Bicarbonate is freely filtered at the glomerulus. Less than 0.1% of filtered bicarbonate is normally excreted in the urine (if plasma [HCO3-] increases, maximum tubular transport is exceeded and some HCO3-is excreted in urine). About 80% of bicarbonate is reabsorbed in the proximal tubule. For each H+secreted into the lumen, one Na+and one HCO3-are reabsorbed into the plasma. H+is recycled so there is little net secretion of H+at this stage. A further 10 – 15% of HCO3-is similarly reabsorbed in the thick ascending limb of the loop of Henle. In the early distal tubule, H+secretion is predominantly by Na+/H+exchange but more distally, the Na+gradient is insufficient so secretion is via H+ATPase and H+/K+ATPase in intercalated cells, which contain plentiful carbonic acid.

As secreted H+is derived from CO2, new HCO3-is formed and returns to the blood.H+secretion is proportional to intracellular [H+] which itself is related to extracellular pH. A fall in blood pH will therefore stimulate renal H+secretion. In the proximal tubule secretion of H+serves to reclaim bicarbonate from glomerular filtrate so it is not lost, but in the distal nephron, secretion leads to net acid excretion and generation of new bicarbonate.

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.

A common complication of long term lithium therapy results in most cases of lithium intoxication. It is caused by reduced excretion of the drug which can be due to several factors including deterioration of renal function, dehydration, hyponatraemia, infections, and co-administration of diuretics or NSAIDs or other drugs that may interact.

Inversion of the foot is achieved by the tibialis anterior which is innervated by the deep fibular nerves, and the tibialis posterior muscles which is innervated by the tibial nerve respectively.

Factors causing bronchoconstriction:

• Via muscarinic receptors
• Parasympathetic stimulation
• Stimulation of irritant receptors
• Inflammatory mediators e.g. histamine, prostaglandins, leukotrienes
• Beta-blockers

Bacteriostatic antibiotics include erythromycin and other macrolides. They work by attaching to the bacterial ribosome’s 50S subunit, preventing translocation and, as a result, inhibit protein synthesis. Macrolide antibiotics are actively concentrated inside leukocytes and delivered into the infection site as a result.

Action Mechanisms- Examples:

Cell wall production is inhibited
Vancomycin
Vancomycin
Cephalosporins

The function of the cell membrane is disrupted
Nystatin
Polymyxins
Amphotericin B

Inhibition of protein synthesis
Chloramphenicol
Macrolides
Aminoglycosides
Tetracyclines

Nucleic acid synthesis inhibition
Quinolones
Trimethoprim
Rifampicin
5-nitroimidazoles
Sulphonamides
Anti-metabolic activity
Isoniazid

Parathyroid hormone (PTH) is a peptide hormone synthesised by the chief cells of the parathyroid glands, located immediately behind the thyroid gland. PTH is primarily released in response to decreasing plasma [Ca2+] concentration. PTH acts to increase plasma calcium levels and decrease plasma phosphate levels.
Parathyroid hormone (PTH) acts to increase calcium reabsorption in the distal tubule of the nephron (by activating Ca2+entry channels in the apical membrane and the Ca2+ATPase pump in the basolateral membrane) and increase phosphate excretion by inhibiting reabsorption in the proximal tubule of the nephron.

The vocal cords of the larynx are strongly
approximated, and the larynx is pulled upward
and anteriorly by the neck muscles. These actions,
combined with the presence of ligaments that
prevent upward movement of the epiglottis, cause
the epiglottis to swing back over the opening
of the larynx. All these effects acting together
prevent the passage of food into the nose and
trachea. Most essential is the tight approximation
of the vocal cords, but the epiglottis helps to
prevent food from ever getting as far as the vocal
cords. Destruction of the vocal cords or of the
muscles that approximate them can cause
strangulation.

Flumazenil is a benzodiazepine antagonist that can be helpful in some overdose situations. It works quickly (in less than a minute), but the effects are fleeting, lasting less than an hour. The dose is 200 micrograms every 1-2 minutes with a maximum dose of 3 milligrams per hour.

Flumazenil should be avoided by patients who are addicted to benzodiazepines or who take tricyclic antidepressants because it can cause withdrawal symptoms. It can cause seizures or cardiac arrest in these situations.

Second line drugs to reduce the severity and duration of anaphylactic symptoms are intravenous or intramuscular chlorpheniramine and hydrocortisone. The recommended dose is 10 mg chlorpheniramine and 200 mg hydrocortisone in adults.

Aspirin is a non-steroidal anti-inflammatory drug (NSAID). Aspirin irreversibly inhibits cyclooxygenase (COX) enzymes and the resulting inhibition of prostaglandin synthesis results in analgesic, antipyretic and to a lesser extent anti-inflammatory actions.

