Giardia lambliainfection occurs through the ingestion of dormant microbial cysts in contaminated water, food or via faceo-oral transmission via poor hygiene.
Following ingestion of the cysts, the trophozoite emerges to an active state of feeding and motility. After the feeding stage they undergo asexual replication through longitudinal binary fission.
They attach to the intestinal wall via a specialised sucking disc. The mechanism for diarrhoea in giardiasis remains unknown but could possibly be due to direct cytotoxicity.
Giardial trophozoites and cysts pass through the digestive system in the faeces and are excreted. While the trophozoites may be found in the faeces, only the cysts are adapted for long-term survival outside the host.

Pectoralis major is a thick, fan-shaped muscle situated in the chest. It makes up the bulk of the chest musculature in the male and lies underneath the breast in the female. It overlies the thinner pectoralis minor muscle.
Superficial muscles of the chest and arm showing pectoralis major (from Gray’s Anatomy)
Pectoralis major has two heads; the clavicular head and the sternocostal head. The clavicular head originates from the anterior border and medial half of the clavicle. The sternocostal head originates from the anterior surface of the sternum, the superior six costal cartilages and the aponeurosis of the external oblique muscle. It inserts into the lateral lip of the bicipital groove of the humerus.
Pectoralis major receives dual innervation from the medial pectoral nerve and the lateral pectoral nerve.
Its main actions are as follows:
Flexes humerus (clavicular head)
Extends humerus (sternocostal head)
Adducts and medially rotates the humerus
Draws scapula anteriorly and inferiorly

A suprascapular nerve injury causes numbness in the shoulder, as well as weakness in abduction and external rotation.

Damage to the axillary nerve can result in shoulder or arm muscle weakness, as well as difficulty lifting the arm. This is because the deltoid and supraspinatus muscles, which are innervated by the axillary and suprascapular nerves, are responsible for abduction of the arm at the shoulder joint.

Many medications, including warfarin, require cytochrome P450 enzymes for their metabolism. When co-prescribing cytochrome p450 enzyme inducers and inhibitors with warfarin, it’s critical to be cautious.

Inhibitors of the cytochrome p450 enzyme potentiate the effects of warfarin, resulting in a higher INR. To remember the most commonly encountered cytochrome p450 enzyme inhibitors, use the mnemonic O DEVICES:

O– Omeprazole
D– Disulfiram
E– Erythromycin (And other macrolide antibiotics)
V– Valproate (sodium valproate)
I– Isoniazid
C– Ciprofloxacin
E– Ethanol (acute ingestion)
S- Sulphonamides

When autonomic reflexes are impaired or intravascular volume is markedly depleted, a significant reduction in blood pressure occurs upon standing, a phenomenon termed Postural Hypotension (orthostatic hypotension). Orthostatic hypotension can cause dizziness, syncope, and even angina or stroke. When autonomic reflexes are impaired, blood pressure falls progressively after standing because the gravitational pooling of blood in the legs cannot be compensated by sympathetic vasoconstriction.

Factors increasing FRC:
Emphysema
Air trapping in asthma
Ageing (due to loss of elastic properties)
Increasing height of patient

Beta-blockers are contraindicated in Prinzmetal’s angina.Beta-blockers may be indicated in:HypertensionPheochromocytoma (only with an alpha-blocker)AnginaSecondary prevention after ACSArrhythmias including atrial fibrillationHeart failureThyrotoxicosisAnxietyProphylaxis of migraineEssential tremorGlaucoma

Platelets are produced in the bone marrow by fragmentation of the cytoplasm of megakaryocytes, derived from the common myeloid progenitor cell. The time interval from differentiation of the human stem cell to the production of platelets averages 10 days. Thrombopoietin is the major regulator of platelet formation and 95% of this is produced by the liver. The normal platelet count is approximately 150 – 450 x 109/L and the normal platelet lifespan is 10 days. Under normal circumstances, about one-third of the marrow output of platelets may be trapped at any one time in the normal spleen.

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

Absolute risk and relative risk are used to assess the strength of a relationship between a disease and a factor that may affect it.

Absolute risk (AR) is the risk of developing a disease over a time period:
AR = the number of events that occur in a group / number of people in that group

The absolute risk reduction (ARR) is the difference between the absolute risk in the control group (ARC) and the absolute risk in the treated group (ART).

ARR = ARC – ART

The control group is the warfarin group, therefore the ARC is 20/500 (0.04).
Treatment group is the ticagrelor group and ART = 30/300 (0.1).

ARR = 0.04 – 0.1 = -0.06. This shows that treatment with ticagrelor increases risk of developing stroke. This is also termed a relative risk increase.

Relative risk, or risk ratio, (RR) is used to compare the risk in the two different groups. It is the ratio of the absolute risks of the disease in the treatment group (ART) to the absolute risk of the disease in the control group (ARC):
RR=ART /ARC

Therefore RR = 0.1 / 0.04 = 2.5
RR < 1 means the intervention reduces the risk of the outcome being studied
RR = 1 means the treatment has no effect on the outcome being studied
RR > 1 means the intervention increased the risk of the outcome being studied
Since RR is 2.5, ticagrelor increases the risk of stroke.

SUMMARY
Absolute risk reduction is -0.06
Absolute risk in warfarin group = 0.04
Relative risk = 2.5
Ticagrelor has no effect on stroke is incorrect because RR is not =1

The popliteal artery divides into the anterior and posterior tibial arteries at the lower border of the popliteus after exiting the popliteal fossa between the gastrocnemius and popliteus muscles.

In its typical anatomical orientation, the heart has 5 surfaces formed by different internal divisions of the heart:

Anterior (or sternocostal) – Right ventricle
Posterior (or base) – Left atrium
Inferior (or diaphragmatic) – Left and right ventricles
Right pulmonary – Right atrium
Left pulmonary – Left ventricle

The silhouette sign of Felson is with respect to the right middle lobe. The right heart border should have a distinct appearance due to the right atrium abutting aerated right middle lobe. The consolidation in the right middle lobe has resulted in loss of this silhouette.

Cyclizine acts by inhibiting histamine pathways and cholinergic pathways involved in transmission from the vestibular apparatus to the vomiting centre. Metoclopramide is a dopamine-receptor antagonist which acts both peripherally in the GI tract and centrally within the chemoreceptor trigger zone. Prochlorperazine is a dopamine-D2 receptor antagonist and acts centrally by blocking the chemoreceptor trigger zone. Metoclopramide and prochlorperazine are both commonly associated with extrapyramidal effects, such as acute dystonic reaction. Cyclizine may rarely cause extrapyramidal effects.

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.

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.

