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.

Phase 2 trials involve patients that are suffering from the disease under study and are associated with determining the efficiency and the optimum dosage of the drug.

Phase 0 trials assist the scientists in studying the behaviour of drugs in humans by micro dosing patients. They are used to speed up the developmental process. They have no measurable therapeutic effect and efficiency.

Phase 1 is associated with assessing whether a drug is safe to use or not. The process is extensive and can take up to several months. It also involves healthy participants (less than 100) that are paid to take part in the study. The side effects upon increasing dosage are also addressed by the study. The effects the drug has on humans including how its absorbed, metabolized and excreted are studied. Approximately 70% of the drugs pass this phase.

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 static-response defines how a measuring system behaves while it is in equilibrium (i.e. when the measured values are not changing). If the value being measured changes over time, the reaction of a measuring system will change as well which would be a dynamic response.
The dynamic response of a measuring system can be subdivided into zero-order, first-order and second-order responses:

Zero-order:
Consider a thermometer that has been left in a room for a week. The thermometer will display the current ambient temperature when you enter the room.

First-order:
Consider the use of a mercury thermometer to check a patient’s temperature. It is comprised of a mercury column that expands as it warms up. The scale’s initial temperature is room temperature, but when it’s placed under the patient’s tongue, the temperature readings rise until they reach body temperature.

Second-order
Consider putting weights on a mechanical weighing scale. The weight as reported on the measuring dial, will wobble around the correct value at first until reaching equilibrium. An example of this is in clinical practice is the direct measurement of arterial pressure with a transducer. The value of the input fluctuates around a central point.

Drift is the progressive deterioration of a measurement system’s precision. With time, the measurement deviates from the genuine, calibrated value. The graph between this measurement and the real value should, ideally, be linear (e.g. on the y-axis the measured end-tidal CO2 against true value of the end-tidal CO2). Drift is split into three types: zero-offset, gradient, and zonal drift.

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).

Selection bias is when randomisation is not achieved and is often a result of in efficient recruiting method.

Recall bias is specifically appropriate to the case control studies that is when ever the memories retrieved by the participants differ in accuracy.

Measurement bias can be characterized by gathering of information in a manner that is distorted.

When the participants of a research study are recruited from the hospitals rather than the general population, its called Berkson Bias.

Confounding bias is the major player here because in this case the effects of smoking can be masked behind and can be read as outcomes of lower socio economic status. This extraneous factor (Smoking), distorts the founding.

Bell’s palsy is facial muscle weakness or paralysis that arises from idiopathic damage to the facial nerve. It can occur at any age but is commonly associated with some conditions:
1. pregnancy
2. diabetes
3. upper respiratory ailment
4. GBS
5. Toxins

The common symptoms of Bell’s palsy are:
1. Abnormal corneal reflex as the facial nerve controls the motor aspect of the corneal reflex.
2. The loss of control of facial muscles and eyelids leads to decreased tear production.
3. mild weakness to total paralysis on one side of the face, occurring within hours to days.
4. Bell’s palsy is a lower motor neuron lesion that usually spares the forehead while the upper motor near lesions, like stroke, involves the entire face.
5. The anterior two-thirds of the tongue is supplied by the chorda tympani branch of the facial nerve, thus resulting in loss of taste.
6. Ptosis can be a feature of Bell’s palsy but Bell’s palsy would typically show unilateral symptoms rather than bilateral.

Soda-lime contains mostly calcium hydroxide (about 94%) and the remaining sodium hydroxide.

CO2 + Ca(OH)2 †’ CaCO3 + H2O + heat
Here in this exothermic reaction, we can see that the production of calcium carbonate does not require heat.

When soda lime is allowed to dry with subsequent use of desflurane, isoflurane, and enflurane, it can lead to the generation of carbon monoxide.

Silicated hardens the granules and can thus prevent disintegration.

The size of soda-lime granules is 4-8 mesh because it allows sufficient surface area for chemical reaction to occur without critically increasing the resistance to airflow.

Phase IIa studies are usually pilot studies designed to demonstrate clinical efficacy or biological activity (‘proof of concept’ studies) whereas phase IIb studies determine the optimal dose at which the drug shows biological activity with minimal side-effects (€˜definite dose-finding’ studies).

Phase III and Phase IV studies are performed on larger set of participants (usually hundreds to thousands) when safety and efficacy have been established.

Small measurement units are denoted by the following SI mathematical prefixes:

1 deci = 0.1
1 milli = 0.001
1 micro = 0.000001
1 nano = 0.000000001
1 pico = 0.000000000001
1 femto = 0.000000000000001 (used to measure red blood cell volume)
1 atto = 0.000000000000000001.

The external urethral sphincter functions to provide voluntary control of urine flow from the bladder to the urethra.

