Klebsiella is a Gram-negative, rod-shaped, non-motile bacteria. The absence of motility distinguishes Klebsiella spp. from most other members of the family Enterobacteriaceae.

K. pneumoniae is the most commonly isolated species and has the distinct feature of possessing a large polysaccharide capsule. The capsule offers the organism protection against phagocytosis and antimicrobial absorption,
contributing to its virulence.

Colonization of gram-negative bacilli in the respiratory tracts of hospitalized patients, particularly by K. pneumoniae, increases with the length of hospital stay. It is a frequent cause of lower respiratory tract infections among hospitalized patients and in immunocompromised hosts such as newborns,
elderly patients, and seriously ill patients on respirators.

Although Ca2+entry during the action potential (AP) is essential for contraction, it only accounts for about 25% of the rise in intracellular Ca2+. The rest is released from Ca2+stores in the sarcoplasmic reticulum (SR). In relaxation, about 80% of Ca2+is rapidly pumped back into the SR (sequestered) by Ca2+ATPase pumps. The Ca2+that entered the cell during the AP is transported out of the cell primarily by the Na+/Ca2+exchanger in the membrane. When more action potentials occur per unit time, more Ca2+enters the cell during the AP plateau, more Ca2+is stored in the SR, more Ca2+is released from the SR and thus more Ca2+is left inside the cell and greater tension is produced during contraction. Increased heart rate increases the force of contraction in a stepwise fashion as intracellular [Ca2+] increases cumulatively over several beats; this is the Treppe effect. Cardiac glycosides such as digoxin have a positive inotropic effect.

Aspirin (at analgesic doses) is contraindicated in:
People with a history of true hypersensitivity to aspirin or salicylates (symptoms of hypersensitivity to aspirin or salicylates include bronchospasm, urticaria, angioedema, and vasomotor rhinitis)
People with active or previous peptic ulceration
People with haemophilia or another bleeding disorder
Children younger than 16 years of age (risk of Reye’s syndrome)
People with severe cardiac failure
People with severe hepatic impairment
People with severe renal impairment

N.B. Owing to an association with Reye’s syndrome, aspirin-containing preparations should not be given to children under 16 years, unless specifically indicated, e.g. for Kawasaki disease.

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

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

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

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

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

The nephron’s blood flow is as follows:
Afferent arteriole – Glomerular capillary – Efferent arteriole – Peritubular capillary – Vasa recta – Afferent arteriole – Glomerular capillary – Efferent arteriole – Peritubular capillary – Vasa recta

The kidney is the only vascular network in the body with two capillary beds. With arterioles supplying and draining the glomerular capillaries, higher hydrostatic pressures at the glomerulus are maintained, allowing for better filtration. A second capillary network at the tubules enables for secretion and absorption in the tubules, as well as concentrating urine.

In the thick ascending limb is the part of the loop of Henle in which there is active reabsorption of Na+and Cl- ions from the tubular fluid. This occurs via the Na+/K+/2Cl-symporter on the apical membrane.
This mechanism is by:
1. Na+ions are transported across the basolateral membrane by Na+pumps and the Cl-ions by diffusion.
2. K+leaks back into the tubular fluid via apical ROMK K+channels which creates a positive charge.
3. This positive charge drives the reabsorption of cations (Na+, K+, Ca2+, Mg2+) through paracellular pathways.
4. Due to the thick ascending limb being impermeable to water, the tubular fluid osmolality is reduced by ion reabsorption, the interstitial fluid osmolality is increased, and an osmotic difference is created.

Doxycycline may be used for malaria prophylaxis and as an adjunct to quinine in the treatment of Plasmodium falciparum malaria.

Fibrinolysis is a normal haemostatic response to vascular injury. Plasminogen, a proenzyme in blood and tissue fluid, is converted to plasmin by activators either from the vessel wall (intrinsic activation) or from the tissues (extrinsic activation). The most important route follows the release of tissue plasminogen activator (TPA) from endothelial cells.

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

A carbuncle is a collection of individual boils clustered together.

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

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

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

Primary hyperaldosteronism occurs when there are excessive levels of aldosterone independent of the renin-angiotensin axis. Secondary hyperaldosteronism occurs due to high renin levels.
The causes of primary hyperaldosteronism include:
Adrenal adenoma (Conn’s syndrome) – the most common cause of hyperaldosteronism (,80% of all cases). These are usually unilateral and solitary and are more common in women.
Adrenal hyperplasia – this accounts for ,15% of all cases. Usually, bilateral adrenal hyperplasia (BAH) but can be unilateral rarely. More common in men than women.
Adrenal cancer – a rare diagnosis but essential not to miss
Familial aldosteronism – a rare group of inherited conditions affecting the adrenal glands
The causes of secondary hyperaldosteronism include:
Drugs – diuretics
Obstructive renal artery disease – renal artery stenosis and atheroma
Renal vasoconstriction – occurs in accelerated hypertension
Oedematous disorders – heart failure, cirrhosis and nephrotic syndrome
Patients are often asymptomatic. When clinical features are present, the classically described presentation of hyperaldosteronism is with:
Hypertension
Hypokalaemia
Metabolic alkalosis
Sodium levels can be normal or slightly raised
Other, less common, clinical features include:
Lethargy
Headaches
Muscle weakness (from persistent hypokalaemia)
Polyuria and polydipsia
Intermittent paraesthesia
Tetany and paralysis (rare)
Often the earliest sign of hyperaldosteronism is from aberrant urea and electrolytes showing hypokalaemia and mild hypernatraemia. If the patient is taking diuretics, and the diagnosis is suspected, these should be repeated after the patient has taken off diuretics.
If the diagnosis is suspected, plasma renin and aldosterone levels should be checked. Low renin and high aldosterone levels (with a raised aldosterone: renin ratio) is suggestive of primary aldosteronism.
If the renin: aldosterone ratio is high, then the effect of posture on renin, aldosterone and cortisol can be investigated to provide further information about the underlying cause of primary hyperaldosteronism. Levels should be measured lying at 9 am and standing at noon:
If aldosterone and cortisol levels fall on standing, this is suggestive of an ACTH dependent cause, e.g. adrenal adenoma (Conn’s syndrome)
If aldosterone levels rise and cortisol levels fall on standing, this is suggestive of an angiotensin-II dependent cause, e.g. BAH
Other investigations that can help to distinguish between an adrenal adenoma and adrenal hyperplasia include:
CT scan
MRI scan
Selective adrenal venous sampling