Capillaries are designed with a small diffusion distance for nutrition and gaseous exchange with the tissues they serve. Because oxygen and carbon dioxide are both highly soluble in lipids (lipophilic), they can easily diffuse along a concentration gradient across the endothelial lipid bilayer membrane. In contrast, glucose, electrolytes, and other polar, charged molecules are lipid-insoluble (hydrophilic). These chemicals are unable to pass through the lipid bilayer membrane directly and must instead travel through gaps between endothelial cells.
Capillaries are divided into three types: continuous, fenestrated, and sinusoidal. Each of these capillary types contains different sized gaps between the endothelial cells that operate as a filter, limiting which molecules and structures can pass through.

The permeability of capillaries is affected by the wall continuity, which varies depending on the capillary type.
Skeletal muscle, myocardium, skin, lungs, and connective tissue all have continuous capillaries. These capillaries are the least permeable. They have a basement membrane and a continuous layer of endothelium. The presence of intercellular spaces allows water and hydrophilic molecules to pass across. Tight connections between the cells and the glycocalyx inhibit passage via these gaps, making diffusion 1000-10,000 times slower than for lipophilic compounds. The diffusion of molecules larger than 10,000 Da, such as plasma proteins, is likewise prevented by this narrow pore system. These big substances can pass through the capillary wall, but only very slowly, because endothelial cells have enormous holes.

The kidneys, gut, and exocrine and endocrine glands all have fenestrated capillaries. These are specialized capillaries that allow fluid to be filtered quickly. Water, nutrients, and hormones can pass via windows or fenestrae in their endothelium, which are connected by a thin porous membrane. They are ten times more permeable than continuous capillaries due to the presence of these fenestrae. Fenestrated capillaries have a healthy basement membrane.
The spleen, liver, and bone marrow all have sinusoidal capillaries, also known as discontinuous capillaries. Their endothelium has huge gaps of >100 nm, and their basement membrane is inadequate. They are highly permeable as a result, allowing red blood cells to travel freely.

Intrinsic factor is essential for the absorption of the small amounts of vitamin B12 normally present in the diet from the terminal ileum. The parietal cells of the stomach produce intrinsic factor, and following a gastrectomy, the absorption of vitamin B12 will be markedly reduced, and a deficiency state will exist.

Hypoxia, hypercalcaemia, hypokalaemia and hypomagnesaemia predispose to digoxin toxicity. Care should also be taken in the elderly who are particularly susceptible to digoxin toxicity. Hypokalaemia may be precipitated by use of diuretics. Although hyponatremia can result in the development of other pathological disturbances, it does not potentiate digoxin toxicity.

Klebsiella pneumoniae is among the most common Gram-negative bacteria encountered by physicians worldwide and accounts for 0.5-5.0% of all cases of pneumonia. This organism can cause extensive pulmonary necrosis and frequent cavitation.

It is one of the causes that could be suspected when there is cavitatory pneumonia with or without a bulging fissure sign. Often, there can be extensive lobar opacification with air bronchograms.

A helpful feature which may help to distinguish from pneumococcal pneumonia is that Klebsiella pneumoniae develops cavitation in 30-50% of cases (in comparison, cavitation is rare in pneumococcal pneumonia). This occurs early and progresses quickly.

Hyponatraemia refers to a serum sodium concentration < 135 mmol/L.
It is safer to quickly correct acute hyponatremia than chronic hyponatremia but correction should not be too fast, especially in chronic hyponatraemia, because of the risk of central pontine myelinolysis. Hyponatraemia is usually associated with a low plasma osmolality.
Under normal circumstances, if serum osmolality is low, then urine osmolality should also be low because the kidneys should be trying to retain solute.
In SIADH, excess ADH causes water retention, but not the retention of solute. Therefore, urine that is concentrated and relatively high in sodium is produced, even though the serum sodium is low (urine osmolality > 100 mosmol/kg).

Poststreptococcal glomerulonephritis (PSGN) is caused by prior infection with specific nephritogenic strains of group A beta-haemolytic streptococcus. The clinical presentation of PSGN varies from asymptomatic, microscopic haematuria to the full-blown acute nephritic syndrome, characterized by red to brown urine, proteinuria (which can reach the nephrotic range), oedema, hypertension, and acute kidney injury.

