Fats are digested almost entirely in the small intestine and are only released from the stomach into the duodenum at the rate at which they can be digested (the presence of fatty acids and monoglycerides in the duodenum inhibits gastric emptying). In the duodenum fat is emulsified by bile acids, a process where larger lipid droplets are broken down into much smaller droplets providing a greater surface area for enzymatic digestion. Pancreatic lipase digests triglyceride into monoglycerides and free fatty acids. The products of fat digestion (fatty acids and monoglycerides), cholesterol and fat-soluble vitamins diffuse passively into the enterocytes. Once inside the epithelial cell, lipid is taken into the smooth endoplasmic reticulum where much of it is re esterified. Dietary and synthesised lipids are then incorporated into chylomicrons in the Golgi body, which are exocytosed from the basolateral membrane to enter lacteals.

A cohort study is a longitudinal, prospective, observational study that follows a defined group (cohort) matched to unexposed controls for a set period of time and investigates the effect of exposure to a risk factor on a particular future outcome. The usual outcome measure is the relative risk (risk ratio). A large sample size is required for a rare outcome of interest so it is not useful for rare diseases.

Fat necrosis typically occurs following either direct trauma or from enzymatic lipolysis in acute pancreatitis, where release of triglyceride elicits a rapid inflammatory response and fat is phagocytosed by neutrophils and macrophages with subsequent fibrosis.

Tetanus is caused by Clostridium tetani, a bacterium. Tetanus can cause mild spasms to severe whole-body contractions, suffocation, and heart attack.

Gas gangrene and food poisoning are both caused by Clostridium perfringens.

Pseudomembranous colitis is caused by Clostridium difficile.

Urinary tract infections, respiratory infections, dermatitis, soft tissue infections, bacteraemia, bone and joint infections, gastrointestinal infections, and a variety of systemic infections are all caused by Pseudomonas aeruginosa.

Pharyngitis, skin infections, acute rheumatic fever, scarlet fever, poststreptococcal glomerulonephritis, toxic shock–like syndrome, and necrotizing fasciitis can all be caused by Streptococcus pyogenes infection.

Give adrenaline 1 mg IV (IO) (10 mL of 1:10,000 solution) after the 2nd shock for adult patients in cardiac arrest with a shockable rhythm. Repeat adrenaline 1 mg IV (IO) every 3-5 minutes whilst ALS continues.

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.

Co-amoxiclav consists of amoxicillin with the beta-lactamase inhibitor clavulanic acid. Clavulanic acid itself has no significant antibacterial activity but, by inactivating beta-lactamases, it makes the combination active against beta-lactamase-producing bacteria that are resistant to amoxicillin.The most common adverse effects of co-amoxiclav include nausea, vomiting, skin rash and diarrhoea. Pseudomembranous colitis should be considered if a person develops severe diarrhoea during or after treatment with co-amoxiclav. Cholestatic jaundice can occur either during or shortly after the use of co-amoxiclav. An epidemiological study has shown that the risk of acute liver toxicity was about 6 times greater with co-amoxiclav than with amoxicillin. Cholestatic jaundice is more common in patients above the age of 65 years and in men; these reactions have only rarely been reported in children. Jaundice is usually self-limiting and very rarely fatal.

Short vessels called arteriovenous anastomoses (AVAs) link tiny arteries and veins. They have a large lumen diameter. The strong and muscular walls allow AVAs to completely clog the vascular lumen, preventing blood flow from artery to vein (acting like a sphincter). When the AVAs open, they create a low-resistance connection between arteries and veins, allowing blood to flow into the limbs’ superficial venous plexuses. There is no diffusion of solutes or fluid into the interstitium due to their strong muscle walls.

AVAs are densely innervated by adrenergic fibres from the hypothalamic temperature-regulation centre. High sympathetic output occurs at normal core temperatures, inducing vasoconstriction of the AVAs and blood flow through the capillary networks and deep plexuses. When the temperature rises, sympathetic output decreases, producing AVA vasodilation and blood shunting from the artery to the superficial venous plexus. Heat is lost to the environment as hot blood rushes near to the skin’s surface.
AVAs are a specialized anatomical adaptation that can only be found in large quantities in the fingers, palms, soles, lips, and pinna of the ear.

The presence of dyspnoea makes alpha-1 antitrypsin deficiency the more likely diagnosis as biliary atresia does not cause respiratory symptoms. Deficiency of the enzyme alpha-1 antitrypsin causes uninhibited elastase activity and a decrease in elastic tissue. This causes liver cirrhosis leading to an elevation of conjugated bilirubin and emphysema in the lungs.

Rhesus disease, hereditary spherocytosis and breast milk jaundice cause an elevation of unconjugated bilirubin thus ruling it out in this case. Breast milk jaundice occurs due to an inability of the newborn to metabolize the proteins in breast milk.

Rhesus disease occurs when an Rh negative mother gives birth to an Rh positive baby. The jaundice would have been accompanied by anaemia and oedema.

Hereditary spherocytosis occurs due to extravascular haemolysis as defective RBCs are removed by the spleen. The patient would present with jaundice, splenomegaly and possibly an aplastic crisis (if Parvovirus B19 infection).

Immunoglobulin A is predominant in saliva.

Angiotensin-converting enzyme (ACE) inhibitors are the most common cause of drug-induced angioedema in the United Kingdom and the United States, owing to their widespread use.

Angioedema is caused by ACE inhibitors in 0.1 to 0.7 percent of patients, with data indicating a persistent and relatively constant risk year after year. People of African descent have a five-fold higher chance of contracting the disease.

Swelling of the lips, tongue, or face is the most common symptom, but another symptom is episodic abdominal pain due to intestinal angioedema. Itching and urticaria are noticeably absent.

The mechanism appears to be activated complement or other pro-inflammatory cytokines like prostaglandins and histamine, which cause rapid vasodilation and oedema.

Other medications that are less frequently linked to angioedema include:
Angiotensin-receptor blockers (ARBs)
Nonsteroidal anti-inflammatory drugs (NSAIDs)
Bupropion (e.g. Zyban and Wellbutrin)
Beta-lactam antibiotics
Statins
Proton pump inhibitors

The majority of these reactions are minor and can be treated by stopping the drug and prescribing antihistamines.

One of the results of Klebsiella pneumoniae is pneumonia that is usually a very severe infection. It is characterised by thick, bloody sputum (red currant jelly sputum), and is associated with complications like lung abscess, cavitation, necrosis, empyema and pleural effusions.

Corneal microdeposits are almost universally present (over 90%) in people who have been taking amiodarone for more than six months, especially at doses above 400 mg/day. Although these deposits usually cause no symptoms, about 10% of patients report seeing a ‘bluish halo.’ This goes away once the treatment is stopped, and it rarely causes vision problems.

