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 missFamilial aldosteronism – a rare group of inherited conditions affecting the adrenal glandsThe causes of secondary hyperaldosteronism include:Drugs – diureticsObstructive renal artery disease – renal artery stenosis and atheromaRenal vasoconstriction – occurs in accelerated hypertensionOedematous disorders – heart failure, cirrhosis and nephrotic syndromePatients are often asymptomatic. When clinical features are present, the classically described presentation of hyperaldosteronism is with:HypertensionHypokalaemiaMetabolic alkalosisSodium levels can be normal or slightly raisedOther, less common, clinical features include:LethargyHeadachesMuscle weakness (from persistent hypokalaemia)Polyuria and polydipsiaIntermittent paraesthesiaTetany 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. BAHOther investigations that can help to distinguish between an adrenal adenoma and adrenal hyperplasia include:CT scanMRI scanSelective adrenal venous sampling

Angiotensin II acts to:Stimulate release of aldosterone from the zona glomerulosa of the adrenal cortex (which in turn acts to increase sodium reabsorption)Cause systemic vasoconstrictionCause vasoconstriction of the renal arterioles (predominant efferent effect thus intraglomerular pressure is stable or increased, thereby tending to maintain or even raise the GFR)Directly increase Na+reabsorption from the proximal tubule (by activating Na+/H+antiporters)Stimulate synthesis and release of ADH from the hypothalamus and posterior pituitary respectivelyStimulate the sensation of thirstPotentiate sympathetic activity (positive feedback)Inhibit renin production by granular cells (negative feedback)

Compressive causes of CN III palsy cause early pupillary dilatation because the parasympathetic fibres run peripherally in the nerve and are easily compressed. In diabetes mellitus the lesions are ischaemic rather than compressive and therefore typically affect the central fibres resulting in pupillary sparing.

Features of cell damage that tend to be reversible include: swelling of endoplasmic reticulum and some mitochondrialoss of ribosomescell stress responseFeatures of cell damage that tend to be irreversible include: loss of nucleolus, no ribosomes, swelling of all mitochondria, nuclear condensation, membrane blebs and holes, lysosome rupture, fragmentation of all inner membranes, nuclear breakup

25-year-old receives immunoglobulin and vaccination after cutting her hand on a drinking glass and not knowing her vaccination history.Because this is not a tetanus-prone wound, immunoglobulin is not recommended. Because you can’t be sure about her vaccination history, now is the best time to start a tetanus vaccination course to ensure coverage later in life. The first vaccination should be administered at the time of presentation; the patient’s own GP should then review the patient’s vaccination history and schedule the rest of the course as needed.8-year-old whose hand was cut with a kitchen knife, received her first round of vaccinations as a baby and a booster at the age of four – receives vaccination:The tetanus vaccinations for this child are up to date, and the next booster should not be given too soon. Immunoglobulin is not required because this is not a tetanus-prone wound.80-year-old diabetic, a rusty nail went through his shoe and into his foot while walking in the woods, and he was uncertain of his vaccination history – he received vaccination and immunoglobulin:A tetanus vaccination course may not have been completed by an 80-year-old UK resident (the vaccination was introduced in 1961). The vaccination should be given at a walk-in clinic, and the patient’s own GP should be contacted to confirm vaccination history and to schedule the rest of the course as needed. Because this is a tetanus-prone wound (puncture wound and potential soil contact), immunoglobulin would be recommended in a patient with incomplete tetanus vaccinations.A 28-year-old Polish man cuts his leg while working in the garden, the wound is heavily contaminated with soil, and his vaccination history is unknown – he receives vaccination:In a patient with an unknown vaccination history, this is a tetanus-prone wound. In this case, the best course of action would be to administer both the vaccination and immunoglobulin at the walk-in clinic, then contact the patient’s own GP to check his or her vaccination history and schedule the rest of the course as needed.30-year-old with a large amount of devitalized tissue in the torso from an electrical burn – has had all vaccinations, so no need for vaccination or immunoglobulin:Because this is a high-risk tetanus wound (with a lot of devitalized tissue), even if the patient has had a full course of vaccinations in the past, immunoglobulin is recommended. There is no need for any additional vaccinations.