Adverse effects of warfarin:
The most common adverse effect of warfarin is bleeding

Other common adverse effects of warfarin include nausea, vomiting, diarrhoea, jaundice, hepatic dysfunction, pancreatitis, pyrexia, alopecia, purpura, and rash

Skin necrosis is a rare but serious adverse effect of warfarin; treatment with warfarin should be stopped if warfarin related skin necrosis is suspected

Calciphylaxis is a rare, but a very serious condition that causes vascular calcification and cutaneous necrosis

Brachioradialis is a fusiform muscle located in the lateral part of the posterior forearm. Along with extensor carpi radialis brevis and extensor carpi radialis longus, it comprises the radial group of forearm muscles, which belong to the superficial layer of posterior forearm muscles. Although anatomically part of the posterior forearm muscles, which are known to be forearm extensors, brachioradialis’ fibre orientation enables it to rather flex the forearm, and aids in supination of the forearm at the radioulnar joint.

The brachioradialis muscle originates from the upper two-thirds of the lateral supracondylar ridge of humerus and the anterior surface of the lateral intermuscular septum of the arm. It slides over the lateral surface of the elbow joint, entering the anterolateral cubital area. The muscle fibres course inferiorly down the radial part of the anterior forearm, forming a thick tendon in approximately the middle of the forearm. This tendon then traverses the remainder of the forearm, inserting near the wrist, just proximal to the styloid process of radius.

Brachioradialis is innervated by the radial nerve (from the root values C5-C6) that stems from the posterior cord of the brachial plexus. Blood supply to the brachioradialis muscle comes from branches of the radial artery, radial recurrent artery and the radial collateral branch of the deep brachial artery.

Phyllocontin continus contains aminophylline (a mixture of theophylline and ethylenediamine), a bronchodilator used in the management of COPD and asthma.
This patient is exhibiting symptoms of theophylline toxicity, which may have been triggered by the prescription of the antibiotic. Quinolone antibiotics, such as ciprofloxacin and levofloxacin, and macrolide antibiotics, such as erythromycin, increase the plasma concentration of theophyllines and can lead to toxicity.
The drugs that commonly affect the half-life and the plasma concentration of theophylline are summarised in the table below:
Drugs increasing plasma concentration of theophylline
Drugs decreasing plasma concentration of theophylline
Calcium channel blockers, e.g. Verapamil
Cimetidine
Fluconazole
Macrolides, e.g. erythromycin
Quinolones, e.g. ciprofloxacin
Methotrexate
Barbiturates
Carbamazepine
Phenobarbitol
Phenytoin (and fosphenytoin)
Rifampicin
St. John’s wort

There is a high suspicion of a thyroid crisis in this patient and emergent treatment should be initiated even before the results of TFT’s have returned. Antiadrenergic drugs like IV propranolol should be administered immediately to minimise sympathomimetic symptoms. Antithyroid medications like propylthiouracil or carbimazole should be administered to block further synthesis of thyroid hormones. After thionamide therapy has been started to prevent stimulation of new hormone synthesis, there should then be delayed administration of oral iodine solution. Hydrocortisone administration is also recommended as it treats possible relative adrenal insufficiency while also decreases peripheral conversion of T4 to T3.

Diabetes ketoacidosis is an acute complication of diabetes mellitus. Insulin is administered to achieve euglycemia, and crystalloids or colloidal solution is administered to achieve euvolemia and euelectrolytaemia.

Potassium levels severely fluctuate during the treatment of DKA, hypokalaemia being more common. Insulin promotes the cell to take up potassium from the extracellular space via increased sodium-potassium pump activity.

It is important to monitor potassium levels during the treatment of DKA regularly. It is widely suggested that the normal saline shall be used for initial resuscitation, and once the potassium level is retrieved, the patient can be started on potassium replacement should the serum potassium level be between 3.3 and 4.5 mmol/L
If potassium levels fall below 3.3 mmol/l, insulin administration may need to be interrupted to correct the hypokalaemia.

Neutrophil polymorphs are the predominant type of white cells in an acute reaction. They pass between endothelial cell junctions to invade damaged tissue so that the effects of injury can be combated. Extravasation occurs with the movement of leukocytes out of the vessel lumen, and is achieved in five phases which are margination, ‘rolling’, adhesion, transmigration and chemotaxis.

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.

Hodgkin’s lymphoma is a malignant tumour of the lymphatic system that is characterised histologically by the presence of Reed-Sternberg cells (multinucleated giant cells). The peak incidence is in young adults aged 20-35, and there is a slight male predominance.