Aspirin (at analgesic doses) is contraindicated in:
People with a history of true hypersensitivity to aspirin or salicylates (symptoms of hypersensitivity to aspirin or salicylates include bronchospasm, urticaria, angioedema, and vasomotor rhinitis)
People with active or previous peptic ulceration
People with haemophilia or another bleeding disorder
Children younger than 16 years of age (risk of Reye’s syndrome)
People with severe cardiac failure
People with severe hepatic impairment
People with severe renal impairment

N.B. Owing to an association with Reye’s syndrome, aspirin-containing preparations should not be given to children under 16 years, unless specifically indicated, e.g. for Kawasaki disease.

Erythrocytes have a normal lifespan of about 120 days. Mature erythrocytes are biconcave discs with no nucleus, ribosomes or mitochondria but with the ability to generate energy as ATP by the anaerobic glycolytic pathway. The red cell membrane consists of a bipolar lipid layer with a membrane skeleton of penetrating and integral proteins anchoring carbohydrate surface antigens. The shape and flexibility of red cells allows them to deform easily and pass through capillaries.

Digoxin is a cardiac glycoside used in the treatment of atrial fibrillation and flutter, and congestive cardiac failure. It acts by inhibiting the membrane Na/K ATPase in cardiac myocytes. This raises intracellular sodium concentration and increases intracellular calcium availability indirectly via Na/Ca exchange. The increase in intracellular calcium levels causes an increases the force of myocardial contraction (positive inotrope), and slows the heart rate (negative chronotrope).

Mannitol is an osmotic diuretic that can be used to treat cerebral oedema and raised intraocular pressure. Mannitol is a low molecular weight compound and is, therefore, freely filtered at the glomerulus and is not reabsorbed. It, therefore, increases the osmolality of the glomerular filtrate and tubular fluid, increasing urinary volume by an osmotic effect. It also does not cross the blood-brain-barrier (BBB).

Lymphomas are a group of diseases caused by malignant lymphocytes that accumulate in lymph nodes and other lymphoid tissue and cause the characteristic clinical feature of lymphadenopathy. The major subdivision of lymphomas is into Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) and this is based on the histological presence of Reed-Sternberg cells present in HL. Hodgkin lymphoma can present at any age but is rare in children and has a peak incidence in young adults. There is an almost 2 : 1 male predominance. Most patients present with painless, asymmetrical, firm and discrete enlargement of superficial lymph nodes. Cervical nodes are involved in 60-70% of cases, axillary nodes in 10-15% and inguinal nodes in 6-12%. Modest splenomegaly occurs during the course of the disease in 50% of patients; the liver may also be enlarged. Bone marrow failure involvement is unusual in early disease. The prognosis depends on age, stage and histology, but overall approximately 85% of patients are cured. Alcohol‐induced pain and pruritus are two well‐known but rare symptoms in HL.

The nephron’s blood flow is as follows:
Afferent arteriole – Glomerular capillary – Efferent arteriole – Peritubular capillary – Vasa recta – Afferent arteriole – Glomerular capillary – Efferent arteriole – Peritubular capillary – Vasa recta

The kidney is the only vascular network in the body with two capillary beds. With arterioles supplying and draining the glomerular capillaries, higher hydrostatic pressures at the glomerulus are maintained, allowing for better filtration. A second capillary network at the tubules enables for secretion and absorption in the tubules, as well as concentrating urine.

Klebsiella spp. are facultatively anaerobic Gram-negative rods, found in the normal intestinal and respiratory flora. These organisms are usually opportunistic pathogens that cause nosocomial infections, most commonly pneumonia and UTI.

Aminophylline has the following properties:
Phosphodiesterase inhibitor that increases intracellular cAMP and relaxes smooth muscle in the bronchial airways and pulmonary blood vessels.
Mast cell stabilization is achieved by using a non-selective adenosine receptor antagonist.

The NICE guidelines for pregnant women with lower UTIs are:
1. Prescribe an antibiotic immediately, taking into account the previous urine culture and susceptibility results or avoiding past antibiotics that may have caused resistance
2. Obtain a midstream urine sample before starting antibiotics and send for urine culture and susceptibility
– Review the choice of antibiotic when the results are available
– change the antibiotic according to susceptibility results if the bacteria are resistant, using a narrow-spectrum antibiotic wherever possible

The first choice of antibiotics for pregnant women aged 12 years and over is:
1. Nitrofurantoin
100 mg modified-release PO BD for 3 days – if eGFR >45 ml/minute

The 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. Amoxicillin
500 mg PO TDS for seven days (ONLY if culture results available and susceptible)
2. Cefalexin
500 mg BD for seven days
Alternative second-choices – consult local microbiologist, choose antibiotics based on culture and sensitivity results

There is a lifelong susceptibility to increased risk of infection from a variety of organisms in patients with hyposplenism, especially in children under 5 years and those with sickle cell anaemia. Patients are most susceptible is to the encapsulated bacteria Streptococcus pneumoniae, Haemophilus influenzae type B and Neisseria meningitidis. Streptococcus pneumoniae is particular concerning as it can cause rapid and fulminant disease, which can be fatal. Malaria and animal bites that become infected also tend to be more severe.

Nosocomial infections are defined as those occurring within 48 hours of hospital admission, 3 days of discharge or 30 days of an operation. They affect 1 in 10 patients admitted to hospital. Annually, this results in 5000 deaths with a cost to the National Health Service of a billion pounds. On average, a patient with hospital acquired infection spent 2.5-times longer in hospital, incurring additional costs of £3000 more than an uninfected patient. Intensive care units (ICU) have the highest prevalence of hospital-acquired infections in the hospital setting.
The current recommendations by NICE and the BNF on the treatment of hospital acquired pneumonia are:
Early onset infection(less than 5 days after admission to hospital): co-amoxiclav or cefuroxime for 7 days
Late-onset infection(more than 5 days after admission to hospital): an antipseudomonal penicillin (e.g. piperacillin with tazobactam), a broad-spectrum cephalosporin (e.g. ceftazidime), or a quinolone (e.g. ciprofloxacin)
If the patient developed a hospital-acquired pneumonia within 5 days of admission – co-amoxiclav would be the most appropriate choice.
If the patient has developed a hospital-acquired pneumonia > 5 days after admission – ciprofloxacin would be the most appropriate choice from the list of options available.

Post-streptococcal glomerulonephritis is a postinfectious immune-mediated reaction secondary to infection with Streptococcus pyogenes. It typically occurs 2 weeks or more after acute/initial infection, and presents with haematuria, reduced urine output, peripheral oedema, proteinuria, and hypertension. Permanent kidney damage is rare.

End-organ damage (e.g. encephalopathy, intracranial haemorrhage, acute myocardial infarction or ischaemia, dissection, pulmonary oedema, nephropathy, eclampsia, papilledema, and/or angiopathic haemolytic anaemia) characterises a hypertensive emergency (also known as ‘accelerated hypertension’ or malignant hypertension’ It’s a life-threatening condition that necessitates rapid blood pressure reduction to avoid end-organ damage and a negative outcome.

