Cardiac conduction

Phase 0 – Rapid depolarization. Opening of fast sodium channels with large influx of sodium

Phase 1 – Rapid partial depolarization. Opening of potassium channels and efflux of potassium ions. Sodium channels close and influx of sodium ions stop

Phase 2 – Plateau phase with large influx of calcium ions. Offsets action of potassium channels. The absolute refractory period

Phase 3 – Repolarization due to potassium efflux after calcium channels close. Relative refractory period

Phase 4 – Repolarization continues as sodium/potassium pump restores the ionic gradient by pumping out 3 sodium ions in exchange for 2 potassium ions coming into the cell. Relative refractory period

Therapeutic index is a measure which relates the dose of a drug required to produce a desired effect to that which produces an undesired effect.

In humans, it is usually defined as the ratio of the toxic dose for 50% of the population (TD50) to the minimum effective dose for 50% of the population (ED50) for some therapeutically relevant effect. In animal studies, the therapeutic index can be defined as the ratio of the median lethal dose (LD50) to the ED50.

Prerenal failure has a serum urea: creatinine ratio of >100, while acute kidney injury has a ratio of 40.
In prerenal failure, ADH levels are typically high, resulting in water, urea, and sodium resorption. The fractional sodium excretion is less than 1%, but it is greater than 2% in acute tubular necrosis.
Prerenal azotaemia has higher serum urea nitrogen/serum creatinine ratios (>20), whereas acute tubular necrosis has lower ratios (10-15). The normal range is between 12 and 20.
Urinary sodium is less than 20 in prerenal failure and greater than 40 in acute tubular necrosis.
Prerenal failure has a urine osmolality of >500, while acute tubular necrosis has an osmolality of 350.
Prerenal failure has a urine/serum creatinine ratio of >40, while acute tubular necrosis has a urine/serum creatinine ratio of 20.

The concentrations of serum urea or creatinine change in inverse proportion to glomerular filtration. Changes in serum creatinine concentrations are more reliable than changes in serum urea concentrations in predicting GFR. Creatinine is produced at a constant rate from creatine, and blood concentrations are almost entirely determined by GFR.

A number of factors influence urea formation, including liver function, protein intake, and protein catabolism rate. Urea excretion is also influenced by hydration status, the amount of water reabsorption, and GFR.

A high serum creatinine level, as well as a urine output of less than 10 mL/hour and the production of concentrated looking urine, do not necessarily indicate a specific cause of oliguria.

The axillary nerve lies behind the axillary artery initially, and in front of the subscapularis. It passes downward to the lower border of the subscapularis muscle.

In company with the posterior humeral circumflex artery and vein, it winds backward through a quadrilateral space bounded above by the subscapularis (anterior) and teres minor (posterior), below by the teres major, medially by the long head of the triceps brachii, and laterally by the humerus (surgical neck).

It then divides into an anterior and a posterior part. The anterior division supplies the deltoid (anterior and middle heads) while the posterior division supplies the teres minor and posterior part of deltoid
The posterior division terminates as the superior lateral cutaneous nerve of the arm.

The heart has two venous drainage systems:
1. Greater venous system – it parallels the coronary arterial circulation and provides 70% venous drainage to the heart
2. Lesser venous system – includes the thebasian veins and provides up to 30% of the venous drainage to the heart

Thebasian veins (also called venae cordis minimae) are the smallest coronary veins and run in the myocardial layer of the heart. They serve to drain the myocardium and are present in all four heart chambers. They are more abundant on the right side of the heart and, more specifically, are most abundant in the right atrium. Thebesian veins drain the subendocardial myocardium either directly, via connecting intramural arteries and veins, or indirectly, via subendocardial sinusoidal spaces.

The normal peak inspiratory flow in healthy individuals is 20-30 L/min during each normal tidal ventilation. This is expected to increase with greater respiratory rate and deeper inspiration.

Face masks are used to facilitate the delivery of oxygen from a breathing system to a patient. Face masks can be divided into two types: fixed performance or variable performance devices.

In fixed performance devices (also known as high air flow oxygen enrichment or HAFOE), fixed inspired oxygen concentration is delivered to the patent, independent and greater than that of the patient’s peak inspiratory flow rate (PIFR). No random entrainment is expected to occur at the time of PIFR, hence, the oxygen concentration in HAFOE devices is not dependent on the patient’s respiratory pattern.

