Classic signs:
Rubor (redness)
Calor (heat)
Dolour (pain)
Tumour (swelling)
Functio laesa (loss of function)
These classic signs are produced by a rapid vascular response and cellular events. The main function of these events is to bring elements of the immune system to the site of injury and prevent further tissue damage.

Features of toxicity include:
Increasing gastrointestinal disturbances (vomiting, diarrhoea, anorexia)
Visual disturbances
Polyuria and incontinence
Muscle weakness and tremor
Tinnitus
CNS disturbances (dizziness, confusion and drowsiness increasing to lack of coordination, restlessness, stupor)
Abnormal reflexes and myoclonus
Hypernatraemia
With severe overdosage (serum-lithium concentration > 2 mmol/L) seizures, cardiac arrhythmias (including sinoatrial block, bradycardia and first-degree heart block), blood pressure changes, electrolyte imbalance, circulatory failure, renal failure, coma and sudden death may occur.

Macrolide antibiotics are bacteriostatic.

They act by binding to the 50S subunit of the bacterial ribosome inhibit protein synthesis.

Macrolide antibiotics are actively concentrated within leukocytes, because of this, they are transported into the site of infection.

Macrolide antibiotics are not effective in meningitis as they do not penetrate the central nervous system well.

They are mainly against Gram-positive organisms and can be used as an alternative in patients with penicillin allergy.

A diagnosis of Haemophilia is supported in this patient by the family history and the presence of hemarthrosis-both characteristics of Haemophilia. Haemophilia A is caused by Factor VIII deficiency, leading to impaired coagulation. This disease typically presents after six months when the child starts crawling.

Von Willebrand disease presents with nosebleeds and hematomas. Idiopathic thrombocytopenic purpura presents with bruises that resemble a rash.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency presents with haemolytic anaemia induced by specific drugs or foods.

Factor V Leiden mutation causes blood clotting rather than bleeding.

All vaccines are contraindicated in individuals with: A confirmed anaphylactic reaction to a previous dose of the vaccine or a vaccine containing the same antigens.
A confirmed anaphylactic reaction to a component in the vaccine e.g. neomycin

There is no evidence that vaccinating pregnant women with inactivated vaccine or toxoids harms the woman or foetus.

The current protocol is that a child with history of egg allergy can be safely vaccinated with Fluenz tetra. However, if they had a previous severe anaphylaxis to egg requiring intensive care, then Flenz tetra is contraindicated.

BCG, yellow fever or oral typhoid vaccinations are not safe in HIV positive patients.

The normal times recommended for immunization of full-term babies should also be applied to premature infants and correction for gestational age should not be implemented.

Concurrent antibiotic therapy is not a contraindication to vaccination.

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.

A typical biochemical profile can help establish a diagnosis of Cushing’s syndrome. The following are the primary characteristics:
Hypokalaemia
Alkalosis metabolique

The neurotransmitter in the synaptic cleft is either eliminated or deactivated after the post-synaptic cell responds to the neurotransmitter.

This can be accomplished in a variety of ways:
Re-uptake
Breakdown
Diffusion

Serotonin is an example of a neurotransmitter that is uptake. Serotonin is absorbed back into the presynaptic neuron via the serotonin transporter (SERT), which is found in the presynaptic membrane. Re-uptake neurotransmitters are either recycled by repackaging into vesicles or broken down by enzymes.
Specific enzymes found in the synaptic cleft can also break down neurotransmitters. The following enzymes are examples of these enzymes:
Acetylcholinesterase (AChE) catalyses the acetylcholine breakdown (ACh)
The enzyme catechol-O-methyltransferase (COMT) catalyses the breakdown of catecholamines like adrenaline , dopamine and noradrenaline.

The breakdown of catecholamines, as well as other monoamines like serotonin, tyramine, and tryptamine, is catalysed by monoamine oxidases (MOA).
Diffusion of neurotransmitters into nearby locations can also be used to eliminate them.

Funnel plots are used to demonstrate the existence of publication bias in meta-analysis. Funnel plots are scatter plots of treatment effects estimated from individual studies on the x axis and some measure of study size on the y axis. Each point on the graph represents one of the studies. A symmetrical inverted funnel shape indicates an absence of publication bias. If there is publication bias, there will be asymmetry of the open wide end due to the absence of small negative results.

Tetanus is caused by Clostridium tetani, a bacterium. Tetanus can cause mild spasms to severe whole-body contractions, suffocation, and heart attack.

