DR.

SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)

IMPORTANT MCQ COLLECTION FOR PART-1 MRCOG FROM PAST EXAMINATIONS.

DR S.KARIM SHAH SHIRAZI
FRCS(Ed), FRCS(Ir), FRCS(Glasg)

CONSULTANT SURGEON
D.H.Q. TEACHING HOSPITAL / SAHIWAL MEDICAL COLLEGE SAHIWAL PAKISTAN Email: surgeonshirazi@yahoo.com Cell No: +92 300 8690150
1

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)

Important MCQ colloction for part-1 MRCOG(1)) 1- Prostaglandin PGI2 (prostacyclin).. A- reduces arterial smooth muscle tone .....................T B- is a product of arachidonic acid metabolism ............................T C- production is inhibited by non-steroidal anti-inflammatory drugs .............T D- increases platelet cyclic AMP concentration ...................T E- inhibits platelet aggregation to damaged vessel walls ...................T 2- The antiphosphopholipid syndrome is associated with: A- myocardial infarction ...............................T B- venous thrombosis ..................................T C- left ventricular thrombus ..........................T D- pulmonary hypertension ..........................T E- recurrent abortion ...................................T Antiphospholipid syndrome is the association of arterial and venous thrombosis with antibodies directed against phospholipids. Originally noted as a complication in approximately 30% of patients with systemic lupus erythematosus, it is now also diagnosed in patients with thrombotic episodes and anti-phospholipid antibodies (aPL) but without clinical features of SLE - primary antiphospholipid syndrome. It is associated with MI, Recurrent miscarriages, DVT, Stroke, pulmonary hypertension (due to thromboembolic disease) and LV thrombus rarely reported. 3- Natural Killer cells ....... A- are a type of T lymphocyte ...................T B- are predominantly found in lymph nodes ..............................F C- express cell surface CD-3 ...................................................F D- kill antibody coated cells ....................................................T E- release tumour necrosis factor ...........................................T a) Natural Killer cells are a lymphocytic lineage discrete from T + B lymphocytes and are involved in defence against malignancy, viruses and probably bacteria and parasites. b) rarely found in thymus / lymph nodes - unlike T cells c) NK cells are CD3-ve and CD16 and CD56 +ve (the opposite is true of T

2

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
cells). d) NK cells kill spontaneously, are stimulated by IL-2 or antibody coated cells through binding to their CD16 receptors. e) and IFN gamma, granulocyte-macrophage colony stimulating factor and colony stimulating factor 1..... Natural Killer (NK) cells are yet another type of lethal lymphocyte. Like cytotoxic T cells, they contain granules filled with potent chemicals. They are called "natural" killers because they, unlike cytotoxic T cells, do not need to recognize a specific antigen before swinging into action. They target tumor cells and protect against a wide variety of infectious microbes. In several immunodeficiency diseases, including AIDS, natural killer cell function is abnormal. Natural killer cells may also contribute to immunoregulation by secreting high levels of influential lymphokines. Both cytotoxic T cells and natural killer cells kill on contact. The killer binds to its target, aims its weapons, and then delivers a lethal burst of chemicals that produces holes in the target cell's membrane. Fluids seep in and leak out, and the cell bursts. 4- Regarding Immunoglobulin: A- Immunoglobulins are secreted from T-lymphocytes. ...................F B- An immunoglobulin G (IgG) comprises 2 antigen-binding sites and a site for the binding of complement. .................T C- The molecular structure of IgG is a Y shape ................T D- IgG constitute approximately 25% of all immunoglobulis in a healthy individual...................F E- IgMs can cross the placenta to the foetus. ...................F Immunoglobulins (antibodies) are secreted from B-lymphocytes (plasma cells) in response to a specific antigen. Both antigen-binding sites are identical and consist of a long and heavy chain. IgGs constitute approximately 75% of all immunoglobulis in a healthy individual. Only IgGs can cross the placenta. This is important as they provide immune protection for the newborn in the first few months of life 5- Disinfectant solutions may become contaminated with: A- Enterobacter species ....................T B- Streptococcus species ................F C- Escherichia coli .........................F D- Pseudomonas aeruginosa (pyocyanea) ...................T E- Staphylococcus pyogenes ........................F 6- Polymerase chain reaction : A- can amplify RNA but not DNA........................F B- It is of no value in prenatal diagnosis .............F C- depends on thermostable Taq DNA polymerase .................T D- requires primer bits either side ........................................T

3

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
E- uses heat to separate two strands of DNA .........................T The Polymerase Chain Reaction (PCR) allows scientists to directly and exponentially amplify small samples of DNA and through reverse transcriptase PCR - RNA. The test may be used for the prenatal diagnosis of conditions such as Cystic fibrosis. d-this is a disadvantage because the primers have to be known 7- Under which circumstances would the efficacy of the combined oral contraceptive be reduced? A- Oral tetracycline two months into treatment for acne .................F B- Oral Rifampicin given as acute prophylaxis for meningitis ..........T C- Oral Omeprazole given for Gastritis ..............F D- Oral metronidazole given for trichomoniasis .............................T E- Oral sodium valproate for epilepsy ...........................................F Certain drugs are known to reduce the effectiveness of the OCP. Hepatic enzymeinducing antiepileptic drugs lower oral contraceptive pill hormone levels by approximately 40 percent. These include carbamazepine, rifampicin, phenytoin. Also antibiotics like ampicillin, tetracyclines and metrondazole may reduce the efficicay of the OCP. After taking tetracyclines for some time (as in acne) the bowel flora adapt and normal efficacy of COCP is reinstated, however, acute courses will result in reduced efficacy. In contrast, valproic acid (Depakene) and gabapentin (Neurontin) do not interfere with the effectiveness of oral contraceptive pills .... Drug decreases effectiveness of oral contraceptive pills Amoxicillin Ampicillin Carbamazepine (Tegretol) Ethosuximide (Zarontin) Metronidazole (Flagyl) Phenobarbital Phenytoin (Dilantin) Primidone (Mysoline) Rifampin (Rifadin) Tetracycline Troglitazone (Rezulin) Oral contraceptive pills decrease effectiveness of drug Clofibrate (Atromid-S) Lorazepam (Ativan) Oxazepam (Serax) Salicylates Temazepam (Restoril) Oral contraceptive pills potentiate effect of drug Benzodiazepines Beta blockers

4

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
Caffeine Corticosteroids Theophylline Tricyclic antidepressants 8- With regard to the DNA structures: A- adenine (A) and guanine (G) are purine bases ...................T

B- guanine (G) always pairs with thymidine (T) and adenine (A) with cytosine (C) ...............F C- each DNA strands have a pentose-phosphate backbone with projecting bases ..................T

D- there are 64 possible codons ....................T

E- each amino acids may be coded by more than one codon. ......T Pyrimidine bases are thymidine (T) and Cytosine (C). G always pairs with C and T with A. 9- The adductor canal :

A- contains an artery which contributes to the genicular anastomosis .........T B- contains a nerve supplying the tensor fascia lata muscle .................F C- contains the deep femoral artery ...........................F D- contains the nerve to the vastus medialis muscle ................T E- contains the saphenous nerve .....................T The adductor canal is a gutter shaped groove between the vastus medialis muscle and in front of the adductor muscle. The gutter is roofed by the sartorius muscle, underneath which a fascia contains the subsartorial plexus. The calan transmits the femoral artery and veing, saphenous nerve and, in the upper part, the nerve to the vastus medialis muscle. The tensor fascia lata muscle is supplied by the superior gluteal nerve (L4, L5, S1), which crosses the buttock and ends in the muscle. 10- Characteristic findings in anorexia nervosa are: A- a decrease in Cortisol levels ...............................F B- an increase in LH levels ......................................F C- impaired glucose tolerance .............................T D- raised androgen levels .....................................F

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DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
E- hyperkalaemia ..................................................F a-Cortisol and growth hormone are elevated. b-LH and FSH low and LH response to LHRH is impaired when weight loss is severe. e-Hypokalaemia, hypoalbuminaemia, anaemia, leukopenia, raised serum carotene. 11- Mitochondrial DNA : A- is inherited from both parents .........................F B- is present in spermatozoa ..............................T C- have their own genome .................................T D- are expressed in neuronal tissue ..................T E- only daughters of an affected mother could transmit the trait .........T the mitochondria are in the tail but not transferred to the ovum and hence the mitochondrial DNA is not inherited from the father c - which code for cytochrome oxidase enzymes d - and other tissues rich in mitochondra resulting in neurological syndromes, myopathies and cardiomyopathies 12- In the human female : A- one of the X chromosomes is activated .........................T B- an inactivated X chromosome occurs in neutrophils as a drumstick on the nucleus ...............T C- X chromosomes carry the gene for glucose-6-phosphate dehydrogenase ....T D- the number of Barr bodies seen is eqivalent to the number of X chromosomes present .....F E- clinically apparent haemophilia A cannot occur ................F The chromatin nodule is the second (inactive) X chromosome; hence its absence in males. In polymorphonuclear leucocytes, a tiny nodule of chromatin (the Barr body, or nuclear drumstick) can be seen near the nuclear membrane of many cells in normal females, but not in normal males. G6PD deficiency is inherited as an X-linked disorder. 1 Barr body is seen in females and represents the one inactivated X chromosome of the pair. Haemophilia A is an X-linked recessive disorder and so it is possible for a female to be affected if a carrier female marries an affected male. 13- The following are true of genes : A- The rate of DNA replication is directly under the control of enhancer sequences. .......F B- Mitochondrial genes are inherited from the mother......................T C- Transcription factors are mainly made of RNA...............................T D- Introns are the portions of a gene which code for protein. .............F E- Most of the human genome encodes polypeptide.........................F

6

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
A gene is a length of DNA that carries information to make a single peptide chain. However, it is estimated that only a few percent of DNA comprising the whole human genome consists of genes encoding protein. Introns are intervening sequences of unknown function in mammalian genes. Regulatory elements of gene transcription include promoters (regions of DNA to which RNA polymerase bind and initiate transcription), enhancer sequences (modify activity of genes on the same chromosome) and transacting proteins (modify genes on both pairs of homologous chromosomes). mRNA are transcripts of DNA, which are attached to transfer RNA and then translated in ribosomes to protein, which then undergo considerable post-translational changes. Mitochondrial inheritance is exclusively maternal, as none of the mitochondria from sperm survives fertilization. 14- C - reactive protein : A- Is produced primarily in the affected tissue ........................F B- Synthesis is initiated by the release of Adrenocorticotropic Hormone (ACTH) ........T C- Is functionally analogous to immunoglobulin G (IgG) ...........................T D- Shows an earlier and more intense increase than the erythrocyte sedimentation rate (ESR) in an acute inflammatory change.......F E- Are increased when a patient is taking non-steroidal anti-inflammatory drugs ......F CRP is an abnormal protein produced by the liver during an acute inflammatory response. Antigenimmune complexes to infecting agents and trauma initiate the synthesis of CRP. Although functionally analogous to IgG it is not antigen specific. CRP is more sensitive and responds more rapidly than ESR. NSAID's reduce the CRP response. 15- Labetalol: A- Has alpha blocking action ............................................................T B- Causes bronchodilation ...............................................................F C- Decreases bile secretion ..............................................................T D- Is 70% protein bound ..................................................................F E- Has a half-life of 2 hours ..............................................................F Labetalol is a combined beta and alpha adrenergic receptor antagonist with a ratio of activity between 2:1 and 5:1 respectively. It is selective for alpha-1 receptors but is non-selective for beta receptors. It is used to treat severe hypertension and pre-eclampsia and in hypotensive anaesthesia. Labetalol has a half-life of approximately four hours (not 2) and is approximately 50% protein bound. It has been shown to cross the placental barrier, but not the blood brain barrier. It is metabolised in the liver and excreted in the urine and faeces. Oral administration of the drug undergoes extensive first-pass metabolism. Severe hepatocellular damage has been reported after both short and long term use and the reduction of bile secretion may rarely lead to jaundice. 16- Which of the following are true about the Y chromosome? A- the long arm is referred to as the p arm ........................................F

7

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
B- the long arm has variable length ..................................................T C- it demonstrates fluorescence with quinacrine .................................T D- the short arm contains gene for testicular formation .......................T E- fragile Y chromosome is associated with mental retardation..............F Fragile X syndrome is associated with mental retardation. The long arm of the Y chromosome is referred to as q, the short arm as p. 17- Autosomal dominant inheritance : A- 25% of offspring are affected with an affected parent .....................F B- is the mode of inheritance in multiple neurofibromatosis. ................T C- affects both sexes equally..............................................................T D- shows a pattern of vertical inheritance in a pedigree.....................T E- always manifests at birth................................................................F Autosomal dominant conditions include Huntingdon's, achondroplasia, MEN type 1. It affects both sexes equally, and 50% of offspring are affected with an affected parent. e- nonsense as illustrated by the disorders mentioned. 18- Regarding the normal human nucleus: A- The chromatin is arranged as 46 Chromosomes ...........................T B- When the centromere is placed off centre, the chromosome is acrocentric ........F C- Chromosomes which are metacentric have long and short arms ......F D- Barbodies are present in males only ............................................F E- The Y chromosome is smaller than the X chromosome ...................T In the normal human there are 46 chromosomes. Metacentric refers to a centrally placed centromere submetacentric refers to a centromere near the end of one arm of the chromosome. Barbodies are found in female cells. The Y chromosome is half the size of the X chromosome. 19- Diazepam : A- has a hypnotic effect ..................................................................T B- has an anticonvulsant effect ........................................................T C- has an antidepressant effect........................................................F D- is a respiratory depressant .........................................................T E- effects may be antagonised by naloxone .......................................F

8

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
Diazepam is a benzodiazepine and acts as a hypnotic, amnesic and anticonvulsnat through agonism at the cerebral GABA receptors. It may cause respiratory depression and these effects can be antagonised by Flumazenil 20- In a laser control area (LCA) : A- Only a laser safety officer (LSO) is permitted to use the Laser.........F B- Must be cleared of all personnel bar the person firing the laser.......F C- Must be coated matt black surfaces. ............................................F D- Eye protection must be worn........................................................T E- Adequate ventilation must be provided...........................................T An LSO is appointed from the staff of each department using the laser and has custody of the laser key. All persons using a laser should de suitable trained and be aware of all safety precautions. There should be control of personnel allowed to enter the area and the entrance should be marked with appropriate illuminated warning signs. Reflective surfaces should be avoided. However, matt black surfaces are not necessary. Eye protection must be appropriate to the type of laser being used. The ventilation should include an extraction system to vent the fumes produced. 21- The human X chromosome : A- has the gene for Duchenne Muscular Dystrophy on its short arm......T B- is associated with the Y chromosome side by side during synapse formation in spermatogenesis..........F C- in the female somatic cell is never completely inactivated...............T D- is a metacentric chromosome........................................................F E- in normal females may be seen as a chromatin body in a buccal smear analysis........T Normally, the female complement is two X sex chromosomes. One is derived from each parent and one of the pair is also randomly inactivated by a process called lyonization at an early developmental stage. A chromtin body may be seen in buccal smears in normal females. It is cleaved from the Y chromosome during spermatogenesis. 22- Human immunodeficiency virus : A- Is a single stranded DNA retrovirus ..............................................F B- Induces a fall in CD4 lymphocytes, monocytes and antigen-presenting cells .........T C- Increases the risk of opportunistic infection ................................T D- Patients can be infective prior to seroconversion illness at about three months ...................T E- The median survival with AIDS is greater than 10 years ..............F

9

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
HIV is a single stranded RNA retrovirus. It induces immunodeficeincy and increases the risk of opportunitsic infection (e.g. histoplasmosis, Pneumocystis carinii) and malignancy (e.g. Kaposi's sarcoma). Patients may have asymptomatic or symptomatic disease for several years before developing AIDS. The median survival with full AIDS is less than two years 23- The following statements about metronidazole are true. A- It may produce a disulfiram-like action with alcohol .......................T B- It may cause peripheral neuropathy with prolonged therapy............T C- It is the treatment of choice for Trichomonas vaginalis infection.......T D- Circulating concentrations may be affected by concomitant cimetidine administration.........T E- It is suitable for the treatment of bacterial vaginosis.......................T Advice should be given to patients to avoid alcohol when taking metronidazole due to a disulphiram reaction - sickness, abdominal pains, headache. Its metabolism is inhobited by cimetidine, which is a hepatic enzyme inhibitor. Other side effects include peripheral neuropathy, discolouration of urine and a metallic taste in the mouth. It is the treatment of choice for trichomonas and bacterial vaginosis. 24- The posterior pituitary gland: A- Releases decapeptide hormones .................................................F B- Synthesizes somatomedins .........................................................F C- Secretes oxytocin .......................................................................T D- Vasopressin release is controlled by the osmotic pressure of extracellular fluid ............T E- Function is inhibited by alcohol ......................................................T ADH, Oxytocin (synthesissed within the hypothalamus and released from the posterior pituitary) are nonapeptides. Somatomedins, IGF-1 and II are produced mostly by the liver under the influence of growth hormone. Vasopressin/ ADH release is controlled by the plasma osmolality and secretion is inhibted by alcohol. 25- The following statements concerning the uterus are correct: A- It is formed from the mesonephric ducts .................................F B- The uterine artery is a branch of the internal iliac artery ...............T C- The uterine artery passes below the ureter ....................................F D- The uterine veins communicate with the vesical plexus of veins .......T E- Pain from the body of the uterus is carried by the pelvic splanchnic nerves ....F At the 10th week there is union of two mullerian ducts with uterus formation, with fusion beginning in the midline then caudally and cephalad. Uterine body formed from mesoderm. Uterine cavity formed as the septum dissolved slowly. The uterine artery is a branch of the anterior division of the internal iliac artery. The vessel gives origin to fundal, cervicovaginal, ovarian, tubal and distal ureteric

10

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
branches. Cervicovaginal branches anastomose with vaginal arteries to form the azygos arteries of the vagina. The ureter passes under the uterine artery. Pain from the cervix is carried by pelvic splanchnic nerves hence bradycardia during cervical dilatation. Pain sensation from the body of the uterus is carried by sympathetic fibres in the hypogastric nerves. 26- By four weeks after fertilization the embryo: A- Is about 2cm in length .................................................................F B- Has a circulation of blood ............................................................T C- Has a closed neural tube .............................................................F D- Has developed limb buds .............................................................F E- Has completed facial development ................................................F At 4 weeks the embryo has a tail, open neural tube, gill arches, a primitive heart, which generates its own electrical rhythm, is located outside the body, allowing the growing organism to circulate nutrients and waste products and is about 0.5 cm in length. Limb buds have developed by about 8 weeks and facial development begins at this stage . 27- The Barr body A- arises from the Y chromosome .............................................F B- is present in subjects with Turner's syndrome ..............................F C- is present in 20% of cells in the male ..........................................F D- appears as a dense rod close to the cell wall ...............................F E- is present in males with Klinefelter's syndrome .............................T The chromatin nodule is the second (inactive) X chromosome. Normal women are thromatin positive. Normal men are chromatin negative. In polymorphonuclear leucocytes, a tiny nodule of chromatin (the Barr body, or nuclear drumstick) can be seen near the nuclear membrane of many cells in normal females, but not in normal males. Turner's XO does not have a Barr body. In Klinefelter's syndrome the sex chromosomal structure is XXY, and in them a chromatin nodule is seen. 28- Regarding surgical infection: A- Primary refers to a planned surgical trauma.................................F B- Always have a focus of infection....................................................T C- Are always associated with tissue necrosis....................................T D- Inflammation is the response to tissue necrosis..............................T E- Antibiotics are advised once a septic focus has been drained...........F Primary surgical infections refer to surgical wounds which appear spontaneously e.g. a skin abscess. Surgical wounds differ from non-surgical wounds in that they always have a source of infection, which

11

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
can be drained surgically. Tissue necrosis results from trauma or through a pathophysiological process. Inflammation leads to the events visible at the surface. Once the source of infection has been drained, antibiotics are usually unnecessary unless the surrounding tissues are infected. 29- Regarding the obturator nerve: A- it emerges from the lateral border of psoas major ..........................F B- is formed from the ventral divisions of 2nd,3rd and 4th lumbar nerves .......T C- supplies the lateral margin of the knee .........................................F D- has a branch separated by adductor brevis ..................................T E- lies below the obturator artery in the obturator foramen ................F The obturator nerve arises from the ventral divisions of the second, third, and fourth lumbar nerves; the branch from the third is the largest, while that from the second is often very small. It descends through the fibers of the Psoas major, and emerges from its medial border near the brim of the pelvis; it then passes behind the common iliac vessels, and on the lateral side of the hypogastric vessels and ureter, which separate it from the ureter, and runs along the lateral wall of the lesser pelvis, above and in front of the obturator vessels, to the upper part of the obturator foramen. Here it enters the thigh, and divides into an anterior and a posterior branch, which are separated at first by some of the fibers of the Obturator externus, and lower down by the Adductor brevis. 30- The greater sciatic foramen transmits the following : A- piriformis muscle .......................................................................T B- internal pudendal vessels ...........................................................T C- Sciatic nerve .............................................................................T D- Posterior femoral cutaneous nerve ..............................................T E- sacrospinous ligament .................................................................F The greater sciatic foramen transmits all of the above, apart from the sacrospinous ligament which forms part of the foramen itself and the tendon of the obturator internus muscle which passes through the lesser sciatic foramen.


