Sixty-seven percent of filtered water is reabsorbed in the proximal tubule. The driving force for water reabsorption is a transtubular osmotic gradient established by reabsorption of solutes (e.g., NaCl, Na+-glucose).

Henle’s loop reabsorbs approximately 25% of filtered NaCl and 15% of filtered water. The thin ascending limb reabsorbs NaCl by a passive mechanism, and is impermeable to water. Reabsorption of water, but not NaCl, in the descending thin limb increases the concentration of NaCl in the tubule fluid entering the ascending thin limb. As the NaCl-rich fluid moves toward the cortex, NaCl diffuses out of the tubule lumen across the ascending thin limb and into the medullary interstitial fluid, down a concentration gradient as directed from the tubule fluid to the interstitium. This mechanism is known as the counter current multiplier.

The distal tubule and collecting duct reabsorb approximately 8% of filtered NaCl, secrete variable amounts of K+ and H+, and reabsorb a variable amount of water (approximately 8%-17%).

Adenosine is the first line for AV nodal re-entry tachycardia. An initial dose of 6 mg is given, and a consequent second dose or third dose of 12 mg is administered if the initial dose fails to terminate the arrhythmia.

Aside from Adenosine, a vagal manoeuvre (e.g. carotid massage) is done to help terminate the supraventricular arrhythmia.

Amiodarone is not a first-line drug for supraventricular tachycardias. Digoxin and Propranolol can be considered if the arrhythmia is of a narrow complex irregular type. Verapamil is an alternative to Adenosine if the latter is contraindicated.

Systemic vascular resistance (SVR), also known as total peripheral resistance (TPR), is the amount of force exerted on circulating blood by the vasculature of the body. Three factors determine the force: the length of the blood vessels in the body, the diameter of the vessels, and the viscosity of the blood within them. The most important factor that determines the systemic vascular resistance (SVR) is the tone of the small arterioles.

These are otherwise known as resistance arterioles. Their diameter ranges between 100 and 450 µm. Smaller resistance vessels, less than 100 µm in diameter (pre-capillary arterioles), play a less significant role in determining SVR. They are subject to autoregulation.

Any change in the viscosity of blood and therefore flow (such as due to a change in haematocrit) might also have a small effect on the measured vascular resistance.

Changes of blood temperature can also affect blood rheology and therefore flow through resistance vessels.

Systemic vascular resistance (SVR) is measured in dynes·s·cm-5

It can be calculated from the following equation:

SVR = (mean arterial pressure ˆ’ mean right atrial pressure) × 80 cardiac output

Charles’ Law states that there is a direct correlation between temperature and volume, where pressure and amount gas are constant. As temperature increases, volume also increases.

Boyle’s Law states that Pressure is inversely proportional to volume, assuming that temperature and amount of gas are constant. As volume increases, pressure decreases. In Dalton’s law of partial pressure, the total pressure exerted by a mixture of gases is equal to the sum of the partial pressure of the gases in mixture.

According to Henry’s Law for concentration of dissolved gases, at a constant temperature, the amount of a given gas that dissolves in a given type and volume of liquid is directly proportional to the partial pressure of that gas in equilibrium with that liquid. An equivalent way of stating the law is that the solubility of a gas in a liquid is directly proportional to the partial pressure of the gas above the liquid.

Gay-Lussac’s Law states that the pressure of a given mass of gas varies directly with the absolute temperature of the gas, when the volume is kept constant. This law is very similar to Charles’ Law, with the only difference being the type of container. Whereas the container in a Charles’ Law experiment is flexible, it is rigid in a Gay-Lussac’s Law experiment.

Oxygen delivery is related to blood flow as most of the oxygen binds to haemoglobin in red blood cells, although a small amount is dissolved in the plasma. Blood flow per 100 g of tissue is greatest in the kidneys.

The following is the oxygen consumption rate of different organs in ml/minute/100g

Hepatoportal = 2.2
Kidney = 6.8
Brain = 3.7
Skin = 0.38
Skeletal muscle = 0.18
Heart = 11.

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.

Both incidence and prevalence are indicators of the disease frequency. While incidence tells us about the number of cases reported per population in a provided time period, prevalence is the factor you should be vigilant about as it tells us about the total number of cases that have been reported in a population at a particular point of time.

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.

Dose response curves are plotted as % response to drug against Logarithm of drug concentration. The graph is usually sigmoid shaped.

Any drug that has high affinity and high intrinsic activity is likely an agonist. A drug with high affinity but no intrinsic activity will act as an antagonist. Displacement of an agonist also depends on the relative concentrations of the two drugs at the receptor sites.

