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
.

Peripheral nerves are nerves that lie outside the brain and spinal cord. Peripheral nerves readily regenerate, while central nervous system axonal injury does not spontaneously regenerate.
If there is damage to the axons of peripheral nerves, the nerves will regenerate at a slow rate of 1 mm per day. The slow regeneration process may lead to muscle atrophy before regeneration is complete.

Each peripheral nerve has a single cell body that supplies nutrients to the growing nerve fibre. The cell body does not undergo mitosis; only the axon is regenerated.

Schwann cells of the peripheral nervous system provide support for this process, while the analogous oligodendrocytes of the central nervous system do not. Schwann cells themselves do not cause regeneration. Schwann cells provide myelin for myelinated fibres and surround non-myelinated fibres with their cytoplasm.

If an axon is completely severed, as in the case of amputation, the axonal fibres regenerating from the cell body may never find their original route back to the muscle. Instead, they may form a traumatic neuroma, a painful collection of nerve fibres and myelin.

Calcium-channel blockers, also known as calcium antagonists, stop calcium from entering cells through the L-type calcium channel. This causes vascular smooth muscle in vessel walls to relax, resulting in a decrease in peripheral vascular resistance.
They can be used for a variety of things, including:
Hypertension
Angina
Atrial fibrillation
Migraine

Calcium-channel blockers can be divided into two categories: dihydropyridines and non-dihydropyridines. The basic chemical structure of these two classes differs, as does their relative selectivity for cardiac versus vascular L-type calcium channels.

Dihydropyridines have a high vascular selectivity and lower systemic vascular resistance and blood pressure. As a result, they’re frequently used to treat hypertension. Modified release formulations are also used to treat angina, but their powerful systemic vasodilator and pressure-lowering effects can cause reflex cardiac stimulation, resulting in increased inotropy and tachycardia, which can counteract the beneficial effects of reduced afterload on myocardial oxygen demand.

The suffix -dpine distinguishes dihydropyridines from other pyridines. Examples of dihydropyridines that are commonly prescribed include:
Amlodipine
Felodipine
Nifedipine
Nimodipine

The phenylalkylamine class and the benzothiazepine class are two subgroups of non-dihydropyridines.

Phenylalkylamines are less effective as systemic vasodilators because they are relatively selective for the myocardium. This group of drugs lowers myocardial oxygen demand and reverses coronary vasospasm, making them useful in the treatment of angina. They are also occasionally used to treat arrhythmias. A phenylalkylamine calcium-channel blocker like verapamil is an example.

In terms of selectivity for vascular calcium channels, benzothiazepines fall somewhere between dihydropyridines and phenylalkylamines. They can lower arterial pressure without producing the same level of reflex cardiac stimulation as dihydropyridines because they have both cardiac depressant and vasodilator effects. Diltiazem is the only benzothiazepine currently in clinical use.

ALL is the most common leukaemia in children, with a peak incidence between the ages of 2 and 5.
ALL has a wide range of clinical symptoms, but many children present with an acute illness that resembles coryza or a viral infection. ALL also has the following features:
Weakness and sluggishness all over
Muscle, joint, and bone pain that isn’t specific
Anaemia
Petechiae and unexplained bruising
Oedema
Lymphadenopathy
Hepatosplenomegaly

The following are typical features of a full blood count in patients with ALL:
Anaemia (normocytic or macrocytic)
Leukopenia affects about half of the patients (WCC 4 x 109/l).
Around 25% of patients have leucocytosis (WCC > 10 x 109/l).
Around 25% of patients have hyperleukocytosis (WCC > 50 x 109/l).
Thrombocytopaenia

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.

Flexor digitorum superficialis is the largest muscle of the anterior compartment of the forearm. It belongs to the superficial flexors of the forearm, together with pronator teres, flexor carpi radialis, flexor carpi ulnaris and palmaris longus. Some sources alternatively classify this muscle as an independent middle/intermediate layer of the anterior forearm, found between the superficial and deep groups.

