Angiotensin-converting enzyme inhibitors (ACE inhibitors) e.g. captopril inhibit the conversion of angiotensin I to angiotensin II, and thus have a vasodilatory effect, lowering both arterial and venous resistance. The cardiac output increases and, because the renovascular resistance falls, there is an increase in renal blood flow. This latter effect, together with reduced aldosterone release, increases Na+ and H2O excretion, contracting the blood volume and reducing venous return to the heart.

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. 

To avoid the spread of infection, infected patients should be isolated. All lesions should be crusted over before children return to nursery or school, even if the standard exclusion time is 5 days.

The following nerves provide cutaneous innervation to the scrotum, and other anatomic structures:The perineal nerve supplies the muscles in the urogenital triangle, and the skin on the posterior surface of the scrotum (or labia majora).The genital branch of the genitofemoral nerve supplies the cremaster muscle, the skin over the anterior surface of the thigh, and the anterolateral surface of the scrotum.The ilioinguinal nerve supplies the external oblique, internal oblique, transversus abdominis, skin of the upper medial aspect of thigh, the root of the penis and the anterior surface of the scrotum in the male, and the mons pubis and labia majora in the female.The posterior cutaneous nerve of the thigh, or posterior femoral cutaneous nerve, supplies the skin over the lower medial quadrant of the buttock, the inferior skin of the scrotum or labium majus, and the back of the thigh and the upper part of the leg.

Case-control studies are suitable when investigating a rare disease or in cases where little is known about the disease and the proposed aetiological factor, as a preliminary study. They have the ability to look at multiple risk-factors (exposures) but can only look at a single outcome.In a case-control study, two groups of patients, one with the disease and one without, are compared on the basis of a proposed causative factor that occurred in the past. They are therefore a retrospective study and useful in hypothesis generation.Cohort studies are better at identifying rare exposures. One group with an exposure is compared to a control group without that exposure.Case-control studies are usually less expensive to run and also shorter in duration compared with prospective cohort studies.

Cardiac muscle is striated, and the sarcomere is the contractile unit, similar to skeletal muscle. Contracture is mediated by the interaction of calcium, troponins, and myofilaments, much as it occurs in skeletal muscle. Cardiac muscle, on the other hand, differs from skeletal muscle in a number of ways.In contrast to skeletal muscle cells, cardiac myocytes have a nucleus in the middle of the cell and sometimes two nuclei. The cells are striated because the thick and thin filaments are arranged in an orderly fashion, although the arrangement is less well-organized than in skeletal muscle.Intercalated discs, which work similarly to the Z band in skeletal muscle in defining where one cardiac muscle cell joins the next, are a very significant component of cardiac muscle.Adherens junctions and desmosomes, which are specialized structures that hold the cardiac myocytes together, are formed by the transverse sections. The lateral sections produce gap junctions, which join the cytoplasm of two cells directly, allowing for rapid action potential conduction. These critical properties allow the heart to contract in a coordinated manner, allowing for more efficient blood pumping.Cardiac myocytes have the ability to create their own action potentials, which is referred to as myogenic’. They can depolarize spontaneously to initiate a cardiac action potential. Pacemaker cells, as well as the sino-atrial (SA) and atrioventricular (AV) nodes, control this.The Purkinje cells and the cells of the bundle of His are likewise capable of spontaneous depolarization. While the bundle of His is made up of specialized myocytes, it’s vital to remember that Purkinje cells are not myocytes and have distinct characteristics. They are larger than myocytes, with fewer filaments and more gap junctions than myocytes. They conduct action potentials more quickly, allowing the ventricles to contract synchronously.Cardiac myocytes contract by excitation-contraction coupling, just like skeletal myocytes. Heart myocytes, on the other hand, utilise a calcium-induced calcium release mechanism that is unique to cardiac muscle (CICR). The influx of calcium ions (Ca2+) into the cell causes a ‘calcium spark,’ which causes more ions to be released into the cytoplasm.An influx of sodium ions induces an initial depolarisation, much as it does in skeletal muscle; however, in cardiac muscle, the inflow of Ca2+ sustains the depolarisation, allowing it to remain longer. Due to potassium ion (K+) inflow, CICR causes a plateau phase in which the cells remain depolarized for a short time before repolarizing. Skeletal muscle, on the other hand, repolarizes almost instantly.Comparison of skeletal and cardiac muscle:Skeletal muscle Cardiac muscleStriation Striated but arrangement less organised Multiple nuclei located peripherally Usually single nucleus (but can be two), located centrallyDiscs None Intercalated discsNo Gap junctions Gap junctions No Pacemaker PacemakerElectrical stimulation: Nervous system (excitation) Pacemaker (excitation)

