A beta-1 adrenoreceptor agonist is most likely the ligand that causes increased automaticity, increased chronotropy, increased excitability, and increased inotropy on the sino-atrial node. However, alpha-1 adrenoreceptor effects may cause an increase in systemic vascular resistance. Noradrenaline, adrenaline, dopamine, and ephedrine are examples of drugs with mixed alpha and beta effects.

Adrenaline, noradrenaline, dopamine, dopexamine, dobutamine, ephedrine, and isoprenaline are examples of drugs that have some beta-1 activity. The beta-1 receptor is a G protein-coupled metabotropic receptor. When the beta-1 agonist binds to the cell surface membrane, it causes a conformational change in the Gs unit, which triggers a cAMP-dependent pathway and a calcium influx into the cell.

Catecholamines also help to relax the heart muscle (positive lusitropy). Dromotropy is the ability to increase the atrioventricular (AV) node’s conduction velocity.

Inodilators cause an increase in intracellular calcium as a result of phosphodiesterase III (PDIII) inhibition. Milrinone, enoximone, and amrinone are some examples. Positive inotropy is caused by increased calcium entry into the myocytes. Lusitropy is also increased by phosphodiesterase inhibitors. Increased cAMP inhibits myosin light chain kinase, resulting in reduced phosphorylation of vascular smooth muscle myosin, lowering systemic and pulmonary vascular resistance.

The mechanism of action of alpha-1 adrenoreceptor agonists is an increase in intracellular calcium caused by an increase in inositol triphosphate (IP3). IP3 is a second messenger that causes an increase in systemic vascular resistance by stimulating the influx of Ca2+ into smooth muscle cells. Reflex bradycardia can occur as a result of the subsequent increase in blood pressure. Phenylephrine and metaraminol are examples of pure alpha-1 agonists.

Levosimendin is a novel inotrope that makes myocytes more sensitive to intracellular Ca2+. It causes a positive inotropy without changing heart rate or oxygen consumption significantly.

The Na-K-ATPase membrane pump in the myocardium is inhibited by digoxin. This inhibition promotes sodium-calcium exchange, resulting in an increase in intracellular Ca2+ and increased contraction force. The parasympathetic effects of digoxin on the AV node result in bradycardia. Systemic vascular resistance will not be affected by it.

The renal arteries branch from the abdominal aorta just below the origin of the superior mesenteric artery. The right renal artery is higher and longer than the left renal artery. The left renal artery passes behind the left renal vein, the body of the pancreas, and the splenic vein.

The important landmarks of vessels arising from the abdominal aorta at different levels of vertebrae are:

T10 – oesophageal opening in the diaphragm

T12 – Coeliac trunk, aortic hiatus in the diaphragm

L1 – Left renal artery

L2 – Testicular or ovarian arteries

L3 – Inferior mesenteric artery

L4 – Bifurcation of the abdominal aorta

Functional residual capacity (FRC) is 1.7 to 3.5L/kg

A capacity is the sum of two or more volumes. The total lung capacity (TLC) is total sum of the volume of gas present in all lung compartments upon maximum inspiration. It is represented mathematically as:

Total lung capacity (TLC) = Vital capacity (VC) + Residual volume (RV)

The residual volume (RV) is the volume of gas still present within the lung post maximum exhalation. It cannot be measured by spirometry, but can be using a body plethysmograph and also with the helium dilution technique.

Closing capacity (CC) is the volume of gas within the lungs at which small airways close upon expiration. It increases with age and is especially important when it surpasses the FRC as it causes changes in ventilation/perfusion mismatch and hypoxia.
In the supine position, a patient with a normal body mass index and no history of lung pathology, the CC equals the FRC at approximately 44, and at approximately 66 at standing position.

Opioid receptors are a large family of seven transmembrane domain receptors. They are of four types:

1) Delta opioid receptor

2) Mu opioid receptor

3) Kappa opioid receptor

4) Orphan receptor-like 1

They contain about 372-400 amino acids and thus their molecular weight is different.