Flexor digitorum superficialis is innervated by muscular branches of the median nerve, derived from roots C8 and T1 that arises from the medial and lateral cords of the brachial plexus. The skin that overlies the muscle is supplied by roots C6-8 and T1.

The primary arterial blood supply to the flexor digitorum superficialis is derived from the ulnar artery and its anterior recurrent branch. In addition to branches of the ulnar artery, the anterior and lateral surfaces of the muscle are supplied by branches of the radial artery; and its posterior surface also receives branches from the median artery.

The main function of flexor digitorum superficialis is flexion of the digits 2-5 at the proximal interphalangeal and metacarpophalangeal joints. Unlike the flexor digitorum profundus, flexor digitorum superficialis has independent muscle slips for all four digits. This allows it to flex the digits individually at their proximal interphalangeal joints. In addition, flexor digitorum superficialis aids the aids flexion of the wrist.

Hyperacusis is increased acuity of hearing with hypersensitivity to low tones resulting from paralysis of the stapedius muscle, innervated by the facial nerve. General sensation to the face and to the anterior two-thirds of the tongue is carried by the divisions of the trigeminal nerve (although taste to the anterior two-thirds of the tongue is supplied by the facial nerve). Eye movements are mediated by the oculomotor, trochlear and abducens nerve. Ptosis results from paralysis of the levator palpebrae superioris, innervated by the oculomotor nerve, or the superior tarsal muscle, innervated by the sympathetic chain.

An overdose of levothyroxine can happen by accident or on purpose. Intentional overdosing is sometimes done to lose weight, but it can also happen in patients who are suicidal. The development of thyrotoxicosis, which can lead to excited sympathetic activity and high metabolism syndrome, is the main source of concern. The time between ingestion and the emergence of clinical features associated with an overdose is often quite long.

After a levothyroxine overdose, the majority of patients are asymptomatic. Symptoms and signs are usually only seen in patients who have taken more than 10 mg of levothyroxine in total.

The following are the most commonly seen clinical features in patients developing clinical features:
Tremor
Agitation
Sweating
Insomnia
Headache
Increased body temperature
Increased blood pressure
Diarrhoea and vomiting
Less common clinical features associated with levothyroxine overdose include:
Seizures
Acute psychosis
Thyroid storm
Tachycardia
Arrhythmias
Coma

The continued absorption of the ingested levothyroxine causes a progressive rise in both total serum T4 and total serum T3 levels in the first 24 hours after an overdose. However, in some cases, the biochemical picture is completely normal. Thyroid function tests are not always recommended after a thyroxine overdose. Although elevated thyroxine levels are common, they have little clinical significance and have no impact on treatment. Following a levothyroxine overdose, the following biochemical features are common:
T4 and T3 levels in the blood are elevated.
Free T4 and Free T3 levels are higher.
TSH levels in the blood are low.
If the patient is cooperative and more than 10 mg of levothyroxine has been consumed, activated charcoal can be given (i.e., likely to become symptomatic)
Within an hour of ingestion, the patient presents.

The treatment is mostly supportive and aimed at managing the sympathomimetic symptoms that come with levothyroxine overdose. If beta blockers aren’t an option, try propranolol 10-40 mg PO 6 hours or diltiazem 60-180 mg 8 hours.

B-cells (20% of lymphocytes) mature in the bone marrow and circulate in the peripheral blood until they undergo recognition of antigen. B-cell immunoglobulin molecules synthesised in the cell are exported and bound to the surface membrane to become the B-cell receptor (BCR) which can recognise and bind to a specific antigen (either free or presented by APCs). The BCR is also important for antigen internalisation, processing and presentation to T helper cells. Most antibody responses require help from antigen-specific T helper cells (although some antigens such as polysaccharide can lead to T-cell independent B-cell antibody production). When the B-cell is activated, the receptor itself is secreted as free soluble immunoglobulin and the B-cell matures into a memory B-cell or a plasma cell (a B-cell in its high-rate immunoglobulin secreting state). Plasma cells are non-motile and are found predominantly in the bone marrow or spleen. Most plasma cells are short-lived (1 – 2 weeks) but some may survive much longer. A proportion of B-cells persist as memory cells, whose increased number and rapid response underlies the augmented secondary response of the adaptive immune system.

