Myeloma laboratory findings include:
– The presence of a paraprotein in serum or urine (the paraprotein is IgG in 60 percent of cases, IgA in 20 percent, and light chain only in almost all the rest),
– Increased serum immunoglobulin-free light chain proteins generated by plasma cells but not coupled with heavy chains 
– Reduced IgG, IgA, and IgM levels in the blood (immune paresis)
– Anaemia, whether normochromic, normocytic, or macrocytic. 
– On a blood film, a Rouleaux formation has been marked.
– In advanced illness, neutropenia and thrombocytopenia are common.
– ESR is high.
– Plasma cells in the bone marrow are overabundant, typically in aberrant forms. – Hypercalcemia
– Creatinine levels are high.
– Serum albumin levels are low in advanced illness.
60 percent of patients have osteolytic lesions, osteoporosis, or pathological fractures.

Normal saline (sodium chloride 0.9%) contains:
Na+150 mmol/L
Cl-150 mmol/L

Absolute risk reduction (ARR) of treatment
= risk of death in control group – risk of death in treatment group
ARR = (10/1000) – (5/1000)
= 5/1000 = 0.005
Number needed to treat (NNT)
= 1/ARR
= 1/0.005
= 200
Therefore 200 people would need to be treated to prevent one extra death.

Cortisol is a steroid hormone produced in the zona fasciculata of the adrenal cortex. It is released in response to stress and low blood glucose concentrations.
Cortisol acts to: raise plasma glucose by stimulating glycolysis and gluconeogenesis in the liver and inhibiting peripheral glucose uptake into storage tissues, increase protein breakdown in skeletal muscle, skin and bone to release amino acids, increase lipolysis from adipose tissues to release fatty acidsand at higher levels and mimic the actions of aldosterone on the kidney to retain Na+ and water and lose K+ ionssuppress the action of immune cells

One of the commonest antispasmodic medications that is used is hyoscine butylbromide. It is an antimuscarinic and typical side effects of this class of drugs include:
– dilation of pupils with loss of accommodation (cycloplegia)
-photophobia resulting in blurred vision (Blind as a bat)
-dry mouth, eyes and skin (Dry as a bone),
-elevated temperature (Hot as a hare)
-skin flushing (Red as a beet)
-confusion or agitation particularly in the elderly (Mad as a hatter)
-reduced bronchial secretions
-transient bradycardia followed by tachycardia, palpitation and arrhythmias
-urinary retention and/or constipation

Noradrenaline (the sympathetic neurotransmitter) is a positive inotrope; it binds to β1-adrenoceptors on the membrane and causes increased Ca2+entry via L-type channels during the AP and thus increases Ca2+release from the SR. Noradrenaline also increases Ca2+sequestration into the SR and thus more Ca2+is available for the next contraction. Cardiac glycosides (e.g. digoxin) slow the removal of Ca2+from the cell by inhibiting the membrane Na+pump which generates the Na+gradient required for driving the export of Ca2+; consequently the removal of Ca2+from the myocyte is slowed and more Ca2+is available for the next contraction. Acidosis is negatively inotropic, largely because H+competes for Ca2+binding sites.

High-dose NSAIDs are the first-line treatment for acute gout. In the absence of any contraindications, Naproxen 750 mg as a stat dose followed by 250 mg TDS is commonly used.

Aspirin is contraindicated in gout. It reduces the urinary clearance of urate and also interferes with the action of uricosuric agents.

Colchicine is preferred in patients with heart failure or in those who are intolerant of NSAIDs. It is as effective as NSAIDs in relieving acute attacks.

Colchicine acts on the neutrophils, binding to tubulin to prevent neutrophil migration into the joint. Where Allopurinol is not tolerated, it has a role in prophylactic treatment of gout.

Allopurinol should not be started in the acute phase of gout as it increases the severity and duration of symptoms. It is used as a prophylaxis in preventing future attacks and acts by reducing serum uric acid levels.