The following are recognised risk factors for Hodgkin’s lymphoma:
Male gender
Age 20-35
Positive family history
Epstein-Barr virus infection
Immunosuppression including HIV infection
Prolonged use of human growth hormone
Most patients present with an enlarged, but otherwise asymptomatic lymph node. The most commonly affected lymph nodes are in the supraclavicular and lower cervical areas. Other common clinical features include shortness of breath and chest discomfort secondary to mediastinal mass. Mediastinal masses are sometimes discovered as incidental findings on routine chest X-rays. Approximately 30% of patients with Hodgkin’s lymphoma develop splenomegaly.
‘B’ symptoms occur in approximately 25% of patients. The ‘B’ symptoms of Hodgkin’s lymphoma are:
Fever (>38ºC)
Night sweats
Weight loss (>10% over 6 months)
Pain after alcohol consumption is a pathognomonic sign of Hodgkin’s lymphoma, it is, however, not a ‘B’ symptom. It is rare though, only occurring in 2-3% of patients with Hodgkin’s lymphoma.

The Ann Arbour clinical staging is as follows:
Stage I: one involved lymph node group
Stage II two involved lymph node groups on one side of the diaphragm
Stage III: lymph node groups involved on both sides of the diaphragm
Stage IV: Involvement of extra-nodal tissues, such as the liver or bone marrow
Diagnosis is made by lymph node biopsy, which should be taken from a sufficiently large specimen or excisional biopsy, as opposed to a fine needle biopsy. The Reed-Sternberg cell is the most useful diagnostic feature. This is a giant cell with twin mirror-image nuclei and prominent ‘owl’s eye’ nucleoli.
The Reed-Sternberg cell of Hodgkin’s Lymphoma
Histological typing depends upon the other cells within the diseased tissue. Nodular sclerosing is the most common type of Hodgkin’s lymphoma. Lymphocyte-depleted and lymphocyte-predominant are rare subtypes.
The majority of cases can be successfully treated, and unlike many other malignancies even if the first-line treatment fails, a cure can often be achieved with second-line therapies. Stage 1 Hodgkin’s lymphoma is usually treated with radiotherapy alone, but more advanced stages require combination chemotherapy. In localised disease treated with irradiation, there is a 5-year survival rate of greater than 80%. In disseminated disease treated with chemotherapy, the 5-year survival falls to around 50%. Overall, a 5-year survival of >70% should be achieved.

Macrolides are bacteriostatic antibiotics. They act by binding to the 50S subunit of the bacterial ribosome and inhibit translocation, therefore, inhibiting protein synthesis.

Insulin is produced by beta cells, located centrally within the islets of Langerhans, in the endocrine tissues of the pancreas. Insulin is a polypeptide hormone consisting of two short chains (A and B) linked by disulphide bonds. Proinsulin is synthesised as a single-chain peptide. Within storage granules, a connecting peptide (C peptide) is removed by proteases to yield insulin. Insulin release is stimulated initially during eating by the parasympathetic nervous system and gut hormones such as secretin, but most output is driven by the rise in plasma glucose concentration that occurs after a meal. The effects of insulin are mediated by the receptor tyrosine kinase.

Gastrin acts to:
Stimulate acid secretion from parietal cells (both directly and indirectly by stimulating release of histamine from ECL cells)
Stimulate pepsinogen secretion from chief cells
Increase gastric motility
Stimulate growth of gastric mucosa

Adverse effects include:
Common: Nausea
Uncommon: Vomiting
Rare: Abdominal pain, hypertension, hypotension, tachycardia

Mitochondria are membrane-bound organelles that are responsible for the production of the cell’s supply of chemical energy. This is achieved by using molecular oxygen to utilise sugar and small fatty acid molecules to generate adenosine triphosphate (ATP). This process is known as oxidative phosphorylation and requires an enzyme called ATP synthase. ATP acts as an energy-carrying molecule and releases the energy in situations when it is required to fuel cellular processes. Mitochondria are also involved in other cellular processes, including Ca2+homeostasis and signalling. Mitochondria contain a small amount of maternal DNA.
Mitochondria have two phospholipid bilayers, an outer membrane and an inner membrane. The inner membrane is intricately folded inwards to form numerous layers called cristae. The cristae contain specialised membrane proteins that enable the mitochondria to synthesise ATP. Between the two membranes lies the intermembrane space, which stores large proteins that are required for cellular respiration. Within the inner membrane is the perimitochondrial space, which contains a jelly-like matrix. This matrix contains a large quantity of ATP synthase.
Mitochondrial disease, or mitochondrial disorder, refers to a group of disorders that affect the mitochondria. When the number or function of mitochondria in the cell are disrupted, less energy is produced and organ dysfunction results.

