When there is a fall in ionised plasma calcium levels, the chief cells of the parathyroid glands are stimulated to secrete parathyroid hormone (PTH).

50% of extracellular calcium occurs as non-ionised, protein- (albumin-)bound calcium.

The degree of ionisation increases with low ph and decreases with high pH.

There is increased renal calcium excretion with secretion of calcitonin.

The common peroneal (fibular) nerve is a peripheral nerve in the lower limb. It arises of the L4-S2 nerve roots and has sensory and motor innervations:

Sensory: Provides innervation of the lateral leg and foot dorsum.

Motor: Provides innervation of the short head of the biceps femoris, as well as muscles of the anterior and lateral leg compartments.

It is the most commonly damaged nerve in the lower extremity, as it is easily compressed by a plaster cast or injured when the fibula is fractured.

Damage to the common peroneal nerve will result in loss of dorsiflexion at ankle (footdrop, as feet are permanently plantarflexed), with the accompanying high stepping gait.

The saphenous and sural nerve only provide sensory innervation.

The tibial nerve arises from the sciatic nerve (like the common peroneal), but it provides motor innervation to the posterior leg compartments and intrinsic foot muscles. Injury to the tibial nerve will cause loss of plantar flexion, toe flexion and weakened foot inversion.

Extreme hip flexion into the lithotomy or Lloyd-Davies position can result in stretch damage to the neurones (sciatic and obturator nerves) or by applying direct pressure (femoral nerve compression).

Insulin is the primary anabolic hormone that dominates regulation of metabolism during digestive phase. It promotes glucose uptake in skeletal myocytes and adipocytes, and other insulin-target cells. It promotes glycogenesis and inhibits gluconeogenesis.

Glucagon is the primary counterregulatory hormone that increases blood glucose levels, primarily through its effects on liver glucose output.

Similar to glucagon, growth hormone, catecholamines and corticosteroids are also counterregulatory factors released in response to decreased glucose concentrations. Growth hormone promotes glycogenolysis and inhibits gluconeogenesis; catecholamines stimulate glycogenolysis and gluconeogenesis; while corticosteroids stimulate glycogenesis and gluconeogenesis.

When the convulsion lasts for five or more than five minutes, or if there are recurrent episodes of convulsions in a 5 minute period without returning to the baseline, it is termed as Status Epilepticus.
The first priority in the patient with seizures is maintaining the airway, breathing, and circulation.

Guideline for the management of Status Epilepticus in children by Advanced Life Support Group is as follow:

Step 1 (Five minutes after the start of seizures):

If intravascular access is available start treatment with lorazepam 0.1 mg/kg IV
If no intravascular access then give buccal midazolam 0.5 mg/kg or rectal diazepam 0.5 mg/kg.

Step 2 (Ten minutes after the start of seizure):

If the convulsions continue then a second dose of benzodiazepine should be given. Senior should be called on-site and phenytoin should be prepared.
No more than two doses or benzodiazepines should be given (including any doses given before arrival at the hospital)
If still no IV access then obtain intraosseous access (IO).

Step 3 (Ten minutes after step 2)

Senior help along with anaesthetic/ICU help should be sought
Phenytoin 20 mg/kg IV over 20 minutes
If the seizure stops before the full dose of phenytoin is given then the infusion should be completed as this provides up to 24 hours of anticonvulsant effect
In children already receiving phenytoin as treatment for epilepsy then an alternative is phenobarbitone 20 mg/kg IV over five minutes
Once the phenytoin is started, senior staff may wish to give rectal paraldehyde 0.4 mg/kg although this is no longer included in the routine algorithm recommended by APLS.

Step 4 (20 minutes after step 3)

If 20 minutes after starting phenytoin the child remains in status epilepticus then rapid sequence induction of anaesthesia with thiopentone and a short acting paralysing agent is needed and the child transferred to paediatric intensive care.

The metabolism of drugs in the liver occurs in 3 phases

Phase I: This involves functionalization reactions, which are of 3 types, namely hydrolysis, oxidation and reduction reactions catalysed by the cytochrome P450 (CYP) enzymes.

Phase II: This involves conjugation or acetylation reactions. The goal is to create water soluble metabolites that can be excreted from the body.

The liver is the second largest organ. It’s smallest functional unit is the acinus which is divided into 3 zones:

Zone I (periportal): This zone receives the largest amount of oxygen supply as it is the closest to the blood vessels. It is the site of plasma protein synthesis.

Zone II (mediolobular): This is located between the portal triad and central vein.

Zone III (centrilobular): This is closest to the central vein and receives the least amount of oxygen supply.

Kupffer cells are specialized macrophages found in the periportal zone of the liver, and function to remove foreign particles and breakdown red blood cells via phagocytosis.