Positive predictive value (PPV) is the proportion of individuals with a positive test result who actually have the disease.Positive predictive value (PPV) = a/(a+b) = 75/200= 0.375 = 37.5%This means there is a 37.5% chance, if the test is positive, that the patient actually has a DVT.

Flexor carpi radialis is innervated by the median nerve.

Features include: AnaemiaJaundice (caused by unconjugated bilirubin in plasma, bilirubin is absent from urine)Pigment gallstonesSplenomegalyAnkle ulcersExpansion of marrow with, in children, bone expansion e.g. frontal bossing in beta-thalassaemia majorAplastic crisis caused by parvovirus

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.

N. meningitidis, the causative agent of meningococcal meningitis, is considered both a commensal and a pathogen. It can be found in the surfaces of mucous membranes such as the nasopharynx and oropharynx. With this, it can be transmitted from a carrier to a new host via respiratory droplet secretions.

Megaloblastic anemia results from inhibition of DNA synthesis during red blood cell production. When DNA synthesis is impaired, the cell cycle cannot progress from the growth stage to the mitosis stage. This leads to continuing cell growth without division, which presents as macrocytosis, with an increase in mean corpuscular volume (MCV). The defect in red cell DNA synthesis is most often due to hypovitaminosis, specifically vitamin B12 deficiency or folate deficiency.Folate is an essential vitamin found in most foods, especially liver, green vegetables and yeast. The normal daily diet contains 200 – 250 μg, of which about 50% is absorbed. Daily adult requirements are about 100 μg. Absorption of folate is principally from the duodenum and jejunum. Stores of folate are normally only adequate for 4 months and so features of deficiency may be apparent after this time.

Arterial baroreceptors are located in the carotid sinus and aortic arch, and detect the mean arterial pressure (MAP). A decrease in MAP (such as in postural hypotension, or haemorrhage) reduces arterial stretch and decreases baroreceptor activity, resulting in decreased firing in afferent nerves travelling via the glossopharyngeal nerve (carotid sinus) and vagus nerve (aortic arch) to the medulla where the activity of the autonomic nervous system is coordinated. Sympathetic nerve activity consequently increases, causing an increase in heart rate and cardiac contractility, peripheral vasoconstriction with an increase in TPR, and venoconstriction with an increase in CVP and thus an increase in cardiac output and blood pressure. Parasympathetic activity (vagal tone) decreases, contributing to the rise in heart rate.

Coagulative necrosis is the most common form of necrosis characterised by the loss of cell nuclei, but with general preservation of the underlying architecture. Dead tissue is macroscopically pale and firm. This is the classic pattern seen in myocardial infarction.Liquefactive necrosis leads to complete loss of cellular structure and conversion into a soft, semi-solid mass. This is typically seen in the brain following cerebral infarction.Caseous necrosis is most commonly seen in tuberculosis. Histologically, the complete loss of normal tissue architecture is replaced by amorphous, granular and eosinophilic tissue with a variable amount of fat and an appearance reminiscent of cottage cheese.Gangrenous necrosis is necrosis with putrefaction of tissues due to exposure to air (dry gangrene) or infection (wet gangrene).

Anaemia is defined as a reduction in haemoglobin concentration below the normal range for the age and sex of the individual. Children tend to have lower haemoglobin than adults, and women tend to have lower haemoglobin than men. Anaemia may occur from an actual reduction in total circulating haemoglobin mass, or with an increase in plasma volume e.g. in pregnancy, causing a dilutional anaemia. After acute major blood loss, anaemia is not immediately apparent because total blood volume is reduced and it takes up to a day for plasma volume to be replaced and hence the degree of anaemia to become apparent. The initial clinical features in acute haemorrhage are therefore a result of reduction in blood volume rather than that of anaemia. When anaemia develops slowly, the associated symptoms are often very mild as the body has time to adapt to the fall in haemoglobin. This involves mechanisms such as an increase in red cell 2,3 -diphosphoglycerate (2,3 – DPG), which shifts the oxygen dissociation curve to the right, allowing enhanced delivery of O2 to the tissues, and an increase in stroke volume and heart rate.

