If SBP is less than 90 mmHg , 500 mL sodium chloride 0.9 percent should be administered intravenously over 10–15 minutes, and repeated if SBP remains less than 90 mmHg. When SBP is greater than 90 mmHg, sodium chloride infusion must be maintained at a rate that replaces the deficit.

Sickling of red blood cells can lead to several different clinical syndromes. If the sickling occurs in the corpora cavernosa, it can lead to a sustained, painful erection of the penis, referred to as priapism. One of the complications is long-term impotence. It is important to seek a urological opinion immediately in this case, but in the interim, treat with perineal ice packs and walk up and down the stairs.

Anti-cyclic citrullinated peptide (anti-CCP) is an antibody present in 60-80% of rheumatoid arthritis patients. It is measured by enzyme-linked immunosorbent assay (ELISA). It may be present years before the onset of the disease and is associated with a more severe disease course.

While most patients with anti-CCP antibodies are also positive for rheumatoid factor (RF), RF antibody is not specific for rheumatoid arthritis as it can occur in patients with other conditions such as infections and other autoimmune conditions.

ESR, antinuclear antibodies(ANA) and Synovial fluid examination are not specific for rheumatoid arthritis.

In patients with exertional stable angina, nitrates improve exercise tolerance, time to onset of angina, and ST-segment depression during exercise testing. In combination with beta-blockers or calcium channel blockers, nitrates produce greater anti-anginal and anti-ischemic effects.
While they act as vasodilators, coronary vasodilators, and modest arteriolar dilators, the primary anti ischemic effect of nitrates is to decrease myocardial oxygen demand by producing systemic vasodilation more than coronary vasodilation. This systemic vasodilation reduces left ventricular systolic wall stress.

About 80% of bicarbonate is reabsorbed in the proximal tubule. HCO3-is not transported directly, tubular HCO3-associates with H+secreted by epithelial Na+/H+antiporters to form carbonic acid (H2CO3) which readily dissociates to form carbon dioxide and water in the presence of carbonic anhydrase. CO2and water diffuse into the tubular cells, where they recombine to form carbonic acid which dissociates to H+and HCO3-. This HCO3-is transported into the interstitium largely by Na+/HCO3-symporters on the basolateral membrane (and H+is secreted back into the lumen). For each H+secreted into the lumen, one Na+and one HCO3-are reabsorbed into the plasma. H+is recycled so there is little net secretion of H+at this stage.

Legionella pneumophilais a Gram negative bacterium that is found in natural water supplies and in the soil, transmitted predominantly via inhalation of aerosols generated from contaminated water (direct person-to-person spread of infected patients does not occur). It is the cause of Legionnaires’ disease. Outbreaks of Legionnaires’ disease have been linked to poorly maintained air conditioning systems, whirlpool spas and hot tubs.

The clinical features of the pneumonic form of Legionnaires’ disease include:
Mild flu-like prodrome for 1-3 days
Cough (usually non-productive and occurs in approximately 90%)
Pleuritic chest pain
Haemoptysis
Headache
Nausea, vomiting and diarrhoea
Anorexia
Legionella pneumophilainfections can be successfully treated with macrolide antibiotics, such as erythromycin, or quinolones, such as ciprofloxacin. Tetracyclines, such as doxycycline, can also be used.
The syndrome of inappropriate antidiuretic hormone secretion (SIADH) can occur with Legionnaires’ disease and will result in hyponatraemia as is seen in this case.
Legionella pneumophilainfections are resistant to amoxicillin but can be successfully treated with macrolide antibiotics, such as erythromycin, or quinolones, such as ciprofloxacin. Tetracyclines, such as doxycycline, can also be used. The majority of cases of Legionnaires’ disease are caused by Legionella pneumophila, however many other species of Legionella have been identified.
Legionella longbeachae is another less commonly encountered species that has also been implicated in outbreaks. It is predominantly found in soil and potting compost, and has caused outbreaks of Pontiac fever, the non-respiratory and less severe variant of Legionnaires’ disease.

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.

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).

Haemoglobin is a 64.4 kd tetramer consisting of two pairs of globin polypeptide chains: one pair of alpha-like chains, and one pair of non-alpha chains. The chains are designated by Greek letters, which are used to describe the particular haemoglobin (e.g., Hb A is alpha2/beta2).

Two copies of the alpha-globin gene (HBA2, HBA1) are located on chromosome 16 along with the embryonic zeta genes (HBZ). There is no substitute for alpha globin in the formation of any of the normal haemoglobins (Hb) following birth (e.g., Hb A, Hb A2, and Hb F). Thus, absence any alpha globin, as seen when all 4 alpha-globin genes are inactive or deleted is incompatible with extrauterine life, except when extraordinary measures are taken.

