Febrile transfusion reactions presents with an unexpected temperature rise (≥ 38ºC or ≥ 1ºC above baseline, if baseline ≥ 37ºC) during or shortly after transfusion. It is usually an isolated finding and the fever is accompanied by chills and malaise occasionally.

Allergic reaction is commonly caused by foreign plasma proteins but may be due to anti-IgA. Allergic type reactions usually present with urticaria, pruritus, hives. Associations include laryngeal oedema or bronchospasm.

Acute haemolytic reaction aka immediate haemolytic transfusion reaction presents with fever, chills, pain at transfusion site, nausea, vomiting, dark urine and feeling of ‘impending doom’. Often, it occurs due to ABO incompatibility.

Transfusion-associated circulatory overload (TACO) presents as acute or worsening respiratory distress within 6 hours of transfusion of a large volume of blood. It is common in patients with diminished cardiac reserve or chronic anaemia. Elderly patients, infants and severely anaemic patients are particularly susceptible. Clinical features of TACO include: Acute respiratory distress, Tachycardia, Hypertension, Acute/worsening pulmonary oedema on chest X-ray. The BNP is usually raised to at least 1.5 times the pre-transfusion baseline.

Transfusion-related lung injury (TRALI) is a form of acute respiratory distress caused by the donor plasma containing antibodies against the patient’s leukocytes. It is defined as hypoxia and bilateral pulmonary oedema that occurs within 6 hours of a transfusion in the absence of other causes of acute lung injury. Clinical features include Breathlessness, cough, frothy sputum, hypertension or hypotension, hypoxia and fever. Chest X-ray shows multiple perihilar nodules with infiltration of the lower lung fields.

Plasma theophylline concentration is usually measured five days after starting oral treatment and three days after each dose adjustment.

A blood sample to check theophylline concentration should usually be taken after 4-6 hours if an IV dose of aminophylline was given.

The purine nucleoside adenosine is used to diagnose and treat paroxysmal supraventricular tachycardia. Adenosine works by stimulating A1-adenosine receptors and opening potassium channels that are sensitive to acetylcholine. This causes the atrioventricular (AV) node’s cell membrane to become hyperpolarized, slowing conduction by inhibiting calcium channels.
Patients who have had a heart transplant are extremely sensitive to the effects of adenosine and should start with a lower dose of 3 mg, then 6 mg, and finally 12 mg.

Dipyridamole potentiates the effects of adenosine, so it should be used with caution in patients who are taking it.

The use of adenosine is contraindicated in the following situations:
Asthma
COPD (chronic obstructive pulmonary disease)
Decompensated heart failure 
Long QT syndrome
AV block in the second or third degree
Sinusitis is a condition in which the sinuses become (unless pacemaker fitted)
Hypotension that is severe

Flecainide is an antiarrhythmic drug of class Ic that works by blocking the Nav1.5 sodium channel in the heart, prolonging the cardiac action potential and slowing cardiac impulse conduction. It has a significant impact on accessory pathway conduction, particularly retrograde conduction, and significantly reduces ventricular ectopic foci.

Many different arrhythmias can be treated with flecainide, including:
Pre-excitation syndromes (e.g. Wolff-Parkinson-White)
Acute atrial arrhythmias
Ventricular arrhythmias
Chronic neuropathic pain

The use of flecainide is contraindicated in the following situations:
Abnormal left ventricular function
Atrial conduction defects (unless pacing rescue available)
Bundle branch block (unless pacing rescue available)
Distal block (unless pacing rescue available)
Haemodynamically significant valvular heart disease
Heart failure
History of myocardial infarction
Long-standing atrial fibrillation where conversion to sinus rhythm not attempted
Second-degree or greater AV block (unless pacing rescue available)
Sinus node dysfunction (unless pacing rescue available)

Flecainide should only be used in people who don’t have a structural heart problem. The CAST trial found a significant increase in sudden cardiac death and all-cause mortality in patients with an ejection fraction of less than 40% after a myocardial infarction, where it tended to be pro-arrhythmic.

