The sinoatrial node receives innervation from multiple nerves arising from the complex cardiac plexus.

The cardiac plexus sends tiny branches into cardiac vessels, alongside the right and left coronary arteries.

The vagal efferent fibres originate from the vagal and accessory nerves in the brainstem, and then travel to the cardiac plexus within the heart. The resulting vagal discharge controls heart rate.

No singular nerve directly innervates the sinoatrial node.

There are two types of defibrillators
AC defibrillator
DC defibrillator

AC defibrillator,
consists of a step-up transformer with primary and secondary winding and two switches. Since secondary coil consists of more turns of wire than the primary coil, it induces larger voltage. A voltage value ranging between 250V to 750V is applied for AC external defibrillator. And used to enable the charging of a capacitor.

DC defibrillator,
consists of auto transformer T1 that acts as primary of the high voltage transformer T2. Is an iron core that transfers energy between 2 circuits by electromagnetic induction. Transformers are used to isolate circuits, change impedance and alter voltage output. transformers do not convert AC to DC.

Diode rectifier composed of 4 diodes made of semiconductor material allows current to flow only in one direction. Alternating current (AC) passing through these diodes produces direct current (DC). Capacitor stores the charge in the form of an electrostatic field.

Capacitor is used to convert the rectified AC voltage to produce DC voltage but capacitors do not directly convert AC to DC.

Inductor induces a counter electromotive force(emf) that reduces the capacitor discharge value.

In step-down transformer primary coils has more turns of wire than secondary coil, so induced voltage is smaller in the secondary coil.

The intrinsic pathway is best assessed by the aPTT time.

D-dimer is a fibrin degradation product which is raised in the presence of blood clots.

A 50:50 mixing study is used to assess if a prolonged PT or aPTT is due to factor deficiency or a factor inhibitor.

The thrombin time is a test used to assess fibrin formation from fibrinogen in plasma. Factors that prolong the thrombin time include heparin, fibrin degradation products, and fibrinogen deficiency.

Intrinsic pathway – Best assessed by APTT. Factors 8,9,11,12 are involved. Prolonged aPTT can be seen in haemophilia and use of heparin.

Extrinsic pathway – Best assessed by Increased PT. Factor 7 involved.

Common pathway – Best assessed by APTT & PT. Factors 2,5,10 involved.

Vitamin K dependent factors are factors 2,7,9,10

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.

The fall in plasma concentration of a drug with time decreases exponentially in a single compartment pharmacokinetic model (wash-out curve).

A straight line is produced when the logarithm (ln) of a drug’s plasma concentration is plotted against time because a constant proportion of the drug is removed from the plasma per unit time. The line’s gradient or slope can be expressed mathematically as k. (the rate constant). The gradient is related to the half life (T1/2) because it can be used to predict a drug’s plasma concentration at any time.

According to the following formula, clearance (CL), volume of distribution (Vd), and elimination rate constant (k) are mathematically related.

CL = Vd x k

For drug A, CL = 1 x 0.1 = 0.1units per minute

For drug B, Cl = 2 x 0.2 = 0.4 units per minute

Hence, it is proved that Drug A has a lower clearance than drug B.

A decrease in the functional residual capacity (FRC) is the most important physiologic change to consider for such patients.

FRC is the sum of the expiratory reserve volume and the residual volume. It is the resting volume of the lung, and is an important marker for lung function. During this time, the alveolar pressure is equal to the atmospheric pressure. When morbidly obese individuals lie supine, the FRC decreases by as much as 40% because the abdominal contents push the diaphragm into the thoracic cavity.

Chest wall compliance is expected to reduce because of fat deposition surrounding adjacent structures.

Inspiratory reserve volume (IRV) is expected to increase, and peak expiratory flow is expected to decrease, however the decrease in FRC is more important to consider because of the risk of hypoxia secondary to premature airway closure and ventilation-perfusion mismatch.

Cardiopulmonary exercise testing (CPX, CPEX, CPET) is a non-invasive testing method used to determine the performance of the heart, lungs and skeletal muscle. It measures the exercise tolerance of the patient.

The parameters measured include:

ECG and ST-segment analysis and blood pressure
Oxygen consumption (VO2)
Carbon dioxide production (VCO2)
Gas flows and volumes
Respiratory exchange ratio (RER)
Respiratory rate
Anaerobic threshold (AT)

The anaerobic threshold (AT) is an estimate of exercise ability. Any measurement below 11 ml/kg/min is usually related with an increase in mortality, especially when there is a background of myocardial ischaemia occurring during the test.

