Applied and Basic sciences Flashcards
Platelets
Platelets are membrane-encapsulated fragments of megakaryoctes.
Although platelets have no nucleus, they are metabolically active and are able to express membrane receptors and release stored substances when triggered. They contain adenosine diphosphate and serotonin.
However, because they have no nucleus they are unable to produce new proteins and therefore aspirin and other drugs affect function for the remainder of the platelet lifespan. Platelet lifespan is approximately 9-10 days in normal individuals.
Platelets are capable of producing nitric oxide, prostaglandins and thromboxane, but not the vasodilator prostacyclin.
Predisposing factors for the development of keloid scars include which of the following?
Male sex Patients of Afro-Caribbean origin with dark complexion Secondary wound closure Steroid therapy Use of local bupivacaine
Keloid scars are characterised by smooth hard nodules caused by excessive collagen production. Keloid scarring is much commoner in people of Afro-Caribbean origin. They also tend to affect young adults a lot more.
Keloid scarring may occur spontaneously but is associated with skin trauma, infection, and surgery.
There is no evidence to suggest that keloid scarring is associated with steroid therapy. However, if keloid scarring is treated with surgical removal then it must be followed by steroid injection or superficial radiotherapy or it may make the problem worse.
There is no evidence to suggest that keloid scarring is associated with wound healing by secondary intention. There is some evidence to suggest that primary wound closure is a risk factor.
Local anaesthetics are not associated with keloid scarring. They can be used in surgical removal of the scar.
Other methods of treatment include triamcinolone injection and compression with silica gels.
Which one of the following gases can be measured by infrared analysers?
Gases with molecules that contain at least two dissimilar atoms absorb radiation in the infrared region of the electromagnetic spectrum. Therefore, carbon dioxide, nitrous oxide and all the halogenated volatile anaesthetic agents can be measured using infrared absorption analysers.
Oxygen, nitrogen, helium and the inert (or noble) gases do not absorb infrared light and cannot be measured using this technology.
Oxygen is measured using the paramagnetic, galvanic or polarographic method.
Oncogenes and tumour suppressor genes
Which genetic abnormality is most strongly associated with BCR-ABL
CML
BCR-ABL is a gene implicated in chronic myeloid leukaemia. The Philadelphia chromosome found in this malignancy results from a reciprocal translocation between chromosomes 9 and 22. The breakpoint on chromosome 22 is at the BCR gene and, on chromosome 9, the ABL gene.
Oncogenes and tumour suppressor genes
Which genetic abnormality is most strongly associated with B-RAF
B-RAF is an oncogene associated with a range of cancers. These include
malignant melanoma
Lymphomas
Non-small cell carcinoma
Adenocarcinoma of the lung.
Oncogenes and tumour suppressor genes
Which genetic abnormality is most strongly associated with BRCA
Breast cancer
BRCAs 1 and 2 are tumour suppressor genes strongly associated with inherited forms of breast cancer. Women with an abnormal BRCA gene have an 85% chance of developing breast cancer before the age of 70. There is also a significantly increased risk of developing ovarian cancer in these patients.
Which of the following is true regarding prostaglandins?
Cause uterine dilatation
Decrease blood flow to the kidneys
Increase gastric acid secretion
Lead to inflammatory responses
Lead to inflammatory responses
Prostaglandins act as chemical messengers at the site where they are synthesised. They are thus different from hormones, which can be transported in the blood and can act in distant sites in the body.
Prostaglandins have a variety of physiological effects including:
- Activate the inflammatory response at the site of tissue injury, leading to pain, swelling, redness and increase in temperature
- Haemostatic properties, such as when there is blood vessel damage (thromboxane stimulates vasoconstriction and activation of platelets)
- Stimulate uterine contractions and thus are effective in inducing labour
- Inhibit acid synthesis (including gastric acid) and increase secretion of protective mucus within the GI tract
- Increase blood flow in kidneys
- Constriction of bronchi, thus exacerbating bronchial asthma.
In the presence of inflammation, which of the following is decreased?
Caeruloplasmin Complement proteins Fibrinogen Platelets Sweating
Inflammation induces high systemic levels of acute-phase proteins.
