The gastric chief cells in the stomach wall releases pepsinogen. Pepsinogen is a proenzyme. It mixes with hydrochloric acid in the stomach and is converted to pepsin. Pepsin breaks down proteins into peptides aiding protein digestion.

High-dose inhaled short-acting beta2-agonists are the first line treatment for acute asthma(salbutamol or terbutaline). Oxygen should only been given to hypoxaemic patients (to maintain oxygen saturations of 94 – 98%). A pressurised metered dose inhaler with spacer device is preferred in patients with moderate to severe asthma (4 puffs initially, followed by 2 puffs every 2 minutes according to response, up to 10 puffs, whole process repeated every 10 – 20 minutes if necessary). The oxygen-driven nebuliser route is recommended for patients with life-threatening features or poorly responsive severe asthma (salbutamol 5 mg at 15 – 30 minute intervals). Continuous nebulisation should be considered in patients with severe acute asthma that is poorly responsive to initial bolus dose (salbutamol at 5 – 10 mg/hour) The intravenous route should be reserved for those in whom inhaled therapy cannot be used reliably.

At rest, saliva is predominantly produced by the submandibular gland (65%) but when stimulated, the parotid glands produce a higher proportion of the total saliva production (50%) than at rest. Saliva is alkaline and hypotonic to plasma. The predominant digestive enzymes in saliva are alpha-amylase and lingual lipase; lingual lipase is not functionally very important, but alpha-amylase is important for the initiation of starch digestion. Saliva production is decreased by inhibition of the parasympathetic nervous system e.g. by sleep, dehydration, anticholinergic drugs and fear.

The volume of air that remains in the lungs after a single breath is known as functional residual capacity (FRC). It is calculated by combining the expiratory reserve volume and residual volume.

The DVLA sends a detailed information sheet about their licence and driving to all drivers with diabetes mellitus. The primary danger of driving while diabetic is hypoglycaemia.

The DVLA must be notified of the following diabetic patients:
All of the drivers are on insulin. (Licenses are being reviewed more frequently.)
Those who are at high risk of hypoglycaemia and have had more than one episode of severe hypoglycaemia in the previous year. (Severe hypoglycaemia is defined as requiring the assistance of another person to manage.)
Those who are unaware of their hypoglycaemia
Anyone who has ever been in a car accident due to hypoglycaemia
Anyone with diabetic retinopathy who needs laser treatment (to both eyes or to a second eye if sight only in one eye)
Patients with diabetes complications that impair their ability to drive.

To drive, drivers with insulin-treated diabetes must meet the following requirements:
They need to be aware of hypoglycaemia.
They must not have had more than one episode of hypoglycaemia in the previous 12 months that necessitated the assistance of another person.
They must check their blood glucose levels no later than 2 hours before the first journey.
While driving, they must check their blood glucose levels every two hours.
The visual acuity and visual field standards must be met.

Any significant changes in their condition must be reported to the DVLA. Furthermore, on days when they are not driving, group 2 licence holders must test their blood glucose twice daily using a metre that can store three months’ worth of readings.

In addition to this advice, the DVLA also offers the following advice to diabetic patients:
When taking tablets that have the potential to cause hypoglycaemia (such as sulfonylureas and glinides), monitoring may be necessary if there has been more than one episode of severe hypoglycaemia.
Drivers must show good control and be able to recognise hypoglycaemia.
Verify that your vision meets the required standard.

If a patient feels hypoglycaemic or has a blood glucose level of less than 4.0 mmol/L, they should not drive. Driving should not be resumed until blood glucose levels have returned to normal, which should take 45 minutes.

If there are any warning signs, patients should carry rapidly absorbed sugar in their vehicle and stop, turn off the ignition, and eat it.

If resuscitation is required, a card stating which medications they are taking should be carried.

If hypoglycaemia causes an accident, a diabetic driver may be charged with driving under the influence of drugs.

The tonsils are collections of lymphatic tissue located within the pharynx. They collectively form a ringed arrangement, known as Waldeyer’s ring: pharyngeal tonsil, 2 tubal tonsils, 2 palatine tonsils, and the lingual tonsil.