Other effects of amiodarone on the eye are much rarer, occurring in only 1-2 percent of patients:
Optic neuropathy is a condition that affects the eyes.
Non-arteritic anterior ischaemic optic neuropathy (N-AION)
Swelling of the optic disc

Glucagon is a peptide hormone that is produced and secreted by alpha cells of the islets of Langerhans, which are located in the endocrine portion of the pancreas. The main physiological role of glucagon is to stimulate hepatic glucose output, thereby leading to increases in glycaemia. It provides the major counter-regulatory mechanism to insulin in maintaining glucose homeostasis.
Hypoglycaemia is the principal stimulus for the secretion of glucagon but may also be used as an antidote in beta-blocker overdose and in anaphylaxis in patients on beta-blockers that fail to respond to adrenaline.
Glucagon then causes:
Glycogenolysis
Gluconeogenesis
Lipolysis in adipose tissue
The secretion of glucagon is also stimulated by:
Adrenaline
Cholecystokinin
Arginine
Alanine
Acetylcholine
The secretion of glucagon is inhibited by:
Insulin
Somatostatin
Increased free fatty acids
Increased urea production

Glycolysis is the metabolic pathway that converts glucose into pyruvate. The free energy released by this process is used to form ATP and NADH. Glycolysis is inhibited by glucagon, and glycolysis and gluconeogenesis are reciprocally regulated so that when one cell pathway is activated, the other is inactive and vice versa.

Glucagon has a minor effect of enhancing lipolysis in adipose tissue. Lipolysis is the breakdown of lipids and involves the hydrolysis of triglycerides into glycerol and free fatty acids. It makes fatty acids available for oxidation.

Inguinal hernias can present with an array of different symptoms. Most patients present with a bulge in the groin area, or pain in the groin. Some will describe the pain or bulge that gets worse with physical activity or coughing. Symptoms may include a burning or pinching sensation in the groin. These sensations can radiate into the scrotum or down the leg. It is important to perform a thorough physical and history to rule out other causes of groin pain. At times an inguinal hernia can present with severe pain or obstructive symptoms caused by incarceration or strangulation of the hernia sac contents. A proper physical exam is essential in the diagnosis of an inguinal hernia. Physical examination is the best way to diagnose a hernia. The exam is best performed with the patient standing. Visual inspection of the inguinal area is conducted first to rule out obvious bulges or asymmetry in groin or scrotum. Next, the examiner palpates over the groin and scrotum to detect the presence of a hernia. The palpation of the inguinal canal is completed last. The examiner palpates through the scrotum and towards the external inguinal ring. The patient is then instructed to cough or perform a Valsalva manoeuvre. If a hernia is present, the examiner will be able to palpate a bulge that moves in and out as the patient increases intra abdominal pressure through coughing or Valsalva.

Groin hernias are categorized into 2 main categories: inguinal and femoral.

Inguinal hernias are further subdivided into direct and indirect. An indirect hernia occurs when abdominal contents protrude through the internal inguinal ring and into the inguinal canal. This occurs lateral to the inferior epigastric vessels. The hernia contents may extend into the scrotum, and can be reduced superiorly then superolaterally. A direct inguinal hernia is protrusion of abdominal contents through the transversalis fascia within Hesselbach’s triangle. The borders of Hesselbach’s triangle are the inferior epigastric vessels superolaterally, the rectus sheath medially, and inguinal ligament inferiorly.

A femoral hernia is a protrusion into the femoral ring. The borders of the femoral ring are the femoral vein laterally, Cooper’s ligament posteriorly, the iliopubic tract/inguinal ligament anteriorly and lacunar ligament medially.

A type I error occurs when the null hypothesis is wrongly rejected when it is actually true and we conclude that there is a difference of effect when in reality there is none (a false positive result).

Malaria is an infectious disease transmitted by female of theAnophelesgenus of mosquito. It is a parasitic infection caused by the genusPlasmodium. Five species are recognized as causing disease in humans;Plasmodium falciparum,Plasmodium ovale,Plasmodium vivax,Plasmodium malariaeandPlasmodium knowlesi.
The classic symptom of malaria is the malarial paroxysm, a cyclical occurrence of a cold phase, where the patient experiences intense chills, a hot stage, where the patient feels extremely hot and finally a sweating stage, where the fever declines and the patient sweats profusely. On examination the patient may show signs of anaemia, jaundice and have hepatosplenomegaly without evidence of lymphadenopathy.

Plasmodium falciparum is the most serious form and is responsible for most deaths. Severe or complicated malaria is suggested by the presence of impaired consciousness, seizures, hypoglycaemia, anaemia, renal impairment, respiratory distress and spontaneous bleeding.
Plasmodium falciparum is the most likely type in this case in view of the presentation.
Haemoglobinuria and renal failure following treatment is suggestive of blackwater fever, which is caused byPlasmodium falciparum. An autoimmune reaction between the parasite and quinine causes haemolysis, haemoglobinuria, jaundice and renal failure. This can be fatal.
The benign malarias: P.vivax, P. malariae and P.ovale are usually treated with chloroquine. A course of primaquine is also required in P.vivax and P.ovale infection. Artesunate is the drug treatment of choice for Plasmodium falciparum malaria. Quinine can still be used where artesunate is not available. Often combination therapy with drugs such as doxycycline or fansidar is also required.

End-organ damage (e.g. encephalopathy, intracranial haemorrhage, acute myocardial infarction or ischaemia, dissection, pulmonary oedema, nephropathy, eclampsia, papilledema, and/or angiopathic haemolytic anaemia) characterises a hypertensive emergency (also known as ‘accelerated hypertension’ or malignant hypertension’ It’s a life-threatening condition that necessitates rapid blood pressure reduction to avoid end-organ damage and a negative outcome.

Hypertensive encephalopathy is a syndrome that includes headaches, seizures, visual changes, and other neurologic symptoms in people who have high blood pressure. It is reversible if treated quickly, but it can progress to coma and death if not treated properly.

Any patient with suspected hypertensive encephalopathy should have an urgent CT scan to rule out an intracranial haemorrhage, as rapid blood pressure reduction could be dangerous in these circumstances.

The drug of choice is labetalol, which reduces blood pressure steadily and consistently without compromising cerebral blood flow.
An initial reduction of approximately 25% in mean arterial pressure (MAP) over an hour should be aimed for, followed by a further controlled MAP reduction over the next 24 hours. In patients who are unable to take beta-blockers, nicardipine can be used as a substitute.

In infants and young children, lymphocytosis often occurs in response to infections that would normally produce a neutrophil reaction in adults.
Lymphocytosis occurs in:
1. Viral infections (e.g. infectious mononucleosis, HIV, rubella, mumps, viral hepatitis, cytomegalovirus, herpes simplex or zoster)
2. Bacterial infections (e.g. pertussis, tuberculosis, toxoplasmosis, syphilis)
3. Chronic lymphoid leukaemias
4. Acute lymphoblastic leukaemias
5. Non-Hodgkin lymphoma
6. Thyrotoxicosis

Anti-D is an IgG antibody that targets the antigen Rhesus D (RhD). Plasma from rhesus-negative donors who have been immunised against the anti-D-antigen is used to make anti-D immunoglobulin.