It receives its innervation from the branches of the pudendal nerve which originate from S2, S3 and S4.

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

Phase 0 trials assist the scientists in studying the behaviour of drugs in humans by micro dosing patients. They are used to speed up the developmental process. They have no measurable therapeutic effect and efficiency.

Phase 1 is associated with assessing whether a drug is safe to use or not. The process is extensive and can take up to several months. It also involves healthy participants (less than 100) that are paid to take part in the study. The side effects upon increasing dosage are also addressed by the study. The effects the drug has on humans including how its absorbed, metabolized and excreted are studied. Approximately 70% of the drugs pass this phase.

Phase 2 trials involve patients that are suffering from the disease under study and are associated with determining the efficiency and the optimum dosage of the drug.

Phase 3 also assesses the efficacy but at a higher scale with larger population sample.

Phase 4 trials are involved with the long term effects and side effects of the drug.

Adrenaline acts on α1, α2, β1, and β2 receptors and also on dopamine receptors (D1, D2) and have sympathomimetic effects.

Natural catecholamines are Adrenaline, Noradrenaline, and Dopamine

Adrenaline is a sympathomimetic amine with both alpha and beta-adrenergic stimulating properties.
Adrenaline is the drug of choice for anaphylactic shock
Adrenaline is also used in patients with cardiac arrest. The preferred route is i.v. followed by the intra-osseous and endotracheal route.

Adrenaline is released by the adrenal glands, acts on α 1 and 2, β 1 and 2 receptors, and is responsible for fight or flight response.

It acts on β 2 receptors in skeletal muscle vessels-causing vasodilation.

It acts on α adrenergic receptors to inhibit insulin secretion by the pancreas. It also stimulates glycogenolysis in the liver and muscle, stimulates glycolysis in muscle.

It acts on β adrenergic receptors to stimulate glucagon secretion in the pancreas. It also stimulates Adrenocorticotrophic Hormone (ACTH) and stimulates lipolysis by adipose tissue

The equation for calculating vaporiser output is:

Vaporiser output (VO) mL = Carrier gas flow (mL/minute) × SVP of agent (kPa)
Ambient pressure (kPa) ˆ’ SVP of agent (kPa)

The saturated vapour pressure of sevoflurane at 1 atm (100 kPa) and 20°C is 21 kPa.

VO = (100 mL × 21 kPa)/(100 kPa ˆ’ 21kPa) for sevoflurane,
VO = 26.6 mL

26.6 mL of 100% sevoflurane and 100 mL bypass carrier gas is being added to the fresh gas flow per minute.

2660 mL of 1% sevoflurane and 100 mL bypass carrier gas is approximately 2.7 L/minute.

Epinephrine is used for the treatment of cardiac arrest because it causes vasoconstriction via the alpha-adrenergic (α1) receptor. This vasoconstriction increases cerebral and coronary blood flow by increasing mean arterial, aortic diastolic, and cerebral pressures. Furthermore, epinephrine is also a β1 and β2 adrenoreceptor agonist which shows inotrope, chronotrope, and bronchodilator effects.
– Adrenaline is also used to prolong the duration of action and decrease the systemic toxicity of local anaesthetics.
– Preferred route of adrenaline in patients with cardiac arrest is i.v. followed by intra-osseous and endotracheal.

Flowmeters measure the rate at which a specific gas, that the flowmeter has been calibrated for, passes through. This calibration is done at room temperature and standard atmospheric pressure with an accuracy of +/- 2%.

Reading the flowmeter is done from the top of a bobbin (the midpoint of a ball). Oxygen is the last gas to be added downstream to the mixture delivered to the back bar as a safety feature. This prevents delivery of a hypoxic mixture.

Inaccurate flow measurements occur when the bobbin sticks to the inside wall of the flowmeter. Stannic oxide has been used as a successful antistatic substance thus, reducing the aforementioned risk.

Carbon dioxide being easily delivered is found on some older machines, but those attached flowmeters are limited by a maximum flow of 500 ml /min. Thus avoiding the delivery of a hypercarbic mixture.

Fractures to the surgical neck of the humerus are common place as it is the weakest point of the proximal humerus bone.

The structures most likely to be damaged are the axillary nerve and the posterior circumflex humeral artery as they surround the surgical neck.

The radial nerve runs along the radial groove, so injury to it would likely occur with a mid-shaft fracture of the humerus.

The brachial artery is most likely to be injured as a result of a supracondylar fracture of the humerus which increases the risk of volkmaan’s ischemic contractures.

Injury to the musculocutaneous nerve is least likely to happen and it very uncommon.

For establishing a cause effect relationship, following criteria must be met:

1. Coherence & Consistency

2. Temporal Precedence

3. Specificity

As can be seen, sensitivity (The probability of a positive test) is not among these deciding factors..

