Approximately 25% of phase-1 drug reactions is made responsible by CYP2D6.

As much as a 1,000-fold difference in the ability to metabolise drugs by CYP2D6 can happen between phenotypes, and this may result in adverse drug reactions (ADRs).

The metabolism of antiemetics, beta-blockers, codeine, tramadol, oxycodone, hydrocodone, tamoxifen, antidepressants, neuroleptics, and antiarrhythmics is also as a result of CYP2D6.

Patients who take drugs that are metabolised by CYP2D6 but have poor CYP2D6 metabolism are more likely to have ADRs. People with ultra-rapid CYP2D6 metabolism may have a decreased drug effect due to low plasma concentrations of these drugs.

All the other CYP enzymes are subject to genetic polymorphism. Variants are less likely to lead to adverse drug reactions.

A person remaining at high altitudes for days, weeks, or years becomes more and more acclimatized to the low PO2, so it causes fewer deleterious effects on the body.

After acclimatization, it becomes possible for the person to work harder without hypoxic effects or to ascend to still higher altitudes. The principal means by which acclimatization comes about are (1) a great increase in pulmonary ventilation, (2) increased numbers of red blood cells, (3) diffusing capacity of the lungs, (4) increased vascularity of the peripheral tissues, and (5) increased ability of the tissue cells to use oxygen despite low PO2.

The cardiac output often increases as much as 30% immediately after a person ascends to high altitude but then decreases back toward normal over a period of weeks as the blood haematocrit increases, so the amount of oxygen transported to the peripheral body tissues remains about normal.

The descending thoracic aorta begins at the lower border of T4 near the midline as a continuation of the arch of the aorta. It descends and ends at the level of T12 at the aortic hiatus in the diaphragm, where it becomes the abdominal aorta.

The aorta gives off the following branches: (descending order)

1. Bronchial arteries
2. Mediastinal arteries
3. Oesophageal arteries
4. Pericardial arteries
5. Superior phrenic arteries

The posterior intercostal arteries are branches that originate throughout the length of the posterior aspect of the descending thoracic aorta.

The inferior thyroid artery is usually derived from the thyrocervical trunk, a branch of the subclavian artery.

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 humeral shaft has two compartments:
1. Anterior:
Brachial artery and vein
Biceps brachii, brachialis, coracobrachialis
Musculocutaneous, median, and ulnar nerves
2. Posterior:
Radial nerve
Triceps

Other significant nerve injuries are:
1. Axillary nerve – surgical neck fracture of the humerus
2. Brachial Artery – supracondylar fracture of the humerus
3. Axillary artery – surgical neck fracture of the humerus, but is relatively uncommon

Incidence tells us about the number of new cases that have been reported while prevalence gives us the idea of existing cases.

In this particular instance, the parameter of the study i.e. the total number of cases has not changed thus the prevalence of the disease remains same. Although, more cases have been reported in the second instance as a result of which incidence has increased.

The blood vessel well is divided into 3 parts, namely:

The tunica intima, which is the deepest layer. It contains endothelial cells separated by gap junctions

The tunica media, primarily consisting of the involuntary smooth muscle fibres, laid out in spiral layers with elastic fibres and connective tissue.

The tunica adventitia, which is the most superficial layer. It consists of the vasa vasorum, fibroblast and collagen.

In the Child-Pugh classification system, the following 5 components are determined or calculated in order:

Ascites

Grade of encephalopathy

Serum bilirubin (?mol/L)

Serum Albumin (g/L)

Prothrombin time or INR

Raised liver enzymes are not the component of the classification system.

Because of the low pH in the stomach, paracetamol absorption is minimal (pKa value is 9.5). Paracetamol is absorbed quickly and completely in the alkaline environment of the small intestine. Oral bioavailability is approaching 100%. As a result, measuring paracetamol levels in plasma after an oral paracetamol dose has been used as a surrogate marker of gastric emptying. This method has been used to investigate the effects of drugs on gastric emptying. At clinically used doses, paracetamol is ideal because it has very few side effects.

Scintigraphic imaging is the gold standard for determining gastric emptying.

Although aspirin (acetyl salicylic acid) is absorbed primarily in the small intestine, some may also be absorbed in the stomach. The oral bioavailability ranges from 70 to 100 percent, making it less reliable than paracetamol.

Propranolol is a lipophilic drug that is rapidly absorbed after administration. However, it is highly metabolised by the liver in the first pass, and only about 25% of propranolol reaches the systemic circulation. It’s not the best indicator of gastric emptying.

Oral bioavailability of gentamicin and vancomycin is low. Only antibiotic-induced pseudomembranous colitis is treated with oral vancomycin.

Erythromycin is a pro-kinetic agent that acts as a motilin receptor agonist.

Because alpha glucosidase inhibitors slow starch digestion in the small intestine, glucose from a meal enters the bloodstream more slowly and can be matched more effectively by an impaired insulin response or sensitivity, glucose from a meal enters the bloodstream more slowly and can be matched more effectively by an impaired insulin response or sensitivity.

Biguanides decrease hepatic glucose output while increasing glucose uptake in peripheral cells.

