Gentamicin, an aminoglycoside antibiotic, acts by binding to the 30S subunit of the bacterial ribosome inhibiting the binding of aminoacyl-tRNA, and thus prevents initiation of protein synthesis.

Gentamicin is given by injection because it is NOT absorbed orally.

It is excreted in the kidneys by glomerular filtration

Gentamicin is not to be used for the treatment of Neisseria meningitidis, Neisseria gonorrhoea, or Legionella pneumophila.There is a risk of patient going into shock from lipid A endotoxin release.

Two of its most notable side effects are hearing loss reversible nephrotoxicity and which are both dose-related and levels should be monitored in patients.

Homeostasis is the property of a system in which variables are regulated so that internal conditions remain relatively constant and stable. Homeostasis is achieved by a negative feedback mechanism.

Negative feedback occurs based upon a set point through receptors, comparators and effectors.

The ‘set point’ is a NARROW range of values within which normal function occurs.

The two body systems that regulate homeostasis are the Nervous system and the Endocrine system.

The smooth muscle of the uterus becomes more active towards the end of pregnancy. This is a POSITIVE feedback.

Throughout the airways, there are irritant receptors which are located between epithelial cells which are made of rapidly adapting afferent myelinated fibres in the vagus nerve. A cough is as a result of receptor stimulation located in the trachea, hyperpnoea is as a result of receptor stimulation in the lower airway. Stimulation may also result in reflex bronchial and laryngeal constriction. Many factors can stimulate irritant receptors. These include irritant gases, smoke and dust, airway deformation, pulmonary congestion, rapid inflation/deflation and inflammation. Deep augmented breaths or sighs seen every 5 – 20 minutes at rest are due to stimulation of these irritant receptors. This reverses the slow lung collapse that occurs in quiet breathing.

A histogram is used to demonstrate the distribution of continuous quantitative data. It is a very familiar graphical display device for representing the distribution of a single batch of data. The range of the data is divided into class intervals or bins, and the number of values falling into each interval is counted. The histogram then consists of a series of rectangles whose widths are defined by the class limits implied by the binwidths, and whose heights depend on the number of values in each bin. Histograms quickly reveal such attributes of the data distribution as location, spread, and symmetry. If the data are multimodal (i.e., more than one “hump” in the distribution of the data), this is quickly evident as well.

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.

An opsonin is any molecule that enhances phagocytosis by marking an antigen for an immune response, for example, immunoglobulin or complement. Opsonisation is the molecular mechanism whereby molecules, microbes, or apoptotic cells are chemically modified to have a stronger attraction to the cell surface receptors on phagocytes and natural killer cells. With the antigen coated in opsonins, binding to immune cells is greatly enhanced. Opsonisation also mediates phagocytosis via signal cascades from cell surface receptors.

Nearly 95% of ectopic pregnancies are implanted in the various segments of the fallopian tube and give rise to fimbrial, ampullary, isthmic, or interstitial tubal pregnancies. The ampulla is the most frequent site, followed by the isthmus. The remaining 5% of non tubal ectopic pregnancies implant in the ovary, peritoneal cavity, cervix, or prior caesarean scar.

A study published in the Cochrane Database of Systematic Reviews in 2010 found that a single 1000-mg dose of aspirin is effective in treating acute migraine. It was discovered that 24 percent of aspirin users were pain-free after two hours, compared to 11 percent of placebo users. Because the BNF recommends a maximum dose of 900 mg for analgesia and most non-proprietary aspirin comes in a dose of 300 mg, a dose of 900 mg is frequently prescribed in the UK.

Because aspirin is not recommended for children under the age of 16 due to the risk of Reye’s syndrome, it would be inappropriate to give it to the 12-year-old with the viral URTI.

For uncomplicated dental pain, aspirin is an acceptable option, but not for patients who are taking warfarin. The combination of aspirin’s antiplatelet action and warfarin’s anticoagulation properties puts the patient at high risk of bleeding. Furthermore, aspirin can deplete the therapeutic levels of warfarin by displacing it from plasma proteins. It would be better to use another NSAID or analgesic.

In gout, aspirin should be avoided because it reduces urate clearance in the urine and interferes with the action of uricosuric agents. Naproxen, diclofenac, and indomethacin are better options.

Although aspirin is useful for inflammatory pains, the dose of aspirin required for an adequate analgesic effect in severe pain is associated with significant side effects. Naproxen would be a better first-line treatment option.

Mannitol is the most widely used osmotic diuretic that is most commonly used to reduce cerebral oedema and intracranial pressure.
It is recommended to use mannitol for the reduction of CSF pressure/cerebral oedema in a dose of 0.25-2 g/kg as an intravenous infusion over 30-60 minutes. This can be repeated 1-2 times after 4-8 hours if needed.

Mannitol has several contraindications and some of them are listed below:
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

Examples of type II reactions include:
Incompatible blood transfusions
Haemolytic disease of the newborn
Autoimmune haemolytic anaemias
Goodpasture’s syndrome
Rheumatic heart disease
Bullous pemphigoid

Etomidate is a carboxylated imidazole derivative with a short half-life that is primarily used to induce anaesthesia.

It is thought to modulate fast inhibitory synaptic transmission in the central nervous system by acting on GABA type A receptors.
The dose for anaesthesia induction is 0.3 mg/kg. Etomidate takes 10-65 seconds to take effect after an intravenous injection, and it lasts 6-8 minutes. With repeated administration, the effects are non-cumulative.

The relative cardiovascular stability of etomidate is noteworthy. During induction, it causes less hypotension than thiopental sodium and propofol. It’s also linked to a quick recovery without the hangover.