These proteins include C-reactive protein and vasopressin, which cause a range of systemic effects including;
Fever Increased blood pressure Decreased sweating and Loss of appetite. Thrombocythaemia occurs with chronic inflammation, for example, in rheumatoid arthritis.
Ferritin is an acute-phase reactant and serum levels rise in inflammation.
Caeruloplasmin is a copper carrying protein that is also an acute phase reactant.
Fibrinogen is a clotting factor and synthesis is increased by the liver in inflammation along with other acute phase proteins.
Complement proteins such as C3a and C5a have multiple roles in inflammation (chemotaxis, bacterial pore lysis) and serum levels rise accordingly.
Which of the following is true regarding Pseudomonas aeruginosa?
Can cause osteomyelitis
Is a Gram positive bacterium
Is an uncommon cause of contact lens acquired infection
Is sensitive to chloramphenicol
Is usually resistant to ciprofloxacin
Osteomyelitis
Infection rates can be reduced by wearing the contact lens for 10 hours or less.
It is a Gram negative aerobic bacillus.
The most common organisms that cause osteomyelitis are Staphylococcus, Haemophilus influenzae, and Salmonella, although P. aeruginosa can cause osteomyelitis.
Chloramphenicol has good activity against Haemophilus influenzae but not P. Aeruginosa.
P. Aeruginosa is sensitive to quinolones which inhibit DNA topoisomerase
Concerning which of the following must an aetiological factor satisfy the following before one can say that it is causally related to a disease?
Exposure to the factor may not necessarily precede the development of the disease
Elimination of the factor does not decreases the risk of the disease
The factor is found more frequently among the diseased than non-diseased
The factor is not found among persons without the disease
The factor is found in all cases with the disease
The factor is found more frequently among the diseased than non-diseased
Hill devised criteria for assessing causation and proposed that the cause must precede the effect.
Again, Hill’s criteria suggest that when assessing causation removing the factor of interest should reduce the risk of disease.
Hill suggested that there should be a dose-response relationship, that is, higher levels of the effect should lead to more severe disease or more rapid disease onset.
To illustrate this principle one can look at rheumatoid factor. It is found in people both with and without rheumatoid arthritis. Again, autoantibody tests illustrate this principle as they can be found in unaffected patients.
Which of the following statements is true of wound infections?
Anaerobic organisms exert their lethal effects by producing endo- and exotoxins
MRSA wound infection is usually the result of wound contamination by the patient
Necrotising fasciitis is commoner in carriers of MRSA
Opportunistic organisms tend to affect young healthy adults
Streptococcus is the most common organism to infect the surgical wound
Anaerobic organisms exert their lethal effects by producing endo- and exotoxins
Staphylococci are aerobic, facultatively anaerobic, Gram positive cocci. They are the most common organism to infect the surgical wound as they are common skin commensals.
MRSA wound infection is hospital acquired and the risk of acquisition can be minimised by basic precautions such as hand washing before wound inspection. Sepsis and its sequelae such as acute respiratory distress syndrome illustrate this principle.
As part of sepsis toxins damage the endothelium of the lung capillaries and the accompanying inflammatory response results in oedematous changes and haemodynamic instability.
Surgical wounds become infected with opportunistic organisms because of the relatively immunocompromised state of the post-operative patient resulting in reduced microbial inhibitions.
Necrotising fasciitis is a deep-seated aggressive infection of subcutaneous tissue and skin. It is commonly caused by group A Streptococci and there is no evidence to suggest it is commoner in carriers of MRSA.
Laparoscopy:
A 1 cm vertical incision was made below the umbilicus at the start of the procedure. Two stay sutures are placed in the fascia and the fascia divided. A blunt instrument was then inserted and a pneumoperitoneum was created.
This is Hassan’s cannula. The description given is that of an open technique (Hassan technique) of creating a pneumoperitoneum. The open technique avoids the relatively rare but potentially disastrous accidental perforation of an intra-abdominal structure during the insertion of a Veress needle (closed technique).
Gynaecologists are still keen on the Veress needle, thus providing general surgical registrars with valuable experience of iatrogenic abdominal injury.
Laparoscopy:
During a laparoscopic cholecystectomy Calot’s triangle is dissected out using which instrument?
A number of instruments are available for dissecting structures laparoscopically. A Petalan’s forceps is usually favoured as it has a curved end and only the upper jaw moves. This provides more controlled dissection.