Depression of the eyeball is produced by the inferior rectus and the superior oblique muscles.

The maximum daily dose of paracetamol in an adult is 4 grams. Doses greater than this can lead to hepatotoxicity and, less frequently, acute kidney injury. Early symptoms of paracetamol toxicity include nausea, vomiting, and abdominal pain, and usually settle within 24 hours. Symptoms of liver damage include right subcostal pain and tenderness, and this peaks 3 to 4 days after paracetamol ingestion. Other signs of hepatic toxicity include encephalopathy, bleeding, hypoglycaemia, and cerebral oedema.

Amitriptyline is a tricyclic antidepressant (TCA) that is most commonly used to treat depression, but it can also be used to treat anxiety disorders, chronic pain, and attention deficit hyperactivity disorder (ADHD). It inhibits reuptake, raising serotonin and noradrenaline levels while also inhibiting acetylcholine action.

TCAs have a number of drawbacks, including:
Acute Porphyria
Arrhythmias
During bipolar disorder’s manic phase
Heart block
After a myocardial infarction, there is an immediate recovery period.

TCA levels in breast milk are too low to be harmful, and use can be continued while breastfeeding.

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.

IV Lidocaine is indicated in Ventricular Arrhythmias or Pulseless Ventricular Tachycardia (after defibrillation, attempted CPR, and vasopressor administration)

Innate immunity, also called non-specific immunity, refers to the components of the immune system naturally present in the body at birth.

The components of innate immunity include:
1) Natural Killer Cells
2) Neutrophils
3) Macrophages
4) Mast Cells
5) Dendritic Cells
6) Basophils.

Acquired or adaptive immunity is acquired in response to infection or vaccination. Although the response takes longer to develop, it is also a more long-lasting form of immunity.

The components of this system include:
1) T lymphocytes
2) B lymphocytes
3) Antibodies

The lumbar plexus gives rise to several branches which supply various muscles and regions of the posterior abdominal wall and lower limb. These branches include the Iliohypogastric, ilioinguinal, genitofemoral, lateral femoral cutaneous, femoral and obturator nerves.

In addition, the lumbar plexus gives off muscular branches from its roots, a branch to the lumbosacral trunk and occasionally an accessory obturator nerve.

This patient with a 150% rise of creatinine above baseline within 7 days has stage 2 Acute kidney injury (AKI).

AKI stages are as follows:
Stage 1
Creatinine rise of 26 micromole/L or more within 48 hours, or
Creatinine rise of 50-99% from baseline within 7 days (1.5-1.99 x baseline),or
Urine output <0.5 mL/kg/hour for more than 6 hours Stage 2
Creatinine rise of 100-199% from baseline within 7 days (2.0-2.99 x baseline),or
Urine output <0.5 mL/kg/hour for more than 12 hours Stage 3
Creatinine rise of 200% or more from baseline within 7 days (3.0 or more x baseline), or
Creatinine rise to 354 micromole/L or more with acute rise of 26 micromole/L or more within 48 hours or 50% or more rise within 7 days, or
Urine output <0.3 mL/kg/hour for 24 hours or anuria for 12 hours

Damage to the Wernicke’s speech area in the temporal lobe can result in a receptive dysphasia. Hemispatial neglect is most likely to occur in a lesion of the parietal lobe. Homonymous hemianopia is most likely to occur in a lesion of the occipital lobe. Expressive dysphasia is most likely to occur in a lesion of the Broca speech area in the frontal lobe. Conjugate eye deviation towards the side of the lesion is most likely to occur in a lesion of the frontal lobe.