Hypertensive encephalopathy is a syndrome that includes headaches, seizures, visual changes, and other neurologic symptoms in people who have high blood pressure. It is reversible if treated quickly, but it can progress to coma and death if not treated properly.

Any patient with suspected hypertensive encephalopathy should have an urgent CT scan to rule out an intracranial haemorrhage, as rapid blood pressure reduction could be dangerous in these circumstances.

The drug of choice is labetalol, which reduces blood pressure steadily and consistently without compromising cerebral blood flow.
An initial reduction of approximately 25% in mean arterial pressure (MAP) over an hour should be aimed for, followed by a further controlled MAP reduction over the next 24 hours. In patients who are unable to take beta-blockers, nicardipine can be used as a substitute.

Fibrinoid necrosis occurs in malignant hypertension where increased arterial pressure results in necrosis of smooth muscle wall. Eosinophilic and fibrinous deposits are seen.

Hutchinson sign relates to involvement of the tip of the nose from facial herpes zoster. It implies involvement of the external nasal branch of the nasociliary nerve which is a branch of the ophthalmic division of the trigeminal nerve.

The nasociliary branch of the trigeminal nerve innervates the apex and lateral aspect of the nose, as well as the cornea. Therefore, lesions on the side or tip of the nose should raise suspicion of ocular involvement.

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.

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.

A median nerve block is a simple, safe, and effective method of obtaining anaesthesia to the palmar aspect of the thumb, index finger, middle finger, radial portion of the palm and ring finger. The median nerve lies deep to the flexor retinaculum and about one centimetre under the skin of the volar wrist.
The palmaris longus tendon lies superficial to the retinaculum and is absent in up to 20% of patients.
The median nerve is located slightly lateral (radial) to the palmaris longus tendon and medial (ulnar) to the flexor carpi radialis tendon.

The procedure is as follows:
– Check sensation and motor function of the median nerve. Wear gloves and use appropriate barrier precautions.
– Locate the flexor carpi radialis and palmaris longus tendons, which become prominent when the patient flexes the wrist against resistance. The palmaris longus tendon is usually the more prominent of the two tendons.
– Needle-entry site: The needle will be inserted adjacent to the radial (lateral) border of the palmaris longus tendon just proximal to the proximal wrist crease. If the palmaris longus tendon is absent, the needle-entry site is about 1 cm ulnar to the flexor carpi radialis tendon.
– Cleanse the site with antiseptic solution. Place a skin wheal of anaesthetic, if one is being used, at the needle-entry site.
– Insert the needle perpendicularly through the skin and advance it slowly until a slight pop is felt as the needle penetrates the flexor retinaculum. When paraesthesia in the distribution of the median nerve confirms proper needle placement, withdraw the needle 1 to 2 mm.
– Aspirate to exclude intravascular placement and then slowly (i.e., over 30 to 60 seconds) inject about 3 mL of anaesthetic. If the patient does not feel paraesthesia, redirect the needle in an ulnar direction, under the palmaris longus tendon. If paraesthesia is still not felt, slowly inject 3 to 5 mL of anaesthetic in the proximity of the nerve 1 cm deep to the tendon.
– Allow about 5 to 10 minutes for the anaesthetic to take effect.

Passive expiration is produced primarily by relaxation of the inspiratory muscles (diaphragm and external intercostal muscles) in addition to the elastic recoil of the lungs.
In expiration, several movements occur. There are:
1. depression of the sternal ends of the ribs (‘pump handle’ movement),
2. depression of the lateral shafts of the ribs (‘bucket handle’ movement) and
3. elevation of the diaphragm.
These result in a reduction of the thorax in an anteroposterior, transverse and vertical direction respectively. There is then a decreased intrathoracic volume and increased intrathoracic pressure and air is forced out of the lungs.

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

Vaccination induces ACTIVE adaptive immunity. Actively acquired immunity involves the development of an immune response either due to vaccination or natural exposure to a pathogen and leads to long-lasting resistance to infection.

Immediate protection is achieved with injection of immunoglobulin. The protection is transient lasting only a few weeks and is useful as post-exposure prophylaxis.

Passively acquired immunity usually leads to short-lasting resistance to infection because it does not involve a host immune response.

With inactivated bacteria, a series of primary vaccinations is usually required to induce an adequate immune response. In most cases, boosters are required to sustain adequate immunity.

The oculomotor nerve is the third cranial nerve. It is the main source of innervation to the extraocular muscles and also contains parasympathetic fibres which relay in the ciliary ganglion. Damage to the third cranial nerve may cause diplopia, pupil mydriasis, and/or upper eyelid ptosis. The clinical manifestations of third cranial nerve dysfunction reflect its constituent parts.

In pregnancy and postpartum, lithium is an effective treatment for relapse prevention in bipolar disorder. However, lithium has also been associated with risks during pregnancy for both the mother and the unborn child. Recent large studies have confirmed the association between first-trimester lithium exposure and an increased risk of congenital malformations.

Lithium levels need to be monitored more frequently throughout pregnancy and the postnatal period.

If given in the 1st-trimester, lithium is associated with a risk of fetal cardiac malformations, such as Ebstein’s anomaly.

If given in the 2nd and 3rd-trimesters, there is a risk of the following:
1. hypotonia
2. lethargy
3. feeding problems
4. hypothyroidism
5. goitre
6. nephrogenic diabetes insipidus in the neonate

Patients at risk of gastro-intestinal ulceration (including the elderly) who need NSAID treatment should receive gastroprotective treatment. The current recommendations by NICE suggest that gastro-protection should be considered if patients have ≥1 of the following:
Using maximum recommended dose of an NSAID
Aged 65 or older
History of peptic ulcer or GI bleeding
Concomitant use of medications that increase risk:
Low dose aspirin
Anticoagulants
Corticosteroids
Anti-depressants including SSRIs and SNRIs
Requirements for prolonged NSAID usage:
Patients with OA or RA at any age
Long-term back pain if older than 45
It is suggested that if required, either omeprazole 20 mg daily or lansoprazole 15-30 mg daily should be the PPIs of choice.
This patient is on 400 mg of ibuprofen TDS, but the maximum recommended dose of ibuprofen is 2.4 g daily. Co-prescription of codeine, raised BMI, and a family history of peptic ulceration would also not prompt gastro-protection.

Etomidate causes less hypotension than thiopental sodium and propofol during induction. However, it 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. Pain on injection is common and there is a high rate of thrombophlebitis in the postoperative period. Postoperative nausea and vomiting commonly occur. Etomidate suppresses adrenocortical function, particularly during continuous administration, and it should not be used for maintenance of anaesthesia. It should be used with caution in patients with underlying adrenal insufficiency, for example, those with sepsis.