According to a 2018 audit conducted by the Royal College of Emergency Medicine (RCEM), the standard of care for children presenting to EDs with fractured limbs has deteriorated, with most patients waiting longer than ever before for pain relief. More than one-tenth of the children who came in with significant pain from a limb fracture received no pain relief at all.

For all patients, including children, the Agency for Health Care Policy and Research (AHCPR) in the United States recommends using the ABCs of pain management:
A – Ask about pain regularly. Assess pain systematically.
B – Believe the patient and family in their reports of pain and what relieves it.
C – Choose pain control options appropriate for the patient, family, and setting.
D – Deliver interventions in a timely, logical, coordinated fashion.
E – Empower patients and their families. Enable patients to control their course to the greatest extent possible.

The RCEM guidelines recommend assessing a child’s pain within 15 minutes of arrival. This is a fundamental requirement. For the assessment of pain in children, a variety of rating scales are available; which one is used depends on the child’s age and ability to use the scale. These are some of them:
Faces of Wong-Baker Scale for assessing pain
Scale of numerical evaluation
The behavioural scale is a scale that measures how people behave.

The RCEM has provided the following visual guide:
The RCEM has established the following guidelines for when patients in severe pain should receive appropriate analgesia:
100% within 60 minutes of arrival or triage, whichever is earliest
75% within 30 minutes of arrival or triage, whichever is earliest
50% within 20 minutes of arrival or triage, whichever is earliest

Nitrates are used in the treatment of angina pectoris and the prevention of myocardial ischaemia. Commonly used examples of nitrates are glyceryl trinitrate and isosorbide dinitrate. Unwanted effects, however, are common and can limit therapy, particularly when angina is severe or when patients are unusually sensitive to the effects of nitrates.
The following are common or very common side effects of nitrates
Arrhythmias
Asthenia
Cerebral ischaemia
Dizziness
Drowsiness
Flushing
Headache
Hypotension
Nausea and vomiting
Diarrhoea, syncope and cyanosis can occur, but these are rare side effects. Dry eyes, bradycardia and metabolic acidosis have not been reported.

Erythromycin and clarithromycin inhibit cytochrome P450-mediated metabolism of warfarin, phenytoin and carbamazepine and may lead to accumulation of these drugs. There is an increased risk of myopathy (due to cytochrome P450 enzyme CYP3A4 inhibition) if erythromycin or clarithromycin is taken with atorvastatin or simvastatin. Erythromycin increases plasma concentrations of theophylline, and theophylline may also reduce absorption of oral erythromycin. All macrolides can prolong the QT-interval and concomitant use of drugs that prolong the QT interval is not recommended.

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.

One of the major complications of gastroenteritis is dehydration. Choosing the correct fluid replacement therapy is essential according to a patient’s hydration status.

Oral rehydration therapy (ORT) refers to the restitution of water and electrolyte deficits in dehydrated patients using an oral rehydration salt (ORS) solution. It is a fluid replacement strategy that is less invasive than other strategies for fluid replacement and has successfully lowered the mortality rate of diarrhoea in developing countries.

Some characteristics of Oral rehydration solutions are:
– slightly hypo-osmolar (about 250 mmol/litre) to prevent the possible induction of osmotic diarrhoea.
– contain glucose (e.g. 90 mmol/L in dioralyte). The addition of glucose improves sodium and water absorption in the bowel and prevents hypoglycaemia.
– also contains essential mineral salts

Current NICE guidance recommends that 50 ml/kg is given over 4 hours to treat mild dehydration.
Once rehydrated, a child should continue with their usual daily fluid intake plus 200 ml ORT after each loose stool. In an infant, give ORT at 1-1.5 x the normal feed volume and in an adult, give 200-400 ml after each loose stool.

Aspirin (at analgesic doses) is contraindicated in severe heart failure. Aspirin irreversibly inhibits cyclooxygenase (COX) enzymes resulting in decreased production of prostaglandins (which can lead to irritation of the gastric mucosa). The analgesic dose is greater than the antiplatelet dose, and taken orally it has a duration of action of about 4 hours. Clinical features of salicylate toxicity in overdose include hyperventilation, tinnitus, deafness, vasodilatation, and sweating.

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

At muscarinic receptors, atropine blocks the action of the parasympathetic neurotransmitter acetylcholine. As a result, it inhibits the vagus nerve’s effects on both the SA and AV nodes, increasing sinus automaticity and facilitating AV node conduction.

At muscarinic receptors, atropine blocks the action of the parasympathetic neurotransmitter acetylcholine. As a result, it inhibits the vagus nerve’s effects on both the SA and AV nodes, increasing sinus automaticity and facilitating AV node conduction.