Gas gangrene and food poisoning are both caused by Clostridium perfringens.

Pseudomembranous colitis is caused by Clostridium difficile.

Urinary tract infections, respiratory infections, dermatitis, soft tissue infections, bacteraemia, bone and joint infections, gastrointestinal infections, and a variety of systemic infections are all caused by Pseudomonas aeruginosa.

Pharyngitis, skin infections, acute rheumatic fever, scarlet fever, poststreptococcal glomerulonephritis, toxic shock–like syndrome, and necrotizing fasciitis can all be caused by Streptococcus pyogenes infection.

Amitriptyline is a tricyclic antidepressant (TCA) that is most commonly used to treat depression, but it can also be used to treat anxiety disorders, chronic pain, and attention deficit hyperactivity disorder (ADHD). It inhibits reuptake, raising serotonin and noradrenaline levels while also inhibiting acetylcholine action.

TCAs have a number of drawbacks, including:
Acute Porphyria
Arrhythmias
During bipolar disorder’s manic phase
Heart block
After a myocardial infarction, there is an immediate recovery period.

TCA levels in breast milk are too low to be harmful, and use can be continued while breastfeeding.

Care and management of the thoracostomy tubes (chest tubes) are subject to the direction and practice pattern of the responsible physician. Therefore, it is difficult to make a “one size fits all” set of instructions about the specific management recommendations for all chest tubes. It is recommended to discuss specific expectations for management with the patient’s attending physician. Facility specific Clinical Practice Guidelines (CPGs) may provide further guidance for one’s practice.

Placement of the appropriately sized chest tube is performed on the affected side. The typical landmark for placement is the 4th or 5th intercostal space (nipple line for males, inframammary fold for females) at the anterior axillary line. The space above the 5th intercostal space and below the base of the axilla that is bordered posteriorly by the trapezius and anteriorly by the pectoralis muscle has recently been described as the safe triangle. Tubes are positioned anteriorly for pneumothoraces and posteriorly for fluid processes.

The mean incubation period for P. falciparum is 12 days.

WHO World Malaria Report 2019 states that an estimated 228 million cases of malaria occurred worldwide in 2018, and reports steadily decreasing the number of cases since 2010. In 2018, nineteen sub-Saharan African countries and India carried approximately 85% of the global malaria burden. The most prevalent and pathogenic malaria parasite, most commonly associated with severe illness and death, especially in the WHO African region, accounting for 99.7% malaria cases, is P. falciparum.

The vector for Plasmodium spp. is a female Anopheles mosquito that inoculates sporozoites contained in her salivary glands into the puncture wound when feeding. Sporozoites enter peripheral bloodstream and are uptake by hepatocytes, where they undergo an asexual pre-erythrocytic liver-stage as liver schizonts lasting up to 2 weeks before the onset of the blood stage.

Intravenous or intramuscular artesunate is the first-line treatment in all patients worldwide and should be used for at least 24 hours and until the oral medication is tolerated.

Blood group AB has both A and B antigens but no antibodies and thus is the universal recipient.

Approximately 65 – 70% of filtered K+is reabsorbed in the proximal tubule. Potassium reabsorption is tightly linked to that of sodium and water. The reabsorption of sodium drives that of water, which may carry some potassium with it. The potassium gradient resulting from the reabsorption of water from the tubular lumen drives the paracellular reabsorption of potassium and may be enhanced by the removal of potassium from the paracellular space via the Na+/K+ATPase pump. In the later proximal tubule, the positive potential in the lumen also drives the potassium reabsorption through the paracellular route.

Glanzmann’s thromboasthenia is a rare platelet disorder in which platelets contain defective or low levels of glycoprotein IIb/IIIa.

Ipratropium bromide is an antimuscarinic drug used in the management of acute asthma and COPD. It can provide short-term relief in chronic asthma, but short-acting β2agonists act more quickly and are preferred.

The BTS guidelines recommend that nebulised ipratropium bromide (0.5 mg 4-6 hourly) can be added to β2agonist treatment for patients with acute severe or life-threatening asthma or those with a poor initial response to β2 agonist therapy.
The aerosol inhalation of ipratropium can be used for short-term relief in mild chronic obstructive pulmonary disease in patients who are not already using a long-acting antimuscarinic drug (e.g. tiotropium).

