ACE inhibitors should be used with caution in patients of Afro-Caribbean descent who may respond less well; calcium channel blockers are first line for hypertension in these patients. ACE inhibitors have a role in the management of diabetic nephropathy. ACE inhibitors are contraindicated in pregnant women. ACE inhibitors inhibit the breakdown of bradykinin; this is the cause of the persistent dry cough. Blocking ACE also diminishes the breakdown of the potent vasodilator bradykinin which is the cause of the persistent dry cough. Angiotensin-II receptor blockers do not have this effect, therefore they are useful alternative for patients who have to discontinue an ACE inhibitor because of persistent cough.

Chronic hepatitis B infection is indicated by the persistence of HBsAg for more than 6 months. Hepatitis B has a long incubation period of about 2 – 6 months. Hepatitis B vaccine has recently been introduced to the routine childhood immunisation schedule – given at 2, 3 and 4 months. It is also given to babies born to hepatitis B infected mothers at birth, four weeks and 12 months old. Treatment of acute hepatitis is supportive. Treatment with antivirals should be considered in chronic infection as responders have a reduced risk of liver damage and liver cancer in the long term.

Clostridium tetani (causing tetanus) produces the exotoxin tetanospasmin which causes its neurotoxic effects.

Hepatitis A usually doesn’t pose a special risk to a pregnant woman or her baby. Maternal infection doesn’t result in birth defects, and a mother typically doesn’t transmit the infection to her baby. HAV is almost always transmitted by the faecal-oral route and is usually acquired through close personal contact or via contaminated food.

When a woman has chickenpox in the first 20 weeks of pregnancy, there is a 1 in 50 chance for the baby to develop a set of birth defects. This is called the congenital varicella syndrome. It includes scars, defects of muscle and bone, malformed and paralyzed limbs, small head size, blindness, seizures, and intellectual disability.

TORCH Syndrome refers to infection of a developing foetus or newborn by any of a group of infectious agents. “TORCH” is an acronym meaning (T)oxoplasmosis, (O)ther Agents, (R)ubella (also known as German Measles), (C)ytomegalovirus, and (H)erpes Simplex.
Infection with any of these agents may cause a constellation of similar symptoms in affected newborns. These may include fever; difficulties feeding; small areas of bleeding under the skin, causing the appearance of small reddish or purplish spots; enlargement of the liver and spleen (hepatosplenomegaly); yellowish discoloration of the skin, whites of the eyes, and mucous membranes (jaundice); hearing impairment; abnormalities of the eyes; and other symptoms and findings.

Angina pectoris is the most common symptom of ischemic heart disease and presents with chest pain relieved by rest and nitro-glycerine.

Nitrates are the first-line treatment to relieve chest pain caused by angina. The commonly used nitrates are:
1. Glyceryl trinitrate
2. Isosorbide dinitrate

The nitrate drugs are metabolized in the following steps:
1. Release Nitrite ions (NO2-), which are then converted to nitric oxide (NO) within cells.
2. NO activates guanylyl cyclase, which causes an increase in the intracellular concentration of cyclic guanosine-monophosphate (cGMP) in vascular smooth muscle cells.
3. Relaxation of vascular smooth muscle.

Although nitrates are potent coronary vasodilators, their principal benefit in the management of angina results from a predominant mechanism of venous dilation:
– Bigger veins hold more blood
– Takes blood away from the left ventricle
– Lowers LVEDV (preload), LA pressure
– Less pulmonary oedema → improved dyspnoea

Disease state vs Serology
Acute hepatitis: BHBsAg, HBeAg, anti-HBc IgM
Chronic hepatitis B (low infectivity): HBsAg (>6/12), anti-HBe, anti-HBc IgG
Chronic hepatitis B (high infectivity): HBsAg (>6/12), HBeAg, anti-HBc IgG
Cleared infection: Anti-HBs, anti-HBe, anti-HBc IgG
Vaccinated: Anti-HBs

During or shortly after transfusion, febrile transfusion reactions, also known as non-haemolytic transfusion reactions, present with an unexpected temperature rise (38oC or 1oC above baseline, if baseline is 37oC). This is usually a one-off occurrence. The fever is sometimes accompanied by chills.

