Respiratory inspiration causes a decreased pressure in the thoracic cavity, which in turn causes more blood to flow into the atrium.

Sitting up decreases venous because of the action of gravity on blood in the venous system.
Hypotension also decreases venous return.
A less compliant aorta, like in aortic stenosis increases end systolic left ventricular volume which decreases stroke volume.

Systemic vascular resistance = mean arterial pressure / cardiac output. Increased vascular resistance impedes the flow of blood back to the heart.

Increased venous return increases end diastolic LV volume as there is more blood returning to the ventricles.

This is a classical case of unstable angina or NSTEMI (Non-ST-elevation myocardial infarction). As soon as the diagnosis of unstable angina or NSTEMI is made the initial treatment is Aspirin and antithrombin therapy.

Betablocker is known to reduce mortality from acute myocardial infarction by reducing oxygen demand. If there is no contraindication (heart block, bradycardia, hypotension, severe left ventricular dysfunction, and asthma), a beta-blocker should be given early. This patient has hypotension and therefore metoprolol is contraindicated.

If three doses of nitroglycerine tablets or Nitrolingual sprays and intravenous beta-blockers too cannot relieve the symptoms intravenous Glyceryl Trinitrate (GTN) should be considered provided that there is no hypotension. But in this case, the patient is hypotensive, and therefore, it is contraindicated.

If the symptoms are not relieved after three serial doses of nitroglycerine or if symptoms recur despite adequate anti-anginal treatment morphine sulphate is indicated.

Control of Substances Hazardous to Health (COSHH) was established by government under the Health and Safety at Work act in 1989. Their employers work on identification and management of those substances that are dangerous to health. The implications for anaesthetists include gas scavenging, equipment contamination and environmental safety. Adequate ventilation is required in areas where anaesthetic gases are present. The minimum air supply that is legally required in each specific area is: Operating theatres: 0.65 m3/second. Anaesthetic rooms: 0.15 m3/s. Preparation rooms: 0.1 m3/s. Recovery rooms need 15 air changes per hour.

Barbituric acid is the barbiturates’ pharmacologically inactive precursor. A pyrimidine heterocyclic nucleus is formed by the condensation of urea and malonic acid. Its pharmacological activity can be influenced by minor structural changes (structure function relationship).

The duration of action and potency as a sedative are influenced by the length of the side chains at C5. Barbiturates with three carbon atoms in their chain last longer than those with two. Anticonvulsant properties are enhanced by branched chains.

The addition of a methyl group at N1 causes a faster onset/offset of action, but it also causes excitatory phenomena (twitching/lower convulsive threshold).

The addition of oxygen and sulphur to C2 increases the molecule’s lipid solubility and thus its potency. Thiopentone (thiobarbiturate) has sulphur groups at C2, making it 20-200 times more lipid soluble than oxybarbiturates.

The epiploic foramen (foramen of Winslow or aditus to the lesser sac) is found behind the free right border of the lesser omentum. A short, 3 cm slit serves as the entrance to the lesser sac from the greater sac.

The epiploic foramen has the following boundaries:
Anteriorly: hepatoduodenal ligament, the bile duct (anteriorly on the right), the hepatic artery (anteriorly on the left), and the portal vein (posteriorly) together with nerves and lymphatics
Superiorly: the peritoneum of the posterior layer of the hepatoduodenal ligament runs over the caudate process of the liver
Posteriorly: inferior vena cava
Floor: upper border of the first part of the duodenum
The anterior and posterior walls of the foramen are normally
apposed, which partly explains why patients can develop large fluid
collections isolated to the greater or lesser sac

Rapid control of the hepatic artery and portal vein can be obtained by compression of the free edge of the lesser omentum (a €˜Pringle’ manoeuvre), which is a potentially useful technique in liver trauma and surgery.

In the Child-Pugh classification system, the following 5 components are determined or calculated in order:

Ascites

Grade of encephalopathy

Serum bilirubin (μmol/L)

Serum Albumin (g/L)

Prothrombin time or INR

Raised liver enzymes are not the component of the classification system.