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.

In the presence of UVB light, 7-dehydrocholesterol is converted to cholecalciferol in the epidermal layer of the skin, resulting in 1,25-dihydroxycholecalciferol.

Cholecalciferol is then converted to 25-hydroxycholecalciferol in the endoplasmic reticulum of liver hepatocytes by 25-hydroxylase (calcifediol).

Finally, 1-alpha-hydroxylase converts 25-hydroxycholecalciferol to 1,25-dihydroxycholecalciferol in the kidney. The key regulatory point in the formation of 1,25-dihydroxycholecalciferol is 1-alpha-hydroxylase, which is induced by parathyroid hormone or hypophosphatemia.

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)

The anterior triangle is the triangular area of the neck found anteriorly to the sternocleidomastoid muscle. It is formed by the anterior border of sternocleidomastoid laterally, the median line of the neck medially and by the inferior border of the mandible superiorly. The apex of the anterior triangle extends towards the manubrium sterni. The anterior triangle contains:
Muscles: thyrohyoid, sternothyroid, sternohyoid muscles
Organs: thyroid gland, parathyroid glands, larynx, trachea, esophagus, submandibular gland, caudal part of the parotid gland
Arteries: superior and inferior thyroid, common carotid, external carotid, internal carotid artery (and sinus), facial, submental, lingual arteries
Veins: anterior jugular veins, internal jugular, common facial, lingual, superior thyroid, middle thyroid veins, facial vein, submental vein, lingual veins
Nerves: vagus nerve (CN X), hypoglossal nerve (CN XII), part of sympathetic trunk, mylohyoid nerve

The posterior triangle is a triangular area found posteriorly to the sternocleidomastoid muscle. It has three borders; anterior, posterior and inferior borders. The anterior border is the posterior margin of the sternocleidomastoid muscle. The posterior border is the anterior margin of the trapezius muscle, while the inferior border is the middle one-third of the clavicle. The investing layer of deep cervical fascia and integument forms the roof of the space, while the floor is covered with the prevertebral fascia along with levator scapulae, splenius capitis and the scalene muscles. The inferior belly of omohyoid subdivides the posterior triangle into a small supraclavicular, and a large occipital, triangle.
Contents:
Vessels: the third part of the subclavian artery, suprascapular and transverse cervical branches of the thyrocervical trunk, external jugular vein, lymph nodes
Nerves: accessory nerve (CN XI), the trunks of the brachial plexus, fibers of the cervical plexus

Gastrin secretion is stimulated by:
The presence of small peptides and amino acids in chyme
Gastric distension
Vagal stimulation directly via acetylcholine and indirectly via gastrin-releasing peptide (GRP)
Raised gastric pH

In life-threatening emergencies, oxygen should be started immediately otherwise, it should be prescribed like any other drug. The prescription should include a target saturation range.

Until blood gases can be measured, initial oxygen should be administered using a controlled concentration of 24% or 28%.
The ideal mask is a Venturi mask.

The other mask are not ideal for initial use

Tombstoning ST elevation myocardial infarction can be described as a STEMI characterized by tombstoning ST-segment elevation. This myocardial infarction is associated with extensive myocardial damage, reduced left ventricle function, serious hospital complications and poor prognosis. Tombstoning ECG pattern is a notion beyond morphological difference and is associated with more serious clinical results.

Studies have shown that tombstoning is more commonly found in anterior than non-anterior STEMI, thus, higher rates of left anterior descending artery disease are observed in patients with tombstoning pattern.

The following ECG leads determine the location and vessels involved in myocardial infarction:

ECG Leads Location Vessel involved
V1-V2 Septal wall Left anterior descending
V3-V4 Anterior wall Left anterior descending
V5-V6 Lateral wall Left circumflex artery
II, III, aVF Inferior wall Right coronary artery (80%) or Left circumflex artery (20%)
I, aVL High lateral wall Left circumflex artery
V1, V4R Right ventricle Right coronary artery
V7-V9 Posterior wall Right coronary artery

An intention tremor is characteristic of cerebellar dysfunction. Resting tremor may be seen in Parkinsonism.

Cushing’s syndrome is the name given to the clinical symptoms and signs induced by chronic glucocorticoid excess.

Extravasation of thiopental during injection can lead to tissue damage. Accidental intra-arterial injection causes vasospasm and may lead to thrombosis and tissue necrosis. Other side effects include involuntary muscle movements on induction, cough and laryngospasm, arrhythmias, hypotension, headache and hypersensitivity reactions. Thiopental sodium has anticonvulsant properties and does not cause seizures.

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.

Polycythaemia vera (PCV), which is also referred to as polycythaemia rubra vera, is a clonal haematological malignancy in which the bone marrow produces too many red blood cells. It may also result in the overproduction of white blood cells and platelets. It is most commonly seen in the elderly and the mean age at diagnosis is 65-74 years.
Patients can be completely asymptomatic and it is often discovered as an incidental finding on a routine blood count. Approximately 1/3 of patients present with symptoms due to thrombosis, of these 3/4 have arterial thrombosis and 1/4 venous thrombosis. Features include stroke, myocardial infarction, deep vein thrombosis and pulmonary embolism.
The other clinical features of PCV include:
Plethoric appearance
Lethargy and tiredness
Splenomegaly (common)
Pruritis (in 40% – particularly after exposure to hot water)
Headaches, dizziness and sweating (in 30%)
Gouty arthritis (in 20%)
Budd-Chiari syndrome (in 5-10%)
Erythromyalgia (in <5% – burning pain and red/blue discolouration of hands and feet)
Increased incidence of peptic ulcer disease (possibly related to increased histamine release from mast cells)
The diagnosis of PCV requires two major criteria and one minor criterion, or the first major criterion and two minor criteria:
Major criteria:
HB > 18.5 g/dl in men, 16.5 g/dl in women
Elevated red cell mass > 25% above mean normal predicted value
Presence of JAK2 mutation

Minor criteria:
Bone marrow biopsy showing hypercellularity with prominent erythroid, granulocytic and megakaryocytic proliferation
Serum erythropoietin level below normal range
Endogenous erythroid colony formation in vitro
The main aim of treatment is to normalize the full blood count and prevent complications such as thrombosis. Venesection is the treatment of choice but hydroxyurea can also be used to help control thrombocytosis.

Bone pain, pathologic fractures, weakness, anaemia, infection, hypercalcemia, spinal cord compression, and renal failure are all signs and symptoms of multiple myeloma (MM). The patient’s condition matched the signs and symptoms of myeloma.

Ambient air is atmospheric air in its natural state. Ambient air is typically 78.6% nitrogen and 20.9% oxygen. The extra 1% is made up of carbon, helium, methane, argon and hydrogen.

