Gentamicin is the aminoglycoside of choice in the UK and is used widely for the treatment of serious infections. It has a broad spectrum but is inactive against anaerobes and has poor activity against haemolytic streptococci and pneumococci. When used for the blind therapy of undiagnosed serious infections it is usually given in conjunction with a penicillin or metronidazole (or both). The main toxic effects are nephrotoxicity and ototoxicity due to damage to the vestibulocochlear nerve (CN VIII).

Gentamicin is contraindicated in myasthenia gravis and should be used with caution in renal disease which may result in accumulation and a greater risk of toxic side effects.

At rest, saliva is predominantly produced by the submandibular gland (65%) but when stimulated, the parotid glands produce a higher proportion of the total saliva production (50%) than at rest. Saliva is alkaline and hypotonic to plasma. The predominant digestive enzymes in saliva are alpha-amylase and lingual lipase; lingual lipase is not functionally very important, but alpha-amylase is important for the initiation of starch digestion. Saliva production is decreased by inhibition of the parasympathetic nervous system e.g. by sleep, dehydration, anticholinergic drugs and fear.

Hepatitis B surface antigen (HBsAg) is a protein on the surface of the hepatitis B virus, that is the first serologic marker to appear in a new acute infection.It can be detected as early as 1 week and as late as 9 weeks. It can be detected in high levels in serum during acute or chronic hepatitis B virus infection. The presence of HBsAg indicates that the person is infectious. The body normally produces antibodies to HBsAg as part of the normal immune response to infection. HBsAg is the antigen used to make hepatitis B vaccine.
Hepatitis B surface antibody (anti-HBs) indicates recovery and immunity from the hepatitis B virus infection. Anti-HBs also develops in a person who has been successfully vaccinated against hepatitis B.
Total hepatitis B core antibody (anti-HBc): Appears at the onset of symptoms in acute hepatitis B and persists for life. The presence of anti-HBc indicates previous or ongoing infection with hepatitis B virus in an undefined time frame. It is not present following hepatitis B vaccination.
IgM antibody to hepatitis B core antigen (IgM anti-HBc) indicates recent infection with hepatitis B virus (<6 months). Its presence indicates acute infection.
The following table summarises the presence of hepatitis B markers according to each situation:
Susceptible to infection:
HBsAg = Negative
Anti-HBc = Negative
Anti-HBs = Negative

Immune due to natural infection:
HBsAg = Negative
Anti-HBc = Positive
Anti-HBs = Positive

Immune due to vaccination:
HBsAg = Negative
Anti-HBc = Negative
Anti-HBs = Positive

Acute infection:
HBsAg = Positive
Anti-HBc = Positive
Anti-HBs = Negative
IgM anti-HBc = Positive

Chronic infection:
HBsAg = Positive
Anti-HBc = Positive
Anti-HBs = Negative
IgM anti-HBc = Negative

Approximately 65 – 70% of filtered K+is reabsorbed in the proximal tubule. Potassium reabsorption is tightly linked to that of sodium and water. The reabsorption of sodium drives that of water, which may carry some potassium with it. The potassium gradient resulting from the reabsorption of water from the tubular lumen drives the paracellular reabsorption of potassium and may be enhanced by the removal of potassium from the paracellular space via the Na+/K+ATPase pump. In the later proximal tubule, the positive potential in the lumen also drives the potassium reabsorption through the paracellular route.

A CT pulmonary angiogram is an angiogram of the blood vessels of the lungs. It is a diagnostic imaging test used to check for pulmonary embolism.

A pulmonary embolism is caused by a blood clot or thrombus that has become lodged in an artery in the lung and blocks blood flow to the lung. A patient with pulmonary embolism may feel an abrupt onset of pleuritic chest pain, shortness of breath, and hypoxia. Also, pulmonary embolism can result in alveolar dead space.

Dead space represents the volume of ventilated air that does not participate in gas exchange. The alveolar dead space is caused by ventilation/perfusion imbalances in the alveoli. It is defined as the sum of the volumes of alveoli that are ventilated but not perfused.

Aside from pulmonary embolism, smoking, bronchitis, emphysema, and asthma are among the other causes of alveolar dead space.

The other types of dead space are the following: Anatomical dead space is the portion of the airways that conducts gas to the alveoli. This is usually around 150 mL, and there is no possibility of gas exchange in these areas. Physiological dead space is the sum of anatomical and alveolar dead spaces.