The interpretation of arterial blood gas (ABG) aids in the measurement of a patient’s pulmonary gas exchange and acid-base balance. The normal values on an ABG vary a little depending on the analyser, but they are roughly as follows:Variable RangepH 7.35 – 7.45PaO2 10 – 14 kPaPaCO2 4.5 – 6 kPaHCO3- 22 – 26 mmol/lBase excess -2 – 2 mmol/lThe patient’s history indicates that she has taken an overdose in this case. Because her GCS is 11/15 and she can communicate with slurred speech, she is clearly managing her own airway, there is no current justification for intubation.The following are the relevant ABG findings:Hypoxia (mild)pH has been lowered (acidaemia)PCO2 levels are low.bicarbonate in its natural stateLactate levels have increasedThe anion gap represents the concentration of all the unmeasured anions in the plasma. It is the difference between the primary measured cations and the primary measured anions in the serum. It can be calculated using the following formula:Anion gap = [Na+] – [Cl-] – [HCO3-]The reference range varies depending on the technique of measurement, but it is usually between 8 and 16 mmol/L.The following formula can be used to compute her anion gap:Anion gap = [143] – [99] – [22]Anion gap = 22As a result, it is clear that she has a metabolic acidosis with an increased anion gap.The following are some of the causes of type A and type B lactic acidosis:Type A lactic acidosisType B lactic acidosisShock (including septic shock)Left ventricular failureSevere anaemiaAsphyxiaCardiac arrestCO poisoningRespiratory failureSevere asthma and COPDRegional hypoperfusionRenal failureLiver failureSepsis (non-hypoxic sepsis)Thiamine deficiencyAlcoholic ketoacidosisDiabetic ketoacidosisCyanide poisoningMethanol poisoningBiguanide poisoning

Actions of adrenaline:Cardiovascular system- Increased rate and force of cardiac contraction- Vasoconstriction of vessels in skin, mucous membranes and splanchnic bed- Vasodilation of skeletal muscle vessels- Increased cardiac output and blood pressureRespiratory system- Bronchodilation- Increased ventilation rateGastrointestinal system- Smooth muscle relaxation- Contraction of sphincters- Metabolism- Decreased insulin release- Increased glucagon release- Increased thermogenesis- Increased glycolysis- Increased lipolysisEye- Pupillary dilation

An exudate is an inflammatory fluid emanating from the intravascular space due to changes in the permeability of the surrounding microcirculation.Some common causes of exudates are: pneumonia, empyema, lung cancer, breast cancer, cancer of the pleura, SLE, rheumatoid arthritis, pericarditis, subphrenic abscess, chylothorax.Myxoedema, nephrotic syndrome, congestive cardiac failure, and liver cirrhosis all cause TRANSUDATE.

Testes are retroperitoneal organs and its lymphatic drainage is to the lumbar and para-aortic nodes along the lumbar vertebrae.The scrotum is the one which drains into the nearby superficial inguinal nodes.The glans penis and clitoris drains into the deep inguinal lymph nodes.

125 mg PO q6hr for 10 days is indicated for treatment of Clostridium difficile (C. difficile)-associated diarrhoea

Entonox is a mixture of 50% Oxygen and 50% nitrous oxide and is given in an inhaled form as a quick form of analgesia. Entonox causes non-competitive inhibition of NMDA (N-methyl-D-aspartate) receptors, which are a subtype of the glutamate receptor. It is stored in blue and white cylinders and administered via a pressure regulator and demand valve. The administration of this medicine reduces pain and anxiety in paediatric and dental procedures ands during labour. Effects are apparent after 20 seconds, and peak action occurs after 3 to 5 minutes as it is a drug with a rapid onset and the patient will also recover rapidly from its effects. Entonox is widely used as it does not accumulate in the body and does not cause many side effects. However, a notable side effect is the inhibition of Vitamin B12 synthesis.