Patellar dislocation is a disabling musculoskeletal disorder which predominantly affects younger people who are engaged in multidirectional physically active pursuits. Conservative (non-operative) treatment is the treatment of choice for FTPD (first time patellar dislocation). Quadriceps strengthening exercises are considered one of the principal management aims for people following FTPD. A United Kingdom (UK) survey of physiotherapy practice has shown that quadriceps strengthening and specific-vastus medialis obliquus (VMO) or distal vastus medialis (VM) muscle strengthening or recruitment exercises were two of the most frequently used interventions for this population. Specific VM exercises are favoured in some quarters based on the assumption that the VM has an important role in preventing excessive lateral patellar translation.

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.

A box and whisker plot is defined as a graphical method of displaying variation in a set of data. In most cases, a histogram analysis provides a sufficient display, but a box and whisker plot can provide additional detail while allowing multiple sets of data to be displayed in the same graph.

The procedure to develop a box and whisker plot comes from the five statistics below:

(1) Minimum value: The smallest value in the data set

(2) Second quartile: The value below which the lower 25% of the data are contained

(3) Median value: The middle number in a range of numbers

(4) Third quartile: The value above which the upper 25% of the data are contained

(5) Maximum value: The largest value in the data set

Oxygen saturation should be 94 – 98% in most acutely ill patients with a normal or low arterial carbon dioxide (PaCO2). In some clinical situations, however, like cardiac arrest and carbon monoxide poisoning, it is more appropriate to aim for the highest possible oxygen saturation until the patient is stable.

An increased affinity of haemoglobin for oxygen, shown by a left shift in the oxygen dissociation curve, is caused in the lungs by a rise in pH, a fall in PCO2,a decrease in temperature and a decrease in 2,3 -DPG. Carbon monoxide (CO) binds 240 times more strongly than O2to haemoglobin and by occupying O2-binding sites, reduces oxygen capacity. CO also increases oxygen affinity, shifting the oxygen haemoglobin curve to the left and making O2release to tissues more difficult.

Angina pectoris is the most common symptom of ischemic heart disease and presents with chest pain relieved by rest and nitro-glycerine.

Nitrates are the first-line treatment to relieve chest pain caused by angina. The commonly used nitrates are:
1. Glyceryl trinitrate
2. Isosorbide dinitrate

The nitrate drugs are metabolized in the following steps:
1. Release Nitrite ions (NO2-), which are then converted to nitric oxide (NO) within cells.
2. NO activates guanylyl cyclase, which causes an increase in the intracellular concentration of cyclic guanosine-monophosphate (cGMP) in vascular smooth muscle cells.
3. Relaxation of vascular smooth muscle.

Although nitrates are potent coronary vasodilators, their principal benefit in the management of angina results from a predominant mechanism of venous dilation:
– Bigger veins hold more blood
– Takes blood away from the left ventricle
– Lowers LVEDV (preload), LA pressure
– Less pulmonary oedema → improved dyspnoea

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

Nitrates are used in the treatment of angina pectoris and the prevention of myocardial ischaemia. Commonly used examples of nitrates are glyceryl trinitrate and isosorbide dinitrate. Unwanted effects, however, are common and can limit therapy, particularly when angina is severe or when patients are unusually sensitive to the effects of nitrates.
The following are common or very common side effects of nitrates
Arrhythmias
Asthenia
Cerebral ischaemia
Dizziness
Drowsiness
Flushing
Headache
Hypotension
Nausea and vomiting
Diarrhoea, syncope and cyanosis can occur, but these are rare side effects. Dry eyes, bradycardia and metabolic acidosis have not been reported.

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

Epstein-Barr virus causes infectious mononucleosis which is a clinical entity characterized by sore throat, cervical lymph node enlargement, fatigue and fever.

It is accompanied by atypical large peripheral blood lymphocytes. These atypical lymphocytes, also known as Downey cells, are actually activated CD8 T lymphocytes, most of which are responding to EBV-infected cells.

Within the central portion of the tooth lies the dental pulp. The pulp chamber provides mechanical support and functions as a barrier from external stimuli and the oral microbiome. The dental pulp is a unique tissue that is richly innervated and has an extensive microvascular network. Maintaining its vitality increases both the mechanical resistance of the tooth and the long-term survival. The junctional epithelium forms a band around the tooth at the base of the gingival sulcus, sealing off the periodontal tissues from the oral cavity.