Krebs’ cycle (tricarboxylic acid cycle or citric acid cycle) is a sequence of reactions to release stored energy through oxidation of acetyl coenzyme A (acetyl-CoA). Some of the products are carbon dioxide and hydrogen atoms.

The sequence of reactions, known collectively as oxidative phosphorylation, only occurs in the mitochondria (not cytoplasm).

The Krebs cycle can only take place when oxygen is present, though it does not require oxygen directly, because it relies on the by-products from the electron transport chain, which requires oxygen. It is therefore considered an aerobic process. It is the common pathway for the oxidation of carbohydrate, fat and some amino acids, required for the formation of adenosine triphosphate (ATP).

Pyruvate enters the mitochondria and is converted into acetyl-CoA. Acetyl-CoA is then condensed with oxaloacetate, to form citrate which is a six carbon molecule. Citrate is subsequently converted into isocitrate, alpha-ketoglutarate, succinyl-CoA, succinate, fumarate, malate and finally oxaloacetate.

The only five carbon molecule in the cycle is Alpha-ketoglutarate.

Systemic vascular resistance (SVR), also known as total peripheral resistance (TPR), is the amount of force exerted on circulating blood by the vasculature of the body. Three factors determine the force: the length of the blood vessels in the body, the diameter of the vessels, and the viscosity of the blood within them. The most important factor that determines the systemic vascular resistance (SVR) is the tone of the small arterioles.

These are otherwise known as resistance arterioles. Their diameter ranges between 100 and 450 µm. Smaller resistance vessels, less than 100 µm in diameter (pre-capillary arterioles), play a less significant role in determining SVR. They are subject to autoregulation.

Any change in the viscosity of blood and therefore flow (such as due to a change in haematocrit) might also have a small effect on the measured vascular resistance.

Changes of blood temperature can also affect blood rheology and therefore flow through resistance vessels.

Systemic vascular resistance (SVR) is measured in dynes·s·cm-5

It can be calculated from the following equation:

SVR = (mean arterial pressure − mean right atrial pressure) × 80 cardiac output

Such a high rise of end-tidal CO2 (EtCO2) in a patient who is spontaneously breathing is often encountered.

Close observation should occur for further rises in EtCO2 and other signs of malignant hyperthermia. If this were to rise even more, it might be wise to ensure that ventilatory support is available.

A lot would depend on whether surgery was almost completed. At this stage of anaesthesia, it would be inappropriate to administer opioid antagonists or respiratory stimulants.

Prostaglandins do not play a major role in regulating RBF in healthy resting individuals. However, during pathophysiological conditions such as haemorrhage and reduced extracellular fluid volume (ECVF), prostaglandins (PGI2, PGE1, and PGE2) are produced locally within the kidneys and serve to increase RBF without changing GFR. Prostaglandins increase RBF by dampening the vasoconstrictor effects of both sympathetic activation and angiotensin II. These effects are important because they prevent severe and potentially harmful vasoconstriction and renal ischemia. Synthesis of prostaglandins is stimulated by ECVF depletion and stress (e.g. surgery, anaesthesia), angiotensin II, and sympathetic nerves.

Non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen and naproxen, potently inhibit prostaglandin synthesis. Thus administration of these drugs during renal ischemia and hemorrhagic shock is contraindicated because, by blocking the production of prostaglandins, they decrease RBF and increase renal ischemia. Prostaglandins also play an increasingly important role in maintaining RBF and GFR as individuals age. Accordingly, NSAIDs can significantly reduce RBF and GFR in the elderly.

The following table shows the compartments and their relative oxygen reserve:
Compartment Factors Room air (mL) 100% O2 (mL)
Lung FAO2, FRC 630 2850
Plasma PaO2, DF, PV 7 45
Red blood cells Hb, TGV, SaO2 788 805
Myoglobin 200 200
Interstitial space 25 160

Oxygen reserves in the body, with room air and after oxygenation.