Maximal response may be achieved by activation of a small proportion of receptor sites.

The following units are derived SI units of measurement.

Energy or work: kg.m2.s-2
The Joule (J) is the energy transferred to an object when a force of one newton acts on that object in the direction of its motion through a distance of one meter or N.m.

Power: kg.m2.s-3
The Watt (W) = rate of transfer of energy or Joule per second J/s.

Force: kg.m.s-2
One Newton (N) which is the international unit of measure for force = 1 kilogram meter per second squared. 1 Newton of force is the force required to accelerate an object with a mass of 1 kilogram 1 meter per second per second.

Volt: kg.m2.s-3.A-1
The volt (V) is defined as the potential difference across a conductor when a current of one ampere dissipates one watt of power or W/A.

Pressure: kg.m-1.s-2
A pascal (Pa) is force per unit area or N/m2.

The central venous pressure (CVP) waveform depicts changes of pressure within the right atrium. Different parts of the waveform are:

A wave: which represents atrial contraction. It is synonymous with the P wave seen during an ECG. It is often eliminated in the presence of atrial fibrillation, and increased tricuspid stenosis, pulmonary stenosis and pulmonary hypertension.

C wave: which represents right ventricle contraction at the point where the tricuspid valve bulges into the right atrium. It is synonymous with the QRS complex seen on ECG.

X descent: which represents relaxation of the atrial diastole and a decrease in atrial pressure, due to the downward movement of the right ventricle as it contracts. It is synonymous with the point before the T wave on ECG.

V wave: which represents an increase in atrial pressure just before the opening of the tricuspid valve. It is synonymous with the point after the T wave on ECG. It is increased in the background of a tricuspid regurgitation.

Y descent: which represents the emptying of the atrium as the tricuspid valve opens to allow for blood flow into the ventricle in early diastole.

A hernia is a protrusion of the abdominal viscera through a defect in the abdominal wall. Inguinal hernias are of two types; Indirect inguinal hernia and Direct inguinal hernia.
– Indirect inguinal hernia is common at young age commonly due to a patent processes vaginalis and bowel passes through the deep inguinal ring lateral to the inferior epigastric artery.
– Direct hernia forms as a result of the weakening of the posterior wall of the inguinal canal more specifically within a region called ‘Hasselbach triangle. It is defined medially by the rectus abdominis muscle, laterally by the epigastric vessels, and inferiorly by the inguinal ligament.

Direct and indirect hernias can be differentiated based on their relation to the inferior epigastric artery. Direct inguinal hernia lies medial to it while indirect inguinal hernia lies lateral to the inferior epigastric artery.

The femoral ring is the site of the femoral hernia.

Iron is a necessary micronutrient for proper erythropoietic function, oxidative metabolism, and cellular immune responses. Although dietary iron absorption (1-2 mg/d) is tightly controlled, it is only just balanced by losses.

The adult body contains 35-45 mg/kg iron (about 4-5 g)

Iron can be found in a variety of forms, including haemoglobin, ferritin, haemosiderin, myoglobin, haem enzymes, and transferrin bound proteins.

Wavelength can be computed as follows:

Wavelength = velocity/frequency

In the given problem, the values stated are:

Frequency = 10 x 10^6
Velocity = 1540 meters per second

Wavelength = 1540/(10×10^6)
Wavelength = 1540/10,000,000 meters
Wavelength = 0.15 millimetres.

Dopamine (DA) is a dopaminergic (D1 and D2) as well as adrenergic α and β1 (but not β2 ) agonist.

The D1 receptors in renal and mesenteric blood vessels are the most sensitive: i.v. infusion of a low dose of DA dilates these vessels (by raising intracellular cAMP). This increases g.f.r. In addition, DA exerts a natriuretic effect by D1 receptors on proximal tubular cells.

Moderately high doses produce a positive inotropic (direct β1 and D1 action + that due to NA release), but the little chronotropic effect on the heart.

Vasoconstriction (α1 action) occurs only when large doses are infused.

At doses normally employed, it raises cardiac output and systolic BP with little effect on diastolic BP. It has practically no effect on nonvascular α and β receptors; does not penetrate the blood-brain barrier€”no CNS effects.

Dopamine is used in patients with cardiogenic or septic shock and severe CHF wherein it increases BP and urine outflow.

It is administered by i.v. infusion (0.2€“1 mg/min) which is regulated by monitoring BP and rate of urine formation

Dopamine (DA) is a dopaminergic (D1 and D2) as well as adrenergic α and β1 (but not β2 ) agonist.