Important MCQ colloction for part-1 MRCOG(2)

A- Are earth referenced generators .................................................F B- Operated in a frequency range of 400-600 kHz .............................F

12

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
C- Isolated machines are inherently safer ........................................F D- Diathermy can only pass back to the generator via the patient plate.....T E- Produce unavoidable large earth leakage currents.........................F Modern diathermy machines are isolated (unearthed) generators as opposed to the old earth referenced generators. The old earth referenced generators tend to produce higher frequency current over a wider range than the narrow range of the isolated generators. Current will only pass back to the generator with no pathway back to earth i.e. a small area of skin touching a metal contact (eg drip stand) will not result in a burn. If the plate is omitted current will not flow. The sophisticated electronics in the isolated generator ensures a considerable reduction in earth leakage currents compared to the earth referenced generators. 32- Non-disjunction of chromosomes during meiosis is a cause of:[/u A- Edward's syndrome ....................................................................T B- Turner's syndrome .....................................................................F C- Cri du chat syndrome ................................................................F D- Patau's syndrome ......................................................................T E- Laurence-Moon-Biedl syndrome ....................................................F Non-dysjunction (the failure of replicated chromosomes to segregate during Anaphase II) during meiosis is responsible most typically for Down's syndrome (trisomy C21), Patau's syndrome (trisomy C13), Turner's syndrome (XO), Klinefelter's (XXY) syndrome and Edwards syndrome (Trisomy C18). Cri du Chat is due to a deletion of a portion of C5. 33- Campylobacter jejuni: A- attack rates are highest in the elderly ..........................................F B- infections are treated with ciprofloxacin ........................................T C- is a recognised pathogen in domestic animals ................................T D- is readily isolated in stool culture .................................................F E- causes colitis ..............................................................................T a-Young adults and children. b-Cipro and Erythromycin, but most are self-limiting. c-Transmitted to humans by milk or water infected by wild and domestic animals and poultry. d-Requires special conditions: 42°C, micro-aerobic atmosphere on blood agar with antimicrobials added. e-Proctocolitis and enterocolitis may be due to sexually transmitted agents such as CampylobacterEntamoeba Lymphogranuloma venereumand may be clinically indistinguishable from non-infective causes. 34- Mast cells:

13

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
A- Contain heparin .......................................................................T B- Degranulation releases lytic enzymes and inflammatory mediators from storage granules ......F C- Are lipophilic cells involved in inflammatory and immune responses ...F D- Cross-linkage of surface IgA molecules by antigen may cause an anaphylactic reaction.......F E- An excess of circulating mast cells causes mastocytosis ...................T Mast cells are basophilic cells (not lipophilic) in the connective and subcutaneous tissues, which are involved in inflammatory and immune responses. They contain storage granules that contain lytic enzymes (e.g. tryptase) and inflammatory mediators, e.g. histamine, heparin, 5-HT, leukotrienes, platelet aggregating factor, leucocyte chemotactic factor and hyaluronidase. Release of these mediators occurs during mast cell degranulation, which can be triggered by: tissue injury; drugs; complement activation; and foreign antigenic material. An anaphylactic reaction occurs when a previously sensitised individual is re-exposed to the antigen. It is an IgE mediated immune response (not IgA). Mastocytosis occurs when excess mast cells are present in the circulation or as tissue infiltrates. 35- The following is true of diathermy safety features : A- The person who applies the diathermy plate is responsible for its correct application......F B- Only isolated diathermy machines alarm when switched on if the plate is not connected to the machine.........F C- The patient plate is applied to ensure the current is moving away from the electrocardiogram electrodes.......T D- The area under the plate should have a good blood supply.............T E- Always shave the skin in contact with the diathermy plate...............T The surgeon using the diathermy has overall responsibility for it and should check the alarm, wiring and plate before use. Isolated and earth referenced monopolar diathermy machines will alarm when switched on if the plate is not connected to the machine, but only a few will alarm if the plate is not attached to the patient. The plate should be applied close to the operation site with the broad side placed perpendicular to a line drawn from the operation site to the plate. A good supply is necessary to dissipate any heat generated. The skin should be shaven in all patients to ensure good contact between the skin and the plate. 36- Which of the following statements regarding meiosis is/are true/false ? A- In meiosis II, whole chromosomes separate..................................F B- In spermatogenesis, meiosis begins at puberty..............................T C- Exchange of paternal and maternal DNA takes place in meiosis II....F D- Anaphase lag leads to numerical chromosome aberrations..............T E- Pairing of X and Y chromosomes in spermatogenesis is end to end....T

14

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
In meiosis there is a separation of the chromosomes and halving of karyotype to form germ cells. Meiosis (I and II) comprises two successive nuclear divisions with only one round of DNA replication. 37- The urinary system A- develops from intermediate mesoderm ........................................T B- During intra uterine life 3 overlapping kidney systems are formed ...T C- The mesonephros develops as the metanephros regresses ..............F D- Bowman's capsule develops in the metanephros ............................T E- The glomerulus forms part of the mesonephros ...............................F The urinary system develops from the intermediate mesoderm. During development of the fetus there are 3 overlapping kidney systems - the pro, meso, and metanephric systems. The metanephros forms the permanent kidney. Bowman's capsule and the glomerulus develop as part of the metanephros. 38- The ureter: A- Passes into the pelvis over the bifurcation of the internal iliac artery...F B- Is seen lying on the tips of the transverse processes of the lumbar ...T C- Has the genitofemoral nerve lying anterior to it ...............................F D- Is surrounded by Waldeyer‘s sheath as it passes through the bladder wall .....T E- Lies anterior to the renal artery at the hilum of the kidney ...............F The ureter passes caudally lying on the psoas muscle and crosses into the pelvis over the bifurcation of the common iliac artery. It is seen lying on the tips of the transverse processes of the lumbar vertebrae on an intravenous urogram. the genitofemoral nerve lies on psoas hence lies posterior to the ureter. Waldeyer's sheath is an investment of muscle surrounding the ureteral opening in the bladder wall. The ureter lies posterior to the renal artery at the hilum of the kidney 39- The herpes group of viruses include: A- Varicella-zoster virus ....................................................................T B- Papilloma virus ............................................................................F C- Rabies virus ................................................................................F D- Epstein-Barr virus ........................................................................T E- Cytomegalovirus ..........................................................................T The Herpesviridae family of viruses are dsDNA viruses that include herpes simplex, varicella zoster, CMV and EBV. The papilloma virus, a small dsDNA virus, is a member of the Papovavius family. Rabies, a ssRNA virus, is a member of the Rhabdovirus family. 39.The structures at risk of damage while cannulating the subclavian vein include:

15

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
A- phrenic nerve ..........................................................................T B- subclavian artery .....................................................................T C- ansa cervicalis .........................................................................F D- anterior ramus of first thoracic nerve ........................................T E- pleura .....................................................................................T The subclavian artery lies inferior to the suclavian vein and may be inadvertently cannulated in an attempt to cannulate the suclavian vein. This may be of serious consequence as it is not possible to put pressure on the subclavian artery to arrest bleeding given its anatomical position. The apical pleura is inferior and caudal to the subclavian vein and pleural puncture, with, or without, pneumothorax are recognised consequences of subclavian vein cannulation. 40.In acute allergic reaction A- there is an increase in bradykinins ...............................................T B- T-helper cells are involved ..........................................................T C- there is an increase in the products of the 5-lipoxygenase pathway ....T D- the gene for allergy is located on chromosome 12 .........................F E- may be triggered by acute complement activation ..........................T c) Leukotrines d) The gene is located on chromosome 6 e) Anaphylatoxins 41.The amnion arises from epithelial cells between the trophoblast A- and ectodermal disc ..................................................................T B- The amnion has 5 layers ...........................................................T C- the chorion has 4 layers ..........................................................T D- the main layer of the chorion is the cellular layer .......................F E- the chorion is surrounded by the blastocyst ................................F The amnion is a layer of epithelial cells between the chorion and the cell mass. It has 5 layers compared to the 4 layer chorion. The chorion surrounds the blastocyst. 42.Concerning grief reactions A- angry outbursts are a typical feature of the natural grieving process ......T B- hallucinations of the deceased can be a feature of the normal grief reaction ......T C- grief reactions may occur many years after the death of the person ....T

16

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
D- suicidal ideations are a common feature of a grief reaction .............F E- Antidepressants is the most appropriate initial therapy ...................F Grief reactions are typically mapped along the lines of anger denial and guilt. Delayed grief is said to occur if it commences two weeks after bereavement. Grief reactions often occur on anniverseries such as weddings, births etc. The most appropriate treatment is conselling and antidepressants should not be routinely used. Suicidal ideations are also abnormal. 43.Which of the following are tumour suppressor genes? A- p53 ...........................................................................................T B- BRAC1 ......................................................................................T C- APC .........................................................................................T D- bcl-2 .......................................................................................F E- c-myc .......................................................................................F Mutations in Tumour suppressor genes have been implicated in malignancy as down regulation of these genes can result in the unrestricted growth of cells and hence predispose to malignancy. These genes include VHL (von Hippel Lindau), p53, Rb1(Retinblastoma), BRAC and APC (adenomatous polyposis coli) genes. Oncogenes, on the other hand are associated with the promotion of cell division and include myc, erb, ras and ret. 44.Trinucleotide repeat sequences are seen in A- cystic fibrosis .............................................................................F B- Duchenne muscular dystrophy ....................................................F C- myotonic dystrophy ...................................................................T D- fragile X syndrome .....................................................................T E- Leber's optic atrophy ..................................................................F also Huntington's chorea In genetics, anticipation is a phenomenon whereby the symptoms of a genetic disorder become apparent at an earlier age as it is passed on to the next generation. In most cases, an increase of severity of symptoms is also noted. It is common in trinucleotide repeat disorders like Huntington's disease, myotonic dystrophy and fragile X syndrome, where a dynamic mutation in DNA occurs. All of these diseases have neurological symptoms. 45.Which of the following drugs are teratogenic A- Warfarin ..................................................................................T B- Oral contraceptive ...................................................................F C- Metformin ..............................................................................F

17

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
D- Simvastatin ...........................................................................T E- Ranitidine ...............................................................................F There is no evidence that ranitidine, metformin or the OCP is teratogenic although it was once believed that aspirin and the OCP were, studies indicate otherwise. Similarly, metformin is often used in PCOs to induce fertility through reduction in insulin resistance. Warfarin is associated with CNS and skeletal abnormalities if foetal exposure occurs in the first trimester, plus foetal haemorrhage is more likely. Statins also are associated with teratogenicity. 46.In haemophilia A A- dental extraction bleeding can be controlled with DDAVP if factor VIII concentration is 2-5% of normal ..............F B- sons of an affected man will be normal ........................................T C- Only about 90% have bleeding before one year of age ...................T D- hepatitis B virus is the most common cause of deranged LFTs .........F E- there is a normal amount of factor VIII-related antigen ...................T Only in mild cases (5-20% activity)is bleeding controlled by DDAVP. Haemophilia A is X-linked recessive. Sons of affected males will inherit a normal Y chromosome, and will be unaffected. Hepatitis C or E would be commoner as a cause of abrnomal LFTs in these patients, as hepatitis B is more easily screened for. Factor VIII related antigen is reduced in von Willibrand's disease. 90% present with bleeding by their first birthday. Only 30% present with bleeding after circumcision. 47.Which of the following are Tocolytic: A- Salbutamol ...............................................................................T B- Suxamethonium .......................................................................F C- Propofol ..................................................................................F D- Progesterone ...........................................................................T E- GTN .........................................................................................T Tocolytic drugs, inhibitors of uterine contraction, include GTN, alcohol, magnesium sulphate, ritodrine, salbutamol, nifedipine and NSAIDs. Progesterone in high concentrations also has some tocolytic activity and promotes the relaxant effects of more conventional tocolytics. 48.Metronidazole: A- Inhibits dihydrofolate reductase. .................................................F B- Has 80% bioavailability if given rectally. ......................................T

18

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
C- Has harmful effects with alcohol. .................................................T D- Discolours the urine....................................................................T E- Causes peripheral neuropathy......................................................T Reduced to active derivative which binds to DNA and inhibits acid synthesis. Disulfiram reaction with alcohol. Some types of Warfarin. Metallic taste, hypotension, peripheral neuropathy and also causes a darkening of the urine. 49.Polymerase chain reaction: A- takes several days to complete ....................................................F B- DNA or RNA can be used as the template ....................................T C- helps in diagnosis of infection ......................................................T D- in diagnostic PCR the exact sequence at both ends of the target region must be known .......T E- Polymorphisms in the viral genome may result in amplification failure .....T The polymerase chain reaction is a rapid technique which produces a result in only a few hours. It is therefore extremely useful for rapid diagnosis of conditions such as tuberculosis where traditional culture methods can take several weeks. DNA is the standard template but viral RNA sequence can also be amplified if the enzyme reverse transcriptase is used. Primers used in the reaction must be complementary to the nucleic acid sequence surrounding the region to be amplified, therefore these sequences must be known. In HIV and perhaps other viruses sequence polymorphism may prevent binding of primers and result in failure of amplification. Primers which were developed for amplification of the predominant clade B strain found in Europeans and Americans have proved unreliable for amplification of other HIV clades from Africa and Asia. 50.The following are true of genes A- The rate of DNA replication is directly under the control of enhancer sequences.............F B- Mitochondrial genes are inherited from the mother..........................T C- Transcription factors are mainly made of RNA................................T D- Introns are the portions of a gene which code for protein................T E- Most of the human genome encodes polypeptide.............................F A gene is a length of DNA that carries information to make a single peptide chain. However, it is estimated that only a few percent of DNA comprising the whole human genome consists of genes encoding protein. Introns are intervening sequences of unknown function in mammalian genes. Regulatory elements of gene transcription include promoters (regions of DNA to which RNA polymerase bind and initiate transcription), enhancer sequences (modify activity of genes on the same chromosome) and transacting proteins (modify genes on both pairs of homologous chromosomes). mRNA are transcripts of DNA, which are attached to transfer RNA and then translated in ribosomes to protein, which then undergo considerable post-translational changes. Mitochondrial inheritance is exclusively maternal, as none of the mitochondria from sperm survives fertilization.

19

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
51.The following mechanisms are involved in the mediation of insulin action: A- adenylate cyclase activation ........................................................F B- cell membrane receptor interaction ..............................................T C- inhibition of hepatic glucose release .............................................T D- receptor tyrosine kinase activity ..................................................T E- hormone receptor DNA binding ....................................................F Insulin acts through a disulfide-bonded heterotetrameric cell surface receptor comprised of an extracellular alpha subunit coupled via disulfide bonds to a transmembrane and intracellular beta subunit. Insulin inhibits gluconeogenesis and promotes glycogen synthesis. Signaling through the insulin receptor occurs through an intracellular tyrosine kinase domain and resultant phosphorylation of the receptor. 52.The seminal vesicles: A- Contain spermatids ...................................................................F B- Contain spermatids .................................................................F C- Secrete acid phosphatase .........................................................F D- Secrete fructose ......................................................................T E- Secrete prostaglandins .............................................................T Seminal vesicles secrete a significant proportion of the fluid that ultimately becomes semen. About 60% of the seminal fluid in humans originates from the seminal vesicles. The seminal vesicles do not contain sperm cells. Seminal vesicle secretions contain proteins, enzymes, fructose, phosphorylcholine and prostaglandins.

53.Regarding the human chromosomes: A- There are 23 pairs of autosomal chromosomes...............................F B- The Y chromosome is larger than the X chromosome......................F C- Cells containing YO chromosome are not compatible with life...........T D- Barr body is caused by the presence of an inactive X chromosome.....T E- Barr body is only found in people who are phenotypically female........F There are 22 pairs of autosomes, and one pair of sex chromosomes. The Y chromosome is smaller than the X chromosome, no YO individuals have been identified, not even aborted foetuses. It has been suggested that there is something fundamental on the X chromosome that is needed for life. The Barr body is visible during interphase and 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

20

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
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 54. Typical adverse effects of combined oral contraceptive preparations include: A- Migraine ...................................................................................T B- Hyperprolactinaemia .................................................................F C- Depression ...............................................................................T D- Breast tenderness ....................................................................T E- Loss of libido ............................................................................F Menstrual migraine: First migraines associated with a hormonal event: menarche, birth control pills, pregnancy, and/or postpartum Worse headaches occur near menstruation Birth controls often make headaches worse; discontinuation may bring some relief. Headache typically occurs the week off birth control pills, Absence of migraine noted in second & third trimesters of pregnancy. Presence of other premenstrual complaints: mood swings, depression, food cravings, fluid retention and breast pain. Side-effects include depression or irritability. The effect on libido is variable. In many women relief from fear of pregnancy removes a restraint on sexual activity and enjoyment; in a very few there will be a loss of libido. The other side effects of greatest concern with the combined OCP are vascular events including DVT and stroke (v rare). 55. The menopause A- Implies cessation of menstrual flow for one year or more ................T B- Is synonymous with the climacteric ..............................................F C- Symptoms may occur long before menstruation ceases..................T D- Occurs on average at age 45.5 years ..........................................F E- Is associated with mennorhagia ..................................................F The menopause is the cessation of normal menstruation. Conventionally a woman has to stop menstruating for 12 months before she is considered to be postmenopausal. Strictly speaking, menopause is defined as cessation of menses for a minimum of 6 months because of inadequate ovarian follicular development and waning oestrogen production. The climacteric is an extended period of gradually declining ovarian function often beginning years before and lasting years after menopause itself. The average age of menopause in the UK is 51 years, with a large majority of women experiencing menopause between the ages of 45 and 55. The cessation of periods, can occur suddenly or may be preceded by light and infrequent periods. The climacteric (rather than the menopause) although typically associated with light periods may be heralded by menorrhagia. 56. The benefits of adding androgen to menopausal hormone replacement therapy include which of the following: A- Increase in high-density lipoprotein cholesterol levels......................F

21

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
B- Increase in libido.........................................................................T C- Decrease in triglyceride levels......................................................T D- Decrease in bone mineral density.................................................F E- Decreased cardiovascular risk .....................................................F Androgens are known to increase libido and may help to protect bone mass. However, lipid profiles change when androgens are added to HRT. The HDL fraction decreases with androgen therapy; however, triglyceride concentrations decrease significantly in patients given oestrogen-androgen combination therapy. 57. Growth Hormone: A- secretion is inhibited by somatostatin analogues ............................T B- is used in the treatment of proliferative retinopathy .......................F C- therapy causes an elevation of IGF-1 concentrations .....................T D- is approved by NICE for the treatment of adult hypopituitarism ......T E- therapy is associated with an increased incidence of breast carcinoma .............F GH therapy produces an elevation of IGF-1 and therapy is monitored through measuring these concentrations. GH therapy is approved for the treatment of adult hypopituitarism and there is no evidence to suggest that it causes an oncreased risk in any malignancy. Treatment is contra-indicated in any active malignancy and indeed proliferative retinopathy. GH secretion is suppressed by somatostatin analogues - eg octreotide, which are used therefore in acromegaly. 58. Proteolytic enzymes are released by the following organisms: A- Neisseria meningitides ................................................................F B- Salmonella typhi .........................................................................F C- Streptococcus pyogenes .............................................................T D- Mycobacterium tuberculosis ........................................................F E- Clostridium perfringens (welchii) .................................................T

Virulence factors are important in the bacterial survival in vivo. In this sense bacterial extracellular proteolytic enzymes can be recognized as the legitimate target for this approach since they are involved either in direct or indirect destruction of an infected/colonized tissue and in dysregulation of many host defense pathways. The best example of the last is an effect of bacterial proteinases on fibrinolytic, kallikrein-kinin and complement cascades, as well as degradation of immunoglobulins, inactivation of endogenous proteinase inhibitors, and dysregulation of cytokine network system. Proteolytic enzymes are responsible for the virulence and activity of organisms such as Strep Pyogenes, Staphylococcus aureus, E coli and Clostridium welchii enabling the necrolytic effects on the

22

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
skin in cellulitis and gangrene 59. The thyroid gland: A- Is stimulated by posterior pituitary hormones ...............................F B- Functions from the 12th week of fetal development ......................T C- Actively traps inorganic iodine from plasma ..................................T D- Stores colloid outside epithelial cells .............................................T E- Enlarges during normal pregnancy ................................................T

Thyroid hormone production is stimulated by the anterior pituitary hormone TSH and secretion begins from approximately the 12th week of gestation. T3 and T4 are manufactured within the thyroid cells through iodination of tyrosine. The synthesized T3 and T4\ are then stored within the colloid at the centre of the thyroid follicles. The thyroid like most other endocrine organs moderately enlarges during pregnancy. 60. The human testis secretes: A- Androstenedione .......................................................................T B- Luteinising hormone ...................................................................F C- Oestradiol ..................................................................................T D- Inhibin .......................................................................................T E- Fructose .....................................................................................F

The testis is responsible for secreting testosterone, androstenedione, Oestradiol, inhibin as well as a small amount of progesterone. The anterior pituitary produces LH and FSH. Fructose and prostaglandins that nourish the spermatozoa are secreted by the seminal vesicles. 61. Staphylococcus epidermidis: A- is coagulase positive .................................................................F B- on microscopy are Gram positive cocci in chains .......................F C- are usually sensitive to penicillin ...................................................F D- grown in blood cultures are due to contamination and should be ignored ...........F E- are destroyed by povodine iodine ...................................................T Staph. epidermidis is part of the normal skin flora. As for Staph. aureus, Gram positive cocci in bunches are seen on microscopy.

