Causes of intravascular haemolysis:
Haemolytic transfusion reactions
G6PD deficiency
Red cell fragmentation syndromes
Some severe autoimmune haemolytic anaemias
Some drug-and infection-induced haemolytic anaemias
Paroxysmal nocturnal haemoglobinuria

Local currents propagate action potentials down the axons of neurons. This local current flow following depolarisation results in the depolarisation of the neighbouring axonal membrane, and when this region approaches the threshold, more action potentials are generated and so forth. Due to the refractory period, portions of the membrane that have recently depolarized will not depolarize again, resulting in the action potential only being able to go in one direction.

The square root of axonal diameter determines the velocity of the action potential; the axons with the biggest diameter have the quickest conduction velocities. When a neuron is myelinated, the speed of the action potential rises as well.
The myelin sheath is an insulating coating that surrounds certain neural axons. By increasing membrane resistance and decreasing membrane capacitance, the myelin sheath improves conduction. This enables faster electrical signal transmission via a neuron, making them more energy-efficient than non-myelinated neuronal axons.
Electrical impulses are quickly transmitted from one node to the next, causing depolarization of the membrane above the threshold and triggering another action potential, which is then transmitted to the next node. An action potential is rapidly conducted down a neuron in this manner. Saltatory conduction is the term for this.
Multiple sclerosis is an example of a clinical disorder in which the myelin sheath is affected. It is an immune-mediated disorder in which certain nerve cells in the brain and spinal cord become demyelinated. The ability of some areas of the nervous system to properly transmit action potentials is disrupted by demyelination, resulting in a variety of neurological symptoms and indications.

Of the filtered sodium, about 65% is reabsorbed in the proximal tubule.

Thyroid hormones have multiple physiological effects on the body. These include:
1. Heat production (thermogenesis)
2. Increased basal metabolic rate
3. Metabolic effects:
(a) Increase in protein turnover (both synthesis and degradation are increased, although overall effect is catabolic)
(b) Increase in lipolysis
(c)Increase in glycogenolysis and gluconeogenesis
4. Enhanced catecholamine effect – Increase in heart rate, stroke volume and thus cardiac output
5. Important role in growth and development

Short vessels called arteriovenous anastomoses (AVAs) link tiny arteries and veins. They have a large lumen diameter. The strong and muscular walls allow AVAs to completely clog the vascular lumen, preventing blood flow from artery to vein (acting like a sphincter). When the AVAs open, they create a low-resistance connection between arteries and veins, allowing blood to flow into the limbs’ superficial venous plexuses. There is no diffusion of solutes or fluid into the interstitium due to their strong muscle walls.

AVAs are densely innervated by adrenergic fibres from the hypothalamic temperature-regulation centre. High sympathetic output occurs at normal core temperatures, inducing vasoconstriction of the AVAs and blood flow through the capillary networks and deep plexuses. When the temperature rises, sympathetic output decreases, producing AVA vasodilation and blood shunting from the artery to the superficial venous plexus. Heat is lost to the environment as hot blood rushes near to the skin’s surface.
AVAs are a specialized anatomical adaptation that can only be found in large quantities in the fingers, palms, soles, lips, and pinna of the ear.

When you take too much aspirin, you have a mix of respiratory alkalosis and metabolic acidosis. Respiratory centre stimulation produces hyperventilation and respiratory alkalosis in the early phases. The direct acid actions of aspirin tend to create a higher anion gap metabolic acidosis in the latter phases.
Below summarizes some of the most common reasons of acid-base abnormalities:

Respiratory alkalosis:
– Hyperventilation (e.g. anxiety, pain, fever)
– Pulmonary embolism
– Pneumothorax
– CNS disorders (e.g. CVA, SAH, encephalitis)
– High altitude
– Pregnancy
– Early stages of aspirin overdose

Respiratory acidosis:
– COPD
– Life-threatening asthma
– Pulmonary oedema
– Respiratory depression (e.g. opiates, benzodiazepines)
– Neuromuscular disease (e.g. Guillain-Barré syndrome, muscular dystrophy
– Incorrect ventilator settings (hypoventilation)
– Obesity

Metabolic alkalosis:
– Vomiting
– Cardiac arrest
– Multi-organ failure
– Cystic fibrosis
– Potassium depletion (e.g. diuretic usage)
– Cushing’s syndrome
– Conn’s syndrome

Metabolic acidosis (with raised anion gap):
– Lactic acidosis (e.g. hypoxaemia, shock, sepsis, infarction)
– Ketoacidosis (e.g. diabetes, starvation, alcohol excess)
– Renal failure
– Poisoning (e.g. late stages of aspirin overdose, methanol, ethylene glycol)

Metabolic acidosis (with normal anion gap):
– Renal tubular acidosis
– Diarrhoea
– Ammonium chloride ingestion
– Adrenal insufficiency

Cardiac glycosides (e.g. digoxin) slow the removal of Ca2+from the cell by inhibiting the membrane Na+pump (Na+/K+ATPase) which generates the Na+gradient required for driving the export of Ca2+by Na+/Ca2+exchange; consequently the removal of Ca2+from the myocyte is slowed and more Ca2+is available for the next contraction.