Standard error can be calculated by the following formula:

Standard Error= (Standard Deviation)/ˆš(Sample Size)
= (12) / ˆš(64)
= 12 / 8
= 1.5

Alpha 1 adrenergic receptor stimulation results in vasoconstriction of peripheral arteries mainly of those of skin, gut and kidney arterioles. This would cause and increase in total peripheral resistance and mean arterial pressure and as a result the perfusion of vital organs i.e. brain, heart and lungs are maintained.

Muscarinic M2 receptor also known as cholinergic receptor are located in heart, where they act to slow the heart rate down to normal sinus rhythm after negative stimulatory actions of parasympathetic nervous system. They also reduce contractile forces of the atrial cardiac muscle, and reduce conduction velocity of AV node. This could worsen the compensation.

Stimulation of beta 2 adrenergic receptor result in dilation of smooth muscle as in bronchodilation.

Beta 3 adrenergic receptors are present on cell surface f both white and brown adipocytes and are responsible for lipolysis, thermogenesis, and relaxation of intestinal smooth muscle.

Alpha 2 adrenergic receptor stimulation results in inhibition of the release of noradrenaline in a form of negative feedback.

The reasons for adding adrenaline to a local anaesthetic solution are:

1. To Increase the duration of block
2. To reduce absorption of the local anaesthetic into the circulation
3. To Increase the upper safe limit of local anaesthetic (2.5 mg/kg instead of 2 mg/kg, in this case).

The addition of adrenaline to bupivacaine does not affect its potency, lipid solubility, protein binding, or pKa(8.1 with or without adrenaline).

The pH of bupivacaine is between 5-7. Premixed with adrenaline, it is 3.3-5.5.
The onset of a local anaesthetic and its ability to penetrate membranes depends upon degree of ionisation. Compared with the ionised fraction, unionised local anaesthetic readily penetrates tissue membranes to site of action. The onset of action of solution B is slower. this is because the relationship between pKa(8.1) and pH(3.3-5.5) of the solution results in a greater proportion of ionised local anaesthetic molecules compared with solution A.

Interleukin-4 is a cytokine which acts to regulate the responses of B and T cells.

Erythropoietin is responsible for the signal that initiated red blood cell production.

Granulocyte-colony stimulating factor stimulates the bone marrow to produce granulocytes.

Interleukin-5 is a cytokine that stimulates the proliferation and activation of eosinophils.

Thrombopoietin is the primary signal responsible for megakaryocyte and thus platelet production.
Platelets are also called thrombocytes. They, like red blood cells, are also derived from myeloid stem cells. The process involves a megakaryocyte developing from a common myeloid progenitor cell. A megakaryocyte is a large cell with a multilobulated nucleus, this grows to become massive where it will then break up to form platelets.

Immune cells are generated from haematopoietic stem cells in bone marrow. They generate two main types of progenitors, myeloid and lymphoid progenitor cells, from which all immune cells are derived.

Using a lean body weight metric encompasses a more scientific approach to weight-based dosing. Lean body weight reflects the weight of all €˜non-fat’ body components, including muscle and vascular organs such as the liver and kidneys. As lean body weight contributes to approximately 99% of a drug’s clearance, it is useful for guiding dosing in obesity.

This metric has undergone a number of transformations. The most commonly cited formula derived by Cheymol is not optimal for dosing across body compositions and can even produce a negative result. A new formula has been developed that appears stable across different body sizes, in particular the obese to morbidly obese.

A practical downfall of the calculation of lean body weight (and other body size descriptors) is the numerical complexity, which may not be palatable to a busy clinician. Often limited time is available for prescribing and an immediate calculation is required. Lean body weight calculators are available online, for example in the Therapeutic Guidelines.

Using total body weight assumes that the pharmacokinetics of the drug are linearly scalable from normal-weight patients to those who are obese. This is inaccurate. For example, we cannot assume that a 150 kg patient eliminates a drug twice as fast as a 75 kg patient and therefore double the dose. Clinicians are alert to toxicities with higher doses, for example nephro- and neurotoxicity with some antibiotics and chemotherapeutics, and bleeding with anticoagulants. Arbitrary dose reductions or €˜caps’ are used to avoid these toxicities, but if too low can result in sub-therapeutic exposure and treatment failure.