The most common type of transfusion reaction is febrile transfusion reactions, which occur in about 1 in every 8 transfusions.

The most common event leading to symptoms of febrile transfusion reactions is cytokine accumulation during storage of cellular components (especially platelet units). White cells secrete cytokines, and pre-storage leucodepletion has reduced this risk.

Recipient antibodies (raised as a result of previous transfusions or pregnancies) reacting to donor human leukocyte antigen (HLA) or other antigens can also cause febrile transfusion reactions. Donor lymphocytes, granulocytes, and platelets all contain these antigens.

Treatment is reassuring. Other causes should be ruled out, and antipyretics like paracetamol can help with fever relief. If another cause of fever is suspected, the transfusion should be stopped; however, if other causes of fever have been ruled out, it can be restarted at a slower rate.

Escherichia coli is the most common cause of urinary tract infection. Uropathic strains are characterised by pili with adhesion proteins that bind to specific receptors on the urinary tract epithelium. The motility of E. coli aids its ability to ascend the urethra into the bladder or ascend the ureter into the kidney.

The hip adductors are a group of five muscles located in the medial compartment of the thigh. These muscles are the adductor longus, adductor brevis, adductor magnus, gracilis, and pectineus.

The hip flexors consist of 5 key muscles that contribute to hip flexion: iliacus, psoas, pectineus, rectus femoris, and sartorius.

Bronchiolitis is a common respiratory infection that occurs in infancy between the ages of 3-6 months and in the winter months. It is most commonly caused by the respiratory syncytial virus (70% of cases)

Although it can also be caused by parainfluenza virus, adenovirus, coronavirus, rhinovirus, and influenza virus, these are not the most common causes

Cardiac myocytes contract by excitation-contraction coupling, just like skeletal myocytes. Heart myocytes, on the other hand, utilise a calcium-induced calcium release mechanism that is unique to cardiac muscle (CICR). The influx of calcium ions (Ca2+) into the cell causes a ‘calcium spark,’ which causes more ions to be released into the cytoplasm.

An influx of sodium ions induces an initial depolarisation, much as it does in skeletal muscle; however, in cardiac muscle, the inflow of Ca2+ sustains the depolarisation, allowing it to remain longer. Due to potassium ion (K+) inflow, CICR causes a plateau phase in which the cells remain depolarized for a short time before repolarizing. Skeletal muscle, on the other hand, repolarizes almost instantly.

The release of Ca2+ from the sarcoplasmic reticulum is required for calcium-induced calcium release (CICR). This is mostly accomplished by ryanodine receptors (RyR) on the sarcoplasmic reticulum membrane; Ca2+ binds to RyR, causing additional Ca2+ to be released.

Hypocalcaemia occurs when there is abnormally low level of serum calcium ( >2.2 mmol/l) after correction for the serum albumin concentration.

Rhabdomyolysis causes hyperphosphatemia, and this leads to a reduction in ionised calcium levels.

Patients with rhabdomyolysis are commonly cared for in a high dependency care setting.

Addison’s disease, hyperthyroidism, thiazide diuretics and lithium all cause hypercalcaemia.

The electron transfer system is responsible for most of the energy produced during respiration. The is a system of hydrogen carriers located in the inner mitochondrial membrane. Hydrogen is transferred to the electron transfer system via the NADH2 molecules produced during glycolysis and the Krebs cycle. As a result, a H+ion gradient is generated across the inner membrane which drives ATP synthase. The final hydrogen acceptor is oxygen and the H+ions and O2 combine to form water.

The most potent diuretics are loop diuretics e.g. furosemide. They work by inhibiting the Na+/K+/2Cl-symporter in the thick ascending limb of the loop of Henle, which inhibits sodium, potassium, and chloride reabsorption. As a result, there is diuresis with loss of these electrolytes. There is a reduction in transcellular voltage difference, paracellular calcium and magnesium reabsorption.
The medullary interstitium becomes more concentrated by salt reabsorption in the ascending limb. Loop diuretics block this process and reduce the ability of the kidney to concentrate urine. In the collecting duct, there is increased sodium delivery to the principal cells, which increases potassium secretion in return for sodium reabsorption.