Etomidate is a strong steroidogenesis inhibitor. The drug inhibits the enzymes responsible for adrenal 11 beta-hydroxylase and cholesterol cleavage, resulting in a decrease in cortisol and aldosterone synthesis for up to 24 hours after administration. It should not be used to maintain anaesthesia because of the adrenocortical suppression.

Other side effects associated with etomidate use include:
Vomiting and nausea
The injection causes pain (in up to 50 percent )
Phlebitis and thrombosis of the veins
Heart block and arrhythmias
Hyperventilation
Apnoea and respiratory depression
It has the potential to cause both hypo- and hypertension.
Critically ill patients have a higher mortality rate.

Metoclopramide is a dopamine-receptor antagonist. Blockade of inhibitory dopamine receptors in the GI tract may allow stimulatory actions of ACh at muscarinic synapses to predominate. Metoclopramide also blocks dopamine D2-receptors within the chemoreceptor trigger zone (CTZ). At high doses, it is also thought to have some 5-HT3antagonist activity.

As the common bile duct descends, it passes posterior to the first part of the duodenum before joining with the pancreatic duct from the pancreas, forming the hepatopancreatic ampulla (ampulla of Vater) at the major duodenal papilla, located in the second part of the duodenum. Surrounding the ampulla is the sphincter of Oddi, a collection of smooth muscle which can open to allow bile and pancreatic fluid to empty into the duodenum.

The clinical and laboratory findings, in this case, support a diagnosis of polycythaemia vera. A plethoric appearance, lethargy, splenomegaly and itching are common in this disease. Patients may also have gouty arthritis, Budd-Chiari syndrome, erythromelalgia, stroke, myocardial infarction or DVT. The average age for diagnosis of Polycythaemia Vera is 65-74 years. It is a haematological malignancy in which there is overproduction of all three cell lines. Venesection is the treatment of choice as it would cause a decrease in the number of red blood cells within the body.

Erythropoietin is given in patients with chronic renal failure as they lack this hormone. Administration of erythropoietin in such patients causes stimulation of the bone marrow to produce red blood cells.

Desferrioxamine is a chelating agent for iron and is given to patients with iron overload due to repeated blood transfusions, e.g. in thalassemia patients.

Penicillamine is a chelating agent for Copper, given as treatment in Wilson’s disease.

P wave = Atrial depolarisation
QRS complex = Ventricular depolarisation
T wave = Ventricular repolarisation

Phaeochromocytomas are catecholamine-secreting tumours which occur in about 0.1% of patients with hypertension. In about 90% of cases they arise from the adrenal medulla. The remaining 10%, which arise from extra-adrenal chromaffin tissue, are termed paragangliomas. Common presenting symptoms include one or more of headache, sweating, pallor and palpitations. Less commonly, patients describe anxiety, panic attacks and pyrexia. Hypertension, whether sustained or episodic, is present in at least 90% of patients. Left untreated phaeochromocytoma can occasionally lead to hypertensive crisis, encephalopathy, hyperglycaemia, pulmonary oedema, cardiac arrhythmias, or even death.

​Primary hyperparathyroidism the commonest cause of hypercalcaemia. It is commonest in women aged 50 to 60.
The commonest cause of primary hyperparathyroidism is a solitary adenoma of the parathyroid gland (approximately 85% of cases).

Primary hyperparathyroidism may present with features of hypercalcaemia such as polyuria, polydipsia, renal stones, bone and joint pain, constipation, and psychiatric disorders.

In primary Hyperparathyroidism:
PTH is elevated
Calcium is elevated
Phosphate is lowered

In secondary Hyperparathyroidism:
PTH is elevated
Calcium is low or low-normal
Phosphate is raised in CRF

In tertiary Hyperparathyroidism:
PTH is elevated
Calcium is elevated
Phosphate is lowered in CRF

A range of one SD above and below the mean (+/- 1 SD) includes 68.2% of the sample values.
A range of two SD above and below the mean (+/- 2 SD) includes 95.4% of the sample values.
A range of three SD above and below the mean (+/- 3 SD) includes 99.7% of the sample values.

The glomerular filtration membrane is composed of fenestrated capillary endothelium, basement membrane, and filtration slits. It is an organized, semipermeable membrane preventing the passage of most of the proteins into the urine.

The anatomical arrangement of the glomerular filtration membrane maximizes the surface area available for filtration. The arrangement of its arterioles results in high hydrostatic pressures and facilitates filtration.

Fenestrated capillary endothelium of the glomerular filtration membrane is with relatively large pores. It allows the free movement of plasma proteins and solutes but still restricts the movement of blood cells.

Filtration slits are the smallest filters and restrict the movement of plasma proteins but still allow free movement of ions and nutrients.

The glomerular basement membrane (GBM) is a critical component of the glomerular filtration membrane. Thus, it is not true that its absence will reduce the resistance of flow. The basement membrane is true to be more selective and contains negatively charged glycoproteins. However, it still allows free passage of water, nutrients, and ions. Severe structural abnormalities of the GBM can result in protein (albumin) leakage.

Relative risk (RR) is a ratio of the probability of an event occurring in the exposed group versus the probability of the event occurring in the non-exposed group.

RR can be computed as the absolute risk of events in the treatment group (ART), divided by the absolute risk of events in the control group (ARC).

RR = ART/ARC
RR = (10/500) / (25/500)
RR = 0.4

Recall that:

If RR < 1, then the intervention reduces the risk of the outcome.
If RR = 1, then the treatment has no effect on the outcome.
If RR > 1, then the intervention increases the risk of the outcome.