23

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
It is usually insensitive to penicillin.Although it is often a contaminant in blood cultures, it is associated with line infections. Central venous catheters are an especially likely site of infection even in the absence of overt exit site sepsis. They should not be ignored but interpreted in the clinical context, and usually the blood cultures should be repeated. In patients with central lines, blood cultures should be taken both peripherally and from the central line as semi-quantitative microbiological techniques are available that may point to the central line as the principle site of infection. 62. The following hepatitis viruses are RNA viruses: A- HAV ...........................................................................................T B- HBV ...........................................................................................F C- HCV ..........................................................................................T D- HDV ..........................................................................................T E- EBV ..........................................................................................F Hepatitis A is an RNA virus spread via the faecal-oral route. Whilst both HBV and HCV are transmitted through blood and blood products, HBV is a DNA virus and Hepatitis C is an RNA flavivirus. Hepatitis D is an incomplete RNA virus, existing only with H epatitis B, spread is with co-infection or superinfection with Hepatitis B. Epstein Barr Virus is a DNA virus, very similar to the other herpes viruses. It is shed in pharyngeal secretions and transmission occurs via close oral contact. 63. Regarding Immunoglobulin: A- Immunoglobulins are secreted from T-lymphocytes. ......................F B- An immunoglobulin G (IgG) comprises 2 antigen-binding sites and a site for the binding of complement.........T C- The molecular structure of IgG is a Y shape ...................................T D- IgG constitute approximately 25% of all immunoglobulis in a healthy individual........F E- IgMs can cross the placenta to the foetus........................................F Immunoglobulins (antibodies) are secreted from B-lymphocytes (plasma cells) in response to a specific antigen. Both antigen-binding sites are identical and consist of a long and heavy chain. IgGs constitute approximately 75% of all immunoglobulis in a healthy individual. Only IgGs can cross the placenta. This is important as they provide immune protection for the newborn in the first few months of life. 64. Disinfectant solutions may become contaminated with: A- Enterobacter species ...................................................................T B- Streptococcus species .................................................................F C- Escherichia coli .........................................................................F D- Pseudomonas aeruginosa (pyocyanea) .......................................T E- Staphylococcus pyogenes ...........................................................F

24

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
Disinfectant solutions have variable bactericidal and fungicidal properties but are usually but there are reports of contamination with Pseudomonas spp, Enterobacter, Serratia, actinomyces and Fungi. 65. Use of the combined oral contraceptive pill is associasted with an increased risk of: A- Ovarian carcinoma .....................................................................F B- Breast Carcinoma ......................................................................T C- Endometrial carcinoma ..............................................................F D- Hepatic carcinoma ......................................................................T E- Cervical carcinoma ....................................................................T The risks of some cancers are associated with use of the OCP. In particular, it appears that breast cancer risk is increased and, use of the OCP for more than 5 years is associated with increased risk of cervical carcinoma. Hepatoma risk may also be increased with use of the OCP. Use may be protective for ovarian carcinoma. 66.Unopposed oestrogen therapy for the postmenopausal female A- Improves the urethral syndrome ...................................................T B- Decreases urinary calcium excretion .............................................T C- Reduces the incidence of myocardial infarction ..............................F D- Causes an increased incidence of endometrial carcinoma ..............T E- Cause hypertension ....................................................................F Low levels of natural oestrogen around and after menopause diminish the body's ability to absorb calcium and to metabolize vitamin D. Low oestrogen levels lead to a thinning of trabecular bone and eventually osteoporosis. This leads to an increased risk of fractures of the hip and wrist and compression fractures of the vertebrae resulting in a dowager hump. Rather than the original belief that postmenopausal HRT reduces CV risk, studies like WHI and HERS show an increased CV mortality and morbidity associated with HRT. Neoplasia of the endometrium may follow unopposed oestrogen; the risk increases with the duration of use:x 3-6 after five years of use. x 10 after ten years. That is why unopposed oestrogens are no longer used in subjects with an intact uterus. 67. The following are precursors of oestradiol A- Cholesterol ..................................................................................T B- Stilboestrol ..................................................................................F C- Arachidonic acid ...........................................................................F D- Dehydroepiandrosterone .............................................................T E- Testosterone ................................................................................T The pathways whereby oestrogens are synthesized in the ovary

25

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
Cholesterol to Pregnenolone then via D4 pathway: Progesterone to 17-hydroxyprogesterone (17-OHP) to Androstenedione (D4) « Testosterone to Oestradiol-17b (E2) or via D5 pathway: 17hydroxypregnenolone to Dehydroepiandrosterone (DHA) to Oestrone (E1) « 68. Prostaglandins are A- Synthesized from cholesterol ......................................................F B- Are small polypeptides ...............................................................F C- Secreted by the pituitary gland ...................................................F D- Secreted by the prostate gland ...................................................T E- Associated with gastrointestinal side effects ..................................T Prostaglandins are long-chain hydroxy fatty acids derived from arachidonic acid, which is released from cell membrane phospholipids and catalysed by the enzymes cyclo-oxygenase and endoperoxidase. Prostaglandins are produced locally. The original source was the prostate. GI side effects include diarrhoea and abdominal pains. 69. The Barr body A- arises from the Y chromosome .................................................F B- is present in subjects with Turner's syndrome ...........................F C- is present in 20% of cells in the male ........................................F D- appears as a dense rod close to the cell wall .............................F E- is present in males with Klinefelter's syndrome .............................T The chromatin nodule is the second (inactive) X chromosome. Normal women are thromatin positive. Normal men are chromatin negative. In polymorphonuclear leucocytes, a tiny nodule of chromatin (the Barr body, or nuclear drumstick) can be seen near the nuclear membrane of many cells in normal females, but not in normal males. Turner's XO does not have a Barr body. In Klinefelter's syndrome the sex chromosomal structure is XXY, and in them a chromatin nodule is seen. 70. Androgens: A- Exert a feedback inhibitory effect on FSH production .....................T B- Produce a release of LH from the ovary ........................................F C- Are produced in the ovary ..........................................................T D- Are secreted by the female adrenal cortex ...................................T E- Are formed in the Leydig cells of the testis ....................................F

Testosterone, like oestradiol, feeds back at the hypothalamus / pituitary to inhibit GnRH secretion and

26

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
switch off both LH and FSH secretion. In the female, testosterone is synthesied in small amounts, probably in the adrenals, but a weak androgen, androstenedione is formed as a step in the metabolism of progesterone. LH stimulates testosterone production from Leydig cells of the testis. 71. IgA: A- Is involved in mucosal immunity....................................................T B- Has 4 distinct sub-groups...............................................................F C- Activates complement via the classical pathway...............................F D- Is manufactured in lymph nodes....................................................F E- Crosses the placenta. ...................................................................F IgA is the major antibody produced by plasma cells near mucosal surfaces, and is found in tears, sweat, lung, gut, urine. IgA avoids digestion by the presence of the secretory piece which is added as it is secreted onto the mucosa. It is an important defence against surface binding of micro-organisms. There are 2 sub-types, IgA1 and IgA2. Only IgG is transferred across the placenta. Complement proteins circulate, therefore, they rarely come into contact with IgA. 72. Circulating anticoagulants have been described in A- Systemic Lupus Erythematosis ......................................................T B- post-partum ................................................................................T C- homocystinuria ..........................................................................F D- haemophilia ...............................................................................T E- the elderly ..................................................................................T Circulating anticoagulant, usually IgG, interfere with coagulation reactions. The main laboratory feature are prolonged PT and PTT which persists if normal plasma is added. a-These are non-specific inhibitors which prolong haemostasis by binding to phospholipids. Anti-factor VIII antibodies may also be seen. b,d and e-Anti-factor VIII antibodies. c-Thrombotic tendency. d-haemophiliacs who have had plasma transfusions. 73. A karyotype A- may be prepared from chorionic villi cells of the placenta................T B- helps in the diagnosis of chromosome disorders.............................T C- is made from cells arrested at telophase of mitosis.........................F D- from a Patau syndrome patient shows an extra chromosome No. 18.....F E- helps in the identification of the Philadelphia chromosome, in chronic myeloid leukaemia......T

27

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
Karyotype is the chromosomal composition of cells- normal karyotype is 46XX or XY. Patau syndrome is associated with trisomy of Chromosome 13. 74. Which of the following organelles have their own self replicating DNA? A- lysosomes ...................................................................................F B- Golgi body ..................................................................................F C- mitochondria ..............................................................................T D- nucleolus ....................................................................................F E- rough ER ....................................................................................F Mitochondria are well recognised to contain DNA and give rise to maternally inherited diseases such as the mitochondrial myopathies - red ragged fibres - DIDMOAD syndrome, Wolfram disease 74. Immunoglobulin G (IgG) A- constitutes the natural haemagglutinins (anti-A and anti-B) ............F B- is the predominant immunoglobulin in normal bronchial secretions ....F C- freely crosses the placenta ..........................................................T D- has a molecular weight of 350,000 daltons ...................................F E- bears only 2 antigen-binding sites ................................................T a) IgM, b) IgA, c) the only Ig to do so, d) 150,000 75. Which of the following statements regarding DNA is/are true/false ? A- Attached to the 2' position of the sugar ring is one of four bases.......F B- The bases lie stacked on each other 3.4 Angstroms apart................T C- During transcription each daughter DNA contains one newly synthesised strand.........F D- The guanine - cytosine bonds are made of two hydrogen bonds. .......F E- The DNA from a single cell is nearly 2 metres long..........................T Individual nucleoside units (bases) are joined together in a nucleic acid in a linear manner, through phosphate groups attached to the 3' and 5' positions of the sugar (deoxyribose). Hence, the full repeating unit in a nucleic acid is a 3',5'-nucleotide. Guanine - cytosine bonds consist of three hydrogen bonds.

28

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)

  
‫ا‬

Important MCQ colloction for part-1 MRCOG(3) 76. Genes on sex chromosomes are responsible for the inheritance of: A- Glucose 6 phosphate dehydrogenase deficiency .............................T B- Achondroplasia ..........................................................................F C- Hairy ear rims ...........................................................................T D- Homocystinuria .........................................................................F E- Hurler's syndrome ......................................................................F Genes on sex chromosomes would typically give rise to X-limked recessive and dominant conditions such as G6PD, haemophilia, vitamin D resistant rickets. 77. Beta-thalassaemia major (homozygous) A- is characterised by persistance of HbF .........................................T B- is associated with a chronic marked reticulocytosis .......................F C- is always associated with a raised proportion of HbA2 ...................F D- is very rarely associated with nucleated red cells .........................F E- is a cause of pathological fracture of long bones ...........................T nucleated red cells always seen, retics low. HbA2 raised in beta-thalassaemia trait. 78. In mitosis A- the number of chromosomes is halved..........................................F B- anaphase lag may produce Turner syndrome................................T C- the stage of metaphase shows separation of whole chromosomes........F D- nondisjunction increases with decreasing maternal age...................F E- an abnormal plane of division of the chromatids produce isochromosomes...............T

29

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)

Each time new cells are produced, there is a mitotic cycle it must go through. They are: •Interphase (before mitosis) •Prophase •Metaphase •Anaphase •Telophase 79. Which of the following are adhesion molecules? A- cadherin ...................................................................................T B- laminin .....................................................................................T C- fibronectin .................................................................................T D- integrin ....................................................................................T E- secretin .....................................................................................F

During an inflammatory response adhesion molecules serve to enhance pairing between many less avid receptors and their ligands and transmit signals that direct specific effector functions. At least four superfamilies of adhesion molecules participate in these events: the selectins, the integrins, certain members of the immunoglobulin superfamily and cadherins. Secretin is a duodenal hormone which stimulates pancreatic exocrine secretion. 80. In the T cell response to antigen: A- A process of affinity maturation of the T cell receptor occurs............F B- Intact antigen is presented in association with self MHC molecules.....F C- Co-operation with other cell types is required for T cell recognition of antigen...............T D- gamma/delta + T cells respond to antigen presented in association with MHC class II molecules...........F E- Interactions of the TcR with an appropriate Ag/MHC complex activates a resting T cell..............F a) Affinity maturation in an ongoing immune response is a feature of the antibody response. There is no evidence that a similar process occurs in the T cell response. b) MHC molecules present short antigen-derived peptides, not the intact antigen. c) T cells recognise antigen only when presented by (self) MHC molecules on an antigen presenting cell. d) MHC class II molecules present antigen to CD4+, alpha/beta+ T cells. It is still not clear how gamma/delta+ T cells recognise antigen, however most gamma/delta+ T cells do not appear to be restricted by (self) MHC molecules. e) Additional 'costimulatory' signals are required to activate a resting

30

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
T cell. Interaction of the TcR of a resting T cell with an appropriate Ag/MHC complex in the absence of costimulatory signals may lead to the induction of anergy. (c) Dr Alan Cann 81. The following techniques are used to directly identify DNA: A- Western blotting ..........................................................................F B- Southern blotting .........................................................................T C- Northern blotting ..........................................................................F D- polymerase chain reaction (PCR) ..................................................T E- denaturing gradient gel electrophoresis ..........................................T Western blotting is used to identify proteins whereas northern blotting is used to identify mRNA. 82. The following are examples of lasers commonly used in surgery. A- Silicon ........................................................................................F B- Carbon dioxide ...........................................................................T C- Helium .......................................................................................F D- NdYAG ......................................................................................T E- Magnesium ..................................................................................F Carbon dioxide is an example of a gaseous lasing medium. Commonly being employed in colposcopy. NdYAG (Neodymium Yttrium Aluminium Garnet) is an example of a crystalline lasing medium. Commonly being employed in endoscopes. 83. The femoral nerve: A- lies within the femoral sheath .......................................................F B- lies lateral to the femoral vein ......................................................T C- has a branch which supplies the skin of the scrotum .....................F D- may supply part of the foot ........................................................T E- shares its origin with the obturator nerve .....................................T The femoral sheath contains the femoral artery and vein as well as lymphatics, but not the nerve. The femoral nerve lies behind and lateral to the sheath. The femoral nerve gives off 3 cutaneous branches - 2 from its anterior division (medial and intermediate cutaneous nerves of thigh which supply the skin of the medial and anterior surfaces of the thigh) and one from its posterior division (saphenous nerve), it has no

31

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
branches to the scrotum. The spahenous nerve runs down the medial side of the leg and supplies the medial side of the calf as far as the medial malleolus, it terminates in the region of the ball of the big toe and may supply the medial side of the dorsum of the foot. The femoral nerve is the largest branch of the lumbar plexus and comes from the same lumbar nerves as the obturator nerve, L2, 3 and 4. 84. The urogenital diaphragm is pierced by the A- ureters ......................................................................................F B- rectum ......................................................................................F C- vagina .....................................................................................T D- urethra ....................................................................................T E- obturator nerve ..........................................................................F It Lies inferior to the urogenital hiatus of the levator anti muscle and supports this potentially weak region of the pelvic floor. The urogenital diaphragm is pierced by the urethra and vagina. 85. The femoral artery A- Is crossed anteriorly by the medial cutaneous nerve of the thigh .........T B- Lies anteriorly to psoas muscle ......................................................T C- Lies medial to the femoral vein .....................................................F D- Is a branch of the internal iliac artery ............................................F E- Lies medial to the lymphatic vessels ..............................................F The femoral artery lies lateral to the vein and lymph vessels and medial to the nerve 86. Regarding Krebs' cycle (also known as the tricarboxylic acid cycle or citric acid cycle) the following statements are true: A- oxidative phosphorylation occurs within the cytoplasm ...................F B- alpha-ketoglutarate is a five carbon molecule ................................T C- only carbohydrates and fats are oxidised in Krebs' cycle ................F D- pyruvate condenses with oxaloacetate to form citrate ....................F E- Krebs' cycle can function under anaerobic conditions .....................F 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

32

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
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 2 carbon molecule from a 3 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 4 carbon acid, oxaloacetate, to form citrate which is a 6 carbon molecule. Citrate is subsequently converted into isocitrate, alpha-ketoglutarate, succinyl-CoA, succinate, fumarate, malate and finally oxaloacetate. Alpha-ketoglutarate is the only 5 carbon molecule in the cycle. 87. The ovarian ligaments A- Contain the ureters ......................................................................F B- Contain the ovarian arteries ........................................................F C- Are attached laterally to the pelvic wall ........................................F D- Lie anterior to the broad ligament ................................................F E- Are homologous to part of the gubernaculum testis in the male ......T The ovarian ligament lies beneath the posterior layer of the broad ligament and passes from the medial pole of the ovary to the uterus just below the point of entry of the fallopian tube. As the ureter crosses the brim of the pelvis it lies in front of the bifurcation of the common iliac artery. It runs downwards and forwards on the lateral wall of the pelvis to reach the pelvic floor, and then passes inwards and forwards, attached to the perineum of the back of the broad ligament, to pass beneath the uterine artery. The ovarian artery arises from the aorta just below the renal artery and runs downwards on the anterior surface of the psoas muscle to the pelvic brim, where it crosses in front of the ureter and then passes into the infundibulopelvic fold of the broad ligament. Through the mesovarium the ovarian vessels and nerves enter the hilum The ovarian ligament passes from the medial pole of the ovary to the uterus just below the point of entry of the fallopian tube. The ovarian ligament lies beneath the posterior layer of the broad ligament. Together, the ovarian and round ligaments are homologous with the gubernaculum testis of the male. 88. The following are correct embryological associations A- Germ cells and the wall of the yolk sac .........................................T B- Mullerian duct and female genital tract ..........................................T C- Mullerian duct and Gartner's cyst .................................................F D- Genital tubercle and clitoris ...........................................................T E- Metanephros and kidney ...............................................................T The germ cells which eventually give rise to the ova migrate from the wall of the yolk sac into the genital ridge. The Mullerian ducts form the fallopian tubes, uterus and upper vagina. In the

33

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
male the Wolffian duct forms the vas deferens, but it degenerates in the female fetus. It can sometimes still be traced in the adult female, when it is know as Gartner's duct. This runs medially through the broad ligament and down the side of the vagina, where cysts may form in it. After 10 weeks differentiation in the female the genital tubercle enlarges slightly to form the clitoris. The pronephros and mesonephros develop to form the primitive kidney but disappears subsequently, and finally the metanephros appears to form the definitive kidney. 89. Adenine A- Is a pyrimidine base ....................................................................F B- Forms base pairs with thymine in RNA ............................................F C- Is synthesized attached to ribose phosphate ..................................F D- Can be converted directly to a nucleotide by the action of phosphoribosyl-transferase enzymes ...................F E- Is degraded by a pathway which involves the enzyme xanthine oxidase ......................T Adenine is one of the two purine bases used in the formation of the nucleotide – adenosine in combination with ribose/deoxyribose. This binds to either Uracil in RNA or thymine in DNA. There is a complex process of conversion to the nucleotides from the nucleosides. Nucleoside = base + sugar DNA= deoxyribose, RNA = ribose. nucleotide = base + sugar + phosphate. Purines are metabolized to xanthine within which xanthine oxidase is involved. 90. The lymphatic drainage of the cervix goes A- To the internal iliac nodes .............................................................T B- To the external iliac nodes ..........................................................T C- Directly to the para-aortic nodes .................................................T D- To the superficial inguinal nodes ..................................................F E- To the obturator node ..................................................................T

The lymphatics from the cervix pass either laterally in the base of the broad ligament or posteriorly along the uterosacral ligaments to reach the side wall of the pelvis. Most of the vessels drain to the internal iliac, obturator and external iliac nodes, but vessels also pass directly to the common iliac and lower para-aortic nodes. 91. In the vulva A- The blood supply is partly derived from the middle rectal artery.........F B- The blood supply is partly derived from the external pudendal artery..........T C- Lymph drains to the inguinal group of nodes. .................................T

34

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
D- Sensory fibres from the skin travel via the pudendal nerve. ............T E- Venous drainage on the right is directly to the inferior vena cava...........F The internal pudendal artery is a branch of the internal iliac artery. It leaves the pelvic cavity through the sciatic foramen and, after winding round the ischial spine, enters the ischiorectal fossa where it gives off the inferior rectal artery. It terminates in branches which supply the perineal and vulval structures, including the erectile tissue of the vestibular bulbs and clitoris. Lymph draining from the lower extremities and the vulval and perineal regions is all filtered through the inguinal and superficial femoral nodes before continuing along the deep pathways on the side wall of the pelvis. As the pudendal nerve passes along the outer wall of the ischiorectal fossa it gives off an inferior rectal branch, and divides into the perineal nerve and the dorsal nerve of the clitoris. The perineal nerve gives the sensory supply to the vulva; it also innervates the anterior part of the external anal sphincter and levator ani, and the superficial perineal muscles. The dorsal nerve of the clitoris is sensory. The ovarian veins on the right ends in the inferior vena cava and that on the left in the left renal vein. 92. Raised aldosterone levels are found in A- normal pregnancy ......................................................................T B- renal artery stenosis ..................................................................T C- therapy with loop diuretics ...........................................................T D- polycystic ovary syndrome .........................................................F E- Liddle's syndrome .......................................................................F Aldosterone is elevated in association with reduced circulating volumes, pregnancy, Conn's syndrome, and raises with diuretic therapy (hence good combination of diuretics and ACEis). Liddle's syndrome is a renal tubular defect due to Na/K channels and is associated with hyporeninaemic hypoaldosteronism with hypokalaemic hypertension. The risks of combined hormone contraception1 •Non-life-threatening adverse effects: ◦Breakthrough bleeding ◦Breast tenderness ◦Acne ◦Mood changes •Venous thromboembolism: ◦Relative risk of venous thromboembolism with COC use can increase up to five-fold compared with non-users. ◦The absolute risk is still low, and considerably lower than the risk in pregnancy. ◦The risk of venous thrombosis is increased with obesity and is greatest in the first year of COC use. Approximate risks:1 ■Healthy non-pregnant women - about 5-10 cases per 100,000 per year ■Second-generation pill users - about 15 per 100,000 per year ■Third-generation pill users - about 25 per 100,000 per year ■Pregnancy - estimated to be about 60 per 100,000 per year

35

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
◦To minimize the risk of venous thrombosis before pelvic surgery or procedures that may require extensive immobilisation, COCs should be stopped 2-4 weeks before the procedure, and should not be resumed until 2 weeks after complete mobility.1 •Myocardial infarction: ◦For COC users who are heavy smokers (more than 15 cigarettes per day) the relative risk of MI may be up to 10 times that of smokers who do not use COCs. Healthy non-smokers have no increased risk of myocardial infarction with COC use.1 ◦COC users with hypertension have a three-fold increased risk of MI compared with COC users without hypertension. •Stroke: ◦Very small increase in the absolute risk of ischaemic stroke with COC use. •Breast cancer: ◦Any increased risk of breast cancer with COC use is likely to be small. ◦After 10 years since last use, the incidence of breast cancer is the same as in women who have never used COCs.1 •Cervical cancer: ◦The use of oral contraceptives for less than 5 years does not increase the risk of cervical cancer. ◦The risk of cervical cancer does increase with more than 5 years of COC use.1 •Liver cancer: ◦Primary liver cancer is rare in developed countries and, although COC use increases the risk, the absolute risk is very small. 92. During human spermatogenesis: A- Sperm production takes place within the Leydig cell ........................F B- New sperms develop within 35 days ...............................................F C- The primary spermatocytes undergo reduction division ....................T D- Each diploid spermatocyte gives rise to four spermatids .................T E- Grossly abnormal spermatozoa are never present in fertile semen ........F

Spermatogenesis takes place between the the Sertoli cells with leydig cells releasing testosterone to encourage the process. The time required for spermatogenesis in humans is approximately 75 days. Spermatozoa develop through a process of meiosis so diploid spermatocytes provide four spermatids. There is a certain percentage of abnormal sperm allowed to be present in a normal semen analysis. 93. Carbimazole: A- May cause fetal hyperthyroidism ...................................................F B- Can be used sublingually ............................................................F C- Is secreted in significant quantities in breast milk .........................T

36

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
D- Is a cause of agranulocytosis .....................................................T E- Is a thiourea derivative ..............................................................T Carbimazole is a thionamide used in the treatment of thyrotoxicosis through blocking the iodination of thyroid hormone. It can be used in pregnancy for treating thyrotoxicosis but the dose is reduced to the smallest dose required to maintain euthyroidism as it crosses the placenta and may cause fetal hypothyroidism. Care has to be exercised with breast feeding. Side effects include rash, hair loss and rarely agranulocytosis. 94. Prolactin: A- Release is stimulated by thyrotropin-releasing hormone ...............T B- Plasma levels are raised in the first trimester of pregnancy ............T C- Is identical to human placental lactogen .........................................F D- Controls milk ejection ..................................................................F E- Release is inhibited by Metoclopramide ..........................................F

Prolactin is produced from the anterior pituitary gland, A number of other hypothalamic releasing hormones induce increased prolactin secretion; Prl rises throughout pregnancy. PRL & HPL are peptide hormones but they are not identical. Human placental lactogen is a single-chain polypeptide with two intramolecular disulfide bridges. The structures of hPL, prolactin, and growth hormone are very similar. Eighty-five percent of its amino acids are identical to human pituitary growth hormone and human pituitary prolactin Furthermore, hPL shares biologic properties with both growth hormone and prolactin Thus, it has primarily lactogenic activity but also exhibits some growth hormone-like activity; therefore, it is also referred to as chorionic growth hormone (hCGH) or human chorionic somatomammotropin (hCS). Oxytocin controls milk ejection. The dopamine antagonist metaclopramide abolishes the pulsatility of prolactin release and increases serum prolactin levels 95.placebo in a clinical trial A- has no effects .............................................................................F B- is pharmacologically inert .............................................................T C- should not be given to patients with carcinoma ..............................F D- should be identical in appearance to the drug being studied ............T E- is best administered by a person who is unaware of the drug's identity ...............T