Lymphatic fluid from the lingual tonsil drains into the jugulodigastric and deep cervical lymph nodes.

Lymphatic fluid from the pharyngeal tonsil drains into the retropharyngeal nodes (which empty into the deep cervical chain), and directly into deep cervical nodes within the parapharyngeal space.

The retropharyngeal and the deep cervical lymph nodes drain the tubal tonsils.

The palatine tonsils drain to the jugulodigastric node, a node of the deep cervical lymph nodes, located inferior to the angle of the mandible.

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.

Endocarditis is infective or non infective inflammation (marantic endocarditis) of the inner layer of the heart and it often involves the heart valves.

Risk factors include:
Prosthetic heart valves
Congenital heart defects
Prior history of endocarditis
Rheumatic fever
Illicit intravenous drug use

In the presentation of endocarditis, the following triad is often quoted:
Persistent fever
Embolic phenomena
New or changing murmur

Flucloxacillin and gentamicin are current recommended by NICE and the BNF for the initial ‘blind’ therapy in endocarditis.

Mannitol is the most widely used osmotic diuretic that is most commonly used to reduce cerebral oedema and intracranial pressure.
Mannitol has four FDA approved uses clinically:
1. Reduction of intracranial pressure and brain mass
2. reduce intraocular pressure if this is not achievable by other means
3. promote diuresis for acute renal failure to prevent or treat the oliguric phase before irreversible damage
4. promote diuresis to promote the excretion of toxic substances, materials, and metabolites

It can be used in rhabdomyolysis-induced renal failure, especially in crush injuries. Mannitol reduces osmotic swelling and oedema in the injured muscle cells and helps restore skeletal muscle function.

It is a low molecular weight compound and can be freely filtered at the glomerulus and not reabsorbed. This way increases the osmolality of the glomerular filtrate and tubular fluid, increasing urinary volume by an osmotic effect. It also does not cross the blood-brain barrier (BBB).

Mannitol causes an expansion of the extracellular fluid space, which may worsen congestive cardiac failure. Contraindications to the use of mannitol include:

1. Anuria due to renal disease
2. Acute intracranial bleeding (except during craniotomy)
3. Severe cardiac failure
4. Severe dehydration
5. Severe pulmonary oedema or congestion
6. Known hypersensitivity to mannitol

Haemophilia B is a bleeding disorder caused by a deficiency of clotting factor IX. It is the second commonest form of haemophilia, and is rarer than haemophilia A. Haemophilia B tends to be similar to haemophilia A but less severe. The two disorders can only be distinguished by specific coagulation factor assays.

The incidence is one-fifth of that of haemophilia A. Laboratory findings demonstrate prolonged APTT, normal PT and low factor IX.
Haemophilia B inherited in an X-linked recessive fashion, affecting males born to carrier mothers.
There is also a variation called Leyden, in which factor IX levels are below 1% until puberty, when they rise, potentially reaching as high as 40-60% of normal. This is thought to be due to the effects of testosterone at puberty.

A patient suffering from acute ischemic stroke can commonly present with hypertensive emergencies. Thrombolytic therapy is contraindicated in a patient with:
1. Systolic blood pressure greater than 185 mmHg
2. Diastolic blood pressure greater than 110 mmHg

But delaying thrombolytic therapy is associated with increased morbidity in patients with acute ischemic stroke.

Managing high blood pressure in acute ischemic stroke requires a slower and more controlled reduction in BP. In the presence of an ischaemic stroke, rapid reduction of MAP can compromise blood flow, causing further ischemia and worsening of the neurological deficit.

Intravenous labetalol is the agent of choice. The dose is 10 mg IV over 1-2 minutes. This dose can be repeated, or an infusion can be set up that runs at 2-8 mg/minute. Thrombolysis can be performed once the blood pressure is brought down to less than 180/105 mmHg.

A nitrate infusion (for example, Isoket) can be used as an alternative in patients with contraindications to the use of beta-blockers (e.g., asthma, heart block, cardiac failure).