FAO2-alveolar fraction of oxygen rises to 95% after administration of 100% oxygen (CO2 = 5%)
FRC- Functional residual capacity – (the most important store of oxygen in the body) – 2,500-3,000 mL in medium sized adults
PaO2-partial pressure of oxygen dissolved in arterial blood (80 mmHg breathing room air and 500 mmHg breathing 100% oxygen)
DF -dissolved form (0.3%)
PV-plasma volume (3L)
TG-total globular volume (5L)
Hb-haemoglobin concentration
SaO2-arterial oxygen concentration (98% breathing air and 100% when preoxygenated)

Phosphate is the principal anion of the intracellular fluid, most of which is bound to either lipids or proteins. They dissociate or associate with different compounds, depending on the enzymatic reaction, thus forming a constantly shifting pool.

Calcium and magnesium are also present intracellularly, however in lesser amounts than phosphate.

Sodium is the most abundant extracellular cation, and Chloride and is the most abundant extracellular anion.

When there is capillary leakage as seen in dependent oedema or ascites, oncotic pressure becomes a problem.

The intracellular sodium concentration is very sensitive to the extracellular sodium concentrations. When there is an imbalance, osmosis occurs resulting in shifts in water between the two compartments.

The microvascular endothelium relies upon osmosis and other processes as it is not freely permeable to water.

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

The commonest and most likely cause of a gradual rise in end-tidal CO2 (EtCO2) occurring during anaesthesia in a spontaneously breathing patient is hypoventilation. This occurs from the respiratory depressant effects of the opioid and sevoflurane.

Malignant hyperthermia should be sought if the EtCO2 shows further progressive rise.

Causes of rebreathing and a rise in the baseline of the capnograph can be caused by exhausted soda lime and inadequate fresh gas flow into the Bain circuit.

A sudden rise in EtCO2 can be caused deflation of the tourniquet.

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 pH of CSF is 7.31 which is lower than plasma.

Compared to plasma, it has a lower concentration of potassium, calcium, and protein and a higher concentration of sodium, chloride, bicarbonate and magnesium.

CSF usually has no cells present but if white cells are present, there should be no more than 4/ml.

The pressure of CSF should be less than 20 cm of water.

The concentration of glucose is approximately two-thirds of that of plasma, and it has a concentration of approximately 3.3-4 mmol/L.

During fetal development, blood oxygenated by the placenta flows to the foetus through the umbilical vein, bypasses the fetal liver through the ductus venosus, and returns to the fetal heart through the inferior vena cava.

Blood returning from the inferior vena cava then enters the right atrium and is preferentially shunted to the left atrium through the patent foramen ovale. Blood in the left atrium is then pumped from the left ventricle to the aorta. The oxygenated blood ejected through the ascending aorta is preferentially directed to the fetal coronary and cerebral circulations.

Deoxygenated blood returns from the superior vena cava to the right atrium and ventricle to be pumped into the pulmonary artery. Fetal pulmonary vascular resistance (PVR), however, is higher than fetal systemic vascular resistance (SVR); this forces deoxygenated blood to mostly bypass the fetal lungs. This poorly oxygenated blood enters the aorta through the patent ductus arteriosus and mixes with the well-oxygenated blood in the descending aorta. The mixed blood in the descending aorta then returns to the placenta for oxygenation through the two umbilical arteries.

Hypoxic Pulmonary vasoconstriction (HPV) reflects the constriction of small pulmonary arteries in response to hypoxic alveoli (.i.e.; PO2 below 80-100mmHg or 11-13kPa).

These blood vessels become independent of the nerve stimulus, when blood with a high PO2 flows through the lung which contains a low alveolar PO2.

Thus a low PO2 within the alveoli has been shown to impact on hypoxic pulmonary vasoconstriction (HPV) more than a low PO2 within the blood.

HPV results in the blood flow being directed away from poorly ventilated areas of the lung and helps to reduce the ventilation/perfusion mismatch (not increase).

