Control of Substances Hazardous to Health (COSHH) was established by government under the Health and Safety at Work act in 1989. Their employers work on identification and management of those substances that are dangerous to health. The implications for anaesthetists include gas scavenging, equipment contamination and environmental safety. Adequate ventilation is required in areas where anaesthetic gases are present. The minimum air supply that is legally required in each specific area is: Operating theatres: 0.65 m3/second. Anaesthetic rooms: 0.15 m3/s. Preparation rooms: 0.1 m3/s. Recovery rooms need 15 air changes per hour

When a person forcefully expires against a closed glottis, changes occur in intrathoracic pressure that dramatically affect venous return, cardiac output, arterial pressure, and heart rate. This forced expiratory effort is called a Valsalva maneuver.

Initially during a Valsalva, intrathoracic (intrapleural) pressure becomes very positive due to compression of the thoracic organs by the contracting rib cage. This increased external pressure on the heart and thoracic blood vessels compresses the vessels and cardiac chambers by decreasing the transmural pressure across their walls. Venous compression, and the accompanying large increase in right atrial pressure, impedes venous return into the thorax. This reduced venous return, and along with compression of the cardiac chambers, reduces cardiac filling and preload despite a large increase in intrachamber pressures. Reduced filling and preload leads to a fall in cardiac output by the Frank-Starling mechanism. At the same time, compression of the thoracic aorta transiently increases aortic pressure (phase I); however, aortic pressure begins to fall (phase II) after a few seconds because cardiac output falls. Changes in heart rate are reciprocal to the changes in aortic pressure due to the operation of the baroreceptor reflex. During phase I, heart rate decreases because aortic pressure is elevated; during phase II, heart rate increases as the aortic pressure falls.

When the person starts to breathe normally again, the intrathoracic pressure declines to normal levels, the aortic pressure briefly decreases as the external compression on the aorta is removed, and heart rate briefly increases reflexively (phase III). This is followed by an increase in aortic pressure (and reflex decrease in heart rate) as the cardiac output suddenly increases in response to a rapid increase in cardiac filling (phase IV). Aortic pressure also rises above normal because of a baroreceptor, sympathetic-mediated increase in systemic vascular resistance that occurred during the Valsava.

The relative risk (also known as risk ratio [RR]) is the ratio of risk of an event in one group (e.g., exposed group) versus the risk of the event in the other group (e.g., nonexposed group).

The odds ratio (OR) is the ratio of odds of an event in one group versus the odds of the event in the other group.

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

T cells function as a part of the body’s adaptive immune system. There are different types of T cells, including:

Cytotoxic T cells: Function as killer cells by releasing cytotoxic granules into the membrane of targeted cells.

T-Helper cells: When activated, they function to activate other immune cell types, assist in antibody production with B cells and releasing cytokines including IL-2.

Memory T cells: Function as to provide immune memory against already encountered antigens.

T cells possess specific glycoproteins and receptors on their surface.

T-Helper cells work with HLA class II antigens on the cell surfaces in order to recognise foreign antigens

T cells survive ranges from a few weeks, to a lifetime depending on the subtype in question.

Immunoglobulins are expressed on the surface of, and secreted by B-lymphocytes.

Native antigens are recognised by B cells. T cells only recognise antigens that have been processed by the cells and presented on the surface of the cell.

Doxazosin is selective alpha 1 blocker (it causes less tachycardia than a non-selective alpha-blocker) and is the drug of choice for a patient with hypertension and benign hyperplasia of the prostate (BHP).

The major adverse effect of an alpha-blocker is first-dose hypotension.

Atenolol and Labetalol are beta blockers. It works by relaxing blood vessels and slowing heart rate to improve blood flow and decrease blood pressure.

Clonidine is an α2A-adrenergic agonist used to treat high blood pressure, ADHD, drug withdrawal (alcohol, opioids, or nicotine), menopausal flushing, diarrhea, spasticity, and certain pain conditions.

Methyldopa is a centrally-acting alpha-2 adrenergic agonist used to manage hypertension alone or in combination with hydrochlorothiazide, and to treat hypertensive crises.

The vertebral (spinal) column is the skeletal central axis made up of approximately 33 bones called the vertebrae.

Cervical disc herniations occur when some or all of the nucleus pulposus extends through the annulus fibrosus. The most commonly affected discs are the C5-C6 and C6-C7 discs. Each vertebrae has a corresponding nerve root which arises at a level above it. This means that a hernation of the C5-C6 disc will cause a compression of the C6 nerve root.

The foramen transversarium is a part of the transverse process of each cervical vertebrae, however, the vertebral artery only runs through the C1-C6 foramen transversarium.

The costal facets are the point of joint formation between a rib and a vertebrae. As such, they are only present on the transverse processes of T1-T10.

The lumbar vertebrae do not form a joint with the ribs, nor do they possess a foramina in their transverse process.

