After the carotid body, the thyroid gland is the second most richly vascular organ in the body.

The global blood flow to the thyroid gland can be measured using:
1. Colour ultrasound sonography
2. Quantitative perfusion maps using MRI of the thyroid gland using an arterial spin labelling (ASL) method.

This table shows the blood flow to various organs of the body at rest:
Organ Blood Flow(ml/minute/100g)
Hepatoportal 58
Kidney 420
Brain 54
Skin 13
Skeletal muscle 2.7
Heart 87
Carotid body 2000
Thyroid gland 560

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.

The Nernst equation is used to calculate the membrane potential at which the ions are in equilibrium across the cell membrane.

The normal resting membrane potential is -70 mV (not + 70 mV).

The equation is:
E = RT/FZ ln {[X]o
/[X]i}

Where:
E is the equilibrium potential
R is the universal gas constant
T is the absolute temperature
F is the Faraday constant
Z is the valency of the ion
[X]o is the extracellular concentration of ion X
[X]i is the intracellular concentration of ion X.

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.

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.

In any alveolar unit, the V/Q ratio affects alveolar oxygen (PAO2) and carbon dioxide tension (PACO2).

The partial pressure of alveolar carbon dioxide (PACO2) is plotted against the partial pressure of alveolar oxygen in a Ventilation-Perfusion (V/Q) ratio graph (PAO2). Given a set of model assumptions, the curve represents all of the possible values for PACO2 and PAO2 that an individual alveolus could have.

In the case of an infinity V/Q ratio (ventilation but no perfusion or dead space), the PACO2 of the alveolus will equal zero, while the PAO2 will approach that of external air (150mmmHg). At the apex of the lung, the V/Q ratio is 3.3, compared to 0.67 at the base.

PACO2 and PAO2 approach the partial pressures for these gases in the venous blood when the V/Q ratio is zero (no ventilation but perfusion). At the base of the lung, the V/Q ratio is 0.67, whereas at the apex, it is 3.3.

PAO2 at the apex is typically 132mmHg, and PACO2 is typically 28mmHg.

The average PAO2 at the base is 89 mmHg, while the average PACO2 is 42 mmHg.

The measurements of GFR are done using renally inert indicators like inulin, where passive rate of filtration at the glomerulus = rate of excretion. Normal value is about 180 litres per day.

GFR is altered by renal blood flow but blood flow does not need to be measured.

The reabsorption of Na leads to a low excretion rate and low urine concentration and therefore its use as an indicator would lead to an erroneously LOW GFR.

If there is tubular secretion of any solute, the clearance value will be higher than that of inulin. This will be either due to tubular reabsorption or the solute not being freely filtered at the glomerulus.

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

In the neonatal stage, the tongue is usually large and comes to the normal size at the age of 1 year. The vocal cords lie inverse C4 and as it reaches the grown-up position inverse C5/6 by the age of 4 (not 1 year).

Due to the immature cricoid cartilage, the larynx lies more anterior in newborn children. That’s why the cricoid ring is the narrowest part of the paediatric respiratory tract, while in the adults the tightest portion of the respiratory route is vocal cords. The epiglottis is generally expansive and slants at a point of 45 degrees to the laryngeal opening.

The carina is the ridge of the cartilage in the trachea at the level of T2 in newborn (T4 in adults), that separates the openings of right and left main bronchi.

Neonates have a comparatively low number of alveoli and then this number gradually increases to a most extreme by the age of 8 (not 3 years).

Neonates are obligatory nose breathers and any hindrance can cause respiratory issues (e.g., choanal atresia).

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.

For this patient, his forced expiratory volume in 1 second (FEV1) will decrease at the same rate as a non-smoker.

There is a notable, but slow, decline in FEV1 when an individual reaches the age of 26. An average reduction of 30 mls every year in non-smokers, while a more significant reduction of 50-70 mls is observed in approximately 20% of smokers.

Considering the age of the patient, individuals who begin smoking cessation by the age of 60 are far less likely to achieve normal FEV1 levels, even in the next five years. It is expected that their FEV1 will be approximately 14% less than their peers of the same age.

The following is the Advanced Trauma Life Support (ATLS) classification of haemorrhagic shock:

Class I haemorrhage:
It has blood loss up to 15%. There is very less tachycardia, and no changes in blood pressure, RR or pulse pressure. Usually, fluid replacement is not required.

Class II haemorrhage:
It has 15-30% blood loss, equivalent to 750 – 1500 ml. There is tachycardia, tachypnoea and a decrease in pulse pressure. Patient may be frightened, hostile and anxious. It can be stabilised by crystalloid and blood transfusion.

Class III haemorrhage:
There is 30-40% blood loss. It portrays inadequate perfusion, marked tachycardia, tachypnoea, altered mental state and fall in systolic pressure. It requires blood transfusion.

Class IV haemorrhage:
There is > 40% blood volume loss. It is a preterminal event, and the patient will die in minutes. It portrays tachycardia, significant depression in systolic pressure and pulse pressure, altered mental state, and cold clammy skin. There is need for rapid transfusion and surgical intervention.

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.

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.

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)

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

The oxygen content of arterial blood can be calculated by the following equation:
(10 x haemoglobin x SaO2 x 1.34) + (PaO2 x 0.0225).
This is the sum of the oxygen bound to haemoglobin and the oxygen dissolved in the plasma.

Oxygen content x cardiac output = The amount of oxygen delivered to the tissues in unit time which is known as the oxygen flux.