Number needed to harm (NNH) corresponds to the number of individuals that must be treated, so that one of them presents an adverse reaction accountable to the treatment.

Hence, a NNH of 100 means that 100 individuals need to be treated in order to produce an adverse effect of the treatment in one individual.

Following a myocardial infarction scar tissue formation will take place at the site of the damaged muscle. This places increased load on the rest of the myocardium causing it to hypertrophy. The left ventricle will hypertrophy first as it is pumping blood against a greater afterload as compared to the right ventricle.

There are three types of cells in the body with regards to the cell cycle: 1. permanent
2. labile
3. stable cells

Permanent cells do not re-enter the cell cycle and remain in G0. If there is a pool of stem cells the stem cells will enter the cell cycle to form more cells. Myocardial cells are a type of permanent cell and there is no pool of stem cells in the heart muscle. The anterior wall will not hypertrophy as it is formed by the right atrium and ventricle and both of these hypertrophy after the left ventricle.

Parainfluenza virus is the most commonly implicated infectious agent in croup.

Overuse of cortisol medication, as seen in the treatment of patients with chronic asthma or rheumatoid arthritis, can cause Cushing’s syndrome.

Weight gain, thin arms and legs, a round face, increased fat around the base of the neck, a fatty hump between the shoulders, easy bruising, wide purple stretch marks primarily on the abdomen, breasts, hips, and under the arms, weak muscles, hirsutism, hypertension, erectile dysfunction, osteoporosis, frontal alopecia, acne, depression, poor wound healing, and polycythaemia are all clinical features of Cushing’s syndrome.

Mucus contains chemicals such as alpha-1-antitrypsin, lysozyme, and IgA that protect the airway from pathogens and damaging proteases released from dead bacteria and immune cells. Early-onset emphysema results from a genetic deficit of alpha-1-antitrypsin, which is caused by unregulated protease activity in the lungs, which results in the degradation of elastin in the alveoli.

25-year-old receives immunoglobulin and vaccination after cutting her hand on a drinking glass and not knowing her vaccination history.

Because this is not a tetanus-prone wound, immunoglobulin is not recommended. Because you can’t be sure about her vaccination history, now is the best time to start a tetanus vaccination course to ensure coverage later in life. The first vaccination should be administered at the time of presentation; the patient’s own GP should then review the patient’s vaccination history and schedule the rest of the course as needed.

8-year-old whose hand was cut with a kitchen knife, received her first round of vaccinations as a baby and a booster at the age of four – receives vaccination:
The tetanus vaccinations for this child are up to date, and the next booster should not be given too soon. Immunoglobulin is not required because this is not a tetanus-prone wound.

80-year-old diabetic, a rusty nail went through his shoe and into his foot while walking in the woods, and he was uncertain of his vaccination history – he received vaccination and immunoglobulin:
A tetanus vaccination course may not have been completed by an 80-year-old UK resident (the vaccination was introduced in 1961). The vaccination should be given at a walk-in clinic, and the patient’s own GP should be contacted to confirm vaccination history and to schedule the rest of the course as needed. Because this is a tetanus-prone wound (puncture wound and potential soil contact), immunoglobulin would be recommended in a patient with incomplete tetanus vaccinations.

A 28-year-old Polish man cuts his leg while working in the garden, the wound is heavily contaminated with soil, and his vaccination history is unknown – he receives vaccination:
In a patient with an unknown vaccination history, this is a tetanus-prone wound. In this case, the best course of action would be to administer both the vaccination and immunoglobulin at the walk-in clinic, then contact the patient’s own GP to check his or her vaccination history and schedule the rest of the course as needed.

30-year-old with a large amount of devitalized tissue in the torso from an electrical burn – has had all vaccinations, so no need for vaccination or immunoglobulin:
Because this is a high-risk tetanus wound (with a lot of devitalized tissue), even if the patient has had a full course of vaccinations in the past, immunoglobulin is recommended. There is no need for any additional vaccinations.