Opioid receptor activation reduces the intracellular cAMP formation and opens K+ channels (mainly through µ and δ receptors) or suppresses voltage-gated N-type Ca2+ channels (mainly κ receptor). These actions result in neuronal hyperpolarization and reduced availability of intracellular Ca2+ which results in decreased neurotransmitter release by cerebral, spinal, and myenteric neurons (e.g. glutamate from primary nociceptive afferents).

However, other mechanisms and second messengers may also be involved, particularly in the long-term

The inflow of blood from the superior vena cava is directed towards the right atrioventricular orifice. It returns deoxygenated blood from all structures superior to the diaphragm, except the lungs and heart.

There are no valves in the superior vena cava which is why it is relatively easy to insert a CVP line from the internal jugular vein into the right atrium. The brachiocephalic vein is similar as it also has no valves.

The right coronary artery supplies the right ventricle, the right atrium, the sinoatrial (SA) node and the atrioventricular (AV) node.

The circumflex artery originates from the left coronary artery and is supplied by it.

The Nernst equation is used to calculate the membrane potential at which the ions are in equilibrium across the cell membrane.

The normal resting membrane potential is -70 mV (not + 70 mV).

The equation is:
E = RT/FZ ln {[X]o
/[X]i}

Where:
E is the equilibrium potential
R is the universal gas constant
T is the absolute temperature
F is the Faraday constant
Z is the valency of the ion
[X]o is the extracellular concentration of ion X
[X]i is the intracellular concentration of ion X.

Electromagnetic waves are categorized according to their frequency or equivalently according to their wavelength. Visible light makes up a small part of the full electromagnetic spectrum.

Electromagnetic waves with shorter wavelengths and higher frequencies include ultraviolet light, X-rays, and gamma rays. Electromagnetic waves with longer wavelengths and lower frequencies include infrared light, microwaves, and radio and televisions waves.

Different electromagnetic waves according to their wavelength from shorter to longer are X-rays, ultraviolet radiations, visible light, infrared radiation, radio waves. X-ray among electromagnetic waves has the shortest wavelength and higher frequency with wavelengths ranging from 10*-8 to 10* -12 and corresponding frequencies.

Lorazepam is an intermediate-acting benzodiazepine that binds to the GABA-A receptor subunit to increase the frequency of chloride channel opening and facilitate membrane hyperpolarization. It is the preferred treatment for status epilepticus, although Diazepam can also be used as an alternative.

Lorazepam has a longer duration of action than Diazepam, and binds with greater affinity to the GABA-A receptor subunit.

Phenobarbital is a barbiturate that acts on the GABA-A receptor site to increase the duration of chloride channel opening. Barbiturates, particularly phenobarbital, is considered the drug of choice for seizures in infants.

Phenytoin is a sodium-channel blocker that is given for generalized tonic-clonic seizures, partial seizures, and status epilepticus. Phenytoin is preferred in prolonged therapy for status epilepticus because it is less sedating.

Propofol or thiopentone is preferred when airway protection is required.

When there is a fall in ionised plasma calcium levels, the chief cells of the parathyroid glands are stimulated to secrete parathyroid hormone (PTH).

50% of extracellular calcium occurs as non-ionised, protein- (albumin-)bound calcium.

The degree of ionisation increases with low ph and decreases with high pH.

There is increased renal calcium excretion with secretion of calcitonin.

The external iliac artery is the larger of the two branches of the common iliac artery. It forms the main blood supply to the lower limbs. The common iliac bifurcates into the internal and external iliac artery anterior to the sacroiliac joint.

The external iliac artery courses on the medial border of the psoas major muscles and exits the pelvic girdle posterior to the inguinal ligament. Here, midway between the anterior superior iliac spine and the pubic symphysis, the external iliac artery becomes the femoral artery and descends along the anteromedial part of the thigh in the femoral triangle.

The pectineus forms the posterior border of the femoral canal.
The femoral vein forms the lateral border of the femoral canal.
The medial border of the adductor longus muscle forms the medial wall of the femoral triangle.
The medial border of the sartorius muscle forms the lateral wall of the femoral triangle.