Only RhD negative women are given Anti-D Ig. Women who are RhD negative do not have the RhD antigen on their RBC. If a foetus has the RhD antigen (i.e. is RhD positive) and the mother is exposed to foetal blood, she may develop antibodies to RhD that pass through the placenta and attack foetal red cells (resulting in newborn haemolytic disease). Anti-D is given to bind and neutralise foetal red cells in the maternal circulation before an immune response is triggered. In the event of a sensitising event, 500 IU Anti-D Ig should be administered intramuscularly.

The following are examples of potentially sensitising events:
Birth
Haemorrhage during pregnancy
Miscarriage
Ectopic pregnancy
Death within the womb
Amniocentesis
Chorionic villus sampling
Trauma to the abdomen

The sooner anti-D is given in the event of a sensitising event, the better; however, it is most effective within 72 hours, and the BNF states that it is still likely to have some benefit if given outside of this time frame.

At 28 and 34 weeks, RhD negative women should receive routine antenatal prophylaxis. This is regardless of whether they have previously received Anti-D for a sensitising event during the same pregnancy.

Prophylactic anti-D is not necessary before 12 weeks gestation, as confirmed by scan, in uncomplicated miscarriage (where the uterus is not instrumented), or mild, painless vaginal bleeding, as the risk of foeto-maternal haemorrhage (FMH) is negligible. In cases of therapeutic termination of pregnancy, whether by surgical or medical means, 250 IU of prophylactic anti-D immunoglobulin should be given to confirmed RhD negative women who are not known to be RhD sensitised.

Escherichia coli produces shiga toxin that causes diarrhoea, hemorrhagic colitis, and haemolytic uremic syndrome.

Haemolytic uremic syndrome is characterized by anaemia, thrombocytopenia, and acute renal failure. Transmission of E. coli is possible after consuming contaminated, undercooked drinks and foods. E. coli enters the body via the faecal-oral pathway.

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.

Beta-thalassaemia major is caused by a complete or almost complete failure of β-globin chain synthesis, severe imbalance of α:β-chains with deposition of α-chains in erythroblasts, ineffective erythropoiesis and extramedullary haemopoiesis. The severe anaemia becomes apparent at 3 – 6 months when the switch from γ-chain to β-chain synthesis normally occurs. Beta-thalassaemia minor is a variable syndrome, milder than thalassaemia major, with later onset and characterised by moderate hypochromic microcytic anaemia with raised haemoglobin A2. Beta-thalassaemia trait is characterised by mild hypochromic, microcytic anaemia with raised red cell count and raised haemoglobin A2.

Gastric emptying is decreased by the presence of fats in the duodenum (by stimulating release of cholecystokinin). Mixing of the food with gastric secretions takes place in the distal body and antrum of the stomach where the muscularis externa layer is thicker. The stomach has an additional inner oblique smooth muscle layer (in addition to the inner circular layer and outer longitudinal layer). Gastric emptying is increased by a low gastric pH and decreased by a low duodenal pH.

Loop diuretics have long been the cornerstone of pulmonary oedema treatment, with furosemide being the most commonly used of these drugs. Premedication with drugs that decrease preload (e.g., nitro-glycerine [NTG]) and afterload (e.g., angiotensin-converting enzyme [ACE] inhibitors) before the administration of loop diuretics can prevent adverse hemodynamic changes.

Cysts are resistant forms and are responsible for transmission of giardiasis. Both cysts and trophozoites can be found in the faeces (diagnostic stages). The cysts are hardy and can survive several months in cold water. Infection occurs by the ingestion of cysts in contaminated water, food, or by the faecal-oral route (hands or fomites).
In the small intestine, excystation releases trophozoites (each cyst produces two trophozoites).
Trophozoites multiply by longitudinal binary fission, remaining in the lumen of the proximal small bowel where they can be free or attached to the mucosa by a ventral sucking disk.
Encystation occurs as the parasites transit toward the colon. The cyst is the stage found most commonly in non diarrheal faeces.
Because the cysts are infectious when passed in the stool or shortly afterward, person-to-person transmission is possible. While animals are infected with Giardia, their importance as a reservoir is unclear.

Giardia lambliainfection occurs through the ingestion of dormant microbial cysts in contaminated water, food or via faceo-oral transmission via poor hygiene.
Following ingestion of the cysts, the trophozoite emerges to an active state of feeding and motility. After the feeding stage they undergo asexual replication through longitudinal binary fission.
They attach to the intestinal wall via a specialised sucking disc. The mechanism for diarrhoea in giardiasis remains unknown but could possibly be due to direct cytotoxicity.
Giardial trophozoites and cysts pass through the digestive system in the faeces and are excreted. While the trophozoites may be found in the faeces, only the cysts are adapted for long-term survival outside the host.

When there are excessive levels of aldosterone independent of the renin-angiotensin aldosterone axis, primary hyperaldosteronism occurs. Secondary hyperaldosteronism occurs due to high renin levels.

Causes of primary hyperaldosteronism include:
Conn’s syndrome
Adrenal hyperplasia
Adrenal cancer
Familial aldosteronism

Causes of secondary hyperaldosteronism include:
Renal vasoconstriction
Oedematous disorders
Drugs – diuretics
Obstructive renal artery disease

Although patients are usually asymptomatic, when clinical features are present, classically hyperaldosteronism presents with:
Hypokalaemia
Sodium levels can be normal or slightly raised
Hypertension
Metabolic alkalosis
Less common, clinical features are:
Lethargy
Headaches
Intermittent paraesthesia
Polyuria and polydipsia
Muscle weakness (from persistent hypokalaemia)
Tetany and paralysis (rare)

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

Norwalk virus is an RNA virus.

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

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

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

Antacids are contraindicated in hypophosphataemia. Liquid preparations are more effective than tablet preparations. Magnesium-containing antacids tend to be laxative whereas aluminium-containing antacids tend to be constipating. Antacids are best taken when symptoms occur or are expected, usually between meals and at bedtime. Antacids should preferably not be taken at the same time as other drugs since they may impair absorption.

Pulmonary oedema causes stimulation of the Juxtacapillary receptors (J receptors) leading to a reflex increase in breathing rate. These receptors are also thought to be involved in the sensation of dyspnoea. The J receptors are sensory cells and are located within the alveolar walls in juxtaposition to the pulmonary capillaries.

Aortic baroreceptor are involved in detecting blood pressure

Central chemoreceptors detect changes in CO2 and hydrogen ion within the brain

Atrial volume receptors regulate plasma volume

Macrolide antibiotics (e.g. clarithromycin and erythromycin) are cytochrome P450 enzyme inhibitors. They increase blood levels of theophylline leading to hypokalaemia, and potentially increasing the risk of Torsades de pointes when they are prescribed together.