Body surface area is traditionally used to dose chemotherapeutics. It is a function of weight and height and has been shown to correlate with cardiac output, blood volume and renal function. However, it is controversial in patients at extremes of size because it does not account for varying body compositions. As a consequence, some older drugs such as cyclophosphamide, paclitaxel and doxorubicin were €˜capped’ (commonly at 2 m^2) potentially resulting in sub-therapeutic treatment. Recent guidelines suggest that unless there is a justifiable reason to reduce the dose (e.g. renal disease), total body weight should be used in the calculation of body surface area, until further research is done. Little research into dosing based on body surface area has been conducted for other medicines.

Ideal body weight was developed for insurance purposes not for drug dosing. It is a function of height and gender only and, like body surface area, does not take into account body composition. Using ideal body weight, all patients of the same height and sex would receive the same dose, which is inadequate and generally results in under-dosing. For example a male who has a total body weight of 150 kg and a height of 170 cm will have the same ideal body weight as a male who is 80 kg and 170 cm tall. Both could potentially receive a mg/kg dose based on 65 kg (ideal body weight).

Cardiac conduction

Phase 0 – Rapid depolarization. Opening of fast sodium channels with large influx of sodium

Phase 1 – Rapid partial depolarization. Opening of potassium channels and efflux of potassium ions. Sodium channels close and influx of sodium ions stop

Phase 2 – Plateau phase with large influx of calcium ions. Offsets action of potassium channels. The absolute refractory period

Phase 3 – Repolarization due to potassium efflux after calcium channels close. Relative refractory period

Phase 4 – Repolarization continues as sodium/potassium pump restores the ionic gradient by pumping out 3 sodium ions in exchange for 2 potassium ions coming into the cell. Relative refractory period

Daptomycin alters the curvature of the membrane, which creates holes that leak ions. This causes rapid depolarization, resulting in loss of membrane potential. Thus it interferes with the outer membrane of gram-positive bacteria resulting in cell death.

Campylobacter is the commonest bacterial cause of infectious intestinal disease in the UK. The majority of cases are caused by the Gram-negative bacillus Campylobacter jejuni which is spread by the faecal-oral route. The incubation period is 1-6 days.

Features include a prodrome phase with headaches and malaise, then diarrhoea occurs which is often bloody.
There is often abdominal pain which may mimic appendicitis.

It is usually self-limiting but treatment is warranted if the infection is severe or the infection occurs in an immunocompromised patient.
Severe infection comprises of high fever, bloody diarrhoea, or more than eight stools per day or symptoms last for more than one week.
This management would include antibiotics and the first-line antibiotic is clarithromycin.
Ciprofloxacin is an alternative but there are strains with decreased sensitivity to ciprofloxacin which can be frequently isolated.

Complications include:
1.Guillain-Barre syndrome may follow Campylobacter
2. Jejuniinfections
3. Reactive arthritis
4. Septicaemia, endocarditis, arthritis

The sinoatrial node receives innervation from multiple nerves arising from the complex cardiac plexus.

The cardiac plexus sends tiny branches into cardiac vessels, alongside the right and left coronary arteries.

The vagal efferent fibres originate from the vagal and accessory nerves in the brainstem, and then travel to the cardiac plexus within the heart. The resulting vagal discharge controls heart rate.

No singular nerve directly innervates the sinoatrial node.

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

T12 – Coeliac trunk

L1 – Left renal artery

L2 – Testicular or ovarian arteries

L3 – Inferior mesenteric artery

L4 – Bifurcation of the abdominal aorta.

Two bonded wires of dissimilar metals, iron/constantan or copper/constantan, make up a thermocouple (constantan is an alloy of copper and nickel). At the tip, a thermojunction voltage is generated that is proportional to temperature (Seebeck effect).

All of the other connections are non-linear.

For a single compartment model, the relationship between a decrease in plasma concentration of an intravenous bolus of a drug and time is a washout exponential.

A sine wave is the relationship between current and degrees or time from a mains power source.

A sigmoid curve represents the relationship between efficacy and log-dose of a pure agonist on mu receptors.

The pressure of a fixed mass of gas and its volume (Boyle’s law) at a fixed temperature are inversely proportional, resulting in a hyperbolic curve.

