Raised platelet levels have emerged as a cancer risk marker, according to a large population-based study published in 2017(link is external). According to the study, 12 percent of men and 6% of women with thrombocytosis were diagnosed with cancer within a year. These figures increased to 18% in men and 10% in women if a second platelet count was taken within 6 months of the first and showed an increased or stable elevated platelet count.The researchers discovered that thrombocytosis linked to cancer is most common in colorectal and lung cancers, and it is linked to a worse prognosis. Furthermore, one-third of the cancer patients in the study had no other symptoms that would have prompted an immediate cancer referral.The exact mechanism by which these cancers cause thrombocytosis is unknown, but one theory proposes the existence of pathogenic feedback loops between malignant cells and platelets, with a reciprocal interaction between tumour growth and metastasis, as well as thrombocytosis and platelet activation. Another hypothesis is that thrombocytosis occurs independently of cancer but aids in its spread and progression.The findings show that routinely testing for thrombocytosis could cut the time it takes to diagnose colorectal and lung cancer by at least two months. In the UK, this could result in around 5500 earlier cancer diagnoses per year.Because the positive predictive value of thrombocytosis in middle age for cancer (10%) is higher than the positive predictive value for a woman in her 50s presenting with a new breast lump (8.5%), this is clearly an important research paper that should be used to adjust future clinical practise. The current NICE guidelines predate these new research findings, so we’ll have to wait and see how they affect cancer referral guidelines in the UK.Because there are so many possible cancers associated with thrombocytosis, the treating clinician should take a thorough history and perform a thorough clinical examination if a patient is diagnosed with it. Further investigation and the most appropriate referral route should be aided by this information.It’s worth noting that the patients in the study had their blood tests done for a medical reason rather than as a random screening test.If there are no other symptoms to guide investigation and referral (one-third of the patients in the study had no other symptoms), keep in mind that the two most common cancers encountered were colorectal and lung cancer, so a chest X-ray and a faecal immunochemical test (FIT) for faecal blood may be reasonable initial investigations.

Lymphoma is a cancer of the lymphatic system, which is part of the body’s germ-fighting network. They are a group of diseases that are caused by malignant lymphocytes. These malignant cells accumulate in lymph nodes and other lymphoid tissue, giving rise to the characteristic clinical feature of lymphadenopathy. They can be subdivided into Hodgkin lymphoma (HL) which are characterised by the presence of Reed-Sternberg cells, and non-Hodgkin lymphoma (NHL). Characteristics of HL include:1. can present at any age but is rare in children and has a peak incidence in young adults, 2. almost 2:1 male predominance. 3. presents with painless, asymmetrical, firm and discrete enlargement of superficial lymph nodes. 4. cervical node involvement in 60-70% of cases, 5. axillary node involvement in 10-15% 6. inguinal node involvement in 6-12%. 7. modest splenomegaly during the course of the disease in 50% of patients8. may occasionally have liver enlargement9. bone marrow failure involvement is unusual in early disease. Approximately 85% of patients are cured, but the prognosis depends on age, stage and histology. Two well‐known but rare symptoms in HL are alcohol‐induced pain and pruritus.

Cardiac output (CO) is calculated by multiplying stroke volume (SV) by heart rate (HR):CO = HR x SVAs a result, both stroke volume and heart rate are exactly proportional to cardiac output. There will be an increase in cardiac output if the stroke volume or heart rate increases, and a reduction in cardiac output if the stroke volume or heart rate lowers.

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 appearanceLethargy and tirednessSplenomegaly (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 18.5 g/dl in men, 16.5 g/dl in womenElevated red cell mass > 25% above mean normal predicted valuePresence of JAK2 mutationMinor criteria:Bone marrow biopsy showing hypercellularity with prominent erythroid, granulocytic and megakaryocytic proliferationSerum erythropoietin level below normal rangeEndogenous erythroid colony formation in vitroThe 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.

