The cardiac action potential has several phases which have different mechanisms of action as seen below:
Phase 0: Rapid depolarisation – caused by a rapid sodium influx.
These channels automatically deactivate after a few ms

Phase 1: caused by early repolarisation and an efflux of potassium.

Phase 2: Plateau – caused by a slow influx of calcium.

Phase 3 – Final repolarisation – caused by an efflux of potassium.

Phase 4 – Restoration of ionic concentrations – The resting potential is restored by Na+/K+ATPase.
There is slow entry of Na+into the cell which decreases the potential difference until the threshold potential is reached. This then triggers a new action potential

Of note, cardiac muscle remains contracted 10-15 times longer than skeletal muscle.

Different sites have different conduction velocities:
1. Atrial conduction – Spreads along ordinary atrial myocardial fibres at 1 m/sec

2. AV node conduction – 0.05 m/sec

3. Ventricular conduction – Purkinje fibres are of large diameter and achieve velocities of 2-4 m/sec, the fastest conduction in the heart. This allows a rapid and coordinated contraction of the ventricles

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

Maintenance therapy aims to replace water and electrolytes lost under ordinary conditions. In the perioperative period, maintenance fluid administration may not sufficiently account for the increased fluid requirements caused by third-space losses into the interstitium and gut. Specific recommendations vary with the patient, the procedure, and the type and amount of fluid administered during the operation. The fluid for maintenance therapy replaces deficits arising primarily from insensible losses and urinary or gastrointestinal (GI) losses.

The maintenance fluid volume can be computed using the Holliday-Segar method.

Body weight Fluid volume
first 10 kg 4 ml/kg/hr
next 10-20 kg 2 ml/kg/hr
>20 kg 1 ml/kg/hr

In the past few years, there has been growing recognition of the increased risk of hyponatremia in hospitalized children in intensive care and postoperative settings who receive hypotonic maintenance fluids. Several studies, including a randomized controlled trial and a Cochrane analysis, found that the use of isotonic fluids is associated with fewer electrolyte derangements and concluded that isotonic maintenance fluids are preferable to hypotonic solutions in hospitalized children.

A European consensus statement suggests that an intraoperative fluid should have an osmolarity close to the physiologic range in children in order to avoid hyponatremia, an addition of 1-2.5% in order to avoid hypoglycaemia, lipolysis or hyperglycaemia and should also include metabolic anions as bicarbonate precursors to prevent hyperchloremic acidosis.

A rate of 40 ml/hr is suboptimal.

If 0.9% NaCl with 0% glucose is given at a rate of 65 ml/hr, despite of the correct infusion rate, large volumes can lead to hyperchloremic acidosis.

If 0.18% NaCl with 4% glucose is given at a rate of 65 ml/hr, infusion of this fluid regimen can lead to hyponatremia because of its hypotonicity.

Respiratory inspiration causes a decreased pressure in the thoracic cavity, which in turn causes more blood to flow into the atrium.

Sitting up decreases venous because of the action of gravity on blood in the venous system.
Hypotension also decreases venous return.
A less compliant aorta, like in aortic stenosis increases end systolic left ventricular volume which decreases stroke volume.

Systemic vascular resistance = mean arterial pressure / cardiac output. Increased vascular resistance impedes the flow of blood back to the heart.

Increased venous return increases end diastolic LV volume as there is more blood returning to the ventricles.

Only 1 percent of the calcium in the human body is found in the plasma where it performs the most critical functions.

Out of this 1 percent, approximately 15% is complexed calcium bound to organic and inorganic anions, 40% is bound to albumin, and the remaining 45% circulates as free ionized calcium.

The Chvostek sign is a clinical finding associated with hypocalcaemia, or low levels of calcium in the blood. This clinical sign refers to a twitch of the facial muscles that occurs when gently tapping an individual’s cheek, in front of the ear.

Prolonged QT interval are associated with hypocalcaemia as reported in multiple studies.

The cardiac muscle’s contractile fibres have a much more stable resting potential than its conductive fibres. In the ventricular fibres it is -90mV and in the atrial fibres it is -80mV.