Following the action potential, Na+channels remain inactive for a time in a period known as the absolute refractory period where they cannot be opened by any amount of depolarisation. Following this there is a relative refractory period where the temporary hyperpolarisation (due to delayed closure of rectifier K+channels) makes the cell more difficult to depolarise and an action potential can be generated only in response to a larger than normal stimulus. The refractory period limits the frequency at which action potentials can be generated, and ensures that, once initiated, an action potential can travel only in one direction. An action potential is an all or nothing response so the amplitude of the action potential cannot be smaller.

Contractility (inotropy) is the intrinsic ability of cardiac muscle to develop force at a given muscle length. It is determined by the intracellular [Ca2+] and can be estimated by the ejection fraction. Increases in contractility cause an increase in stroke volume/cardiac output for any level of right atrial pressure or end-diastolic volume, and hence shift the Starling curve upwards. Decreases in contractility cause a decrease in stroke volume/cardiac output for any level of right atrial pressure or end-diastolic volume and hence shift the Starling curve downwards.

Metronidazole and the other 5-nitroimidazole agents inhibit nucleic acid synthesis by forming toxic free radical metabolites in the bacterial cell that damage DNA.

Vancomycin inhibits cell wall peptidoglycan formation by binding the D-Ala-D-Ala portion of cell wall precursors.

Erythromycin inhibits protein synthesis and blocks translocation by binding to the 23S rRNA of the 50S ribosomal subunit.

Chloramphenicol blocks peptidyl transferase at 50S ribosomal subunit.

Gentamicin, an aminoglycoside antibiotic, acts by binding to the 30S subunit of the bacterial ribosome inhibiting the binding of aminoacyl-tRNA and thus preventing initiation of protein synthesis.

An overview of the different mechanisms of action of the various types of antimicrobial agents is shown below:
1. Inhibition of cell wall synthesis
– Penicillins
– Cephalosporins
– Vancomycin
2. Disruption of cell membrane function
– Polymyxins
– Nystatin
– Amphotericin B
3. Inhibition of protein synthesis
– Macrolides
– Aminoglycosides
– Tetracyclines
– Chloramphenicol
4. Inhibition of nucleic acid synthesis
– Quinolones
– Trimethoprim
– 5-nitroimidazoles
– Rifampicin
5. Anti-metabolic activity
– Sulphonamides
– Isoniazid

The maximum flow rate generated during a forceful exhalation, after maximal inspiration is the peak expiratory flow rate (PEFR).

PEFR is dependent upon initial lung volume. It is, therefore, dependant on patient’s age, sex and height.

PEFR is dependent on voluntary effort and muscular strength of the patient.

PEFR is decreased with increasing airway resistance, e.g. in asthma, and it correlates well with the forced expiratory volume in one second (FEV1) value measured in spirometry. This correlation decreases in patients with asthma as airflow decreases.

By binding EF-G-GDP, fusidic acid prevents both peptide translocation and ribosome disassembly, which slows protein synthesis. Because it has a novel structure and mechanism of action, it is unlikely to cause cross-resistance with existing antibiotics.

Transfusion-associated circulatory overload (TACO) presents as acute or worsening respiratory distress within 6 hours of transfusion of a large volume of blood. It is common in patients with diminished cardiac reserve or chronic anaemia. Elderly patients, infants and severely anaemic patients are particularly susceptible. Typical clinical features of TACO include: Acute respiratory distress, Tachycardia, Hypertension, Acute/worsening pulmonary oedema on chest X-ray. The BNP is usually raised to at least 1.5 times the pre-transfusion baseline.

Febrile transfusion reaction presents with a 1 degree rise in temperature from baseline during transfusion. Patient may have chills and malaise. It is the most common transfusion reaction (1 in 8 transfusions) and is usually caused by cytokines released from leukocytes in transfused red cell or platelet components.

TRALI (Transfusion Related Acute Lung Injury) is a clinical syndrome with abrupt onset of non-cardiogenic pulmonary oedema within 6 hours of transfusion not explained by another risk factor. Associated with the presence of antibodies in the donor blood to recipient leukocyte antigens. patients present with dyspnoea, hypertension, hypotension, acute leukopenia.