The D1 receptors in renal and mesenteric blood vessels are the most sensitive: i.v. infusion of a low dose of DA dilates these vessels (by raising intracellular cyclic adenosine monophosphate).

Moderately high doses produce a positive inotropic (direct β1 and D1 action + that due to NA release), but the little chronotropic effect on the heart.

Vasoconstriction (α1 action) occurs only when large doses are infused.

At doses normally employed, it raises cardiac output and systolic BP with little effect on diastolic BP. It has practically no effect on nonvascular α and β receptors; does not penetrate the blood-brain barrier€”no Central nervous system effects.

Dopamine is less arrhythmogenic than adrenaline

Regarding dopamine part of the dose is converted to Noradrenaline in sympathetic nerve terminals.

An agonist is a molecule with intrinsic efficacy and affinity for a receptor. The ability of a drug-receptor interaction to produce a maximal response is referred to as intrinsic efficacy or activity. Efficacy also refers to a drug’s ability to have a therapeutic or beneficial effect. Although the potencies of morphine and fentanyl differ, they both have the same intrinsic efficacy.

The amount of drug required to produce a given effect is referred to as potency. If drug X is effective in a dose of 100 mcg, its potency is greater than if drug Y is effective in a dose of 10 mg.

The therapeutic index, also known as the margin of safety, is a ratio of the lethal or serious side effect dose of a drug divided by the therapeutic dose of the same drug.

The term bioavailability refers to the ability of a substance to be absorbed. The area under a curve (AUC) of a graphic plot of plasma concentration and time is used to calculate oral bioavailability. It’s used to figure out how much of a drug to take and when to take it.

With regards to the autonomic nervous system (ANS)

1. It is not under voluntary control
2. It uses reflex pathways and different to the somatic nervous system.
3. The hypothalamus is the central point of integration of the ANS. However, the gut can coordinate some secretions and information from the baroreceptors which are processed in the medulla.

With regards to the central nervous system (CNS)
1. There are myelinated preganglionic fibres which lead to the
ganglion where the nerve cell bodies of the non-myelinated post ganglionic nerves are organised.
2. From the ganglion, the post ganglionic nerves then lead on to the innervated organ.

Most organs are under control of both systems although one system normally predominates.

The nerves of the sympathetic nervous system (SNS) originate from the lateral horns of the spinal cord, pass into the anterior primary rami and then pass via the white rami communicates into the ganglia from T1-L2.

There are short pre-ganglionic and long post ganglionic fibres.
Pre-ganglionic synapses use acetylcholine (ACh) as a neurotransmitter on nicotinic receptors.
Post ganglionic synapses uses adrenoceptors with norepinephrine / epinephrine as the neurotransmitter.
However, in sweat glands, piloerector muscles and few blood vessels, ACh is still used as a neurotransmitter with nicotinic receptors.

The ganglia form the sympathetic trunk – this is a collection of nerves that begin at the base of the skull and travel 2-3 cm lateral to the vertebrae, extending to the coccyx.

There are cervical, thoracic, lumbar and sacral ganglia and visceral sympathetic innervation is by cardiac, coeliac and hypogastric plexi.

Juxta glomerular apparatus, piloerector muscles and adipose tissue are all organs under sole sympathetic control.

The PNS has a craniosacral outflow. It causes reduced arousal and cardiovascular stimulation and increases visceral activity.

The cranial outflow consists of
1. The oculomotor nerve (CN III) to the eye via the ciliary ganglion,
2. Facial nerve (CN VII) to the submandibular, sublingual and lacrimal glands via the pterygopalatine and submandibular ganglions
3. Glossopharyngeal (CN IX) to lungs, larynx and tracheobronchial tree via otic ganglion
4. The vagus nerve (CN X), the largest contributor and carries ¾ of fibres covering innervation of the heart, lungs, larynx, tracheobronchial tree parotid gland and proximal gut to the splenic flexure, liver and pancreas

The sacral outflow (S2 to S4) innervates the bladder, distal gut and genitalia.

The PNS has long preganglionic and short post ganglionic fibres.
Preganglionic synapses, like in the SNS, use ACh as the neuro transmitter with nicotinic receptors.
Post ganglionic synapses also use ACh as the neurotransmitter but have muscarinic receptors.

Different types of these muscarinic receptors are present in different organs:
There are:
M1 = pupillary constriction, gastric acid secretion stimulation
M2 = inhibition of cardiac stimulation
M3 = visceral vasodilation, coronary artery constriction, increased secretions in salivary, lacrimal glands and pancreas
M4 = brain and adrenal medulla
M5 = brain

The lacrimal glands are solely under parasympathetic control.