37

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
Placebo controlled studies are most appropriately undertaken in a double blind fashion with both the observer and the patient blinded to treatment. Although you might think that placebo has no effect, in fact there may well be a huge placebo (psychological) effect. Placebo studies are undertaken in patients with cancer particularly to establish the palliative value of drugs or the effectiveness of a new treatment where none exists. 96. Beta-thalassaemia is characterised by A- hepatosplenomegaly ..................................................................T B- overgrowth of maxillary regions of face ......................................T C- a lower incidence of infections than in the normal population ...........F D- a normal reticulocyte count .........................................................F E- characteristic changes on X-ray of the skull ..................................T 97. Nitric oxide: A- is generated from glutamine ........................................................F B- is produced by both inducible and constitutive forms of nitric oxide synthetase .................T C- raises systemic vascular resistance .............................................F D- is inactivated by oxygen free radicals ............................................T E- is increased by cyclic AMP activation. ..............................................F 98. The following mechanisms are involved in the mediation of insulin action: A- adenylate cyclase activation ........................................................F B- cell membrane receptor interaction .............................................T C- inhibition of hepatic glucose release ............................................T D- receptor tyrosine kinase activity ..................................................T E- hormone receptor DNA binding .....................................................F Insulin acts through a disulfide-bonded heterotetrameric cell surface receptor comprised of an extracellular alpha subunit coupled via disulfide bonds to a transmembrane and intracellular beta subunit. Insulin inhibits gluconeogenesis and promotes glycogen synthesis. Signaling through the insulin receptor occurs through an intracellular tyrosine kinase domain and resultant phosphorylation of the receptor 99. The following statements concerning the uterus are correct: A- It is formed from the mesonephric ducts ........................................F

38

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
B- The uterine artery is a branch of the internal iliac artery .................T C- The uterine artery passes below the ureter ...................................F D- The uterine veins communicate with the vesical plexus of veins .......T E- Pain from the body of the uterus is carried by the pelvic splanchnic nerves ...............F At the 10th week there is union of two mullerian ducts with uterus formation, with fusion beginning in the midline then caudally and cephalad. Uterine body formed from mesoderm. Uterine cavity formed as the septum dissolved slowly. The uterine artery is a branch of the anterior division of the internal iliac artery. The vessel gives origin to fundal, cervicovaginal, ovarian, tubal and distal ureteric branches. Cervicovaginal branches anastomose with vaginal arteries to form the azygos arteries of the vagina. The ureter passes under the uterine artery. Pain from the cervix is carried by pelvic splanchnic nerves hence bradycardia during cervical dilatation. Pain sensation from the body of the uterus is carried by sympathetic fibres in the hypogastric nerves. 100. Oxytocin is: A- synthesised in the anterior hypothalamic nuclei ..............................T B- stored in the anterior pituitary ......................................................F C- an oligopeptide hormone .............................................................T D- an anti-diuretic in action .............................................................T E- important as a cause of uterine contractions in early pregnancy .......F 101. The femoral nerve: A- lies within the femoral sheath ......................................................F B- lies lateral to the femoral vein ......................................................T C- has a branch which supplies the skin of the scrotum .......................F D- may supply part of the foot ..........................................................T E- shares its origin with the obturator nerve ......................................T 102. In X-linked recessive disease A- mothers will always carry the affected gene ..................................T B- fathers never transmit to their sons .............................................T C- there is variable expression in females due to random inactivation ........T D- 50% of daughters of carrier females will be carriers ......................T

39

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
E- incidence increases with maternal age ...........................................F 103. The corpus luteum of pregnancy produces: A- Relaxin .......................................................................................T B- Progesterone .............................................................................T C- 17 Alpha-Hydroxyprogesterone ...................................................T D- Human chorionic gonadotrophin ...................................................F E- Oestradiol ...................................................................................T 104. The source of oestrogen in a postmenopausal woman is believed to be attributed to A- Face cream with hormone content ................................................F B- Ovarian stromal origin ................................................................T C- Small amounts from the bone marrow ...........................................F D- Adrenal origin .............................................................................F E- Hepatic origin ..............................................................................F 105. The progestogenic side-effects of oral contraception include A- Heavy menstrual flow ..................................................................F B- Fluid retention ............................................................................T C- Depression ..................................................................................T D- Reduced libido ............................................................................F E- Vaginal discharge ........................................................................F 106. Peritoneal ridges A- The medial umbilical ligament is also called the urachus ..................F B- The urachus is the remains of the fetal allantois ............................T C- The urachus extends from the bladder to the umbilicus .................T D- The lateral umbilical ligaments are the obliterated Umbilical veins .........F E- The lateral umbilical ligaments pass from the internal Iliac arteries to the umbilicus ...........T

40

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
The median umbilical ligament (urachus) is the remains of the fetal allantois. The lateral umbilical ligaments are the obliterated umbilical arteries. 107. Insulin: A- is secreted mainly as proinsulin ....................................................F B- has equal biological activity to C-peptide .......................................F C- release from the pancreatic beta cell is stimulated by biguanides ...........F E- has a half life of less than 8 minutes when given intravenously ...................T E- >80% is degraded by the liver and kidney .....................................T

Insulin (and C-peptide which is inactive) is secreted by the beta cells within the islets of Langherhan as the active molecule following cleavage from preproinsulin, then proinsulin. It is metabolised in the liver and undergoes renal excretion. Half life is roughly 4 mins. 108. The following are recognised carcinogens A- nicotine ......................................................................................F B- electromagnetic microwaves .......................................................F C- Infra-red radiation .....................................................................F D- beta-naphthylamine .....................................................................T E- Arsenic .......................................................................................T 109. Concerning gonadal development: A- The histological appearance of the primitive gonad is similar in both sexes until 42 days after fertilization .............................................T B- The ovary develops in the medulla of the primitive gonad. ...............F C- The histo-differentiation of the testis begins later than that of the ovary ...............F D- Primary sex cells (gonocytes) have a haploid number of chromosomes ............F E- Mitosis in oogonia is not completed by the end of the first year of life ................F

The appearance of the primitive gonad is similar in both sexes until 42 days after fertilization when seminiferous differentiation occurs. At 10 weeks conception there is meiotic entry of

41

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
oocytes in the medulla of the primitive gonad of the developing foetus. Gonocytes are diploid and only become haploid in the gonad via meiosis. Mitosis in oogonia is completed 7th month of fetal life. The ovary develops from the primitive cortex not medulla. 110. The urinary system A- develops from intermediate mesoderm .........................................T B- During intra uterine life 3 overlapping kidney systems are formed .............T C- The mesonephros develops as the metanephros regresses ..............F D- Bowman's capsule develops in the metanephros ............................T E- The glomerulus forms part of the mesonephros ...............................F

The urinary system develops from the intermediate mesoderm. During development of the fetus there are 3 overlapping kidney systems - the pro, meso, and metanephric systems. The metanephros forms the permanent kidney. Bowman's capsule and the glomerulus develop as part of the metanephros 111. Regarding Escherichia Coli A- Is a gram positive rod ...................................................................F B- grows anaerobically .....................................................................T C- characteristically produces a malodourous infection ..........................F D- Most strains are not pathogenic .....................................................F E- produces an enterotoxin .............................................................T E coli is a gram negative anaerobe and produces both endotoxins and enterotoxins (enterotoxigenic E Coli). It does not typically produce a malodourous infection as it is likely that other anaerobes are responsible for this - eg Bacteroides etc. Most strains have the potential to be pathogenic. 112. Hypokalaemia may be caused by: A- Bendroflumethiazide ....................................................................T B- Digoxin ......................................................................................F C- Spironolactone ............................................................................F D- Carbenoxolone ............................................................................T

42

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
E- Amiloride ..........................................................................................F

Carbenoxolone may cause hypokalaemic hypertension like liquorice through inhibition of 11beta hydroxysteroid dehydrogenase (11bHSD). Bendroflumethiazide is a thiazide diuretic and promotes potassium excretion. Amiloride, like spironolactone is a potassium sparing diuretic and causes hyperkalaemia. Digoxin toxicity is exacerbated by hypokalaemia but it does not cause hypokalaemia 113. Thrombocytopenia is a recognised adverse effect of the following drugs: A- aspirin .........................................................................................T B- oxymethalone .............................................................................F C- thiazide diuretics .........................................................................F D- gold ...............................................................................................T E- dapsone .......................................................................................F A - aspirin causes reduced platelet function, thrombocytopaenia and increased bleeding time. For further details on thrombocytopaenia. Thrombocytopaenia is a decrease in the number of platelets in the blood - it reduces the ability of the blood to clot and is thus a bleeding diathesis. It is defined as a platelet count less than 100 x 10^9/L (<100,000 per cubic mm). In addition, it is important to consider also the causes of apparent thrombocytopaenia - i.e. conditions where there is platelet dysfunction. Neonatal thrombocytopaenia has a modified differential diagnosis. 114. Which of the following are effective in the treatment of menopausal flushes? A- Raloxifene ..................................................................................F B- Clonidine .....................................................................................T C- 17 beta-oestradiol .......................................................................T D- Norethisterone ............................................................................F E- Venlafaxine ..................................................................................T

There are numerous drugs other than oestrogens that are effective in the treatment of PM flushing. Venlafaxine the SSRI has some benefit in reducing fluches particularly in those subjects that are unable to use osestrogens. Clonidine is well established for this purpose also. Progestogens do not help flushes but are used in as combined HRT with estrogens in women with an intact uterus. Raloxifene, the SERM, may exacerbate flushes.

43

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
115. Glucocorticoid therapy may cause: A- hypokalaemia .............................................................................T B- lymphopenia ................................................................................T C- hypertrichosis .............................................................................T D- amenorrhoea .............................................................................T E- aseptic necrosis of the femoral head ..............................................T

Glucocorticoids , steroids, may cause iatrogenic cushing's, with thin skin ease of bruising, glucose intolerance/diabetes, hypertension and hypokalaemia, hirsutism, osteoporosis and it may result in hypogonadotrophic hypogonadism (hence amenorrhoea). Therapy may also be associated with aseptic necrosis of the femoral head. 116. Which of the following are potassium sparing diuretics? A- Triamterene ...............................................................................T B- Bendroflumethiazide ...................................................................F C- Furosemide .................................................................................F D- Spironolactone ............................................................................T E- Captopril .....................................................................................F

Potassium sparing diuretics include spironolactone, trimaterene and amiloride. They act on the distal convoluted tubule inhibiting through various mechanisms the loss of potassium in exchange for sodium. Furosemide is a loop diuretic and bendroflumethiazide a thiazide diuretic. Captopril is not a diuretic but an ACE inhibitor. 117. Wound healing by secondary intention takes place: A- when the wound does not break apart ...........................................F B- when the wound edges are brought together .................................F C- when there is irrepairable skin loss ..............................................F D- much more slowly than healing by first intention ...........................T E- when the wound becomes infected ................................................T

44

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)

Healing by secondary intention occurs when the wound edges are apart. Angiogenesis and fibroblast proliferation result in the formation of granulation tissue, which contracts to reduce the wound area and allows epithelialisation across it's surface to achieve wound closure. Where the wound edges are apposed, healing proceeds rapidly to closure and this is known as primary healing. If there is irrepairable skin loss then the process would be very slow and the resultant healed surface is a thin layer of epithelium on scar tissue that may not prove durable in the longterm. Healing by secondary intention is a slower process due to the formation and contraction of granulation tissue resulting in a slow apposition of the opposing skin appendages. When the wound is infected it should heal by secondary intention. Attempting to heal the wound by primary measures would leave an underlying infection, that would lead to wound breakdown.

118. The following micro-organisms are generally sensitive to Benzylpenicillin: A- Streptococcus Pneumonaie ..........................................................T B- Cryptococcus neoformans ...........................................................F C- Bordetella pertussis ....................................................................F D- Streptococcus viridans .................................................................T E- Mycoplasma pneumoniae .............................................................F Penicillin binds to specific penicillin-binding proteins (PBP's) in the cell wall, mainly of gram positive organisms. Penicillin resistance is usually due to production of altered PBPs or betalactamases which leave the penicillin molecule. Penicillin is mainly useful for Group A Strep., Group B Strep., meningococcal and pneumococcal infections, though and anthrax are also sensitive. Pneumococci with modified PBPs are an increasing problem. 119. Regarding the capsulated bacteria: A- Meningococci are carried by farm animals .....................................F B- Streptococcus pneumoniae produces a -haemolysis when cultured on blood agar ....................T C- Neisseria species are Gram positive ..............................................F D- Escherichia coli carries V antigens which allow serotyping .....................F E- Neisseria lactamica and Neisseria meningitidiscan be differentiated on the basis of carbohydrate utilisation ................T

45

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
The meningococcus (Neisseria meningitidis) is carried by humans – up to 20% of the population. S. pneumoniae is a-haemolytic, giving green (partial) haemolysis on blood agar culture, and is differentiated from other a-haemolytic streptococci by sensitivity to optochin. Neisseria species are Gram negative cocci E.coli are subtyped on the basis of O antigens (cell envelope antigens), H (flagellar antigens) and in some K (cpasular) antigens 120. Physiological effects of metoclopramide include: A- stimulates upper gastrointestinal motility ........................................T B- increases gastric acid secretion .....................................................F C- increases gastric fluid pH ..............................................................F D- acts on central dopaminergic receptors ..........................................T E- increases gastroesophageal sphincter tone .....................................T Metoclopramide causes increased GI motility, increases sphincter tone and also has central antiemetic actions mediated through dopaminergic receptors. 121. The thyroid gland A- lies posterior to the parathyroid glands ...........................................F B- is closely related to the internal carotid artery .................................F C- is histologically composed of papillae ............................................F D- normally weighs 100 grams .........................................................F E- internalises iodine through active transport ....................................T The parathyroids lie posteriorly to the thyroid gland and the recurrent laryngeal nerves lie posteromedially. The gland is composed of follicles and iodine is internalised by an active transport system - the iodide symporter. The normal weight of the gland is approximately 30 grams. 122. The following are known complications of Phenytoin therapy: A- Ataxia .........................................................................................T B- Hirsutism ....................................................................................T C- Alopecia .....................................................................................F D- Dental caries ..............................................................................F E- Megaloblastic anaemia .................................................................T Gingival hypertrophy and tenderness as well as coarse facial features and hirsuitism may

46

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
occur. Haematological side effects include megaloblastic anaemia, aplastic anaemia, thrombocytopaenia. Neurological side effects include peripheral neuropathy, ataxia, and rarely nystagmus and dyskinesias as well as granulocytosis. Eye involvement may occur in cases of overdosages including blurred vision and nystagmus. Cataracts are not associated with phenytoin use . 123.The following are recognised carcinogens A- nicotine .......................................................................................F B- electromagnetic microwaves ........................................................F C- Infra-red radiation .......................................................................F D- beta-naphthylamine ....................................................................T E- Arsenic ........................................................................................T Nicotine is not a carcinogen, it is the hydrocarbons/tar in the smoke that predisposes to carcinoma. Naphthas are associated with bladder tumours. Arsenic may predispose to skin cancers as does UV radiation (not infra -red). There is no demonstrable association between infra-red waves and risk of malignancy . 124. Antimicrobial agents effective against Pseudomonas aeruginosa infections include: A- gentamicin ..................................................................................T B- flucloxacillin .................................................................................F C- cephalexin ...................................................................................F D- carbenicillin .................................................................................T E- metronidazole .............................................................................F others ceftazidime + ciprofloxacin 125. Which of the following are classed as loop diuretics: A- Metolazone .................................................................................F B- Spironolactone ............................................................................F C- Furosemide ................................................................................T D- Bumetanide ................................................................................T E- Triameterne .................................................................................F Loop diuretics are so called as they inhibit reabsorption of sodium and hence water from the

47

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
ascending limb of the loop of Henle. They are therefore potent diuretics and include Bumetanide, Furosemide (Furosemide) and Torasemide. Metolazone and Bendroflumethiazide are thiazide diuretics whilst Triameterene, Amiloride and Spironolactone are potassium sparing diuretics and act on the distal convoluted tubule. 126. Benzyl penicillin A- can be administered orally ...........................................................F B- undergoes first pass hepatic metabolism .....................................F C- is an effective treatment for cellulitis .............................................T D- is an effective treatment for spontaneous bacterial peritonitis .........F E- is effective against Clostridium Tetani ............................................T Benzyl Penicillin (Penicillin G) is inactivated by gastric acid and so must be given parenterally (unlike penicillin V). It is an effective treatment for strep infections eg cellulitis and is also effective for tetanus. It is not appropriate for SBP where thrid generation cephalosporins are advocated. 127. Aminoglycosides: A- are active against streptococcus ....................................................T B- acts on the bacterial cell wall ........................................................F C- are useful against anaerobes ........................................................F D- should not be used in patients with renal failure .............................F E- damages the cochlear nerve ........................................................T These antibiotics are derived from Streotomyces spp. and are active against streptococcal species. They interrupt bacterial protein synthesis by inhibiting ribosomal function. Anaerobes produce phosphorylating adenylating or acetylating enzymes that inactivate aminoglycoside antibiotics. Aminoglycosides are nephrotoxic but this is a dose-related effect. Blood levels must be checked and caution taken with other nephrotoxic agents This is a group of antibacterial antibiotics that are derived from the various species of Streptomyces, in which case they have the spelling -mycin, and micromonospora in which case the spelling is -micin. They act by binding to the 30S ribosome and preventing proper functioning by leading to misreading of tRNA. Included in this group are gentamicin and streptomycin. Side effects include: • aminoglycosides may cause vertigo • streptomycin may cause nerve deafness 128. The following drugs have anti-cholinergic effects: A- Propantheline bromide ..................................................................T

48

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
B- Carbachol ....................................................................................F C- Distigmine bromide ......................................................................F D- Benzhexol ....................................................................................T E- Atropine ........................................................................................T Carbachol has cholinergic properties and Distigmine is an acetylcholine esterase. The others all have anticholinergic effects. 129. Warfarin metabolism may be inhibited by A- Oral contraceptive .......................................................................F B- Omeprazole .................................................................................T C- Aspirin ........................................................................................F D- Rifampicin ...................................................................................F E- Metronidazole ..............................................................................T The anti-coagulant effects of warfarin may be exacerbated through the inhibition of its metabolism by cytoP450. Omeprazole, Metronidazole, cimetidine and amiodarone may all do this and so INR should be carefully monitored. However, Rifampicin induces P450 and so would reduce the anticoagulant effects of Warfarin (as may other inducers of P450 such as some anticonvulsants). Oestrogen may reduce the anticoagulant effect independently of P450. 130. Vancomycin-resistant enterococci: A- cause resistant infective diarrhoea ................................................F B- produce an enzyme that inactivates vancomycin .............................F C- may be found in healthy community volunteers not recently hospitalized ................T D- high dose ampicillin is the treatment of choice ................................F E- are commonly vancomycin-dependent ...........................................F a-When they cause clinical problems they are usually UTI, bacteraemia, wound infections, neonatal infections, endocarditis etc. b-They alter peptidoglycan precursors used to build cell walls. Vancomycin binds to D-ala-D-ala but the resistant enterococci have D-ala-D-lac or D-ala terminating precursors. They aquire genes that produce enzymes to change the precursors. c2% in UK general practice, 28% in Belgium. Community reservoir in meat, poultry and ?cheese. d-only if the MIC of ampicillin is not too high. Anecdotal evidence exists for its use in E. faecalis endocarditis. (20g / day) e-Some strains only. An explanation for this curious process is that there is an inability to produce cell walls because the vancomycin-sensitive precursor genes have been turned off and the resistant ones only appear in the presence of vancomycin.

49

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
131. Listeria monocytogenes: A- Can grow at 6°C ..........................................................................T B- Is a gut commensal ......................................................................T C- Is a Gram negative bacillus ..........................................................F D- Infections is best treated with benzyl penicillin ...............................F E- Is a cause of septicaemia in neonates ...........................................T Listeria can survive in temperatures of 4°C - 60°C. It is found in the intestinal tract of animals and humans, milk, leaf vegetables, processed foods and soil. It is a gram positive bacilli. It can be treated with ampicillin, trimethoprim or chloramphenicol. Listerosis in late pregnancy can give rise to septicaemia in neonates. 132. The following drugs can cause bronchoconstriction: A- Propranolol ..................................................................................T B- Atropine.......................................................................................F C- Morphine ....................................................................................T D- Ritodrine .....................................................................................F E- Aspirin .......................................................................................T These bronchoconstrictors act in the following manner - Propranolol by being a beta blocker and Morphine causes histamine release. Aspirin induced bronchoconstriction is thought to be due to shunting of arachidonic acid into the lipo-oxygenase pathway or removal of cyclooxygenase product which prevent bronchospasm. Ritodrine is a beta sympathomimetic and atropine is an anticholinergic agent that causes bronchodilation. 133. Which of the following is/are a selective oestrogen receptor modulator (SERM)? A- Cyproterone acetate ....................................................................F B- Tibolone ......................................................................................F C- Tamoxifen .................................................................................T D- Raloxifene ..................................................................................T E- Metformin ...................................................................................F Cyproterone acetate is a progestogen and a constituent of the OCP dianette. Both Tamoxifen and Raloxifene are SERMs with both agonist and anatagonist action on the varying oestrogen receptors. Metformin is a biguanide and insulin sensitiser used in diabetes, but more recently as an effective treatment in PCOs. Tibolone is an oestrogen agonist.

50

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
134. Opsonization: A- Enhances phagocytosis..................................................................T B- Is mediated by certain complement components............................T C- Does not involve immunoglobulins.................................................F D- May utilize fibronectin...................................................................T E- Is MHC restricted..........................................................................F a) Phagocytosis, though possible in a saline medium, is enhanced in the presence of fresh serum. This is due to substances called opsonins. b) Opsonins include C3b, for which phagocytic cells possess a receptor. c) Immunoglobulins, especially IgG1 and IgG3, for the Fc portion of which phagocytic cells possess receptors, are potent opsonizing agents. d) Fibronectin acts as a glue for neutrophil-target interaction. It is a glycoprotein. e) Opsonization is not MHC-restricted. Mechanism Both the membrane of a phagocytosing cell, as well as its target, have a negative charge (zeta-potential), making it difficult for the two cells to come close together. During the process of opsonization (alternatively opsonisation), antigens are bound by antibody and/or complement molecules. Phagocytic cells express receptors, CR1 and Fc receptors, that bind opsonin molecules, C3b and antibody, respectively. With the antigen coated in these molecules, binding of the antigen to the phagocyte is greatly enhanced. Most phagocytic binding cannot occur without opsonization of the antigen. Furthermore, opsonization of the antigen and subsequent binding to an activated phagocyte will cause increased expression of complement receptors on neighboring phagocytes.