Graft versus host disease(GVHD) is an immune mediated condition that arises from a complex interaction between donor and recipients adaptive immunity. It presents as dermatitis, hepatitis and enteritis developing within 100 days after stem cell or bone marrow transplant.

Acute haemolytic reaction aka immediate haemolytic transfusion reaction presents with fever, chills, pain at transfusion site, nausea, vomiting, dark urine and feeling of ‘impending doom’. Often, it occurs due to ABO incompatibility.

Somatostatin-producing cells present in the pyloric antrum, duodenum, and pancreatic islets are known as D-cells or delta-cells. Somatostatin inhibits gastric acid secretion by acting directly on acid-producing parietal cells in the stomach via a G-protein coupled receptor. By suppressing the release of other hormones such as gastrin, secretin, and histamine, somatostatin can indirectly reduce stomach acid output, slowing the digesting process.
The table below summarizes the many cell types found in the stomach, as well as the substances secreted by each cell type and the function of the secretion:

Cell type/ Substance secreted/ Function of secretion
Parietal cells/ Hydrochloric acid/ Kills microbes and activates pepsinogen
Parietal cells/ Intrinsic factor/Binds to vitamin B12 and facilitates its absorption
Chief cells/ Pepsinogen/ Protein digestion
Chief cells/ Gastric lipase/ Fat digestion
G-cells/ Gastrin/ Stimulates gastric acid secretion
Enterochromaffin-like cells (ECL cells) /Histamine/ Stimulates gastric acid secretion
Mucous-neck cells/ Mucous and bicarbonate/ Protects stomach epithelium from acid
D-cells/ Somatostatin/ Inhibits gastric acid secretion

Caseous necrosis is most commonly seen in tuberculosis. Histologically, the complete loss of normal tissue architecture is replaced by amorphous, granular and eosinophilic tissue with a variable amount of fat and an appearance reminiscent of cottage cheese.

Antidiuretic hormone is synthesised in the hypothalamus and transported to the posterior pituitary within nerve fibres where it is stored in secretory granules. ADH binds V2 receptors on renal principal cells in the late distal tubule and collecting ducts, raising cAMP levels and causing intracellular vesicles to fuse with the apical membrane. In their membrane these vesicles have water channels called aquaporins, which increase the water permeability allowing greater water reabsorption and concentration of urine. Excess levels of ADH results in syndrome of inappropriate ADH secretion (SIADH) characterised by hyponatremia with concomitant hypo-osmolality and high urine osmolality.

Lithium is the drug of choice for bipolar disorders but is commonly associated with side effects and toxicity.

Fine hand tremor is very commonly seen and reported in as many as 50% of patients during the first week of therapy with Lithium. The tremor tends to reduce with time and is only present in around 5% of patients taking the medication two years or longer. Lithium tremors are more common with older age, presumably due to the additive effects of age-related essential tremors.

Option The normal therapeutic range is 2.0-2.5 mmol/l: Lithium should be carefully monitored as it has a very low therapeutic index. The normal therapeutic range is 0.4-0.8 mmol/l. Levels should be checked one week after starting therapy and one week after every change in dosage. (Option Levels should be checked one month after starting therapy)

Option It can induce hyperthyroidism: Lithium has a known effect on thyroid function. Lithium decreases the production of T4 and T3 and commonly causes hypothyroidism. More rarely, lithium causes hyperthyroidism due to thyroiditis.

Option It can induce diabetes mellitus: Lithium can induce nephrogenic diabetes insipidus but not diabetes mellitus.

Colonic mass movement describes the intense contraction that begins halfway along the transverse colon and pushes the intestinal contents in the proximal colon towards the rectum. It occurs shortly after a meal due to distension of the stomach and duodenum as part of the gastrocolic reflex and if faeces is present in the rectum, stimulates the urge to defecate. Distention of the rectum causes firing of afferent cholinergic parasympathetic fibres. The internal sphincter is made up of circular smooth muscle innervated by the autonomic fibres, and the more distal external sphincter is composed of striated muscle innervated by motor fibres from the pudendal nerve. During defaecation, relaxation of pelvic muscles straightens the rectum.