Anti-arrhythmic drugs have a limited and ineffective role in the treatment of atrial flutter. It’s important to keep in mind that flecainide shouldn’t be used by itself to treat atrial flutter. When used alone, there is a risk of inducing 1:1 atrioventricular conduction, which results in an increase in ventricular rate that is paradoxical. As a result, it should be used in conjunction with a beta-blocker or a calcium channel blocker with a rate-limiting effect.

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.

Around 30% of filtered K+is reabsorbed in the thick ascending limb of the loop of Henle, primarily via the luminal Na+/K+/2Cl-cotransporter, but there is also significant paracellular reabsorption, encouraged by the positive potential in the tubular lumen.

Enterochromaffin-like cells (ECL cells) are a type of neuroendocrine cell located beneath the epithelium in the stomach glands. They’re most typically located near the parietal cells of the stomach. The ECL cells’ primary role is to produce histamine, which stimulates the formation of stomach acid by the parietal cells.

The table below summarizes the many cell types found in the stomach, as well as the substances secreted by each cell type and the function of the secretion:

Cell type/ Substance secreted/ Function of secretion
Parietal cells/ Hydrochloric acid/ Kills microbes and activates pepsinogen
Parietal cells/ Intrinsic factor/Binds to vitamin B12 and facilitates its absorption
Chief cells/ Pepsinogen/ Protein digestion
Chief cells/ Gastric lipase/ Fat digestion
G-cells/ Gastrin/ Stimulates gastric acid secretion
Enterochromaffin-like cells (ECL cells) /Histamine/ Stimulates gastric acid secretion
Mucous-neck cells/ Mucous and bicarbonate/ Protects stomach epithelium from acid
D-cells/ Somatostatin/ Inhibits gastric acid secretion

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

Insulin receptor (IR), in addition to being activated by insulin, is also activated by IGF-I and IGF-II.

The IR is a dimer with two identical subunits spanning the cell membrane and are connected by a single disulphide bond. The two sub-units include: The alpha chain situated on the exterior of the cell membrane and the beta chain spanning the cell membrane in a single segment.

When insulin is detected, the alpha chains move together folding around the insulin making the beta chains move together, converting them into an active tyrosine kinase. This initiates a phosphorylation cascade increasing the expression of GLUT4 and allowing uptake of glucose by cells.

Haemoglobin is composed of four polypeptide globin chains each with its own iron containing haem molecule. Haem synthesis occurs largely in the mitochondria by a series of biochemical reactions commencing with the condensation of glycine and succinyl coenzyme A under the action of the key rate-limiting enzyme delta-aminolevulinic acid (ALA) synthase. The globin chains are synthesised by ribosomes in the cytosol. Haemoglobin synthesis only occurs in immature red blood cells.
There are three types of haemoglobin in normal adult blood: haemoglobin A, A2 and F:
– Normal adult haemoglobin (HbA) makes up about 96 – 98 % of total adult haemoglobin, and consists of two alpha (α) and two beta (β) globin chains. 
– Haemoglobin A2 (HbA2), a normal variant of adult haemoglobin, makes up about 1.5 – 3.5 % of total adult haemoglobin and consists of two α and two delta (δ) globin chains.
– Foetal haemoglobin is the main Hb in the later two-thirds of foetal life and in the newborn until approximately 12 weeks of age. Foetal haemoglobin has a higher affinity for oxygen than adult haemoglobin. 
Red cells are destroyed by macrophages in the liver and spleen after , 120 days. The haem group is split from the haemoglobin and converted to biliverdin and then bilirubin. The iron is conserved and recycled to plasma via transferrin or stored in macrophages as ferritin and haemosiderin. An increased rate of haemoglobin breakdown results in excess bilirubin and jaundice.

Apoptosis is a controlled form of cell death in which no cellular contents are released from the dying cell, and thus no inflammatory reaction is seen. Apoptosis may occur physiologically or pathologically. Apoptosis may be induced in two main ways: by the engagement of surface death receptors e.g. TNF-alpha (extrinsic pathway) or through cellular injury (intrinsic pathway). The end result is the activation of proteases enzymes called caspases which dismantle the cell cytoplasm and nucleus. Apoptotic cells shrink down and fragment into apoptotic bodies, each of which retains an intact cell membrane; apoptotic bodies are then targeted or rapid removal by adjacent cells. Disordered apoptosis is thought to be central to a number of important disease processes, particularly carcinogenesis.

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.