Adverse effects of loop diuretics include:Mild gastrointestinal disturbances, pancreatitis and hepatic encephalopathyHyperglycaemiaAcute urinary retentionWater and electrolyte imbalanceHyponatraemia, hypocalcaemia, hypokalaemia, hypomagnesaemia, hypochloraemiaHypotension, hypovolaemia, dehydration, and venous thromboembolismMetabolic alkalosisHyperuricaemiaBlood disorders (bone marrow suppression, thrombocytopenia, and leucopenia)Visual disturbance, tinnitus and deafnessHypersensitivity reactions

A median nerve injury affecting the extrinsic and intrinsic muscles of the hand will present with:Loss of sensation to the lateral palm and the lateral three and a half fingers.Weakness of flexion at the metacarpophalangeal joints of the index and middle finger. This is because of paralysis of the lateral two lumbricals. Weakness of flexion of the proximal interphalangeal joints of all four fingers due to paralysis of the flexor digitorum superficialisWeakness of flexion at the distal interphalangeal joints of the index and middle finger following paralysis of the lateral half of the flexor digitorum profundus.Weakness of thumb flexion, abduction and opposition due to paralysis of the flexor pollicis longus and thenar muscles

A negative correlation coefficient means that the two variables are inversely related e.g. socio-economic class and mortality.

A L’Abbé plot is a scatter plot with the risk in the control group on the x-axis and the risk in the experimental group on the y-axis. It can be used to evaluate heterogeneity in meta-analysis. Furthermore, this plot can aid to choose a summary measure (odds ratio, risk ratio, risk difference) that will result in more consistent results.

Clinical features of hypoglycaemia: Autonomic  symptoms: Sweating, feeling hot, anxiety/agitation, palpitations, shaking, paraesthesia, dizzinessNeuroglycopaenic symptoms: Weakness, blurred vision, difficulty speaking, poor concentration, poor coordination, drowsiness, confusion, seizures, comaOther symptoms: Nausea, fatigue, hunger

Neisseria gonorrhoeae is a Gram-negative diplococcus that causes gonorrhoea. Gonorrhoea is an acute pyogenic infection of nonciliated columnar and transitional epithelium; infection can be established at any site where these cells are found. Gonococcal infections are primarily acquired by sexual contact and occur primarily in the urethra, endocervix, anal canal, pharynx, and conjunctiva.In men, acute urethritis, usually resulting in purulent discharge and dysuria (painful urination), is the most common manifestation. The endocervix is the most common site of infection in women. Symptoms of infection, when present, include dysuria, cervical discharge, and lower abdominal pain. Some cases in women may be asymptomatic leading to complications such as pelvic inflammatory disease. Blood-borne dissemination occurs in less than 1% of all infections, resulting in purulent arthritis and rarely septicaemia. Fever and a rash on the extremities can also be present. Other conditions associated with N. gonorrhoeae include anorectal and oropharyngeal infections. Infections in these sites are more common in men who have sex with men but can also occur in women. Pharyngitis is the chief complaint in symptomatic oropharyngeal infections, whereas discharge, rectal pain, or bloody stools may be seen in rectal gonorrhoea. Approximately 30% to 60% of women with genital gonorrhoea have concurrent rectal infection. Newborns can acquire ophthalmia neonatorum, a gonococcal eye infection, during vaginal delivery through an infected birth canal. Specimens collected for the recovery of N. gonorrhoeae may come from genital sources or from other sites, such as the rectum, pharynx, and jointfluid. According to the 2010 STD Treatment guidelines, cephalosporins (e.g., ceftriaxone, cefixime) are currently recommended treatments.

Clostridium difficile, a Gram-positive, anaerobic, spore forming bacteria is present in the gut of approximately 3% of healthy adults (2012 UK HPA estimates). Following use of broad spectrum antibiotics, which alter normal gut flora, Clostridium difficile infection (CDI) occurs. About 80% of Clostridium Difficile infections are seen in people over the age of 65 and its main clinical features are:Abdominal cramps, severe bloody and/or watery diarrhoea, offensive smelling diarrhoea, and fever. CDI is the most severe consequence of antibiotic treatment and is a major cause of morbidity and mortality. Risk for CDI has been found to be greatest with clindamycin followed by fluoroquinolones Tetracyclines are not associated with risk for CDI.

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)

Diabetes insipidus (DI) may result from a deficiency of ADH secretion (cranial DI) or from an inappropriate renal response to ADH (nephrogenic DI). As a result, fluid reabsorption at the kidneys is impaired, resulting in large amounts of hypotonic, dilute urine being passed with a profound unquenchable polydipsia.The biochemical hallmarks of DI are:High plasma osmolality (> 295 mOsm/kg)Low urine osmolality (< 300 mOsm/kg)Hypernatraemia (> 145 mmol/L)High urine volume

The glossopharyngeal nerve, which is responsible for the afferent pathway of the gag reflex, the vagus nerve, which is responsible for the efferent pathway of the gag reflex, and the spinal accessory nerve all exit the skull through the jugular foramen. These nerves are most frequently affected if the jugular foramen is compressed. As a result, the patient’s gag reflex is impaired. The vestibulocochlear nerve is primarily responsible for hearing. The trigeminal nerve provides sensation in the face. The facial nerve innervates the muscles of face expression (including those responsible for closing the eye). Tongue motions are controlled mostly by the hypoglossal nerve.