Calcium-channel blockers, also known as calcium antagonists, stop calcium from entering cells through the L-type calcium channel. This causes vascular smooth muscle in vessel walls to relax, resulting in a decrease in peripheral vascular resistance.
They can be used for a variety of things, including:
Hypertension
Angina
Atrial fibrillation
Migraine

Calcium-channel blockers can be divided into two categories: dihydropyridines and non-dihydropyridines. The basic chemical structure of these two classes differs, as does their relative selectivity for cardiac versus vascular L-type calcium channels.

Dihydropyridines have a high vascular selectivity and lower systemic vascular resistance and blood pressure. As a result, they’re frequently used to treat hypertension. Modified release formulations are also used to treat angina, but their powerful systemic vasodilator and pressure-lowering effects can cause reflex cardiac stimulation, resulting in increased inotropy and tachycardia, which can counteract the beneficial effects of reduced afterload on myocardial oxygen demand.

The suffix -dpine distinguishes dihydropyridines from other pyridines. Examples of dihydropyridines that are commonly prescribed include:
Amlodipine
Felodipine
Nifedipine
Nimodipine

The phenylalkylamine class and the benzothiazepine class are two subgroups of non-dihydropyridines.

Phenylalkylamines are less effective as systemic vasodilators because they are relatively selective for the myocardium. This group of drugs lowers myocardial oxygen demand and reverses coronary vasospasm, making them useful in the treatment of angina. They are also occasionally used to treat arrhythmias. A phenylalkylamine calcium-channel blocker like verapamil is an example.

In terms of selectivity for vascular calcium channels, benzothiazepines fall somewhere between dihydropyridines and phenylalkylamines. They can lower arterial pressure without producing the same level of reflex cardiac stimulation as dihydropyridines because they have both cardiac depressant and vasodilator effects. Diltiazem is the only benzothiazepine currently in clinical use.

The hookworm life cycle begins with the passage of eggs from an adult host into the stool. Hookworm eggs hatch in the soil to release larvae that mature into infective larvae. Infection is usually transmitted by larval penetration into human skin (duodenal infection may also be transmitted by the oral route). From the skin, larvae migrate into the blood vessels and are carried to the lungs, where they penetrate the pulmonary alveoli, ascend the bronchial tree to the pharynx, and are swallowed.

Angiotensin I is converted to angiotensin II by the removal of two C-terminal residues by the enzyme angiotensin-converting enzyme (ACE). This primarily occurs in the lungs, although it does also occur to a lesser degree in endothelial cells and renal epithelial cells.
The main actions of angiotensin II are:
Vasoconstriction of vascular smooth muscle (resulting in increased blood pressure)
Vasoconstriction of the efferent arteriole of the glomerulus (resulting in an increased filtration fraction and preserved glomerular filtration rate)
Stimulation of aldosterone release from the zona glomerulosa of the adrenal cortex
Stimulation of anti-diuretic hormone (vasopressin) release from the posterior pituitary
Stimulation of thirst via the hypothalamus
Acts on the Na+/H+ exchanger in the proximal tubule of the kidney to stimulate Na+reabsorption and H+excretion

Calcium deficiency (low Ca2+ diet or hypocalcemia) activates 1-alpha-hydroxylase in the cells of the renal proximal tubule which catalyses the conversion of vitamin D to its active form, 1,25-dihydroxycholecalciferol. Increased parathyroid hormone (PTH) and hypophosphatemia also stimulate the enzyme. Chronic renal failure is associated with a constellation of bone diseases, including osteomalacia caused by failure of the diseased renal tissue to produce the active form of vitamin D.

Immediately after the closure of the semilunar valves, the ventricles rapidly relax and ventricular pressure decreases rapidly but the AV valves remain closed as initially the ventricular pressure is still greater than atrial pressure. This is isovolumetric relaxation. Atrial pressure continues to rise because of venous return, with the v wave of the JVP waveform peaking during this phase. Rapid flow of blood from the atria into the ventricles during the ventricular filling phase causes thethird heart sound, which is normal in children but, in adults, is associated with disease such as ventricular dilation.