Among the types of muscles, cardiac muscles have the greatest number if mitochondria due to the heart energy requirements.

Approximately 35% of the cardiac muscle volume is due to the mitochondria. While in skeletal and smooth muscles, it comprises 3-8% of the muscle volume.

Type I muscle fibre has a slow contraction velocity, with a red fibre colour, and predominantly uses oxidative phosphorylation to produce a sustained contraction. It contains more mitochondria and myoglobin than type II, and is often used for endurance training.

Type II muscle fibre has a fast contraction velocity, a white fibre colour, and predominantly uses anaerobic glycolysis. It has fewer mitochondria and myoglobin, and is often used for weight or resistance training and sprinting.

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.

Low molecular weight heparin (LMWH) creates a complex by binding to antithrombin. This complex binds with and inactivates factor Xa.

There is less risk of bleeding with LMWH because it binds less to platelets, endothelium and von Willebrand factor.

LMW binds Xa more readily. The shorter chains are less likely to bind both antithrombin and thrombin.

There is need for monitoring in renal impairment because LMHW is excreted in the urine (and partly by hepatic metabolism)

LMWH have been shown to be as efficacious as unfractionated heparin. It is also safer and have improved inpatient stay and reduced hospital cost.

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.

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

Work up bias involves comparing the novel diagnostic test with the current standard test. A portion of the patients undergo the standard test while others undergo the new test as the standard test is costly. The result can be alteration in specify and sensitivity.

Selection bias is when randomisation is not achieved.

Attention bias refers to the person’s failure to consider various alternatives when he pre occupied by some other thoughts.

Instrument bias is related to the experience and extent of familiarization of the participating individuals with the test.

Co intervention bias is characterized by the groups receiving different co interventions.

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 emulsification and absorption of fats requires Bile salts.

Absorption of fats is associated with the activation of lipases in the intestine.

Bile salts are involved in fat soluble vitamin absorption and are reabsorbed in the terminal ileum (B12 is NOT fat soluble).

Although Vitamin B12 is also absorbed in the terminal ileum, it is a water soluble vitamin (as are B1, nicotinic acid, folic acid and vitamin C) .

The gastric parietal cells secretes Intrinsic factor that is essential for the absorption of B12.

The ideal volatile agent for a day case surgery inhalational induction should have the following characteristics:

It has a pleasant scent that is not overpowering.
Breathing difficulties, coughing, or laryngeal spasm are not caused by this substance.
The action has a quick onset and a quick reversal.

The blood:gas partition coefficient is a physicochemical property of a volatile agent that determines the onset and offset of anaesthesia. The greater an agent’s insolubility in plasma, the faster its alveolar concentration rises.

The blood gas partition coefficients of the most commonly used volatile anaesthetic agents are as follows:
Halothane 2.3
Desflurane 0.45
Sevoflurane 0.6
Nitrous oxide 0.47
Isoflurane 1.4

Although halothane has a pleasant odour, it has a slower offset than sevoflurane.

Sevoflurane also has a pleasant odour and is less likely than desflurane to cause airway irritation and breath-holding.

The choice of agent for inhalational induction is unaffected by potency/lipid solubility measures such as the oil: gas partition coefficient and MAC.

In this case, an agent’s saturated vapour pressure is irrelevant.

Selection of a chest drain will depend on the external circumference.

A cannula, whether intravenous or intra-arterial, are classified according to standard wire gauge, which refers to the number of wires that can fit into the same hole. If a cannula is labelled 22G, then 22 wires will fit into the standard size hole.

A more popular measurement than SWG nowadays is cross sectional area.

When the concern for selecting equipment is the rate of flow, then it is important to consider the diameter and the radius of a parallel sided tube. These, however, are not routinely considered when comparing sizes of a cannula.

The metabolism of drugs in the liver occurs in 3 phases

Phase I: This involves functionalization reactions, which are of 3 types, namely hydrolysis, oxidation and reduction reactions catalysed by the cytochrome P450 (CYP) enzymes.

Phase II: This involves conjugation or acetylation reactions. The goal is to create water soluble metabolites that can be excreted from the body.

The liver is the second largest organ. It’s smallest functional unit is the acinus which is divided into 3 zones:

Zone I (periportal): This zone receives the largest amount of oxygen supply as it is the closest to the blood vessels. It is the site of plasma protein synthesis.

Zone II (mediolobular): This is located between the portal triad and central vein.

Zone III (centrilobular): This is closest to the central vein and receives the least amount of oxygen supply.

Kupffer cells are specialized macrophages found in the periportal zone of the liver, and function to remove foreign particles and breakdown red blood cells via phagocytosis.

Ito cells are fat-storing liver cells found in the space of Disse. Their function is to take-uo, store and secrete retinoids, as well as manufacture and release proteins that make up the extracellular matrix.