it is false.A type I error occurs when the null hypothesis has been rejected when it is true. A type II error occurs when the null hypothesis has been accepted when it is actually false.

Heparin is a polymer of glycosaminoglycan. It occurs naturally and is found in mast cells. Clinically, it is used in two forms:1. Unfractionated: widely varying polymer chain lengths2. Low molecular weight: Smaller polymers only Heparin works by binding to and activating the enzyme inhibitor antithrombin III. Antithrombin III inactivates thrombin (factor IIa) by forming a 1:1 complex with thrombin. The heparin-antithrombin III complex also inhibits factor Xa and some other proteases involved with clotting. The heparin-ATIII complex can also inactivate IX, XI, XII, and plasmin.Heparin is not thrombolytic or fibrinolytic. It prevents the progression of existing clots by inhibiting further clotting. The lysis of existing clots relies on endogenous thrombolytics.Heparin is used for:1. Prevention and treatment of venous thromboembolism2. Treatment of disseminated intravascular coagulation3. Treatment of fat embolism4. Priming of haemodialysis and cardiopulmonary bypass machinesThere is no evidence that heparin is superior to low-molecular-weight heparins in preventing mortality from thrombosis.Vitamin K is used to reverse the effects of warfarin but not heparin. For heparin, protamine sulphate is used to counteract its effects.

Features include: AnaemiaJaundice (caused by unconjugated bilirubin in plasma, bilirubin is absent from urine)Pigment gallstonesSplenomegalyAnkle ulcersExpansion of marrow with, in children, bone expansion e.g. frontal bossing in beta-thalassaemia majorAplastic crisis caused by parvovirus

Bartter’s syndrome is an autosomal recessive renal tubular disorder characterized by hypokalaemia, hypochloraemia, metabolic alkalosis, and hyperreninemia with normal blood pressure. The underlying kidney abnormality results in excessive urinary losses of sodium, chloride, and potassium. Bartter’s syndrome does not cause an elevated potassium level, but instead causes a decrease in its concentration (hypokalaemia). The other choices are causes of hyperkalaemia or elevated potassium levels. Renal failure, Addison’s disease (adrenal insufficiency), congenital adrenal hyperplasia, renal tubular acidosis (type 4), rhabdomyolysis, burns and trauma, tumour syndrome, and acidosis are non-drug causes of hyperkalaemia. On the other hand, drugs that can cause hyperkalaemia include ACE inhibitors, angiotensin receptor blockers, NSAIDs, beta-blockers, digoxin, and suxamethonium.

Starling’s equation for fluid filtration describes fluid flow at the capillary bed.Filtration forces (capillary hydrostatic pressure and interstitial oncotic pressure) stimulate fluid movement out of the capillary, while resorption forces promote fluid movement into the capillary (interstitial hydrostatic pressure and plasma oncotic pressure). Although the forces fluctuate along the length of the capillary bed, overall filtration is achieved.At the capillary bed, there is fluid movement.The reflection coefficient (σ), the surface area accessible (S), and the hydraulic conductance of the wall (Lp) are frequently used to account for the endothelium’s semi-permeability, yielding:Volume / min = LpS [(Pc- Pi) –  σ(πp– πi)]Volume /min = (Pc-Pi) – (πp–πi) describes the fluid circulation at the capillaries.Where:Pc= capillary hydrostatic pressurePi= interstitial hydrostatic pressureπp= plasma oncotic pressureπi= interstitial oncotic pressure

An ulnar injury may result in abnormal sensations in the little finger and ring finger, usually on the palm side, weakness, and loss of coordination of the fingers. A claw like deformity of the hand and wrist is present. Pain, numbness, decreased sensation, tingling, or burning sensation in the areas controlled by the nerve are also possible.