The meglitinides are secretagogues that act on a different site of the KATP receptors.

Insulin secretion is stimulated by sulphonylureas, which stimulate insulin secretion from pancreatic beta cells. The KATP channels are inhibited by these substances.

Insulin-sensitive genes are influenced by thiazolidinediones, which increase the production of mRNAs for insulin-dependent enzymes. As a result, the cells make better use of glucose.

The tibial nerve lies on top of the vessels contained within the inferior aspect of the popliteal fossa.

In the superior aspect of the fossa, the tibial nerve runs lateral to the vessels, before then travelling superficial to the vessels, and then finally changing course to lie medial to the vessels.

The popliteal artery is the most deep structure present in the popliteal fossa

The most common cause of hypoparathyroidism is injury or removing the parathyroid glands. They can be injured accidentally during surgery to remove the thyroid as they are located posterior to the thyroid gland.

A result of both low parathyroid hormone and low calcium is likely to mean that the parathyroid glands are not responding to hypocalcaemia. The hypocalcaemia can cause confusion, and the stay in the hospital is likely to refer to her surgery.

While a parathyroid adenoma is fairly common and can cause hypoparathyroidism, it much more likely causes hyperparathyroidism.

Chronic kidney disease is likely to cause hypocalcaemia, which would increase parathyroid hormone production in an attempt to increase calcium levels, causing hyperparathyroidism. Vitamin D is activated by the kidneys and then binds to calcium to be absorbed in the terminal ileum so that a deficiency would cause hyperparathyroidism.

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.

Randomisation allows for performance of experimental trials in a random order. Using this method gives us control over the confounding variables that are not supposed to be held constant.

For an instance, by employing randomisation we get to control biological differences among individual human beings during experimental trials.

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.

Oxytocin is secreted by the posterior pituitary along with Antidiuretic Hormone (ADH). It increases the contraction of the upper segment (fundus and body) of the uterus whereas the lower segment is relaxed facilitating the expulsion of the foetus.

Oxytocin acts through G protein-coupled receptor and phosphoinositide-calcium second messenger system to contract uterine smooth muscle.

It has 0.5 to 1 % ADH activity introducing possibilities of water intoxication when used in high doses.

The sensitivity of the uterus to oxytocin increases as the pregnancy progresses.

It is used for induction of labour in post maturity and uterine inertia.

Attributable proportion is the proportion of disease that is caused due to exposure. It refers to the proportion of disease that would be eradicated from a particular population if the disease rate was diminished to match that of the unexposed group.

Risk ratio (relative risk) compares the probability of an event in an exposed (experimental) group to that of an event in the unexposed (control) group. Thus two are not the same.

The attributable risk is the rate of a disease in an exposed group to that of a group that has not been exposed to it i.e. how many deaths did the exposure cause.

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.

The arterial blood gas analysis indicates presence of acute respiratory acidosis.

Central chemoreceptors are located in the ventral medulla and respond directly to presence of hydrogen ions in the CSF. When stimulated, it causes an increase in respiratory rate.

It is believed that hydrogen ions may be the only important direct stimulus for these neurons, however, CO2 is believed to stimulate these neurons secondarily by changing the hydrogen ion concentration.

Changes in O2 concentration have virtually no direct effect on the respiratory centre itself to alter respiratory drive. Although, O2 changes do have an indirect effect by acting through the peripheral chemoreceptors.

The area described in the question is supplied by the intercostobrachial nerve, which provides sensory innervation to the portions of the axilla, tail of the breast, lateral chest wall and medial side of the arm.

It is a common for it to be ‘missed’ during administration of local anaesthesia because of its very superficial anatomic course. It may be anesthetized by giving an analgesia from the upper border of the biceps at the anterior axillary fold, to the margin of the triceps by the axillary floor.

A is correct. Common myeloid progenitor cells are involved in the anaphylaxis reaction.
B is incorrect. The common lymphoid lineage gives rise to T-cells, B-cell and NK cells.
C is incorrect as megakaryocytes give rise to platelets.
D is incorrect – Neural crest cells give rise to various cells throughout the body, including melanocytes, enterochromaffin cells and Schwann cells. However, they do not give rise to mast cells.
E is incorrect. Reticulocytes give rise to erythrocytes.

This is a classic case of anaphylaxis. In this situation, IgE previously raised against antigens (in this case peanut antigen) bind to mast cells, and this causes them to degranulate.
There is release of vasoactive substances like histamine into the blood, and this is responsible for the symptoms seen. Therefore, the main type of cells involved in the pathogenesis of the disease is mast cells.

The functional residual capacity (FRC) is the volume in the lungs at the end of passive expiration. It is determined by opposing forces of the expanding chest wall and the elastic recoil of the lung. A normal FRC = 1.7 to 3.5 L. It a marker for lung function, and, during this time, the alveolar pressure is equal to the atmospheric pressure.

FRC cannot be measured by spirometry because it contains the residual volume.

Tidal volume, inspiratory reserve volume, forced expiratory volume in 1 second, and vital capacity can be measured directly.

The glucose molecule enters the Bowman’s capsule freely and becomes part of the filtrate.