Hydrochloric acid is lost when you vomit for a long time (HCl). As a result, the following can be expected, in varying degrees of severity:

Hypokalaemia
Hypochloraemia
Increased bicarbonate to compensate for chloride loss and metabolic alkalosis

The alkalosis causes potassium to move from the intracellular to the extracellular compartment at first. Long-term vomiting and dehydration cause potassium to be excreted by the kidneys in order to conserve sodium. Dehydration can cause urea and creatinine levels to rise.

The actual base excess is always greater than the standard base excess.

The actual base excess (BE) is a measurement of a base’s contribution to a blood gas picture’s metabolic component. It’s the amount of base that needs to be added to a blood sample to bring the pH back to 7.4 after the respiratory component of a blood gas picture has been corrected (PaCO2 of 40 mmHg or 5.3 kPa). The BE has a normal range of +2 to 2. A large positive BE indicates a severe metabolic alkalosis, while a large negative BE indicates a severe metabolic acidosis. As a result, the actual BE in vitro is unaffected by CO2.

In vivo, however, standard BE is not independent of pCO2 because blood with haemoglobin acts as a better buffer than total ECF.

As a result, it is impossible to tell the difference between compensating for a respiratory disorder and compensating for the presence of a primary metabolic disorder.

The differences between in vitro and in vivo behaviour can be mostly eliminated if the BE is calculated for a haemoglobin concentration of 50 g/L (the ‘effective’ or virtual value of Hb if it was distributed throughout the extracellular space) rather than the actual haemoglobin. Because haemoglobin has a lower buffering capacity, the standard BE is higher than the actual BE. It reflects the BE better in the extracellular space rather than just the intravascular compartment.

The solid state of matter has a definite volume and shape and particles are packed closely together and are incompressible. Within this tight lattice, there is enough thermal energy to produce vibration of particles.

Liquids however have a volume but no definite shape. These particles are less tightly packed together. Although there is free movement within the volume, they are incompressible.

Gases, however, have no finite shape or volume and particles are free to move rapidly in a state of random motion. They are compressible and are completely shaped by the space in which they are held. Vapours exist as a gas phase in equilibrium with identical liquid or solid matter below its boiling point.

The most prevalent state of matter in the universe is plasma which is formed by heating atoms to very high temperatures to form ions.

Decreased platelet concentrations with eclampsia were described as early as 1922 by Stancke. The platelet count is routinely measured in women with any form of gestational hypertension. The frequency and intensity of thrombocytopenia vary and are dependent on the severity and duration of the preeclampsia syndrome and the frequency with which platelet counts are performed.

Overt thrombocytopenia defined by a platelet count < 100,000/microliter - indicates severe disease. In general, the lower the platelet count, the higher the rates of maternal and fetal morbidity and mortality. In most cases, delivery is advisable because thrombocytopenia usually continues to worsen. After delivery, the platelet count may continue to decline for the first day or so. It then usually increases progressively to reach a normal level within 3-5 days. In some instances with HELLP syndrome, the platelet count continues to fall after delivery. If these do not reach a nadir until 48 to 72 hours, then preeclampsia syndrome may be incorrectly attributed to one of the thrombotic microangiopathies. The following are other severe features associated with preeclampsia: Proteinuria: >/= 300 mg/24 hours; or urine protein: creatinine ratio >/= 0.3; or dipstick 1+

Renal insufficiency: serum creatinine > 1.1 mg/dL or doubling of creatinine in the absence of other renal disease

Impaired liver function: two times elevated AST/ALT or unexplained right upper quadrant pain or epigastric pain unresponsive to medications

Pulmonary oedema

Cerebral or visual symptoms: headache, visual disturbances.

The commonest and most likely cause of a gradual rise in end-tidal CO2 (EtCO2) occurring during anaesthesia in a spontaneously breathing patient is hypoventilation. This occurs from the respiratory depressant effects of the opioid and sevoflurane.

Malignant hyperthermia should be sought if the EtCO2 shows further progressive rise.

Causes of rebreathing and a rise in the baseline of the capnograph can be caused by exhausted soda lime and inadequate fresh gas flow into the Bain circuit.

A sudden rise in EtCO2 can be caused deflation of the tourniquet.