A homotetramer of only alpha-globin chains is not thought to occur, but in the absence of alpha chains, beta and gamma homotetramers (HbH and Bart’s haemoglobin, respectively) can be found, although they lack cooperativity and function poorly in oxygen transport. The single beta-globin gene (HBB) resides on chromosome 11, within a gene cluster consisting of an embryonic beta-like gene, the epsilon gene (HBE1), the duplicated and nearly identical fetal, or gamma globin genes (HBG2, HBG1), and the poorly expressed delta-globin gene (HBD). A heme group, consisting of a single molecule of protoporphyrin IX co-ordinately bound to a single ferrous (Fe2+) ion, is linked covalently at a specific site to each globin chain. If the iron is oxidized to the ferric state (Fe3+), the protein is called methaemoglobin.

Alpha globin chains contain 141 amino acids (residues) while the beta-like chains contain 146 amino acids. Approximately 75 percent of haemoglobin is in the form of an alpha helix. The non helical stretches permit folding of the polypeptide upon itself. Individual residues can be assigned to one of eight helices (A-H) or to adjacent non helical stretches.

Heme iron is linked covalently to a histidine at the eighth residue of the F helix (His F8), at residue 87 of the alpha chain and residue 92 of the beta chain. Residues that have charged side groups, such as lysine, arginine, and glutamic acid, lie on the surface of the molecule in contact with the surrounding water solvent. Exposure of the hydrophilic (charged) amino acids to the aqueous milieu is an important determinant of the solubility of haemoglobin within the red blood cell and of the prevention of precipitation.

The haemoglobin tetramer is a globular molecule (5.0 x 5.4 x 6.4 nm) with a single axis of symmetry. The polypeptide chains are folded such that the four heme groups lie in clefts on the surface of the molecule equidistant from one another.

Achlorhydria is an autoimmune illness of the gastric parietal cells that causes insufficient stomach acid production. The parietal cells that have been injured are unable to create the necessary amount of stomach acid. As a result, the pH of the stomach rises, food digestion suffers, and the risk of gastroenteritis rises.

The secretion of hydrochloric acid and intrinsic factor is controlled by the gastric parietal cells, which are epithelial cells in the stomach. These cells can be found in the gastric glands, the fundus lining, and the stomach body.

In response to the following three stimuli, the stomach parietal cells release hydrochloric acid:

H2 Histamine receptors are stimulated by histamine (most significant contribution)
Acetylcholine stimulates M3 Receptors via parasympathetic action.
CCK2 receptors are stimulated by Gastrin.

Intrinsic factor, which is essential for vitamin B12 absorption, is also produced by stomach parietal cells.
Omeprazole is a proton pump inhibitor that is both selective and irreversible. It inhibits the H+/K+-ATPase system present on the secretory membrane of gastric parietal cells, which lowers stomach acid secretion.
Ranitidine inhibits histamine H2-receptors in a competitive manner. The reversible inhibition of H2-receptors in gastric parietal cells reduces both the volume and concentration of gastric acid.

Allopurinol is a treatment for the prevention of gout. The initiation of treatment may precipitate an acute attack, and should be covered with an NSAID or colchicine, continued for at least one month after the hyperuricaemia has been corrected. Colchicine is not indicated for long term prevention of gout. NSAIDs are first line for acute gout; colchicine is an alternative in whom NSAIDs are contraindicated, not tolerated or ineffective (including in people taking anticoagulants). Ibuprofen is not recommended for acute gout, given it has only weak anti-inflammatory properties; naproxen, diclofenac or indometacin are indicated instead.

On standing from a prone position, gravity causes blood to pool in veins in the legs. Central venous pressure (CVP) falls, causing a fall in stroke volume and cardiac output (due to Starling’s law) and thus a fall in blood pressure. Normally this fall in BP is rapidly corrected by the baroreceptor reflex which causes venoconstriction (partially restoring CVP), and an increase in heart rate and contractility, so restoring cardiac output and blood pressure. Impaired autonomic nervous activity in the elderly accounts for the greater likelihood of postural hypotension. Any symptoms of dizziness, blurred vision or syncope is due to a transient fall in cerebral perfusion that occurs before cardiac output and mean arterial pressure (MAP) can be corrected.