Laparoscopy:
Once the cystic duct and artery are clearly identified they are ligated and divided close to the gallbladder.
Three clips are placed on the cystic duct and on the artery. The artery and duct are then divided between the two clips nearest the gallbladder.
Antibiotic prophylaxis prior to operations
Antibiotic prophylaxis is used to prevent infection and is based on the degree of contamination involved in the surgical procedure.
Breast, thyroid and hernia repair operations, where there is minimal risk of wound contamination, are classed as clean surgery. Antibiotic prophylaxis is controversial in this group. Most surgeons choose no antibiotics at all or one single shot of broad spectrum antibiotic at induction.
Operations such as cholecystectomy, elective/interval appendicectomy or bowel resection, where the contamination of the wound can be contained/controlled, are classed as clean contaminated wounds and require broad spectrum antibiotics given at induction and every six hours intra-operatively if the surgery is prolonged. The use of post-operative antibiotics is debatable in these situations.
Emergency operations or those where the amount of contamination is difficult to contain or estimate (including traumatic wounds) are classed as contaminated and are shown to benefit from 72 hours of intravenous broad spectrum antibiotics. Uncomplicated, early appendicitis generally only requires anaerobic cover with induction.
Grossly contaminated wounds before the start of surgery are classed as dirty wounds and need therapeutic antibiotics as opposed to prophylaxis - the choice of antibiotic being empirical as determined by the source of contamination.
Certain special conditions need specific antibiotic prophylaxis, as otherwise they could result in severe infections anywhere in the body. These include immune compromised states (including splenectomy and steroid therapy).
As outlined in the NICE guidance on Prophylaxis against infective endocarditis (CG64), routine antibiotic prophylaxis is no longer recommended for dental procedures or routine surgery for patients with congenital or acquired heart disease.
Intravenous broad spectrum antibiotics, including anaerobic cover, commencing in the operating theatre with the induction of anaesthesia.
Emergency sigmoid colectomy
No antibiotic prophylaxis.
Dental procedure for patient with atrial septal defect
Penicillin G
Splenectomy
Intravenous metronidazole during the induction of anaesthesia.
Emergency appendicectomy
A 45-year-old male with pyloric stenosis presents with profuse vomiting and abdominal pain. What else besides a hypokalaemia may be expected?
Metabolic alkalosis
Patients with pyloric stenosis develop hypochloraemic hypokalaemic alkalosis, as they lose chloride ions with hydrogen ions when they vomit.
A 60-year-old man with villous adenoma presents with profuse diarrhoea.
Hypokalaemia
Villous adenoma is associated with profuse watery diarrhoea, which is typically associated with hypokalaemia.
A 62-year-old man presents to the emergency department with a six hour history of severe pain and altered sensation in his left leg. On examination, the pulses are absent beyond the femoral artery, his foot is cold and sensation is reduced. He is in atrial fibrillation and duplex scan of the femoral artery reveals a blockage in the common femoral artery.
Femoral embolectomy
This patient has got an acute embolic event, possibly from the underlying atrial fibrillation. He is manifesting signs of severe vascular compromise which if left untreated would soon progress to critical ischaemia. The six cardinal signs of critical ischaemia are: pain, pallor, pulselessness, paralysis, paraesthesia and cold to touch (perishing with cold). In this patient, since there is no pulsation beyond the superficial femoral artery and the duplex scan reveals a blockage in the common femoral artery, the most appropriate procedure would be a femoral embolectomy which can be undertaken either under general or local anaesthesia.
A 65-year-old man presents to the vascular outpatient clinic with a four month history of pain in his legs whilst walking. He claudicates at around 75-100 yards. He has no rest pain. He is fit and well apart from osteoarthritis in his knees. Angiogram reveals occlusion of the lower end of abdominal aorta including the bifurcation but patent femoral vessels.
Aorto=bifemoral bypass
This patient is suitable for an aorto-bifemoral bypass grafting since his blockage is limited to the aorta and the bifurcation but has patent femoral vessels. He is also medically fit to undergo this procedure. Aorto-bifemoral bypass grafting has the highest patency rate of any bypass procedures to the femoral vessels.