The partial pressure of any gas can be calculated using this formula: P = atmospheric pressure (760 mmHg) x percent content in the mixture.

Atmospheric pressure is the sum of all of the partial pressures of the atmospheric gases added together: The formula for atmospheric pressure is: Patm = PN2 + PO2 + PH2O + PCO2. The atmospheric pressure is known to be 760 mmHg.

The partial pressures of the various gases can be estimated to have partial pressures of approximately 597.4 mmHg for nitrogen, 158.8 mm Hg for oxygen, and 7.6 mmHg for argon.

Because of the shift of water from the intracellular to the extracellular compartment as a result of hyperglycaemia and increased plasma osmolality, dilutional hyponatraemia is common in diabetic ketoacidosis (DKA).

If intravenous fluids are not delivered with caution, hyponatraemia might worsen, which can lead to increased degrees of disorientation. Hyponatraemia has also been linked to an increased risk of cerebral oedema, especially if blood glucose levels drop too quickly following treatment.

Headache, recurrence of vomiting, irritability, Glasgow Coma Scale score, inappropriate heart rate slowing, and rising blood pressure are the most common causes of death in paediatric DKA, and children should be monitored for the symptoms mentioned above. To prevent this from developing,  s low osmolarity normalization, attention to glucose and salt levels, as well as hydration over 48 hours, is necessary. 

Angina pectoris is the most common symptom of ischemic heart disease and presents with chest pain relieved by rest and nitro-glycerine.

Nitrates are the first-line treatment to relieve chest pain caused by angina. The commonly used nitrates are:
1. Glyceryl trinitrate
2. Isosorbide dinitrate

Side effects to nitrate therapy are common especially
The most common side effects are:
1. Headaches
2. Feeling dizzy, weak, or tired
3. Nausea
4. Flushing

The serious but less likely to occur side effects are:
1. Methemoglobinemia (rare)
2. Syncope
3. Prolonged bleeding time
4. Exfoliative dermatitis
5. Unstable angina
6. Rebound hypertension
7. Thrombocytopenia

Dry eyes, bradycardia, and metabolic acidosis have not been reported.

Gentamicin, an aminoglycoside antibiotic, acts by binding to the 30S subunit of the bacterial ribosome inhibiting the binding of aminoacyl-tRNA, and thus prevents initiation of protein synthesis.

Two of its most notable side effects are reversible nephrotoxicity(caused by the inhibition of protein synthesis in renal cells, which causes acute tubular necrosis) and hearing loss (caused by damage to the vestibular apparatus of the inner ear).

Both side effects are dose-related and occur commonly in the elderly.

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.

A cricothyrotomy involves making an opening in the median cricothyroid ligament (the medial part of the cricothyroid membrane), between the cricoid cartilage below and the thyroid cartilage above.

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.

Because clearance varies greatly in critically ill patients, plasma concentrations cannot be predicted reliably from infusion rates.
Dopamine is given as an intravenous infusion, and because extravasation can cause tissue necrosis and sloughing, a central line is usually used (especially at higher doses >240 g/min). In an emergency, however, dopamine can be administered through a large vein (cephalic or basilic) while a central line is being prepared. Alkaline intravenous solutions inactivate it, so sodium bicarbonate should not be infused with it.

The following are the most common dopamine side effects:
Nausea and vomiting
Tachycardia
Dysrhythmias
Angina
Hypertension

Diazepam boosts GABA’s effects, giving it sedative, hypnotic, anxiolytic, anticonvulsant, and muscle-relaxing properties. It can be administered orally, rectally, or intravenously.

With a half-life of 20-100 hours, it is a long-acting benzodiazepine. Midazolam, oxazepam, and alprazolam are examples of short-acting benzodiazepines with a half-life of less than 12 hours (Xanax).

If used in the presence of hepatic impairment, benzodiazepines can cause coma. If treatment is necessary, benzodiazepines with shorter half-lives should be used in lower doses. Diazepam is a sedative that crosses into breast milk and should be avoided by breastfeeding mothers.

Peripheral nerves are nerves that lie outside the brain and spinal cord. Peripheral nerves readily regenerate, while central nervous system axonal injury does not spontaneously regenerate.
If there is damage to the axons of peripheral nerves, the nerves will regenerate at a slow rate of 1 mm per day. The slow regeneration process may lead to muscle atrophy before regeneration is complete.

Each peripheral nerve has a single cell body that supplies nutrients to the growing nerve fibre. The cell body does not undergo mitosis; only the axon is regenerated.

Schwann cells of the peripheral nervous system provide support for this process, while the analogous oligodendrocytes of the central nervous system do not. Schwann cells themselves do not cause regeneration. Schwann cells provide myelin for myelinated fibres and surround non-myelinated fibres with their cytoplasm.

If an axon is completely severed, as in the case of amputation, the axonal fibres regenerating from the cell body may never find their original route back to the muscle. Instead, they may form a traumatic neuroma, a painful collection of nerve fibres and myelin.

Autosomal dominant polycystic kidney disease (ADPKD) presents with abdominal or loin discomfort due to the increasing size of the kidneys, acute loin pain with or without haematuria, hypertension, and male infertility. It is the most common cause of serious renal disease and the most common inherited cause of renal failure in adults.

Alport syndrome has hearing loss and eye abnormalities in addition to symptoms of kidney disease.

Renal cell carcinoma presents with additional features of unexplained weight loss, loss of appetite, fever of unknown origin and anaemia.

Anti-nuclear antibodies are auto-antibodies directed against a variety of nuclear antigens. There are different staining patterns and each pattern is suggestive of a different disorder.

Speckled staining is suggestive of mixed connective tissue disease.

Nucleolar staining is suggestive of scleroderma, while homogenous staining is suggestive of lupus.

Anti-double stranded DNA is suggestive of SLE while anti-histone antibodies are suggestive of drug-induced lupus.

ELISA testing is cheaper but not the most accurate means of testing for ANAs. Indirect immunofluorescence testing is the most accurate.

The presence of ANAs in rheumatoid arthritis is suggestive of Felty’s syndrome. Felty’s syndrome is characterized by a combination of rheumatoid arthritis, splenomegaly and neutropenia.

Erythema is redness of the skin or mucous membranes caused by hyperaemia of superficial capillaries caused by skin injury, infection or inflammation. Erythema blanches when pressure is applied whereas ecchymosis, purpura and petechiae do not.

Ecchymosis are discolouration of the skin or mucous membranes caused by extravasation of blood. They are usually red or purple in colour and measure greater than 1 cm in diameter and do not blanch on applying pressure.

A macule is a flat, well circumscribed area of discoloured skin less than 1 cm in diameter with no changes in the thickness or texture of the skin.