Erysipelas is a rare infection of the skin and subcutaneous tissues observed frequently in elderly patients. It is characterized by an acute spreading skin lesion that is intensely erythematous with a plainly demarcated but irregular edge. It is most commonly caused by Streptococcus pyogenes or Group A Streptococcus (GAS).GAS are susceptible to penicillin, which remains the drug of choice for treatment. For patients allergic to penicillin, erythromycin can be used.S. pyogenes colonizes the throat and skin on humans, making these sites the primary sources of transmission. Infections resulting from S. pyogenes include pharyngitis, scarlet fever, skin or pyodermal infections, and other septic infections. In addition, the sequelae rheumatic fever and acute glomerulonephritis can occur as a result of infection with S. pyogenes.Agammaglobulinemia is mostly associated with S. pneumoniae.The M protein is attached to the peptidoglycan of the cell wall and extends tothe cell surface. The M protein is essential for virulence. The polysaccharide capsule is characteristic of S. pneumoniae.

Angiotensin II acts to:Stimulate release of aldosterone from the zona glomerulosa of the adrenal cortex (which in turn acts to increase sodium reabsorption)Cause systemic vasoconstrictionCause vasoconstriction of the renal arterioles (predominant efferent effect thus intraglomerular pressure is stable or increased, thereby tending to maintain or even raise the GFR)Directly increase Na+reabsorption from the proximal tubule (by activating Na+/H+antiporters)Stimulate synthesis and release of ADH from the hypothalamus and posterior pituitary respectivelyStimulate the sensation of thirstPotentiate sympathetic activity (positive feedback)Inhibit renin production by granular cells (negative feedback)

Typically, granuloma has Langhan’s cells (large multinucleated cells ) surrounded by epithelioid cell aggregates, T lymphocytes and fibroblasts.Antigen presenting monocytic cells found in the skin are known as Langerhan’s cells.

Injury to the intercostal artery (ICA) is an infrequent but potentially life-threatening complication of all pleural interventions. Traditional anatomy teaching describes the ICA as lying in the intercostal groove, protected by the flange of the rib. This is the rationale behind the recommendation to insert needles just above the superior border of the rib. Current recommendations for chest drain insertion suggest that drains should be inserted in the ‘safe triangle’ in order to avoid the heart and the mediastinum and be above the level of the diaphragm. The safe triangle is formed anteriorly by the lateral border of the pectoralis major, laterally by the lateral border of the latissimus dorsi, inferiorly by the line of the fifth intercostal space and superiorly by the base of the axilla. Imaging guidance also aids in the safety of the procedure.

Etomidate is a carboxylated imidazole derivative with a short half-life that is primarily used to induce anaesthesia.It is thought to modulate fast inhibitory synaptic transmission in the central nervous system by acting on GABA type A receptors.The dose for anaesthesia induction is 0.3 mg/kg. Etomidate takes 10-65 seconds to take effect after an intravenous injection, and it lasts 6-8 minutes. With repeated administration, the effects are non-cumulative.The relative cardiovascular stability of etomidate is noteworthy. During induction, it causes less hypotension than thiopental sodium and propofol. It’s also linked to a quick recovery without the hangover.Etomidate is a strong steroidogenesis inhibitor. The drug inhibits the enzymes responsible for adrenal 11 beta-hydroxylase and cholesterol cleavage, resulting in a decrease in cortisol and aldosterone synthesis for up to 24 hours after administration. It should not be used to maintain anaesthesia because of the adrenocortical suppression.Other side effects associated with etomidate use include:Vomiting and nauseaThe injection causes pain (in up to 50 percent )Phlebitis and thrombosis of the veinsHeart block and arrhythmiasHyperventilationApnoea and respiratory depressionIt has the potential to cause both hypo- and hypertension.Critically ill patients have a higher mortality rate.