An 89-year-old man presents to the vascular outpatient clinic with inability to walk beyond 20-30 yards and severe rest pain. On examination, his legs are manifesting evidence of impending critical ischaemia. He has a type I diabetes, is hypertensive and has severe ischaemic heart disease. Angiogram reveals complete occlusion of the aorta but patent femoral vessels bilaterally.
Axillo-bifemoral bypass graft
Since this patient is elderly, has serious underlying medical problems, and is manifesting signs of impending critical ischaemia, an axillo-bifemoral bypass graft would be the most appropriate procedure. This type of grafting should be considered in surgically/anaesthetically unfit patients who have or are manifesting early signs of critical ischaemia. This procedure is less traumatic and complicated than an aorto-bifemoral bypass for the simple reason that it does not involve a laparotomy or clamping the aorta. It is not an appropriate procedure in patients with intermittent claudication.
Which of the following is regarded as an Indication for tonsillectomy?
The indications for tonsillectomy are controversial. Undoubtedly, upper airway obstruction, particularly if associated with hypoxaemia or apnoea, is a clear indication.
In most cases, recurrent tonsillitis with pus requiring antibiotic therapy more than three times a year for three successive years would encourage the surgeon to remove the tonsils. This is particularly the case if there has been a previous abscess.
However, if there is no history of chronic tonsillitis, the chance of a recurrence of quinsy is only about 10%, so isolated incision and drainage with antibiotics is all that is required.
Which of the following is correct regarding pulse oximetry?
Pulse oximetry is a non-invasive method of assessing arterial oxygen saturation and heart rate.
Any cause of poor peripheral perfusion causes unreliable readings, including external compression by a blood pressure cuff.
Though there may be mechanical causes for poor pulse oximetry readings you should always look for a physiological cause first. For example, vasoconstriction is one of the first compensatory mechanisms employed by the body following blood loss.
In these situations it is often helpful to check pulse rate in comparison to the electrocardiogram (ECG).
Other causes of error include abnormal pigments such as bilirubin, methaemoglobin and carboxyhaemoglobin. Jaundice underestimates the actual oxygen saturation, whereas carbon monoxide poisoning overestimates the level of saturation.
When the partial pressure of oxygen is plotted against percentage saturation, a sigmoidal curve is produced. The middle range of the curve is therefore particularly important as small changes in partial pressure will cause large changes in saturation.
Certain factors may result in ‘shifts’ in the curve. The following cause a right shift in the curve:
reduced pH increased temperature partial pressure of carbon dioxide, and 2-3 diphosphoglycerates. This means that haemoglobin gives up oxygen more easily to the tissues.
Which one of the following is unlikely to inhibit wound healing?
Excessive methionine in the diet High doses of corticosteroids Low temperatures Malnutrition Vitamin C (ascorbic acid) deficiency
Wound healing is delayed in
Zinc deficiency Methionine deficiency Vitamin C deficiency (scurvy) Hypothermia Diabetes Malnutrition Cushing's syndrome.
Alpha-ketoglutarate is a five carbon molecule
Krebs’ cycle (tricarboxylic acid cycle or citric acid cycle) is a sequence of reactions in which acetyl coenzyme A (acetyl-CoA) is metabolised to carbon dioxide and hydrogen atoms.
The sequence of reactions is known collectively as oxidative phosphorylation, which only occurs in the mitochondria (not cytoplasm).
The cycle requires oxygen and does not function under anaerobic conditions. It is the common pathway for the oxidation of carbohydrate, fat and some amino acids, required for the formation of high energy phosphate bonds in adenosine triphosphate (ATP).
Pyruvate enters the mitochondria and is converted into acetyl-CoA, which represents the formation of a two carbon molecule from a three carbon molecule (with the loss of one CO2 and the formation of one NADH molecule). Acetyl-CoA is then condensed with the anion of a four carbon acid, oxaloacetate, to form citrate which is a six carbon molecule.
Citrate is subsequently converted into isocitrate, alpha-ketoglutarate, succinyl-CoA, succinate, fumarate, malate and finally oxaloacetate.
Alpha-ketoglutarate is the only five carbon molecule in the cycle.
Which of the following electrocardiogram (ECG) changes is associated with a suspected myocardial infarction?