Physiological dead space can account for up to 30% of the tidal volume.

The primary hip extensors are the gluteus maximus and the hamstrings such as the long head of the biceps femoris, the semitendinosus, and the semimembranosus. The extensor head of the adductor magnus is also considered a primary hip extensor.

The hip abductor muscle group is located on the lateral thigh. The primary hip abductor muscles include the gluteus medius, gluteus minimus, and tensor fasciae latae.
The secondary hip abductors include the piriformis, sartorius, and superior fibres of the gluteus maximus.

Hepatitis D virus (HDV) is an RNA virus that was discovered in 1977 and is structurally unrelated to the hepatitis A (HAV), hepatitis B (HBV), and hepatitis C (HCV) viruses. HDV causes a unique infection that requires the assistance of HBV viral particles to replicate and infect hepatocytes. Its clinical course is varied and ranges from acute, self-limited infection to acute, fulminant liver failure. Chronic liver infection can lead to end-stage liver disease and associated complications (including accelerated fibrosis, liver decompensation, and hepatocellular carcinoma).

The I-cells in the duodenum generate and release cholecystokinin (CCK), a peptide hormone. It has a crucial role in the digestion process as a hormonal regulator.

CCK cells are concentrated in the proximal small intestine, and when food is consumed, the hormone is produced into the bloodstream. The presence of partly digested lipids and proteins in the duodenum is one of the most powerful stimulus for CCK synthesis.

CCK’s key physiological effects include:

Encourages the pancreas to release digesting enzymes into the small intestine.
Stimulates gallbladder contraction and sphincter of Oddi relaxation, resulting in bile delivery into the duodenum.
Gastric emptying is inhibited, and gastric acid output is reduced.
Satiety induction is a process that involves inducing a feeling of fullness.

The latissimus dorsi muscle is a broad, flat muscle that occupies the majority of the lower posterior thorax. The muscle’s primary function is of the upper extremity but is also considered to be a respiratory accessory muscle.

Latissimus dorsi is a climbing muscle. With the arms fixed above the head, it can raise the trunk upwards, together with the help of pectoralis major.

Functionally, the latissimus dorsi muscle belongs to the muscles of the scapular motion. This muscle is able to pull the inferior angle of the scapula in various directions, producing movements on the shoulder joint (internal rotation, adduction and extension of the arm). It is innervated by the thoracodorsal nerve (C6 – C8) from the posterior cord of the brachial plexus, which enters the muscle on its deep surface.

Inhaled corticosteroids suppresses airway inflammation seen in asthma by downregulating pro-inflammatory proteins.
They also appear to reverse components of asthma-induced structural changes (airway remodelling), including increased vascularity of the bronchial wall.
Corticosteroids reduces the number of inflammatory cells (eosinophils, T lymphocytes, mast cells, and dendritic cells) in the airways.

Calcium homeostasis is primarily controlled by three hormones: parathyroid hormone, activated vitamin D and calcitonin.

Parathyroid hormone acts on the kidneys to increase calcium reabsorption in the distal tubule by activating Ca2+entry channels in the apical membrane and the Ca2+ATPase pump in the basolateral membrane (and to decrease phosphate reabsorption in the proximal tubule).

Activated vitamin D acts to increase calcium reabsorption in the distal tubule via activation of a basolateral Ca2+ATPase pump (and to increase phosphate reabsorption).

Calcitonin acts to inhibit renal reabsorption of calcium (and phosphate).

Historically, MRSA has been treated successfully with outpatient oral sulphonamides, clindamycin, rifampin, doxycycline, or a combination of these agents. With the development of increasing drug resistance of MRSA to these traditional antimicrobials, there has been a search for more effective antibiotics. One recent study demonstrated that vancomycin, linezolid, and quinupristin-dalfopristin were the most effective antibiotics against multiple strains of MRSA.

Lymph from the medial anterior two thirds of the tongue travels to the deep cervical lymph nodes.
Lymph from the lateral anterior tongue goes to the submandibular nodes.

Sensory innervation to the external ear is supplied by both cranial and spinal nerves. Branches of the trigeminal, facial, and vagus nerves (CN V, VII, X) are the cranial nerve components, while the lesser occipital (C2, C3) and greater auricular (C2, C3) nerves are the spinal nerve components involved. The lateral surface of the tympanic membrane, the external auditory canal, and the external acoustic meatus are all innervated by nervus intermedius (a branch of CN VII), the auriculotemporal nerve (CN V3), and the auricular branch of the vagus nerve. The concha receives split innervation from nervus intermedius, the auricular branch of the vagus nerve, and the greater auricular (spinal) nerve. Beyond the concha, the anteromedial and anterosuperior parts of the pinna are innervated by the auriculotemporal nerve, and a portion of the lateral helix by the lesser occipital nerve. The greater auricular nerve provides innervation to the area of the pinna inferolateral to the lobule.