Examples Examples of opsonin molecules include: antibodies: IgG and IgA components of the complement system: C3b, C4b, and iC3b Mannose-binding lectin (initiates the formation of C3b) The most important are IgG and C3b 135. Octreotide: A- is a somatostatin analogue ............................................................T B- is an effective treatment for Cushing's syndrome ............................F C- is an effective treatment for carcinoid syndrome .............................T D- is used in the treatment of polycystic ovarian syndrome ..................F

51

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
E- is associated with the development of biiary calculi ..........................T Octreotide is a somatostatin analogue that is used in the treatment of acromegaly (not diagnosis which is the oral glucose tolerance test), carcinoid syndrome and also in the acute treatment of oesophageal varices. Side effects include biliary stasis and hence biliary calculi. is an octapeptide that mimics natural somatostatin pharmacologically, though it is a more potent inhibitor of growth hormone, glucagon, and insulin than the natural hormone. Pharmaceutical Effects Since octreotide resembles somatostatin in physiological activities, it can: Inhibit secretion of many hormones, such as gastrin, cholecystokinin, glucagon, growth hormone, insulin, secretin, pancreatic polypeptide, TSH, and vasoactive intestinal peptide. Reduce secretion of fluids by the intestine and pancreas. Reduce gastrointestinal motility and inhibit contraction of the gallbladder. Inhibit the action of certain hormones from the anterior pituitary. Cause vasoconstriction in the blood vessels. It has also been shown to produce analgesic effects, most probably acting as a partial agonist at the mu opioid receptor 136. Which of the following may produce severe hyperkalaemia in combination: A- Lisinopril and spironolactone .........................................................T B- Furosemide and Amiloride ............................................................F C- Propranolol and verapamil ...........................................................F D- Aspirin and allopurinol .................................................................F E- Losartan and amiloride .................................................................T The combination of ACE inhibitors/Angiotensin blockers with potassium sparing diuretics such as spironolactone and amiloride may produce dangerous hyperkalaemia. Amiloride is often given with Furosemide (co-amilofruse) to replete potassium stores. Propranolol is not given with verapamil due to the induction of severe bradycardia 137. Diazepam A- has a hypnotic effect ....................................................................T B- has an anticonvulsant effect ..........................................................T C- has an antidepressant effect..........................................................F D- is a respiratory depressant ...........................................................T E- effects may be antagonised by naloxone ........................................F

52

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
Diazepam is a benzodiazepine and acts as a hypnotic, amnesic and anticonvulsnat through agonism at the cerebral GABA receptors. It may cause respiratory depression and these effects can be antagonised by Flumazenil 138. Labetalol: A- Has alpha blocking action ..............................................................T B- Causes bronchodilation ................................................................F C- Decreases bile secretion ..............................................................T D- Is 70% protein bound ..................................................................F E- Has a half-life of 2 hours ...............................................................F Labetalol is a combined beta and alpha adrenergic receptor antagonist with a ratio of activity between 2:1 and 5:1 respectively. It is selective for alpha-1 receptors but is non-selective for beta receptors. It is used to treat severe hypertension and pre-eclampsia and in hypotensive anaesthesia. Labetalol has a half-life of approximately four hours (not 2) and is approximately 50% protein bound. It has been shown to cross the placental barrier, but not the blood brain barrier. It is metabolised in the liver and excreted in the urine and faeces. Oral administration of the drug undergoes extensive first-pass metabolism. Severe hepatocellular damage has been reported after both short and long term use and the reduction of bile secretion may rarely lead to jaundice. 139. Typical adverse effects of combined oral contraceptive preparations include: A- Migraine ......................................................................................T B- Hyperprolactinaemia ....................................................................F C- Depression .................................................................................T D- Breast tenderness ........................................................................T E- Loss of libido ................................................................................F Headaches Nausea Breakthrough bleeding Breast tenderness Mood changes Weight gain Dizziness Amenorrhea 140. Metformin: A- stimulates the release of insulin from the beta cells of the pancrease ..........F

53

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
B- therapy is associated with lactic acidosis...............................................T C- therapy reduces prolactin concentrations in polycystic ovarian syndrome .............F D- therapy improves the rate of conception in polycystic ovarian syndrome ............T E- therapy causes hypoglycaemic events ............................................F Metformin is a bigunaide and acts to improve insulin sensitivity through improving hepatic and muscular glucose utilisation. PCOs is associated with increased insulin resistance and conception, oligomennorrhoea and hirsutism may be improved thorugh metformin. Side effects include lactic acidosis (rarely) and it should not be used in subjects whose creatinine clearance is above 130 micromol/l or heart failure. As it improves insulin sensitivity it is not per se associated with hypoglycaemia. 141. Co-trimoxazole: A- Contains two different drugs ............................................................T B- Inhibits folic acid synthesis ............................................................T C- Potentiates the action of warfarin ..................................................T D- Is bacteriostatic ................................................................................F E- Displaces methotrexate from protein binding sites ...................................T Combination of sulphonamide and trimethorpim, with synergistic bactericidal effect through inhibition of folic acid synthesis. It potentiates the effects of warfarin (like erythromycin, isoniazid) and the sulphonamide component can displace methotrexate from its plasma protein binding site. 142. Metronidazole A- Is effective against Giardia lamblia .................................................T B- Is effective when administered per rectum ......................................T C- Should not be administered intravenously .......................................F D- Is usually effective against Entamoeba histolytica ............................T E- Interferes with ethanol metabolism .................................................T Metronidazole is effective for treating against infections with protozoa such as Trichomonas vaginalis, ameba, and giardia. It also is effective against anaerobic bacterial infections. It can be administered rectally and can cause a ‗disulfiram-like‘ reaction when taken with alcohol. Indications

54

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
Systemic metronidazole is indicated for the treatment of: Bacterial Bacterial vaginosis, commonly associated with overgrowth of Gardnerella species and coinfective anerobes (Mobiluncus, Bacteroides), in symptomatic patients Pelvic inflammatory disease in conjunction with other antibiotics such as ofloxacin, levofloxacin, or ceftriaxone Anaerobic bacterial infections such as Bacteroides fragilis, spp, Fusobacterium spp, Clostridium spp, Peptostreptococcus spp, Prevotella spp, or any other anaerobes in intra-abdominal abscess, peritonitis, empyema, pneumonia, aspiration pneumonia, lung abscess, diabetic foot ulcer, meningitis and brain abscess, bone and joint infections, septicemia, endometritis, tuboovarian abscess, or endocarditis Pseudomembranous colitis due to Clostridium difficile Helicobacter pylori eradication therapy, as part of a multi-drug regimen in peptic ulcer disease Protozoal Vaginitis due to Trichomonas vaginalis infection in both symptomatic patients as well as their asymptomatic sexual contacts - always consult the GP and contact all previous partners Protozoal infections due to Entamoeba histolytica (Amoebic dysentery or Hepatic abscesses), and Giardia lamblia (Giardiasis) should be treated alone or in conjunction with iodoquinol or diloxanide furoate With amphotericin B and certain other drugs, it is used as an adjunct in the attempted treatment of primary amoebic meningoencephalitis caused by Naegleria fowleri infection of the bowels Nonspecific

Prophylaxis for those undergoing potentially contaminated colorectal surgery or appendectomies and may be combined with neomycin Acute gingivitis and other dental infections (TGA approved, non-Food and Drug Administration (FDA) approved) Crohn's disease with colonic or perianal involvement (non-FDA approved)- believed to be more effective in combination with ciprofloxacin Topical metronidazole is indicated for the treatment of rosacea, and in the treatment of malodorous fungating wounds 143. Which of the following antihypertensives are ACE inhibitors A- Verapamil ....................................................................................F B- Propranolol ..................................................................................F C- Lisinopril .....................................................................................T D- Ramipril ......................................................................................T

55

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
E- Losartan ......................................................................................F Verapamil is a calcium antagonist and propanolol a beta blocker. Lisinopril, Trandolapril, Ramipril, Enalapril and Captopril are ACE inhibitors . Losartan like Irbesartan and Eprosartan are Angiotensin receptor blockers. 144. The following compounds are predominantly progestogens: A- Buserelin .....................................................................................F B- Dydrogesterone ...........................................................................T C- Norethisterone .............................................................................T D- 17 Alpha Hydroxyprogesterone .....................................................T E- Androstenedione ..........................................................................F Progestogens are a subclass of sex steroid with key effects on preparing the female genital tract for reception of fertilized ovum and maintenance of pregnancy. Progestogens include dydrogesterone, cyproterone acetate, norethisterone, medroxyprogesterone, norgestrel and of course 17OHP. Androstenedione is an androgen and Buserelin is a LHRH analogue. 145. The following substances are sympathomimetic amines: A- Amphetamines .............................................................................T B- Ephedrine ...................................................................................T C- Histamine ...................................................................................F D- Isoprenaline ...............................................................................T E- Chlorpromazine ...........................................................................F Sympathomimetic amines include Ephedrine, Amphetamine and isoprenaline. Histamine is a vasoactive amine. Chlorpromazine is an antipsychotic belonging to the phenothiazine class of drug 146. Lidocaine: A- inhibits the uptake of sodium into nerve cell membranes ...................T B- has a local vasodilatory effect ........................................................T C- toxicity should be suspected if the patient develops slurred speech ............T D- is an alkaline solution ...................................................................T E- 1% solution contains 1 g of lidocaine in 100 ml fluid ................................T

56

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
Lidocaine blocks fast sodium channels. Most local anaesthetics, with the exception of cocaine, cause dilation of blood vessels. Toxic effects associated with local anaesthetics usually result from excessively high plasma concentrations. Other signs of toxicity include inebriation and lightheadedness followed by sedation, circumoral paraesthesia and twitching. Lidocaine is an alkaline solution and the pH of the surrounding tissues influences both the pharmacokinetics and pharmacodynamics of lidocaine. 0.5% solution = 5mg/ml ( 1% solution = 10mg/ml ( 100ml of solution = 1000mg or 1g of lidocaine. is a common local anesthetic and antiarrhythmic drug. Lidocaine is used topically to relieve itching, burning and pain from skin inflammations, injected as a dental anesthetic, and in minor surgery Anesthesia Lidocaine alters depolarization in neurons, by blocking the fast voltage gated sodium (Na+) channels in the cell membrane With sufficient blockade, the membrane of the presynaptic neuron will not depolarize and so fail to transmit an action potential, leading to its anaesthetic effects. Careful titration allows for a high degree of selectivity in the blockage of sensory neurons, whereas higher concentrations will also affect other modalities of neuron signaling Indications Topical lidocaine has been shown to relieve postherpetic neuralgia in some patients, though there is not enough study evidence to recommend it as a first-line treatment. It also has uses as a temporary fix for tinnitus. Although not completely curing the illness, it has been shown to reduce the effects by around two thirds . Contraindications for the use of lidocaine include: Heart block, second or third degree (without pacemaker) . Severe sinoatrial block (without pacemaker) . Serious adverse drug reaction to lidocaine or amide local anaesthetics . Concurrent treatment with quinidine, flecainide, disopyramide, procainamide (Class I antiarrhythmic agents) . Prior use of Amiodarone hydrochloride . Hypotension not due to Arrhythmia . Bradycardia . Accelerated idioventricular rhythm . Pacemaker . 147. Which of the following is/are true regarding Tramadol: A- is an opioid receptor agonist with a higher affinity for the delta receptor ....................F B- acts on peripheral receptors .......................................................................F C- is a neuronal noradrenaline reuptake inhibitor ...........................................T D- decreases serotonin release ..........................................................F

57

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
E- is secreted in breast milk ...............................................................T Tramadol is a commonly used, centrally-acting opioid analgesic. It is a non-selective pure agonist at mu, delta and kappa receptors with a higher affinity for the mu receptor. Other mechanisms which contribute to its analgesic effect are inhibition of neuronal reuptake of noradrenaline and enhancement of serotonin release. Small quantities of Tramadol and its metabolites are found in human breast milk. Tramadol ......... is a centrally acting analgesic, used for treating moderate to severe pain. It is a synthetic opioid and it appears to have actions at the μ-opioid receptor as well as the noradrenergic and serotonergic systems . 148. Metronidazole: A- Inhibits dihydrofolate reductase......................................................F B- Has 80% bioavailability if given rectally...........................................T C- Discolours the urine......................................................................T D- Causes peripheral neuropathy.......................................................T E- Has 80% bioavailability if given rectally .........................................T 149. Which of the following are Tocolytic: A- Salbutamol ..................................................................................T B- Suxamethonium ...........................................................................F C- Propofol ......................................................................................F D- Progesterone ...............................................................................T E- GTN .............................................................................................F These are drugs that inhibit uterine contractions. 1- Beta-sympathomimetics ; Action Relaxation of the smooth muscle fibres by stimulating the beta receptors present on the cell membrane. Examples: **Ritodrine (Yutopar): Side effects Maternal: Tachycardia,

58

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
hypotension (relaxation of the smooth muscle fibres in the blood vessels wall), flushing, sweating nausea, vomiting, headache, anxiety, tremors, hyperglycaemia, hypokalaemia, acidosis and pulmonary oedema. Foetal: Tachycardia, arrhythmia, loss of beat-to-beat variation, neonatal hypotension and hypoglycaemia. Contraindications Heart disease. Hypertension or hypotension. Hyperthyroidism. Antepartum haemorrhage (dilatation of the uterine arteries may increase the bleeding). Diabetes. [/b][/i] 2- β-sympathomimetic drugs Example ....... **Terbutaline, **Isoxuprine (Duvadilan - vasoxiprine) 20 mg 3-4 times daily. **Salbutamol. 3- Calcium Antagonists ; Action: Antagonise the action of calcium within the myometrial cells so reduce its contractility. ** Nifedipine 10 mg oral tablet. 4- Magnesium Sulphate Action: The intracellular calcium is displaced by magnesium ion leading to inhibition of the uterine activity. 5- Prostaglandin Inhibiting Agents Action: Inhibition of uterine contractions by inhibiting prostaglandin synthesis. Dosage: e.g. indomethacin 100 mg suppository initially, followed by 25 mg orally every 6 hours for up to 24 hours after contractions ceased.

59

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)

6- Ethyl Alcohol : Action Inhibits the release of oxytocin from the posterior pituitary gland. Suppresses the myometrial activity directly. Inhibits prostaglandin F2 a synthesis. Dosage It is given IV and the dose is adjusted to maintain blood alcohol level of 0.9-1.6 mg/litre. Side effects Nausea, vomiting and depression. Drunken mother and foetus. Maternal and foetal acidosis. 150.


Important MCQ colloction for part-1 MRCOG(5) : A- Hyoscine hydrobromide .................................................................T B- Morphine sulphate .........................................................................F C- Chloropropamide .........................................................................T D- Promethazine hydrochloride ..........................................................T E- Perphenazine ...............................................................................T

Hyoscine is an alkaloid, Promethazine is an antihistamine, Perphenazine is an antipsychotic and all 3 have antiemetic properties. The sulphonyl urea chloropropramide may have antiemetic properties and has thus been marked as true. Morphine has an emetic action. An antiemetic is a drug that is effective against vomiting and nausea. Anti-emetics are typically used to treat motion sickness and the side effects of opioid analgesics, general anaesthetics and chemotherapy directed against cancer. 1- Promethazine

60

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
Promethazine is also known as phenergan and mepergan. It is also used to treat motion sickness, reduce allergic symptoms, and for sedation. It is one of the drugs of the phenothiazine type. In addition to other qualities, it is an antihistamine 2- Prochlorperazine Prochlorperazine is also known as compazine. Like promethazine, it is a member of the class of phenothiazines. Unlike promethazine, however, prochlorperazine also belongs to the class of drugs known as antipsychotics, or neuroleptics. Antipsychotic drugs are used to treat psychoses and other psychiatric disorders. In addition to its use as an antiemetic and antipsychotic drug, prochlorperazine is also used to treat non-psychotic anxiety. 3- Serotonin Receptor Antagonists The serotonin receptor antagonists include granisetron (kytril), dolasetron (anzemet), and ondansetron (zofran). These drugs are used for postoperative nausea and emesis as well as nausea and vomiting associated with chemotherapy, and are often used in combination with a corticosteroid. Ondansetron is approved for nausea and vomiting associated with radiation therapy. 4- Neurokinin Receptor Antagonists The Neurokinin receptor antagonists are a new class of antiemetics. Aprepitant (Emend) was approved in 2004 for use in cancer patients. It is used in combination with other antiemetics for relief of acute and delayed nausea and vomiting caused by high-dose chemotherapy, most often caused by the chemotherapy drug cisplatin. 5- Dronabinol Dronabinol (marinol) is used to combat anorexia in AIDS patients, and emesis in cancer patients who haven't responded to other antiemetics. Marinol is the synthetic or extracted form of the active ingredient found in marijuana. 6- Other Antipsychotic (Neuroleptic) Drugs The other neuroleptic (antipsychotic) drugs used to treat nausea and emesis are droperidol (inapsine), halo-peridol (haldol), chlorpromazine (thorazine), and perphenazine (trilafon). One other antipsychotic, triethylperazine (torecan or norzine), was used as an antiemetic, but is no longer widely available. Some of the antipsychotics are also used to treat aggressive or violent behavior or incontrollable hiccups (chlorpromazine). These drugs are similar to prochlorperazine in terms of their actions and potentially severe side effects. 151. Beta sympathomimetic drugs may: A- Cause bronchospasm ....................................................................F B- Reduce the frequency of uterine contractions ..................................T C- Cause heart block ........................................................................T D- Reduce diastolic blood pressure .....................................................F

61

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
E- Increase blood glucose concentration ............................................T

These drugs have the following effects vasodilation, bronchial relaxation, intestinal and genitourinary wall relaxation, cardiac stimulation, renin release, glycogenolysis, gluconeogenesis, lipolysis 152. Thiopentone sodium administration intravenously: A- Is a potent muscle relaxant ...........................................................F B- Is predominantly excreted by the kidney .......................................F C- Binds to protein ...........................................................................T D- Is fat soluble ...............................................................................T E- Crosses the placenta ....................................................................T

Thiopentone sodium produces general anaesthesia. Although bound to plasma proteins thiopentone sodium rapidly crosses the blood-brain barrier. Thiopentone sodium is slowly metabolised by the liver. Only a small proportion of the active drug is excreted in the urine. 153. The following antibiotics act on bacterial walls: A- Penicillin .....................................................................................T B- Ceftazidime ................................................................................T C- Metronidazole ..............................................................................F D- Clindamycin ................................................................................F E- Gentamicin ..................................................................................F

Mode of action of antibiotics can be classified as below 1.Inhibition of nucleic acid synthesis- Metronidazole 2.Inhibition of protein synthesis - Clindamycin, Gentamicin 3.Action on cell membrane - Polymyxin 4.Interference with enzyme system (antimetabolites) - Trimethoprim 5.Action on cell wall - Penicillins and Cephalosporins 154. Isoprenaline

62

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
A- Is potentiated by Propranolol .........................................................F B- Can be used sublingually ...............................................................T C- Has a minimal action on alpha receptors .........................................T D- Causes bradycardia .....................................................................F E- Is a bronchodilator ........................................................................T Isoprenaline is an beta adrenoreceptor agonist whose effects are antagonized by propranolol. It improves cardiac output, causes bronchodilatation and induces a tachycardia, but its use is generally limited to the treatment of low output states associated with heart block. It is usually used as an IV infusion but can be administered SL or Orally. Isoprenaline ...1- is a sympathomimetic beta adrenergic agonist medication. It is structurally similar to epinephrine (adrenaline) but acts selectively on beta receptors, activating β1 and β2 receptors equally Acts almost exclusively on b-adrenergic receptors • Causes i) Inotrope [b1-receptors ii) Chronotrope [b1-receptors] iii) Vasodilator [b2-receptors]—potent effect iv) Bronchodilation [b2-receptors] • Reduces SVR & PVR via vasodilation & pulmonic vasodilation

2) Indications • Ventricular dysfunction especially RV(combination of pulmonary dilation & inotropic support) • Bronchoconstriction • Bradycardias • Pulmonary hypertension (inotrope of choice if require inotropic support in such a patient)

3) Effects on organs—side effects • Also increases venous return to heart 4) Toxic effects/ precautions with administration • Tachycardias, dysrythmias (due to b1 effects)

63

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
• Reduced coronary diastolic perfusion pressures (due to b2 effects) • Increased MVO2 (due to tachycardia) plus reduced myocardial O2 supply (due to reduced coronary diastolic perfusion pressures) may extend ischaemic areas 5) Contraindications • Idiopathic hypertrophic subaortic stenosis • Tetralogy of Fallot with RV outflow tract obstruction (as may constrict pulmonary vasculature exacerbating preexisting pulmonary hypertension or right ventricular dysfunction 6) Important drug interactions • Should not be administered concommitantll with adrenaline as will dangerously exacerbate adrenergic effects resulting in arrythmias • Risk of arrythmias with volatile anaesthetics 155. Prostaglandins A- Synthesized from cholesterol .........................................................F B- Are small polypeptides ..................................................................F C- Secreted by the pituitary gland .....................................................T D- Secreted by the prostate gland .....................................................T E- Associated with gastrointestinal side effects ...................................T

Prostaglandins are long-chain hydroxy fatty acids derived from arachidonic acid, which is released from cell membrane phospholipids and catalysed by the enzymes cyclo-oxygenase and endoperoxidase. Prostaglandins are produced locally. The original source was the prostate. GI side effects include diarrhoea and abdominal pains. Every prostaglandin contains 20 carbon atoms, including a 5-carbon ring. They are mediators and have a variety of strong physiological effects. Prostaglandins are found in most tissues and organs. They are produced by all nucleated cells except lymphocytes. They are autocrine and paracrine lipid mediators that act upon platelets, endothelium, uterine and mast cells. They are synthesized in the cell from the essential fatty acids .......... Function

64

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
cause constriction or dilation in vascular smooth muscle cells cause aggregation or disaggregation of platelets sensitize spinal neurons to pain decrease intraocular pressure regulate inflammatory mediation regulate calcium movement control hormone regulation control cell growth Prostaglandins are potent but have a short half-life before being inactivated and excreted. Therefore, they send only paracrine (locally active) or autocrine (acting on the same cell from which it is synthesized) signals. There are a variety of physiological effects including: 1. Activation of the inflammatory response, production of pain, and fever. When tissues are damaged, white blood cells flood to the site to try to minimize tissue destruction. Prostaglandins are produced as a result. 2. Blood clots form when a blood vessel is damaged. A type of prostaglandin called thromboxane stimulates constriction and clotting of platelets. Conversely, PGI2, is produced to have the opposite effect on the walls of blood vessels where clots should not be forming. 3. Certain prostaglandins are involved with the induction of labor and other reproductive processes. PGE2 causes uterine contractions and has been used to induce labor. 4. Prostaglandins are involved in several other organs such as the gastrointestinal tract (inhibit acid synthesis and increase secretion of protective mucus), increase blood flow in kidneys, and leukotriens promote constriction of bronchi associated with asthma. 156. Prostaglandins A- Are involved in the onset of labour .................................................T B- Maintain the corpus luteum in early pregnancy ................................F C- Have a role in causing dysmenorrhoea ..........................................T D- May be important in the development of menorrhagia .....................T E- Are Oxytocic ................................................................................T

Prostaglandins are believed to be important mediators of uterine contractions in women. Furthermore, there appears to be good correlation between the amount of prostaglandin production and cramps associated with dysmenorrhoea. It is now thought that as prostaglandin production increases, there is increased uterine cramping that results in uterine ischaemia and pain. Studies have shown that prostaglandin production increased during the first 48-72 hours of menstrual flow. Decreasing prostaglandin production with medications can decrease the pain. Since the arteriolar contraction and endometrial necrosis are caused by prostaglandins, it is apparent that prostaglandins play a pivotal role in controlling menstrual blood loss. PGF2a and PGE2 cause myometrial contraction and hence oxytocic. Prostaglandins are useful in obstetrics for induction of labour and termination of pregnancy

65

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
157. Which of the following antibiotics are considered bactericidal? A- Clindamycin .................................................................................F B- Amoxicillin ...................................................................................T C- Erythromycin ...............................................................................F D- Tetracycline .................................................................................F E- Gentamicin ...................................................................................T

Both penicillins and the aminoglycosides such as gentamicin are bactericidal whereas the others are bacteriostatic 158. Following are characteristics of hypoxic cell death a- apoptosis b- Phagocytosis c -Pyknosis d- Poiklocytosis e- Release of Phospholipids 159. Oestrogen receptors ....... A- Is localised to the nucleus only following ligand binding B- Does not undergo nucleocytoplasmic shuttling C- Binds heat shock protein 90 on activation D- Is regulated by phosphorylation E- Is similar to the androgen receptor 160. Copper-containing IUCDs A- Should be changed every year B- Have a higher incidence of actinomycosis colonization than plastic devices C- Causes a relative increase in ectopic pregnancies D- Have been implicated as a cause of fatal infection in pregnancies E- Do not cause menorrhagia

66

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
Copper-containing IUDs **The copper IUD has been approved for use for up to 10 years and can be effective for up to 12 years . **The advantage of the copper IUD is that it is hormone-free providing a suitable option for women who experience problems with hormonal methods. Another role of the copper IUD is as an emergency contraceptive. It can prevent up to 99% of pregnancies when inserted within 5 days of unprotected sex.