The latissimus dorsi muscle is a broad, flat muscle that occupies the majority of the lower posterior thorax. The muscle’s primary function is of the upper extremity but is also considered to be a respiratory accessory muscle.

Latissimus dorsi is a climbing muscle. With the arms fixed above the head, it can raise the trunk upwards, together with the help of pectoralis major.

Functionally, the latissimus dorsi muscle belongs to the muscles of the scapular motion. This muscle is able to pull the inferior angle of the scapula in various directions, producing movements on the shoulder joint (internal rotation, adduction and extension of the arm). It is innervated by the thoracodorsal nerve (C6 – C8) from the posterior cord of the brachial plexus, which enters the muscle on its deep surface.

Osmosis is the passive movement of water across a semipermeable membrane from a region of low solute concentration to a region of higher solute concentration.
When hypertonic fluid is ingested:
The plasma becomes CONCENTRATED.

The cells lose water and shrink
The intracellular fluid becomes more concentrated.
Water and ions move freely from the plasma into the interstitial fluid and the interstitial fluid becomes more concentrated.
The increased osmotic potential draws water out of the cells.

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.

Factors increasing the surface area include:The small intestine is very long – about 5 m in length.The inner wall of the small intestine is covered by numerous folds of mucous membrane called plicae circulares.The lining of the small intestine is folded into many finger-like projections called villi.The surface of the villi is covered with a layer of epithelial cells which, in turn, have many small projections called microvilli that project towards the lumen of the intestine (forming the brush border).

About 20% of patients that suffer an anaphylactic reaction suffer a biphasic response 4-6 hours after the initial response (sometimes up to 72 hours after).

Varicella-zoster immunoglobulin (VZIG) is indicated for post exposure prevention and treatment of varicella. It is recommended as prophylaxis for high-risk patients with no known immunity (i.e. no known previous chickenpox) who have had a significant exposure to varicella-zoster (considered >4 hours close contact).

The high-risk groups are:
1. Neonates
2. Pregnant women
3. The immunocompromised (e.g. cancer, immunosuppressive therapies)
4. Those on high dose steroids (children on more than 2 mg/kg/day for more than 14 days, or adults on 40 mg/day for more than a week)

This patient is at high risk of developing adrenal insufficiency and may need a temporary increase in her steroid dose during infection or stress. It would be inappropriate to stop or wean down her dose of prednisolone and can cause side effects.

Since he is on steroids without immunity for chickenpox, he is at risk of developing severe varicella infection, with possible complications including pneumonia, hepatitis and DIC.

If he develops a varicella infection, he will need to be admitted and require a specialist review and intravenous Acyclovir.

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

The following are organisms that are capable of producing acute, bloody diarrhoea:
– Campylobacter jejuni
– Escherichia coli O157:H7
– Salmonella species
– Shigella species
– Yersinia species
– Entamoeba histolytica

Other E. coli strains, Giardia, Vibrio, and other parasites are associated with watery, but not bloody, diarrhoea.

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.

It’s crucial that thrombin’s impact is restricted to the injured site. Tissue factor pathway inhibitor (TFPI), which is produced by endothelial cells and found in plasma and platelets, is the first inhibitor to function. It accumulates near the site of harm induced by local platelet activation. Xa and VIIa, as well as tissue factor, are inhibited by TFPI. Other circulating inhibitors, the most potent of which is antithrombin, can also inactivate thrombin and other protease factors directly. Coagulation cofactors V and VIII are inhibited by protein C and protein S. Tissue plasminogen activator (TPA) from endothelial cells facilitates fibrinolysis by promoting the conversion of plasminogen to plasmin.

Coagulative necrosis is the most common form of necrosis characterised by the loss of cell nuclei, but with general preservation of the underlying architecture. Dead tissue is macroscopically pale and firm. This is the classic pattern seen in myocardial infarction.Liquefactive necrosis leads to complete loss of cellular structure and conversion into a soft, semi-solid mass. This is typically seen in the brain following cerebral infarction.Caseous necrosis is most commonly seen in tuberculosis. Histologically, the complete loss of normal tissue architecture is replaced by amorphous, granular and eosinophilic tissue with a variable amount of fat and an appearance reminiscent of cottage cheese.Gangrenous necrosis is necrosis with putrefaction of tissues due to exposure to air (dry gangrene) or infection (wet gangrene).