Ito cells are fat-storing liver cells found in the space of Disse. Their function is to take-uo, store and secrete retinoids, as well as manufacture and release proteins that make up the extracellular matrix.

The glucose molecule enters the Bowman’s capsule freely and becomes part of the filtrate.

All glucose is reabsorbed in the proximal convoluted tubule when blood glucose concentrations are below a certain threshold (approximately 11 mmol/L) (PCT). Active transportation makes this possible. In the proximal tubular cells, sodium/glucose cotransporters (SGLT1 and SGLT2) are the proteins responsible.

Glucose does not normally appear in the urine below the renal threshold.

The renal glucose threshold is not set in stone and is affected by a variety of factors, including GFR, TmG, and the quantity of splay.

The different absorptive and filtering capacities of individual nephrons cause splay, which is the rounding of a glucose reabsorption curve.

The SGLT proteins have a high affinity for glucose, but not an infinite affinity. As a result, some glucose may escape reabsorption before the TmG. A decrease in renal threshold may be caused by an increase in splay.

Because the filtered glucose load is reduced and the PCT can reabsorb all of the filtered glucose despite hyperglycaemia, a low GFR causes an increase in TmG. In contrast, lowering the TmG lowers the threshold because the tubules’ ability to reabsorb glucose is reduced.

A reduction in GFR caused by severe dehydration and reduced perfusion pressure is the most obvious cause of the discrepancy between plasma and urinary glucose in this scenario.

The following are some basic assumptions:

Extracellular fluid (ECF) makes up one-third of total body water (TBW), while intracellular fluid makes up the other two-thirds (ICF).
One-quarter of ECF is plasma, and three-quarters is interstitial fluid (ISF).
The volume receptors have a 7-10% blood volume change threshold. The osmoreceptors are sensitive to changes in osmolality of 1-2 percent.
Prior to the transfusion, the plasma osmolality is normal (between 287 and 290 mOsm/kg).
[Na+] in 0.9 percent N. saline is 154 mmol/L, which is similar to that of extracellular fluid. When given intravenously, this limits its distribution within the extracellular space, resulting in a plasma compartment:ISF volume ratio of 1:3.
In this time frame, one litre of 0.9 percent N. saline will increase plasma volume by about 250 mL, which could be the threshold for activation of the volume receptors in the atria, resulting in the release of atrial natriuretic peptide (ANP).

Because 0.9 percent N. saline is isosmotic, after a 1 L infusion, plasma osmolality will not change. No changes in antidiuretic hormone secretion will be detected by the hypothalamic osmoreceptors.

Because normal saline is protein-free, the oncotic pressure in the blood is slightly reduced after the saline infusion. As a result, fluid movement into the ISF is favoured (Starling’s hypothesis), and the lower oncotic pressure causes an immediate increase in the glomerular filtration rate (GFR) and a reduction in water reabsorption in the proximal tubule.

The flow of urine increases. There is no hormonal intermediary in this effect, so it is strictly local. Urine flow immediately increases. The fluid returns to the intravascular compartment, and urine flow continues until all of the transfused fluid has been excreted.

Blood pressure changes associated with a 1 L fluid infusion are unlikely to affect high-pressure baroreceptors in the carotid sinus.

The juxta-glomerular cells of the afferent arteriole are adjacent to the specialised cells (macula densa) of distal tubules. The sodium and chloride ions in the tubular fluid are detected by the macula densa. Renin release is inhibited when the tubular fluid contains too much sodium chloride. Hormonal changes take longer to manifest than physical changes that control glomerulotubular balance.
Hypertonic saline, not 0.9 percent N saline, is an osmotic diuretic.

A person remaining at high altitudes for days, weeks, or years becomes more and more acclimatized to the low PO2, so it causes fewer deleterious effects on the body.

After acclimatization, it becomes possible for the person to work harder without hypoxic effects or to ascend to still higher altitudes. The principal means by which acclimatization comes about are (1) a great increase in pulmonary ventilation, (2) increased numbers of red blood cells, (3) diffusing capacity of the lungs, (4) increased vascularity of the peripheral tissues, and (5) increased ability of the tissue cells to use oxygen despite low PO2.

The cardiac output often increases as much as 30% immediately after a person ascends to high altitude but then decreases back toward normal over a period of weeks as the blood haematocrit increases, so the amount of oxygen transported to the peripheral body tissues remains about normal.

Central cord syndrome is the most commonly occurring type of partial spinal cord lesion. It is more likely to occur in older patients with cervical spondylosis and a hyperextension injury. The injury to the spinal cord occurs in the grey matter causing the following symptoms:

Disproportionally higher motor function weakness in the upper limbs than in lower limbs
Dysfunction of the bladder
Degrees of sensory loss below the level of the lesion

An anterior spinal artery infarction will interrupt the corticospinal tract resulting in paralysis of motor function, loss of pain and temperature sensation, all occurring below the level of the injury.

