Naloxone is a specific antagonist of mu(μ)-opioid receptors, the specific antidote for opioid overdose and will reverse respiratory depression and coma if given at sufficient dosage. The initial dose is usually 0.8 mg (2 mL) intravenously (the dose range suggested by BNF is 0.4-2 mg). It can also be given by intramuscular injection if the intravenous route is not feasible.
As naloxone has a shorter duration of action than most opioids, close monitoring and repeated injections are necessary according to the respiratory rate and depth of coma. The dose is generally repeated every 2-3 minutes to a maximum of 10 mg. When repeated doses are needed, naloxone may be given by a continuous infusion adjusted according to the vital signs. Initially, the infusion rate can be set at 60% of the initial resuscitative IV dose per hour.
In opioid addicts, naloxone administration may precipitate a withdrawal syndrome with abdominal cramps, nausea and diarrhoea, but these usually settle within 2 hours.

Hemagglutinin (HA) or Haemagglutinin (BE) is an antigenic glycoprotein found on the surface of the influenza viruses. It is responsible for binding the virus to the cell that is being infected. The name hemagglutinin comes from the protein’s ability to cause red blood cells (erythrocytes) to clump together (agglutinate) in vitro.

Antidiuretic hormone is synthesised in the hypothalamus and transported to the posterior pituitary within nerve fibres where it is stored in secretory granules. ADH binds V2 receptors on renal principal cells in the late distal tubule and collecting ducts, raising cAMP levels and causing intracellular vesicles to fuse with the apical membrane. In their membrane these vesicles have water channels called aquaporins, which increase the water permeability allowing greater water reabsorption and concentration of urine. Excess levels of ADH results in syndrome of inappropriate ADH secretion (SIADH) characterised by hyponatremia with concomitant hypo-osmolality and high urine osmolality.

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.

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.

An acute focal or diffuse suppurative inflammation of the prostate gland is called acute bacterial prostatitis.

According to the National Institute for Health and Care Excellence (NICE), acute prostatitis should be suspected in a man presenting with:
A feverish illness of sudden onset which may be associated with rigors, arthralgia, or myalgia; Irritative urinary voiding symptoms; acute urinary retention; perineal or suprapubic pain and an exquisitely tender prostate on rectal examination.

Treatment of acute prostatitis as recommended by NICE and the BNFare:
Ciprofloxacin or ofloxacin for 14 days
Alternatively, trimethoprim can be used. Duration of treatment is still 14 days

Foetal haemoglobin (HbF) has a higher affinity for oxygen than adult haemoglobin (HbA) because it’s gamma chains bind 2,3-DPG less avidly than beta chains of HbA. The HbF dissociation curve lies to the left of that for HbA. In the placenta PCO2moves from the foetal to the maternal circulation, shifting the maternal curve further right and the foetal curve further left (the double Bohr effect). The higher affinity of HbF relative to HbA helps transfer oxygen from mother to foetus. Therefore even through blood returning from the placenta to the foetus in the umbilical vein has a PO2of only about 4 kPa, its saturation is 70%. Oxygen transport in the foetus is also helped by a high Hb of about 170 – 180 g/L.

Infective causes of bloody diarrhoea include:
Salmonella spp
Campylobacter spp
Schistosomiasis
Entamoeba histolytica (Amoebiasis )
Shigella spp
Clostridium difficile
Yersinia spp
Enteroinvasive Escherichia coli

Enterotoxigenic Escherichia coli is non-invasive and does not cause inflammation of the gut and bloody diarrhoea. It presents with copious watery diarrhoea and usually are not associated with abdominal cramping.

Adjacent cardiac myocytes are connected to each other by intercalated discs. The intercalated discs provide both a structural attachment by ‘glueing’ cells together at desmosomes and an electrical contact made up of proteins called connexons, called a gap junction, which essentially creates a low-resistance pathway between cells.

The gracilis muscles is innervated by the anterior branch of the obturator nerve (L2-L4).

The Loop of Henle connects the proximal tubule to the distal convoluted tubule and lies parallel to the collecting ducts. It consists of three major segments, including the descending thin limb, the ascending thin limb, and the ascending thick limb. These segments are differentiated based on structure, anatomic location, and function.

The main function of the loop of Henle is to recover water and sodium chloride from urine. When fluid enters the loop of Henle, it has an osmolality of approximately 300 mOsm, and the main solute is sodium.

