The hindgut is from the distal third of the transverse colon down to the upper one-third of the anal canal. The inferior mesenteric artery supplies the hindgut.

The inferior mesenteric artery arises from the aorta behind the inferior border of the third part of the duodenum 3–4 cm above the aortic bifurcation, at the third lumbar vertebra level.

The important landmarks of vessels arising from the abdominal aorta at different levels of vertebrae are:

T12 – Coeliac trunk

L1 – Left renal artery

L2 – Testicular or ovarian arteries

L3 – Inferior mesenteric artery

L4 – Bifurcation of the abdominal aorta

Sodium-chloride symporter inhibitor.

The thiazide sensitive sodium chloride symporter is inhibited by thiazides at the proximal portion of the distal convoluted tubule leading to increased sodium and water excretion. Increased delivery of sodium to the distal portion of the distal convoluted tubule promotes potassium loss. This is why thiazides are associated with hyponatraemia and hypokalaemia.

Carbonic anhydrase inhibitors are used mainly in the treatment of glaucoma. They act on the proximal convoluted tubule to promote bicarbonate, sodium and potassium loss.

Sodium potassium chloride symporter is inhibited by Loop diuretics.
Epithelial sodium channels are inhibited by Amiloride.
Drugs which lead to nephrogenic diabetes insipidus such as lithium and demeclocycline, are Inhibitors of vasopressin.

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 ECG changes seen in hypomagnesaemia include:

Prolonged PR interval
Prolonged QT interval
Flattening of T waves
ST segment depression
Prominent U waves

These changes are almost the same as those of hypokalaemia.

There is an increased risk of digoxin toxicity and a risk of atrial and ventricular ectopic and ventricular arrhythmias.

There is impaired synthesis and release of parathyroid hormone (PTH) in chronic hypomagnesaemia leading to impaired target organ response to PTH. This produces secondary hypocalcaemia.

The use of potassium ‘wasting’ diuretics (e.g. loop diuretics like furosemide) may lead to Hypomagnesaemia.

A tall T wave is seen in hypermagnesemia.

Cell membrane pore formation, Bacterial DNA damage, Peptidoglycan cross-linking inhibition, and peptidoglycan synthesis inhibitor are always lethal and such mechanisms are possible only in bactericidal drugs. But Protein synthesis inhibition would only prevent cell replication or cell growth and is responsible for bacteriostatic effects of the drug.

The gag reflex is a protective mechanism that prevents any foreign material to enter the aerodigestive tract.

This reflex has afferent (sensory) and effect (motor) components.
– Glossopharyngeal nerve form the afferent limb
– Vagus nerve form the efferent limb

The central venous pressure (CVP) waveform depicts changes of pressure within the right atrium. Different parts of the waveform are:

A wave: which represents atrial contraction. It is synonymous with the P wave seen during an ECG. It is often eliminated in the presence of atrial fibrillation, and increased tricuspid stenosis, pulmonary stenosis and pulmonary hypertension.

C wave: which represents right ventricle contraction at the point where the tricuspid valve bulges into the right atrium. It is synonymous with the QRS complex seen on ECG.

X descent: which represents relaxation of the atrial diastole and a decrease in atrial pressure, due to the downward movement of the right ventricle as it contracts. It is synonymous with the point before the T wave on ECG.

V wave: which represents an increase in atrial pressure just before the opening of the tricuspid valve. It is synonymous with the point after the T wave on ECG. It is increased in the background of a tricuspid regurgitation.

Y descent: which represents the emptying of the atrium as the tricuspid valve opens to allow for blood flow into the ventricle in early diastole.

Canon waves: which refer to large waves present on the trace that do not correspond to the A, V or C waves. They usually occur in a background of complete heart blocks or junctional arrythmias.

Second messengers relay signals to target molecules in the cytoplasm or nucleus when an agonist interacts with a receptor on the cell surface. They also amplify the strength of the signal. The most ubiquitous and abundant second messenger is calcium and it regulates multiple cellular functions in the body.

These include:
Muscle contraction (skeletal, smooth and cardiac)
Exocytosis (neurotransmitter release at synapses and insulin secretion)
Apoptosis
Cell adhesion to the extracellular matrix
Lymphocyte activation
Biochemical changes mediated by protein kinase C.

cAMP is either inhibited or stimulated by G proteins.

The receptors in the body that stimulate G proteins and increase cAMP include:

Beta (?1, ?2, and ?3)
Dopamine (D1 and D5)
Histamine (H2)
Glucagon
Vasopressin (V2).

The second messenger for the action of nitric oxide (NO) and atrial natriuretic peptide (ANP) is cGMP.