Moreover, in HAFOE masks, the concentration of oxygen at a given oxygen flow rate is determined by the size of the constriction; a device with a greater entrainment aperture delivers a lower oxygen concentration. Therefore, a 40% Venturi device will have lesser entrainment aperture when compared to a 31% Venturi. Venturi masks allow relatively fixed concentrations of supplemental oxygen to be inspired e.g. 24%, 28%, 31%, 35%, 40% and 60% oxygen. These are colour coded and marked with the recommended oxygen flow rate.

Variable performance devices deliver variable inspired oxygen concentration to the patient, and is dependent on the PIFR. The PIFR can often exceed the flow rate at which oxygen or an oxygen/air mixture is supplied by the device, depending on a patient’s inspiratory effort. In addition, these masks allow expired air to be released through the holes in the sides of the mask. Thus, with increased respiratory rate, rebreathing of alveolar gas from inside the mask may occur.

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).

ANOVA is based upon within group variance (i.e. the variance of the mean of a sample) and between group variance (i.e. the variance between means of different samples). The test works by finding out the ratio of the two variances mentioned above. (Commonly known as F statistic).

Standard error can be calculated by the following formula:
Standard Error= (Standard Deviation)/ˆš(Sample Size)
= (16) / ˆš(100)
= 16 / 10
= 1.6

Femoral nerve lesion (L2,L3 and L4) is characterised by weakness of the quadriceps femoris muscle. This results in weakness of extension of the knee, loss of sensation over the front of the thigh, and loss of the knee jerk reflex.

The skin over the lateral aspect of the thigh and knee, and the lower lateral quadrant of the buttock is supplied by the lateral cutaneous nerve of the thigh (L1,2).

The adductors of the hip are supplied by the obturator nerve (L2-4). This nerve also supplies sensation to the inner thigh.

The response of cerebral blood flow (CBF) to hyperoxia (PaO2 >15 kPa, 113 mmHg), the cerebral oxygen vasoreactivity is less well defined. A study originally described, using a nitrous oxide washout technique, a reduction in CBF of 13% and a moderate increase in cerebrovascular resistance in subjects inhaling 85-100% oxygen. Subsequent human studies, using a variety of differing methods, have also shown CBF reductions with hyperoxia, although the reported extent of this change is variable. Another study assessed how supra-atmospheric pressures influenced CBF, as estimated by changes in middle cerebral artery flow velocity (MCAFV) in healthy individuals. Atmospheric pressure alone had no effect on MCAFV if PaO2 was kept constant. Increases in PaO2 did lead to a significant reduction in MCAFV; however, there were no further reductions in MCAFV when oxygen was increased from 100% at 1 atmosphere of pressure to 100% oxygen at 2 atmospheres of pressure. This suggests that the ability of cerebral vasculature to constrict in response to increasing partial pressure of oxygen is limited.

Increases in arterial blood CO2 tension (PaCO2) elicit marked cerebral vasodilation.

CBF increases with general anaesthesia, ketamine anaesthesia, and hypoviscosity.

An intra-operative air embolism occurs when air becomes trapped in the blood vessels during surgery.

A transoesophageal echocardiography (OE) uses invasive echocardiography to monitor the integrity and performance of the heart. It is the gold standard as it provides real-time imaging of the heart to enable early diagnosis and treatment.

Precordial doppler ultrasonography can also be used to detect into-operative air emboli. It is non-invasive and more practical, but is less sensitive.

A change in end-tidal CO2 could be indicative of and increase in physiological dead-space, but could also be indicative of any processes that reduces the excretion or increases the production of CO2, making it non-specific.

A transoesophageal stethoscope can be used to listen for the classic mill-wheel murmur produced by a large air embolus.

Barbiturates are derived from barbituric acid, which itself is nondepressant, but appropriate side-chain substitutions result in CNS depressant activity that varies in potency and duration with carbon chain length, branching, and saturation.

Oxybarbiturates retain an oxygen atom on number 2-carbon atom of the barbituric acid ring.

Thiobarbiturates replace this oxygen atom with a sulphur atom, which confers greater lipid solubility. Generally speaking, a substitution such as sulphuration that increases lipid solubility is associated with greater hypnotic potency and more rapid onset, but shorter duration of action.

Addition of a methyl group to the nitrogen atom of the barbituric acid ring, as with oxybarbiturate methohexital, also results in a compound with a short duration of action.

All of the muscles of the larynx are innervated by the recurrent laryngeal nerve, except the cricothyroid muscle.