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

Synthesis of platelets occurs in the bone marrow by fragmentation of megakaryocytes cytoplasm, derived from the common myeloid progenitor cell. The average time for differentiation of the human stem cell to the production of platelets is about 10 days. The major regulator of platelet formation is thrombopoietin and 95% of this is produced by the liver. Normal platelet count is 150 – 450 x 109/L and the normal lifespan of a platelet is about 10 days. Usually about one-third of the marrow output of platelets may be trapped at any one time in the normal spleen.

Advantages of LMWHGreater ability to inhibit factor Xa directly, interacting less with platelets and so may have a lesser tendency to cause bleedingGreater bioavailability and longer half-life in plasma making once daily subcutaneous administration possibleMore predictable dose response avoiding the need for routine anticoagulant monitoringLower associated risk of heparin-induced thrombocytopenia or of osteoporosis

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.

Bronchiolitis is a common respiratory infection that occurs in infancy between the ages of 3-6 months and in the winter months. It is most commonly caused by the respiratory syncytial virus (70% of cases)

Although it can also be caused by parainfluenza virus, adenovirus, coronavirus, rhinovirus, and influenza virus, these are not the most common causes

After primary infection, VZV remains latent in sensory ganglia and in about 20% of patients will reactivate resulting in shingles, a painful vesicular rash in the related dermatome. Shingles usually affects older people and the immunocompromised. Shingles lesions are infectious to non-immune individuals who are at risk of developing chickenpox. Shingles can not be contracted directly from chickenpox, or from other cases of shingles. Shingles is treated with systemic antiviral treatment to reduce the severity and duration of pain, reduce complications, and reduce viral shedding.

A nominal variable is a type of variable that is used to name, label or categorize particular attributes that are being measured. It takes qualitative values representing different categories, and there is no intrinsic ordering of these categories.
A nominal variable is one of the 2 types of categorical variables and is the simplest among all the measurement variables. Some examples of nominal variables include gender, name, phone, etc.

A nominal variable is qualitative, which means numbers are used here only to categorize or identify objects. They can also take quantitative values. However, these quantitative values do not have numeric properties. That is, arithmetic operations cannot be performed on them. If the variable is nominal, the mode is the only measure of central tendency to use.

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

A bitemporal hemianopia is most likely due to compression at the optic chiasm. This may be caused by pituitary tumour, craniopharyngioma, meningioma, optic glioma or aneurysm of the internal carotid artery. A posterior cerebral stroke will most likely result in a contralateral homonymous hemianopia with macular sparing.

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.

Opioids should be avoided in people who have:
A risk of paralytic ileus (opioids reduce gastric motility)
Acute respiratory depressionAn acute exacerbation of asthma (opioids can aggravate bronchoconstriction as a result of histamine release)
Conditions associated with increased intracranial pressure including head injury (opioids can interfere with pupillary response making neurological assessment difficult and may cause retention of carbon dioxide aggravating the increased intracranial pressure)

Amiodarone has a chemical structure that is similar to that of thyroxine and can bind to the nuclear thyroid receptor. It can cause both hypothyroidism and hyperthyroidism, though hypothyroidism is far more common, with 5-10% of patients suffering from it.

Local currents propagate action potentials down the axons of neurons. Following depolarization, this local current flow depolarizes the next axonal membrane, and when this region crosses the threshold, more action potentials are formed, and so on. Due to the refractory period, portions of the membrane that have recently depolarized will not depolarize again, resulting in the action potential only being able to go in one direction.

The square root of axonal diameter determines the velocity of the action potential; the axons with the biggest diameter have the quickest conduction velocities. When a neuron is myelinated, the speed of the action potential rises as well.

The myelin sheath is an insulating coating that surrounds certain neural axons. By increasing membrane resistance and decreasing membrane capacitance, the myelin coating increases conduction. This enables faster electrical signal transmission via a neuron, making them more energy-efficient than non-myelinated neuronal axons.