Flowmeters measure the rate at which a specific gas, that the flowmeter has been calibrated for, passes through. This calibration is done at room temperature and standard atmospheric pressure with an accuracy of +/- 2%.

Reading the flowmeter is done from the top of a bobbin (the midpoint of a ball). Oxygen is the last gas to be added downstream to the mixture delivered to the back bar as a safety feature. This prevents delivery of a hypoxic mixture.

Inaccurate flow measurements occur when the bobbin sticks to the inside wall of the flowmeter. Stannic oxide has been used as a successful antistatic substance thus, reducing the aforementioned risk.

Carbon dioxide being easily delivered is found on some older machines, but those attached flowmeters are limited by a maximum flow of 500 ml /min. Thus avoiding the delivery of a hypercarbic mixture.

Insulin is secreted from the β cells of the pancreas. It consists of 51 amino acids arranged in two chains. It interacts with cell surface receptors (not the nuclear receptors and thus mechanism of action is not similar to steroids).
Since insulin can pass from plasma to interstitium and lymphatics, it can be measured in lymph but the concentrations here can be up to 30% less than that of plasma.

It decreases blood glucose by stimulating the entry of glucose in muscle and fat (by increasing the synthesis of Glucose transporters)

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.

The clinical picture best describes a probable drug interaction with pethidine.

Phenelzine, a monoamine oxidase (MAO) inhibitor, when given with pethidine, an opioid analgesic, may lead to episodes of hypertension, rigidity, excitation, hyperpyrexia, seizures, coma and death. Studies have shown that pethidine reacts more significantly with MAO inhibitors than morphine.

When pethidine is metabolised to normeperidine, it acts as a serotonin reuptake inhibitor and cause an increase in serotonin levels in the brain. MAO inhibitors can also lead to elevated levels of serotonin because of its mechanism of action by inhibiting the enzyme monoamine oxidase that degrades serotonin.

The excess serotonin levels may lead to serotonin syndrome, of which some of the common precipitating drugs are selective serotonin reuptake inhibitors, MAO inhibitors, tricyclic antidepressants, meperidine, and St. John’s Wort. Onset of symptoms is within hours, which includes fever, agitation, tremor, clonus, hyperreflexia and diaphoresis.

Drug interaction between phenelzine and paracetamol do not commonly precipitate serotonin syndrome.

Neuroleptic malignant syndrome is due to dopamine antagonism, precipitated commonly by antipsychotics. Its onset of symptoms occur in 1 to 3 days, and is characterized by fever, encephalopathy, unstable vitals signs, elevated CPK, and rigidity.

Altered mental status is the most common manifestation of sepsis-associated encephalopathy. Patient also exhibit confusional states and inappropriate behaviour. In some cases, this may lead to coma and death.

The cardiac action potential has several phases which have different mechanisms of action as seen below:
Phase 0: Rapid depolarisation – caused by a rapid sodium influx.
These channels automatically deactivate after a few ms

Phase 1: caused by early repolarisation and an efflux of potassium.

Phase 2: Plateau – caused by a slow influx of calcium.

Phase 3 – Final repolarisation – caused by an efflux of potassium.

Phase 4 – Restoration of ionic concentrations – The resting potential is restored by Na+/K+ATPase.
There is slow entry of Na+into the cell which decreases the potential difference until the threshold potential is reached. This then triggers a new action potential

Of note, cardiac muscle remains contracted 10-15 times longer than skeletal muscle.

Different sites have different conduction velocities:
1. Atrial conduction – Spreads along ordinary atrial myocardial fibres at 1 m/sec

2. AV node conduction – 0.05 m/sec

3. Ventricular conduction – Purkinje fibres are of large diameter and achieve velocities of 2-4 m/sec, the fastest conduction in the heart. This allows a rapid and coordinated contraction of the ventricles

Serum specific IgE assays against allergen sources/molecules are the most commonly used in vitro diagnostic approach. The measurement of specific IgE recognizing allergenic epitopes can be achieved both through the usage of single reagents (singleplex) or with a pre-defined panel of a number of molecules to be tested simultaneously (multiplex).