Carbamazepine is primarily used to treat epilepsy, and it is effective for both focal and generalised seizures. It is not, however, effective in the treatment of absence or myoclonic seizures. It’s also commonly used to treat neuropathic pain, as well as a second-line treatment for bipolar disorder and as a supplement for acute alcohol withdrawal.

Carbamazepine works as a sodium channel blocker that preferentially binds to voltage-gated sodium channels in their inactive state. This prevents an action potential from firing repeatedly and continuously.

Passive expiration is produced primarily by relaxation of the inspiratory muscles (diaphragm and external intercostal muscles) and the elastic recoil of the lungs. In expiration, depression of the sternal ends of the ribs (‘pump handle’ movement), depression of the lateral shafts of the ribs (‘bucket handle’ movement) and elevation of the diaphragm result in a reduction of the thorax in an anteroposterior, transverse and vertical direction respectively. This results in a decreased intrathoracic volume and increased intrathoracic pressure and thus air is forced out of the lungs.

Antinuclear antibodies (ANA) are autoantibodies to the cells’ nucleus.

The ANA test is the most sensitive diagnostic test for verifying the disease’s diagnosis.

Other autoantibodies that may be found in SLE patients include rheumatoid factor, antiphospholipid antibodies, and antimitochondrial antibodies.

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/coma
Depression of the central nervous system
Phaeochromocytoma

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.

Extensor hallucis longus is innervated by the deep fibular nerve (root value L5 and S1).

Escherichia coli strain 0157 causes enterohaemorrhagic diarrhoea and can lead to renal failure, haemolytic anaemia and thrombocytopenia.

Norwalk virus is an RNA virus.

Although transmission of rotavirus is primarily through the faeco-oral route, airborne spread has been seen in some cases.

Cryptosporidium are protozoa with acid fast walls and are resistant to both chlorine treatment and conventional filtering methods.

There is no therapy effective in treating cryptosporidium diarrhoea as the protozoa is not susceptible to antibiotics.

C. difficile is normally found in the gut flora but its growth is normally suppressed by more dominant anaerobes. It has exotoxin-mediated effects causing profuse diarrhoea. Oral clindamycin (a broad spectrum antibiotic) is commonly implicated in precipitating C. difficile colitis; first line treatment is with oral metronidazole. Tetanolysin is a toxin produced by Clostridium tetani bacteria.

For hip extension, the gluteus maximus and hamstring muscles work together. To compensate for gluteus maximus weakness, the hamstring frequently acts as the primary hip extensor.

Both ventilation and perfusion increase towards the lung base, because of the effects of gravity, but the gravitational effects are greater on perfusion than ventilation and therefore there is a regional variation in V/Q ratio from lung apex (high V/Q) to lung base (low V/Q). In a pure shunt, there is normal perfusion but absent ventilation and the V/Q ratio = 0. In a true shunt increasing oxygen fraction has no effect because the oxygen-enriched air fails to reach the shunted blood. An increased A-a gradient is seen in V/Q mismatch.

Clinical Effects of vitamin deficiency include:
Vitamin C – Scurvy
Thiamine (Vitamin B1) – Beriberi/Wernicke-Korsakoff syndrome
Vitamin B12 – Megaloblastic anaemia/Subacute combined degeneration of spinal cord
Folate – Megaloblastic anaemia
Vitamin D – Osteomalacia/Rickets
Vitamin K – Defective clotting
Vitamin A – Blindness

Bacterial infections are common in the following situations:

Platelet transfusions are associated with a higher risk of bacterial infection (as platelets are stored at room temperature)
Immersion in a water bath thawed previously frozen components.
Components of red blood cells that have been stored for several weeks
Gram-positive and Gram-negative bacteria have both been linked to transfusion-transmitted bacterial infection, but Gram-negative bacteria are linked to a higher rate of morbidity and mortality.
Yersinia enterocolitica is the most common bacterial organism linked to transfusion-transmitted bacterial infection. This organism can multiply at low temperatures while also utilising iron as a nutrient. As a result, it’s well-suited to proliferating in blood banks.