Foramen ovale, ductus arteriosus (DA) and ductus venosus (DV) are the three important cardiac shunts in-utero.

At birth the umbilical vessels constrict in response to stretch as they are clamped. Blood flow through the ductus venosus (DV) decreases but the DV closes passively in 3-10 days.

As the pulmonary circulation is established, there is a drastic fall in pulmonary vascular resistance and an increased pulmonary blood flow. This increases flow and pressure in the Left Atrium that exceeds that of the right atrium. The difference in pressure usually leads to the IMMEDIATE closure of the foramen ovale.

The DA is functionally closed within the first 36-hours of birth in a healthy full-term newborn. Subsequent endothelial and fibroblast proliferation leads to permanent anatomical closure within 2 – 3 weeks.

Oxygenated blood from the placenta passes via the umbilical vein to the liver. Blood also bypasses the liver via the ductus venosus into the inferior vena cava (IVC). The Crista dividens is a tissue flap situated at the junction of the IVC and the right atrium (RA). This flap directs the oxygen-rich blood, along the posterior aspect of the IVC, through the foramen ovale into the left atrium (LA).

The Eustachian valve also known as the valve of The IVC is a remnant of the crista dividens.

The inferior phrenic nerves are at the highest risk of damage as they are the first branches of the abdominal aorta. The potential space at the level of the diaphragmatic hiatus is a potentially useful site for aortic occlusion. However, leaving the clamp applied for more than 10 -15 minutes usually leads to poor outcomes.

The superior phrenic artery branches from the thoracic aorta.

The abdominal aorta begins at the level of the body of T12 near the midline, as a continuation of the thoracic aorta. It descends and bifurcates at the level of L4 into the common iliac arteries.

The branches of the abdominal aorta (with their vertebra level) are:
1. Inferior phrenic arteries: T12 (upper border)
2. Coeliac artery: T12
3. Superior mesenteric artery: L1
4. Middle suprarenal arteries: L1
5. Renal arteries: Between L1 and L2
6. Gonadal arteries: L2 (in males, it is the testicular artery, and in females, the ovarian artery)
7. Inferior mesenteric artery: L3
8. Median sacral artery: L4
9. Lumbar arteries: Between L1 and L4.

Malignant hyperthermia (MH) is a autosomal dominant inherited medical condition which predisposes affected individuals to a clinical syndrome of hypermetabolism which involves abnormal ryanodine receptors in skeletal muscle causing a deregulation of calcium in muscle.

It is a life threatening condition requiring immediate medical intervention. It often lies dormant until triggered in susceptible individuals mostly by volatile inhaled anaesthetic agents and succinylcholine which is a muscle relaxant.

The signs and symptoms of MH are related to this hypermetabolism, which includes an increase in carbon dioxide production, metabolic and respiratory acidosis, accelerated oxygen consumption, heat production, activation of the sympathetic nervous system, hyperkalaemia, disseminated intravascular coagulation (DIC), and multiple organ dysfunction and failure.

Early signs of MH to look out for in patients includes an uptick in end-tidal carbon dioxide (even with increasing minute ventilation), tachycardia, muscle rigidity, tachypnoea, and hyperkalaemia. Later signs include fever, myoglobinuria, and multiple organ failure.

In vitro muscle contracture test (IVCT) is the standard for determining individual susceptibility to MH. It is conducted by measuring the force of muscle contraction after exposing the patient’s muscle sample to halothane and caffeine., the sample is normally taken from the vastus medialis or lateralis under regional anaesthesia.

The posterior tibial artery originates from the popliteal artery in the popliteal fossa. It passes posterior to the popliteus muscle to pierce the soleus muscle. It descends between the tibialis posterior and flexor digitorum longus muscles.

The posterior tibial artery supplies blood to the posterior compartment of the lower limb. The artery can be palpated posterior to the medial malleolus.

There are 4 main pulse points for the lower limb:

1. Femoral pulse 2-3 cm below the mid-inguinal point
2. Popliteal partially flexed knee to loosen the popliteal fascia
3. Posterior tibial behind and below the medial ankle
4. Dorsal pedis dorsum of the foot over the navicular bone.

The posterior inferior cerebellar artery is the largest branch arising from the distal portion of the vertebral artery which forms the basilar artery. It is one of the arteries responsible for providing blood supply to the brain’s cerebellum.