ADH binds V2 receptors on renal principal cells in the late distal tubule and collecting ducts, raising cAMP levels and causing intracellular vesicles to fuse with the apical membrane. In their membrane these vesicles have water channels called aquaporins, which increase the water permeability allowing greater water reabsorption and concentration of urine. ADH also binds to V1 receptor receptors on vascular smooth muscle, causing vasoconstriction and enhancing the effect of aldosterone on sodium reabsorption in the distal tubule. ADH release is stimulated primarily by raised plasma osmolality detected by osmoreceptors in the anterior hypothalamus. Other factors that increase ADH release include: extracellular fluid volume depletion, angiotensin II, nausea, pain, stress, exercise, emotion, hypoglycaemia. ADH release is inhibited by low plasma osmolality, alcohol, caffeine, glucocorticoids and atrial natriuretic peptide (ANP). ADH deficiency (or an inadequate response to ADH) results in diabetes insipidus. Excess levels of ADH results in syndrome of inappropriate ADH secretion (SIADH).

Immunodeficiency is present in all patients with chronic lymphocytic leukaemia (CLL), though it is often mild and not clinically significant. Infections are the leading cause of death in 25-50 percent of CLL patients, with respiratory tract, skin, and urinary tract infections being the most common.

Hypogammaglobulinemia is the most common cause of immunodeficiency in CLL patients, accounting for about 85 percent of all cases.

An avulsion fracture of the base of the fifth metatarsal happens when the ankle is twisted inwards.

When the ankle is twisted inwards a muscle called the fibularis brevis contracts to stop the movement and protect the ligaments of the ankle.

The base of the fifth metatarsal is where this muscle is attached. The group of lateral leg muscles that function to plantarflex the foot includes the fibularis brevis and the fibularis longus.

CLL (chronic lymphocytic leukaemia) is the most common type of chronic lymphoid leukaemia, with a peak incidence between the ages of 60 and 80. It is the most common type of leukaemia in Europe and the United States, but it is less common elsewhere.

The CLL tumour cell is a mature B-cell with low immunoglobulin surface expression (IgM or IgD). The average age at diagnosis is 72 years, with only 15% of cases occurring before the age of 50.

The male-to-female ratio is about 2:1. Over 80% of cases are identified by the results of a routine blood test, which is usually performed for another reason.

Lymphocytic anaemia, thrombocytopenia, and normochromic normocytic anaemia are common laboratory findings. Aspiration of bone marrow reveals up to 95% lymphocytic replacement of normal marrow elements.

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

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

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

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

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).
Mannitol is primarily used to reduce the pressure and volume of cerebrospinal fluid (CSF). It decreases the volume of CSF by:
Decreasing the rate of CSF formation,and;
Withdrawing extracellular fluid from the brain across the BBB
Other uses of mannitol include:
Short-term management of glaucoma
Treatment of rhabdomyolysis
Preserve renal function in peri-operative jaundiced patients
To initiate diuresis in transplanted kidneys
Bowel preparation prior to colorectal procedures
The recommended dose of mannitol for the reduction of CSF pressure/cerebral oedema is 0.25-2g/kg as an intravenous infusion over 30-60 minutes. This can be repeated 1-2 times after 4-8 hours if needed.
Circulatory overload and rebound increases in intracranial pressure may occur following the use of mannitol. It is irritant to tissues and veins and can cause inflammation and phlebitis.
Mannitol causes an expansion of the extracellular fluid space, which may worsen congestive cardiac failure. Contraindications to the use of mannitol include:
Anuria
Intracranial bleeding (except during craniotomy)
Severe cardiac failure
Severe dehydration
Severe pulmonary oedema