Both the medial and lateral pterygoids are innervated by the mandibular division of the trigeminal nerve.

Angiotensin II constricts both the afferent and efferent arterioles, but preferentially increases efferent resistance. The net effect of the more prominent increase in efferent tone is that the intraglomerular pressure is stable or increased, thereby tending to maintain or even raise the GFR. Renin is produced by granular cells of the juxtaglomerular apparatus. Renin cleaves plasma angiotensinogen (produced in the liver) into angiotensin I. Angiotensin I is converted by angiotensin-converting enzyme (ACE) on pulmonary endothelial cells to angiotensin II. Angiotensin II acts to potentiate sympathetic activity (positive feedback).

Diabetes insipidus is the inability to produce concentrated urine. It is characterised by the presence of excessive thirst, polyuria and polydipsia. There are two distinct types of diabetes insipidus:
Cranial (central) diabetes insipidus and;
Nephrogenic diabetes insipidus
Cranial diabetes insipidus is caused by a deficiency of vasopressin (anti-diuretic hormone). Patients with cranial diabetes insipidus can have a urine output as high as 10-15 litres per 24 hours, but adequate fluid intake allows most patients to maintain normonatraemia. 30% of cases are idiopathic, and a further 30% are secondary to head injuries. Other causes include neurosurgery, brain tumours, meningitis, granulomatous disease (e.g. sarcoidosis) and drugs, such as naloxone and phenytoin. A very rare inherited form also exists that is associated with diabetes mellitus, optic atrophy, nerve deafness and bladder atonia.
Nephrogenic diabetes insipidus is caused by renal resistance to the action of vasopressin. As with cranial diabetes insipidus, urine output is markedly elevated. Serum sodium levels can be maintained by secondary polydipsia or can be elevated. Causes of nephrogenic diabetes insipidus include chronic renal disease, metabolic disorders (e.g. hypercalcaemia and hypokalaemia) and drugs, including long-term lithium usage and demeclocycline.
In view of the history of long-term lithium use, in this case, nephrogenic diabetes insipidus is the most likely diagnosis.

Dietary iron may be in the form of haem or non-haem iron. Haem iron is degraded after absorption through the cell surface to release Fe2+. Most non-haem iron is in the form Fe3+, which is reduced at the luminal surface to the more soluble Fe2+, facilitated by hydrochloric acid in gastric secretions (and enhanced by ascorbic acid). Fe2+is taken across the enterocyte apical membrane by the divalent metal transporter (DMT1). In the enterocyte, Fe2+is then either stored in enterocyte epithelial cells as ferritin, or released into portal plasma via the molecule ferroportin at the basolateral membrane.

Absolute risk reduction (ARR) is computed as the difference between the absolute risk in the control group (ARC) and the absolute risk in the treatment group (ART).

ARR = ARC-ART
ARR = (25/500) – (10/500)
ARR = 0.03

Glucagon is a peptide hormone that is produced and secreted by alpha cells of the islets of Langerhans, which are located in the endocrine portion of the pancreas. The main physiological role of glucagon is to stimulate hepatic glucose output, thereby leading to increases in glycaemia. It provides the major counter-regulatory mechanism to insulin in maintaining glucose homeostasis.
Hypoglycaemia is the principal stimulus for the secretion of glucagon but may also be used as an antidote in beta-blocker overdose and in anaphylaxis in patients on beta-blockers that fail to respond to adrenaline.
Glucagon then causes:
Glycogenolysis
Gluconeogenesis
Lipolysis in adipose tissue
The secretion of glucagon is also stimulated by:
Adrenaline
Cholecystokinin
Arginine
Alanine
Acetylcholine
The secretion of glucagon is inhibited by:
Insulin
Somatostatin
Increased free fatty acids
Increased urea production

Glycolysis is the metabolic pathway that converts glucose into pyruvate. The free energy released by this process is used to form ATP and NADH. Glycolysis is inhibited by glucagon, and glycolysis and gluconeogenesis are reciprocally regulated so that when one cell pathway is activated, the other is inactive and vice versa.