The ideal gas equation makes the following assumptions:

The gas particles have a small volume in comparison to the volume occupied by the gas.
Between the gas particles, there are no forces of interaction.
Individual gas particle collisions, as well as gas particle collisions with container walls, are elastic, meaning momentum is conserved.
PV = nRT
Where:

P = pressure
V = volume
n = moles of gas
T = temperature
R = universal gas constant

Helium is a monoatomic gas with a small helium atom. The attractive forces between helium atoms are small because the helium atom is spherical and has no dipole moment. Because helium atoms are spherical, collisions between them approach the ideal state of elasticity.

Most real gases behave qualitatively like ideal gases at standard temperatures and pressures. When intermolecular forces and molecular size become important, the ideal gas model tends to fail at lower temperatures or higher pressures. It also fails to work with the majority of heavy gases.

Helium, argon, neon, and xenon are noble or inert gases that behave the most like an ideal gas. Xenon is a noble gas with a much larger atomic size than helium.

Each kidney is composed of about 1.2 million uriniferous tubules. Each tubule consists of two parts that are embryologically distinct from each other. They are as follows:
a) Excretory part, called the nephron, which elaborates urine
b) Collecting part which begins as a junctional tubule from the distal convoluted tubule.

There are two types of nephrons in the kidney:
The cortical nephron comprises 80% of the total nephron and its major function is the excretion of waste products in urine whereas the juxtamedullary nephron comprises 20% of the total nephron and its major function is the concentration of urine by counter current mechanism.
In the superficial (cortical) nephrons, peritubular capillaries branch off the efferent arterioles and deliver nutrients to epithelial cells as well as serve as a blood supply for reabsorption and secretion. In juxtamedullary nephrons, the peritubular capillaries have a specialization called the vasa recta, which are long, hairpin-shaped blood vessels that follow the same course as a loop of Henle. The vasa recta serve as osmotic exchangers for the production of concentrated urine.

The kidney receives about 25% of cardiac output and about 20% of this is filtered at the glomeruli of the kidney. Thus, renal blood flow is 1200 ml/minute and renal plasma flow is 650 ml/minute

There is minimum mixing of blood passing through the vessels.

The cerebral hemispheres are supplied by arteries that make up the Circle of Willis. The Circle of Willis is formed by the anastomosis of the two internal carotid arteries and two vertebral arteries. It lies in the subarachnoid space within the basal cisterns that surround the optic chiasma and infundibulum.

Each half of the circle is formed by:
1. Anterior communicating artery
2. Anterior cerebral artery
3. Internal carotid artery
4. Posterior communicating artery
5. Posterior cerebral arteries and the termination of the basilar artery

The circle and its branches supply; the corpus striatum, internal capsule, diencephalon, and midbrain

Monosynaptic reflexes is a type of reflex arc providing direct communication between motor and sensory innervation in a muscle. It occurs very quickly as it arises and ends in the same muscle. Examples include: biceps reflex, brachioradialis reflex, extensor digitorum reflex, triceps reflex, Achilles reflex and patellar reflex.

Polysynaptic reflexes facilitates contraction and inhibition in muscle by providing communication between multiple muscles.

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

There are different classes of electrical equipment that can be classified in the table below:

Class 1 – provides basic protection only. It must be connected to earth and insulated from the mains supply

Class II – provides double insulation for all equipment. It does not require an earth.

Class III – uses safety extra low voltage (SELV) which does not exceed 24 V AC. There is no risk of gross electrocution but risk of microshock exists.

Type B – All of above with low leakage currents (0.5mA for Class IB, 0.1 mA for Class IIB)

Type BF – Same as with other equipment but has ‘floating circuit’ which means that the equipment applied to patient is isolated from all its other parts.

Type CF – Class I or II equipment with ‘floating circuits’ that is considered to be safe for direct connection with the heart. There are extremely low leakage currents (0.05mA for Class I CF and 0.01mA for Class II CF)

Cardiopulmonary exercise testing (CPX, CPEX, CPET) is a non-invasive testing method used to determine the performance of the heart, lungs and skeletal muscle. It measures the exercise tolerance of the patient.