Petechiae are discolouration of the skin measuring less than 3 mm in diameter

Purpura are discolouration of the skin measuring between 0.3 cm and 1 cm in diameter.

Fat necrosis typically occurs following either direct trauma or from enzymatic lipolysis in acute pancreatitis, where release of triglyceride elicits a rapid inflammatory response and fat is phagocytosed by neutrophils and macrophages with subsequent fibrosis.

The risk of mortality in the control group (usual therapy) minus the risk of death in the treatment group equals the absolute risk reduction (ARR) of treatment.
30/1000 minus 10/1000 = 20/1000 = 0.02

NNT = 1/ARR = 1/0.02 = 50
As a result, 50 people would need to be treated in order to prevent one additional fatality, and 500 people would need to be treated in order to avoid 10 additional deaths.

Clinical features of hyperkalaemia may include:
paraesthesia, muscle weakness or paralysis, cardiac conduction abnormalities and dysrhythmias.

Clinical features of hypokalaemia may include:
muscle weakness, muscle cramps, rhabdomyolysis and myoglobinuria, ascending paralysis resulting in respiratory failure, constipation, gut ileus with distension, anorexia, nausea and vomiting, impaired ADH action with polyuria and polydipsia, ECG changes and cardiac arrhythmias.

Cryptococcus neoformans is found in bird droppings and transmission is by inhalation of spores, thus the lung is the primary site of infection.

Examples of type IV reactions includes:
Contact dermatitis
Hashimoto’s thyroiditis
Primary biliary cholangitis
Tuberculin skin test (Mantoux test)
Chronic transplant rejection
Granulomatous inflammation (e.g. sarcoidosis, Crohn’s disease)

Amiodarone is a class III potassium channel blocker used to treat multiple types of arrhythmias.

Side effects include:
1. pulmonary fibrosis
2. blue discolouration of the skin
3. phototoxicity
4. corneal deposits
5. hepatic necrosis
6. thyroid dysfunction
7. sleep disturbances
8. peripheral neuropathy.

Xanthopsia is a condition where the patient complains of seeing yellow lines and is seen in digoxin overdose.

Digoxin is a cardiac glycoside that is used to treat atrial fibrillation and flutter, as well as congestive heart failure. In cardiac myocytes, it works by inhibiting the membrane Na/K ATPase. Through Na/Ca exchange, this raises intracellular sodium concentration and indirectly increases intracellular calcium availability. Increased intracellular calcium levels have both a positive inotropic and negative chronotropic effect.

Digoxin therapeutic plasma levels are typically between 1.0 and 1.5 nmol/l, though higher concentrations may be required, and the value varies between laboratories. At concentrations greater than 2 nmol/l, the risk of toxicity increases dramatically.

In patients with normal renal function, digoxin has a long plasma half-life of 36 to 48 hours. This can take up to 5 days in patients with impaired renal function.

Hypokalaemia, rather than hyperkalaemia, has been shown to increase the risk of digoxin toxicity.

In the treatment of persistent and permanent atrial fibrillation, digoxin is no longer widely used. Beta-blockers, also known as rate-limiting calcium channel blockers, are now the first-line treatment for this condition.

Flumazenil is a benzodiazepine antagonist used for the reversal of the sedative effects of benzodiazepines after anaesthesia, sedation and similar procedures.

The movement of a material against a concentration gradient, i.e. from a low to a high concentration, is known as active transport. Primary active transport is defined as active transport that involves the use of chemical energy, such as adenosine triphosphate (ATP). Secondary active transport occurs when an electrochemical gradient is used.

The sodium-potassium pump, calcium ATPase pump, and proton pump are all key active transport systems that use ATP. An electrochemical gradient is used by the sodium-calcium co-transporter, which is an example of secondary active transport.

The sodium-dependent hexose transporter SGLUT-1 transports glucose and galactose into enterocytes. Secondary active transport is exemplified here.

A likelihood ratio is a measure of the diagnostic value of a test. Likelihood ratios show how many times more likely patients with a disease are to have a particular test result than patients without the disease. Likelihood ratios are more useful than predictive values because they are calculated from sensitivity and specificity and therefore remain constant even when the prevalence of the disorder changes.

Heparin acts as an anticoagulant by enhancing the inhibition rate of clotting proteases by antithrombin III impairing normal haemostasis and inhibition of factor Xa. Low molecular weight heparins have a small effect on the activated partial thromboplastin time and strongly inhibit factor Xa. Enoxaparin is derived from porcine heparin that undergoes benzylation followed by alkaline depolymerization.

The deep fibular nerve was previously referred to as the anterior tibial nerve.

It starts at the common fibular nerve bifurcation, between the fibula and the proximal part of the fibularis longus. Damage to this nerve can cause foot drop or loss of dorsiflexion since this nerve controls the anterior leg muscles.

Klebsiellais a genus of non-motile,Gram-negative, rod-shaped bacteriawith a prominent polysaccharide-based capsule. They are routinely found in the nose, mouth and gastrointestinal tract as normal flora, however, they can also behave as opportunistic pathogens.
Infections with Klebsiella spp. areusually nosocomial. They are an important cause of ventilator-associated pneumonia (VAP), urinary tract infection, wound infection and bacteraemia. Outbreaks of infections with Klebsiellaspp. in high-dependency units have been described and are associated with septicaemia and high mortality rates. Length of hospital stay and performance of invasive procedures are risk factors forKlebsiellainfections.
Primary pneumonia withKlebsiella pneumoniaeis a rare,severe, community-acquired infection associated with a poor outcome.
Klebsiella rhinoscleromatis causes a progressive granulomatous infection of the nasal passages and surrounding mucous membranes. This infection is mainly seen in the tropics.
Klebsiella ozanae is a recognised cause of chronic bronchiectasis.
Klebsiella organisms are resistant to multiple antibiotics including penicillins. This is thought to be a plasmid-mediated property. Agents with high intrinsic activity againstKlebsiellapneumoniaeshould be selected for severely ill patients. Examples of such agents include third-generation cephalosporins (e.g cefotaxime), carbapenems (e.g. imipenem), aminoglycosides (e.g. gentamicin), and quinolones (e.g. ciprofloxacin). These agents may be used as monotherapy or combination therapy. Aztreonam may be used in patients who are allergic to beta-lactam antibiotics.
Species with ESBLs (Extended spectrum beta-lactamase) are resistant to penicillins and also cephalosporins such as cefotaxime and ceftriaxone
.

IV Lidocaine is indicated in Ventricular Arrhythmias or Pulseless Ventricular Tachycardia (after defibrillation, attempted CPR, and vasopressor administration)

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)

Fusidic acid is a narrow spectrum antibiotic used for staphylococcal infections, primarily topically for minor staphylococcal skin (impetigo) or eye infection. It is sometimes used orally for penicillin-resistant staphylococcal infection, including osteomyelitis or endocarditis, in combination with other antibacterials.