Cricothyroid muscle is located deep in the anterior neck, between the cricoid and thyroid cartilage and is innervated by the external laryngeal nerve. Any injury to this muscle can cause paralysis and lead to hoarseness. When cricothyroid muscle contracts, it leads to tightening, stretching and thinning of the vocal folds. This produces higher-pitched sounds during vocalization.

A patient experiencing hoarseness due to possible injury to the external laryngeal nerve should be reassured that the hoarseness will resolve in time due to increased compensation from the other muscles.

The heart receives blood supply from coronary arteries. The right and left coronary arteries branch off the aorta and supply oxygenated blood to all heart muscle parts.

The left main coronary artery branches into:
1. Circumflex artery – supplies the left atrium, side, and back of the left ventricle. The left marginal artery arises from the left circumflex artery. It travels along the obtuse margin of the heart.
2. Left Anterior Descending (LAD) artery – supplies the front and bottom of the left ventricle and front of the interventricular septum

The left anterior descending coronary artery is the largest coronary artery. It courses anterior to the interventricular septum in the anterior interventricular groove, extending from the base of the heart to its apex. Around the apex, the LAD anastomosis with the terminal branches of the posterior descending artery (branch of the right coronary artery).
Atherosclerosis or thrombotic occlusion of LAD causes myocardial infarction in large areas of the anterior, septal, and apical portions of the heart muscle. It can lead to a serious deterioration in heart performance.

Occlusion of the LAD causes anteroseptal myocardial infarction, which is evident on the ECG with changes in leads V1-V4. Occlusion of the left circumflex artery causes lateral, posterior, or anterolateral MI. However, as it does not run towards the apex in the interventricular septum of the heart, it is not the correct answer for this question.

The right coronary artery branches into:
1. Right marginal artery
2. Posterior descending artery

The right coronary artery supplies the right atrium, right ventricle, interatrial septum, and the inferior posterior third of the interventricular septum. Occlusion of the right coronary artery causes inferior MI, which is indicated on ECG with changes in leads II, III, and aVF.

At rest, the heart has the greatest a-vO2 difference, a high capillary to myocyte ratio, short diffusion distances, and a high mitochondrial density. The flow of blood through the coronary arteries is also tightly controlled. At rest, 70-80 percent of the oxygen available to the cardiac muscle is extracted, increasing to 90 percent during exercise.

The a-vO2 difference indicates the body’s or an individual organ’s ability to extract oxygen from the blood.

CaO2 is influenced by a number of factors, including Hb concentration, PaO2 and pulmonary diffusion capacity.

CvO2 is influenced by a number of factors, including capillary density, regional blood flow, heart, resting skeletal muscle, kidney, intestine and skin.

The external urethral sphincter functions to provide voluntary control of urine flow from the bladder to the urethra.

It receives its innervation from the branches of the pudendal nerve which originate from S2, S3 and S4.

Level 1 – High-quality randomised controlled trial with statistically significant difference or no statistically significant difference but narrow confidence intervals (prospective controlled)

Level 2 – Prospective comparative study (prospective uncontrolled)

Level 3 – Case-control study, retrospective comparative study (retrospective controlled)

Level 4 – Case series (retrospective uncontrolled)

Level 5 – Expert opinion.

The action of class 1 anti-arrhythmic is sodium channel blockade. Subclasses of this action reflect effects on the action potential duration (APD) and the kinetics of sodium channel blockade.

Drugs with class 1A prolong the APD and refractory period, and dissociate from the channel with intermediate kinetics.

Drugs with class 1B action shorten the APD in some tissues of the heart, shorten the refractory period, and dissociate from the channel with rapid kinetics.

Drugs with class 1C action have minimal effects on the APD and the refractory period, and dissociate from the channel with slow kinetics.

Type I – immediate hypersensitivity reaction

Examples are: Atopy, urticaria, Anaphylaxis, Asthma( IgE mediated).

Type II – Antibody mediated cytotoxic reaction

Examples are: Autoimmune haemolytic anaemia, Thrombocytopenia( IgM or IgG mediated).

Type III – Immune complex mediated reaction

Examples are: Serum sickness,SLE – IgG., Farmers lungs, rheumatoid arthritis

Type IV – Delayed hypersensitivity reaction

Examples are: Contact dermatitis, drug allergies.

Type V – Autoimmune

Graves’
Myasthenia – IgM or IgG.

