A case-control study is a longitudinal, retrospective, observational study which investigates the relationship between a risk factor and one or more outcomes. This is done by selecting patients who already have a specific disease (cases), matching them to patients who do not (controls) and then collecting data from the patients to compare past exposure to a possible risk factor. The usual outcome measure is the odds ratio.

Isoniazid is an antibiotic used in the treatment of tuberculosis. It can cause acute, dose-dependent, hepatitis but is not a recognised cause of cholestatic jaundice.

The drugs that cause cholestatic jaundice are the following:
1. Nitrofurantoin
2. Erythromycin
3. Cephalosporins
4. Verapamil
5. NSAIDs
6. ACE inhibitors
7. Tricyclic antidepressants
8. Phenytoin
9. Azathioprine
10. Carbamazepine
11. Oral contraceptive pills
12. Diazepam
13. Ketoconazole
14. Tamoxifen

Intrinsic factor, produced by the parietal cells of the stomach, is essential for the absorption of vitamin B12 from the terminal ileum.
After a gastrectomy, the absorption of vitamin B12 is markedly reduced, and a deficiency will occur.

ADH binds V2 receptors on renal principal cells in the late distal tubule and collecting ducts, raising cAMP levels and causing intracellular vesicles to fuse with the apical membrane. In their membrane these vesicles have water channels called aquaporins, which increase the water permeability allowing greater water reabsorption and concentration of urine. ADH also binds to V1 receptor receptors on vascular smooth muscle, causing vasoconstriction and enhancing the effect of aldosterone on sodium reabsorption in the distal tubule. ADH release is stimulated primarily by raised plasma osmolality detected by osmoreceptors in the anterior hypothalamus. Other factors that increase ADH release include: extracellular fluid volume depletion, angiotensin II, nausea, pain, stress, exercise, emotion, hypoglycaemia. ADH release is inhibited by low plasma osmolality, alcohol, caffeine, glucocorticoids and atrial natriuretic peptide (ANP). ADH deficiency (or an inadequate response to ADH) results in diabetes insipidus. Excess levels of ADH results in syndrome of inappropriate ADH secretion (SIADH).

Benzodiazepines are used to treat symptoms in patients with acute alcohol withdrawal syndrome.
Benzodiazepines are contraindicated in:
Respiratory depression
Marked neuromuscular respiratory weakness, such as unstable myasthenia gravis
Obstructive sleep apnoea syndrome (symptoms may be aggravated)
Severe hepatic impairment (the elimination half-life of diazepam may be prolonged; increased risk of coma)
Phobic or obsessional states, chronic psychosis or hyperkinesis (paradoxical reactions may occur).

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.

Hypokalaemia can occur with both thiazide and loop diuretics. The risk of hypokalaemia depends on the duration of action as well as the potency and is thus greater with thiazides than with an equipotent dose of a loop diuretic. Hypokalaemia is dangerous in severe cardiovascular disease and in patients also being treated with cardiac glycosides. Often the use of potassium-sparing diuretics avoids the need to take potassium supplements. In hepatic failure, hypokalaemia caused by diuretics can precipitate encephalopathy, particularly in alcoholic cirrhosis.

Amiodarone has a lot of potential toxic side effects, so it’s important to get a full clinical evaluation before starting treatment with it.

The following are some of the most common amiodarone side effects:

Arrhythmias
Corneal microdeposits
Hepatic disorders
Hyperthyroidism
Hypothyroidism
Hepatic disorders and jaundice
Nausea
Peripheral neuropathy
Respiratory disorders (including lung fibrosis)
Sleep disturbance
Skin reactions
QT prolongation

Amiodarone can cause optic neuritis, which is a very rare side effect. If this happens, the amiodarone should be stopped right away because it poses a risk of blindness.

Most people who take amiodarone develop corneal microdeposits, which go away once the medication is stopped and rarely cause vision problems.

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.

Parasympathetic preganglionic neurones originate in the brainstem from which they run in cranial nerves III, VII, IX and X and also from the second and third sacral segments of the spinal cord. Parasympathetic preganglionic neurones release acetylcholine into the synapse, which acts on cholinergic nicotinic receptors on the postganglionic fibre. Parasympathetic peripheral ganglia are generally found close to or within their target, whereas sympathetic peripheral ganglia are located largely in two sympathetic chains on either side of the vertebral column (paravertebral ganglia), or in diffuse prevertebral ganglia of the visceral plexuses of the abdomen and pelvis. Parasympathetic postganglionic neurones release acetylcholine, which acts on cholinergic muscarinic receptors.