Common side effects of adenosine include:ApprehensionDizziness, flushing, headache, nausea, dyspnoeaAngina (discontinue)AV block, sinus pause and arrhythmia (discontinue if asystole or severe bradycardia occur)

Myofibrils, which are around 1 m in diameter, make up each myofiber. The cytoplasm separates them and arranges them in a parallel pattern along the cell’s long axis. These myofibrils are made up of actin and myosin filaments that are repeated in sarcomeres, which are the myofiber’s basic functional units.Myofilaments are the filaments that make up myofibrils, and they’re made mostly of proteins. Myofilaments are divided into three categories:Myosin filaments are thick filaments made up mostly of the protein myosin.Actin filaments are thin filaments made up mostly of the protein actin.Elastic filaments are mostly made up of the protein titin.The sarcomere is a Z-line segment that connects two adjacent Z-lines.The I-bands are thin filament zones that run from either side of the Z-lines to the thick filament’s beginning.Between the I-bands is the A-band, which spans the length of a single thick filament.The H-zone is a zone of thick filaments that is not overlaid by thin filaments in the sarcomere’s centre. The H-zone keeps the myosin filaments in place by surrounding them with six actin filaments each.The M-band (or M-line) is a disc of cross-connecting cytoskeleton elements in the centre of the H-zone.The thick filament is primarily made up of myosin. The thin filament is primarily made up of actin. Actin, tropomyosin, and troponin are found in a 7:1:1 ratio in thin filaments.

A diagnosis of Haemophilia is supported in this patient by the family history and the presence of hemarthrosis-both characteristics of Haemophilia. Haemophilia A is caused by Factor VIII deficiency, leading to impaired coagulation. This disease typically presents after six months when the child starts crawling. Von Willebrand disease presents with nosebleeds and hematomas. Idiopathic thrombocytopenic purpura presents with bruises that resemble a rash. Glucose-6-phosphate dehydrogenase (G6PD) deficiency presents with haemolytic anaemia induced by specific drugs or foods. Factor V Leiden mutation causes blood clotting rather than bleeding.

Brachioradialis is innervated by the radial nerve (from the root values C5-C6) that stems from the posterior cord of the brachial plexus.

Approximately half of total serum calcium is in the free or ionised Ca2+ state, 40% is attached to plasma proteins (mostly albumin), and the remaining 10% is in complexes with organic ions like citrate and phosphate. The ionized form is the only one that works.

Gastrin acts to:Stimulate acid secretion from parietal cells (both directly and indirectly by stimulating release of histamine from ECL cells)Stimulate pepsinogen secretion from chief cellsIncrease gastric motilityStimulate growth of gastric mucosa

Rubella can be contagious from 7 days before to 7 days after the rash appears.Patients with measles are contagious from 1-2 days before the onset of symptoms.A person with chickenpox is considered contagious beginning 1 to 2 days before rash onset until all the chickenpox lesions have crusted (scabbed). The infectious period of mumps is considered from 2 days before to 5 days after parotitis onset.Hepatitis A is highly transmissible and has an average incubation period of 28 to 30 days (range 15–50 days). The maximum infectivity is during the second half of the incubation period (i.e. while asymptomatic) and most cases are considered non-infectious after the first week of jaundice.