Glucagon has a minor effect of enhancing lipolysis in adipose tissue. Lipolysis is the breakdown of lipids and involves the hydrolysis of triglycerides into glycerol and free fatty acids. It makes fatty acids available for oxidation.

Abciximab (ReoPro) is a glycoprotein IIb/IIIa receptor antagonist that is a chimeric monoclonal antibody. It is primarily used during and after coronary artery procedures such as angioplasty to inhibit platelet aggregation.

The use of abciximab is contraindicated in the following situations:
Internal bleeding is present.
Within the last two months, you’ve had major surgery, intracranial surgery, or trauma.
Stroke in the previous two years
Intracranial tumour
Aneurysm or arteriovenous malformation
Haemorrhagic diathesis is a type of haemorrhagic diathesis.
Vasculitis
Retinopathy caused by hypertension

Hartmann’s pouch is a diverticulum that can occur at the neck of the gallbladder. It is one of the rarest congenital anomalies of the gallbladder. Hartmann’s gallbladder pouch is a frequent but inconsistent feature of normal and pathologic human gallbladders. It is caused by adhesions between the cystic duct and the neck of the gallbladder. As a result, it is classified as a morphologic rather than an anatomic entity.

There is a significant association between the presence of Hartmann’s pouch and gallbladder stones. It is the most common location for gallstones to become lodged and cause cholestasis.

Alterations in the international normalized ratio (INR) brought about by the concurrent use of antibiotics and warfarin may result in either excessive clotting or excessive bleeding if they are deemed to have a high risk for interaction. As such, there should be careful consideration of the class of antibiotic to be used.

Antibiotics from the following drug classes should generally be avoided as they have a high risk for interaction with warfarin, possible enhancing the anticoagulant effects of warfarin resulting in bleeding: Fluoroquinolones (e.g. ciprofloxacin, levofloxacin), Macrolides (e.g. clarithromycin, erythromycin, azithromycin), Nitroimidazoles (e.g. metronidazole), Sulphonamides (e.g. co-trimoxazole, a combination of trimethoprim and sulfamethoxazole), Trimethoprim, Tetracyclines (e.g. doxycycline).

Low risk antibiotics that have low risk for interaction with warfarin includes cephalexin, from the cephalosporin class, and clindamycin which is a lincomycin.

Each subdivision of the pharynx has a different sensory innervation:the nasopharynx is innervated by the maxillary nervethe oropharynx is innervated by the glossopharyngeal nervethe laryngopharynx is innervated by the vagus nerve.

Oral rehydration therapy (ORT) is a fluid replacement strategy used to prevent or treat dehydration. It is less invasive than other strategies for fluid replacement and has successfully lowered the mortality rate of diarrhoea in developing countries. Oral rehydration solutions should be slightly hypo-osmolar (about 250 mmol/litre) to prevent the possible induction of osmotic diarrhoea.
ORT contains glucose (e.g. 90 mmol/L in dioralyte). The addition of glucose improves sodium and water absorption in the bowel and prevents hypoglycaemia. It also contains essential mineral salts.
Current NICE guidance recommends that 50 ml/kg is given over 4 hours for the treatment of mild dehydration.
Once rehydrated, a child should continue with their usual daily fluid intake plus 200 ml ORT after each loose stool. In an infant, give ORT at 1-1.5 x the normal feed volume and in an adult, give 200-400 ml after each loose stool.

The heart sounds are as a result of the various parts of the cardiac cycle.
Heart Sound – Phase of Cardiac Cycle – Mechanical Event:
1st heart sound – Systole starts – there is closure of the atrioventricular (mitral & tricuspid) valves
2nd heart sound – Systole ends – there is closure of the semilunar (aortic and pulmonary) valves
3rd heart sound – Early diastole – this is caused by rapid flow of blood from the atria into the ventricles during the ventricular filling phase
4th heart sound – Late diastole – this is caused by filling of an abnormally stiff ventricle in atrial systole

In infants and young children, lymphocytosis often occurs in response to infections that would normally produce a neutrophil reaction in adults.
Lymphocytosis occurs in:
1. Viral infections (e.g. infectious mononucleosis, HIV, rubella, mumps, viral hepatitis, cytomegalovirus, herpes simplex or zoster)
2. Bacterial infections (e.g. pertussis, tuberculosis, toxoplasmosis, syphilis)
3. Chronic lymphoid leukaemias
4. Acute lymphoblastic leukaemias
5. Non-Hodgkin lymphoma
6. Thyrotoxicosis