Pipeline gases (in the UK this includes: Oxygen, Nitrous oxide, Medical air, and Entonox) are supplied at 4 bar (or 400 kPa), and compressed air is supplied at 7 bar for power tools.

Carbon dioxide and nitric oxide are usually only supplied in cylinders.

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.

Rifampicin is a derivative of a rifamycin (other derivatives are rifabutin and rifapentine). It is bactericidal against both dividing and non-dividing mycobacterium and acts by inhibiting DNA-dependent RNA polymerase. Thus this drug inhibits RNA synthesis.

The shaft of the humerus has two prominent features:
1. Deltoid tuberosity – attachment for the deltoid muscle
2. Radial or spiral groove – The radial nerve and profunda brachii artery lie in the groove

Mid-shaft fractures of the humerus usually occur after a direct blow to the upper arm, which can occur after a fall or RTAs. The most important clinical significance of a mid-shaft humeral fracture is an injury to the radial nerve. The radial nerve originates from the brachial plexus and has roots of C5-T1. It crosses the spiral groove on the posterior side of the shaft of the humerus.
On examination, the patient may have a wrist drop, loss or weakness of finger extension, and decreased or absent sensation to the posterior forearm, digits 1 to 3, and the radial half of the fourth digit.

The following parts of the humerus are in direct contact with the indicated
nerves:
Surgical neck: axillary nerve.
Radial groove: radial nerve.
Distal end of humerus: median nerve.
Medial epicondyle: ulnar nerve.

The amount of energy required to change the temperature of 1 kg of a substance by 1°C is its specific heat capacity.

Energy required to increase the temperature of any object is given by the equation:

E = m × c × θ

Where:
E = energy required to heat an object
m = mass of object
c = specific heat capacity of the substance
θ = temperature change

The specific heat capacity of water is 4181 J/(kg°C)

Therefore the energy required to raise 1kg of water by 10°C is:

1 kg × 4181 J/(kg°C) × 10°C = 41810 J

A 1 kW or 1000 W heater would be expected to supply 1000 J/s.

The approximate time it would take the 1 kW heater to raise the temperature of one Litre of water by 10°C is:

41810/1000 = 41.8 seconds.

The vertebral artery originates from the subclavian artery and ascends through the neck in the transverse foramen of the C1-C6 vertebrae. C2 vertebra is called the axis vertebra. A part of the vertebral artery lies in a groove on the upper surface of the atlas’s (C1) posterior arch. It enters the vertebral canal below the inferior border of the posterior atlantooccipital membrane. The vertebral arteries then enter the skull via the foramen magnum.

Iron is a necessary micronutrient for proper erythropoietic function, oxidative metabolism, and cellular immune responses. Although dietary iron absorption (1-2 mg/d) is tightly controlled, it is only just balanced by losses.

The adult body contains 35-45 mg/kg iron (about 4-5 g)

Iron can be found in a variety of forms, including haemoglobin, ferritin, haemosiderin, myoglobin, haem enzymes, and transferrin bound proteins.

Cardiac output = stroke volume x heart rate

Left ventricular ejection fraction = (stroke volume / end diastolic LV volume ) x 100%

Stroke volume = end diastolic LV volume – end systolic LV volume

Pulse pressure = Systolic Pressure – Diastolic Pressure

Systemic vascular resistance = mean arterial pressure / cardiac output
Factors that increase pulse pressure include:
-a less compliant aorta (this tends to occur with advancing age)
-increased stroke volume

The diaphragm divides the thoracic cavity from the abdominal cavity. Structures penetrate the diaphragm at different vertebral levels through openings in the diaphragm to communicate between the two cavities. The diaphragm has openings at three vertebral levels:

T8: vena cava, terminal branches of the right phrenic nerve
T10: oesophagus, vagal trunks, left anterior phrenic vessels, oesophageal branches of the left gastric vessels
T12: descending aorta, thoracic duct, azygous and hemi-azygous vein.

The diaphragm divides the thoracic cavity from the abdominal cavity. Structures penetrate the diaphragm at different vertebral levels through openings in the diaphragm to communicate between the two cavities. The diaphragm has openings at three vertebral levels:

T8: vena cava, terminal branches of the right phrenic nerve
T10: oesophagus, vagal trunks, left anterior phrenic vessels, oesophageal branches of the left gastric vessels
T12: descending aorta, thoracic duct, azygous and hemi-azygous vein.