E. coli may cause several different gastrointestinal syndromes. Based on virulence factors, clinical manifestation, epidemiology, and different O and H serotypes, there are five major categories of diarrheagenic E. coli, enterotoxigenic E. coli (ETEC), enteroinvasive E. coli (EIEC), enteropathogenic E. coli (EPEC), enterohemorrhagic E. coli (EHEC), and enteroadherent, which includes diffusely adherent E. coli (DAEC) and enteroaggregative E. coli (EAEC). These five categories are sometimes
collectively referred to as enterovirulent E. coli or diarrheagenic E. coli.

Norwalk virus is part of the Caliciviridae family of viruses which are single-stranded RNA viruses and are the most common cause of infectious gastroenteritis in the US.

Rotaviruses are the most common cause of viral gastroenteritis
in infants and children. With the introduction in 2006 of a human-bovine rotavirus vaccine (RV5; RotaTeq, Merck), a delay in the onset of rotavirus
season was seen. RotaTeq is a series of three oral vaccines beginning at 6 to 12 weeks of age. A second vaccine, Rotarix (RV1; GlaxoSmithKline, Middlesex, England), was approved in June 2008.

Cryptosporidium causes an illness characterized by abdominal cramping, watery diarrhoea, vomiting, fever, and anorexia. This organism is resistant to chlorine, so public swimming pools can be the source of an outbreak.

G. lamblia has a worldwide distribution and has frequently been identified as the causative agent of outbreaks of gastroenteritis and traveller’s diarrhoea.

C. diphtheriae, which is the causative agent of diphtheria, is carried in the upper respiratory tract and spread by droplet infection or hand-to-mouth contact. The incubation period averages 2 to 5 days.

Infectious mononucleosis is caused by Epstein-Barr virus (EBV). The incubation period for EBV varies from 2 weeks to 2 months.

The incubation for Hepatitis A virus is approximately 1 month.

The incubation period for Hepatitis C ranges from 2 weeks to 6 months.

The period from infection to development of anti-HIV antibodies is usually less than 1 month but may be up to 3 months.

Hepatitis A usually doesn’t pose a special risk to a pregnant woman or her baby. Maternal infection doesn’t result in birth defects, and a mother typically doesn’t transmit the infection to her baby. HAV is almost always transmitted by the faecal-oral route and is usually acquired through close personal contact or via contaminated food.

When a woman has chickenpox in the first 20 weeks of pregnancy, there is a 1 in 50 chance for the baby to develop a set of birth defects. This is called the congenital varicella syndrome. It includes scars, defects of muscle and bone, malformed and paralyzed limbs, small head size, blindness, seizures, and intellectual disability.

TORCH Syndrome refers to infection of a developing foetus or newborn by any of a group of infectious agents. “TORCH” is an acronym meaning (T)toxoplasmosis, (O)ther Agents, (R)ubella (also known as German Measles), (C)ytomegalovirus, and (H)erpes Simplex.
Infection with any of these agents may cause a constellation of similar symptoms in affected newborns. These may include fever; difficulties feeding; small areas of bleeding under the skin, causing the appearance of small reddish or purplish spots; enlargement of the liver and spleen (hepatosplenomegaly); yellowish discoloration of the skin, whites of the eyes, and mucous membranes (jaundice); hearing impairment; abnormalities of the eyes; and other symptoms and findings.

Loop diuretics have long been the cornerstone of pulmonary oedema treatment, with furosemide being the most commonly used of these drugs. Premedication with drugs that decrease preload (e.g., nitro-glycerine [NTG]) and afterload (e.g., angiotensin-converting enzyme [ACE] inhibitors) before the administration of loop diuretics can prevent adverse hemodynamic changes.

The fifth cervical nerve passes between the fourth and fifth cervical vertebrae, and the fourth thoracic nerve passes between the fourth and fifth thoracic vertebrae. Therefore, when the cancer metastasizes in this area, they are most likely affected.

An ambulatory blood pressure reading of >150/95 is classified as stage 2 hypertension, according to the NICE care pathway for hypertension, and the patient should be treated with an antihypertensive drug.

A calcium-channel blocker, such as amlodipine, would be the most appropriate medication for a 59-year-old Caucasian man.

A papule is a solid, well circumscribed, skin elevation measuring less than 0.5 cm in diameter.

A nodule is a solid, well circumscribed, raised area that lies in or under the skin and measures greater than 0.5 cm in diameter. They are usually painless.

A bulla is a visible collection of clear fluid measuring greater than 0.5 cm in diameter.

A furuncle, or boil, is a pyogenic infection of the hair follicle commonly caused by infection with Staphylococcus aureus.

A pustule is a small visible skin elevation containing an accumulation of pus.

Damage to the superficial fibular nerve results in loss of eversion of the foot and loss of sensation over the lower anterolateral leg and the dorsum of the foot.

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.

Cushing’s syndrome has a wide range of clinical manifestations that are dependent on the degree of cortisol overproduction. The appearance might be vague and the diagnosis difficult to detect when cortisol levels are just somewhat elevated. On the other hand, in long-term cases of severely increased cortisol levels, the presentation might be colourful and the diagnosis simple.

Cushing’s syndrome has the following clinical features:
Obesity and weight growth in the true sense
Supraclavicular fat pads are fat pads that are located above the clavicle.
Buffalo hump
Fullness and plethora of the face (‘moon facies’)
Muscle atrophy and weakening at the proximal level
Diabetes mellitus, also known as impaired glucose tolerance
Hypertension
Skin thinning and bruising
Depression
Hirsutism
Acne
Osteoporosis
Amenorrhoea or oligomenorrhoea

Cortisol levels fluctuate throughout the day, with the greatest levels occurring around 0900 hours and the lowest occurring at 2400 hrs during sleep. The diurnal swing of cortisol levels is lost in Cushing’s syndrome, and levels are greater during the whole 24-hour period. In the morning, levels may be normal, but they may be high at night-time, when they are generally repressed. As a result, random cortisol testing is not an effective screening technique and is not advised.

The following are the two most common first-line screening tests:
Cortisol levels in the urine are measured every 24 hours.
A diagnosis of Cushing’s syndrome can be made if more than two collections measure cortisol excretion more than three times the upper limit of normal.
Physical stress (e.g., excessive exercise, trauma), mental stress (e.g., sadness), alcohol or drug misuse, complex diabetes, and pregnancy can all cause false positives.
Renal dysfunction, inadequate collection, and cyclical Cushing’s disease can all cause false negatives.
The overnight low-dose dexamethasone suppression test (LDDST) involves giving 1 mg of dexamethasone at 11 p.m. and measuring blood cortisol levels at 8 a.m. the next day.
Cushing’s syndrome is diagnosed when cortisol is not suppressed to less than 50 nmol/L.
It might be difficult to tell the difference between mild Cushing’s disease and normal cortisol production.
False positives can occur as a result of depression, severe systemic sickness, renal failure, prolonged alcohol misuse, old age, and the use of hepatic enzyme-inducing medicines, among other things.
False negatives are extremely uncommon in Cushing’s disease patients.