Phenytoin is a commonly used antiepileptic drug. A well-recognized side-effect of phenytoin is gingival enlargement and occurs in about 50% of patients receiving phenytoin. It is believed that reduced folate levels may cause this, and evidence suggests that folic acid supplementation may help prevent this in patients starting phenytoin.

As evidence suggests, drug-induced gingival enlargement may also improve by substituting with other anticonvulsant drugs and reinforcing a good oral hygiene regimen. Surgical excision of hyperplastic gingiva is often necessary to correct the aesthetic and functional impairment associated with this condition to manage it successfully.

Phenytoin is also the only anticonvulsant therapy associated with the development of Dupuytren’s contracture.
Other side effects are:
1. Ataxia
2. Drug-induced lupus
3. Hirsutism
4. Pruritic rash
5. Megaloblastic anaemia
6. Nystagmus

HBsAg is the serological hallmark of HBV infection. After an acute exposure to HBV, HBsAg appears in serum within 1 to 10 weeks. Persistence of this marker for more than 6 months implies chronic HBV infection.

Anti-HBs is known as a neutralizing antibody, and confers long-term immunity. In patients with acquired immunity through vaccination, anti-HBs is the only serological marker detected in serum.

HBcAg is an intracellular presence in infected hepatocyte, thus it is not identified in the serum. During acute infection, anti-HBc IgM and IgG emerges 1–2 weeks after the presence of HBsAg along with raised serum aminotransferase and symptoms. After 6 months of acute infection, anti-HBc IgM wears off. Anti-HBc IgG continues to detect in both patients with resolved HBV infection and chronic hepatitis B.

Hepatitis D virus, also known as the delta hepatitis virus, is a defective ssRNA virus that requires HBV for replication. The infection can occur in one of two clinical forms, co-infection or superinfection. In a co-infection, the patient is simultaneously infected with HBV and HDV. In a superinfection, an HDV infection develops in a patient with a chronic HBV infection.

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

A carbuncle is a collection of individual boils clustered together.

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

A vesicle is a visible collection of clear fluid measuring less than 0.5 cm in diameter.

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

Cushing’s syndrome is a collection of symptoms and signs caused by prolonged exposure to elevated levels of either endogenous or exogenous glucocorticoids.

The most common cause of Cushing’s syndrome is the iatrogenic administration of corticosteroids. The second most common cause of Cushing’s syndrome is Cushing’s disease.

Cushing’s disease should be distinguished from Cushing’s syndrome and refers to one specific cause of the syndrome, an adenoma of the pituitary gland that secretes large amounts of ACTH and, in turn, elevates cortisol levels. This patient has a diagnosis of Cushing’s disease, and this is, therefore, the underlying cause in this case.

The endogenous causes of Cushing’s syndrome include:
Pituitary adenoma (Cushing’s disease)
Ectopic corticotropin syndrome, e.g. small cell carcinoma of the lung
Adrenal hyperplasia
Adrenal adenoma
Adrenal carcinoma

Advantages: ideal for studying associations between an exposure and an outcome when the exposure is uncommon, the time sequence of events can be assessed, they can provide information on a wide range of disease outcomes, the absolute and relative risk of disease can be measured directly, they can give a direct estimation of disease incidence rates
Disadvantages: costly and can take long periods of time if the outcome is delayed, subject to subject-selection and loss to follow-up bias, large sample size required for rare outcome of interest so it is not useful for rare diseases, prone to confounding

Anaphylaxis is characterised by sudden onset and rapidly developing, life-threatening airway, breathing and circulation problems associated with skin and/or mucosal changes. Reactions can vary greatly, from hypotension alone, to reactions with predominantly asthmatic features, to cardiac/respiratory arrest. Skin or mucosal changes may be absent or subtle in up to 20% of cases but skin or mucosal changes alone are not a sign of an anaphylactic reaction.

Electrolytes are compounds that may conduct an electrical current and dissociate in solution. Extracellular and intracellular fluids contain these chemicals. The predominant cation in extracellular fluid is sodium, whereas the major anion is chloride. Potassium is the most abundant cation in the intracellular fluid, while phosphate is the most abundant anion. These electrolytes are necessary for homeostasis to be maintained.

Compression of the thecal sac causes metastatic Spinal Cord Compression (MSCC) due to a Metastatic tumour and its components. It can cause symptoms of limb weakness, sensory disturbances and back pain depending on the extent and level of Compression.

The most common source of a tumour causing MSCC is a prostate carcinoma that metastasized to the spinal cord via the vertebral venous plexus.