The cardiac action potential has several phases which have different mechanisms of action as seen below:

Phase 0: Rapid depolarisation – caused by a rapid sodium influx.
These channels automatically deactivate after a few ms. (QRS complex)

Phase 1: caused by early repolarisation and an efflux of potassium.

Phase 2: Plateau – caused by a slow influx of calcium.

Phase 3 – Final repolarisation – caused by an efflux of potassium.

Phase 4 – Restoration of ionic concentrations – The resting potential is restored by Na+/K+ATPase.
There is slow entry of Na+into the cell which decreases the potential difference until the threshold potential is reached. This then triggers a new action potential

Of note, cardiac muscle remains contracted 10-15 times longer than skeletal muscle.

Different sites have different conduction velocities:
1. Atrial conduction – Spreads along ordinary atrial myocardial fibres at 1 m/sec

2. AV node conduction – 0.05 m/sec

3. Ventricular conduction – Purkinje fibres are of large diameter and achieve velocities of 2-4 m/sec, the fastest conduction in the heart. This allows a rapid and coordinated contraction of the ventricles

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

Potassium maintains the resting potential of cardiac myocytes, with depolarization triggered by a rapid influx of sodium ions, and repolarization due to efflux of potassium. A slow influx of calcium is responsible for the longer duration of a cardiac action potential compared with skeletal muscle.

The cardiac action potential has several phases which have different mechanisms of action as seen below:

Phase 0: Rapid depolarisation – caused by a rapid sodium influx.
These channels automatically deactivate after a few ms.

Phase 1: caused by early repolarisation and an efflux of potassium.

Phase 2: Plateau – caused by a slow influx of calcium.

Phase 3 – Final repolarisation – caused by an efflux of potassium.

Phase 4 – Restoration of ionic concentrations – The resting potential is restored by Na+/K+ATPase.
There is slow entry of Na+into the cell which decreases the potential difference until the threshold potential is reached. This then triggers a new action potential

Of note, cardiac muscle remains contracted 10-15 times longer than skeletal muscle.

Different sites have different conduction velocities:
1. Atrial conduction – Spreads along ordinary atrial myocardial fibres at 1 m/sec

2. AV node conduction – 0.05 m/sec

3. Ventricular conduction – Purkinje fibres are of large diameter and achieve velocities of 2-4 m/sec, the fastest conduction in the heart. This allows a rapid and coordinated contraction of the ventricles

The correct answer is the clotting cascade, which occurs via a positive feedback mechanism. As clotting factors are attracted to a site, their presence attracts further clotting factors. This continues until a functioning clot is formed.

This patient has presented with symptoms of hypothyroidism and symptoms include weight gain, lethargy, cold intolerance, dry skin, coarse hair and constipation. It can be treated by replacing the missing thyroid hormone with levothyroxine which is a synthetic version of thyroxine (T4).

Serum carbon dioxide (CO2) is controlled via a negative feedback mechanism as well. Chemoreceptors can detect when the serum CO2 is high, and send an impulse to the respiratory centre of the brain to increase the respiratory rate. As a result, more CO2 is exhaled which lowers the serum concentration.

Cortisol is also released according to a negative feedback mechanism. Cortisol acts on both the hypothalamus and the anterior pituitary. Its action serve to decrease the formation of corticotrophin releasing hormone (CRH) and adrenocorticotropic hormone (ACTH), respectively. CRH acts on the anterior pituitary to release ACTH. This then acts on the adrenal gland to cause the release of cortisol. Thus, inhibition of CRH and ACTH formation results in high levels of cortisol which inhibit its further release.

Blood pressure (BP) is controlled via a negative feedback mechanism. Low BP results in renin-angiotensin-aldosterone system (RAAS) activation. This leads to vasoconstriction and retention of salt and water which increased BP.
Blood sugar is controlled via a negative feedback mechanism. A rise in blood sugar causes insulin to be released. Insulin acts to transport glucose into the cell which lowers blood sugar.

The extrinsic pathway is best assessed by the PT 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