Adverse effects of loop diuretics include:
Mild gastrointestinal disturbances, pancreatitis and hepatic encephalopathy
Hyperglycaemia
Acute urinary retention
Water and electrolyte imbalance
Hyponatraemia, hypocalcaemia, hypokalaemia, hypomagnesaemia, hypochloraemiaHypotension, hypovolaemia, dehydration, and venous thromboembolism
Metabolic alkalosis
Hyperuricaemia
Blood disorders (bone marrow suppression, thrombocytopenia, and leucopenia)
Visual disturbance, tinnitus and deafness
Hypersensitivity reactions

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.

A pareto diagram, or pareto chart, consists of a vertical bar graph in which values are plotted in decreasing order of relative frequency from left to right. The independent variables on the chart are shown on the horizontal axis and the dependent variables are portrayed as the heights of bars.

A point-to-point graph, which shows the cumulative relative frequency, may be superimposed on the bar.

Because the values of the statistical variables are placed in order of relative frequency, the graph clearly reveals which factors have the greatest impact and where attention is likely to yield the greatest benefit. It is extremely useful for analysing what problems need attention first, because the taller bars on the chart clearly illustrate which variable have the greatest cumulative effect on a given system.

Beta-thalassaemia major is caused by a complete or almost complete failure of β-globin chain synthesis, severe imbalance of α:β-chains with deposition of α-chains in erythroblasts, ineffective erythropoiesis and extramedullary haemopoiesis. The severe anaemia becomes apparent at 3 – 6 months when the switch from γ-chain to β-chain synthesis normally occurs. Beta-thalassaemia minor is a variable syndrome, milder than thalassaemia major, with later onset and characterised by moderate hypochromic microcytic anaemia with raised haemoglobin A2. Beta-thalassaemia trait is characterised by mild hypochromic, microcytic anaemia with raised red cell count and raised haemoglobin A2.

Hyperkalaemia causes a rapid reduction in resting membrane potential leading to increased cardiac depolarisation and muscle excitability. This in turn results in ECG changes which can rapidly progress to ventricular fibrillation or asystole. Very distinctive ECG changes that progressively change as the K+level increases:
K+>5.5 mmol/l – peaked T waves (usually earliest sign of hyperkalaemia), repolarisation abnormalities
K+>6.5 mmol/l – P waves widen and flatten, PR segment lengthens, P waves eventually disappear
K+>7.0 mmol/l – Prolonged QRS interval and bizarre QRS morphology, conduction blocks (bundle branch blocks, fascicular blocks), sinus bradycardia or slow AF, development of a sine wave appearance (a pre-terminal rhythm)
K+>9.0 mmol/l – Cardiac arrest due to asystole, VF or PEA with a bizarre, wide complex rhythm.

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 vast majority of systems within the body work by negative feedback mechanisms. This negative feedback refers to the way that effectors act to move the variable in the opposite direction to the change that was originally detected. Because there is an inherent time delay between detecting a change in a variable and effecting a response, the negative feedback mechanisms cause oscillations in the variable they control. There is a narrow range of values within which a normal physiological function occurs and this is called the ‘set point’. The release of oxytocin in childbirth is an example of positive feedback.

Pabrinex is indicated in patients that require rapid therapy for severe depletion or malabsorption of water-soluble vitamins B and C, particularly in alcoholism detoxification.

Pabrinex has the following:
1. Thiamine (vitamin B1)
2. Riboflavin (vitamin B2)
3. Nicotinamide (Vitamin B3, niacin and nicotinic acid)
4. Pyridoxine (vitamin B6)
5. Ascorbic acid (vitamin C)
6. Glucose

Suspected or established Wernicke’s encephalopathy is treated by intravenous infusion of Pabrinex/ The dose is 2-3 pairs three times a day for three to five days, followed by one pair once daily for an additional three to five days or for as long as improvement continues.

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.

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)
Thyroid hormone (parathyroid hormone) Calcium reabsorption in the tubules of the kidneys is increased, but renal phosphate reabsorption is decreased.

The biceps brachii muscle is one of the chief muscles of the arm. The origin at the scapula and the insertion into the radius of the biceps brachii means it can act on both the shoulder joint and the elbow joint, which is why this muscle participates in a few movements of the arm. It derives its name from its two heads which merge in one unique distal body, defining the unusual structure of the muscle.

The biceps brachii muscle is supplied by the musculocutaneous nerve (C5-C6), a branch of the brachial plexus.