Clostridium tetani causes tetanus.
Scarlet fever is caused by Streptococcus pyogenes.
Toxic shock syndrome is caused by Staphylococcus aureus or Streptococcus pyogenes.
Gas gangrene is primarily caused by Clostridium perfringens.
Pseudomembranous colitis is commonly caused by Clostridium difficile.

Interleukin-1, which is released by leukocytes and acts on the thermoregulatory centre of the hypothalamus, causes fever. Because prostaglandins mediate this process, antipyretics such as NSAIDs, paracetamol, and aspirin reduce prostaglandin levels by inhibiting cyclooxygenase enzymes. Malignant disease secretes interleukins, which cause the B-symptoms seen in lymphoma, for example. Bacterial toxins can also cause interleukins to be produced.

Pyrexia of unknown origin (PUO) is defined as a fever of greater than 38.3 degrees Celsius that lasts for more than 2-3 weeks with no clear diagnosis despite extensive investigation.

Investigation necessitates a thorough understanding of the conditions that can cause febrile illness, which may be missed during an initial investigation, as well as a thorough history, examination, and investigation centred on that list.

Pyrexia of unknown origin has a wide differential diagnosis, which includes:
Infection
Bacterial
Pyogenic abscess
Tuberculosis
Infective endocarditis
Brucellosis
Lyme disease
Viral
HIV
Epstein Barr Virus
Cytomegalovirus
Parasite
Toxoplasmosis
Malignancy
Leukaemia
Lymphoma
Renal cell carcinoma
Hepatocellular carcinoma
Vasculitides
Still’s disease
Granulomatosis with polyangiitis (formerly Wegener’s)
Systemic lupus erythematosus
Giant cell arteritis
Rheumatoid arthritis
Polymyalgia rheumatica
Miscellaneous
Drug induced fevers
Familial Mediterranean fever
Thyrotoxicosis
Inflammatory bowel disease
Sarcoidosis
Factitious fever
Exaggerated normal circadian fluctuation

The patient might need to be admitted to the hospital for observation and further investigation. Because infection is still a possibility, blood cultures should be repeated on a regular basis, and inflammatory markers should be closely monitored. CT, PET, and MRI imaging have largely replaced diagnostic laparotomy as a diagnostic tool.

Cetirizine is a competitive inhibitor at the H1-receptor (an antihistamine).

The reduced indirect inguinal hernia can be controlled by pressure over the internal ring; a direct inguinal hernia cannot.

An indirect inguinal hernia can be reduced superiorly then superolaterally, while a direct inguinal hernia can be reduced superiorly then posteriorly.

An indirect inguinal hernia takes time to reach full size, but a direct inguinal hernia appears immediately upon standing.

Indirect inguinal hernias are seen as elliptical swelling, while direct inguinal hernias appear as symmetric, circular swelling.

Bile functions to eliminate endogenous and exogenous substances from the liver (including bilirubin), to neutralise gastric acid in the small intestine, and to emulsify fats in the small intestine and facilitate their digestion and absorption. Bile salts also act as bactericides, destroying many of the microbes that may be present in the food. Bile doesn’t contain digestive enzymes for digestion of lipids into monoglycerides and fatty acids; this is performed mainly by pancreatic lipase.

Flexion of the thigh at the hip joint is produced by the sartorius, psoas major, iliacus and pectineus muscles, assisted by the rectus femoris muscle, all innervated by the femoral nerve (except for the psoas major, innervated by the anterior rami of L1 – 3).

As the contents of the intestine are isotonic with body fluids and mostly have the same concentration of the major electrolytes, their absorption is active. Water cannot be moved directly, but follows osmotic gradients set up by the transport of ions, primarily mediated by the sodium pump.Na+/K+ ATPase located on the basolateral membrane of the epithelial cells pumps three Na+ ions from the cell in exchange for two K+ ions, against their respective concentration gradients. This leads to a low intracellular concentration of Na+ and a high intracellular concentration of K+. The low intracellular concentration of Na+ ensures a movement of Na+ from the intestinal contents into the cell down its concentration gradient by both membrane channels and transporter protein mechanisms. Na+ is then rapidly pumped again by the basolateral sodium pump. K+ leaves the cell across the basolateral membrane down its concentration gradient linked to an outward movement of Cl- against its concentration gradient (Cl- having entered the cell across the luminal membrane down its concentration gradient).

ALL affects children predominantly.

The CNS is commonly involved in ALL.

The Philadelphia chromosome is present in 25% of adult ALL and 5% of childhood ALL cases.

The cure rate in children is approximately 80% in children and 50% in adults.