Extrapyramidal side effects are most common with piperazine phenothiazines (fluphenazine, prochlorperazine, and trifluoperazine) and butyrophenones (fluphenazine, prochlorperazine, and trifluoperazine) (benperidol and haloperidol). The most common causative antipsychotic drug is haloperidol.Tardive dyskinesia (rhythmic, involuntary movements of the tongue, face, and jaw) is most commonly associated with long-term or high-dose treatment. It is the most serious form of extrapyramidal symptoms because withdrawal of the causative drug may make it irreversible, and treatment is usually ineffective.Dystonia (abnormal facial and body movements) is more common in children and young adults, and it usually shows up after only a few doses. Procyclidine 5 mg IV or benzatropine 2 mg IV as a bolus can be used to treat acute dystonia.An unpleasant feeling of restlessness characterises akathisia. The inability to initiate movement is known as akinesia.Renal impairment causes increased cerebral sensitivity, so lower doses should be used.In elderly patients with dementia-related psychosis who are treated with haloperidol, there is an increased risk of death. This appears to be due to a higher risk of heart attacks and infections like pneumonia.The following are some of the antipsychotic drugs’ contraindications:Reduced level of consciousness/comaDepression of the central nervous systemPhaeochromocytoma

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

Haemophilia B is a bleeding disorder caused by a deficiency of clotting factor IX. It is the second commonest form of haemophilia, and is rarer than haemophilia A. Haemophilia B tends to be similar to haemophilia A but less severe. The two disorders can only be distinguished by specific coagulation factor assays.The incidence is one-fifth of that of haemophilia A. Laboratory findings demonstrate prolonged APTT, normal PT and low factor IX.Haemophilia B inherited in an X-linked recessive fashion, affecting males born to carrier mothers.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.

Negative feedback loops, also known as inhibitory loops, play a crucial role in controlling human health. It is a self-regulating mechanism of some sort. A negative feedback system is made up of three main components: a detector (often neural receptor cells) that measures the variable in question and provides input to the comparator; a comparator (usually a neural assembly in the central nervous system) that receives input from the detector, compares the variable to the variable set point, and determines whether or not a response is required. The comparator activates an effector (typically muscular or glandular tissue) to conduct the appropriate reaction to return the variable to its set point.

Clostridium spp. are obligatory anaerobic spore-forming Gram-positive bacilli. Toxin production is the main pathogenicity mechanism.

The following are the lesions of the cranial nerves:1. Olfactory nerve (I)Reduced taste and smell, but not to ammonia which stimulates the pain fibres carried in the trigeminal nerve2. Optic nerve (II)Manifested by visual field defects, pupillary abnormalities, optic neuritis, optic atrophy, papilledema3. Oculomotor nerve (III)A fixed, dilated pupil which doesn’t accommodate, ptosis, complete internal ophthalmoplegia (masked by ptosis), unopposed lateral rectus causes outward deviation of the eye. If the ocular sympathetic fibres are also affected behind the orbit, the pupil will be fixed but not dilated.4. Trochlear nerve (IV)Diplopia due to weakness of downward and inward eye movement. The most common cause of a pure vertical diplopia. The patient tends to compensate by tilting the head away from the affected side.5. Trigeminal nerve (V)Reduced sensation or dysesthesia over the affected area. Weakness of jaw clenching and side-to-side movement. If there is a lower motor neuron (LMN) lesion, the jaw deviates to the weak side when the mouth is opened. There may be fasciculation of temporalis and masseter.6. Abducens nerve (VI)Inability to look laterally. The eye is deviated medially because of unopposed action of the medial rectus muscle.7. Facial nerve (VII)Facial weakness. In an LMN lesion the forehead is paralysed – the final common pathway to the muscles is destroyed; whereas the upper facial muscles are partially spared in an upper motor neurone (UMN) lesion because of alternative pathways in the brainstem. There appear to be different pathways for voluntary and emotional movement. CVAs usually weaken voluntary movement, often sparing involuntary movements (e.g., spontaneous smiling). The much rarer selective loss of emotional movement is called mimic paralysis and is usually due to a frontal or thalamic lesion.8. Vestibulocochlear nerve (VIII)Unilateral sensorineural deafness, tinnitus. Slow-growing lesions seldom present with vestibular symptoms as compensation has time to occur.9. Glossopharyngeal nerve (IX)Unilateral lesions do not cause any deficit because of bilateral corticobulbar connections. Bilateral lesions result in pseudobulbar palsy. These nerves are closely interlinked.10. Vagus nerve (X)Palatal weakness can cause ‘nasal speech’ and nasal regurgitation of food. The palate moves asymmetrically when the patient says ‘ahh’. Recurrent nerve palsy results in hoarseness, loss of volume and ‘bovine cough’.11. Accessory nerve (XI)Weakness and wasting of sternocleidomastoid and trapezius muscles12.Hypoglossal nerve (XII)An LMN lesion produces wasting of the ipsilateral side of the tongue, with fasciculation; and on attempted protrusion the tongue deviates towards the affected side, but the tongue deviates away from the side of a central lesion.