Several clinical entities have been described and those occurring immediately after drug exposure are immunoglobulin E (IgE)-mediated and explored by skin testing and by the in vitro measurement of serum-specific IgE. The sensitivity of these tests is not 100% and even for patients with a clear positive history, a drug provocation test may be required in order to confirm the diagnosis. The advantages of the in vitro determination of specific IgE antibodies when compared with in vivo testing are that the former poses no direct risk to the patient and does not require personnel with expertise. Even though in vitro tests are recommended in immediate hypersensitivity reactions, their exact place in the diagnostic procedure is not clear and certain authors do not use this method in daily practice. In one study, in terms of sensitivity, 11 of 26 patients (42%) with negative skin tests and a positive drug provocation challenge (or repeated clinical history) had specific IgE to benzylpenicilloyl or amoxicilloyl (4). The specificity of the test was 95€“100%. Therefore, IgE measurements can avoid a potentially harmful drug provocation test.

An elevated serum tryptase does not differentiate between type 1 and type 2 hypersensitivity reaction. It indicates mast cell degranulation.

RAST is a useful aid to improve the overall diagnosis of drug allergies by using radioactive detection. This, however, is now rarely used.

Quantification of basophil activation by CD63 expression can be done by flow cytometry, which forms the basis of experimental drug-induced basophil stimulation tests.

Patients who present for surgery may be on prescription medication or natural/herbal therapies. These have relevance for anaesthesia since they can cause drug interactions.

Ephedra (Ma Huang) is a drug derived from the plant Ephedra sinica that is used as a CNS stimulant, weight reduction aid, and asthma therapy. It is a combination of alkaloids that includes ephedrine which stimulates noradrenaline release from pre-synaptic neurones by acting directly on alpha and beta adrenoreceptors. The use of sympathomimetic drugs together can cause cardiovascular instability.

Ginkgo Biloba contains anti-oxidant characteristics and is used to treat Alzheimer’s disease, vascular dementia, and peripheral vascular disease. It lowers platelet adhesiveness and raises the risk of bleeding by decreasing platelet activating factor (PAF), especially in individuals who are also taking anticoagulants and antiplatelet drugs.

The extract from St. John’s Wort is utilised as an antidepressant because it is a cytochrome P450 isoenzyme inhibitor as well as a serotonin uptake inhibitor. When drugs like fentanyl or tramadol are used during an anaesthetic, there is a risk of serotonin syndrome developing.

The root of a pepper is used to make kava (Piper methysticum). It is a weak GABAA agonist which has the potential to augment the effects of propofol and benzodiazepines, which are volatile anaesthetics.

Garlic is made from the allium sativum plant and is used to treat hypertension and hyperlipidaemia. It includes cysteine, which inhibits platelet aggregation irreversibly, amplifying the effects of aspirin and NSAIDs.

Echinacea is a common herbal medicine that stimulates the immune system by modulating cytokine signalling. In individuals who require organ transplantation, it should be avoided.

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 = 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

Prerenal failure has a serum urea: creatinine ratio of >100, while acute kidney injury has a ratio of 40.
In prerenal failure, ADH levels are typically high, resulting in water, urea, and sodium resorption. The fractional sodium excretion is less than 1%, but it is greater than 2% in acute tubular necrosis.
Prerenal azotaemia has higher serum urea nitrogen/serum creatinine ratios (>20), whereas acute tubular necrosis has lower ratios (10-15). The normal range is between 12 and 20.
Urinary sodium is less than 20 in prerenal failure and greater than 40 in acute tubular necrosis.
Prerenal failure has a urine osmolality of >500, while acute tubular necrosis has an osmolality of 350.
Prerenal failure has a urine/serum creatinine ratio of >40, while acute tubular necrosis has a urine/serum creatinine ratio of 20.

The concentrations of serum urea or creatinine change in inverse proportion to glomerular filtration. Changes in serum creatinine concentrations are more reliable than changes in serum urea concentrations in predicting GFR. Creatinine is produced at a constant rate from creatine, and blood concentrations are almost entirely determined by GFR.

A number of factors influence urea formation, including liver function, protein intake, and protein catabolism rate. Urea excretion is also influenced by hydration status, the amount of water reabsorption, and GFR.

A high serum creatinine level, as well as a urine output of less than 10 mL/hour and the production of concentrated looking urine, do not necessarily indicate a specific cause of oliguria.