The second messengers for angiotensin and thyroid stimulating hormone are inositol triphosphate (IP3) and diacylglycerol (DAG).

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 clinical potency of the anaesthetic agent is measured using minimal alveolar concentration(MAC).

MAC and oil: gas partition coefficient is inversely related. Anaesthetic agent Oil/gas partition coefficient and Minimal alveolar concentration (MAC) is given respectively as

Desflurane 18 6
Isoflurane 90 1.2
Nitrous oxide 1.4 104
Sevoflurane 53.4 2
Xenon 1.9 71

With these data, we can conclude Isoflurane is the most potent with the highest oil/gas partition coefficient of 90 and the lowest MAC of 1.2

Warming, humidifying, and filtering inspired anaesthetic gases is done by heat and moisture exchangers (HME) and breathing system filters. They are made of glass fibres materials and are supported by a sturdy frame. Pleating increases the surface area to reduce resistance to air flow and boost efficiency.

Filters’ effectiveness is determined by the amount and size of particles they keep out of the patient’s airway. The efficiency of filters might be classified as 95, 99.95, or 99.97 percent. Pores with a diameter of 0.2 µm are common. The following are examples of typical particle sizes:
Red blood cell – 5 µm
Lymphocyte – 5-8 µm
Viruses – 0.02-0.3 µm
Bacteria – 0.5-1 µm
Depending on particle size, gas flow speed, and charge, particles are collected via a number of processes. Mechanical sieve, interception, diffusion, electrostatic filtration, and inertial impaction are some of the options:

Sieve:
The diameter of the particle the filter is supposed to collect is smaller than the apertures of the filter’s fibres.

Interception:
When a particle following a gas streamline approaches a fibre within one radius of itself, it becomes attached and captured.
Diffusion:

A particle’s random (Brownian) zig-zag path or motion causes it to collide with a fibre.
By attracting and capturing a particle from within the gas flow, it generates a lower-concentration patch within the gas flow into which another particle diffuses, only to be captured. At low gas velocities and with smaller particles (0.1µm diameter), this is more common.

Electrostatic:

These filters use large diameter fibre media and rely on electrostatic charges to improve fine particle removal effectiveness.

Impaction due to inertia:

When a particle is too large to respond fast to abrupt changes in streamline direction near a filter fibre, this happens. Because of its inertia, the particle will continue on its original course and collide with the filter fibre. When high gas velocities and dense fibre packing of the filter media are present, this sort of filtration mechanism is most prevalent.

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

The inferior thyroid artery is derived from the thyrocervical trunk.

Fentanyl is a pethidine congener, 80–100 times more potent than morphine, both in analgesia and respiratory depression. Fentanyl is ten times more potent than alfentanil.

Alfentanil has a more rapid onset than fentanyl even if fentanyl is more lipid-soluble because both are basic compounds and alfentanil has lower pKa, so a greater proportion of alfentanil is unionized and is more available to cross membranes.

Elimination of alfentanil is higher than fentanyl due to its lower volume of distribution.

Haemorrhage, including intracranial bleeding, is a common and potentially fatal side effect of warfarin therapy, and reversing anticoagulation quickly and completely can save lives. When complete and immediate correction of the coagulation defect is required in orally anticoagulated patients with life-threatening haemorrhage, clotting factor concentrates are the only viable option.

For rapid reversal of vitamin K anticoagulants, prothrombin complex concentrates (PCC) are recommended. They contain the vitamin K-dependent clotting factors II, VII, IX, and X and are derived from human plasma. They can be used as an adjunctive therapy in patients with major bleeding because they normalise vitamin K dependent clotting factors and restore haemostasis.

The most common treatments are fresh frozen plasma (FFP) and vitamin K. The efficacy of this approach is questioned due to the variable content of vitamin K-dependent clotting factors in FFP and the effects of dilution. Significant intravascular volume challenge, as well as the possibility of rare complications like transfusion-associated lung injury or blood-borne infection, are all potential issues.

To avoid anaphylactic reactions, vitamin K should be given as a slow intravenous infusion over 30 minutes. Regardless of the route of administration, the reversal of INRs with vitamin K can take up to 24 hours to reach its maximum effect.

Reversal of anticoagulation in patients with warfarin-associated intracranial haemorrhage may be considered with factor VIIa (recombinant), but its use is controversial. There are concerns about thromboembolic events following treatment, as well as questions about assessing efficacy in changes in the INR. If the drug is to be administered, patients should be screened for an increased risk of thrombosis before the drug is given.

The axillary nerve lies behind the axillary artery initially, and in front of the subscapularis. It passes downward to the lower border of the subscapularis muscle.