The parameters measured include:

ECG and ST-segment analysis and blood pressure
Oxygen consumption (VO2)
Carbon dioxide production (VCO2)
Gas flows and volumes
Respiratory exchange ratio (RER)
Respiratory rate
Anaerobic threshold (AT)

The anaerobic threshold (AT) is an estimate of exercise ability. Any measurement below 11 ml/kg/min is usually related with an increase in mortality, especially when there is a background of myocardial ischaemia occurring during the test.

Peak VO2 <20 mL/kg with a low AT have a correlation with postoperative complications and a 30 day mortality. The CPX test is used for risk-testing patients prior to surgery to determine the appropriate postoperative care facilities. The V slope measured in CPX testing represents VO2 versus VCO2 relationship. During AT, the ramp of V slope increases, but does not provide a picture of postoperative mortality.

The diaphragm divides the thoracic cavity from the abdominal cavity. Structures penetrate the diaphragm at different vertebral levels through openings in the diaphragm to communicate between the two cavities. The diaphragm has openings at three vertebral levels:

T8: vena cava, terminal branches of the right phrenic nerve
T10: oesophagus, vagal trunks, left anterior phrenic vessels, oesophageal branches of the left gastric vessels
T12: descending aorta, thoracic duct, azygous and hemi-azygous vein

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

The number of osmoles (Osm) of solute per litre (L) of solution (Osmol/L) is the unit of measurement for solute concentration. The calculated serum osmolality assumes that the primary solutes in the serum are sodium salts (chloride and bicarbonate), glucose, and urea nitrogen.

2 (Na + K) + Glucose + Urea (all in mmol/L) = calculated osmolarity

313 mOsm/L = 2 (144 + 6) + 9.5 + 3.5

Sodium and potassium ions clearly contribute the most to plasma osmolarity. Glucose and urea, on the other hand, are less so.

The osmolarity of normal serum is 285-295 mOsm/L. Temperature and pressure affect osmolality, and this calculated variable is less than osmolality for a given solution.

The number of osmoles (Osm) of solute per kilogramme (Osm/kg) is a measure of osmolality, which is also a measure of solute concentration. Temperature and pressure have no effect on the value. An osmometer is used to measure it in the lab. Osmometers rely on a solution’s colligative properties, such as a decrease in freezing point or a rise in vapour pressure.

The osmolar gap (OG) is calculated as follows:

OG = osmolaRity calculated from measured serum osmolaLity

Excess alcohols, lipids, and proteins in the blood can all contribute to the difference.

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.

Even though aprotinin reduces fibrinolysis and therefore bleeding, there is an associated increased risk of death. It was withdrawn in 2007.
Protein C is dependent upon vitamin K and this may paradoxically increase the risk of thrombosis during the early phases of warfarin treatment.

The coagulation cascade include two pathways which lead to fibrin formation:
1. Intrinsic pathway – these components are already present in the blood
Minor role in clotting
Subendothelial damage e.g. collagen
Formation of the primary complex on collagen by high-molecular-weight kininogen (HMWK), prekallikrein, and Factor 12
Prekallikrein is converted to kallikrein and Factor 12 becomes activated
Factor 12 activates Factor 11
Factor 11 activates Factor 9, which with its co-factor Factor 8a form the tenase complex which activates Factor 10

2. Extrinsic pathway – needs tissue factor that is released by damaged tissue)
In tissue damage:
Factor 7 binds to Tissue factor – this complex activates Factor 9
Activated Factor 9 works with Factor 8 to activate Factor 10

3. Common pathway
Activated Factor 10 causes the conversion of prothrombin to thrombin and this hydrolyses fibrinogen peptide bonds to form fibrin. It also activates factor 8 to form links between fibrin molecules.