The mechanism of IUDs is not well understood. It's known however that the presence of a device in the uterus prompts the release of leukocytes and prostaglandins by the endometrium. Copper IUDs act by impairing sperm function and movement through the uterus, as copper is toxic to sperm. They do this by instigating a reaction which induces cellular and humoural inflammatory response to the presence of the copper within the cervical mucous, uterine cavity and fallopian tube. The copper and the inflammatory response are both spermicidal. They also cause changes in the lining of the uterus which prevents an egg attaching to the endometrium if it does happens to get fertilised. It is this irritation that leads to the increased bleeding and heavier periods. The more modern copper IUDs are associated with less blood loss and are also more efficacious 1- Copper releasing IUDs can cause cramps, longer and heavier menstrual periods, and spotting between periods. 2- The intrauterine system does NOT provide protection against the transmission of sexually transmitted diseases .On average, menstrual blood loss increases by 20–50% after insertion of a copper-T IUD; increased menstrual discomfort is the most common medical reason for IUD removal. 3- Development of PID is very rare despite earlier beliefs that they occur commonly in women using IUDs. The risk of PID is highest within the first 3 weeks following insertion, while after that the risk is minimal. Women with cervical infections caused by chlamydia or gonorrhoea at the time of insertion have a 3-5% chance of developing an infection in the first 20 days. Screening for vaginal and cervical infections should be carried out prior to insertion to reduce risk of infection being passed to the uterus. Symptoms of infection : •Pain or tenderness in lower abdomen; •Unusual bleeding from vagina; •Fever or chills; •Discharge from vagina; •Pain during intercourse; •Burning sensation when passing urine. 4- The risk of ectopic pregnancy to a woman using an IUD is lower than the risk of ectopic pregnancy to a woman using no form of birth control. However, of pregnancies that do occur during IUD use, a higher than expected percentage (3–4%) are ectopic .

67

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
5- The pregnancy rate during IUD use is very low (less than 1% per year). If pregnancy does occur, the IUD should be removed. Although IUDs are not teratogenic , presence of the IUD increases the risk of miscarriage, particularly during the second trimester. It also increases the risk of premature delivery. Although the Dalkon Shield IUD was associated with septic abortions (infections associated with miscarriage), other brands of IUD are not. IUDs are also not associated with birth defects ... 6- expulsion and uterine perforation. Uterine perforation is generally caused by an inexperienced provider and is very rare. Expulsion is more common in younger women, women who have not had children, and when an IUD is inserted immediately after childbirth or abortion. Women should check the string of the IUD at least once per menstrual cycle to verify that it is still in place / 161. The following increase insulin secretion: A- Glucagon --------------------------------------------------------------------T B- Glibenclamide ---------------------------------------------------------------T C- Propranolol -----------------------------------------------------------------F D- Bendroflumethiazide -------------------------------------------------------T E- Arginine ----------------------------------------------------------------------T

Insulin secretion is stimulated by glucose, amino acids (arginine) and triglycerides. Pharmacologically its secretion is stimulated by sulphonylureas such as glibenclamide, and also glucagon (stimulating glucose release). Bendroflumethiazide may produce a deterioration in insulin sensitivity and hene increase insulin secretion. Propanolol may inhibit insulin secretion. 162. Nitric oxide: A- is generated from glutamine ----------------------------------------------F B- is produced by both inducible and constitutive forms of nitric oxide synthetase ------------T C- raises systemic vascular resistance --------------------------------------F D- is inactivated by oxygen free radicals -----------------------------------T E- is increased by cyclic AMP activation -------------------------------------F Nitric oxide is produced from l-arginine by nitric oxide synthase and is produced by the vascular endothelium in response to haemodynamic stress and produces smooth muscle relaxation and reduced vascular resistance. Nitric oxide is a free radical and may be inactivated through interaction with other oxygen free radicals e.g. oxidised LDL. It causes the production of cGMP as a second messenger

68

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
163. Insulin action: A- increases liver glycogenolysis ---------------------------------------------F B- increases muscle glycogen synthesis -------------------------------------T C- increases liver gluconeogenesis ------------------------------------------F D- increases liver fatty acid synthesis ---------------------------------------T E- facilitates red blood cell glucose uptake ----------------------------------F Insulin acts to inhibit lipolysis and gluconeogenesis by promoting glycogenesis. Insulin promotes synthesis of fatty acids in the liver. e-Does not increase uptake into brain or liver either. 164. Concerning the female breast: A- It is firmly attached to the pectoralis major muscle --------------------F B- There is a subareolar lymph plexus --------------------------------------T C- Axillary lymph nodes receive more than half the lymph from the breast --------------------T D- Lymph from the lateral part of breast may drain to the para-sternal nodes -----------------T E- Approximately 90% of the lymph passes to the posterior infraclavicular nodes --------F

The female breast extends from the 2nd to the 6th rib in the mid clavicular line, overlying pectoralis major. Beneath the breast there is a condensation of superficial fascia, which acts as a posterior capsule for the breast. There is a subareloar lymphatic plexus. Most of the lymph of the breast drains to the axilla, with lymph from the lateral breast draining into the axillary and infraclavicular nodes. Medially the lymph drains through the intercostal spaces into the parasternal (internal thoracic) nodes. However lymph from the breast may drain into any of the lymphatic basins and if one pathway becomes blocked, another is utilized. 165. Recognised features of acromegaly include A- hypocalciuria ----------------------------------------------------------------F B- intestinal polyposis --------------------------------------------------------T C- splenomegaly --------------------------------------------------------------T D- palpable peripheral nerves ----------------------------------------------T

69

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
E- proximal myopathy --------------------------------------------------------T Features of acromegaly include large hands, feet, macroglossia, organomegaly and prognathism. a-hypercalciuria. Compression of the optic chiasm may produce a bitemporal hemianopia. Proximal myopathy can occur as well as diabetes mellitus, glucose intolerance and hypertension. Diagnosed on basis of non suppression of GH concentrations with the oral glucose tolerance testThe following congenital 166. abnormalities are associated with a characteristic karyotype A- Klinefelter syndrome ------------------------------------------------------T B- cri-du-chat syndrome -----------------------------------------------------T C- ovarian dysgenesis --------------------------------------------------------T D- Pierre-Robin syndrome ---------------------------------------------------F E- meningomyelocoele --------------------------------------------------------F Klinefleter's - XXY, Cri-du-Chat Deletion Chromosome 5p, Turner's/gonadal dysgenesis - XO. 167. The long-term treatment of acne with tetracycline: A- is unsuccessful in 75% of patients ----------------------------------------F B- may predispose to scarring of the skin ----------------------------------F C- predisposes to Candida infection -----------------------------------------T C- may damage the fetus in utero -------------------------------------------T D- may predispose to gram negative folliculitis ----------------------------T Tetracyclines are a frequent and successful treatment of acne but are associated with side effects including staining of teeth in utero and should be used with caution in renal impairment. Similarly they may predispose to fungal infection. 1- When used for acne vulgaris, skin can be extremely dry and flaky if overused 2- May interfere with methotrexate by displacing it from the various protein binding sites 3- Can cause breathing complications as well as anaphylactic shock in some individuals 4- Should be avoided during pregnancy as it may affect bone growth of fetus. 5- Passes into breast milk and is harmful to breast-fed infants, and should therefore be avoided during breastfeeding if possible 168. The following drugs are unsafe in the last 4 weeks of pregnancy A- warfarin ---------------------------------------------------------------------T

70

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
B- cotrimoxazole --------------------------------------------------------------T C- paracetamol ----------------------------------------------------------------F D- methylpenecillin ------------------------------------------------------------F E- tetracycline ------------------------------------------------------------------T a-crosses placenta and cause haemorrhage. Warfarin is also teratogenic in the first trimester. b-neonatal haemolysis and methaemoglobinaemia. Also teratogenic in 1st trimester. c,d-safe e-dental discolouration, maternal hepatotoxicity (in large doses). Beware of the exact wording - tetracycline best avoided but not 'unsafe' in limited doses. 169. Prostaglandin PGI2 (prostacyclin) A- reduces arterial smooth muscle tone -------------------------------------T B- is a product of arachidonic acid metabolism -----------------------------T C- production is inhibited by non-steroidal anti-inflammatory drugs ------T D- increases platelet cyclic AMP concentration ------------------------------T E- inhibits platelet aggregation to damaged vessel walls ------------------T Prostacyclins reduce arterial tone, is produced from arachidonic acid and this synthesis is inhiobited by NSAIDs. It is involved in platelet aggregation through increasing cAMP concentration. 170. Bromocriptine: A- will suppress lactation in the puerperium --------------------------------T B- may be a useful adjunct in acromegaly ----------------------------------T C- may cause enlargement of the pituitary in a patient with a prolactinoma ------------T D- inhibits dopamine receptors -----------------------------------------------F E- is an ergot derivative ------------------------------------------------------T b - Reduces growth hormone levels in the majority of patients. Improves visual fields, diabetes and may even shrink tumour. High doses needed - 10-20mg per day. Usually produces marked reduction in size of prolactinoma but Tumour enlargement and apoplexy has rarely been associated with bromocriptine use. d - Dopamine (DA 2) receptor agonist. 171.Common features of phaeochromocytoma include: A- panic attacks ---------------------------------------------------------------T

71

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
B- bradycardia ----------------------------------------------------------------F C- diarrhoea -------------------------------------------------------------------T D- hypoglycaemia -------------------------------------------------------------F E- hypokalaemia ---------------------------------------------------------------F Typical features of phaeochromocytoma include paroxysmal panic attacks, sweats, anxiety, tremor, palpitations associated with variable hypertension - postural hypotension can also occur but is not common. Diabetes is a biochemical feature as is hypokalaemia. It is detected usually through elevated urine free metaadrenaline/normetadrenaline with a high sensitivoty and specificity. b-Reflex bradycardia. d-Hyperglycaemia. 172. In congenital adrenal hyperplasia caused by 21-hydroxylase deficiency the following are seen in increased amounts in the serum: A- 17 alpha hydroxyprogesterone -------------------------------------------T B- cortisol ----------------------------------------------------------------------F C- aldosterone ----------------------------------------------------------------F D- 11-deoxy corticosterone -------------------------------------------------F E- ACTH ------------------------------------------------------------------------T The characteristic biochemical abnormalities in 21 OHase deficiency CAH are reduced cortisol plus aldosterone at the expense of elevated testosterone, 17OHP and as the pituitary detects a deficiency of cortisol there is increased ACTH. Plasma renin activity may also be elevated. 11 deoxycorticosterone may be increased in the much rarer 11-Hydroxylase deficiency 173.Regarding diagnostic ultrasound: A- Is pulsatile ------------------------------------------------------------------T B- Is ionising ------------------------------------------------------------------T C- Is associated with a 1oC rise in body temperature after 15 mins of scanning ------------------F D- High frequency ultrasound has greatest tissue penetration --------------------F E- Cavitation is a recognised effect ----------------------------------------------------T As a sound beam passes through tissue, some of the energy of this sound wave is absorbed by the tissue. However for low intensities of ultrasound, the heat deposited is quickly dissipated and does not build up. Cavitation is due to the generation, growth, vibration and possible collapse of microbubbles in the tissue. These microbubbles are generated by the ultrasound waves. These bubbles may ―move‖ with the sound beam or some may oscillate so strongly that the bubbles collapse suddenly producing local effects

72

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
174. Concerning radiation physics: A- An electron has a greater mass than a proton ---------------------------F B- A positron has the same charge as an electron -------------------------F C- A proton has a positive charge -------------------------------------------T D- A neutron has almost the same mass as a proton ---------------------T E- The hydrogen nucleus is a neutron ---------------------------------------F The atom is composed of a nucleus containing the positively charged protons and neutral neutrons of roughly equal mass orbited by the smaller negatively charged electrons. A positron is an elementary particle of roughly equal size to an electron but positively charged. Hydrogen atomic weight 1 is composed of a proton in its nucleus. 175. In experimental conditions, ultrasound may produce biological effects on tissue by the following means: A- Acceleration of cell division -----------------------------------------------F B- Heat generation ------------------------------------------------------------T C- Cavitation ------------------------------------------------------------------T D- Duplication of chromosome numbers ------------------------------------F E- Microstreaming -------------------------------------------------------------T There are two principle bioeffects of ultrasound: Thermal and mechanical. Thermal is created through the impact of acoustic energy upon tissue. Mechanical bioeffects include cavitation through particulate streaming associated with the violent agitation of particles within the medium. 176. A 30-year-old female undergoes a Chest and abdominal X-ray arranged by her GP and does not realise that she is 7 weeks pregnant. Increased risk to which of the following are found in those children exposed in utero to such X irradiation A- Acute lymphoblastic Leukaemia ------------------------------------------T B- Intra-uterine growth retardation -----------------------------------------F C- Mental retardation -------------------------------------------------------F D- Diabetes -------------------------------------------------------------------F E- Cerebral gliomas ---------------------------------------------------------T

73

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)

It should be appreciated that the risks to the fetus are small following exposure to chest Xrays but the far more with direct exposure following abdominal exposure. Generally there is an increased risk of childhood leukaemias and cancers. There appears to be no evidence for IUGR, diabetes nor mental retardation - although IQ on a population basis is significantly lower.

74

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)

Impartant MCQS FOR MECOG 1- the following substances are freely transferred across the placenta a-insulin. (false) b-thyroxine. (false) c-IgG. (true) d-warfarin (true). e-glucose. (true) Comments: There are many drugs that freely cross the placenta including the oral hypoglycaemic agents hence insulin is preferred in pregnancy. Warfarin also ocross the placenta hence the preferred use of heparin. Glucose a nutrient obviously cross the placenta. IgG pass but not IgM pass placenta. Thyroxine does not cross the placenta hence the reason for not using a block and replace regimen for treating thyrotoxicosis as carbimazole and propyl thiouracil does cross the placenta. 2- 2- in a consanguineous marriage a- the risk of a serious disease or defect is double that for an unrelated mating. (true) b-the risk of recurrence for autosomal recessive disorders is 50%.(false) c-there is an increased risk of producing mentally retarded child. (true) d-when it is between second cousins, does not carry an increased risk. (true) e-there is an increased risk of producing a deaf child. (true) Comments: Consanguinity (marriage to a blood relative) is associated with an increased risk of inherited disorders, birth defects as down syndrome and tends to be approximately double that of unrelated couples but not near 50%. This risk is attenuated as relationship between partners becomes more distant. 3- 3-Autoimmune addison's disease is associated with a-premature ovarian failure. (true) b-hypokalemia.(false) c-hypothyroidism. (true) d-vitiligo. (true) e-Sjogren's syndrome. (true) Comments: b- hyperkalemia. e-in 47% of patients with autoimmune Addison's disease at least one other autoimmune disorder was present. Primary hypothyroidism has the highest prevalence (20%) followed by vitiligo(9%), non toxic goiter, premature menopause, grave's disease, pernicious anaemia, sjogren's disease, hypoparathyroidism,type 1 diabetes mellitus and celiac disease. 4- 4- the following drugs cause hypokalemia a- commencement of digoxin for atrial fibrillation.(false) b-ACE inhibitors.(false) c-salbutamol for asthma. (true) d-vitamin B12 for the treatment of pernicious anaemia. (true)

75

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
e-cimetidine for duodenal ulcer.(false) Comments: a-only toxicity of digoxin cause toxicity. b-hyperkalaemia. c-especially high dose in nebulisers for acute asthma. d-paarticularly at the beginning of the treatment. 5- 5-Regarding the climacteric menopause a-the average age of the menopause in the united kingdom is about 50 years. (true) b-demineralization of bones take place after the menopause. (true) c-the level of prolactin rises after the last period.(false) d-the severity of flushing has been shown to be related to the level of oestrogen in the blood.(false) e-clinical studies have shown that the later the menarche the earlier the menopause.(false) Comments: Average age for menopause is approximately 50 years and is associated with sharp reduction in bone mineral density and increase in cardiovascular risk c- it falls. d-there is no relationship with severity. The presence of sweating is more likely in women with low oestrogen level e-no relation between menarche and menopause. 6- 12-hypoparathyroidism is associated with a-increased incidence of Addison's disease. (true) b-chronic mucocutaneous candidiasis. (true) c-basal ganglia calcification commonly causing parkinsonism. (false) d-short 4th and 5th metacarpals.(false) e-good response of hypocalcaemia to calcium and vitamin D treatment (true) Comments: a-Hypoparathyroidism is associated with Addison,s disease. c- short 4th and 5th metacarpals is associated with pseudohyperparathyroidism. d-basal ganglia calcification is common but usually cause chorea. e- the condition is treated buy vitamin D. 7- 13-Gastrin a-Stimulates gastric acid secretion in response to meals (true) b-stimulates the growth of cells in the gastric mucosa. (true) c-is predominantly produced by G cells located in the pancreas (false) d-levels are decreased in atrophic gastritis(pernicious anaemia) (false) e-stimulates insulin secretion particularly after a carbohydrate meal. (false) Comments: The main action of gastrin is stimulation of gastric acid and pepsin secretion and stimulation of growth of mucosa of the stomach and intestine.It is produced by G cells in the gastric antrum ,duodenum, fetal pancreas and in adults with pancreatic tumors as gastrinoma .Levels are increased in conditions of low acid production e.g:atrophic gastritis and proton pump inhibitor therapy due to loss of negative feed back. Gastrin levels only reach high enough levels following a protein meal to stimulate insulin secretion. 8- 14-Galactorhoea may be caused by treatment with a-levodopa. (false)

76

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
b-cimetidine. (true) c-aspirin. (false) d-spironolactone. (false) e-haloperidol. (true) Comments: Hyperprolactinaemia caused by dopamine antagonism (TCA, major tranquilizers, haloperidol, high dose SSRI may push up prolactin producing galactorrhoea a-levodopa does not cause hyperprolactinaemia but methyl dopa does. d-causes of gynaecomastia but not galactorrhoea (not cause hyperprolactinaemia) 9- 15-Sulphonyl urea therapy: a-may increase weight.(true) b-is useful in all type 2 diabetics.(false) c-enhances glucose stimulated insulin release from the pancreas. (true) d-stimulates peripheral glucose utilization. (false) e-has hyponatraemia as a side effect (true) Comments: Sulphonylurea therapy stimulate insulin secretion from the beta cells of pancreas through potassium channel opening . metformin cause increased glucose utilization . These agents may cause SIADH. 10- 16- drugs which can be given in near normal dosage in severe renal failure include a- benzyl penicillin. (false) b-digitoxin. (true) c-doxycycline. (flase) d-streptomycin. (false) e-rifampicin. (true) Comments: Drugs whose concentration may accumulate in renal failure include digoxin (digitoxin metabolized by liver),streptomycin,penicillin,statins,furosomide,doxycycline can worsen renal failure. 11- 17-Hypercalcaemia is associated with: a-thyrotoxicosis. (true) b-secondary hyperpaprathyroidism. (false) c-excessive absorbable alkali reserve. (true) d-sarcoidosis. (true) e-acute adrenal failure. (true) Comments: Hypercalcaemia may occur in association with hyperpaprathyroidism, vitaminosis D, sarcoidosis, Addison's disease, milk alkali syndrome,thyrotoxicosis. Secondary hyperparathyroidism is associated with hypocalcaemia with chronic renal failure and impairment of 1 alpha hydroxylation of vitamin D by the kidneys. 12- 18-Testicular feminization syndrome a-is characterisedby XXY chromosomal pattern. (false) b-have a female phenotype. (true) c-is associated with low serum testosterone levels (false) d-have undetectable serum oestrogen concentrations (false) e-is an x-linked disorder. (true) Comments: a-it is XY.