Cardiac myocytes contract by excitation-contraction coupling, just like skeletal myocytes. Heart myocytes, on the other hand, utilise a calcium-induced calcium release mechanism that is unique to cardiac muscle (CICR). The influx of calcium ions (Ca2+) into the cell causes a ‘calcium spark,’ which causes more ions to be released into the cytoplasm.

An influx of sodium ions induces an initial depolarisation, much as it does in skeletal muscle; however, in cardiac muscle, the inflow of Ca2+ sustains the depolarisation, allowing it to remain longer. Due to potassium ion (K+) inflow, CICR causes a plateau phase in which the cells remain depolarized for a short time before repolarizing. Skeletal muscle, on the other hand, repolarizes almost instantly.

The release of Ca2+ from the sarcoplasmic reticulum is required for calcium-induced calcium release (CICR). This is mostly accomplished by ryanodine receptors (RyR) on the sarcoplasmic reticulum membrane; Ca2+ binds to RyR, causing additional Ca2+ to be released.

Enterochromaffin-like cells (ECL cells) are a type of neuroendocrine cell located beneath the epithelium in the stomach glands. They’re most typically located near the parietal cells of the stomach. The ECL cells’ primary role is to produce histamine, which stimulates the formation of stomach acid by the parietal cells.

The table below summarizes the many cell types found in the stomach, as well as the substances secreted by each cell type and the function of the secretion:

Cell type/ Substance secreted/ Function of secretion
Parietal cells/ Hydrochloric acid/ Kills microbes and activates pepsinogen
Parietal cells/ Intrinsic factor/Binds to vitamin B12 and facilitates its absorption
Chief cells/ Pepsinogen/ Protein digestion
Chief cells/ Gastric lipase/ Fat digestion
G-cells/ Gastrin/ Stimulates gastric acid secretion
Enterochromaffin-like cells (ECL cells) /Histamine/ Stimulates gastric acid secretion
Mucous-neck cells/ Mucous and bicarbonate/ Protects stomach epithelium from acid
D-cells/ Somatostatin/ Inhibits gastric acid secretion

Approximately one-third of patients who suffer DVT or PE have an identifiable heritable risk factor, although additional risk factors are usually present when they develop the thrombosis. The history of a spontaneous DVT in a close relative increases an individual’s risk of DVT even if no known genetic predisposition can be identified.

Noradrenaline (the sympathetic neurotransmitter) is a positive inotrope; it binds to β1-adrenoceptors on the membrane and causes increased Ca2+entry via L-type channels during the AP and thus increases Ca2+release from the SR. Noradrenaline also increases Ca2+sequestration into the SR and thus more Ca2+is available for the next contraction. Cardiac glycosides (e.g. digoxin) slow the removal of Ca2+from the cell by inhibiting the membrane Na+pump which generates the Na+gradient required for driving the export of Ca2+; consequently the removal of Ca2+from the myocyte is slowed and more Ca2+is available for the next contraction. Acidosis is negatively inotropic, largely because H+competes for Ca2+binding sites.

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.

Pancreatic exocrine secretion is controlled by:
Parasympathetic stimulation which enhances secretion of both the enzyme and aqueous components
Sympathetic stimulation which inhibits pancreatic secretion
Secretin which stimulates secretion of the alkaline-rich fluid from ductal cells
Cholecystokinin which stimulates secretion of the enzyme-rich fluid from acinar cellsSomatostatin which inhibits secretion from both acinar and ductal cells
Gastrin which stimulates pancreatic acinar cells to secrete digestive enzymes

Natural killer (NK) cells are cytotoxic CD8 positive cells that lack the T-cell receptor. They are large cells with cytoplasmic granules. NK cells are designed to kill target cells that have a low level of expression of HLA class I molecules, such as may occur during viral infection or on a malignant cell. NK cells do this by displaying several receptors for HLA molecules on their surface. When HLA is expressed on the target cell these deliver an inhibitory signal into the NK cell. When HLA molecules are absent on the target cell this inhibitory signal is lost and the NK cell can then kill its target. In addition, NK cells display antibody-dependent cell-mediated cytotoxicity. In this, antibody binds to antigen on the surface of the target cell and then NK cells bind to the Fc portion of the bound antibody and kill the target cell.