In animals, volatile anaesthetic agents can diminish HPV, while in adults, the evidence proves less persuading, in spite of the fact that it certainly doesn’t strengthen the effects.

HPV response will be suppressed by 20 parts per million (ppm) of nitric oxide.

The minimal alveolar concentration (MAC) is the concentration of an inhalation anaesthetic agent in the lung alveoli required to stop a response to the surgical stimulus in 50% of the patient.

Following factors don’t affect the MAC of the inhaled anaesthetic agents:

Gender, acidosis, alkalosis, hypothyroidism, hyperthyroidism, body weight, serum potassium level, and the duration of the anaesthesia.

MAC increase in children, elevated temperature, high metabolic rate, sympathetic increase and chronic alcoholism.

MAC decrease in low temperature, low oxygen level, old age, hypotension (<40 mmHg), depressant drugs e.g. opioids and low level of catecholamines; alpha methyl dopa. Carbon dioxide O2 at the pressure > 120mmHg is being used in anesthetic-Hinkman as an additive effect to decrease MAC, however, increase concentration of CO2 activates the sympathetic system resulting the MAC increases.

Osmolarity refers to the osmotic pressure generated by the dissolved solute molecules in 1 L of solvent. Measurements of osmolarity are temperature dependent because the volume of the solvent varies with temperature. The higher the osmolarity of a solution, the more it attracts water from an opposite compartment.

Osmolarity can be computed using the following formulas:

Osmolarity = Concentration x number of dissociable particles; OR
Plasma osmolarity (Posm) = 2([Na+]) + (glucose in mmol/L) + (BUN in mmol/L)

Posm = 2 (144) + 3.5 + 9.5 = 301 mOsm/L

Suppose there is electrical neutrality, the formula will double the cation activity to account for the anions.

Plasma osmolarity (Posm) = 2([Na+] + [K+]) + (glucose in mmol/L) + (BUN in mmol/L)

Posm = 2 (144 + 6) + 3.5 + 9.5 = 313 mOsm/L

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.

In contrast to the arterial system, which contains 15% of the circulating blood volume, the body’s veins contain 70% of it.

In severe haemorrhage, when sympathetic stimulation causes venoconstriction, venous tone is important in maintaining the return of blood to the heart.

Because the liver receives about 30% of the resting cardiac output, it is a very vascular organ. The hepatic vascular system is dynamic, which means it can store and release blood in large amounts – it acts as a reservoir within the general circulation.

In a normal situation, the liver contains 10-15% of total blood volume, with the sinusoids accounting for roughly 60% of that. The liver dynamically adjusts its blood volume when blood is lost and can eject enough blood to compensate for a moderate amount of haemorrhage.

In the portal venous and hepatic arterial systems, sympathetic nerves constrict the presinusoidal resistance vessels. More importantly, sympathetic stimulation lowers the portal system’s capacitance, allowing blood to flow more efficiently to the heart.

Net transcapillary absorption of interstitial fluid from skeletal muscle into the intravascular space compensates for blood loss effectively during haemorrhage. The decrease in capillary hydrostatic pressure (Pc), caused by reflex adrenergic readjustment of the ratio of pre- to postcapillary resistance, is primarily responsible for fluid absorption. Within a few hours of blood loss, these fluid shifts become significant, further diluting haemoglobin and plasma proteins.

Albumin synthesis begins to increase after 48 hours.

The juxtamedullary complex releases renin in response to a drop in mean arterial pressure, which causes an increase in aldosterone level and, eventually, sodium and water resorption. Increased antidiuretic hormone (ADH) levels also contribute to water retention.

Bilirubin is the tetrapyrrole and a catabolic product of heme. 70-90% of bilirubin is end product of haemoglobin degradation in the liver.

Bilirubin circulates in the blood in 2 forms; unconjugated and conjugated bilirubin.