Effects of beta-blockers:
Cardiovascular system:
Reduce blood pressure
Reduce heart rate, contractility and cardiac output
Increase AV conduction time, refractoriness and suppress automaticity

Eye:
Reduce intraocular pressure

Respiratory system:
Cause bronchoconstriction

Paracetamol is a non-opioid analgesic, similar in efficacy to aspirin, with antipyretic properties but no anti-inflammatory properties. It is well absorbed orally and does not cause gastric irritation. Paracetamol is a suitable first-line choice for most people with mild-to-moderate pain, and for combination therapy.

The femoral nerve runs down the front of the leg from the pelvis. It gives the front of the thigh and a portion of the lower leg sensation.

Extension of the leg at the knee joint, flexion of the thigh at the hip are produced by muscles that is primarily innervated by the femoral nerve.

Each motor unit contracts in an all or nothing fashion, i.e. if a motor unit is excited, it will stimulate all of its muscle fibres to contract. The force of contraction of a muscle is controlled by varying the motor unit recruitment (spatial summation), and by varying the firing rate of the motor units (temporal summation). During a gradual increase in contraction of a muscle, the first units start to discharge and increase their firing rate, and, as the force needs to increase, new units are recruited and, in turn, also increase their firing rate. For most motor units, the firing rate for a steady contraction is between 5 and 8 Hz. Because the unitary firing rates for each motor unit are different and not synchronised, the overall effect is a smooth force profile from the muscle. Increasing the firing rate of motor units is temporal summation where the tension developed by the first action potential has not completely decayed when the second action potential and twitch is grafted onto the first and so on. If the muscle fibres are stimulated repeatedly at a faster frequency, a sustained contraction results where it is not possible to detect individual twitches. This is called tetanus.

Theophylline and Ethylenediamine are combined in a 2:1 ratio to form Aminophylline. Its solubility is improved by the addition of Ethylenediamine. It has a lower potency and a shorter duration of action than Theophylline.
It is used to treat the following conditions:
Heart failure
It is used to treat the following conditions:
COPD
Bradycardias

Aminophylline has the following properties:
Phosphodiesterase inhibitor that increases intracellular cAMP and relaxes smooth muscle in the bronchial airways and pulmonary blood vessels.
Mast cell stabilization is achieved by using a non-selective adenosine receptor antagonist.
It has slight positive inotropic and chronotropic effects, increasing cardiac output and decreasing systemic vascular resistance, lowering arterial blood pressure. It has been used historically in the treatment of refractory heart failure and is indicated by the current ALS guidelines as a substitute treatment for bradycardia.

The daily oral dose for adults is 900 mg, divided into 2-3 doses. For severe asthma or COPD, a loading dosage of 5 mg/kg over 10-20 minutes is given, followed by a continuous infusion of 0.5 mg/kg/hour. The therapeutic range is small (10-20 microgram/ml), hence assessments of aminophylline plasma concentrations are useful during long-term treatment.

Inguinal hernias are subdivided into direct and indirect.

An indirect hernia occurs when abdominal contents protrude through the internal inguinal ring and into the inguinal canal. This occurs lateral to the inferior epigastric vessels. The hernia contents may extend into the scrotum.

A direct inguinal hernia is protrusion of abdominal contents through the transversalis fascia within Hesselbach’s triangle. The borders of Hesselbach’s triangle are the inferior epigastric vessels superolaterally, the rectus sheath medially, and inguinal ligament inferiorly.

The deep (internal) inguinal ring is located above and halfway between the pubic tubercle and the anterior superior iliac spine. This serves as the entrance to the inguinal canal. The superficial (external) inguinal ring lies immediately above and medial to the pubic tubercle. This triangular opening is a defect in the external oblique aponeurosis, and forms the exit of the inguinal canal.

Relative risk (RR) is a ratio of the probability of an event occurring in the exposed group versus the probability of the event occurring in the non-exposed group.

RR can be computed as the absolute risk of events in the treatment group (ART), divided by the absolute risk of events in the control group (ARC).