The most common cause of asystole during cardiac arrest is primary myocardial pathology, not excessive vagal tone, and there is no evidence that atropine is helpful in the treatment of asystole or PEA. As a result, it is no longer included in the ALS algorithm’s non-shockable section. Atropine is most commonly used in the peri-arrest period. It is used to treat bradycardia (sinus, atrial, or nodal) or AV block when the patient’s haemodynamic condition is compromised by the bradycardia.

If any of the following adverse features are present, the ALS bradycardia algorithm recommends a dose of 500 mcg IV:
Shock
Syncope
Myocardial ischaemia
Heart failure

Atropine is also used for the following purposes:
Topically as a cycloplegic and mydriatic to the eyes
To cut down on secretions (e.g. in anaesthesia)
Organophosphate poisoning is treated with
Atropine’s side effects are dose-dependent and include:
Mouth is parched
Vomiting and nausea
Vision is hazy
Retention of urine
Tachyarrhythmias
It can also cause severe confusion and hallucinations in patients, especially the elderly.

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.

A type IV hypersensitivity reaction occurred in this patient. Allergic contact dermatitis is an inflammatory skin reaction occurring in response to an external stimulus, acting either as an allergen or an irritant, caused by a type IV or delayed hypersensitivity reaction. They usually take several days to develop.

Evidence-based medicine may be defined as the systematic, quantitative, preferentially experimental approach to obtaining and using medical information. Therefore, meta-analysis, a statistical procedure that integrates the results of several independent studies, plays a central role in evidence-based medicine.

Meta-analysis is a quantitative, formal, epidemiological study design used to systematically assess previous research studies to derive conclusions about that body of research. Outcomes from a meta-analysis may include a more precise estimate of the effect of treatment or risk factor for disease, or other outcomes, than any individual study contributing to the pooled analysis.

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.

ACTH secretion is stimulated by corticotropin-releasing hormone (CRH) from the hypothalamus.

Parathyroid hormone (PTH) is a polypeptide containing 84 amino acids. It is the principal controller of free calcium in the body.
PTH is synthesised by and released from the chief cells of the four parathyroid glands that are located immediately behind the thyroid gland.
PTH is released in response to the following stimuli:
Decreased plasma calcium concentration
Increased plasma phosphate concentration (indirectly by binding to plasma calcium and reducing the calcium concentration)
PTH release is inhibited by the following factors:
Normal/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)

Pancreatic exocrine secretion is controlled by:
Parasympathetic stimulation which enhances secretion of both the enzyme and aqueous components
Sympathetic stimulation which inhibits pancreatic secretion
Secretin which stimulates secretion of the alkaline-rich fluid from ductal cells
Cholecystokinin which stimulates secretion of the enzyme-rich fluid from acinar cellsSomatostatin which inhibits secretion from both acinar and ductal cells
Gastrin which stimulates pancreatic acinar cells to secrete digestive enzymes

Blood loss from the gastrointestinal (GI) tract is the most common cause of iron deficiency anaemia in adult men and postmenopausal women.

Deficiency of Factor IX causes Haemophilia B, and like the other Haemophilia’s, it has an X-linked recessive pattern of inheritance, affecting males born to carrier mothers.

Haemophilia B is the second commonest form of haemophilia and is rarer than haemophilia A. Haemophilia B is similar to haemophilia A but is less severe. You can distinguish the two disorders by specific coagulation factor assays.

The incidence of Haemophilia B is one-fifth of that of haemophilia A.

In laboratory findings, you get prolonged APTT, normal PT and low factor IX for Haemophilia B.

There is also a variation called Leyden, in which factor IX levels are below 1% until puberty, when they rise, potentially reaching as high as 40-60% of normal. This is thought to be due to the effects of testosterone at puberty.

On standing from a prone position, gravity causes blood to pool in veins in the legs. Central venous pressure (CVP) falls, causing a fall in stroke volume and cardiac output (due to Starling’s law) and thus a fall in blood pressure. Normally this fall in BP is rapidly corrected by the baroreceptor reflex which causes venoconstriction (partially restoring CVP), and an increase in heart rate and contractility, so restoring cardiac output and blood pressure. Impaired autonomic nervous activity in the elderly accounts for the greater likelihood of postural hypotension. Any symptoms of dizziness, blurred vision or syncope is due to a transient fall in cerebral perfusion that occurs before cardiac output and mean arterial pressure (MAP) can be corrected.

Prednisolone is four times more potent than hydrocortisone, and therefore, a dose of 25 mg would be equivalent to 100 mg of hydrocortisone.
The following table summarises the relative potency of the main corticosteroids compared with hydrocortisone:
Corticosteroid
Potency relative to hydrocortisone
Prednisolone
4 times more potent
Triamcinolone
5 times more potent
Methylprednisolone
5 times more potent
Dexamethasone
25 times more potent