Arterial supply to the biceps brachii muscle varies considerably, coming from up to eight vessels originating from the brachial artery in the middle third of the arm.

In the shoulder joint both muscle heads partially enforce opposite movements. The long head pulls the arm away from the trunk (abduction) and turns it inwards (inward rotation) whereas the short head pulls the arm back towards the trunk (adduction). When both heads contract simultaneously it leads to an arm bend (flexion). In the elbow joint the muscle bends the forearm (flexion) and rotates it outwards (supination). The supination is most powerful in a flexed elbow. In addition to the movement functions, the biceps has the important task to support the humeral head within the shoulder joint. Its antagonist is the triceps brachii in the posterior compartment of the arm.

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.

The primary blood supply to the head of the femur is from branches of the medial femoral circumflex artery.

The superior and inferior gluteal arteries supply the hip joint but not the head of femur.

The lateral circumflex artery anastomoses with the medial femoral circumflex artery and assists in supplying the head of femur.

The obturator artery is an important source of blood supply in children up to about 8 years. It gives rise to the artery of the head of femur which runs in the ligamentum teres and is insufficient to supply the head of femur in adults.

The stomach produces gastric acid, which is a digesting fluid. The stomach secretes about 2-3 litres every day. It is involved in tissue breakdown, the conversion of pepsinogen to active pepsin, and the creation of soluble salts with calcium and iron, and has a pH range of 1.5-3.5. It also serves as an immune system by destroying microbes.

The following substances are found in gastric acid:
Water
Acid hydrochloride
Pepsinogen
mucous
Intrinsic factor

The parietal cells in the proximal 2/3 (body) of the stomach release gastric acid. The concentration of hydrogen ions in parietal cell secretions is 1-2 million times that of blood. Chloride is released against both a concentration and an electric gradient, and active transport is required for the parietal cell to produce acid.

The following is how stomach acid is secreted:

1. Gastric acid secretion is dependent on the H+/K+ ATPase (proton pump) situated in the canalicular membrane. The breakdown of water produces hydrogen ions within the parietal cell. The hydroxyl ions produced in this reaction mix quickly with carbon dioxide to generate bicarbonate ions. Carbonic anhydrase is the enzyme that catalyses this process.

2. In return for chloride, bicarbonate is carried out of the basolateral membrane. The ‘alkaline tide’ occurs when bicarbonate is released into the bloodstream, resulting in a modest rise in blood pH. The parietal cell’s intracellular pH is maintained by this procedure. Conductance channels carry chloride and potassium ions into the lumen of canaliculi.

3. Through the action of the proton pump, hydrogen ions are pushed out of the cell and into the lumen in exchange for potassium; potassium is thus efficiently recycled.

4. The canaliculi accumulate osmotically active hydrogen ions, which creates an osmotic gradient across the membrane, allowing water to diffuse outward.

Corticotropin-releasing hormone (CRH) is a neurotransmitter and peptide hormone. It is generated by cells in the hypothalamic paraventricular nucleus (PVN) and released into the hypothalamo-hypophyseal portal system at the median eminence through neurosecretory terminals of these neurons. Stress causes the release of CRH.

The CRH is carried to the anterior pituitary through the hypothalamo-hypophyseal portal system, where it activates corticotrophs to release adrenocorticotropic hormone (ACTH). Cortisol, glucocorticoids, mineralocorticoids, and DHEA are all produced in response to ACTH.

Excessive CRH production causes the size and quantity of corticotrophs in the anterior pituitary to expand, which can lead to the creation of a corticotrope tumour that generates too much ACTH.

The incubation period for Chickenpox is 7-23 days (usually around 2 weeks).

Incubation period of botulism is 18-36 hours

Incubation period of Meningococcaemia is 1-7 days.

Incubation period of Gonorrhoea is 3-5 days.

Incubation period of Hepatitis A is 3-5 weeks.
Other infectious with an incubation period of between 1 and 3 weeks are:
Whooping cough (7-10 days)
Brucellosis (7-21 days)
Leptospirosis (7-12 days)
Malaria (7-40 days depending on strain)
Typhoid (8-21 days)
Measles (10-18 days)
Mumps (14-18 days)
Rubella (14-21 days)

Ciprofloxacin is recommended for use as meningococcal chemoprophylaxis in all age groups and in pregnancy, and is the most appropriate for this patient.