RR = ART/ARC
RR = (5/100) / (15/100)
RR = 0.33

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.

Erb’s palsy can be caused by a traumatic force downward on the upper arm and shoulder that damages the upper root of the brachial plexus.

The patient will lose shoulder abduction (deltoid, supraspinatus), shoulder external rotation (infraspinatus), and elbow flexion as a result of this condition (biceps, brachialis).

Local currents propagate action potentials down the axons of neurons. Following depolarization, this local current flow depolarizes the next axonal membrane, and when this region crosses the threshold, more action potentials are formed, and so on. 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 coating increases conduction. This enables faster electrical signal transmission via a neuron, making them more energy-efficient than non-myelinated neuronal axons.

Nodes of Ranvier are periodic holes in a myelinate axon when there is no myelin and the axonal membrane is exposed. There are no gated ion channels in the portion of the axon covered by the myelin sheath, but there is a high density of ion channels in the Nodes of Ranvier. Action potentials can only arise at the nodes as a result of this.
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.

A granuloma is a collection of five or more epithelioid macrophages, with or without attendant lymphocytes and fibroblasts; epithelioid macrophages are altered macrophages which have turned themselves over to becoming giant phagocytosing and killing machines, they often fuse to become multinucleate (Langhans) giant cells.

Positive predictive value (PPV) is the proportion of individuals with a positive test result who actually have the disease.
PPV = a/(a+b)

Most cells have insulin receptors present on them which can be sequestered into the cell to inactivate them. These receptors consist of two extracellular alpha subunits which contain the insulin-binding site and two transmembrane beta subunits. Because insulin is a polypeptide hormone, it must act via cell surface receptors as it is unable to readily cross the cell membrane. On binding to the receptor, the beta subunit of insulin autophosphorylation, which activates tyrosine kinase. As a result, there is an intracellular cascade of phosphorylation, causing a translocation of the glucose transporter GLUT4 and GLUT-1 to the plasma membrane of the affected cell. This facilitates glucose entry.

Dopamine is a catecholamine that occurs naturally and is used to treat low cardiac output, septic shock, and renal failure. It is both adrenaline and noradrenaline’s immediate precursor.

Dopamine acts on D1 and D2 dopamine receptors in the renal, mesenteric, and coronary beds at low doses (1-5 g/kg/min). Dopamine causes a significant decrease in renal vascular resistance and an increase in renal blood flow at these doses. Within this dose range, it is also involved in central modulation of behaviour and movement.

Dopamine stimulates beta- and alpha-adrenergic receptors directly and indirectly at higher doses. Beta-stimulation predominates at a rate of 5-10 g/kg/min, resulting in a positive inotropic effect that increases cardiac output and coronary blood flow. Alpha-stimulation predominates at infusion rates greater than 15 g/kg/min, resulting in peripheral vasoconstriction and an increase in venous return and systolic blood pressure.

Below is a summary of the mechanisms and effects of various inotropic agents:
Inotrope
Mechanism
Effects
Adrenaline (epinephrine)
Beta-1 and -2 agonist at increasing doses;
Alpha-agonist at high doses
Increased cardiac output;
Vasoconstriction at higher doses
Noradrenaline (norepinephrine)
Mainly alpha-agonist;
Beta-1 and -2 agonist at increasing doses
Vasoconstriction;
Some increased cardiac output
Dopamine
Dopamine agonist at low doses;
Beta-1 and -2 agonist at increasing doses;
Alpha-agonist at high doses
Increased cardiac output;
Vasoconstriction at higher doses
Dobutamine
Mainly beta-1 agonist
Increased cardiac output

Fick’s law describes the rate of diffusion in a solution. Fick’s law states that:
Jx = -D A (ΔC / Δx)
Where:
Jx = The amount of substance transferred per unit time
D = Diffusion coefficient of that particular substance
A = Surface area over which diffusion occurs
ΔC = Concentration difference across the membrane
Δx = Distance over which diffusion occurs
The negative sign reflects movement down the concentration gradient

A low anion gap is frequently caused by hypoalbuminemia. Albumin is a negatively charged protein and its loss from the serum results in the retention of other negatively charged ions such as chloride and bicarbonate. As bicarbonate and chloride anions are used to calculate the anion gap, there is a subsequent decrease in the gap. The anion gap is sometimes reduced in multiple myeloma, where there is an increase in plasma IgG (paraproteinaemia).