Its maximum effect occurs 30-60 minutes after use; its duration of action is 3-6 hours, and bronchodilation can usually be maintained with treatment three times per day.
The commonest side effect of ipratropium bromide is dry mouth. It can also trigger acute closed-angle glaucoma in susceptible patients. Tremor is commonly seen with β2agonists but not with antimuscarinics. Ipratropium bromide should be used with caution in: Men with prostatic hyperplasia and bladder-outflow obstruction (worsened urinary retention has been reported in elderly men), People with chronic kidney disease (CKD) stages 3 and above (because of the risk of drug toxicity), People with angle-closure glaucoma (nebulised mist of antimuscarinic drugs can precipitate or worsen acute angle-closure glaucoma)

Chickenpox (varicella zoster) is a highly contagious airborne disease and has an incubation period of between 7-21 days. It often has a prodromal phase when there is a fever, aches and headaches, dry cough, and sore throat before onset of rash.

Some recognized complications of chickenpox are:
Orchitis
Hepatitis
Pneumonia
Encephalitis
Infected spots
Otitis media
Myocarditis
Glomerulonephritis
Appendicitis
Pancreatitis

Treatment is symptomatic and includes using paracetamol to manage fever. There is a link between use of ibuprofen in patients with chicken-pox and necrotizing fasciitis so Ibuprofen should NOT be used.

An emollient and antihistamine can be used to ease the itchy rash and oral hydration is encouraged.

Gastric emptying is increased by:
Distension of the pyloric antrum
A fall in the pH of chyme in the stomach
Parasympathetic stimulation (via vagus)
Gastrin
The hormones secretin, cholecystokinin and gastric inhibitory polypeptide (GIP) inhibit gastric emptying.

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.

Dobutamine is a synthetic isoprenaline derivative that is used to provide inotropic support to patients with low cardiac output caused by septic shock, myocardial infarction, or other cardiac conditions.

Dobutamine is a sympathomimetic drug that stimulates beta-1 adrenergic receptors in the heart to produce its primary effect. As a result, it has inotropic properties that increase cardiac contractility and output. It also has a small amount of alpha1- and beta-2-adrenergic activity.

It is infused intravenously after being diluted to a volume of at least 50 ml in a suitable crystalloid solution. The dose is titrated to response and ranges from 0.5 to 40 g/kg/min. Extravasation-induced skin necrosis is uncommon, and dobutamine can be administered through a peripheral line.

At doses below 10 g/kg/min, side effects are rare, but at higher doses, they can include:
Nausea and vomiting
Tachycardia
Dysrhythmias
Angina
Hypertension
Headache

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 hip adductors are a group of five muscles located in the medial compartment of the thigh. These muscles are the adductor longus, adductor brevis, adductor magnus, gracilis, and pectineus.

The hip flexors consist of 5 key muscles that contribute to hip flexion: iliacus, psoas, pectineus, rectus femoris, and sartorius.

PTH is synthesised and released from the chief cells of the four parathyroid glands located behind the thyroid gland.
It is a polypeptide containing 84 amino acids and it controls free calcium in the body.

The following stimuli causes release of PTH:
Increased plasma phosphate concentration
Decreased plasma calcium concentration

PTH release is inhibited by:
Normal or increased plasma calcium concentration
Hypomagnesaemia

The main actions of PTH are:
Increases plasma calcium concentration
Decreases plasma phosphate concentration
Increases osteoclastic activity (increasing calcium and phosphate resorption from bone)
Increases renal tubular reabsorption of calcium
Decreases renal phosphate reabsorption
Increases renal conversion of 25-hydroxycholecalciferol to 1,25-dihydroxycholecalciferol (via stimulation of 1-alpha hydroxylase)
Increases calcium and phosphate absorption in the small intestine (indirectly via increased 1,25-dihydroxycholecalciferol)

The O’Donoghue unhappy triad or terrible triad often occurs in contact and non-contact sports, such as basketball, football, or rugby, when there is a lateral force applied to the knee while the foot is fixated on the ground. This produces an abduction-external rotation mechanism of injury.

The O’Donoghue unhappy triad comprises three types of soft tissue injury that frequently tend to occur simultaneously in knee injuries. O’Donoghue described the injuries as: anterior cruciate ligament tear, medial collateral ligament injury, and medial meniscal tear (lateral compartment bone bruise).

In experimental studies, the researcher introduces an intervention and studies the effect. The study subjects are allocated into different groups by the investigator through the use of randomisation. Randomisation serves to remove any potential bias.