The usual ECG changes following an acute myocardial infarction include S-T elevation greater than 1 mm (convex upwards, concave downwards) developing within the first few hours. Tall peaked T waves may also be seen in the acute stages.
Pathological Q waves (representing transmural infarction), a reduction in R wave height and deeply inverted T waves (in the leads facing the infarcted muscle) may develop over the next 72 hours.
The absence of Q waves implies partial-thickness infarction. A subendocardial MI is associated with flat S-T depression (not elevation) and T wave inversion in leads facing the infarction.
The S-T segment changes following a myocardial infarct usually resolve within days. The T wave changes often persist for weeks but may be permanent. The Q waves are usually, but not always permanent.
It is possible to diagnose an acute MI in the presence of right bundle branch block and also in left bundle branch block when using non-standard ECG criteria.
True posterior left ventricular infarction is characterised by tall R waves, S-T depression and peaked upright (not inverted) T waves in leads V1 and V2.
Right ventricular infarction does not produce a specific pattern in the standard 12 lead ECG, so the use of right-sided precordial leads (V4R - V6R) is required.
transcutaneous liver biopsy is considered for an 80-year-old female
Contraindications?
A haemoglobin concentration of 9.9 g/dl (NR 11.5-15.5)
A platelet count of 140 ×109 (NR 150-400)
Age
An INR of 1.5
Extra-hepatic biliary obstruction
Contraindications to liver biopsy include:
Bacterial cholangitis because of the risk of causing peritonitis or septic shock.
A platelet count below 80,000/mm3 (there is no absolute agreed lower level: 50,0003 may be acceptable. Platelet function is more important than absolute numbers (eg stop clopidogrel a week before)
A deranged INR above 1.5 (this value is debatable as 90% of bleeds occur in patients with an INR
Regarding prostate specific antigen (PSA), which of the following is correct?
Elevated concentrations are expected following digital rectal examination (DRE)
Is a serine protease
Is found only in the prostate
Is required for sperm motility
Mutations of the PSA gene are aetiological in the development of prostate cancer
PSA was thought to be specific for the prostate but we now realise that it is found in the peri-urethral glands, peri-anal glands and also in breast tumours.
Concentrations are elevated in benign prostatic hyperplasia, prostate cancer and following procedures such as biopsy.
Although there may be a small rise in PSA following digital rectal examination (DRE), elevated concentrations are not expected.
Gene mutations are not associated with prosate cancer - which is associated with oncogenes such as c-myc, etc.
Its role is in the liquefaction of seminal gel not in sperm motility.
A normal PSA does not exclude prostate cancer with studies showing a risk of 15% of prostate Ca in subjects with a PSA less than 4 ng/ml.
Barr body is caused by the presence of an inactive X chromosome
Barr body is only found in people who are phenotypically female
Cells containing YO chromosome are compatible with life
The Y chromosome is larger than the X chromosome
There are 23 pairs of autosomal chromosomes
During interphase chromosomes are too tenuous to be stained and seen by light microscopy. However, a dense, stainable structure, called a Barr body (after its discoverer) is seen in the interphase nuclei of female mammals. The Barr body is one of the X chromosomes. Its compact appearance reflects its inactivity.
People with XXY or XXXY karyotypes are males (because of their Y chromosome), and display the features of Klinefelter’s syndrome. The phenotypic effects of the extra X chromosomes are mild because, just as in females, the extra Xs are inactivated and converted into Barr bodies.
No YO individuals have been identified, not even aborted fetuses. It has been suggested that there is something fundamental on the X chromosome that is needed for life.
The Y chromosome is smaller than the X chromosome.
There are 22 pairs of autosomes, and one pair of sex chromosomes.
Regarding Staphylococcus aureus Is a Gram positive motile organism Is arranged in chains Is typically anaerobic Produces a coagulase Produces endotoxin
Staph aureus is a Gram positive, non-motile, aerobic coccus whose colonies are arranged in grape-like clusters.
Strains are responsible for food poisoning through the production of an enterotoxin and pathogenicity is also associated with coagulase positivity.
A 45-year-old female is noted to have a mean cell volume (MCV) of 102 fl (80-96) on full blood count.
Causes of a high MCV include folate or B12 deficiency (pernicious anaemia), alcoholism and hypothyroidism.