The labyrinthine artery (auditory artery) is a long and slender artery which arises from the basilar artery and runs alongside the facial and vestibulocochlear nerves into the internal auditory meatus.

The posterior cerebellar artery is one of two cerebral arteries supplying the occipital lobe with oxygenated blood. It is usually bigger than the superior cerebellar artery. It is separated from the vessel near its origin by the oculomotor nerve.

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.

The blood brain barrier (BBB) consists of the ultrafiltration barrier in the choroid plexus and the barrier around cerebral capillaries. The barrier is made by endothelial cells which line the interior of all blood vessels. In the capillaries that form the blood€“brain barrier, endothelial cells are wedged extremely close to each other, forming so-called tight junctions.

Outside of the BBB lies the hypothalamus, third and fourth ventricles and the chemoreceptor trigger zone (CTZ).

Water, oxygen and carbon dioxide cross the BBB freely but glucose is controlled. The ability of chemicals to cross the barrier is proportional to their lipid solubility, not their water solubility. It’s ability to cross is inversely proportional to their molecular size and charge.

In neonates, the BBB is less effective than in adults. This is why there is increased passage of opioids and bile salts (kernicterus) into the neonatal brain.

In meningitis, the effectiveness and permeability of the BBB is affected, and as a result, this effect helps the passage of antibiotics which would otherwise not normally be able to cross.

Endotoxins are the lipopolysaccharides found in the outer cell wall of Gram-negative bacteria. They are responsible for providing the structure and stability of the cell wall.

They cannot be destroyed by normal sterilisation as they are heat stable molecules. They require the use of certain sterilant such as superoxide, peroxide and hypochlorite to be neutralised.

They stimulate strong immune responses, but can only be destroyed partially by specific antibodies. Repeat infections occur as memory T cells cannot be formed.

It can cause septicaemia and associated symptoms such as fever, shock, hypotension and nausea.

It activates the alternative complement pathway and the coagulation pathway using secreted cytokines.

It is not involved in botulism as clostridium botulinum, the responsible organism, secretes a neurotoxic exotoxin.

Dopamine (DA) is a dopaminergic (D1 and D2) as well as adrenergic α and β1 (but not β2 ) agonist.

The D1 receptors in renal and mesenteric blood vessels are the most sensitive: i.v. infusion of a low dose of Dopamine dilates these vessels (by raising intracellular cAMP). This increases g.f.r. In addition, DA exerts a natriuretic effect by D1 receptors on proximal tubular cells.

Moderately high doses produce a positive inotropic (direct β1 and D1 action + that due to NA release), but the little chronotropic effect on the heart.

Vasoconstriction (α1 action) occurs only when large doses are infused.

At doses normally employed, it raises cardiac output and systolic BP with little effect on diastolic BP. It has practically no effect on nonvascular α and β receptors; does not penetrate the blood-brain barrier€”no CNS effects.

Dopamine is less arrhythmogenic than adrenaline

Regarding dopamine part of the dose is converted to Noradrenaline in sympathetic nerve terminals.

Monoamine oxidase (MOA) enzymes are responsible for the catalyses of monoamine oxidative deamination. It assists the degradation of serotonin, norepinephrine (NE) and dopamine.

They are found in the mitochondria of most central and peripheral nerve tissues.

There are 2 different types:

Type A: Whose main function it to inactivate dopamine, tyramine, norepinephrine and 5-hydroxytryptamine. In addition to the nervous system, it is also found in the liver, brain gastrointestinal tract, pulmonary endothelium and placenta
Type B: Whose main function is to inactivate dopamine, tyramine, tryptamine and phenylethylamine. In addition to the nervous system, it is also found in the liver, brain (especially in the basal ganglia) and blood platelets.

There are four parathyroid glands that lie on the medial half of the posterior surface of each lobe of the thyroid gland, inside its sheath. There are two superior and two inferior parathyroid glands.

The common carotid artery is a lateral relation of the inferior parathyroid.

Reflexes are a routine part of clinical examination. Hyperreflexia (abnormally brisk reflexes) is the sign of upper motor neuron damage whereas diminished or absent jerks are most commonly due to lower motor neuron lesions. Reflexes may be Monosynaptic (deep tendon reflexes) or polysynaptic (superficial reflexes)

Here are deep tendon reflexes with their nerve root
Biceps = C5, C6
Supinator (Brachioradialis) = C5, C6
Triceps = C6, C7
Knee reflex = L3,L4
Ankle reflex = S1

Polysynaptic superficial reflexes with their nerve root are listed below
Planter response = S1-2
Abdominal reflexes = T8-12
Cremasteric reflex = L1-2.