However, rifampicin is the drug of choice for meningococcal chemoprophylaxis because it is licensed for chemoprophylaxis, but multiple doses are necessary and it is not readily available in community pharmacies. It also interacts with oral contraceptives.

Once muscle tissue is damaged, there will be healing via diffuse formation of fibrous tissue, especially due to the widespread ischemia.

Callus formation takes place in the healing of bone, not muscle.

Organised scar formation occurs when a lacerated wound is approximated by sutures so that primary intention wound healing can occur.

Liquefaction degeneration occurs following ischemia in the brain.

Volkmann’s ischemic contracture may occur, but it is not the primary type of healing that will take place but rather the effect of the fibrous scar formation.

Cardiac muscle is striated, and the sarcomere is the contractile unit, similar to skeletal muscle. Contracture is mediated by the interaction of calcium, troponins, and myofilaments, much as it occurs in skeletal muscle. Cardiac muscle, on the other hand, differs from skeletal muscle in a number of ways.

In contrast to skeletal muscle cells, cardiac myocytes have a nucleus in the middle of the cell and sometimes two nuclei. The cells are striated because the thick and thin filaments are arranged in an orderly fashion, although the arrangement is less well-organized than in skeletal muscle.

Intercalated discs, which work similarly to the Z band in skeletal muscle in defining where one cardiac muscle cell joins the next, are a very significant component of cardiac muscle.

Adherens junctions and desmosomes, which are specialized structures that hold the cardiac myocytes together, are formed by the transverse sections. The lateral sections produce gap junctions, which join the cytoplasm of two cells directly, allowing for rapid action potential conduction. These critical properties allow the heart to contract in a coordinated manner, allowing for more efficient blood pumping.

Cardiac myocytes have the ability to create their own action potentials, which is referred to as myogenic’. They can depolarize spontaneously to initiate a cardiac action potential. Pacemaker cells, as well as the sino-atrial (SA) and atrioventricular (AV) nodes, control this.

The Purkinje cells and the cells of the bundle of His are likewise capable of spontaneous depolarization. While the bundle of His is made up of specialized myocytes, it’s vital to remember that Purkinje cells are not myocytes and have distinct characteristics. They are larger than myocytes, with fewer filaments and more gap junctions than myocytes. They conduct action potentials more quickly, allowing the ventricles to contract synchronously.
Cardiac myocytes contract by excitation-contraction coupling, just like skeletal myocytes. Heart myocytes, on the other hand, utilise a calcium-induced calcium release mechanism that is unique to cardiac muscle (CICR). The influx of calcium ions (Ca2+) into the cell causes a ‘calcium spark,’ which causes more ions to be released into the cytoplasm.

An influx of sodium ions induces an initial depolarisation, much as it does in skeletal muscle; however, in cardiac muscle, the inflow of Ca2+ sustains the depolarisation, allowing it to remain longer. Due to potassium ion (K+) inflow, CICR causes a plateau phase in which the cells remain depolarized for a short time before repolarizing. Skeletal muscle, on the other hand, repolarizes almost instantly.

Klebsiella is a type of bacteria commonly found in nature. In humans, the bacteria are often present in parts of the digestive tract and respiratory flora, where they do not generally cause problems. They are anaerobic Gram-negative rods. They are usually opportunistic pathogens which cause nosocomial infections, the most common ones being pneumonia and UTI.

An exudate is an inflammatory fluid that leaks out of the intravascular space due to increased vascular permeability and intravascular pressure. It is mostly caused by local processes and can occur in the following conditions:
1) Infection (e.g. pneumonia)
2) Malignancy
3) Pericarditis
4) Collagen vascular diseases, e.g., Rheumatoid Arthritis

Myxoedema is a state of severe hypothyroidism in which deposition of mucopolysaccharides occurs in the dermis. This causes a transudative effusion, typically in the pretibial region.

Factor V Leiden gene mutation is the most common inherited cause of an increased risk of venous thrombosis. Activated protein C normally breaks down activated factor V and so should slow the clotting reaction and prolong the APTT, but a mutation in the factor V gene makes factor V less susceptible to cleavage by activated protein C, resulting in increased levels of activated factor V.Heterozygotes for factor V Leiden are at an approximately five- to eight- fold increased risk of venous thrombosis compared to the general population (but only 10% of carriers will develop thrombosis in their lifetime). Homozygotes have a 30 – 140-fold increased risk. The incidence of factor V Leiden in patients with venous thrombosis is approximately 20 – 40%. It does not increase the risk of arterial thrombosis.