Intervertebral discs are thickest in the cervical and lumbar regions of the spinal column. However, there are no discs between C1 and C2.

Correlation doesn’t justify causality. Correlation coefficient gives us an idea whether or not the two parameters provide have any relation of some sort or not i.e. does change in one prompt any change in other? It has nothing to do with predictions. For that purpose linear regression is used.

The pectinate muscles (musculi pectinati) are parallel muscular ridges that extend anterolaterally on the right atrial walls. The most prominent pectinate muscle, which forms the bridge of the sulcus terminalis internally, is the taenia sagittalis (second crest or septum spurium).

In the left atrium, the pectinate muscles are confined to the inner surface of its atrial appendage. They tend to be fewer and smaller than in the right atrium. This is due to the embryological origin of the auricles, which are the true atria.

Pectinate muscles of the atria are different from the trabeculae carneae, which are found on the inner walls of both ventricles.

The interior of the right atrium has five distinct features:
1. Sinus venarum – smooth, thin-walled posterior part of the right atrium where the SVC, IVC, and coronary sinus open
2. Musculi pectinati – a rough anterior wall of pectinate muscles
3. Tricuspid valve orifice – the opening through which the right atrium empties blood into the right ventricle
4. Crista terminalis – separates the rough (musculi pectinati) from the smooth (sinus venarum) internally
5. Fossa ovalis – a thumbprint size depression in the interatrial septum, which is a remnant of the oval foramen and its valve in the foetus

Aldosterone is produced in the zona glomerulosa of the adrenal cortex and acts to increase sodium reabsorption via intracellular mineralocorticoid receptors in the distal tubules and collecting ducts of the nephron.

Its release is stimulated by hypovolaemia, blood loss ,and low plasma sodium and is inhibited by hypertension and increased sodium. It is regulated by the renin-angiotensin system.

This scenario describes rebreathing management.

Changes is exhaustion of the soda lime and a progressive rise in circuit deadspace is the most likely explanation for the capnograph.

It is important that the soda lime canister is inspected for a change in colour of the granules. Initially fresh gas flow should be increased and then if necessary, replace the soda lime granules. Other strategies include changing to another circuit or bypassing the soda lime canister after the fresh gas flow is increased.

Any other causes of increased equipment deadspace should be excluded.

Intraoperative hypercarbia can be caused by:

1. Hypoventilation – Breathing spontaneously; drugs which include anaesthetic agents, opioids, residual neuromuscular blockade, pre-existing respiratory or neuromuscular disease and cerebrovascular accident.
2. Controlled ventilation- circuit leaks, disconnection, miscalculation of patient’s minute volume.
3. Rebreathing – Soda lime exhaustion with circle, inadequate fresh gas flow into Mapleson circuits, increased breathing system deadspace.
4. Endogenous source – Tourniquet release, hypermetabolic states (MH or thyroid storm) and release of vascular clamps.
5. Exogenous source – Absorption of CO2 absorption from the pneumoperitoneum.

Mast cell tryptase is a reliable marker of mast cell degranulation. Tryptase is a protease enzyme that acts via widespread protease-activated receptors (PARs).

The portal vein arises from the splenic and mesenteric veins, and is the biggest vessel in the portal venous system, accounting for about 75% of the hepatic blood flow.

It is responsible for draining blood from parts of the gastrointestinal system, the spleen, the pancreas and the gallbladder into the liver.

Bernoulli’s principle states that as the speed of a moving fluid increases, there is a simultaneously decrease in static pressure or a decrease in the fluid’s potential energy.
This is seen in the simultaneous increase in speed and kinetic energy and fall in pressure that causes entrainment of large volumes of air into a flow of 100% oxygen in the nozzle of HAFOE masks.

The reduction in fluid pressure that happens when a fluid flows through a constriction in a tube is the Venturi effect.

When a flow of gas or liquid attaches itself to a nearby surface and remains attached even when the surface curves away from the initial direction of flow, this is the Coanda effect.

The branch of engineering and technology that is concerned with the building of devices that use the flow and pressure of a fluid for functions usually performed by electronic devices is Fluidics . Fluidic logic is used to power some ventilators.

The branch of engineering that utilises pressurised gases is Pneumatics.

Insulin is the primary anabolic hormone that dominates regulation of metabolism during digestive phase. It promotes glucose uptake in skeletal myocytes and adipocytes, and other insulin-target cells. It promotes glycogenesis and inhibits gluconeogenesis.

Glucagon is the primary counterregulatory hormone that increases blood glucose levels, primarily through its effects on liver glucose output.

Similar to glucagon, growth hormone, catecholamines and corticosteroids are also counterregulatory factors released in response to decreased glucose concentrations. Growth hormone promotes glycogenolysis and inhibits gluconeogenesis; catecholamines stimulate glycogenolysis and gluconeogenesis; while corticosteroids stimulate glycogenesis and gluconeogenesis.