77

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
Testicular feminization syndrome or androgen insensitivity syndrome(AIS) is when a person has XY genotype but is resistant to androgens. As a result the individual has some or all of the physical characteristics of a woman, despite having genetic make up of a man. Its types complete and incomplete. Complete AIS results in someone who looks as a female. In incomplete AIS the degree of sexual ambiguity varies widely from individual to other. Testosterone concentrations are in normal male range but the receptor defect prevents the testosterone from exerting its effects. Oestradiol concentrations are measurable and produced from the peripheral conversion of testosterone as well as by the gonads. 13- 19- which of the following predispose to microbial invasion a-urinary obstruction. (true) b-ciliary dyskinesia. (true) c-cystic fibrosis. (true) d-skin ulceration. (true) e-neutrophil deficiency. (true) 14- 20-Autosomal dominant inheritance a-25% of offspring are affected with an affected parent. (false) b-is the mode of inheritance in multiple neurofibromatosis. (true) c-afects both sexes equally. (true) d-shows a pattern of vertical inheritance in a pedigree. (true) e-always manifests at birth. (false) Comments: Autosomal dominant conditions include huntington's chorea, achondroplasia, MEN type 1. It affects both sexes equally and 50% of offspring are affected with an affected parent. 21- In the treatment of cushing's disease a-long term metyrapone may be used. (true) b-cabergoline is used in patients unfit for surgery. (false) c-after bilateral adrenalectomy, Nelson's syndrome is prevented by adequate glucocorticoid replacement . (false) d-recurrence of cd after transphenoidal surgery is virtually zero. (false) e-yttrium implantation is indicated in the treatment of pituitary tumors compressing the optic hiasma. (false) Comments: Cushing's disease equates the pituitary dependant disorder while cushing syndrome include all the other causes as ectopic and adrenal. Cabergoline is used in prolactinomas not CD. Metyrapone blocks cortisol production. Recurrence after pituitary surgery is of the order of 20-40%. Yttrium implantation is never used these days. 15- 22-Polycystic ovary syndrome is characterized by a-hirsutism .(true) b-raised serum LH. (true) c-raised serum testosterone. (true) d-raised FSH. (false) e-menorrhagia. (false) Comments: PCOS is characterized by hirsutism, oligomenorhoea(usually with normal oestrogen concentration)and obesity. Insulin resistance is thought to play a major part in evolution of oligomenorrhoea and contribute to elevated LH with normal FSH and a

78

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
slightly elevated testosterone. 23-Polymerase chain reaction(PCR) a-can amplify RNA but not DNA. (false) b-it is of no value in prenatal diagnosis. (false) c-depends on thermostable taq DNA polymerase. (true) d-requires primer bits either side. (true) e-use heat to separate 2 strands of DNA. (True) Comments: PCR allows amplification of small samples of DNA and through reverse transcriptase RNA. It can be used for prenatal diagnosis of disease as cystic fibrosis. d-this is a disadvantage because the primers have to be known. 16- 24-Characteristic finding in anorexia nervosa are a-a decrease in cortisol levels. (false) b-increase in LH levels. (false) c-impaired glucose tolerance. (true) d-raised androgen levels. (false) e-hyperkalemia. (false) Comments: a-cortisol and growth hormones are elevated. b-LH and FSH low and LH response to LHRH is impaired when weight loss is severe. e-hypokalemia, hypoalbuminaemia, anaemia, leukopenuia, raised serum carotene. 17- 25- Acidosis may result in a-potassium retention. (true) b-a rise in plasma chloride (true) c-a low pCO2 . (true) d-peripheral vasodilatation. (true) e-tetany. (false) Comments: Acidosis is associated with potassium retention and rise in chloride with maintainance of the anion gap.Peripheral vasodilation occurs to improve oxygenation of metabolizing tissue. Alkalosis is associated with tetany and reduction of ionized calcium.in an effort to correct acidosis respiration increase with reduction of pCO2. 18- 26-primary hyperparathyroidism a-is associated with hypocalcuria due to elevated PTH levels . (false) b-PTH is secreted in a pulsatile manner from the posterior pituitary and acts through PTH receptors on parathyroid cell membranes . (false) c-is usually caused by an adenoma of a single parathyroid gland. (true) d-progresses to tertiary hyperparathyroidism with time. (false) e-is associated with bone resorption by PTH to restore depressed serum calcium levels to normal. (false) Comment: Associated with hypercalcaemia, hypophosphataemia and there is usually hypercalcuria. It is usually a consequence of a single adenoma but may be associate with hyperplasia and rarely carcinoma where PTH concentrations may be particularly high d- secondary progress to tertiary. 19- 27-Recognized features of acromegaly include: a-hypocalcuria. (false)

79

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
b-intestinal polyposis. (true) c-splenomegaly. (true) d-Palpable peripheral nerves. (true) e-proximal myopathy. (true) Comment: Features of acromegaly include large hands, feet, macroglossia, organomegaly and prognathism. a-hypercalcuria. b-compression of the optic chiasma may produce a bitemporal hemianopia.proximal myopathy can occur as well as diabetes mellitus, glucose intolerance and hypertension. Diagnosis on the basis o non suppression of GH concentrations with the oral glucose tolerance test. 20- 28-the following are true: a-an elevated TSH level excludes the diagnosis of hyperthyroidism. (false) b-free thyroxine levels are elevated in normal pregnancy. (false) c-most circulating thyroxine s bound to thyroglobulin. (false) d-phenytoin may reduce total thyroxine levels.(true) e-amiodarone treatment may cause hyperthyroidism. (true) comments: Elevated normal TSH is expected in secondary hyperthyroidism.Total T4 concentrations are usually low or normal in normal pregnancy due to dilutional effects. Best to regard the TSH concentration. However. Early pregnancy may be associated with slight rise in T4 associated with elevated HCG which declines as pregnancy progresses.75% of T4 is bound to thyroid binding globulin not thyroglobulin.Phenytoin treatment of euthyroid patients results in a 30 to 40% decrease in serum T4 and free T4 levels and either normal or slightly decreased levels of T3 and free T3 .Amiodarone may cause hyper as well as hypothyroidism. 21- 29-The following may be associated with hypocalcaemia: a-convulsions. (true) b-psychosis. (true) c-restless legs. (false) d-Peripheral neuropathy. (false) e-Papilloedaema. (true) Comments: And depression , raised ICP and prolonged QT interval. 22- 30-the following cause multiple painful genital ulcers: a-circinate balanitis. (false) b-herpes simplex. (true) c-chancroid. (true) d-Primary syphilis. (false) e-granuloma inguinale. (false) Comments: A+d+e usually are painless . Painful ulceration includes herpes simplex/zoster and genital herpes. Behcet's disease,Reiter's,chancroid and gonocoocal disease. 23- 31-raised aldosterone levels are found in: a-normal pregnancy. (true) b-renal artery stenosis. (true) c-loop diuretics therapy. (true)

80

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
d-polycystic ovariansyndrome.(false) e-Liddle syndrome (false) Comments: Aldosterone is elevated in association with reduced circulating volumes,pregnancy,conn's syndrome,and raised with diuretic therapy (hence good combination of diuretics and ACEI). Liddle's disease is a renal tubular defect due to Na/K channels and is associated with hyporenninaemic hypoaldosteronism with hypokalaemic hypertension. 24- 32-Which of the following are found in multiple endocrine neoplasia type 1 syndrome: a-phaeochromocytoma. (false) b-medullary carcinoma of the thyroid. (false) c-hyperparathyroidism. (true) d-prolactinoma. (true) e-insulinoma. (true) Comments: MEN type 1 is associated with pituitary, parathyroid, and pancreatic tumours. MEN type 2 is associated with medullary thyroid carcinoma. 25- 33-Turner syndrome: a-is seen only in females. (true) b-may have one chromosome as an isochromosome. (true) c-is usually associated with severe mental retardation. (false) d-pateints usually present with primary amenorrhoea. (true) e-cannot be detected at birth. (false) Comments: Turner syndrome XO is associated with a female phenotype with webbed neck,short stature, cardiac abnormalities and streak gonads. Intelligence is usually unaffected. 26- 34-In diabetic ketoacidosis: a-leukocytosis is common and does not confirm infection. (true) b-Amylase levels may be raised in the absence of pancreatitis. (true) c-urinary stick testing for ketosis may be negative. (true) d-plasma glucose may be low. (false) e-a normal plasma potassium level excludes significant potassium defeicienc. (false) Comments: DKA is typically associated with increased plasma glucose,leukocytosis,reduced pH,bicarbonate, pCO2 and pO2. However it is well recognized that DKAmay still be associated with normal or not so high eg:15mmol/L .Usually ketones are found in urinebut occasionally are absent for reasons as impaired clearance during DKA. Due to excess renal losses, total body potassium is typically low even if plasma potassium is high. 27- 35-Causes of anovulation include: a-hyperprolactinaemia. (true) b-weight loss. (true) c-Obesity (true) d-polycystic ovary syndrome . (true) e-propranolol. (false) Comments: Anovulation may occur in association with poly cystic ovarian syndrome,

81

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
anorexia/marked weight loss but is also associated with obesity.Hyperprolactnaemia through negative feedback on gonadotrophes in the pituitary produces hypogonadotrophic hypogonadism and amenorrhoea. Propranolol is not associated with anovulation. 28- 36-Karyotypic abnormalities are found in the following: a-Huntington's disease. (true) b-Burkitts lymphoma. (true) c-Chronic granulocytic leukemia. (true) d-phenylketonuria. (false) e-Acute lymphocytic leukaemia. (true) Comments: a-if very large number of triplet repeats. d-autosomal recessive single gene defect. 29- 37-Abnormal colouration of urine in absence of haematuria may be due to: a-consumption of beetroot. (true) b-treatment with codanthramer.( true) c-phenylketonuria. (false) d-porphyria cutanea tarda. (true) e-acute intravascular haemolysis. (true) Comments: b-may be pink if rifampicin or isoniazid c-alkaptonuria. d-the urine is darker in porphyria cutanea tarda.It has red fluorescence under wood's light. e-haemoglobinuria. 30- 38-the following congenital abnormalities are associated with a characteristic karyotype: a-Klinefelter's syndrome. (true) b-cri-du-chat syndrome. (true) c-Ovarian dysgenesis. (true) d-Pierre-Robin syndrome. (false) e-meningomyelocoele. (false) Comments: Klinefelter's syndrome-XXY,cri-du-chat deletion chromosome 5p. Turner /gonadal dysgenesis-XO. 31- 39-Epstein-Barr virus is associated with: a-Burkitt's lymphoma. (true) b-Cervical neoplasia. (false) c-nasopharyngeal carcinoma. (true) d-pharyngitis. (true) e-autoimmune haemolytic anaemia. (true) Comments: b-No association with cervical neoplasia unlike human papilloma virus. c-Anaplastic nasopharyngeal carcinoma.common in SE china, virtually all cases have evidence of EBin the tumour tissue. d-infectious mononucleosis usually severe pharyngitis. e-usually resolves after 1-2 months.

82

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
32- 40-The following drugs in pharmaceutical doses have been shown to cause a rise in: a-thiazide diuretics. (true) b-ethanol. (false) c-Aspirin. (false) d-gliclazide. (false) e-Atenolol. (false) Comments: Drugs that may cause hperglycaemia include: corticosteroids, thiazides, glucagon. Atenolol is associated with hypoglycaemia. Gliclazide is an oral hypoglycaemic b-it causes a fall. c-It causes a fall. 33- 41-Causes of metabolic acidosis include: a-starvation. (true) b-thiazide diuretics. (false) c-uraemia. (true) d-pyloric stenosis. (false) e-Sulphonylurea. (false) Comments: a-starvation ketoacidosis. b-can cause metabolic alkalosis. c-may be caused by diversion of glutamate metabolism to the liver and the consequent bicarbonate consuming effect of hepatic ureagenesis. d-an important cause of metabolic alkalosis. e-biguanides however are associated with lacticacidosis. Comments: The primary host response to bacterial infectionsis dependant on mononuclear phagocytes and neutrophils. T-lymphocytes are involved in cell mediated acquired immune responses where as B-lymphocytes are involved in humoral immunity and produce immunoglobulins. T-lymphocytes compose the majority of circulating lymphocytes in plasma. Epstein-Barr virus infects B-lymphocytes and squamous epithelial cells of the oropharynx. The virus can transform B cells and epithelial cells to produce Burkitt's lymphoma, a subset of hodgkin's lymphoma.Nasopharyngeal carcinoma and oral hairy leukaemia. T cell lymphoma makes up 10 to 20% of non Hodgkin lymphoma and has a worse prognosis than B cell lymphoma. 34- 43-The action of noradrenaline released at sympathetic nerve endings is terminated by: a-enzymatic decarboxlation. (false) b-enzymatic inactivation by catechol O methyl transferase. (false) c-re-uptake of nordrenaline by the axonal terminals. (true) d-oxidative deamination by monoamine oxidase. (false) e-it is removed by the circulating blood. (false) Comments: Popular pathway to be asked . 35- 44-which of the following conditions are a consequence of chromosomal aberrations: a-fragile X syndrome. (true) b-phenylketonuria. (false) c-Cri du chat syndrome. (true)

83

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
d-Osteogenesis imperfect. (false) e-Down's syndrome. (true) Comments: Fragile X syndrome is due to micodeletions on the X chromosom giving the appearance of fragile notch in this chromosome. Cri du chat is due to a deletion in 5p. Down's syndrome may be due to trisomy of chromosome 21 or translocation of 14 to 21. OI is autosomal recessive as is phenylketonuria. 36- 45-Side effects of alpha methyl dopa include: a-pyrexia. (true) b-visual disturbance. (false) c-Oedema. (true) d-nasal congestion. (true) e-depression. (true) Comments: Also haemoytic anaemia, weight gain, GI disturbance,arthralgia,parkinsonism,nightmares,gyaecomastia,galactorhea, hepatitis. 37- 46-In the normal neonate: a-the white cell count may be 25x10(9). (true) b-haemoglobin F is the predominant haemoglobin. (true) c-The platelet count is in the normal adult range. (true) d-nucleated red cells are rarely seen in the peripheral blood. (false) e-the mean cell volume is greater than 100 fl. (true) 38- 47-In mitosis: a-the number of chromosomes is halved. (false) b-anaphase lag may produce turner syndrome. (true) c-the stage of metaphase shows separation of whole chromosome. (false) d-non disjunction increases with decreasing maternal age. (false) e-an abnormal plane of division of the chromatids produce isochromosomes. (true) Comments: Each time new cells are produced there is a mitotic cycle it must go through. They are interphase, prophase, metaphase, anaphase, telophase. 39- 48-Which of the following organelles have their own self replicating DNA: a-lysosymes. (false) b-golgi bodies.(false) c-mitochondria.(true) d-nucleus. (false) e-rough ER. (false) Comments: Mitochondria have DNA and give rise to maternally inherited disease as mitochondrial myopathies, red ragged fibres, DIDMOAD syndrome, wolfram disease 40- 49-Hypothyroidism: a-is more common than hyperthyroidism . (false) b-is associated with low serum carotene. (false) c-is a cause of pericardial effusion. (true) d-may present with cerebellar ataxia. (true) e-is associated with a reduced CSF protein. (false) Comments:

84

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
Hyperthyroidism is 8 times commoner. b-increased. e-elevated. 41- 50-Common features of cushing's syndrome due to adrenal carcinoma include: a-retarded growth in children. (true) b-Clitoromegaly. (true) c-subconjunctival oedema. (true) d-marked hyperpigmentation. (false) e-supraclavicular fat pads. (true) Comments: Adrenal carcinoma and cushing are rare.typically more than 4 cm. Growth retardation due to increased cortisol is typical in children. Co secretion of androgen may produce clitoromegaly.Typical features of Cushing include fat pad or buffalo hump,thin skin, easy bruising and subconjunctival oedema d-this may be seen in Cushing's syndrome due to ectopic ACTH.

42 -51-In hypopituitarism: a-selective gonadotrohin deficiency may be present. (true) b-concomitant diabetes inspidus may be masked by anterior pituitary failure.(true) c-adrenal steroid replacement must be started before thyroid replacement. (true) d-mineralocorticoid replacement is usually necessary. (false) e-in men,androgen replacement will cause masculinisation and restore fertility. (false) Comments: Hypopituitarism is typically caused by a non functional pituitary tumour with a staged loss of hormones first GH then LH and FSH then ACTH and finally TSH.The secretion of aldosterone is unaffected as it depend on rennin secretion.Testosterone restores masculinatoin but not fertility. 52-Congenital hypothyroidism a-Cannot confidently be diagnosed before the age of 3 months. (false) b-is in some cases associated with a goiter. (true) c-affects approximately 1 in 10,000 infants. (false) d-may present with jaundice.(true) e-requires thyroxine treatment fro life. ( true) Comments: Diagnosis is possible within neonatal period, a goiter may be seen in the child and the disorder affects 1:3500 births.Jaundice, hypotonia, growth retardation and appearance may prompt diagnosis. Causes include embryological or congenital abnormalities plus maternal drugs thionamides. 53-Carbimazole: a-is contraindicated in breast feeding mothers. (false) b-may cause lymphadenopathy. (true) c-is a prodrug. (true) d-may cause reversible agranulocytosis. (true) e-is teratogenic. (false)

85

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
Comments: It may be used in breastfeeding although the dose needs to be the low as the drug is excreted in breast milk. It is converted to methimazole which can cause a serum sickness like adverse effect including lyphadennopathy. It is used in pregnancy and is not teratogenic.But the dose again needs to be minimized to avoid neonatal hypothyroidism. 54-The following enzymes are involved in the synthesis of the neurotransmitterswith which hey are paired: a-cholinesterase: acetylcholine. (false) b-dopa decarboxylase :noradrenaline. (true) c-catechol-o-methyl transferase:dopamine. (false) d-monoamine oxidase:serotonin. (false) e-glutamic acid decarboxylase:gamma amino butyric acid (GABA) .(true) Comments: a-breakdown. b-dopa to dopamine beta oxidase. c-metabolism of NA to VMA. d-breakdown to 5 HIAA. 55-pnemocystis carinii pneumonia: a-is the commeest presenting feature in European AIDS patients. (true) b-is the commonest presenting feature in Ugandan AIDS patients. (false) c-can be successfully prevented with nebulised inhaled pentamidine. (true) d-may be present despite a clear chest X-ray. (true) e-occurs in non-HIV infected individuals. (true) Comments: PCP is the commonest mode of presentation of HIV infection and represents an AIDS defining illness.It can occur in other immunocompromised patients as leukaemia. CXR may be clear but a tell tale feature is hypoxia with mild exertion. b-slim disease with cachexia. Its treatment depends on cotrimoxazole and pentamidine is also effective. 56-The long term treatment of acne with tetracycline: a-is unsuccessful in 75% of patients. (false) b-may predispose to scarring of the skin. (false) c-predispose to candida infection. (true) d-may damage the fetus in utero. (true) e-may predispose o gram negative folliculitits. (true) Comments: Tetracyclines are a frequent and successful treatment of acne but are associated with side effects as teeth staining in utero and should be used in caution in renal impairment.they may predispose to fungal infection. 57-The coomb's antiglobulin test is characteristically positive in haemolytic anaemia associated with : a-chronic lymphocytic leukaemia. (true) b-thalassaemia. (false) c-Systemic lupus erythematosus. (true) d-methyl dopa therapy. (true) e-administration of primaquine. (false)

86

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
58-The production rate of aldosterone: a-increases when sodium intake is reduced. (true) b-is increased when the serum sodium levels falls following administration of water and vasopressin. (false) c-falls to nil after hypophysectomy. (false) d-may be increased in the presence of oedema. (true) e-is increased by a dose of angiotensin which is insufficient to raise the arterial blood pressure. (true) Comments: Aldosterone secretion is increased by rennin secreted by juxtaglomerular apparatus.This is released through reduced circulating plasma volume. Hypovolaemia, hypotension. This causes hypervolaemia which will not stimulate rennin d- example CCF. 59-Opsonization: a-enhances phagocytosis. (true) b-is mediated by certain complement components. (true) c-does not involve immunoglobulins. (false) d-may utilize fibronectin. (true) e-is MHC restricted. (false) comments: a-phagocytosis though possible in saline medium is enhanced in the presence of fresh serum. This is due to opsonins. b-opsonins include C3b, for which phagocytic cells possess a receptor. c-immunoglobulins specially IgG 1 and 3, for the Fc portion of which phagocytic cells possess receptors, are potent opsinizing agents. d-fibronectin acts as a glue for neutrophil-target interaction.it is a glycoprotein. e-opsonization is not MHC restricted. 60-The X chromosome a-carries the gene for sickle cell anaemia.(false) b-of the male forms a Barr body in a buccal smear test. (false) c-is not found in the nuclei of all spermatozoa. (true) d-may show an increased fragility in some conditions. (true) e-carries the gene for the Xg blood group. (true) Comments: The X chromosome/sex chromosome carries the gene responsible for sexual differentiation and may be foud as an inactive Barr body in females ina buccal smear.The gene for sickle cell disease is carried on chromosome 11,whereas X linked conditions as haemophilia A is carried on the X chromosome. Spermatozoa carry 22 autosomes and either X or Y chromosomes. Fragile X condition is associated with narrowing of the arm of the X chromosome. 61-Tricyclic antidepressants: a-relieve depression more quickly than electro-convulsant therapy. (false) b-are associated with an increased incidence of cerebrovascular accidents . (true) c-may cause acute dystonias. (false) d-may cause postural hypotension. (true) e-may cause paralytic ileus in the elderly. (true) Comments:

87

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
TCA effects on depression are much slower than ECT. Like antipsychotics such as respiridine they are associated with an increased risk of CVAs. They have little effect on dopamine receptors ad so do not cause dystonias(metoclopromide typical for this). The postural hypotension, tachycardia, dry mouth, blurred vision, urinary retention, constipation may ensue from anticholinergic effects. 62-Elevated prolactin levels are associated with: a-acromegaly. (true) b-dopamine agonists. (false) c-pregnancy. (true) d-metoclopromide. (true) e-external beam radiotherapy treatment of pituitary tumours. (true) Comments: Acromegaly associated with hyperprolactinaemia either through stalk compression or co secretion of prolactin with growth hormone. b-bromocriptine suppress prolactin secretion unlike metoclopromide which is a dopamine antagonist e-acute though laterhypopituitarism ensues-believed to be related to hypothalamic involvement and reduced dopaminergic control. 63-The following drugs are unsafe in the last 4 weeks of pregnancy: a-warfarin. (true) b-cotrimoxazole. (true) c-Paracetamol. (false) d-methylpenicillin. (false) e-tetracycline. (true) Comments: a-crosses placena and cause haemorrhage. Warfarin is also teratogenic in first trimester. b-neonatal haemolysis and methaemoglobinaemia. Also teratogenic in 1st trimester. C+d are safe. e-dental discolouration, maternal hepatotoxicity in large doses tetracycline best avoided but not unsafe in limited doses. 64-Drugs that reduce gastric acid secretion include: a-aluminum hydroxide. (false) b-omeprazol. (true) c-cimetidine. (true) d-misoprostol. (true) e-prednisolone. (false) Comments: a-simple antacid neutralizes acid but not reduce production. b-proton pump inhibitor, powerful acid suppressor. c-H2 antagonist. d-Prostaglandin E2 analogue,increase mucosal protection and has some antisecretory properties,reduce acid and gastrin secretion. 65-The following drugs have been shown to interact with alcohol: a-griseofulvin. (true) b-triazolam. (true) c-chlorpropamide. (true) d-Metronidazole. (true)