Co-prescription with theophylline should be avoided.

Factors that enhance theophylline clearance include cigarette smoking, carbamazepine, phenobarbital, phenytoin, primidone, and rifampin.
Medications that inhibit clearance include ethanol, ciprofloxacin, erythromycin, verapamil, propranolol, ticlopidine, tacrine, allopurinol, and cimetidine.

Flow through a tube is dependent upon:
The pressure difference across the ends of the tube (P1– P2)
The resistance to flow provided by the tube (R)
This is Darcy’s law, which is analogous to Ohm’s law in electronics:
Flow = (P1– P2) / R
Resistance in the tube is defined by Poiseuille’s law, which is determined by the diameter of the tube and the viscosity of the fluid. Poiseuille’s law is as follows:
Resistance = (8VL) / (πR4)
Where:
V = The viscosity of the fluid
L = The length of the tube
R = The radius of the tube
Therefore, in simple terms, resistance is directly proportional to the viscosity of the fluid and the length of the tube and inversely proportional to the radius of the tube. Of these three factors, the most important quantitatively and physiologically is vessel radius.
It can be seen that small changes in the radius can have a dramatic effect on the flow of the fluid. For example, the constriction of an artery by 20% will decrease the flow by approximately 60%.
Another important and frequently quoted example of this inverse relationship is that of the radius of an intravenous cannula. Doubling the diameter of a cannula increases the flow rate by 16-fold (r4). This is the reason the diameter of an intravenous cannula in resuscitation scenarios is so important.
*Please note that knowledge of the detail of Poiseuille’s law is not a requirement of the RCEM Basic Sciences Curriculum.

When there are excessive circulating levels of aldosterone, hyperaldosteronism occurs. There are two main types of hyperaldosteronism:

Primary hyperaldosteronism (,95% of cases)
Secondary hyperaldosteronism (,5% of cases)

Primary causes of hyperaldosteronism include:
Adrenal adenoma (Conn’s syndrome)
Adrenal hyperplasia
Adrenal cancer
Familial aldosteronism
Secondary causes of hyperaldosteronism include:
Drugs
Obstructive renal artery disease
Renal vasoconstriction
Oedematous disorders syndrome

Adrenal adenoma is the commonest cause of hyperaldosteronism (seen in ,80% of all cases).

Aerosols are airborne particles less than 5 µm in size, containing infective organisms that usually cause infection of the upper or lower respiratory tract.

Examples of organisms commonly spread by aerosol transmission are:
Measles virus
Varicella zoster virus
Mycobacterium tuberculosis

The following table summarises the various routes of transmission with example organisms:
Route of transmission
Example organisms
Aerosol (airborne particle < 5 µm)
Mycobacterium tuberculosis
Varicella zoster virus
Measles virus

Hepatitis A and Rotavirus are spread by the faeco-oral route.

Neisseria gonorrhoea is spread by sexual route.

Staphylococcus aureus is spread by direct contact.

The main function of the spinothalamic tract is to carry pain and temperature via the lateral part of the pathway and crude touch via the anterior part. The spinothalamic tract pathway is an imperative sensory pathway in human survival because it enables one to move away from noxious stimuli by carrying pain and temperature information from the skin to the thalamus where it is processed and transmitted to the primary sensory cortex. The primary sensory cortex communicates with the primary motor cortex, which lies close to it, to generate rapid movement in response to potentially harmful stimuli. Furthermore, the spinothalamic tract has a role in responding to pruritogens, causing us to itch. Interestingly, itching suppresses the spinothalamic tract neuron response to the histamine effect.

Fusidic acid is a narrow spectrum antibiotic used for staphylococcal infections, primarily topically for minor staphylococcal skin (impetigo) or eye infection. It is sometimes used orally for penicillin-resistant staphylococcal infection, including osteomyelitis or endocarditis, in combination with other antibacterials.

Bacteriostatic antibiotics include erythromycin and other macrolide antibiotics. They work by attaching to the bacterial ribosome’s 50S subunit, preventing translocation and thereby protein synthesis. Macrolide antibiotics are actively concentrated inside leukocytes and delivered to the infection site as a result.

Erythromycin is an orally active antibiotic that can also be given intravenously. It is metabolized in the liver and eliminated in the bile and has a biological half-life of 1.5 hours.

It has a similar antibacterial spectrum to benzylpenicillin (i.e., a narrow spectrum, primarily against Gram-positive pathogens) and can be used as a penicillin substitute in people who are allergic to penicillin.
Erythromycin is unsuccessful in the treatment of meningitis because it does not penetrate the central nervous system well enough. It is efficient against a variety of unusual pathogens, unlike penicillin.

Extensor carpi ulnaris is a fusiform muscle in the posterior forearm. It spans between the elbow and base of the little finger. This muscle belongs to the superficial forearm extensor group, along with anconaeus, brachioradialis, extensor carpi radialis longus, extensor carpi radialis brevis, extensor digitorum and extensor digiti minimi muscles.

Like all the muscles of this compartment, extensor carpi ulnaris works as an extensor of the wrist. Moreover, due to its specific course, this muscle also acts to adduct the hand.

Extensor carpi ulnaris is innervated by the posterior interosseous nerve (C7, C8), a branch of the deep division of the radial nerve. The radial nerve stems from the posterior cord of the brachial plexus.

Blood supply to the extensor carpi ulnaris muscle is provided by branches of the radial recurrent and posterior interosseous arteries, which stem from the radial and ulnar arteries, respectively.

Negative feedback loops, also known as inhibitory loops, play a crucial role in controlling human health. It is a self-regulating mechanism of some sort.

A negative feedback system is made up of three main components: a detector (often neural receptor cells) that measures the variable in question and provides input to the comparator; a comparator (usually a neural assembly in the central nervous system) that receives input from the detector, compares the variable to the variable set point, and determines whether or not a response is required.

The comparator activates an effector (typically muscular or glandular tissue) to conduct the appropriate reaction to return the variable to its set point.

Buffers are weak acids or bases that can donate or accept H+ions respectively and therefore resist changes in pH. Buffering does not alter the body’s overall H+load, ultimately the body must get rid of H+by renal excretion if the buffering capacity of the body is not to be exceeded and a dangerous pH reached. Bicarbonate and carbonic acid (formed by the combination of CO2 with water, potentiated by carbonic anhydrase) are the most important buffer pair in the body, although haemoglobin provides about 20% of buffering in the blood, and phosphate and proteins provide intracellular buffering. Buffers in urine, largely phosphate, allow the excretion of large quantities of H+.

Hypotonia means decreased muscle tone. It can be a condition on its own, called benign congenital hypotonia, or it can be indicative of another problem where there is progressive loss of muscle tone, such as muscular dystrophy or cerebral palsy. It is usually detected during infancy. Hypotonia is characteristic of cerebellar dysfunction.

Rubella can be contagious from 7 days before to 7 days after the rash appears.

Patients with measles are contagious from 1-2 days before the onset of symptoms.