The thin descending limb has a high water permeability but a low ion permeability. Because it lacks solute transporters, it cannot reabsorb sodium. Aquaporin 1 (AQP1) channels are used to passively absorb water in this area. The peritubular fluid becomes increasingly concentrated as the loop descends into the medulla, causing water to osmose out of the tubule. The tubular fluid in this area now equalizes to the osmolality of the peritubular fluid, to a maximum of approximately 1200 mOsm in a long medullary loop of Henle and 600 mOsm in a short cortical loop of Henle.

The thin ascending limb is highly permeable to ions and impermeable to water. It allows the passive movement of sodium, chloride, and urea down their concentration gradients, so urea enters the tubule and sodium and chloride leave. Reabsorption occurs paracellularly due to the difference in osmolarity between the tubule and the interstitium.

The thick ascending limb is also impermeable to water but actively transports sodium, potassium, and chloride out of the tubular fluid. The osmolality of the tubular fluid is lower compared to the surrounding peritubular fluid. This area is water impermeable. This results in tubular fluid leaving the loop of Henle with an osmolality of approximately 100 mOsm, which is lower than the osmolality of the fluid entering the loop, and urea being the solute.

Anaphylaxis is an example of a type I hypersensitivity reaction.

It is IgE mediated.

It requires a prior exposure to the antigen. The initial exposure sensitizes the body to the antigen and a second exposure to that antigen leads to an anaphylactic reaction.

Massive calcium influx into the cells leads to mast cell degranulation.

The Immunoglobulin antigen complex binds to Fc receptors on the surface of mast cells. The result is mast cell degranulation and release of histamine, proteoglycans and serum proteases from cytoplasmic granules.

Atelectasis is a complete or partial collapse of the lung. It occurs when the alveoli deflate or are filled with alveolar fluid. It is considered a ventilation defect of the alveoli due to cystic fibrosis. It is not a perfusion defect. A perfusion defect will produce pathological dead space in which the lung alveoli are ventilated adequately but are not perfused, and there is no gas exchange. While with atelectasis, the alveoli remain perfused. However, there is impaired oxygen delivery and intrapulmonary shunting of blood will be present in the collapsed area. Since there is no exchange of gas at the capillary-alveolar interface of the collapsed segments, the pulmonary capillary blood will have similar PO2 and PCO2.

Causes of neutropaenia:
Drug-induced (e.g. chemotherapy, chloramphenicol, co-trimoxazole, phenytoin, carbamazepine, carbimazole, furosemide, chloroquine, clozapine, some DMARDs)
Benign (racial or familial)
Cyclical
Immune (e.g. SLE, Felty’s syndrome, hypersensitivity and anaphylaxis)
Leukaemia
Infections (e.g. HIV, hepatitis, fulminant bacterial infection)
General Pancytopaenia
Hypersplenism, aplastic anaemia, malignant infiltration of bone marrow, megaloblastic anaemia, chemotherapy, myelodysplasia

Malaria is an infectious disease transmitted by female of theAnophelesgenus of mosquito. It is a parasitic infection caused by the genusPlasmodium. Five species are recognized as causing disease in humans;Plasmodium falciparum,Plasmodium ovale,Plasmodium vivax,Plasmodium malariaeandPlasmodium knowlesi.
The classic symptom of malaria is the malarial paroxysm, a cyclical occurrence of a cold phase, where the patient experiences intense chills, a hot stage, where the patient feels extremely hot and finally a sweating stage, where the fever declines and the patient sweats profusely. On examination the patient may show signs of anaemia, jaundice and have hepatosplenomegaly without evidence of lymphadenopathy.

Plasmodium falciparum is the most serious form and is responsible for most deaths. Severe or complicated malaria is suggested by the presence of impaired consciousness, seizures, hypoglycaemia, anaemia, renal impairment, respiratory distress and spontaneous bleeding.
Plasmodium falciparum is the most likely type in this case in view of the presentation.
Haemoglobinuria and renal failure following treatment is suggestive of blackwater fever, which is caused byPlasmodium falciparum. An autoimmune reaction between the parasite and quinine causes haemolysis, haemoglobinuria, jaundice and renal failure. This can be fatal.
The benign malarias: P.vivax, P. malariae and P.ovale are usually treated with chloroquine. A course of primaquine is also required in P.vivax and P.ovale infection. Artesunate is the drug treatment of choice for Plasmodium falciparum malaria. Quinine can still be used where artesunate is not available. Often combination therapy with drugs such as doxycycline or fansidar is also required.

Norovirus is spread primarily by faecal-oral contact, but it can also be spread through contact with an infected person, ingestion of contaminated food or water, or contact with contaminated surfaces or items.

Cross-sectional studies aim to provide data about population health, normal ranges of biological parameters, and disease prevalence or severity by observing the entire population, or a representative subset, at a single point in time. Cross-sectional studies are relatively simple and quick to perform and can be used to study multiple outcomes, but are subject to confounding and recall bias and are not suitable for studying rare diseases. Cross-sectional studies cannot be used to assess causation or to consider trends over time.