ALL is classified into 3 groups using the French-American-British (FAB) classification:
ALL-L1: small uniform cells
ALL-L2: large varied cells
ALL-L3: large varied cells with vacuoles.

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

Ketamine is a dissociative anaesthetic with analgesic, amnesic, and hypnotic effects. It is the only anaesthetic agent which causes all three of these effects.

Ketamine exerts its action by non-competitive antagonism at the NMDA (N-methyl-D-aspartate) receptor. Due to its analgesic property, Ketamine is given so that patients do not retain memories of short term procedures. Ketamine is used for the induction and maintenance of anaesthesia in general surgery and for treating burn wounds, battlefield injuries, and children who cannot tolerate other anaesthetic or analgesic agents.

It can be given by both intravenous and intramuscular routes. Ketamine causes cardiac stimulation by increasing the sympathetic tone. The major side effect is increased intracranial pressure as an increase in the sympathetic tone causes vasoconstriction and an increase in the MAP.

Like all muscles in the deep posterior compartment of the leg, flexor digitorum longus muscle is innervated by branches of the tibial nerve (root value L5, S1 and S2) which is a branch of sciatic nerve.

Pectoralis minor is a thin, triangular muscle that is situated in the upper chest. It is thinner and smaller than pectoralis major. It is innervated by the medial pectoral nerve.
The origin of pectoralis minor is the 3rdto the 5thribs, near the costal cartilages. It inserts into the medial border and superior surface of the coracoid process of the scapula.
The main action of pectoralis minor is to draw the scapula inferiorly and anteriorly against the thoracic wall. This serves to stabilise the scapula.

In the majority of patients the commonest causative organism for osteomyelitis isStaphylococcus aureus.Salmonella spp. are the commonest cause in patients with sickle cell disease.
Other bacteria that can cause osteomyelitis include:
Enterobacter spp.
Group A and B streptococcus
Haemophilus influenzae
The current recommendations by NICE and the BNF on the treatment of osteomyelitis are:
Flucloxacillin first-line
Consider adding fusidic acid or rifampicin for initial 2 weeks
If penicillin allergic use clindamycin
If MRSA is suspected use vancomycin
Suggested duration of treatment is 6 weeks for acute infection

Aldosterone is a steroid hormone produced in the adrenal cortex’s zona glomerulosa. It is the most important mineralocorticoid hormone in the control of blood pressure. It does so primarily by promoting the synthesis of Na+/K+ATPases and the insertion of more Na+/K+ATPases into the basolateral membrane of the nephron’s distal tubules and collecting ducts, as well as stimulating apical sodium and potassium channel activity, resulting in increased sodium reabsorption and potassium secretion. This results in sodium conservation, potassium secretion, water retention, and a rise in blood volume and blood pressure.

Aldosterone is produced in response to the following stimuli:

Angiotensin II levels have risen.
Potassium levels have increased.
ACTH levels have risen.
Aldosterone’s principal actions are as follows:
Na+ reabsorption from the convoluted tubule’s distal end
Water resorption from the distal convoluted tubule (followed by Na+)
Cl is reabsorbed from the distal convoluted tubule.
K+ secretion into the convoluted distal tubule’s 
H+ secretion into the convoluted distal tubule’s 

Acromioclavicular joint injuries account for more than forty percent of all shoulder injuries. Mild injuries are not associated with any significant morbidity, but severe injuries can lead to significant loss of strength and function of the shoulder. Acromioclavicular injuries may be associated with a fractured clavicle, impingement syndromes, and more rarely neurovascular insults.

The AC joint is a diarthrodial joint defined by the lateral process of the clavicle articulating with the acromion process as it projects anteriorly off the scapula. The joint is primarily stabilized by the acromioclavicular ligament, which is composed of an anterior, posterior, inferior, and superior component. Of note, the superior portion of the AC ligament is the most important component for the stability of the AC joint. Supporting structures include two coracoclavicular ligaments (trapezoid and conoid ligaments), which provide vertical stability, as well as the coracoacromial ligament.

Patients with an AC joint injury typically present with anterosuperior shoulder pain and will describe a mechanism of injury of blunt trauma to the abducted shoulder or landing on an outstretched arm, suggestive of this type of injury. They may describe pain radiating to the neck or shoulder, which is often worse with movement or when they try to sleep on the affected shoulder. On examination, the clinician may observe swelling, bruising, or a deformity of the AC joint, depending on the degree of injury. The patient will be tender at that location. They may have a restriction in the active and passive range of motion secondary to pain. Piano key sign may be seen, with an elevation of the clavicle that rebounds after inferior compression.