A person with chickenpox is considered contagious beginning 1 to 2 days before rash onset until all the chickenpox lesions have crusted (scabbed).

The infectious period of mumps is considered from 2 days before to 5 days after parotitis onset.

Hepatitis A is highly transmissible and has an average incubation period of 28 to 30 days (range 15–50 days). The maximum infectivity is during the second half of the incubation period (i.e. while asymptomatic) and most cases are considered non-infectious after the first week of jaundice.

Depression of the mandible is generated by the digastric, geniohyoid, mylohyoid and lateral pterygoid muscles on both side, assisted by gravity. The lateral pterygoid muscles are also involved as this movement also involves protraction of the mandible. The masseter muscle is a powerful elevator of the mandible.

Klebsiellais a genus of non-motile,Gram-negative, rod-shaped bacteriawith a prominent polysaccharide-based capsule. They are routinely found in the nose, mouth and gastrointestinal tract as normal flora, however, they can also behave as opportunistic pathogens.
Infections with Klebsiella spp. areusually nosocomial. They are an important cause of ventilator-associated pneumonia (VAP), urinary tract infection, wound infection and bacteraemia. Outbreaks of infections with Klebsiellaspp. in high-dependency units have been described and are associated with septicaemia and high mortality rates. Length of hospital stay and performance of invasive procedures are risk factors forKlebsiellainfections.
Primary pneumonia withKlebsiella pneumoniaeis a rare,severe, community-acquired infection associated with a poor outcome.
Klebsiella rhinoscleromatis causes a progressive granulomatous infection of the nasal passages and surrounding mucous membranes. This infection is mainly seen in the tropics.
Klebsiella ozanae is a recognised cause of chronic bronchiectasis.
Klebsiella organisms are resistant to multiple antibiotics including penicillins. This is thought to be a plasmid-mediated property. Agents with high intrinsic activity againstKlebsiellapneumoniaeshould be selected for severely ill patients. Examples of such agents include third-generation cephalosporins (e.g cefotaxime), carbapenems (e.g. imipenem), aminoglycosides (e.g. gentamicin), and quinolones (e.g. ciprofloxacin). These agents may be used as monotherapy or combination therapy. Aztreonam may be used in patients who are allergic to beta-lactam antibiotics.
Species with ESBLs (Extended spectrum beta-lactamase) are resistant to penicillins and also cephalosporins such as cefotaxime and ceftriaxone
.

Most NSAIDs act as non-selective inhibitors of the enzyme cyclo-oxygenase (COX). They inhibit both COX-1 and COX-2 isoenzymes.

Only about 60% of patients will respond to any given NSAID.

It can take 21 days of treatment for a clinically appreciable reduction in inflammation to be apparent. If no improvement is seen after 21 days, the NSAID should be changed.

The use of NSAIDs in the 3rd trimester of pregnancy is associated with the following risks: delayed onset of labour, premature closure of ductus arteriosus and foetal kernicterus.

Side effects are lowest in Ibuprofen and highest in indomethacin. so side effects are more commonly seen with indomethacin than naproxen.

Ecchymosis are discolouration of the skin or mucous membranes caused by extravasation of blood. They are usually red or purple in colour and measure greater than 1 cm in diameter and do not blanch on applying pressure.

A macule is a flat, well circumscribed area of discoloured skin less than 1 cm in diameter with no changes in the thickness or texture of the skin.

Petechiae are discolouration of the skin measuring less than 3 mm in diameter

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

Erythema is redness of the skin or mucous membranes caused by hyperaemia of superficial capillaries caused by skin injury, infection or inflammation. Erythema blanches when pressure is applied whereas ecchymosis, purpura and petechiae do not.

Predisposing factors for digoxin toxicity include hypoxia, hypercalcaemia, hypokalaemia and hypomagnesaemia There should also be care taken in the elderly who are particularly susceptible to digoxin toxicity. Hypokalaemia may be precipitated by use of diuretics. Hyponatremia can result in the development of other pathological disturbances, but it does not make digoxin toxicity worse.

When there is a high suspicion of gonorrhoea from clinical features, empiric treatment should be commenced whilst waiting for laboratory confirmation.
The first line treatment for uncomplicated anogenital and pharyngeal disease includes ceftriaxone 500 mg IM (single dose) + azithromycin 1 g orally as a single dose. This covers concomitant chlamydia infection. For all people who have been treated for gonorrhoea, a test of cure is recommended

Haemostasis is your body’s defence against an injury that causes bleeding. It stops bleeding in three main steps:

1) Primary haemostasis – formation of a weak platelet plug
– The primary reaction of the body is to cause local vasoconstriction at the site of injury and decrease blood flow to the affected area
– the release of cytokines and inflammatory markers lead to adhesion of platelets and aggregation at the site of injury forming a platelet plug
– the injured vessel wall has exposed subendothelial collagen that releases von Willebrand factor

Any damage to the vessel wall causes the release of the Von Willebrand factor, which is necessary for platelet adhesion. Tissue Thromboplastin is also released, which activates the coagulation pathway, a component of secondary haemostasis. The coagulation cascade ultimately results in the conversion of fibrinogen to fibrin.

2) Secondary haemostasis
3) Fibrinolysis

Fibrin (factor Ia) is a long, thin protein with branches produced at the end of the coagulation cascade when fibrinogen (factor I) is converted to fibrin, which stabilizes the blood clot.

Flumazenil is a benzodiazepine antagonist used for the reversal of the sedative effects of benzodiazepines after anaesthesia, sedation and similar procedures.

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.

The common carotid artery runs through the neck and divides into internal and external carotid arteries on both sides near the upper thyroid cartilage. In emergency situations, carotid sinus massage is also used to diagnose or treat paroxysmal supraventricular tachycardia.

During the procedure, to maximize access to the carotid artery, the patient is put in a supine position with the neck extended (i.e. elevating the chin away from the chest). The carotid sinus is normally positioned inferior to the angle of the jaw, near the arterial impulse, at the level of the thyroid cartilage. For 5 to 10 seconds, pressure is administered to one carotid sinus.

Although pulsatile pressure applied in a vigorous circular motion may be more effective, continuous pressure is preferred since it is more reproducible. If the predicted reaction is not obtained, the operation is repeated on the opposite side after a one- to two-minute wait.

Gastric emptying is decreased by:
Enterogastric inhibitory reflexes stimulated by – Distension of the duodenum, The presence of fats in the duodenum (by stimulating release of cholecystokinin), A fall in the pH of chyme in the duodenum, An increase in the osmolality of chyme in the duodenum, Irritation of the mucosal lining of the duodenum, Hormones: Cholecystokinin, Secretin

Anaphylaxis is a type I hypersensitivity reaction that is severe and life-threatening. It is marked by the fast onset of life-threatening airway and/or circulatory issues, which are generally accompanied by skin and mucosal abnormalities. When an antigen attaches to specific IgE immunoglobulins on mast cells, degranulation and the release of inflammatory mediators takes place (e.g. histamine, prostaglandins, and leukotrienes).