Only a very small fraction of the thyroid hormones circulating in the blood are free. The majority is bound to transport proteins. Only the free thyroid hormones are biologically active, and measurement of total thyroid hormone levels can be misleading. The relative percentages of bound and unbound thyroid hormones are:Bound to thyroid-binding globulin -70%Bound to albumin -15-20%Bound to transthyretin -10-15%Free T3 -0.3%Free T4 -0.03%

Hypothyroidism occurs when there is a deficiency of circulating thyroid hormones. It is commoner in women and is most frequently seen in the age over 60.Iodine deficiency is the commonest cause of hypothyroidism worldwide.In the UK and other developed countries, iodine deficiency is not a problem and autoimmune thyroiditis is the commonest cause.

The female Anopheles mosquito is the vector for Plasmodium falciparum transmission. Treponema pallidum is transmitted through sexual transmission or direct skin contact. Clostridium perfringens is spread by direct skin contact or through oral-faecal route. The oral-faecal pathway is how Vibrio cholerae spreads. Mycoplasma tuberculosis is spread via the airborne route.

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.

IV adrenaline 1 mg (10 mL of 1:10,000 solution) should be given after 3 shocks and every 3 – 5 minutes/after alternate shocks thereafter.

DIC is characterised by a widespread inappropriate intravascular deposition of fibrin with consumption of coagulation factors and platelets. This may occur as a consequence of many disorders that release procoagulant material into the circulation or cause widespread endothelial damage or platelet aggregation. Increased activity of thrombin in the circulation overwhelms its normal rate of removal by natural anticoagulants. In addition to causing increased deposition of fibrin in the microcirculation and widespread platelet aggregation to the vessels, intravascular thrombin formation interferes with fibrin polymerisation. Intense fibrinolysis is stimulated by thrombi on vascular walls and the release of fibrin degradation products again interferes with fibrin polymerisation. The combined action of thrombin and plasmin causes depletion of fibrinogen and all coagulation factors, compounded by thrombocytopaenia caused by platelet consumption.

The glomerular filtration membrane is composed of fenestrated capillary endothelium, basement membrane, and filtration slits. It is an organized, semipermeable membrane preventing the passage of most of the proteins into the urine. The anatomical arrangement of the glomerular filtration membrane maximizes the surface area available for filtration. The arrangement of its arterioles results in high hydrostatic pressures and facilitates filtration. Fenestrated capillary endothelium of the glomerular filtration membrane is with relatively large pores. It allows the free movement of plasma proteins and solutes but still restricts the movement of blood cells. Filtration slits are the smallest filters and restrict the movement of plasma proteins but still allow free movement of ions and nutrients. The glomerular basement membrane (GBM) is a critical component of the glomerular filtration membrane. Thus, it is not true that its absence will reduce the resistance of flow. The basement membrane is true to be more selective and contains negatively charged glycoproteins. However, it still allows free passage of water, nutrients, and ions. Severe structural abnormalities of the GBM can result in protein (albumin) leakage.

The spinal cord starts at the foramen magnum, where it is continuous with the medulla oblongata, which is the most caudal portion of the brainstem.It then extends inferiorly through the vertebral canal. In adults, it usually ends at the level of the first or second lumbar vertebra.

Campylobacter spp. are a common cause of acute infective gastroenteritis, particularly in children, with Campylobacter jejuni responsible for 90% of Campylobacter gastroenteritis. Infection typically follows ingestion of contaminated meat (most frequently undercooked poultry), unpasteurised milk or contaminated water, following which the microorganism invades and colonises the mucosa of the small intestine.

CSF analysis typically shows: cloudy turbid appearanceraised WCC – predominantly neutrophilshigh proteinlow glucose (typically < 40% of serum glucose)Gram-negative diplococci seen under microscopy

Gastrin is a peptide hormone that aids in gastric motility by stimulating the generation of gastric acid by the parietal cells of the stomach. G-cells in the stomach’s pyloric antrum, the duodenum, and the pancreas release it.The following stimuli cause the release of gastrin:Stimulation of the vagus nerveHypercalcaemiastomach bloatingProteins that have been partially digested, particularly amino acids.The presence of acid and somatostatin inhibits the release of gastrin.Gastrin’s main actions are as follows:Gastric parietal cells are stimulated to release hydrochloric acid.ECL cells are stimulated to produce histamine.Gastric parietal cell maturation and fundal growth stimulationCauses the secretion of pepsinogen by the gastric chief cells.Improves antral muscle mobility stimulates gastric contractionsIncreases gastric emptying rate and stimulates pancreatic secretionGallbladder emptying is induced.