Standard X-rays are adequate to make a diagnosis of acromioclavicular joint injury and should be used to evaluate for other causes of traumatic shoulder pain.

Clostridium perfringens, a Gram-positive, anaerobic, spore forming rod-shaped, pathogenic bacterium is the most commonly associated with gas gangrene (85-90% of cases), although other species can also be implicated.

Clostridium perfringens is capsulate and produces a range of toxins. Alpha-toxin is the most important and is the cause of gas gangrene.

Gas gangrene develops when a devitalized wound becomes infected with Clostridium perfringens spores from the environment. The spores germinate and multiplies in the ischaemic conditions, releasing toxins, which further damage tissues.

Usually, the clinical features of gas gangrene appear within 24 hours of injury.

Clostridium perfringens spores are not destroyed by cooking. During slow cooling and unrefrigerated storage, they germinate to form vegetative cells.

Infective causes of bloody diarrhoea include:
Salmonella spp
Campylobacter spp
Schistosomiasis
Entamoeba histolytica (Amoebiasis )
Shigella spp
Clostridium difficile
Yersinia spp
Enteroinvasive Escherichia coli

Enterotoxigenic Escherichia coli is non-invasive and does not cause inflammation of the gut and bloody diarrhoea. It presents with copious watery diarrhoea and usually are not associated with abdominal cramping.

Abciximab (ReoPro) is a glycoprotein IIb/IIIa receptor antagonist that is a chimeric monoclonal antibody. It is primarily used during and after coronary artery procedures such as angioplasty to inhibit platelet aggregation.

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.

Cellulitis is most commonly caused by bacteria from the group Aß-hemolytic streptococcus.

Cellulitis can be caused by animal bites. For uncomplicated cellulitis, flucloxacillin is the first-line antibiotic. Because it is beta-lactamase stable, it is efficient against Staphylococcus aureus.

Blood transfusion can be a life-saving treatment with significant clinical benefits, but it also comes with a number of risks and potential complications, including:
Immunological side effects
Errors in administration (episodes of ‘wrong blood’)
Viruses and Infections (bacterial, viral, possibly prion)
Immunodilution

A culture of better safety procedures as well as steps to reduce the use of transfusion has emerged as a result of growing awareness of avoidable risk and improved reporting systems. Transfusion errors, on the other hand, continue to occur, and some serious adverse reactions go unreported.

Transfusion-associated graft-vs-host disease (TA-GVHD) is a rare blood transfusion complication that causes fever, rash, and diarrhoea 1-4 weeks after the transfusion. Pancytopenia and liver function abnormalities are common laboratory findings.

TA-GVHD, unlike GVHD following allogeneic marrow transplantation, causes profound marrow aplasia with a mortality rate of >90%. Survival is uncommon, with death occurring within 1-3 weeks of the onset of symptoms.

Because of immunodeficiency, severe immunosuppression, or shared HLA antigens, viable T lymphocytes in blood components are transfused, engraft, and react against the recipient’s tissues, and the recipient is unable to reject the donor lymphocytes.
The following is a list of the most common transfusion reactions and complications:

1) Reaction to a febrile transfusion
The temperature rises by one degree from the baseline. Chills and malaise are also possible symptoms.
The most common response (1 in 8 transfusions).
Cytokines from leukocytes in transfused red cell or platelet components are usually to blame.
Only supportive. The use of paracetamol is beneficial.

2) Acute haemolytic reaction is a type of haemolytic reaction that occurs when the
Fever, chills, pain at the transfusion site, nausea, vomiting, and dark urine are all symptoms of a transfusion reaction.
Early on, many people report a sense of ‘impending doom.’
The most serious reaction. ABO incompatibility is frequently caused by a clerical error.
STOP THE TRANSFUSION OF INFORMATION. IV fluids should be given. It’s possible that diuretics will be required.

3) Haemolytic reaction that is delayed
It usually happens 4 to 8 days after a blood transfusion.
Fever, anaemia, jaundice, and haemoglobinuria are all symptoms that the patient has.
Positive Coombs test for direct antiglobulin.
Because of the low titre antibody, it is difficult to detect in a cross-match, and it is unable to cause lysis at the time of transfusion.
The majority of delayed haemolytic reactions are harmless and do not require treatment.
Anaemia and renal function should be monitored and treated as needed.