Unconjugated bilirubin is insoluble in water. It travels through the bloodstream to the liver, where it changes from insoluble into a soluble form (i.e.; unconjugated into conjugated form).

This conjugated bilirubin travels from the liver into the small intestine and the gut bacteria convert bilirubin into urobilinogen and then into urobilin (not urobilin to urobilinogen). A very small amount passes into the kidneys and is excreted in urine.

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.

PaCO2 is one of the most important factors that regulate cerebral vascular tone. CO2 induces cerebral vasodilatation and as a result, it increases CBF. Between 20 mmHg (2.7 kPa) and 80 mmHg (10.7 kPa), there is a linear increase of PaCO2.

Sometimes, there are areas where auto regulation has failed locally but not globally. Similarly, local vs. systemic acidosis will have similar effects. When the PaO2 falls below 50 mmHg (6.5 kPa), the CBF progressively increases.

An increase in the cerebral metabolic rate for oxygen (CMRO2) and therefore CBF can be caused by hyperthermia.
A late feature of cerebral injury is hyperthermia secondary to hypothalamic injury. Therefore this is not the most likely cause of an increased CBF in this scenario.

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.

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.

The derived unit of energy, work or amount of heat is joule (J). It is defined as the amount of energy expended if a force of one newton (N) is applied through a distance of one metre (N·m)

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

Kinetic energy (KE) = ½ MV2

An object with a mass of 1500 kg moving at 30 m/s correlates to 675 kJ:

KE = ½ (1500) × (30)2 = 750 × 900 = 675 kJ

Total energy released when 1 kg fat is metabolised to CO2 and water is 37 MJ. 1 g fat produces 37 kJ/g, therefore 1 kg fat produces 37,000 × 1000 = 37 MJ.

Raising the temperature of 1 kg water from 0°C to 100°C correlates to 420 kJ. The amount of energy needed to change the temperature of 1 kg of the substance by 1°C is the specific heat capacity. We have 1 kg water therefore:

4,200 J × 100 = 420,000 J = 420 kJ

In order to calculate the energy involved in raising a 100 kg mass to a height of 1 km against gravity, we need to calculate the potential energy (PE) of the mass:

PE = mass × height attained × acceleration due to gravity
PE = 100 kg × 1000 m × 10 m/s2 = 1 MJ

The heat generated when a direct current of 10 amps flows through a heating element for 10 seconds when the potential difference across the element is 1000 volts can be calculated by applying Joule’s law of heating:

Work done (WD) = V (potential difference) × I (current) × t (time)
WD = 10 × 10 × 1000 = 100 kJ

A preplanned preinduction strategy includes the consideration of various interventions designed to facilitate intubation should a difficult airway occur. Non-invasive interventions intended to manage a difficult airway include, but are not limited to: (1) awake intubation, (2) video-assisted laryngoscopy, (3) intubating stylets or tube-changers, (4) SGA for ventilation (e.g., LMA, laryngeal tube), (5) SGA for intubation (e.g., ILMA), (6) rigid laryngoscopic blades of varying design and size, (7) fibreoptic-guided intubation, and (8) lighted stylets or light wands.

Most supraglottic airway devices (SADs) are designed for use during routine anaesthesia, but there are other roles such as airway rescue after failed tracheal intubation, use as a conduit to facilitate tracheal intubation and use by primary responders at cardiac arrest or other out-of-hospital emergencies. Supraglottic airway devices are intrinsically more invasive than use of a facemask for anaesthesia, but less invasive than tracheal intubation. Supraglottic airway devices can usefully be classified as first and second generation SADs and also according to whether they are specifically designed to facilitate tracheal intubation. First generation devices are simply ‘airway tubes’, whereas second generation devices incorporate specific design features to improve safety by protecting against regurgitation and aspiration.

Heme a exists in cytochrome a and heme c in cytochrome c; they are both involved in the process of oxidative phosphorylation. 5′-Aminolevulinic acid synthase (ALA-S) is the regulated enzyme for heme synthesis in the liver and erythroid cells.