In company with the posterior humeral circumflex artery and vein, it winds backward through a quadrilateral space bounded above by the subscapularis (anterior) and teres minor (posterior), below by the teres major, medially by the long head of the triceps brachii, and laterally by the humerus (surgical neck).

It then divides into an anterior and a posterior part. The anterior division supplies the deltoid (anterior and middle heads) while the posterior division supplies the teres minor and posterior part of deltoid
The posterior division terminates as the superior lateral cutaneous nerve of the arm

The subclavian artery and vein have a similar path throughout their course, with the subclavian vein running anterior to the subclavian artery. The artery and vein are separated by the insertion of the scalenus anterior muscle.

There are three scalene muscles, found on each side of the neck:
1. Anterior scalene
2. Middle scalene
3. Posterior scalene

The scalenus anterior muscle is the anterior most of the three scalene muscles. It originates from the transverse processes of vertebrae C3-C6 and is inserted in the first rib.

A compound that contains an asymmetric centre (chiral atom or chiral centre) and thus can occur in two non-superimposable mirror-image forms (enantiomers) are called chiral compounds.

Desflurane, Halothane, and isoflurane are chiral compounds but Sevoflurane is not a chiral compound.

The fall in plasma concentration of a drug with time decreases exponentially in a single compartment pharmacokinetic model (wash-out curve).

A straight line is produced when the logarithm (ln) of a drug’s plasma concentration is plotted against time because a constant proportion of the drug is removed from the plasma per unit time. The line’s gradient or slope can be expressed mathematically as k. (the rate constant). The gradient is related to the half life (T1/2) because it can be used to predict a drug’s plasma concentration at any time.

According to the following formula, clearance (CL), volume of distribution (Vd), and elimination rate constant (k) are mathematically related.

CL = Vd x k

For drug A, CL = 1 x 0.1 = 0.1units per minute

For drug B, Cl = 2 x 0.2 = 0.4 units per minute

Hence, it is proved that Drug A has a lower clearance than drug B.

In patients with an intact hypothalamic-pituitary axis, serial TSH measurements are used to determine the adequacy of treatment with thyroid hormones . changes in TSH levels becoming apparent after approximately eight weeks of therapy with thyroid hormone replacement. Change in T3/T4 levels are seen before changes in TSH .

In patients taking thyroid replacement therapy, the most frequent reason for persistent elevation of serum TSH is poor compliance. Patients who do not regularly take their L-thyroxine try and catch up just before a visit to a clinician for blood test.

Tissue-level unresponsiveness to thyroid hormone is caused by mutation in the gene controlling a receptor for T3 and is rare.

Reduced responsiveness of target tissues to thyroid hormone aka resistance to thyroid hormones (rTH) occurs when there is a mutation in the thyroid hormone receptor ? gene. It is a rare autosomal dominant inherited syndrome of reduced end-organ responsiveness to thyroid hormone and has two types:

Generalised resistance (GrTH)
Pituitary resistance (PrTH)

Patients with rTH have normal or slightly elevated serum thyroid stimulating hormone (TSH) level, elevated serum free thyroxine (FT4) and free triiodothyronine (FT3) concentrations.

Drugs that increase metabolism of thyroxine include:

Warfarin
Rifampin
Phenytoin
Phenobarbital
St John’s Wort
Carbamazepine

These drugs lower circulating thyroid hormones and would be associated with a raised TSH but low T3/T4.

Number needed to treat (NNT) is a time specific epidemiological measure that indicates how many patients would be require for an intervention to prevent one additional bad outcome. A perfect NNT would be 1, where everyone improves with treatment, thus the higher the NNT, the less effective the treatment.

Thus if you treat 1000 patients then you will expect to have 50 fewer strokes.

The liver receives blood supply from two sources.
1. Hepatic artery proper
It arises from the celiac trunk via the common hepatic artery and brings oxygenated blood to the liver.
It contributes to approximately 30% of the blood supply of the liver.
2. Hepatic portal vein – supplies the liver with partially deoxygenated blood, carrying nutrients absorbed from the small intestine. It gets tributaries from the inferior mesenteric vein, splenic vein, and superior mesenteric vein

The inferior mesenteric artery supplies the hindgut.
The superior mesenteric artery supplies the pancreas and intestine up to the proximal two-thirds of the transverse colon.
The inferior phrenic artery supplies the inferior surface of the diaphragm and oesophagus.

Caudal analgesia using bupivacaine is a widely employed technique for achieving both intraoperative and early postoperative pain relief. 0.5 ml/kg of 0.25% plain bupivacaine is favoured by many practitioners who employ this fixed scheme for procedures involving sacral dermatomes (circumcision, hypospadias repair) as well as lower thoracic dermatomes (orchidopexy). However, there are other dosing regimens for caudal blocks with variable analgesic success rates: These include 0.75 ml/kg, 1.0 ml/kg and 1.25 ml/kg.