4) Reaction to allergens
Foreign plasma proteins are usually to blame, but anti-IgA could also be to blame.
Urticaria, pruritus, and hives are typical allergic reactions. It’s possible that it’s linked to laryngeal oedema or bronchospasm.
Anaphylaxis is a rare occurrence.
Antihistamines can be used to treat allergic reactions symptomatically. It is not necessary to stop transfusions.
If the patient develops anaphylaxis, the transfusion should be stopped and the patient should be given adrenaline and treated according to the ALS protocol.

5) TRALI (Transfusion Related Acute Lung Injury)
Within 6 hours of transfusion, there was a sudden onset of non-cardiogenic pulmonary oedema.
It’s linked to the presence of antibodies to recipient leukocyte antigens in the donor blood.
The most common cause of death from transfusion reactions is this.
STOP THE TRANSFUSION OF INFORMATION. Oxygen should be given to the patient. Around 75% of patients will require aggressive respiratory support.
The use of diuretics should be avoided.

6) TACO (Transfusion Associated Circulatory Overload)
Acute or worsening respiratory distress within 6 hours of a large blood transfusion. Fluid overload and pulmonary and peripheral oedema can be seen. Rapid blood pressure rises are common. BNP is usually 1.5 times higher than it was before the transfusion. It is most common in the elderly and those who have chronic anaemia.

Blood transfusions should be given slowly, over the course of 3-4 hours.

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

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

The other mask are not ideal for initial use

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

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

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

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

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

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

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

In the cancer patient, hyponatremia is usually caused by the syndrome of inappropriate antidiuretic hormone (SIADH). This develops more frequently with small cell lung cancer (SCLC) than with other malignancies. The pathogenesis of this is as a result of the process whereby ADH binds V2 receptors on renal principal cells in the late distal tubule and collecting ducts, resulting in elevation of cAMP levels. Increased cAMP levels cause fusion of intracellular vesicles with the apical membrane. There are water channels called aquaporins in their membranes of these vesicles, and these increase the water permeability, thus facilitating increased water reabsorption and urine concentration. Thus, by increasing water retention, ADH causes blood to be diluted, which then decreases the concentration of solutes like sodium.

Insulin, a peptide hormone, is produced in the pancreas by the beta-cells of the islets of Langerhans.

The beta-cells first synthesise an inactive precursor called preproinsulin which is converted to proinsulin by signal peptidases, which remove a signal peptide from the N-terminus.

Proinsulin is converted to insulin by the removal of the C-peptide.

Insulin has a short half-life in the circulation of about 5-10 minutes.
Glucagon and parasympathetic stimulation stimulates insulin release.

Homonymous quadrantanopia is not a disease; it is a clinical finding that points towards a lesion of the optic radiations coursing through the temporal lobe.
Homonymous superior quadrantanopia is caused by damage to the contralateral inferior parts of the posterior visual pathway: the inferior optic radiation (temporal Meyer loop), or the inferior part of the occipital visual cortex below the calcarine fissure.

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

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

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

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

For anaesthesia, nitrous oxide is commonly used in a concentration of around 50 – 66% in oxygen in association with other inhalation or intravenous agents. Nitrous oxide cannot be used as the sole anaesthetic agent due to lack of potency, but is useful as part of a combination of drugs since it allows reduction in dosage of other agents. Exposure to nitrous oxide for prolonged periods, either by continuous or by intermittent administration, may result in megaloblastic anaemia as a result of interference with the action of vitamin B12. Nitrous oxide increases cerebral blood flow and should be avoided in patients with, or at risk of, raised intracranial pressure. Nitrous oxide may be administered by any trained personnel experienced in its use.

In the posterior mediastinum where the oesophagus is crossed by the pulmonary trunk offers the least resistance when nasogastric tube is inserted from the nose to the stomach.

Treponema pallidum is an obligate pathogen. Obligate pathogens are almost always associated with disease and usually cannot survive outside of the body for long periods of time. Examples include and HIV.

Staphylococcus aureus and Bacteroides fragilis are conditional pathogens. These are pathogens that usually cause disease only if certain conditions are met.

Pneumocystis jiroveci and Pseudomonas aeruginosa, are opportunistic pathogens. These are pathogens that can only cause disease in an immunocompromised host or under unusual circumstances.

The Meissner’s plexus (submucosal plexus), an enteric nervous plexus, acts as the main control for gastrointestinal secretion and local blood flow within the gut.

It is located in the submucosal layer on the inner surface of the muscularis externa.

Common side effects of amiodarone include: Bradycardia, Nausea and vomiting, Thyroid disorders – hypothyroidism and hyperthyroidism, Persistent slate grey skin discoloration, Photosensitivity, Pulmonary toxicity (including pneumonitis and fibrosis), Hepatotoxicity, Corneal microdeposits (sometimes with night glare), Peripheral neuropathy and Sleep disorders.