The following are some of the most common clinical signs and symptoms of a bacterial infection transmitted through a blood transfusion. These symptoms usually appear shortly after the transfusion begins:
Fever is very high.
Rigours and chills
Vomiting and nausea
Tachycardia
Hypotension
Collapse of the circulatory system

If a bacterial infection from a transfusion is suspected, the transfusion should be stopped right away. Blood cultures and a Gram stain should be requested, as well as broad-spectrum antibiotics. In addition, the blood pack should be returned to the blood bank for an urgent culture and Gram-stain.

Angiotensin I is converted to angiotensin II by the removal of two C-terminal residues by the enzyme angiotensin-converting enzyme (ACE). This primarily occurs in the lungs, although it does also occur to a lesser degree in endothelial cells and renal epithelial cells.
The main actions of angiotensin II are:
Vasoconstriction of vascular smooth muscle (resulting in increased blood pressure)
Vasoconstriction of the efferent arteriole of the glomerulus (resulting in an increased filtration fraction and preserved glomerular filtration rate)
Stimulation of aldosterone release from the zona glomerulosa of the adrenal cortex
Stimulation of anti-diuretic hormone (vasopressin) release from the posterior pituitary
Stimulation of thirst via the hypothalamus
Acts on the Na+/H+ exchanger in the proximal tubule of the kidney to stimulate Na+reabsorption and H+excretion

Most cells have insulin receptors present on them which can be sequestered into the cell to inactivate them. These receptors consist of two extracellular alpha subunits which contain the insulin-binding site and two transmembrane beta subunits. Because insulin is a polypeptide hormone, it must act via cell surface receptors as it is unable to readily cross the cell membrane. On binding to the receptor, the beta subunit of insulin autophosphorylation, which activates tyrosine kinase. As a result, there is an intracellular cascade of phosphorylation, causing a translocation of the glucose transporter GLUT4 and GLUT-1 to the plasma membrane of the affected cell. This facilitates glucose entry.

Pericardiocentesis is a procedure that removes excess fluid from the pericardium. As a result, it’s used in cases of cardiac tamponade, which occurs when there’s too much fluid in the space around the heart.

During the procedure, a needle and a small catheter are inserted 1 to 2 cm inferior and to the left of the xiphochondral junction into the pericardial cavity.

Features of sickle cell disease include:
Anaemia (symptoms are usually mild because the O2 dissociation curve of Hb S is shifted to the right)
Vaso-occlusive crisis
Visceral sequestration crisis
Aplastic crisisIncreased susceptibility to infection
Other clinical features: Pigment gallstones with cholecystitis
Chronic leg ulcers
Avascular necrosis of the femoral and humeral heads or other bones
Cardiomyopathy
Pulmonary hypertension
Proliferative retinopathy
Priapism
Renal papillary necrosis
Stroke

Calcium homeostasis is primarily controlled by three hormones: parathyroid hormone, activated vitamin D and calcitonin.

Parathyroid hormone acts on the kidneys to increase calcium reabsorption in the distal tubule by activating Ca2+entry channels in the apical membrane and the Ca2+ATPase pump in the basolateral membrane (and to decrease phosphate reabsorption in the proximal tubule).

Activated vitamin D acts to increase calcium reabsorption in the distal tubule via activation of a basolateral Ca2+ATPase pump (and to increase phosphate reabsorption).

Calcitonin acts to inhibit renal reabsorption of calcium (and phosphate).

Heparin works by binding to and activating the enzyme inhibitor antithrombin III.

Antithrombin III inactivates thrombin (factor IIa) by forming a 1:1 complex with thrombin. The heparin-antithrombin III complex also inhibits factor Xa and some other proteases involved with clotting. The heparin-ATIII complex can also inactivate IX, XI, XII, and plasmin.

Heparin is a polymer of glycosaminoglycan. It occurs naturally and is found in mast cells. Clinically, it is used in two forms:
1. Unfractionated: widely varying polymer chain lengths
2. Low molecular weight: Smaller polymers only

Heparin is not thrombolytic or fibrinolytic. It prevents the progression of existing clots by inhibiting further clotting. The lysis of existing clots relies on endogenous thrombolytics.

Heparin is used for:
1. Prevention and treatment of venous thromboembolism
2. Treatment of disseminated intravascular coagulation
3. Treatment of fat embolism
4. Priming of haemodialysis and cardiopulmonary bypass machines