Brown-Sequard syndrome occurs as a result of the hemisection of the spinal cord. Its symptoms include ipsilateral upper motor neurone paralysis and loss of proprioception, with contralateral loss of pain and temperature sensation.

Spinal cord infarctions rarely occur in the posterior spinal artery.

Cauda equina syndrome occurs as a result of compression of the lumbosacral spinal nerve roots below the level of the conus medullaris. Injury to these nerves will cause partial or complete loss of movement and sensation in this distribution.

The Glasgow Coma Scale (GCS) has been used in outcome models as a measure of physiological derangement and as a tool for assessing head trauma.

Eye opening (E):

4 Spontaneously
3 Responds to voice
2 Responds to painful stimulus
1 No response.

Best verbal response (V):

5 Orientated, converses normally
4 Confused, disoriented conversation, but able to answer basic questions
3 Inappropriate responses, words discernible
2 Incomprehensible speech
1 Makes no sounds.

Best motor response (M):

6 Obeys commands for movement
5 Purposeful movement to painful stimulus
4 Withdraws from pain
3 Abnormal (spastic) flexor response to painful stimuli, decorticate posture
2 Extensor response to painful stimuli, decerebrate posture
1 No response.

In this case, GCS = 2+3+5 = 10.

Chronic obstructive pulmonary disease (COPD) is an obstructive, inflammatory lung condition. It encompasses symptoms of emphysema, chronic bronchitis and asthma.

Inhaling high dose steroids are prescribed to treat COPD. They are effective at reducing symptoms and improving lung function. They also work to reduce the number of hospitalisations by decreasing the number of acute exacerbation events. Despite providing effective symptom relief, it cannot slow down the decline of FEV1 as COPD is an irreversible condition.

COPD reduces the FEV1 measurements, as well as the FEV1/FVC ratio.

Breathlessness is a major COPD symptom and can occur at any point in the disease progression, including at an FEV1 >50%.

FEV1 is used in COPD staging, and it is classed as follows:
>80%: Mild or stage I
50 – 79%: Moderate or stage II
30 – 49%: Severe or stage III
<30%: Very severe or stage IV
Patients with mild COPD are usually able to manage their condition on their own, however once the disease progresses to moderate, more GP visits are required, with those in the severe category requiring frequent hospitalisation.

Asthma is correlated to an increase in transfer factor. COPD (emphysema) is correlated to a decreased transfer factor.

COPD predisposes to eventual pulmonary hypertension as a result of an increase in pulmonary vascular resistance.

This is a classical case of unstable angina or NSTEMI (Non-ST-elevation myocardial infarction). As soon as the diagnosis of unstable angina or NSTEMI is made the initial treatment is Aspirin and antithrombin therapy.

Betablocker is known to reduce mortality from acute myocardial infarction by reducing oxygen demand. If there is no contraindication (heart block, bradycardia, hypotension, severe left ventricular dysfunction, and asthma), a beta-blocker should be given early. This patient has hypotension and therefore metoprolol is contraindicated.

If three doses of nitroglycerine tablets or Nitrolingual sprays and intravenous beta-blockers too cannot relieve the symptoms intravenous Glyceryl Trinitrate (GTN) should be considered provided that there is no hypotension. But in this case, the patient is hypotensive, and therefore, it is contraindicated.

If the symptoms are not relieved after three serial doses of nitroglycerine or if symptoms recur despite adequate anti-anginal treatment morphine sulphate is indicated.

Warfarin prevents reductive metabolism of the inactive vitamin K epoxide back to its active hydroquinone form. Thus, warfarin inhibits the synthesis of vitamin K dependent clotting factors: X, IX, VII, II (prothrombin), and of the anticoagulants protein C and protein S. The therapeutic range for oral anticoagulant therapy is defined in terms of an international normalized ratio (INR). The INR is the prothrombin time ratio (patient prothrombin time/mean of normal prothrombin time for lab)ISI, where the ISI exponent refers to the International Sensitivity Index and is dependent on the specific reagents and instruments used for the determination. A prolonged INR is widely used as an indication of integrity of the coagulation system in liver disease and other disorders, it has been validated only in patients in steady state on chronic warfarin therapy.

Prothrombin complex concentrate (PCC) is used to replace congenital or acquired vitamin-K deficiency warfarin-induced anticoagulant effect, particularly in the emergent setting.

Intravenous vitamin K has a slower onset of action compared to PCC, but is useful for long term therapy.

Fresh frozen plasma (FFP) prepared from freshly donated blood is the usual source of the vitamin K-dependent factors and is the only source of factor V. The factors needed, however, are found in small quantities compared to PCC.

Cryoprecipitate is indicated for hypofibrinogenemia/dysfibrinogenemia, von Willebrand disease, haemophilia A, factor XIII deficiency, and management of bleeding related to thrombolytic therapy.