The most important medicine for treating anaphylactic responses is adrenaline. It decreases oedema and reverses peripheral vasodilation as an alpha-adrenergic receptor agonist. Its beta-adrenergic effects widen the bronchial airways, enhance the force of cardiac contraction, and inhibit the release of histamine and leukotriene. The first medicine to be given is adrenaline, and the IM route is optimal for most people.

In anaphylaxis, age-related dosages of IM adrenaline are:
150 mcg (0.15 mL of 1:1000) for a child under 6 years
300 mcg (0.3 mL of 1:1000) for a child aged 6 to 12 years
500 mcg (0.5 mL of 1:1000) for children aged 12 and above
500 mcg for adults (0.5 mL of 1:1000)

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.

Meckel’s diverticulum has certain classic characteristics.
1. It lies on the antimesenteric border of the middle-to-distal ileum
2. It is approximately 2 feet proximal to the ileocaecal junction
3. It appears as a blind-ended tubular outpouching of bowel
4. It is about 2 inches long,
5. It occurs in about 2% of the population,
6. It may contain two types of ectopic tissue (gastric and pancreatic).
7. The diverticulum is supplied by the superior mesenteric artery.
8. Proximal to the major duodenal papilla the duodenum is supplied by the gastroduodenal artery (branch of the coeliac trunk)
9. Distal to the major duodenal papilla it is supplied by the inferior pancreaticoduodenal artery (branch of superior mesenteric artery).
10. The arterial supply to the jejunoileum is from the superior mesenteric artery.

Fick’s law tells us that the rate of diffusion of a gas increases:
the larger the surface area involved in gas exchange
the greater the partial pressure gradient across the membrane
the thinner the membrane
the more soluble the gas in the membrane
the lower the molecular weight of the gas

Etomidate causes less hypotension than thiopental sodium and propofol during induction. However, it is associated with a high incidence of extraneous muscle movements, which can be minimised by an opioid analgesic or a short-acting benzodiazepine given prior to induction. Pain on injection is common and there is a high rate of thrombophlebitis in the postoperative period. Postoperative nausea and vomiting commonly occur. Etomidate suppresses adrenocortical function, particularly during continuous administration, and it should not be used for maintenance of anaesthesia. It should be used with caution in patients with underlying adrenal insufficiency, for example, those with sepsis.

Infection of the genital mucosa by Neisseria gonorrhoeae involves attachment to and invasion of epithelial cells. Initial adherence of gonococci to columnar epithelial cells is mediated by type IV pili assembled from pilin subunit PilE proteins and pilus tip-associated PilC proteins, it then invades the epithelial layer, triggering a local acute inflammatory response.

Foetal haemoglobin (HbF) makes up about 0.5 – 0.8 % of total adult haemoglobin and consists of two α and two gamma (γ) globin chains.

Norovirus is the most common viral cause of epidemic gastroenteritis worldwide; it is also a common cause of endemic diarrhoea in community settings. In the United Kingdom, norovirus has become the most common cause of gastroenteritis in adults and children since the introduction of rotavirus vaccination.

Lithium is the drug of choice for recurrent bipolar illness but should be carefully monitored as it has a very low therapeutic index. The normal therapeutic range is 0.4-0.8 mmol/l.

The lower end of the range is usually the target for the elderly and as maintenance therapy. Toxicity is usually seen at levels >1.5 mmol/l. Samples should be taken 12 hours after the dose, and levels should be checked one week after starting therapy and one week after every change in dosage.

The fifth cervical nerve passes between the fourth and fifth cervical vertebrae, and the fourth thoracic nerve passes between the fourth and fifth thoracic vertebrae. Therefore, when the cancer metastasizes in this area, they are most likely affected.

Damage to the femoral nerve results in weakness of hip flexion and knee extension and loss of sensation over the anterior thigh and the anteromedial knee, medial leg and medial foot.

Short vessels called arteriovenous anastomoses (AVAs) link tiny arteries and veins. They have a large lumen diameter. The strong and muscular walls allow AVAs to completely clog the vascular lumen, preventing blood flow from artery to vein (acting like a sphincter). When the AVAs open, they create a low-resistance connection between arteries and veins, allowing blood to flow into the limbs’ superficial venous plexuses. There is no diffusion of solutes or fluid into the interstitium due to their strong muscle walls.

AVAs are densely innervated by adrenergic fibres from the hypothalamic temperature-regulation centre. High sympathetic output occurs at normal core temperatures, inducing vasoconstriction of the AVAs and blood flow through the capillary networks and deep plexuses. When the temperature rises, sympathetic output decreases, producing AVA vasodilation and blood shunting from the artery to the superficial venous plexus. Heat is lost to the environment as hot blood rushes near to the skin’s surface.
AVAs are a specialized anatomical adaptation that can only be found in large quantities in the fingers, palms, soles, lips, and pinna of the ear.

Dietary iron may be in the form of haem or non-haem iron. Haem iron is degraded after absorption through the cell surface to release Fe2+. Most non-haem iron is in the form Fe3+, which is reduced at the luminal surface to the more soluble Fe2+, facilitated by hydrochloric acid in gastric secretions (and enhanced by ascorbic acid). Fe2+is taken across the enterocyte apical membrane by the divalent metal transporter (DMT1). In the enterocyte, Fe2+is then either stored in enterocyte epithelial cells as ferritin, or released into portal plasma via the molecule ferroportin at the basolateral membrane.

All of the muscles of the tongue are innervated by the hypoglossal nerve, except for the palatoglossus, which is innervated by the vagus nerve.

The UK national census is an example of a cross-sectional study.

Cross-sectional studies can be used to assess the prevalence of a condition, and support or refute inferences of cause and effect.

Cross-sectional studies are observations of the frequency and characteristics of a disease in a given population at one particular point in time.

Cross-sectional studies do not differentiate between cause and effect and also do not establish the sequence of events.

Cross-sectional studies cannot be used to calculate the relative risk of a condition.

Glucose reabsorption occurs exclusively in the proximal convoluted tubule by secondary active transport through the Na.Glu co-transporters, driven by the electrochemical gradient for sodium.
The co-transporters transport two sodium ions and one glucose molecule across the apical membrane, and the glucose subsequently crosses the basolateral membrane by facilitated diffusion.

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

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

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

Cephalosporins of the first generation  include cephalexin, cefradine, and cefadroxil. Urinary tract infections, respiratory tract infections, otitis media, and skin and soft-tissue infections are all treated with them.

Second-generation cephalosporins include cefuroxime, cefaclor, and cefoxitin. These cephalosporins are less vulnerable to beta-lactamase inactivation than the ‘first-generation’ cephalosporins. As a result, they’re effective against germs that are resistant to other antibiotics, and they’re especially effective against Haemophilus influenzae.