Extensor pollicis brevis is a short and slender muscle located in the posterior compartment of the forearm, extending from the posterior surface of radius to the proximal phalanx of thumb. It is one of the deep extensors of the forearm, together with supinator, abductor pollicis longus, extensor pollicis longus and extensor indicis muscles.

Extensor pollicis brevis is a deep extensor of the thumb that lies deep to extensor digitorum muscle. It sits directly medial to abductor pollicis longus and posterolateral to extensor pollicis longus muscle. Just above the wrist, extensor pollicis brevis obliquely crosses the tendons of extensor carpi radialis brevis and extensor carpi radialis longus muscles.

Extensor pollicis brevis is innervated by posterior interosseous nerve which is a continuation of a deep branch of radial nerve (root value C7 and C8).

Extensor pollicis brevis receives its blood supply by posterior interosseous artery and perforating branches from the anterior interosseous artery, which are the branches of common interosseous artery. The common interosseous artery arises immediately below the tuberosity of radius from the ulnar artery.

Together with extensor pollicis longus, extensor pollicis brevis is in charge of extension of the thumb in the first metacarpophalangeal joint. It also extends the thumb in the carpometacarpal joint of the thumb. This movement is important in the anatomy of the grip, as it enables letting go of an object. As it crosses the wrist, extensor pollicis brevis also participates in the extension and abduction of this joint.

Abductor pollicis brevis is innervated by the recurrent (thenar) branch of median nerve (root value C8 and T1).

Thyroid hormones have multiple physiological effects on the body. These include:
1. Heat production (thermogenesis)
2. Increased basal metabolic rate
3. Metabolic effects:
(a) Increase in protein turnover (both synthesis and degradation are increased, although overall effect is catabolic)
(b) Increase in lipolysis
(c)Increase in glycogenolysis and gluconeogenesis
4. Enhanced catecholamine effect – Increase in heart rate, stroke volume and thus cardiac output
5. Important role in growth and development

A box and whisker plot is defined as a graphical method of displaying variation in a set of data. In most cases, a histogram analysis provides a sufficient display, but a box and whisker plot can provide additional detail while allowing multiple sets of data to be displayed in the same graph.

The procedure to develop a box and whisker plot comes from the five statistics below:

(1) Minimum value: The smallest value in the data set

(2) Second quartile: The value below which the lower 25% of the data are contained

(3) Median value: The middle number in a range of numbers

(4) Third quartile: The value above which the upper 25% of the data are contained

(5) Maximum value: The largest value in the data set

Opponens digiti minimi is a triangular-shaped muscle in the hand that forms part of the hypothenar eminence. It originates from the hook of the hamate bone and the flexor retinaculum and inserts into the medial border of the 5thmetacarpal.
Opponens digiti minimi is innervated by the deep branch of the ulnar nerve and receives its blood supply from the ulnar artery.
Opponens digiti minimi draws the fifth metacarpal bone anteriorly and rotates it, bringing the fifth digiti into opposition with the thumb.

Bile acids are synthesised from cholesterol by hepatocyte and excreted into bile. Bile acids are essential for lipid digestion and absorption. Of the bile acids excreted into the intestine, about 95% are reabsorbed into the portal circulation by active transport mechanisms in the distal ileum and recycled by the liver. Many of the bile salts are reabsorbed unaltered, some are converted by intestinal bacteria into secondary bile acids (deoxycholic acid and lithocholic acid) and then reabsorbed and a small proportion escapes reabsorption and is excreted in the faeces.

Dopamine is a catecholamine that occurs naturally and is used to treat low cardiac output, septic shock, and renal failure. It is both adrenaline and noradrenaline’s immediate precursor.

Dopamine acts on D1 and D2 dopamine receptors in the renal, mesenteric, and coronary beds at low doses (1-5 g/kg/min). Dopamine causes a significant decrease in renal vascular resistance and an increase in renal blood flow at these doses. Within this dose range, it is also involved in central modulation of behaviour and movement.

Dopamine stimulates beta- and alpha-adrenergic receptors directly and indirectly at higher doses. Beta-stimulation predominates at a rate of 5-10 g/kg/min, resulting in a positive inotropic effect that increases cardiac output and coronary blood flow. Alpha-stimulation predominates at infusion rates greater than 15 g/kg/min, resulting in peripheral vasoconstriction and an increase in venous return and systolic blood pressure.