A cohort study is a form of longitudinal, observational study that follows a group of patients (the cohort) over a period of time to monitor the effects of exposure to a proposed aetiological factor upon them.

A case-control study is a type observational study. Here, patients who have developed a disease are identified and compared on the basis of proposed causative factors that occurred in the past, to a control group.

Clinical trials are experimental studies. Examples include: double blind, single blind, and unblinded studies(both patient and researcher are aware of the treatment they receive)

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.

The following are the lesions of the cranial nerves:
1. Olfactory nerve (I)
Reduced taste and smell, but not to ammonia which stimulates the pain fibres carried in the trigeminal nerve

2. Optic nerve (II)
Manifested by visual field defects, pupillary abnormalities, optic neuritis, optic atrophy, papilledema

3. Oculomotor nerve (III)
A fixed, dilated pupil which doesn’t accommodate, ptosis, complete internal ophthalmoplegia (masked by ptosis), unopposed lateral rectus causes outward deviation of the eye. If the ocular sympathetic fibres are also affected behind the orbit, the pupil will be fixed but not dilated.

4. Trochlear nerve (IV)
Diplopia due to weakness of downward and inward eye movement. The most common cause of a pure vertical diplopia. The patient tends to compensate by tilting the head away from the affected side.

5. Trigeminal nerve (V)
Reduced sensation or dysesthesia over the affected area. Weakness of jaw clenching and side-to-side movement. If there is a lower motor neuron (LMN) lesion, the jaw deviates to the weak side when the mouth is opened. There may be fasciculation of temporalis and masseter.

6. Abducens nerve (VI)
Inability to look laterally. The eye is deviated medially because of unopposed action of the medial rectus muscle.

7. Facial nerve (VII)
Facial weakness. In an LMN lesion the forehead is paralysed – the final common pathway to the muscles is destroyed; whereas the upper facial muscles are partially spared in an upper motor neurone (UMN) lesion because of alternative pathways in the brainstem. There appear to be different pathways for voluntary and emotional movement. CVAs usually weaken voluntary movement, often sparing involuntary movements (e.g., spontaneous smiling). The much rarer selective loss of emotional movement is called mimic paralysis and is usually due to a frontal or thalamic lesion.

8. Vestibulocochlear nerve (VIII)
Unilateral sensorineural deafness, tinnitus. Slow-growing lesions seldom present with vestibular symptoms as compensation has time to occur.

9. Glossopharyngeal nerve (IX)
Unilateral lesions do not cause any deficit because of bilateral corticobulbar connections. Bilateral lesions result in pseudobulbar palsy. These nerves are closely interlinked.

10. Vagus nerve (X)
Palatal weakness can cause ‘nasal speech’ and nasal regurgitation of food. The palate moves asymmetrically when the patient says ‘ahh’. Recurrent nerve palsy results in hoarseness, loss of volume and ‘bovine cough’.

11. Accessory nerve (XI)
Weakness and wasting of sternocleidomastoid and trapezius muscles

12.Hypoglossal nerve (XII)
An LMN lesion produces wasting of the ipsilateral side of the tongue, with fasciculation; and on attempted protrusion the tongue deviates towards the affected side, but the tongue deviates away from the side of a central lesion.

The pectoralis major is a muscle that runs across the top of the chest and connects to a ridge on the back of the humerus (the bone of the upper arm).

Adduction, or lowering, of the arm (opposed to the deltoideus muscle) and rotation of the arm forward around the axis of the body are two of its main functions.

Alveolar type II cells are responsible for four primary functions: surfactant synthesis and secretion, xenobiotic metabolism, water transepithelial transport, and alveolar epithelium regeneration following lung injury.

Erythropoietin is a glycoprotein hormone that regulates the formation of red blood cells (red cell production). It is mostly produced by interstitial fibroblasts in the kidney, which are located near the PCT. It is also produced in the liver’s perisinusoidal cells, however this is more common during the foetal and perinatal periods.

The kidneys produce and secrete erythropoietin in response to hypoxia. On red blood cells, erythropoietin has two main effects:
– It encourages stem cells in the bone marrow to produce more red blood cells.
– It protects red blood cell progenitors and precursors from apoptosis by targeting them in the bone marrow.
As a result of the increased red cell mass, the oxygen-carrying capacity and oxygen delivery increase.