Cephalosporins of the third generation include cefotaxime, ceftazidime, and ceftriaxone. They are more effective against Gram-negative bacteria than second generation’ cephalosporins. They are, however, less effective against Gram-positive bacteria such Staphylococcus aureus than second-generation cephalosporins.

Prevention of spread of measles is extremely important and infected patients should be isolated. The infectious stage is from 3 days before the rash emerges and patients are advised to stay away from school/nursery/work for 4 days from onset of the rash.

Clearance of a substance can provide an accurate estimate of the glomerular filtration rate (GFR) provided that the substance is:freely filterednot reabsorbed in the nephronnot secreted in the nephronnot synthesised or metabolised by the kidney

Extensor pollicis longus is part of the deep extensors of the forearm together with extensor pollicis brevis, abductor pollicis longus, extensor indicis and supinator muscles. It is located on the posterior aspect of forearm, extending from the middle third of the ulna, and adjacent interosseous membrane, to the distal phalanx of the thumb.

Extensor digitorum is innervated by posterior interosseous nerve which is a continuation of a deep branch of radial nerve (root value C7 and C8).

Extensor pollicis brevis receives its blood supply from the posterior interosseous artery and perforating branches of the anterior interosseous artery.

The main action of extensor pollicis longus is extension of the thumb at the metacarpophalangeal and interphalangeal joints. Extension at the metacarpophalangeal joint occurs in synergy with extensor pollicis brevis muscle. When the thumb reaches the full extension or abduction, extensor pollicis longus can also assist in adduction of the thumb.

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.

A diagnosis of Haemophilia is supported in this patient by the family history and the presence of hemarthrosis-both characteristics of Haemophilia. Haemophilia A is caused by Factor VIII deficiency, leading to impaired coagulation. This disease typically presents after six months when the child starts crawling.

Von Willebrand disease presents with nosebleeds and hematomas. Idiopathic thrombocytopenic purpura presents with bruises that resemble a rash.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency presents with haemolytic anaemia induced by specific drugs or foods.

Factor V Leiden mutation causes blood clotting rather than bleeding.

Gluteus maximus is the main extensor muscle of the hip and assists with lateral rotation of the thigh at the hip joint. It also acts as a hip adductor, steadies the thigh, and assists in raising the trunk from a flexed position.
Gluteus maximus is innervated by the inferior gluteal nerve.

Testes are retroperitoneal organs and its lymphatic drainage is to the lumbar and para-aortic nodes along the lumbar vertebrae.

The scrotum is the one which drains into the nearby superficial inguinal nodes.

The glans penis and clitoris drains into the deep inguinal lymph nodes.

Carbohydrates are the main energy source of most diets. They provide 17 kJ (4 kcal) of energy per gram. Most dietary carbohydrate is in the form of polysaccharides. The principal ingested polysaccharides are starch which is derived from plant sources and glycogen which is derived from animal sources. Dietary fibre consists of indigestible carbohydrate (found in plant foods) such as cellulose, lignin and pectin.

Following the action potential, Na+channels remain inactive for a time in a period known as the absolute refractory period where they cannot be opened by any amount of depolarisation. Following this there is a relative refractory period where the temporary hyperpolarisation (due to delayed closure of rectifier K+channels) makes the cell more difficult to depolarise and an action potential can be generated only in response to a larger than normal stimulus. The refractory period limits the frequency at which action potentials can be generated, and ensures that, once initiated, an action potential can travel only in one direction. An action potential is an all or nothing response so the amplitude of the action potential cannot be smaller.

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 nerve

2. Optic nerve (II)
Manifested by visual field defects, pupillary abnormalities, optic neuritis, optic atrophy, papilledema

3. 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 muscles

12.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.

Hyperthyroidism results from an excess of circulating thyroid hormones. It is commoner in women, and incidence increases with age.

Hyperthyroidism can be subclassified into:
Primary hyperthyroidism – the thyroid gland itself is affected
Secondary hyperthyroidism – the thyroid gland is stimulated by excessive circulating thyroid-stimulating hormone (TSH).

Graves’ disease is the most common cause of hyperthyroidism (estimates are that it causes between 50 and 80% of all cases).

Although toxic multinodular goitre, thyroiditis,TSH-secreting pituitary adenoma and drug-induced hyperthyroidism also causes hyperthyroidism, the commonest cause is Graves’ disease.

Pilocytic astrocytoma (PCA), previously known as cystic cerebellar astrocytoma or juvenile pilocytic astrocytoma, was first described in 1931 by Harvey Cushing, based on a case series of cerebellar astrocytomas; though he never used these terms but rather described a spongioblastoma. They are low-grade, and usually well-circumscribed tumours, which tend to occur in young patients. By the World Health Organization (WHO) classification of central nervous system tumours, they are considered grade I gliomas and have a good prognosis.

PCA most commonly occurs in the cerebellum but can also occur in the optic pathway, hypothalamus, and brainstem. They can also occur in the cerebral hemispheres, although this tends to be the case in young adults. Presentation and treatment vary for PCA in other locations. Glial cells include astrocytes, oligodendrocytes, ependymal cells, and microglia. Astrocytic tumours arise from astrocytes and are the most common tumour of glial origin. The WHO 2016 categorized these tumours as either diffuse gliomas or other astrocytic tumours. Diffuse gliomas include grade II and III diffuse astrocytomas, grade IV glioblastoma, and diffuse gliomas of childhood. The other astrocytic tumours group include PCA, pleomorphic xanthoastrocytoma, subependymal giant cell astrocytoma, and anaplastic pleomorphic xanthoastrocytoma.

PCA can present with symptoms secondary to the posterior fossa mass effect. This may include obstructive hydrocephalus, with resultant headache, nausea and vomiting, and papilledema. If hydrocephalus occurs before the fusion of the cranial sutures (<18-months-of-age), then an increase in head circumference will likely occur. Lesions of the cerebellar hemisphere result in peripheral ataxia, dysmetria, intention tremor, nystagmus, and dysarthria. In contrast, lesions of the vermis cause a broad-based gait, truncal ataxia, and titubation. Posterior fossa lesions can also cause cranial nerve palsies. Diplopia may occur due to abducens palsy from the stretching of the nerve. They may also have blurred vision due to papilledema. Seizures are rare with posterior fossa lesions.

A pareto diagram, or pareto chart, consists of a vertical bar graph in which values are plotted in decreasing order of relative frequency from left to right. The independent variables on the chart are shown on the horizontal axis and the dependent variables are portrayed as the heights of bars.

A point-to-point graph, which shows the cumulative relative frequency, may be superimposed on the bar.

Because the values of the statistical variables are placed in order of relative frequency, the graph clearly reveals which factors have the greatest impact and where attention is likely to yield the greatest benefit. It is extremely useful for analysing what problems need attention first, because the taller bars on the chart clearly illustrate which variable have the greatest cumulative effect on a given system.

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.