The facial nerve (the labyrinthine segment) is the seventh cranial nerve, or simply CN VII. It emerges from the pons of the brainstem, controls the muscles of facial expression, and functions in the conveyance of taste sensations from the anterior two-thirds of the tongue.
Motor innervation of the nasal muscles of facial expression is provided by the facial nerve (CN VII).

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

Anti-nuclear antibodies are auto-antibodies directed against a variety of nuclear antigens. There are different staining patterns and each pattern is suggestive of a different disorder.

Speckled staining is suggestive of mixed connective tissue disease.

Nucleolar staining is suggestive of scleroderma, while homogenous staining is suggestive of lupus.

Anti-double stranded DNA is suggestive of SLE while anti-histone antibodies are suggestive of drug-induced lupus.

ELISA testing is cheaper but not the most accurate means of testing for ANAs. Indirect immunofluorescence testing is the most accurate.

The presence of ANAs in rheumatoid arthritis is suggestive of Felty’s syndrome. Felty’s syndrome is characterized by a combination of rheumatoid arthritis, splenomegaly and neutropenia.

Damage to the tibial nerve results in loss of plantarflexion of the ankle and weakness of inversion of the foot resulting in a shuffling gait, clawing of the toes and loss of sensation in its cutaneous distribution.

Anti-D is an IgG antibody that targets the antigen Rhesus D (RhD). Plasma from rhesus-negative donors who have been immunised against the anti-D-antigen is used to make anti-D immunoglobulin.

Only RhD negative women are given Anti-D Ig. Women who are RhD negative do not have the RhD antigen on their RBC. If a foetus has the RhD antigen (i.e. is RhD positive) and the mother is exposed to foetal blood, she may develop antibodies to RhD that pass through the placenta and attack foetal red cells (resulting in newborn haemolytic disease). Anti-D is given to bind and neutralise foetal red cells in the maternal circulation before an immune response is triggered. In the event of a sensitising event, 500 IU Anti-D Ig should be administered intramuscularly.

The following are examples of potentially sensitising events:
Birth
Haemorrhage during pregnancy
Miscarriage
Ectopic pregnancy
Death within the womb
Amniocentesis
Chorionic villus sampling
Trauma to the abdomen

The sooner anti-D is given in the event of a sensitising event, the better; however, it is most effective within 72 hours, and the BNF states that it is still likely to have some benefit if given outside of this time frame.

At 28 and 34 weeks, RhD negative women should receive routine antenatal prophylaxis. This is regardless of whether they have previously received Anti-D for a sensitising event during the same pregnancy.

Prophylactic anti-D is not necessary before 12 weeks gestation, as confirmed by scan, in uncomplicated miscarriage (where the uterus is not instrumented), or mild, painless vaginal bleeding, as the risk of foeto-maternal haemorrhage (FMH) is negligible. In cases of therapeutic termination of pregnancy, whether by surgical or medical means, 250 IU of prophylactic anti-D immunoglobulin should be given to confirmed RhD negative women who are not known to be RhD sensitised.

Cardiac muscle is striated, and the sarcomere is the contractile unit, similar to skeletal muscle. Contracture is mediated by the interaction of calcium, troponins, and myofilaments, much as it occurs in skeletal muscle. Cardiac muscle, on the other hand, differs from skeletal muscle in a number of ways.

In contrast to skeletal muscle cells, cardiac myocytes have a nucleus in the middle of the cell and sometimes two nuclei. The cells are striated because the thick and thin filaments are arranged in an orderly fashion, although the arrangement is less well-organized than in skeletal muscle.

Intercalated discs, which work similarly to the Z band in skeletal muscle in defining where one cardiac muscle cell joins the next, are a very significant component of cardiac muscle.

Adherens junctions and desmosomes, which are specialized structures that hold the cardiac myocytes together, are formed by the transverse sections. The lateral sections produce gap junctions, which join the cytoplasm of two cells directly, allowing for rapid action potential conduction. These critical properties allow the heart to contract in a coordinated manner, allowing for more efficient blood pumping.

Cardiac myocytes have the ability to create their own action potentials, which is referred to as myogenic’. They can depolarize spontaneously to initiate a cardiac action potential. Pacemaker cells, as well as the sino-atrial (SA) and atrioventricular (AV) nodes, control this.