A likelihood ratio is a measure of the diagnostic value of a test. Likelihood ratios show how many times more likely patients with a disease are to have a particular test result than patients without the disease. Likelihood ratios are more useful than predictive values because they are calculated from sensitivity and specificity and therefore remain constant even when the prevalence of the disorder changes.

The endocervix is the most common site of Neisseria gonorrhoeae infection in women. Symptoms of infection, when present, include dysuria, cervical discharge, and lower abdominal pain. However, 50% of cases in women may be asymptomatic leading to complications such as pelvic inflammatory disease (PID), which may cause sterility, ectopic pregnancy, or perihepatitis.

PID is also known as Fitz-Hugh-Curtis syndrome is defined as an inflammation of the upper genital tract due to an infection in women. The disease affects the uterus, fallopian tubes, and ovaries. It is typically an ascending infection, spreading from the lower genital tract.

The recommended intramuscular or oral regimens for PID are as follows:

Ceftriaxone at 500 mg IM in a single dose (for persons weighing ≥150 kg, administer 1 g of ceftriaxone); plus doxycycline at 100 mg PO BID for 14 days with metronidazole at 500 mg PO BID for 14 days.

Digoxin does not cause hypokalaemia, but hypokalaemia does potentiate digoxin toxicity. The adverse effects of digoxin are frequently due to its narrow therapeutic window and include:
Cardiac adverse effects – Sinoatrial and atrioventricular block, Premature ventricular contractions, PR prolongation and ST-segment depression
Nausea, vomiting and diarrhoea
Blurred or yellow vision
CNS effects – weakness, dizziness, confusion, apathy, malaise, headache, depression, psychosis
Thrombocytopenia and agranulocytosis (rare)
Gynaecomastia in men in prolonged administration

The stomach produces gastric acid, which is a digesting fluid. The stomach secretes about 2-3 litres every day. It is involved in tissue breakdown, the conversion of pepsinogen to active pepsin, and the creation of soluble salts with calcium and iron, and has a pH range of 1.5-3.5. It also serves as an immune system by destroying microbes.

The following substances are found in gastric acid:
Water
Acid hydrochloride
Pepsinogen
mucous
Intrinsic factor

The parietal cells in the proximal 2/3 (body) of the stomach release gastric acid. The concentration of hydrogen ions in parietal cell secretions is 1-2 million times that of blood. Chloride is released against both a concentration and an electric gradient, and active transport is required for the parietal cell to produce acid.

The following is how stomach acid is secreted:

1. Gastric acid secretion is dependent on the H+/K+ ATPase (proton pump) situated in the canalicular membrane. The breakdown of water produces hydrogen ions within the parietal cell. The hydroxyl ions produced in this reaction mix quickly with carbon dioxide to generate bicarbonate ions. Carbonic anhydrase is the enzyme that catalyses this process.

2. In return for chloride, bicarbonate is carried out of the basolateral membrane. The ‘alkaline tide’ occurs when bicarbonate is released into the bloodstream, resulting in a modest rise in blood pH. The parietal cell’s intracellular pH is maintained by this procedure. Conductance channels carry chloride and potassium ions into the lumen of canaliculi.

3. Through the action of the proton pump, hydrogen ions are pushed out of the cell and into the lumen in exchange for potassium; potassium is thus efficiently recycled.

4. The canaliculi accumulate osmotically active hydrogen ions, which creates an osmotic gradient across the membrane, allowing water to diffuse outward.

The Auerbach’s plexus, also known as the myenteric plexus, is a collection of ganglia that controls peristalsis and is located in the gut wall.

In the muscular layer of the wall, it is located between the circular and longitudinal muscle layers. It is a linear network of linked neurons that runs the length of the gastrointestinal system. The myenteric plexus generates an increase in gut wall tone and the strength of rhythmical contractions when stimulated.