Below is a summary of the mechanisms and effects of various inotropic agents:
Inotrope
Mechanism
Effects
Adrenaline (epinephrine)
Beta-1 and -2 agonist at increasing doses;
Alpha-agonist at high doses
Increased cardiac output;
Vasoconstriction at higher doses
Noradrenaline (norepinephrine)
Mainly alpha-agonist;
Beta-1 and -2 agonist at increasing doses
Vasoconstriction;
Some increased cardiac output
Dopamine
Dopamine agonist at low doses;
Beta-1 and -2 agonist at increasing doses;
Alpha-agonist at high doses
Increased cardiac output;
Vasoconstriction at higher doses
Dobutamine
Mainly beta-1 agonist
Increased cardiac output

The common peroneal nerve often referred to as the common fibular nerve, is a major nerve that innervates the lower extremity. It is one of the two major branches off the sciatic nerve and receives fibres from the posterior divisions of L4 through S2 nerve roots. The common peroneal nerve separates from the sciatic nerve in the distal posterior thigh proximal to the popliteal fossa. After branching off of the sciatic nerve, it continues down the thigh, running posteroinferior to the biceps femoris muscle, and crosses laterally to the head of the lateral gastrocnemius muscle through the posterior intermuscular septum. The nerve then curves around the fibular neck before dividing into two branches, the superficial peroneal nerve (SPN) and the deep peroneal nerve (DPN). The common peroneal nerve does not have any motor innervation before dividing; however, it provides sensory innervation to the lateral leg via the lateral sural nerve.

The superficial peroneal nerve innervates the lateral compartment of the leg, and the deep peroneal nerve innervates the anterior compartment of the leg and the dorsum of the foot. These two nerves are essential in the eversion of the foot and dorsiflexion of the foot, respectively. The superficial and deep peroneal nerves provide both motor and sensory innervation.

The most common presentation with common peroneal nerve injury or palsy is acute foot drop, although symptoms may be progressive and can include sensory loss or pain. Weakness in foot eversion may occur if the superficial peroneal nerve component is involved.

Mitochondria are membrane-bound organelles that are responsible for the production of the cell’s supply of chemical energy. This is achieved by using molecular oxygen to utilise sugar and small fatty acid molecules to generate adenosine triphosphate (ATP). This process is known as oxidative phosphorylation and requires an enzyme called ATP synthase. ATP acts as an energy-carrying molecule and releases the energy in situations when it is required to fuel cellular processes. Mitochondria are also involved in other cellular processes, including Ca2+homeostasis and signalling. Mitochondria contain a small amount of maternal DNA.
Mitochondria have two phospholipid bilayers, an outer membrane and an inner membrane. The inner membrane is intricately folded inwards to form numerous layers called cristae. The cristae contain specialised membrane proteins that enable the mitochondria to synthesise ATP. Between the two membranes lies the intermembrane space, which stores large proteins that are required for cellular respiration. Within the inner membrane is the perimitochondrial space, which contains a jelly-like matrix. This matrix contains a large quantity of ATP synthase.
Mitochondrial disease, or mitochondrial disorder, refers to a group of disorders that affect the mitochondria. When the number or function of mitochondria in the cell are disrupted, less energy is produced and organ dysfunction results.

Bence Jones proteins are monoclonal immunoglobulin light chains found in urine (and plasma) of some patients with myeloma. Because of their relatively small size, light chains are readily excreted into the urine. The presence of significant amounts of Bence Jones proteins in urine is indicative of malignant B cell proliferation.

Diagnosis of tapeworm is by direct visualisation of characteristic eggs in stool. Humans may be infected by pork or beef tapeworm. Treatment is with praziquantel or niclosamide. Specialist advice should be sought for the management of neurocysticercosis.Iron-deficiency anaemia is typically seen in hookworm infection. Threadworms migrate from the intestine at night to lay eggs on the perianal skin. Mebendazole is first line treatment for threadworms.

In 2016 the SOFA guideline was introduced, also called the Sepsis-related Organ Failure Assessment, to make a sepsis diagnosis easier and prevent mortality.

According to this guideline, sepsis was defined as a life-threatening organ dysfunction due to a dysregulated host response to infection.

Septic shock was defined as a subset of sepsis in which the circulatory and metabolic abnormalities would lead to a greater risk of mortality than sepsis alone. Patients with septic shock would be clinically identified by a need for vasopressors to maintain MAP greater than 65 mmHg and serum lactate greater than two mmol/L.

Approximately one-third of patients who suffer DVT or PE have an identifiable heritable risk factor, although additional risk factors are usually present when they develop the thrombosis. The history of a spontaneous DVT in a close relative increases an individual’s risk of DVT even if no known genetic predisposition can be identified.