Aspirin (at analgesic doses) is contraindicated in severe heart failure. Aspirin irreversibly inhibits cyclooxygenase (COX) enzymes resulting in decreased production of prostaglandins (which can lead to irritation of the gastric mucosa). The analgesic dose is greater than the antiplatelet dose, and taken orally it has a duration of action of about 4 hours. Clinical features of salicylate toxicity in overdose include hyperventilation, tinnitus, deafness, vasodilatation, and sweating.

At altitude, the oxygen fraction is unaltered but the barometric pressure and thus partial pressure of oxygen is reduced.

Side effects of metoclopramide are commonly associated with extrapyramidal effects and hyperprolactinemia. Therefore its use must be limited to short-term use. Metoclopramide can induce acute dystonic reactions which involve facial and skeletal muscle spasms and oculogyric crises. These dystonic effects are more common in the young girls and young women, and in the very old. These symptoms usually occur shortly after starting treatment with this drug and subside within 24 hours of stopping it. Abortion of dystonic attacks can be carried out by injection of an antiparkinsonian drug like procyclidine.

Anti-nuclear antibodies(ANAs) also referred to as anti-nuclear factors (ANFs) are autoantibodies that bind to contents of the cell nucleus. They can be of any immunoglobulin class.

CREST syndrome is usually associated with anti-centromere antibodies.

ELISA testing is cheaper but not the most accurate means of testing for ANAs. Indirect immunofluorescence testing is the most reliable.

Nucleolar staining is suggestive of scleroderma, while homogenous staining is suggestive of lupus.

Anti-dsDNA antibodies are found in 80 – 90% of patients with SLE

Erythropoietin is a glycoprotein hormone that regulates the formation of red blood cells (red cell production). It is mostly produced by interstitial fibroblasts in the kidney, which are located near the PCT. It is also produced in the liver’s perisinusoidal cells, however this is more common during the foetal and perinatal periods.

The kidneys produce and secrete erythropoietin in response to hypoxia. On red blood cells, erythropoietin has two main effects:
– It encourages stem cells in the bone marrow to produce more red blood cells.
– It protects red blood cell progenitors and precursors from apoptosis by targeting them in the bone marrow.
As a result of the increased red cell mass, the oxygen-carrying capacity and oxygen delivery increase.

Colchicine is used to prevent or treat gout attacks (flares). It works by reducing swelling and the development of uric acid crystals, which cause pain in the affected joint(s).

Colchicine should be avoided by patients who have blood dyscrasias or bone marrow disorders.

The pain associated with external haemorrhoids is carried by a branch of the pudendal nerve, specifically the somatic fibres (S2-S4).

It innervates the external anal sphincter and most of the skin over the perineum.

Arterial baroreceptors are located in the carotid sinus and aortic arch, and detect the mean arterial pressure (MAP). A decrease in MAP (such as in postural hypotension, or haemorrhage) reduces arterial stretch and decreases baroreceptor activity, resulting in decreased firing in afferent nerves travelling via the glossopharyngeal nerve (carotid sinus) and vagus nerve (aortic arch) to the medulla where the activity of the autonomic nervous system is coordinated. Sympathetic nerve activity consequently increases, causing an increase in heart rate and cardiac contractility, peripheral vasoconstriction with an increase in TPR, and venoconstriction with an increase in CVP and thus an increase in cardiac output and blood pressure. Parasympathetic activity (vagal tone) decreases, contributing to the rise in heart rate.

Inferior medial pontine syndrome, also known as Foville syndrome, is one of the brainstem stroke syndromes which occurs when there is infarction of the medial inferior aspect of the pons due to occlusion of the paramedian branches of the basilar artery.

It is characterized by ipsilateral sixth nerve palsy, facial palsy, contralateral hemiparesis, contralateral loss of proprioception and vibration, ipsilateral ataxia, ipsilateral facial weakness, and lateral gaze paralysis and diplopia.

Non-Hodgkin’s Lymphoma (NHL) causes neoplastic transformation of both B cell (85%) and T cell (15%) lines.

The most common presentation is with enlarged, rubbery, painless lymph nodes. The patient may also have B symptoms which consist of night sweats, weight loss and fevers. Multiple myeloma most commonly presents with bone pain, especially in the back and ribs.

The presence of Reed-Sternberg cells characterises Hodgkin’s lymphoma. Acute lymphoblastic leukaemia will present with features of anaemia, thrombocytopenia and leukopenia. The most common symptoms of chronic lymphocytic leukaemia are fatigue, night sweats and low-grade fever.

The peak incidence of NHL is in the 50-70 years age group, it affects men and women equally, but affects the Caucasian population more commonly than black and Asian ethnic groups.
The following are recognised risk factors for NHL:
Chromosomal translocations and molecular rearrangements
Epstein-Barr virus infection
Human T-cell leukaemia virus type-1 (HTLV-1)
Hepatitis C
Congenital and acquired immunodeficiency states
Autoimmune disorders, e.g. Sjogren’s syndrome and Hashimoto’s thyroiditis

The cervical spinal cord is the section of the spinal cord that goes through the bones of the neck.

It is injured incompletely in the central cord syndrome (CCS). This will result in arm weakness more than leg weakness.

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.

When more fluid is filtered out of the capillaries than can be returned to the circulation by the lymphatics, oedema occurs. Changes that increase capillary hydrostatic pressure or decrease plasma oncotic pressure will increase filtration.
Arteriolar constriction reduces hydrostatic capillary pressure and transiently increase absorption of fluid.
Dehydration increases plasma protein concentration and therefore increases plasma oncotic pressure and absorption. Capillary hydrostatic pressure and filtration are increased when there is increased venous pressure.

Lactic acidosis is defined as a pH <7.35 and a lactate >5 mmol/L. It is a common finding in critically ill patients and is often associated with other serious underlying pathologies. The anion gap is raised in lactic acidosis.
There are major adverse consequences of severe acidaemia, which affect all body systems, and there is an associated increase in mortality of critically ill patients with a raised lactate. The mortality associated with lactic acidosis despite full supportive treatment remains at 60-90%.
Acquired lactic acidosis is classified into two subtypes:
Type A is due to tissue hypoxia
Type B is due to non-hypoxic processes affecting the production and elimination of lactate
Lactic acidosis can be extreme after a seizure but usually resolves spontaneously within a few hours.
Left ventricular failure typically results in tissue hypoperfusion and a type A lactic acidosis.
Some causes of type A and type B lactic acidosis are shown below:
Type A lactic acidosis
Type B lactic acidosis
Shock (including septic shock)
Left ventricular failure
Severe anaemia
Asphyxia
Cardiac arrest
CO poisoning
Respiratory failure
Severe asthma and COPD
Regional hypoperfusion
Renal failure
Liver failure
Sepsis (non-hypoxic sepsis)
Thiamine deficiency
Alcoholic ketoacidosis
Diabetic ketoacidosis
Cyanide poisoning
Methanol poisoning
Biguanide poisoning