During glycolysis, 2,3-diphosphoglycerate (2,3-DPG) is
created in erythrocytes by the Rapoport-Luebering shunt.

The production of 2,3-DPG increases for several conditions
in the presence of decreased peripheral tissue O2 availability.
Some of these conditions include hypoxaemia, chronic lung
disease anaemia, and congestive heart failure. Thus,
2,3-DPG production is likely an important adaptive mechanism.

High levels of 2,3-DPG cause a shift of the curve to the right.
Low levels of 2,3-DPG cause a shift of the curve to the left,
as seen in states such as septic shock and hypophosphatemia.

When drugs are bound to proteins, drugs cannot cross membranes and exert their effect. Only the free (unbound) drug can be absorbed, distributed, metabolized, excreted and exert pharmacologic effect. Thus, when amide local anaesthetics are bound to ?1-glycoproteins, their duration of action are reduced.

The potency of local anaesthetics are affected by lipid solubility. Solubility influences the concentration of the drug in the extracellular fluid surrounding blood vessels. The brain, which is high in lipid content, will dissolve high concentration of lipid soluble drugs. When drugs are non-ionized and non-polarized, they are more lipid-soluble and undergo more extensive distribution. Hence allowing these drugs to penetrate the membrane of the target cells and exert their effect.

Tissue pKa and pH will determine the degree of ionization.

30 mmol Na+ and 30 mmol Cl- are found in 1 litre of 0.18 percent N. saline with 4% dextrose. Percent (percent) refers to the number of grammes of a compound per 100 mL, so a litre of 4 percent dextrose solution contains 40 grammes.

As a result, a 500 mL bag of 1/5th N. saline and 4% dextrose contains approximately 15 mequivalents of sodium and 20 g of glucose. It is hypotonic due to its osmolarity of 284.

Because of the risk of hyponatraemia, it is no longer considered the crystalloid of choice for fluid maintenance in children.

While the brain only weighs 3% of the body weight, 15% of the cardiac output goes towards the brain.

Between mean arterial pressures (MAP) of 60-130 mmHg, autoregulation of cerebral blood flow (CBF) occurs. Exceeding this, the CBF is maintained at a constant level. This is controlled mainly by the PaCO2 level, and the autonomic nervous system has minimal role.

Beyond these limits, the CBF is directly proportional to the MAP, not the systolic blood pressure.

The diaphragm has three opening through which different structures pass from the thoracic cavity to the abdominal cavity:

Inferior vena cava passes at the level of T8.

Oesophagus, oesophageal vessels and vagi at T10.

Aorta, thoracic duct and azygous vein through T12.

Sympathetic trunk and pulmonary branches of vagus nerve form a posterior pulmonary plexus at the root of the lung. Fibres continue posteriorly from superficial cardiac plexus to form Anterior pulmonary plexus. It contains vagi nerves and superficial cardiac plexus. These fibres then follow the blood vessel and bronchi into the lungs.

The lower border of the pleura is at the level of:

8th rib in the midclavicular line

10th rib in the lower level of midaxillary line

T12 at its termination.

Both lungs have oblique fissure while right lung has transverse fissure too.

The trachea expands from the lower edge of the cricoid cartilage (at the level of the 6th cervical vertebra) to the carina.

The ‘ideal’ alveolar PO2 minus arterial PO2 is the alveolar-arterial (A-a) oxygen difference.

The ‘ideal’ alveolar PO2 is derived from the alveolar air equation and is the PO2 that the lung would have if there was no ventilation-perfusion (V/Q) inequality and it was exchanging gas at the same respiratory exchange ratio as real lung.

The amount of oxygen in the blood is measured directly in the arteries.

The A-a oxygen difference (or gradient) is a useful measure of shunt and V/Q mismatch, and it is less than 2 kPa in normal adults breathing air (15 mmHg). Because the shunt component is not corrected, the A-a difference increases when breathing 100 percent oxygen, and it can be up to 15 kPa (115 mmHg).

An abnormally low or abnormally high V/Q ratio within the lung can cause an increased A-a difference, though the former is more common. Atelectasis, which results in a low V/Q ratio, is the most likely cause of an A-a difference in a healthy adult breathing 100 percent oxygen.