A characteristic biochemical picture might also be helpful in confirming the diagnosis of Cushing’s syndrome. The following are the primary characteristics:
Hypokalaemia
Alkalosis metabolique

The common carotid artery runs through the neck and divides into internal and external carotid arteries on both sides near the upper thyroid cartilage. In emergency situations, carotid sinus massage is also used to diagnose or treat paroxysmal supraventricular tachycardia.

During the procedure, to maximize access to the carotid artery, the patient is put in a supine position with the neck extended (i.e. elevating the chin away from the chest). The carotid sinus is normally positioned inferior to the angle of the jaw, near the arterial impulse, at the level of the thyroid cartilage. For 5 to 10 seconds, pressure is administered to one carotid sinus.

Although pulsatile pressure applied in a vigorous circular motion may be more effective, continuous pressure is preferred since it is more reproducible. If the predicted reaction is not obtained, the operation is repeated on the opposite side after a one- to two-minute wait.

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.

Acetazolamide is a non-competitive, reversible inhibitor of carbonic anhydrase found in the cytosol of cells and on the brush border of the proximal convoluted tubule. Bicarbonate and hydrogen ions are converted to carbonic acid by carbonic anhydrase, which then converts carbonic acid to carbon dioxide and water. As a result, acetazolamide reduces the availability of hydrogen ions, causing sodium and bicarbonate ions to accumulate in the renal tubule, resulting in diuresis.
The mechanism of action of the various types of diuretics is summarised below:

1) Loop diuretics, e.g. furosemide, bumetanide
Act on the Na.K.2Cl co-transporters in the ascending loop of Henlé to inhibit sodium, chloride and potassium reabsorption.

2) Thiazide diuretics, e.g. Bendroflumethiazide, hydrochlorothiazide
Act on the Na.Cl co-transporter in the distal convoluted tubule to inhibit sodium and chloride reabsorption.

3) Osmotic diuretics, e.g. mannitol
Increases the osmolality of the glomerular filtrate and tubular fluid, increasing urinary volume by an osmotic effect.

4) Aldosterone antagonists, e.g. spironolactone
Acts in the distal convoluted tubule as a competitive aldosterone antagonist resulting in inhibition of sodium reabsorption and increasing potassium reabsorption.

5) Carbonic anhydrase inhibitors, e.g. acetazolamide
Inhibit the enzyme carbonic anhydrase preventing the conversion of bicarbonate and hydrogen ions into carbonic acid.

Neostigmine is used specifically for reversal of nondepolarizing (competitive) blockade and is anticholinesterase. It acts within one minute of intravenous injection, and the effects last for 20 to 30 minutes. After this time period, a second dose may then be necessary.

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 overdose

Respiratory 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)
– Obesity

Metabolic alkalosis:
– Vomiting
– Cardiac arrest
– Multi-organ failure
– Cystic fibrosis
– Potassium depletion (e.g. diuretic usage)
– Cushing’s syndrome
– Conn’s syndrome

Metabolic 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

Severe hyperkalaemia can result in a heart attack or a life-threatening arrhythmia.

T waves become narrow-based, pointed, and tall if hyperkalaemia is not treated.

The QRS complex widens and eventually merges with the T wave, resulting in a classic sine-wave electrocardiogram. Ventricular fibrillation and asystole are likely to follow.

Muscle heals with fibrous tissue to form a scar. Once cut, it will never regain its previous bulk or power. Within the scar a small number of myocytes (muscle cells) may be seen, which are formed from satellite cells but they contribute little to the function of the muscle overall.
In more widespread ischaemic injury, such as critical ischaemic limb due to arterial compromise, or in compartment syndrome, damaged myocytes are replaced diffusely with fibrous tissue. This fibrous tissue contracts and reduces movement, and in extreme cases can pull the limb into abnormal positions such as in Volkmann’s ischaemic contracture of the forearm.

Damage to the long thoracic nerve results in weakness/paralysis of the serratus anterior muscle. Loss of function of this muscle causes the medial border, and particularly the inferior angle, of the scapula to elevate away from the thoracic wall, resulting in the characteristic ‘winging’ of the scapula. This deformity becomes more pronounced if the patient presses the upper limb against a wall. Furthermore, normal elevation of the arm is no longer possible.

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.

Angina pectoris is the most common symptom of ischemic heart disease and presents with chest pain relieved by rest and nitro-glycerine.

Nitrates are the first-line treatment to relieve chest pain caused by angina. The commonly used nitrates are:
1. Glyceryl trinitrate
2. Isosorbide dinitrate

The nitrate drugs are metabolized in the following steps:
1. Release Nitrite ions (NO2-), which are then converted to nitric oxide (NO) within cells.
2. NO activates guanylyl cyclase, which causes an increase in the intracellular concentration of cyclic guanosine-monophosphate (cGMP) in vascular smooth muscle cells.
3. Relaxation of vascular smooth muscle.

Although nitrates are potent coronary vasodilators, their principal benefit in the management of angina results from a predominant mechanism of venous dilation:
– Bigger veins hold more blood
– Takes blood away from the left ventricle
– Lowers LVEDV (preload), LA pressure
– Less pulmonary oedema → improved dyspnoea

Parasympathetic supply is from the pelvic splanchnic nerves (S2 – S4) and inferior hypogastric plexus.

Endocarditis is infective or non infective inflammation (marantic endocarditis) of the inner layer of the heart and it often involves the heart valves.

Risk factors include:
Prosthetic heart valves
Congenital heart defects
Prior history of endocarditis
Rheumatic fever
Illicit intravenous drug use

In the presentation of endocarditis, the following triad is often quoted:
Persistent fever
Embolic phenomena
New or changing murmur

A combination of vancomycin, rifampicin and gentamicin is advised if the patient has a cardiac prostheses, is penicillin allergic, or if methicillin-resistant Staphylococcus aureus (MRSA) is suspected. In this case the patient has a prosthetic valve making this the most appropriate initial treatment regimen.

Flucloxacillin and gentamicin are current recommended by NICE and the BNF for the initial ‘blind’ therapy in endocarditis. This patient has prostheses and this is not the most appropriate initial treatment regimen.

Other features that may be present include heart failure, splenomegaly, finger clubbing, renal features (haematuria, proteinuria, nephritis), and vasculitic features (splinter haemorrhages, Osler’s nodes, Janeway lesions, Roth’s spots).