The umbilical vein closes once the umbilical cord is clamped following birth. This causes a rise in systemic vascular resistance, closing the ductus venosus.

Upon birth, the pulmonary vascular resistance is decreased as the lungs are aerated.

At birth, there is a rise in oxygen tension which causes the corresponding constriction of the ductus arteriosus. This prevents a left to right shunt as it stops aortic blood and blood from the pulmonary artery from mixing. The ventricles do no have an opening connecting them.

The foramen ovale closes soon after birth. It is the septum opening between the left and right atrium.

An adult’s cardiac output is expected to be 5 L/min

When the eye is compressed or the extra-ocular muscles are tractioned, the oculocardiac reflex causes a decrease in heart rate.

The ophthalmic division of the trigeminal nerve provides the afferent limb. This synapses with the vagus nerve’s visceral motor nucleus in the brainstem. The efferent signal is carried by the vagus nerve to the heart, where increased parasympathetic tone reduces sinoatrial node output and slows heart rate.

The most common symptom is sinus bradycardia, but junctional rhythm and asystole can also occur.

Aldosterone is produced in the zona glomerulosa of the adrenal cortex and acts to increase sodium reabsorption via intracellular mineralocorticoid receptors in the distal tubules and collecting ducts of the nephron.

Its release is stimulated by hypovolaemia, blood loss ,and low plasma sodium and is inhibited by hypertension and increased sodium. It is regulated by the renin-angiotensin system.

Bilirubin is formed by metabolizing heme, mostly from haemoglobin in red blood cells.

Bilirubin is conjugated to glucuronic acid in the hepatocytes by the glucuronyl transferase enzyme in order to enable it to become soluble and allow for its secretion across the canalicular membrane and into bile.

The conjugation process is increased by rifampicin and decreased by valproate.

Gilbert’s syndrome is caused by a decrease in glucuronyl transferase in the hepatic system, decreasing the transport of bilirubin into the hepatocyte, causing unconjugated bilirubinaemia.

Crigler-Najjer syndrome is caused by mutations in the genes responsible for hepatic glucuronyl transferase, decreasing the activity of the enzyme, meaning bilirubin cannot be conjugated, causing unconjugated bilirubinaemia.

Dubin-Johnson syndrome does not cause an impairment in the conjugation of bilirubin, but it blocks the transport of bilirubin out of the hepatocyte resulting in conjugated bilirubinaemia.

A post-tetanic count of 5 denotes a deep neuromuscular blockade.

Post tetanic count (PTC) is a well-established method of evaluating neuromuscular recovery during intense neuromuscular blockade. It cam ne used when there is no response to single twitch, tetanic, or train-of-four (TOF) stimulation to assess the intensity of neuromuscular blockade and to estimate the duration after which the first twitch in the TOF (T1) is likely to reappear.

During a nondepolarizing block, the high frequency of tetanic stimulation will induce a transient increase in the amount of acetylcholine released from the presynaptic nerve ending, such that the intensity of subsequent muscle contractions will be increased (potentiated) briefly (period of post-tetanic potentiation, which may last 2 to 5 min. The neuromuscular response to stimulation during post tetanic potentiation can be used to gauge the depth of block when TOF stimulation otherwise evokes no responses. The number of post tetanic responses is inversely proportional to the depth of block: fewer post tetanic contractions denote a deeper block. When the post tetanic count (PTC) is 6 to 8, recovery to TOF count = 1 is likely imminent from an intermediate-duration blocking agent; when the PTC is 0, the depth of block is profound, and no additional NMBA should be administered.

This sudden change in pulse rate is due to the oculocardiac reflex. It is a >20% reduction in pulse rate as a result of placing pressure directly on the eyeball. The reflex arc has an afferent and efferent arm:

The afferent (sensory) arm: The trigeminal nerve (CN V)

The efferent arm: The vagus nerve (CN X)

The most appropriate action is to ask the surgeon to stop retraction of the extraocular muscles, Assess for hypoxia, and give 100% oxygen if indicated.

Atropine of glycopyrrolate can be administered to counteract the reflex, and also prevent any further vagal reflexes.

Administration of fentanyl may increase patient’s risk of bradycardia and sinus arrest in this case.

Adrenaline is not indicated here as other treatment options will provide sufficient relief from arrhythmia.

Acute pulmonary embolism occurs when a blood clot becomes embedded in a pulmonary artery and restricts lung blood flow.

Thrombolysis is recommended in patients with extremely compromised circulation rather than reduced oxygen in the blood. It is effective when administered via a peripheral vein or a pulmonary artery catheter.

Anticoagulant therapy (heparin use) decreases the risk of further embolic evens and decreases constriction of pulmonary vessels.

An ECG may be normal in patients with an acute pulmonary embolism.