Any factor that increases the metabolic demand will encourage oxygen offloading from the haemoglobin in the tissues and this causes the oxygen dissociation curve (ODC) to shift to the right. This subsequently reduced the oxygen content of arterial blood.

Conditions like fever, metabolic or respiratory acidosis lowers the oxygen content and shifts the ODC to the right.
A low level of 2,3 diphosphoglycerate (2,3-DPG) is usually related to an increased oxygen content as there is less offloading, and so the ODC is shifted to the left.

So for a given PaO2, a high blood oxygen content is related to any factors that can shift the ODC to the left and not to the right.

A low haematocrit usually means that there is a decreased haemoglobin concentration, and therefore is associated with decreased oxygen binding to haemoglobin.

Sodium concentration for different fluids
3% N saline 513 mmol/L
5% N saline 856 mmol/L
0.9% N saline 154 mmol/L
Hartmann’s solution 131 mmol/L
0.45% N saline with 5% glucose 77 mmol/L

This means that:

500 mL 5% N saline contains 428 mmol of sodium
1000 mL 3% N saline contains 513 mmol of sodium
3500 mL 0.9% N saline contains 539 mmol of sodium
4000 mL Hartmann’s contains 524 mmol of sodium
6000 mL 0.45% N saline with 5% glucose contains 462 mmol of sodium.

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.

Krebs’ cycle (tricarboxylic acid cycle or citric acid cycle) is a sequence of reactions in which acetyl coenzyme A (acetyl-CoA) is metabolised and this results in carbon dioxide and hydrogen atoms production.

This series of reactions occur in the mitochondria of eukaryotic cells, not the cytoplasm. The cycle requires oxygen and so, cannot function under anaerobic conditions.

It is the common pathway for carbohydrate, fat and some amino acids oxidation and is required for high energy phosphate bond formation in adenosine triphosphate (ATP).

When pyruvate enters the mitochondria, it is converted into acetyl-CoA. This represents the formation of a 2 carbon molecule from a 3 carbon molecule. There is loss of one CO2 but formation of one NADH molecule. Acetyl-CoA is condensed with oxaloacetate, the anion of a 4 carbon acid, to form citrate which is a 6 carbon molecule.

Citrate is then converted into isocitrate, alpha-ketoglutarate, succinyl-CoA, succinate, fumarate, malate and finally oxaloacetate.

The only 5 carbon molecule in the cycle is alpha-ketoglutarate.

Body fluid compartments in a 70kg male:
Total volume=42L (60% body weight)
Intracellular fluid compartment (ICF) =28L
Extracellular fluid compartment (ECF) = 14L

ECF comprises:
Intravascular fluid (plasma) = 3L
Extravascular fluid = 11L

Extravascular fluids comprises:
Interstitial fluid = 10.5L
Transcellular fluid = 0.5L

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.

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%).

A mercury barometer can be used to determine absolute pressure. A glass tube with one closed end serves as the barometer. The open end is inserted into a mercury-filled open vessel. The mercury in the container is pushed into the tube by atmospheric pressure exerted on its surface. Absolute pressure is the distance between the tube’s meniscus and the mercury surface.

Pressure is defined as force in newtons per unit area (F) (A). 

Mass of mercury = area (A) × density (ρ) × length (L)
Pressure = ((A × ρ × L) × 9.8 m/s2)/A
Pressure = ρ × L x 9.8
Pressure is proportional to L

The numerator and denominator of the above equation, area (A), cancel out. The constants are density and the gravitational acceleration value.

The length is proportional to the applied pressure.

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.

After a paediatric case, you’ll frequently have to calculate and prescribe maintenance fluids. The ‘4-2-1 rule’ should be used as a guideline:

1st 10 kg – 4 ml/kg/hr
2nd 10 kg – 2 ml/kg/hr
Subsequent kg – 1 ml/kg/hr

Hence

1st 10 kg = 4 × 10 = 40 ml
2nd 10 kg = 2 × 10 = 20 ml
Subsequent kg = 1 × 1 = 1 ml
Total = 61 ml/hr

61 × 12 = 732 ml over 12 hrs.

A major source of caloric expenditure and oxygen consumption in the body is work of breathing (WOB) and 70% of this is to overcome elastic forces. The remaining 30% is for flow-resistive work

In a normal patient breathing normally, the total area of hysteresis pressure volume curve represents the flow-resistive WOB.

The area of the expiratory resistive work increases during an asthma attack making the compliance curve larger in area. The larger the area the greater the work required to breathe.

Skeletal muscle blood flow is in the range of 1-4 ml/min per 100 g when at rest. Blood flow can reach 50-100 ml/min per 100 g during exercise. With maximal vasodilation, blood flow can increase 20 to 50 times.

The adrenal medulla releases catecholamines and increases neural sympathetic activity during exercise. Normally, alpha-1 and alpha-2 would cause vasoconstriction in the muscle groups being used, but vasodilatory metabolites override these effects, resulting in a so-called functional sympathectomy. Local hypoxia and hypercarbia, nitric oxide, K+ ions, adenosine, and lactate are some of the stimuli that cause vasodilation.

However, the splanchnic and cutaneous circulations, which supply inactive muscles, vasoconstrict.

Sympathetic cholinergic innervation of skeletal muscle arteries is found in some species (such as cats and dogs, but not humans). Vasodilation is induced by stimulating smooth muscle beta-2 adrenoreceptors, but at rest, the alpha-adrenoreceptor effects of adrenaline and noradrenaline predominate. During exercise, the skeletal muscle pump promotes venous emptying, but it does not necessarily increase blood flow.

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.