The Purkinje cells and the cells of the bundle of His are likewise capable of spontaneous depolarization. While the bundle of His is made up of specialized myocytes, it’s vital to remember that Purkinje cells are not myocytes and have distinct characteristics. They are larger than myocytes, with fewer filaments and more gap junctions than myocytes. They conduct action potentials more quickly, allowing the ventricles to contract synchronously.
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.

Comparison of skeletal and cardiac muscle:
Skeletal muscle
Cardiac muscle
Striation
Striated but arrangement less organised
Multiple nuclei located peripherally
Usually single nucleus (but can be two), located centrally
Discs None
Intercalated discs
No Gap junctions
Gap junctions
No Pacemaker
Pacemaker
Electrical stimulation: Nervous system (excitation)
Pacemaker (excitation)

Molecular weight is the main factor in determining whether a substance is filtered or not – molecules < 7 kDa in molecular weight are filtered freely e.g. glucose, amino acids, urea, ions but larger molecules are increasingly restricted up to 70 kDa, above which filtration is insignificant. Negatively charged molecules are further restricted, as they are repelled by negative charges, particularly in the basement membrane. Albumin has a molecular weight of 69 kDa and is negatively charged, thus only very small amounts are filtered (and all of the filtered albumin is reabsorbed in the proximal tubule), whereas small molecules such as ions, glucose, amino acids and urea pass the filter without hindrance. This means that ultrafiltrate is virtually protein free, but otherwise has an identical composition of that of plasma. The epithelial lining of the Bowman's capsule consists of a single layer of cells called podocytes. The glomerular capillary endothelium is perforated by pores (fenestrations) which allow plasma components with a molecular weight of < 70 kDa to pass freely.

Calcium is stored in bones for nearly all of the body’s calcium, but it is also found in some cells (most notably muscle cells) and the blood. The average adult diet comprises roughly 25 mmol of calcium per day, of which the body absorbs only about 5 mmol.

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.

Kaplan-Meier estimate is one of the best options to be used to measure the fraction of subjects living for a certain amount of time after treatment. In clinical trials or community trials, the effect of an intervention is assessed by measuring the number of subjects survived or saved after that intervention over a period of time. The time starting from a defined point to the occurrence of a given event, for example death, is called as survival time and the analysis of group data as survival analysis.

The graph plotted between estimated survival probabilities/estimated survival percentages (on Y axis) and time past after entry into the study (on X axis) consists of horizontal and vertical lines.

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

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

Lysosomes are formed by the Golgi apparatus or the endoplasmic reticulum. Lysosome releases its enzymes and digests the cell when the cell dies.

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

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

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.

The collection of abnormalities found in these patients is referred to as a hyposplenic film.
The following features can be seen on hyposplenic blood films:
Howell-Jolly bodies
Heinz’s bodies
Target cells
RBCs with nuclei on occasion
Lymphocytosis
Macrocytosis
Acanthocytes
Teardrop cells, also known as dacrocytes, are named for their teardrop-shaped shape.

Dacrocytosis is a condition in which a large number of these cells are present. Myelofibrosis and beta thalassemia major both have dacrocytes, but hyposplenism does not.

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.

Lung compliance is defined as change in volume per unit change in distending pressure.

Lung compliance is calculated using the equation:
Lung compliance = ΔV / ΔP
Where:
ΔV is the change in volume
ΔP is the change in pleural pressure.

Static compliance is lung compliance in periods without gas flow, and is calculated using the equation:
Static compliance = VT / Pplat − PEEP
Where:
VT = tidal volume
Pplat = plateau pressure
PEEP = positive end-expiratory pressure

JVP Waveform in Cardiac Cycle Physiology: a wave Right atrial contraction causes atrial systole (end diastole). the c wave During right isovolumetric ventricular contraction, the tricuspid valve bulges into the right atrium, resulting in isovolumetric contraction (early systole). descent by x Rapid ventricular ejection (mid systole) is caused by a combination of right atrial relaxation, tricuspid valve downward movement during right ventricular contraction, and blood ejection from both ventricles. the v-wave Ventricular ejection and isovolumetric relaxation (late systole) occur as a result of venous return filling the right atrium. y lineage Ventricular filling occurs when the tricuspid valve opens, allowing blood to flow rapidly from the right atrium to the right ventricle.

Direct inguinal hernias are most often caused by a weakness in the muscles of the abdominal wall that develops over time, or are due to straining or heavy lifting.

A direct inguinal hernia protrudes through the Transversalis fascia.

A common cause of gastroenteritis, Salmonella enteritidis, and Salmonella typhi, which causes enteric fever, are both group D. Therefore, serotype D Salmonella species are most commonly associated with gastroenteritis.