Absolute risk reduction (ARR) is computed as the difference between the absolute risk in the control group (ARC) and the absolute risk in the treatment group (ART).ARR = ARC-ARTARR = (25/500) – (10/500)ARR = 0.03

During quiet respiration, the approximate position of the right oblique fissure can be marked by a line on the thoracic wall that begins at the spinous process of vertebra T4, crosses the fifth intercostal space laterally and then follows the contour of rib 6 anteriorly.

Thyroid hormones have multiple physiological effects on the body. These include:1. Heat production (thermogenesis)2. Increased basal metabolic rate3. Metabolic effects: (a) Increase in protein turnover (both synthesis and degradation are increased, although overall effect is catabolic)(b) Increase in lipolysis(c)Increase in glycogenolysis and gluconeogenesis4. Enhanced catecholamine effect – Increase in heart rate, stroke volume and thus cardiac output5. Important role in growth and development

Ectopic pregnancy most commonly occurs in the ampulla (70% of cases).

Non-specific signs of anaemia include: 1. pallor of mucous membranes or nail beds (if Hb < 90 g/L), 2. tachycardia3. bounding pulse4. wide pulse pressure5. flow murmurs 6. cardiomegaly 7. signs of congestive cardiac failure (in severe cases)

The common peroneal nerve often referred to as the common fibular nerve, is a major nerve that innervates the lower extremity. It is one of the two major branches off the sciatic nerve and receives fibres from the posterior divisions of L4 through S2 nerve roots. The common peroneal nerve separates from the sciatic nerve in the distal posterior thigh proximal to the popliteal fossa. After branching off of the sciatic nerve, it continues down the thigh, running posteroinferior to the biceps femoris muscle, and crosses laterally to the head of the lateral gastrocnemius muscle through the posterior intermuscular septum. The nerve then curves around the fibular neck before dividing into two branches, the superficial peroneal nerve (SPN) and the deep peroneal nerve (DPN). The common peroneal nerve does not have any motor innervation before dividing; however, it provides sensory innervation to the lateral leg via the lateral sural nerve.The superficial peroneal nerve innervates the lateral compartment of the leg, and the deep peroneal nerve innervates the anterior compartment of the leg and the dorsum of the foot. These two nerves are essential in the eversion of the foot and dorsiflexion of the foot, respectively. The superficial and deep peroneal nerves provide both motor and sensory innervation.The most common presentation with common peroneal nerve injury or palsy is acute foot drop, although symptoms may be progressive and can include sensory loss or pain. Weakness in foot eversion may occur if the superficial peroneal nerve component is involved.

Acute lymphocytic leukaemia (ALL) is more common in children than chronic leukaemias, which generally occur in adults. Bone marrow failure occurs early on in the course of the disease in acute leukaemias, and there is the massive proliferation of undifferentiated cells with functioning cells being crowded out. Hepatosplenomegaly occurs in both acute and chronic forms of leukaemia and is not a differentiating feature.