Hypoventilation may cause an increase in alveolar (and thus arterial) CO2, lowering alveolar PO2 according to the alveolar air equation.

The alveolar PO2 is also reduced at high altitude.

Healthy people are unlikely to have a right-to-left shunt or an oxygen transport diffusion defect.

The derived SI unit of force is Newton.
F = m·a (where a is acceleration)
F = 1 kg·m/s2

The joule (J) is a converted unit of energy, work, or heat. When a force of one newton (N) is applied over a distance of one metre (Nm), the following amount of energy is expended:

J = 1 kg·m/s2·m =
J = 1 kg·m2/s2 or 1 kg·m2·s-2

The unit of velocity is metres per second (m/s or ms-1).

The watt (W), or number of joules expended per second, is the SI unit of power:

J/s = kg·m2·s-2/s
J/s = kg·m2·s-3

Pressure is measured in pascal (Pa) and is defined as force (N) per unit area (m2):
Pa = kg·m·s-2/m2
Pa = kg·m-1·s-2

Glycolysis occurs in the cytoplasm of the cell. It converts 1 glucose molecule (6-carbon) to pyruvate (two 3-carbon molecules) and produces 4 ATP molecules and 2NADH but uses 2 ATP in the process with an overall net energy production of 2 ATP.

Pyruvate is then oxidised to acetyl coenzyme A (generating 2 NADH per pyruvate molecule). This takes place in the mitochondria and then enters the Krebs cycle (citric acid cycle). It produces 2 ATP, 8 NADH and 2 FADH2 per glucose molecule.

Electron transport phosphorylation takes place in the mitochondria. The aim of this process is to break down NADH and FADH2 and also to pump H+ into the outer compartment of the mitochondria. It produces 32 ATP with an overall net production of 36ATP.

In anaerobic respiration which occurs in the cytoplasm, pyruvate is reduced to NAD producing 2 ATP.

The concentration of solute particles per litre (mosm/L) = the osmolarity of a solution. Changes in water content, ambient temperature, and pressure affects osmolarity. The osmolarity of any solution can be calculated by adding the concentration of key solutes in it.

Individual manufacturers of crystalloids and colloids may have different absolute values but they are similar to these.

0.45% N. Saline with 5% glucose:
Tonicity – hypertonic
Osmolarity – 405 mosm/L
Kilocalories (kCal) – 107

0.9% N. Saline:
Tonicity – isotonic
Osmolarity – 308 mosm/L
Kilocalories (kCal) – 0

5% Dextrose:
Tonicity – isotonic
Osmolarity – 253 mosm/L
Kilocalories (kCal) – 170

Gelofusine (154 mmol/L Na, 120 mmol/L Cl):
Tonicity – isotonic
Osmolarity – 274 mosm/L
Kilocalories (kCal) – 0

Hartmann’s solution:
Tonicity – isotonic
Osmolarity – 273 mosm/L
Kilocalories (kCal) – 9

An elevated arterial blood lactate level and an increase anion gap ([Na + K] – [Cl + HCO3]) of >20mmol gives rise to lactic acidosis. It can also be a result of overproduction and/or reduced metabolism of lactic acid.

The liver and kidney are the main sites of lactate metabolism, not skeletal muscle.

The two types of lactic acidosis that are known are:

Type A – due to tissue hypoxia, inadequate tissue perfusion and anaerobic glycolysis. These may be seen in cardiac arrest, shock, hypoxaemia and anaemia. The management of type A lactic acidosis involves reversing the underlying cause of the tissue hypoxia.

Type B – occurs in the absence of tissue hypoxia. Some of the causes of this include hepatic failure, renal failure, diabetes mellitus, pancreatitis and infection. Some drugs can also cause this lie aspirin, ethanol, methanol, biguanides and intravenous fructose.

The mainstay of treatment involves:
1. Optimising tissue oxygen delivery
2. Correcting the cause
3. Intravenous sodium bicarbonate

In resistant cases, peritoneal dialysis can be performed.