Midazolam is the benzodiazepine in question. It’s the only benzodiazepine that undergoes tautomeric transformation (dynamic isomerism). The molecule is ionised and water soluble at pH 3.5, but when injected into the body at pH 7.4, it becomes unionised and lipid soluble, allowing it to easily pass through the blood brain barrier.

The half-life of midazolam is only 2-4 hours.

It is a GABAA receptor agonist because it is a benzodiazepine. GABAA receptors are found in abundance throughout the central nervous system, particularly in the cerebral cortex, hippocampus, thalamus, basal ganglia, and limbic system. GABAA receptors are ligand-gated ion channels, with the inhibitory neurotransmitter gamma-aminobutyric acid as the endogenous agonist. It is a pentameric protein (2, 2 and one subunit) that spans the cell membrane, and when the agonist interacts with the alpha subunit, a conformational change occurs, allowing chloride ions to enter the cell, resulting in neuronal hyperpolarization.

For status epilepticus, midazolam is not the drug of choice. Lorazepam is the benzodiazepine of choice for status epilepticus.

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.

Impaired ventricular relaxation reduces diastolic filling and therefore preload.

Decreased blood volume decreases preload due to reduced venous return.

Heart failure is characterized by reduced ejection fraction and therefore stroke volume.

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 (is increased by stroke volume) = 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
Aortic stenosis would decrease stroke volume as end systolic volume would increase.
This is because of an increase in afterload, an increase in resistance that the heart must pump against due to a hard stenotic valve.

Mixed venous oxygen content (CvO2) is the oxygen concentration in 100mL of mixed venous blood taken from the pulmonary artery. It is usually 12-17 mL/dL (70-75%). It is represented mathematically as:

CvO2 = (1.34 x Hgb x SvO2 x 0.01) + (0.003 x PvO2)

Where,

1.34 = Huffner’s constant
Hgb = Haemoglobin level (g/dL)
SvO2 = % oxyhaemoglobin saturation of mixed venous blood
PvO2 = 0.0225 = mL of O2 dissolved per 100mL plasma per kPa, or 0.003 mL per mmHg

Therefore,

CvO2 = (1.34 x 10 x 70 x 0.01) + (0.003 x 50)

CvO2 = 9.38 + 0.15 = 9.53 mL/100mL

Campylobacter is the commonest bacterial cause of infectious intestinal disease in the UK. The majority of cases are caused by the Gram-negative bacillus Campylobacter jejuni which is spread by the faecal-oral route. The incubation period is 1-6 days.

Features include a prodrome phase with headaches and malaise, then diarrhoea occurs which is often bloody.
There is often abdominal pain which may mimic appendicitis.

It is usually self-limiting but treatment is warranted if the infection is severe or the infection occurs in an immunocompromised patient.
Severe infection comprises of high fever, bloody diarrhoea, or more than eight stools per day or symptoms last for more than one week.
This management would include antibiotics and the first-line antibiotic is clarithromycin.
Ciprofloxacin is an alternative but there are strains with decreased sensitivity to ciprofloxacin which can be frequently isolated.

Complications include:
1.Guillain-Barre syndrome may follow Campylobacter
2. Jejuniinfections
3. Reactive arthritis
4. Septicaemia, endocarditis, arthritis

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.

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.

Observation bias occurs when the behaviour of an individual changes that results from their awareness of being observed.

Recall bias introduced when participants in a study are systematically more or less likely to recall and relate information on exposure depending on their outcome status.

Attrition bias is a systematic error caused by unequal loss of participants from a randomized controlled trial (RCT). In clinical trials, participants might dropout due to unsatisfactory treatment or efficacy, intolerable adverse events, or even death.

Selection bias introduced when the individuals are not chosen randomly to take a part in the study. It usually occurs when the research decides who is going to be studied, they are not the representative of the population.

Lead-time bias occurs when a disease is detected by a screening test at an earlier time point rather than it would have been diagnosed by its clinical appearance. In this bias, earlier detection improves the survival time in the intervention group.

The international system of units, or system international d’unites (SI) is a collection of measurements derived from expanding the metric system.

There are seven base units, which are:

Metre (m): a unit of length
Second (s): a unit of time
Kilogram (kg): a unit of mass
Ampere (A): a unit of electrical current
Kelvin (K): a unit of thermodynamic temperature
Candela (cd): a unit of luminous intensity
Mole (mol): a unit of substance.

This may be the classical case of blood transfusion reaction due to ABO incompatibility.

Here red cells are destroyed in the bloodstream with the release of haemoglobin in circulation (causing haemoglobinuria). Here, IgM or IgG anti-A or anti-B antibody can cause rapid activation of complement cascade usually the classical pathway. This is called intravascular haemolysis.

There may be extravascular haemolysis by cells of the mononuclear phagocyte system situated in the liver and spleen. Extravascular red cell destruction can increase breakdown products of haemoglobin, such as bilirubin and urobilinogen.