The tricuspid valve allows the tip of a pulmonary artery catheter to pass through the right atrium and into the right ventricle.

The balloon will be inflated before crossing the pulmonary valve and entering the pulmonary artery, where it will eventually wedge or occlude the artery, providing an indirect measure of left atrial pressure.

0-12 mmHg in the right atrium
2-25 mmHg in the right ventricle
12-25 mmHg in the pulmonary artery
8-12 mmHg is the occlusion pressure

The midgut gives rise to the appendix.
At week 6, the caecal diverticulum appears and is the precursor for the cecum and vermiform appendix. The cecum and appendix undergo rotation and descend into the right lower abdomen. The appendix can take up various positions:
1. Retrocecal appendix: behind the cecum
2. Retrocolic appendix: behind the ascending colon
3. Pelvic appendix: appendix descends into the pelvis

The appendix grows in length so that at birth, it is long and worm-shaped, or vermiform. After birth, the caecal wall grows unequally, and the appendix comes to lie on its medial side.

The midgut develops into the distal duodenum, jejunum, ileum, cecum, appendix, ascending colon, and proximal 2/3 of the transverse colon.

There are 4 different types of globin chains which surround 4 heme molecules in haemoglobin (Hb) – α (alpha), β (beta), γ (gamma), and δ (delta)
α chains are essential.
δ2β2 and β2γ2 are not found in a healthy adult.
97% of the Hb in a healthy adult is made of α2β2 (2 α chains and 2 β chains).
α2δ2 accounts for around 1.5-3% of the adult Hb.
α2γ2 accounts for less than 1%.

With respect to oxygen transport in cells, almost all oxygen is transported within erythrocytes. There is limited solubility and only 1% is carried as solution. Thus, the amount of oxygen transported depends upon haemoglobin concentration and its degree of saturation.

Haemoglobin is a globular protein composed of 4 subunits. Haem is made up of a protoporphyrin ring surrounding an iron atom in its ferrous state. The iron can form two additional bonds – one is with oxygen and the other with a polypeptide chain. There are two alpha and two beta subunits to this polypeptide chain in an adult and together these form globin. Globin cannot bind oxygen but can bind to CO2 and hydrogen ions. The beta chains are able to bind to 2,3 diphosphoglycerate. The oxygenation of haemoglobin is a reversible reaction. The molecular shape of haemoglobin is such that binding of one oxygen molecule facilitates the binding of subsequent molecules.

Certain skeletal muscles are more resistant to the effects of neuromuscular blocking agents, both non-depolarizing and depolarizing. The diaphragm is the most resistant. The muscles of the larynx and the corrugator supercilii are less resistant. The abdominal, orbicularis oris, and limb peripheral muscles are the most sensitive muscles.

Twitch stimulation patterns:

Supramaximal single stimulus:

The frequency ranges from 1 Hz to 0.1 Hz (one every second to one every 10 seconds)
The response is proportional to the frequency of the event.
It has limited clinical utility because it only tells you whether or not a patient is paralysed (no information on degree of paralysis).

Over the course of 0.5 seconds (2 Hz), four supramaximal stimulate were applied:

It is possible to see ‘fade’ and use it as a basis for evaluation.
This stimulation pattern is used to determine the degree of blockade (1-2 twitches is appropriate for abdominal surgery)
If the train of four (TOF) count is 1-2, reversal agents can be used in conjunction with medium-acting neuromuscular blocking agents.

Ratio of TOF:

This is the ratio of the 4th twitch amplitude to the 1st twitch amplitude.
The ratio decreases with non-depolarising block and is inversely proportional to the degree of block, allowing objective measurement of residual neuromuscular blockade.
To achieve adequate reversal, the ratio (as measured by accelerography) must be between 0.7 and 0.9.

Count of twitches after a tetanic experience(PTC):

50 Hz for 5 seconds, then a 3 second pause, followed by a single 1 Hz twitch stimulus.
When the TOF count is zero, this stimulation pattern is used to assess deep blockade (that is, in neurosurgery, microsurgery or ophthalmic surgery when even small movements of a patient will disturb the surgical field)
It gives an estimate of how long it will take for the response to return to single twitches, allowing assessment of blocks that are too deep for any other technique.
A palpable post-tetanic count (PTC) of 2 indicates no twitch response for about 20-30 minutes, and a PTC of 5 indicates no twitch response for about 10-15 minutes.

This is without a doubt the best way to keep track of paralysis in patients who need to avoid diaphragmatic movement. It’s best to use drug infusions and aim for a PTC of 2. After a tetanic stimulus, acetylcholine is mobilised, causing post-tetanic potentiation.

Stimulation in Two Bursts:

750 milliseconds between two short bursts of 50 Hz
This stimulation pattern is used to assess small amounts of residual blockade manually (tactile).