Peak VO2 <20 mL/kg with a low AT have a correlation with postoperative complications and a 30 day mortality. The CPX test is used for risk-testing patients prior to surgery to determine the appropriate postoperative care facilities. The V slope measured in CPX testing represents VO2 versus VCO2 relationship. During AT, the ramp of V slope increases, but does not provide a picture of postoperative mortality.

Myoglobin is a haemoglobin-like, iron-containing pigment that is found in muscle fibres. It has a high affinity for oxygen and it consists of a single alpha polypeptide chain. It binds only one oxygen molecule, unlike haemoglobin, which binds 4 oxygen molecules.

The myoglobin ODC is a rectangular hyperbola. There is a very low P50 0.37 kPa (2.75 mmHg). This means that it needs a lower P50 to facilitate oxygen offloading from haemoglobin. It is low enough to be able to offload oxygen onto myoglobin where it is stored. Myoglobin releases its oxygen at the very low PO2 values found inside the mitochondria.

P50 is defined as the affinity of haemoglobin for oxygen: It is the PO2 at which the haemoglobin becomes 50% saturated with oxygen. Normally, the P50 of adult haemoglobin is 3.47 kPa(26 mmHg).

Foetal haemoglobin has 2 ? and 2 ?chains. The ODC is left shifted – this means that P50 lies between 2.34-2.67 kPa [18-20 mmHg]) compared with the adult curve and it has a higher affinity for oxygen. Foetal haemoglobin has no ? chains so this means that there is less binding of 2.3 diphosphoglycerate (2,3 DPG).

Carbon monoxide binds to haemoglobin with an affinity more than 200-fold higher than that of oxygen. This therefore decreases the amount of haemoglobin that is available for oxygen transport. Carbon monoxide binding also increases the affinity of haemoglobin for oxygen, which shifts the oxygen-haemoglobin dissociation curve to the left and thus impedes oxygen unloading in the tissues.

In sickle cell disease, (HbSS) has a P50 of 4.53 kPa(34 mmHg).

Changes in the osmolality of body fluids (changes as minor as 1% are sufficient) play the most important role in regulating AVP secretion. The receptors that monitor changes in osmolality of body fluids (termed osmoreceptors) are distinct from the cells that synthesize and secrete AVP, and are located in the organum vasculosum of the lamina terminalis (OVLT) of the hypothalamus. The osmoreceptors sense changes in body osmolality by either shrinking or swelling. When the effective osmolality of the plasma increases, the osmoreceptors send signals to the AVP synthesizing/secreting cells located in the supraoptic and paraventricular nuclei of the hypothalamus, and AVP synthesis and secretion are stimulated. Conversely, when the effective osmolality of the plasma is reduced, secretion is inhibited. Because AVP is rapidly degraded in the plasma, circulating levels can be reduced to zero within minutes after secretion is inhibited.

In this scenario, the osmolality of the plasma will decrease to an estimate of 2.5%, hence inhibition of AVP.

Stimulation of atrial stretch receptors is incorrect because the increase in plasma volume is still below the threshold for its activation.

Osmotic diuresis is incorrect because 5% dextrose is isotonic, hence osmotic diuresis is not probable.

Renin is inhibited when an excess of NaCl in the tubular fluid is sensed by the macula densa.

In general practice, majority of phase 3 trials and some of the trials conducted in phase 2 are randomized. Because phase 4 trials require a huge sample size, they are not randomized as much. The primal reason behind conducting phase 3 trials is to test the efficiency and safety in a significant sample population. At this point it is assumed that the drug is effective up to a certain extent.

During a case-control study, subjects that exhibit outcomes of interest are compared with those who don’t show the expected outcome. The extent of exposure to a particular risk factor is then matched between cases and controls. If the exposure among cases surpasses controls, it becomes a risk factor for the outcome that is being studied.

Pilot studies are conducted on a lower and much smaller level, to assess if a randomized controlled trial of the crucial components of a study will be plausible.

Phase 4 trials are the ones that are conducted after its established that the drug is effective and is approved by the regulating authority for use. These trials are concerned with the side effects and potential risks associated with the long term usage of the drug.