All glucose is reabsorbed in the proximal convoluted tubule when blood glucose concentrations are below a certain threshold (approximately 11 mmol/L) (PCT). Active transportation makes this possible. In the proximal tubular cells, sodium/glucose cotransporters (SGLT1 and SGLT2) are the proteins responsible.

Glucose does not normally appear in the urine below the renal threshold.

The renal glucose threshold is not set in stone and is affected by a variety of factors, including GFR, TmG, and the quantity of splay.

The different absorptive and filtering capacities of individual nephrons cause splay, which is the rounding of a glucose reabsorption curve.

The SGLT proteins have a high affinity for glucose, but not an infinite affinity. As a result, some glucose may escape reabsorption before the TmG. A decrease in renal threshold may be caused by an increase in splay.

Because the filtered glucose load is reduced and the PCT can reabsorb all of the filtered glucose despite hyperglycaemia, a low GFR causes an increase in TmG. In contrast, lowering the TmG lowers the threshold because the tubules’ ability to reabsorb glucose is reduced.

A reduction in GFR caused by severe dehydration and reduced perfusion pressure is the most obvious cause of the discrepancy between plasma and urinary glucose in this scenario.

The potency of local anaesthetics is directly proportional to lipid solubility because they need to penetrate the lipid-soluble membrane to enter the cell.

Protein binding has a direct relationship with the duration of action because the higher the ability of the drug to bind with membrane protein, the higher is the duration of action.

Higher the pKa of a drug, slower the onset of action. Because a drug with higher pKa will be more ionized than the one with lower pKa at a given pH. Local anaesthetics are weak bases, and unionized form diffuses more rapidly across the nerve membrane than the protonated form. As a result drugs with higher pKa will be more ionized will diffuse less across the nerve membrane.

During glycolysis, 2,3-diphosphoglycerate (2,3-DPG) is
created in erythrocytes by the Rapoport-Luebering shunt.

The production of 2,3-DPG increases for several conditions
in the presence of decreased peripheral tissue O2 availability.
Some of these conditions include hypoxaemia, chronic lung
disease anaemia, and congestive heart failure. Thus,
2,3-DPG production is likely an important adaptive mechanism.

High levels of 2,3-DPG cause a shift of the curve to the right.
Low levels of 2,3-DPG cause a shift of the curve to the left,
as seen in states such as septic shock and hypophosphatemia.

The adrenal (suprarenal) gland is composed of two main parts: the adrenal cortex, which is the largest and outer part of the gland, and the adrenal medulla. The adrenal cortex consists of three zones: 1. Zona glomerulosa (outermost layer) is responsible for the production of mineralocorticoids, mainly aldosterone, which regulates blood pressure and electrolyte balance. 2. Zona fasciculata (middle layer) is responsible for the production of glucocorticoids, predominantly cortisol, which increases blood sugar levels via gluconeogenesis, suppresses the immune system, and aids in metabolism. It also produces 11-deoxycorticosterone and corticosterone in addition to cortisol. 3. Zona reticularis (innermost layer) is responsible for the production of gonadocorticoids, mainly dehydroepiandrosterone (DHEA), which serves as the starting material for many other important hormones produced by the adrenal gland, such as oestrogen, progesterone, testosterone, and cortisol. It is also responsible for administering these hormones to the reproductive regions of the body.

The adrenal medulla majorly secretes epinephrine (adrenaline), and norepinephrine in small quantity. Both hormones have similar functions and initiate the flight or fight response.

Catecholamine is mediated by cholinergic nicotinic transmission through changes in sympathetic nervous system (T5 – T11), being increased during stress and hypoglycaemia.

Blood supply to the adrenal gland is by these three arteries: superior suprarenal arteries, middle suprarenal artery and inferior suprarenal artery. Venous drainage is via the suprarenal vein to the left renal vein or directly to the inferior vena cava on the right side. There is no portal (venous) system between cortex and medulla.

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 deep inguinal ring is the entrance of the inguinal canal. It is an opening in the transversalis fascia around 1 cm above the inguinal ligament. Therefore, the superolateral wall is made by the transervalis fascia.

The inferior epigastric vessels run medially to the deep inguinal ring forming its inferomedial border.

The inguinal canal extends obliquely from the deep inguinal ring to the superficial inguinal ring.
An indirect inguinal hernia arises through the deep inguinal ring lateral to the inferior epigastric vessels.

Giardiasis is known to have a longer incubation time and doesn’t cause bloody diarrhoea.

Cholera usually doesn’t cause bloody diarrhoea.

Generally, most of the E.coli strains do not cause bloody diarrhoea.

Diverticulitis can be a cause of bloody stool but the history here points out to an infectious cause.

Campylobacter infection is the most probable cause as it is characterized by a prodrome, abdominal pain and bloody diarrhoea

The surface marking for locating the femoral artery is the mid-inguinal point, which is the halfway point between the anterior superior iliac spine (ASIS) and the pubic symphysis.

The other mentioned options are not specific for any landmark.

However, it is important to note the difference between the mid inguinal point and the midpoint of the inguinal ligament, which is travels from the ASIS to the pubic tubercle.