Blood loss, as in peptic ulceration or menorrhagia, is associated with iron deficiency and microcytosis.
By which of the following is HIV not reliably inactivated?
Chlorhexidine Glutaraldehyde Hypochlorites The autoclave The hot-air oven
Chlorhexidine is effective, but does not guarantee complete clearance of HIV.
Which factor does not affect the performance of a disinfectant?
Concentration of disinfectant Number of organisms present pH Type of organisms Water hardness
The concentration of disinfectant, as well as the type of organism, are also important factors.
Numbers of organisms - high numbers of organisms leads to clump formation. Organisms inside of the clump are shielded from the control method.
pH plays an important role in the performance of a disinfectant. Many organisms have an optimum pH at which they work best. Deviation from this optimum value results in loss of activity.
Water hardness was historically a problem for disinfectants dissolved in water. However, modern disinfectants are able to withstand water hardness.
Temperature is also an important factor: warm liquid disinfectants are more effective than colder ones, as increasing the temperature decreases surface tension whilst also increasing the rate of chemical reactions.
Which of the following statements concerning intravenous fluids is correct?
0.9% saline solution has a similar pH to plasma
Colloids generally have lower sodium concentrations than 0.9% saline
Hartmann’s solution has a higher chloride concentration than 0.9% saline
Hydroxyethyl starch solutions interfere with blood cross-matching
Pruritis is associated with the use of hydroxyethyl starch solutions
Hartmann’s solution contains
131 mmol per litre of sodium ions 111 mmol per litre of chloride ions 2 mmol per litre of calcium ions 5 mmol per litre of potassium ions 29 mmol per litre of lactate ions. It therefore has a lower chloride concentration than 0.9% saline (154 mmol per litre of sodium and chloride ions).
0.9% saline has a pH of 5.5, whereas plasma pH is approximately 7.4.
Hydroxyethyl starch solutions do not interfere with blood cross-matching, unlike the dextrans, although rouleaux formation may occur.
Artificial colloids are suspensions of large molecules in 0.9% saline and so contain 154 mmol per litre of sodium (the same).
The hydroxyethyl starches are removed from the circulation by the reticuloendothelial system and are deposited in the skin.
Pruritis is therefore a relatively common and significant sequel of over-enthusiastic administration of starches.
Which of the following is true regarding penicillins?
Are bacteriostatic
Exert their actions by combining with a transpeptidase
Have a spectrum of action which is independent of the beta-lactam side chain
Have significant toxic effects on humans
May be activated by enzymes which are plasmid coded
Exert their actions by combining with a transpeptidase
Penicillins are generally bactericidal and exert their effect by combining with and inhibiting the transpeptidase enzyme which cross-links the peptidoglycans in the cell wall. This weakens the cell wall and allows the cell to lyse under the influence of an osmotic gradient.
The widespread resistance to penicillins is due to beta-lactamase enzymes which break the beta-lactam ring and inactivate the drug.
The beta-lactamase enzyme is often encoded in the bacterial plasmid. The plasmid is bacterial DNA (separate from the main chromosome) that can be translocated from bacterium to bacterium and it is for this reason that resistance may be also transferred.
Although the penicillins have similar spectra of action, their specific spectra may be changed by altering the beta-lactam side chain.
They do not have significant toxic effects on humans, but allergy is common.
Which one of the following statements regarding intravenous fluids is correct?
5% dextrose has a pH of 6.0
Haemaccel causes histamine release
Hartmann’s solution contains 154 mmol/l of sodium
Normal saline contains 150 mmol/l of both potassium and chloride
The average particle size in hydroxyethyl starch is 300,000 kDa
Haemaccel causes histamine release
All dextrose containing crystalloid solutions has a pH of 4.0 (not 6.0).
Haemaccel does cause histamine release and at 0.15% has a low incidence of allergic reactions.
Hartmann’s solution (compound sodium lactate or Ringer’s lactate) contains
131 mmol/l of sodium 111 mmol/l of chloride 5 mmol/l of potassium 2 mmol/l of calcium 29 mmol/l of lactate. Normal saline or 0.9% sodium chloride contains 154 mmol/l of both sodium and chloride in water, and it does not contain potassium.
At 70,000 kDa hydroxyethyl starch has an average particle size similar to albumin.