4. Fibrinolysis
Plasminogen is converted to plasmin to facilitate clot resorption

9 & 27 can be obtained by subtracting and adding 9 from the mean. 9 is three times the standard deviation and we know that 99.7% values lie within 3 standard deviations from the mean. We can find the interval for 99.7% to verify in the following way:

For 99.7% confidence interval, you can find the range as follows:

1. Multiply the standard error by 3.

2. Subtract the answer from mean value to get the lower limit.

3. Add the answer obtained in step 1 from the mean value to get the upper limit.

4. The range turns out to be 9-27 kg.

When responsiveness diminishes rapidly after administration of a drug, the response is said to be subject to tachyphylaxis. This may be due to frequent or continuous exposure to agonists, which often results in short-term diminution of the receptor response.

Many mechanisms may be responsible, such as blocking access of G protein to activated receptor, or receptor molecules internalized by endocytosis to prevent exposure to extracellular molecules.

Tolerance occurs when larger doses are required to produce the same effect. This may be due to changes in receptor number or function due to exposure to the drug.

Desensitization refers to the common situation where the biological response to a drug diminishes when it is given continuously or repeatedly. It is a chronic loss of response, occurring over a longer period than tachyphylaxis. It may be possible to restore the response by increasing the dose (or concentration) of the drug but, in some cases, the tissues may become completely refractory to its effect.

Drug dependence is defined as a psychic and physical state of the person characterized by behavioural and other responses resulting in compulsions to take a drug, on a continuous or periodic basis in order to experience its psychic effect and at times to avoid the discomfort of its absence.

Bucks fascia refers to the layer of loose connective tissue, nerves and blood vessels that encapsulates the penile erectile bodies, the corpa cavernosa and the anterior part of the urethra, including the entirety of the spongiose part of the urethra.

It runs with the external spermatic fascia and the penile suspensory ligament.

The deep inguinal ring lies approximately 1.5-2cm above the midpoint of the inguinal ligament, the halfway point between the anterior superior iliac spine and the pubic tubercle, next to the epigastric vessels.

It is an important point in determining the nature of an inguinal hernia (direct or indirect). The patient is asked to cough after the hernia is reduced, with pressure applied to the deep inguinal ring. The hernia reappearing indicates it is direct, moving through the posterior wall of the inguinal canal.

Inferior and lateral to the pubic tubercle is the normal anatomical position of the neck of a femoral hernia.

Superior and medial to the pubic tubercle is the site of the superficial inguinal ring, and the normal anatomical position of the neck of an inguinal hernia.

The mid-inguinal point is located halways between the pubic symphysis and the anterior superior iliac spine. It is the surface marking for taking the femoral pulse.

Venous cutdown is a surgical procedure when venous access is difficult, and other procedures like the Seldinger technique, ultrasound-guided venous access, and intraosseous vascular access have failed.

The vein of choice for venous cutdown is the long/great saphenous vein. It is part of the superficial venous collecting system of the lower extremity. It is the preferred vein as the long saphenous vein has anatomic consistency and is superficially located at the ankle anterior to the medial malleolus. It is also the most commonly used conduit for cardiovascular bypass operations.

Origin- in the foot at the confluence of the dorsal vein of the first digit and the dorsal venous arch of the foot
Route- runs ANTERIOR to the medial malleolus and travels up in the medial leg and upper thigh.
Termination: in the femoral vein within the femoral triangle

Regarding the other options:
The short saphenous vein passes posterior to the lateral malleolus.
The dorsalis pedis vein accompanies the dorsalis pedis artery on the anterior foot.
The posterior tibial vein is part of the deep venous system accompanying the posterior tibial artery. There is no significant sural vein (there is a sural nerve), but the sural veins accompany the sural arteries and drain to the popliteal vein.

Porphyria is a group of disorders in which there is excess production and excess excretion of porphyrins and their precursors. They are usually genetic and are caused due to defects in the haem metabolic pathway. However, other factors like infection, pregnancy, mensuration, starvation may precipitate the attack.

Sulphonamides, barbiturates (methohexitone and thiopental), and phenytoin are considered to be precipitants so are not safe to use
Chloral hydrate is thought to be safe to use.
Etomidate lacks proper studies and may be used with caution but it is generally advised not to use this drug especially if other alternatives are available.