Hyperaemia is the process where the body adjusts blood flow to meet the metabolic needs of different tissues in health and disease. Vasoactive mediators that take part in this process include K+, adenosine, CO2, H+, phosphates and H2O2. Although the mechanism is not clear, all these mediators likely contribute to some extent at different points.

Specific organs are more sensitive to specific metabolites:
K+ and adenosine are the most potent vasodilators in skeletal muscles

CO2 and K+ are the most potent vasodilators in cerebral circulation.

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.

Autoregulation is the ability to maintain a constant blood flow despite variations in blood pressure (between 50 – 170 mmHg). It is particularly important in the brain, kidney and heart. There are two main methods contributing to autoregulation:
The myogenic mechanism involves arterial constriction in response to stretching of the vessel wall, probably due to activation of smooth muscle stretch-activated Ca2+channels and Ca2+entry. A reduction in pressure and stretch closes these channels, causing vasodilation.
The second mechanism of autoregulation is due to locally produced vasodilating factors; an increase in blood flow dilutes these factors causing vasoconstriction, whereas decreased blood flow has the opposite effect.

Gluteus minimus is innervated by the superior gluteal nerve.
Gluteus medius is innervated by the superior gluteal nerve.
Gluteus maximus is innervated by the inferior gluteal nerve.

Legionella species are ubiquitous, Gram-negative bacilli acquired primarily through inhalation. Infections caused by Legionella spp. produce a spectrum of symptoms ranging from mild upper respiratory tract infections to pneumonia. Legionella spp. are responsible for 2% to 15% of community-acquired pneumonia.

Clinical manifestations of Legionella infections include febrile disease with pneumonia (legionnaires’ disease), febrile disease without pulmonary involvement (Pontiac fever), and asymptomatic infection.
The mode of transmission and the number of infecting organisms in the inoculum play a role in the clinical features of the infection. In addition, host factors, such as a suppressed immune system, chronic lung disease, alcoholism, and heavy smoking, predispose individuals to legionnaires’ disease.

Legionella spp. can tolerate chlorine concentrations of 3 mg/L, they resist water treatment and subsequently gain entry into and colonize human-made water supplies and distribution systems. Hot water systems, cooling towers, and evaporative condensers are major reservoirs. Other sources include cold water systems, ornamental fountains, whirlpool spas, humidifiers, respiratory
therapy equipment, and industrial process waters.

Caput medusae is a condition that consists of collateral veins radiating from the umbilicus and results from recanalization of the umbilical vein.

Under normal conditions, the portal venous blood traverses the liver and drains into the inferior vena cava of the systemic venous circulation by way of the hepatic veins. This is the direct route. However, other, smaller communications exist between the portal and systemic systems, and they become important when the direct route becomes blocked. These communications are as follows:

At the lower third of the oesophagus, the oesophageal branches of the left gastric vein (portal tributary) anastomose with the oesophageal veins draining the middle third of the oesophagus into the azygos veins (systemic tributary).

Halfway down the anal canal, the superior rectal veins (portal tributary) draining the upper half of the anal canal anastomosis with the middle and inferior rectal veins (systemic tributaries), which are tributaries of the internal iliac and internal pudendal veins, respectively.

The paraumbilical veins connect the left branch of the portal vein with the superficial veins of the anterior abdominal wall (systemic tributaries). The paraumbilical veins travel in the falciform ligament and accompany the ligamentum teres.

The veins of the ascending colon, descending colon, duodenum, pancreas, and liver (portal tributary) anastomose with the renal, lumbar, and phrenic veins (systemic tributaries).

Cholera is caused by Vibrio cholerae, a motile, Gram-negative, curved bacillus. It is transmitted through water and food (especially seafood) and is primarily a disease seen in developing countries where there is poor sanitation and lack of safe water supplies.

The cholera toxin leads to stimulation of adenyl cyclase, ADP-ribosylation of the G regulatory protein, inactivation of GTPase leading to active outpouring of NaCl.

The cholera toxin consists of an A (the toxin) and B subunit. The B subunit attaches to the gut mucosa and presents the A subunit to the cell. The toxin stimulates adenyl cyclase by irreversible ADP-ribosylation of the GTP binding domain of adenyl cyclase leading to the opening of chloride channels resulting in an outpouring of NaCl and water into the lumen of the gut and causing secretory diarrhoea.

Incubation period is between 2 and 5 days, but can be as short as just a few hours.