There are two forms of ALA Synthase, ALAS1, and ALAS2.

The half life of Retinol binding protein (RBP) is 10-12 hours and therefore reflects more acute changes in protein metabolism than any of these proteins. Therefore it is not commonly used as a parameter for nutritional assessment.

The half life of Transthyretin (thyroxine binding pre-albumin) is only one to two days and so levels are less sensitive and this protein is not an albumin precursor. 15 mg/dL represents early malnutrition and a need for nutritional support.

Albumin levels have been frequently as a marker of nutrition but this is not a very sensitive marker. It’s half life more than 30 days and significant change takes some time to be noticed. Also, synthesis of albumin is decreased with the onset of the stress response after burns. Unrelated to nutritional status, the synthesis of acute phase proteins increases and that of albumin decreases.

A more accurate indicator of protein stores is transferrin. It’s response to acute changes in protein status is much faster. The half life of serum transferrin is shorter (8-10 days) and there are smaller body stores than albumin. A low serum transferrin level is below 200 mg/dL and below 100 mg/dL is considered severe. Serum transferrin levels can also affect serum transferrin level.

Fibronectin is used a nutritional marker but levels decrease after seven days of starvation. It is a glycoprotein which plays a role in enhancing the phagocytosis of foreign particles.

CBF is defined as the blood volume that flows per unit mass per unit time in brain tissue and is typically expressed in units of ml blood/100 g tissue/minute. The normal average CBF in adults human is about 50 ml/100 g/min, with lower values in the white matter (,20 ml/100 g/min) and greater values in the gray matter (,80 ml/100 g/min).

Low CBF levels between 30-40 ml/100 g/min may begin to show poor prognostic EEG. EEG findings consistently associated with a poor outcome are isoelectric EEG, low voltage EEG, and burst suppression (specifically burst suppression with identical bursts), as well as the absence of EEG reactivity.

Sixty-seven percent of filtered water is reabsorbed in the proximal tubule. The driving force for water reabsorption is a transtubular osmotic gradient established by reabsorption of solutes (e.g., NaCl, Na+-glucose).

Henle’s loop reabsorbs approximately 25% of filtered NaCl and 15% of filtered water. The thin ascending limb reabsorbs NaCl by a passive mechanism, and is impermeable to water. Reabsorption of water, but not NaCl, in the descending thin limb increases the concentration of NaCl in the tubule fluid entering the ascending thin limb. As the NaCl-rich fluid moves toward the cortex, NaCl diffuses out of the tubule lumen across the ascending thin limb and into the medullary interstitial fluid, down a concentration gradient as directed from the tubule fluid to the interstitium. This mechanism is known as the counter current multiplier.

The distal tubule and collecting duct reabsorb approximately 8% of filtered NaCl, secrete variable amounts of K+ and H+, and reabsorb a variable amount of water (approximately 8%-17%).

Glucose transport is a highly regulated process accomplished mostly by facilitated diffusion using carrier proteins to cross cell membranes.

There are many transporters, but the most important are known as glucose transporters (GLUTs).

Stresses in various form of acute and chronic forms affect the activity of glucose transporters.
They are responsive to many types of metabolic stress, including hypoxia, injury, hypoglycaemia, numerous metabolic inhibitors, stress hormones, and other influences such as growth factors.

Numerous signalling pathways appear to be involved in transporter regulation.

New evidence suggests that stresses regulating GLUTs are not only acute biological stresses. In addition, chronic low-grade inflammation, and their associated chronic diseases also lead to altered glucose transport. These include obesity, type 2 diabetes, cardiovascular disease, and the growth and spread of many tumours that are affected by altered glucose transporters. Some of these glucose transport effects are compensatory, while others are pathogenic.

Ultimately, deliberate manipulation of GLUTs could be used as treatment for some of these chronic diseases.