The ventilatory anaerobic threshold (VAT), formerly referred to as the anaerobic threshold, is an index used to estimate exercise capacity. During the initial (aerobic) phase of CPET, which lasts until 50–60% of Vo2max is reached, expired ventilation (VE) increases linearly with Vo2 and reflects aerobically produced CO2 in the muscles. Blood lactate levels do not change substantially during this phase, since muscle lactic acid production is minimal.

During the latter half of exercise, anaerobic metabolism occurs because oxygen supply cannot keep up with the increasing metabolic requirements of exercising muscles. At this time, there is a significant increase in lactic acid production in the muscles and in the blood lactate concentration. The Vo2 at the onset of blood lactate accumulation is called the lactate threshold or the VAT. The VAT is also defined as the point at which minute ventilation increases disproportionately relative to Vo2, a response that is generally seen at 60–70% of Vo2max.

The VAT is a useful measure as work below this level encompasses most daily living activities. The ability to achieve the VAT can help distinguish cardiac and non‐cardiac (pulmonary or musculoskeletal) causes of exercise limitation, since patients who fatigue before reaching VAT are likely to have a non‐cardiac problem.

When VAT is detected, patients with PVo2 of ⩽10 ml/kg/min have a high event rate.

Selective ?1 -Blockers like prazosin, terazosin, doxazosin, and alfuzosin cause a decrease in blood pressure with lesser tachycardia than nonselective blockers (due to lack of ?2 blocking action.

The major adverse effect of these drugs is postural hypotension. It is seen with the first few doses or on-dose escalation (First dose effect).

Its half-life is approximately three hours.

It is excreted primarily through bile and faeces (not through kidneys)

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).

Glutamic acid decarboxylase is responsible for the catalyses of glutamate to gamma-aminobutyric acid (GABA)

Catechol-o-methyl transferase catalyses the degradation and inactivation of dopamine into 3-methoxytyramine, epinephrine into metanephrine, and norepinephrine into normetanephrine and vanylmethylmandelic acid (VMA).

Monoamine oxidase catalyses the oxidation of norepinephrine to vanylmethylmandelic acid (VMA) and serotonin to 5-hydeoxyindole acetic acid (5-HIAA).

Cholinesterase functions to catalyse the split of acetylcholine into choline and acetic acid.

Pulmonary vascular resistance (PVR) refers to the resistance to blood flow to the left atrium from the pulmonary artery.
It is derived mathematically by:

PVR = MPAP – PCWP
CO
where,
MPAP: Mean pulmonary artery pressure
PCWP: Pulmonary capillary occlusion pressure
CO: Cardiac output

For this patient:
PVR = 10 – 5 = 1mmHg
5

Remember, multiply by correction factor 80 to change units:

PVR = 1mmHg x 80 = 80 dynes·s·cm-5

Normal values range between 20-130 dynes·s·cm-5

The patient’s diagnosis is microcytic hypochromic anaemia which is often as a result of iron deficiency and thalassaemia.

Macrocytic anaemia is often caused by folate and B12 deficiencies and alcohol abuse.

Normocytic normochromic anaemia is often caused by acute blood loss, haemolytic anaemia, anaemia of chronic disease and leucoerythroblastic anaemias.

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.

The left subclavian artery originates from the aortic arch, while the right subclavian artery originates from the brachiocephalic artery.

The subclavian artery gives off branches on both sides of the body:
1. Vertebral artery
2. Internal thoracic artery
3. Thyrocervical trunk
4. Costocervical trunk
5. Dorsal scapular artery

The superior thyroid artery is the first branch of the external carotid artery. The other branches of the external carotid artery are:
1. Superior thyroid artery
2. Ascending pharyngeal artery
3. Lingual artery
4. Facial artery
5. Occipital artery
6. Posterior auricular artery
7. Maxillary artery
8. Superficial temporal artery

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.

The respiratory quotient is the ratio of CO2 produced to O2 consumed while food is being metabolized:

RQ = CO2 eliminated/O2 consumed

Most energy sources are food containing carbon, hydrogen and oxygen. Examples include fat, carbohydrates, protein, and ethanol. The normal range of respiratory coefficients for organisms in metabolic balance usually ranges from 1.0-0.7.

Granulated sugar is a refined carbohydrate with no significant fat, protein or ethanol content.

The RQ for carbohydrates is = 1.0

The RQ for the rest of the compounds are:

Fats RQ = 0.7
The chemical composition of fats differs from that of carbohydrates in that fats contain considerably fewer oxygen atoms in proportion to atoms of carbon and hydrogen.

Protein RQ = 0.8
Due to the complexity of various ways in which different amino acids can be metabolized, no single RQ can be assigned to the oxidation of protein in the diet; however, 0.8 is a frequently utilized estimate.