Antacids are contraindicated in hypophosphataemia. Liquid preparations are more effective than tablet preparations. Magnesium-containing antacids tend to be laxative whereas aluminium-containing antacids tend to be constipating. Antacids are best taken when symptoms occur or are expected, usually between meals and at bedtime. Antacids should preferably not be taken at the same time as other drugs since they may impair absorption.

Ipratropium bromide is an antimuscarinic drug. It is used in the management of acute asthma and COPD.

It provides short-term relief in chronic asthma. Short-acting β2agonists are preferred and act more quickly.

The commonest side effect of ipratropium bromide is dry mouth. Tremor is commonly seen with β2agonists.

It can trigger acute closed-angle glaucoma in patients that are susceptible.

First-line treatment for moderate asthma attacks is short-acting β2agonists.

The BTS guidelines recommend that nebulised ipratropium bromide (0.5 mg 4-6 hourly) be added to β2agonist treatment in patients with a poor initial response to β2agonist therapy or with acute severe or life-threatening asthma.

Its duration of action is 3-6 hours, maximum effect occurs 30-60 minutes after use, and bronchodilation can be maintained with three times per day dosing.

In restrictive lung disorders there is a reduction in the forced vital capacity (FVC) and the forced expiratory volume in one second (FEV1). The decline in the FVC is greater than that of the FEV1, resulting in preservation of the FEV1/FVC ratio (>0.7%).
In obstructive lung disease, FEV1is reduced to <80% of normal and FVC is usually reduced but to a lesser extent than FEV1. The FEV1/FVC ratio is reduced to <0.7.
According to the latestNICE guidelines(link is external), airflow obstruction is defined as follows:
Mild airflow obstruction = an FEV1 of >80% in the presence of symptoms
Moderate airflow obstruction = FEV1 of 50-79%
Severe airflow obstruction = FEV1 of 30-49%
Very severe airflow obstruction = FEV1<30%.
Spirometry is a poor predictor of durability and quality of life in COPD but can be used as part of the assessment of severity.
COPD can only be diagnosed on spirometry if the FEV1 is <80% and FEV1/FVC ratio is < 0.7.

For an action potential to occur, the membrane must become more permeable to Na+and the Na+influx must be greater than the K+efflux. An action potential occurs when depolarisation of the membrane reaches threshold potential. The membrane must be out of the absolute refractory period, however an action potential can still occur in a relative refractory period but only in response to a larger than normal stimulus.

Proinsulin is synthesised as a single-chain peptide. A connecting peptide (C peptide) within storage granules is removed by proteases to yield insulin.

Insulin:
1. is a polypeptide hormone consisting of two short chains (A and B) linked by disulphide bonds.
2. is produced by beta cells, located centrally within the islets of Langerhans, in the endocrine tissues of the pancreas.
3. release is stimulated initially during eating by the parasympathetic nervous system and gut hormones such as secretin. However, most output is driven by the rise in plasma glucose concentration that occurs after a meal.
4. effects are mediated by the receptor tyrosine kinase.

The mitochondria is responsible for the production of the cell’s supply of chemical energy. It does this by using molecular oxygen, sugar and small fatty acid molecules to generate adenosine triphosphate (ATP) by a process ss known as oxidative phosphorylation. An enzyme called ATP synthase is required.

Transcription of ribosomal RNA occurs in the nucleolus

Production of messenger RNA occur in the nucleus

Production of lysosome occurs in the Golgi apparatus

The post-translational processing of newly made proteins occurs in the endoplasmic reticulum

Acute lymphoblastic leukaemia (ALL) is the most common childhood cancer that primarily affects children. ALL is most common between the ages of 2 and 4, and it is uncommon in adults.

At the start of the cardiac cycle, towards the end of diastole, the whole of the heart is relaxed. The atrioventricular (AV) valves are open because the atrial pressure is still slightly greater than the ventricular pressure. The semilunar valves are closed, as the pressure in the pulmonary artery and aorta is greater than the ventricular pressures. The cycle starts when the sinoatrial node (SAN) initiates atrial systole.

Etomidate is associated with a high incidence of extraneous muscle movements, which can be minimised by an opioid analgesic or a short-acting benzodiazepine given prior to induction. Etomidate causes less hypotension than thiopental sodium and propofol during induction. Etomidate is associated with rapid recovery without a hangover effect. The rate of respiratory depression and tachycardia is not higher in etomidate.