A study indicated that plain bupivacaine 0.25% at a dose of 0.75 ml/kg compared to a dose of 0.5 ml/kg when administered for herniotomies provided improved quality of caudal analgesia with a low side effects profile. There were consistently more patients with favourable objective pain scale (OPS) scores at all timelines, increased the time to the analgesic request with similar postoperative consumption of paracetamol in the group of patients who received 0.75 ml/kg of 0.25% bupivacaine.

Ketamine, a phencyclidine derivative, is an antagonist at the NMDA receptor. It causes depression of the CNS that is dose dependent and induces a dissociative anaesthetic state with profound analgesia and amnesia.

Ketamine has a chiral centre usually presented as a racemic mixture with two optical isomers, S (+) and R (-) forms. These isomers are in equal proportions. The S (+) isomer is about three times more potent than the R (-) form. The S (+) form is less likely to cause emergence delirium and hallucinations.

Ketamine is extensively metabolised by hepatic microsomal cytochrome P450 enzymes producing norketamine as its main metabolite. Norketamine has a one third to one fifth as potency as its parent compound.
It increases the CMRO2, cerebral blood flow and potentially increase intracranial pressure.

The shaft of the humerus has two prominent features:
1. Deltoid tuberosity – attachment for the deltoid muscle
2. Radial or spiral groove – The radial nerve and profunda brachii artery lie in the groove

Mid-shaft fractures of the humerus usually occur after a direct blow to the upper arm, which can occur after a fall or RTAs. The most important clinical significance of a mid-shaft humeral fracture is an injury to the radial nerve. The radial nerve originates from the brachial plexus and has roots of C5-T1. It crosses the spiral groove on the posterior side of the shaft of the humerus.
On examination, the patient may have a wrist drop, loss or weakness of finger extension, and decreased or absent sensation to the posterior forearm, digits 1 to 3, and the radial half of the fourth digit.

The following parts of the humerus are in direct contact with the indicated
nerves:
Surgical neck: axillary nerve.
Radial groove: radial nerve.
Distal end of humerus: median nerve.
Medial epicondyle: ulnar nerve.

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.

The abdominal aorta begins at the level of the body of T12 near the midline, as a continuation of the thoracic aorta. It descends and bifurcates at the level of L4 into the common iliac arteries.

An abdominal aortic aneurysm is a swelling in the abdominal aorta. It most commonly occurs in men over 65 years old of age. Smoking, diabetes, hypertension, and hypercholesterolemia are other risk factors contributing to the disease.

The NHS screening program for abdominal aortic aneurysms involves an ultrasound test for men aged 65 or over if they have not undergone screening for a one-off screening test.

Cardiac output = stroke volume x heart rate

Left ventricular ejection fraction = (stroke volume / end diastolic LV volume ) x 100%

Stroke volume = end diastolic LV volume – end systolic LV volume

Pulse pressure = Systolic Pressure – Diastolic Pressure

Systemic vascular resistance = mean arterial pressure / cardiac output
Factors that increase pulse pressure include:
-a less compliant aorta (this tends to occur with advancing age)
-increased stroke volume

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.

The arch of aorta gives rise to three main branches:
1. Brachiocephalic artery
2. Left common carotid artery
3. Left subclavian artery

The brachiocephalic artery then gives rise to the right subclavian artery and the right common carotid artery.

The right common carotid artery arises from the brachiocephalic trunk posterior to the sternoclavicular joint.

The coeliac trunk is a branch of the abdominal aorta.
The ascending aorta supplies the coronary arteries.

Asthma is a lung condition that causes reversible narrowing and swelling of airway passages. It is classified by the frequency and severity of symptoms.

The following are symptoms of moderate asthma:

Symptoms include cough, wheezing, chest tightness, or difficulty breathing which occurs daily
Decreased activity levels due to flare-ups
Night-time symptoms 5 or more times a month
Lung function test FEV1 is 60-80% of predicted normal values
Peak flow has more than 30% variability

With moderate asthma attacks, the arterial pCO2 levels may decrease, but as severity increases, so does the pCO2, reaching normal levels, and then exceeding them in severe asthma attacks.

Airway obstruction increases the functional residual capacity.

Concentration of serum bicarbonate would not increase in moderate asthma, but it could possibly increase in life-threatening asthma via the same mechanism as what increases arterial PCO2.

FEV1 is a good measure of airway obstruction. and is reduced in acute asthma attacks.

In the case of a pneumothorax, a decrease in arterial PO2 is higher.