Aerosols are airborne particles less than 5 µm in size containing infective organisms. They usually cause infection of both the upper and/or lower respiratory tract.The organisms can remain suspended in the air for long periods and also survive outside the body. They can be transmitted through the ventilation systems and can spread over great distances. Some examples of organisms transmitted by the aerosol route include: Varicella zoster virus, Mycobacterium tuberculosis and measles virus

A histogram is used to demonstrate the distribution of continuous quantitative data. It is a very familiar graphical display device for representing the distribution of a single batch of data. The range of the data is divided into class intervals or bins, and the number of values falling into each interval is counted. The histogram then consists of a series of rectangles whose widths are defined by the class limits implied by the binwidths, and whose heights depend on the number of values in each bin. Histograms quickly reveal such attributes of the data distribution as location, spread, and symmetry. If the data are multimodal (i.e., more than one “hump” in the distribution of the data), this is quickly evident as well.

Hodgkin’s lymphoma is a malignant tumour of the lymphatic system that is characterised histologically by the presence of Reed-Sternberg cells (multinucleated giant cells). The annual incidence of Hodgkin’s lymphoma in the UK is approximately 3 per 100,000 per year. The peak incidence is in young adults aged 20-35, and there is a slight male predominance.The following are recognised risk factors for Hodgkin’s lymphoma:Male genderAge 20-35Positive family historyEpstein-Barr virus infectionImmunosuppression including HIV infectionProlonged use of human growth hormoneMost patients present with an enlarged, but otherwise asymptomatic lymph node. The most commonly affected lymph nodes are in the supraclavicular and lower cervical areas. Other common clinical features include shortness of breath and chest discomfort secondary to mediastinal mass. Mediastinal masses are sometimes discovered as incidental findings on routine chest X-rays. Approximately 30% of patients with Hodgkin’s lymphoma develop splenomegaly.‘B’ symptoms occur in approximately 25% of patients. The ‘B’ symptoms of Hodgkin’s lymphoma are:Fever (>38ºC)Night sweatsWeight loss (>10% over 6 months)Pain after alcohol consumption is a pathognomonic sign of Hodgkin’s lymphoma, it is, however, not a ‘B’ symptom. It is rare though, only occurring in 2-3% of patients with Hodgkin’s lymphoma.The Ann Arbour clinical staging is as follows:Stage I: one involved lymph node groupStage II two involved lymph node groups on one side of the diaphragmStage III: lymph node groups involved on both sides of the diaphragmStage IV: Involvement of extra-nodal tissues, such as the liver or bone marrowDiagnosis is made by lymph node biopsy, which should be taken from a sufficiently large specimen or excisional biopsy, as opposed to a fine needle biopsy. The Reed-Sternberg cell is the most useful diagnostic feature. This is a giant cell with twin mirror-image nuclei and prominent ‘owl’s eye’ nucleoli.The Reed-Sternberg cell of Hodgkin’s LymphomaHistological typing depends upon the other cells within the diseased tissue. Nodular sclerosing is the most common type of Hodgkin’s lymphoma. Lymphocyte-depleted and lymphocyte-predominant are rare subtypes.The majority of cases can be successfully treated, and unlike many other malignancies even if the first-line treatment fails, a cure can often be achieved with second-line therapies. Stage 1 Hodgkin’s lymphoma is usually treated with radiotherapy alone, but more advanced stages require combination chemotherapy. In localised disease treated with irradiation, there is a 5-year survival rate of greater than 80%. In disseminated disease treated with chemotherapy, the 5-year survival falls to around 50%. Overall, a 5-year survival of >70% should be achieved.

Although Ca2+entry during the action potential (AP) is essential for contraction, it only accounts for about 25% of the rise in intracellular Ca2+. The rest is released from Ca2+stores in the sarcoplasmic reticulum (SR). APs travel down invaginations of the sarcolemma called T-tubules, which are close to, but do not touch, the terminal cisternae of the SR. During the AP plateau, Ca2+enters the cell and activates Ca2+sensitive Ca2+release channels in the sarcoplasmic reticulum allowing stored Ca2+to flood into the cytosol; this is called Ca2+-induced Ca2+release. The amount of Ca2+released is dependent on how much is stored, and on the size of the initial Ca2+influx during the AP.