Nodes of Ranvier are periodic holes in a myelinate axon when there is no myelin and the axonal membrane is exposed. There are no gated ion channels in the portion of the axon covered by the myelin sheath, but there is a high density of ion channels in the Nodes of Ranvier. Action potentials can only arise at the nodes as a result of this.
Electrical impulses are quickly transmitted from one node to the next, causing depolarization of the membrane above the threshold and triggering another action potential, which is then transmitted to the next node. An action potential is rapidly conducted down a neuron in this manner. Saltatory conduction is the term for this.

The tidal volume(TV) is the amount of air that moves in and out of the lungs with each respiratory cycle. In a healthy male, the usual volume is 0.5 L (,7 ml/kg body mass).

The vital capacity(VC) is the maximum amount of air that can be exhaled following maximal inspiration. The usual volume in a healthy male is 4.5 L.

The residual volume(RV) is the amount of air remaining in the lungs after maximum expiration. The usual volume in a healthy male is 1.0 L.

The inspiratory reserve volume(IRV) is the maximum amount of air that can be breathed in forcibly after normal inspiration. The usual volume in a healthy male is 3.0 L.

The expiratory reserve volume(ERV) is the volume of air that can be breathed out forcibly after normal expiration. The usual volume in a healthy male is 1.0 L.

Total lung capacity(TLC) is the volume of air the lungs can accommodate. TLC = RV+VC. The usual volume in a healthy male is 5.5 L.

Because digoxin has a narrow therapeutic index, it can cause toxicity both during long-term therapy and after an overdose. Even when the serum digoxin concentration is within the therapeutic range, it can happen.

Acute digoxin toxicity usually manifests itself within 2-4 hours of an overdose, with serum levels peaking around 6 hours after ingestion and life-threatening cardiovascular complications following 8-12 hours.

Chronic digoxin toxicity is most common in the elderly or those with impaired renal function, and it is often caused by a coexisting illness. The clinical signs and symptoms usually appear gradually over days to weeks.

The following are characteristics of digoxin toxicity:
Nausea and vomiting
Diarrhoea
Abdominal pain
Confusion
Tachyarrhythmias or bradyarrhythmias
Xanthopsia (yellow-green vision)
Hyperkalaemia (early sign of significant toxicity)

Some precipitating factors are as follows:
Elderly patients
Renal failure
Myocardial ischaemia
Hypokalaemia
Hypomagnesaemia
Hypercalcaemia
Hypernatraemia
Acidosis
Hypothyroidism
Spironolactone
Amiodarone
Quinidine
Verapamil
Diltiazem

The hormone-active metabolite of vitamin D is 1,25-dihydroxycholecalciferol (commonly known as calcitriol). Its activities raise calcium and phosphate levels in the bloodstream.

The following are the primary effects of 1,25-dihydroxycholecalciferol:

Calcium and phosphate absorption in the small intestine is increased.
Calcium reabsorption in the kidneys is increased.
Increases phosphate reabsorption in the kidneys.
Increases the action of osteoclastic bacteria (increasing calcium and phosphate resorption from bone)
Inhibits the action of 1-alpha-hydroxylase in the kidneys (negative feedback)
Thyroid hormone (parathyroid hormone) Calcium reabsorption in the tubules of the kidneys is increased, but renal phosphate reabsorption is decreased.

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.

The use of abciximab is contraindicated in the following situations:
Internal bleeding is present.
Within the last two months, you’ve had major surgery, intracranial surgery, or trauma.
Stroke in the previous two years
Intracranial tumour
Aneurysm or arteriovenous malformation
Haemorrhagic diathesis is a type of haemorrhagic diathesis.
Vasculitis
Retinopathy caused by hypertension

Passive diffusion is a process that describes the movement down a concentration gradient. This process accounts for movement across small distances like within the cytosol or across membranes. Factors that affect the diffusion of a substance across a membrane are the permeability (p) of the membrane, a difference in concentration across the membrane and the membrane area over which diffusion occurs. The membrane thickness and composition, and the diffusion coefficient of the substance also affects the permeability. Fick’s law describes the rate of diffusion of a substance within a solution, which can be modified to describe the rate of diffusion across a membrane.

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

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