88

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
e-Furosemide. (false) Comments: a-alcohol potentiates its effect. b-alcohol potentiates its effect. c- alcohol potentiates its effect. d-an antabuse reaction occurs due to interference with alcohol dehydrogenase making the side effects of alcohol worse. 66-1,25 dihydroxy cholecalciferol (vitminD):(calcitriol) a-stimulates the absorption of calcium and phosphate from the gut. (true) b-facilitates calcium and phosphate reabsorption from bone. (false) c-stimulates the execretion of calcium and phosphate into renal tubules. (false) d-levels are low during lactation.(false) e-is more active than 24.25(OH)2 vitamin D. (true) Comments: Calcitriol acts on intestines, kidney, and bone to increase calcium and phosphate levels in serum. 24,25 vitamin D is relatively inactive. The main site of action is the intestine,where calcitriol stimulates calcium and phosphate absorption. In the kidney calcitriol promotes renal phosphate resorption in PCT and calcium resorption in DCT. In bone calcitriol facilitates the action of PTH on osteoblasts to increase bone formation. 67-Myxaedaema ay present with: a-fits. (true) b-ataxic gait. (true) c-dementia. (true) d-loss of vision. (false) e-dipolpia. (false) Comments: Other unusual ones include: normocytic/microcytic anaemia, dilutional hyponatraemia, menorrhagia. 68-which of the following are found in pseudohypoparathyroidis: a-brachydactly. (true) b-hypothyroidism. (true) c-low serum calcium, high serum phosphate, normal PTH. (false) d-low serum calcium, high serum phosphate, high PTH. (true) e-Digeorge's syndrome. (false) Comments: Pseudohypoparathyroidism is associated with low serum calcium, high serum phosphate(same abnormalities as hypoparathyroidism) but elevated PTH (hence pseudo).Brachydactly(short 4th metacarpal)is seen. DIGeorge's is absent parathyroid and thymus associated with chromosomal abnormality. 69-The following may cause hypothyroidism: a-amiodarone. (true) b-Allopurinol. (false) c-Doxycycline. (false) d-lthiuim. (true) e-Probenicid. (false) Comments: Also cobal, iodides, butazolidine, sulphonylurea, antithyroid drugs. Amiodarone is a typical drug associated with both hypothyroidism (interferes with

89

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
conversion of T4 to T3 )and hyperthyroidism. 70-Within lymph nodes: a-B lymphocytes predominate in the paracortex. (false) b-primary follicles are aggregates of B cells. (true) c-secondary follicles develop following antigenic stimulation. (true) d-lymph flows from the hilum of the node outwards to the marginal sinus. (false) e-the medulla is rich in plasma cells. (true) Comments: a-B lymphocytes predominate in the follicles in the cortex. T lymphocyte in the paracortex. d-flow of lymph is from marginal sinus through node to afferent lymphatic. e-large numbers of plasma cells are found in the medullary cords. 71-Which of the following regarding Y chromosome is/are true: a-it carries a few loci concerned with metabolism. (true) b-it is the only acrocentric chromosome seen in humans. (false) c-it carries the testis determining factor on its short arm. (true) d-Klinefelter's syndrome has 2 Y chromosomes. (false) e-It may be detected in some phenotypic females. (true) Comments: The main Y gene is called the SRY gene, which specifies maleness and male features.it is the single gene that sets off the initial cascade of hormonal changes that make a person a male.it is not the entire chromosome but just this gene that is necessary for maleness.There is evidence for this in disease where SRY is missing. People who are genetically male with XY chromosomes but with mutation or deletion of this SRY gene on the Y chromosome will be female despite having most of the Y chromosome.and people who are genetically female with XX but have tiny pieces of Y chromosome with this gene will become male despite their XX chromosomes. 72-Natural killer cells: a-are a type of T lymphocyte. (true) b-are predominantly found in lymph nodes. (false) c-express cell surface CD3. (false) d-kill antibody coated cells. (true) e-release tumour necrosis factor. (true) Comments: a-Natural killer cells are type of B or T lymphocyte and are involved in defence against malignancy, virus, bacteria, and parasites. b-rarely found in thymus or lymph nodes unlike T cells. c- NK cells are CD3 negative and have CD16/56(opposite T cells) d-NK kill spontaneously and are stimulated by IL2 or antibody coated cells through binding to their CD16 receptors. e-and IFN gamma, granulocyte, macrophage colony stimulating factor and CSF 1. 73-Long term corticosteroid therapy may be associated wih: a-hypochloraemic alkalosis. (true) b-positive nitrogen balance. (false) c-thrombophlebitis. (false) d-increased gastric acidity. (true) e-sleeplessness. (true)

90

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
Comments: Effects include hyperlycaemia,increased catabolism with increased urea, weight gain, salt and water retension and hypertension, increased osteoclastic activity(reduced bone density and osteoporosis) and CNS effects(depression, anxiety and poor sleep).increased incidence of peptic ulcer wih increased gastric acid secretion and reduces mucosal protection. 74-The thyroid gland: a-develops from the endoderm between the 2nd and 3rd pharyngeal pouches. (false) b-has C cells that are derived from the ultimobranchial body. (true) c-usually weighs about 100g. (false) d-is at the level of the 5th to 7th cervical and 1st thoracic vertebrae. (true) e-may have accessory nodules in the tongue. (true) Comments: a-1st and 2nd pouches. The C cells are responsible for the secretion of calcitonin. c-25 g 75-Cryptospoidiosis in HIV positive patients: a-present with bloody diarrhea.(false) b-can produce up to 10 litres of liquid faeces per day. (true) c-is the commonest cause of diarrhea in these patients. (false) d-is effectively terminated by spiramycin (false) e-can produce sclerosing cholangitits with inflammation and ulceration of intra and extra hepatic bile ducts. (true) Comments: a-eatery c-everyday stool pathogens are commoner.

76-the following can give a biochemical picture indistinguishable from extra hepatic obstructive jaundice: a-chlorpromazine. (true) b-halothane. (false) c-methyltestosterone. (true) d-isoniazid. (false) e-erythromycin estolate. (true) Comments: Extra hepatic would suggest raised bilirubin with raised alkaline phosphatase and GGT B+d- hepatic picture (raised AST and ALT ) c- dose related. 77-mycoplasma pneumonia: a-infection is associated with the development of agglutinins to a non haemolytic streptococcus. (true) b-can be grown on a cell free medium. (true) c-predominantly causes infection n the elderly. (false) d-infection is associated with polymorph nuclear leucocytosis. (false)

91

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
e-infection is associated with steven's Johnson syndrome. (true) Comments: a+cold agglutinins to group O RBCs b-the medium is a complex mixture of heart infusion, peptone, yeast extract, salts, glucose or arginine and horse serum(5-25%) mycoplasma contaminate cell cultures. In the host they form extracellular branched mycellioid structures. 78-Prostaglandin PGI2(prostacyclin) a-reduces arterial smooth muscle tone. (true) b-is a product of arachidonic acid metabolism. (true) c-production is inhibited by NSAID. (true) d-increases platelets cyclic AMP concentration. (true) e-inhibits platelet aggregation to damaged vessel walls. Comments: Prostacyclins reduce arterial tone, is produced from arachidonic acid and is inhibited by NSAIDs. It is involved in platelet aggregation through increasing cAMP concentration. 79-Rubella a-typically has an incubation period of 7-10 days. (false) b-is more frequently associated with palpable splenomegaly than is infectious mononucleosis. (false) c-may be complicated by polyarthralgia. (true) d-is an indication for termination if it occurs in the first 2 months pregnancy. (true) e-can be prevented by vaccination in over 80% of individuals. (true) Comments: Rubella has an incubation period of 14-23 days,the rash lasts about 3 days and is rarely associated with splenomegaly unlike IM. Congenital rubella is a serious problem with gross developmental interference and cardiac abnormalities associated with infection of a non immune patient. Early infection is worse due to organogenesis at this stage. MMR vaccination is very effective with a claim of 90% protection . 80-In non-iatrogenic Cushing's syndrome the following are true. a-the commonest cause in adults is pituitary dependant disease. (true Cushing's disease). (true) b-in the majority of patients with cushing's disease the pituitary fossa on lateral skull x-ray appears normal. (true) c-hypokalaemia is more common in ectopic ACTH syndrome than Cushing disease. (true) d-in Cushing's syndrome associated with bronchial carcinoma the classical findings are usually florid. (false) e-the skin may peel after successful restoration of the eucorticoid state. (true) Comments: Non iatrogenic cushing's syndrome could be due to a pituitary ACTH adenoma(80% of subjects and usually micoadenoma), ectopic ACTH secretion (bronchial carcinoid or bronchogenic carcinoma-signs are often absent as rapid development )or a cortisol secreting adrenal adenoma. (low ACTH) 81-Hirsutism in females: a-when idiopathic is associated with normal plasma testosterone levels. (true) b-can be caused by phenytoin. (true)

92

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
c-when ovarian in oriin, is most commonly due to arrhenoblastoma. (false) d-is a presenting symptom of hyperprolactinaemia. (false) e-may be due to congenital adrenal hyperplasia. (true) Comments: Commonest cause of hirsutism is polycystic ovarian syndrome, can also be caused by medication such as phenytoin and has been associated with valproate. Hirsutism is not a presenting feature of hyperprolactinaemia but hyperprolactinaemia may be associated . i.e:PCOs. Usuallu testosterone concentrations are normal with idiopathic hirsutism but may also be slightly elevated. 82-Beta-thalassaemia major(homozygous) a-is characterized by persistence of Hb F. (true) b-is associated with a chronic marked reticulocytosis. (false) c-is always associated with a raised proportion of HbA2. (false) d-is very rarely associated with nucleated red cells. (false) e-is a cause of pathological fracture of long bones. (true) Comments: Nucleated red cells are always seen, retics low, HbA2 raised in B thalassaemia trait. 83-Actions of glucagon include a-glycogenolysis in the liver. (true) b-inhibition of insulin secretion. (false) c-gluconeogenesis in the liver. (true) d-inhibition of adenyl cyclase. (false) e-a positive inotropic effect on the heart. (true) Comments: Glucagon causes the recruitment of glucose from hepatic stores and has a positive inotropic effect on the heart. Paradoxically stimulates insulin release. 84-The normal metabolic response to a major surgical operation includes: a-antidiiuresis for 12-24 hours. (true) b-retention of sodium. (true) c-increased utilization of glucose. (false) d-increased renal excretion of nitrogen. (true) e-increased rernal excretion of potassium. (true) Comments: Physiological effects of surgery include antidiuresis (increased ADH secretion in an effort to retain water and increase BP), increased catecholamine, cortisol and aldosterone release(increased sodium retention and increased potassium losses)and increased nitrogen excretion. There is decreased utilization of glucose as a consequence of the excess secretion of cortisol/catecholamines. 85-Insulin action: a-Increases liver glycogenolysis. (false) b-increases muscle glycogen synthesis. (true) c-increases liver gluconeogenesis. (true) d-increases liver fatty acid synthesis. (true) e-facilitates red blood cell glucose uptake. (false) Comments: Insulin acts to inhibit lipolysis and gluconeogenesis by promoting glycogenesis. Insulin promotes synthesis of fatty acids in the liver. e-does not increase uptake into brain or liver either.

93

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
86-The following statements concerning syphilis are correct: a-in the primary stage all serological tests for the disease may be negative. (true) b-repeatedly significant treponemal antibody titres are diagnostic of latent syphilis. (false) c-a patient with syphilitic aortitis is at special risk of death following the administration of penicillin. (true) d-in the secondary stage serological tests for the disease are positive in over 90% of cases. (true) e-a baby born to an adequately treated syphilitic woman should be treated if serological tests for the disease are positive in cord blood. (false) Comments: Unlike secondary syphilis where the serology is usually always positive, the serology may well be negative in primary syphilis and the diagnosis depends on the demonstration of T.pallidum in the exudates taken from the chancre. False positive treponemal antibody tests are recognized with Yaws. Due to Jarisch-Herxheimer reaction where there is an acute exacerbation of features following the introduction of therapy patients with syphilitic aortitis or neurosphilis are most at risk. 87-Thiazide dieuretics: a-act on the loop of henle distal to the major site of sodium reabsorption. (true) b-cause hypokalaemia by blocking the sodium potassium exchange site in the distal tubule. (false) c-increase the renal excretion of calcium. (false) d-increase the renal excretion of magnesium, (true) e-elevate LDL cholesterol in long term use. (true) Comments: a-proximal tubule. b-potassium sparing act here. c-decrease,thiazides reduce ion excretion and may lead to hypercalcuria. Other metabolic effects include hyperglycaemia, hyperuricaemia and dyslipidaemia. 88-The human X chromosome: a-has the gene for Duchene muscular dystrophy on its short arm. (true) b-is associated with the Y chromosome side by side during synapse formation in spermatogenesis. (false) c-in the female somatic cell is never completely inactivated. (true) d-is a metacentric chromosome. (false) e-in normal females may be seen as a chromatin body in a buccal smear analysis. (true) Comments: Normally the female complement is 2 X sex chromosomes. One is derived from each parent and one of the pair is also randomly inactivated by a process called lionization at an early developmental stage. A chromatin body may be seen in buccal smears in normal females. It is cleaved from the Y chromosomes during spermatogenesis. 89-Which of the following statements regarding multifactorial inheritance are true or false? a-most isolated neural tube defects belong to this category. (true) b-the recurrence risk in this type does not depend on the previous incidence of the same condition in the family. (false) c-Blood groups are inherited in this manner. (false)

94

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
d-It is due to the effects of a large number of genes and the environment. (true) e-can be diagnosed by chromosome culture. (false) Comments: Polygenic or multifactorial inheritance occurs in conditions as diabetes mellitus, rheumatoid arthritis, NTDs,cardiac defects. Blood groups have a specifeic pattern of mendelian inheritance. 90-Genetic deficiency of thyroid hormaone production. (dyshormonogenesis) a-leads to the formation of a goiter. (true) b-is associated with a diminished ptake of radioactive iodine. (false) c-may be associated with congenital nerve deafness. (true) d-is best treated with iodine in mild cases. (false) e-may produce no signs or symptoms of thyroid deficiency. (true) Comments: Dyshormonogenesis results from a deficiency or absence of one or more of the enzymes involved in thyroid hormone synthesis or secretion. The most common enzyme abnormality is absent or insufficient thyroid peroxidase activity which results in failure of oxidation.(organification. )of iodide to iodine.The iodine will be trapped but not organified. These patients may have enlarged or may be normal gland, an elevated TSH due to decreased levels of thyroid hormones, and a high uptake of I-123 at 4 hours,and Tc pertechnetate. T4 and FTI are usually decreased . The perchlorate washout test will be positive in these patients. Deficient peroxidase activity associated with a familial goiter and deafness or hearing loss is referred to as Pendred's syndrome. 91-Hyperthyroidism: a-diagnosis is untenable if patients gains weight. (false) b-may cause short stature in childhood. (false) c-may be caused by subacute thyroiditis. (true) d-is usually associated with raised serum T3 and reverse T3. (true) e-may be associated with periodic paralysis. (true) Comments: c-in the early stages thyroid hormone may be released from the gland causing transient hyperthyroidism. Typically there is a high ESR and depressed R AIU. 92-X-linked recessive inheritance is recognized in a-Tay-Sach's disease. (false) b-hypophophataemic vitamin D resistant rickets. (false) c-Wisckott-Aldrich syndrome. (true) d-icthyosis. (true) e-Hunter's syndrome. (true) Comments: X-linked recessive inheritance is typified by haemophilia A.can be associated with congenital adrenal hyperplasia although this is usually autosomal recessive a-AR. b-X-linked dominant d-although icthyosis is typically autosomal dominant it can be inherited as X-linked recessive. 93-Campylobacter jejuni: a-attack rates are higher in the elderly. (false)

95

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
b-infections are treated with ciprofloxacin. (true) c-is a recognized pathogen in domestic animals. (true) d-is readily isolated in stool culture. (false) e-cause colitits. (true) Comments: a-young adults and children. b-cipro and erythromycin but most are self limiting. c-transmitted to humans by milk or water infected by wild and domestic animals and poultry. d-requires special conditions:42°c ,microaerobic atmosphere on blood agar with antimicrobials added. e-proctocolitits and enterocolitits may be due to sexually transmitted agents such as campylobacter entamaeba,lymphogranulomma venereum and may be clinically indistinguishable from non infective causes. 94-Tumour necrosis factor: a-is a cytokine released by activated monocytes. (true) b-is formed in the necrotic centres of tumours. (false) c-is involved in cachexia syndrome. (true) d-is the cause of gram negative endotoxin induced toxic shock syndrome. (true) e-causes increased capillary wall permeability. (true) Comments: TNF alpha is a cytokine and induces acute phase proteins from the liver.The main sources in vivo are stimulated monocytes, fibroblasts, and endothelial cells. Physiological stimuli for the synthesis of TNF alpha are IL1, bacterial endotoxins, TNF, PDGF, and oncostatin M. c-also, fever,osteoclastic bone resorption. 95-Bromocriptine: a-will suppress lacation in the puerperium. (true) b-may be a useful adjunct in acromegaly. (true) c-may cause enlargement of the pituitary in a patient with a prolactinoma. (true) d-inhibits dopamine receptors. (false) e-is an ergot derivative. (true) Comments: b-reduces growth hormone in most patients, improve visual fields, diabetes and may even shrink tumour. High doses needed, 10-20 mg/day.Usually produces marked reduction in size of prolactinoma but tumour enlargement and apoplexy has rarely been associated with bromocriptine use. d-Dopamine(DA2) receptor agonist.

96-Hypothyroidism: a-carpal tunnel syndrome is caused by amyloid deposits with the flexor ratinaculum. (false) b-may be associated with a microcytic or macrocytic anaemia. (true) c-may be caused by hashimoto's thyroiditis . (true) d-is the end result of subacute thyroiditis. (false) e-is often associated with pretibial myxoedema. (false) Comments: a-Myxoedematous change.

96

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
d-most end up euthyroid. e-is associated with Graves disease and therefore usually thyrotoxicosis. 97-A female taking an oral contraceptive regularly may complain of breakthrough bleeding or pregnancy if she also took the following drugs: a-cimetidine. (false) b-carbamazepine. (true) c-phenytoin. (true) d-indomethacin. (false) e-rifampicin. (true) Comments: Liver enzyme inducers as carbamazepine, phenytoin, alcohol, smoking, omeprazole and rifampicin would cause increased metabolism of the OCP and result in reduced efficacy. Cimetidine inhibits cyto P450. 98-In an adolescent with insulin dependant diabetes mellitus the following support a diagnosis of diabetic ketoacidosis: a-abdominal pain at onset. (false) b-serum bicarbonate. (true) c-serum glucose 14 mmol/L. (false) d-increased appetite in the past few days. e-shallow respiration. (false) Comments: a-An unusual but recognized feature particularly in children. However does not support diagnosis of DKA. b-suggests metabolic acidosis. c-normoglycaemic DKA can occur and a glucose of 14 does not rule out the diagnosis but it does not support the diagnosis. d-ususally patients are unwell with infections and anorexia. e-respiratory compensation leads to rapid deep (Kussmaul's)breathing 99-Metronidazole: a-is a dihydrofolate reductase inhibitor. (false) b-80% of a per rectal dose is absorbed. (true) c-the dose needs to be adjusted in renal failure. (true) d-is associated with disulfiram like reaction. (true) e-causes peripheral neuropathy. (true) Comments: a-its action is not fully undersood but causes cytotoxic effects in anaerobes by a reduction reaction probably via the hydroxylamine derivative. b-59-94% c-accumulation of metabolites can occur. d- in some patients. e-primariy with high doses of long duration in children. Most commonly ild sensory and reversible. 100-Etidronate: a-decreases the incidence of vertebral frctures in postmenopausal females when used cyclically with calcium. (true) b-binds to hydroxyapatite in bone. (true) c-inhibits osteoclastic resorption of bone. (true)

97

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
d-if used as monotherapy is associated with inhibited bone mineralization. (true) e-exacerbate paget's diseasaae of bone.. (false) Comments: Etidronate a so called bisphosphonates increases bone mineralization and is a treatment for osteoporosis through the inhibition of bone resorption by osteocalsts. d-and can cause fractures. e-is used in the treatment of paget's. _________________ [ 101-Polymerase chain reaction: a-takes several days to complete.(false) b-DNA or RNA can be used as the template. (true) c-helps in diagnosis of infection. (true) d-in diagnostic PCR the exact sequence at both ends of the target region must be known. (true) e-Polymorphisms in the viral genome my result in amplification failure. (true) Comments: PCR is a rapid technique which produces a result in a ew hours.So used for rapid diagnosis of TB where culture mwthods take several weeks.DNA is the standard template but viral RNA can be amplified if enzyme reverse transcriptase is used. Primers used in the reaction must be complementary to the nucleic acid sequence surrounding the region to be amplified therefore these sequences must be known. In HIV and other viruses sequence polymorphism may prevent binding of primers and result in failure of amplification. Primers which were developed for amplification of the predominant clade B strain found in Europeans and Americans have proved unreliable for amplification of other HIV clades from Africa and Asia. 102-causes of thrombocytopenia include: a-low molecular weight heparin. (true) b-aspirin. (true) c-isoniazid. (false) d-D-penicillamine. (true) e-bendroflumethiazide. (true) Comments: a-although it is more typical with unfractionated heparin. b-causes a qualitative reduction in platelet activity and numbers. c-but can cause agranulocytosis. e-and more rarelt pancytopenia. 103-Insulin: a-is secreted mainly as proinsulin. (false) b-has equal biological activity to C-peptide. (false) c-release from he pancreatic beta cell is stimulated by biguanides. (false) d-has a half life of less than 8 minutes when given intravenously. (true) e- › 80% is degraded by the liver and kidney. (true) Comments: Insulin (and C-peptide which is inactive)is secreted by the beta cells within the langerhan as the active molecule following cleavage from preproinsulin, then proinsulin.it is metabolized in the liver and undergoes renal excretion. 104-The Wasserman reaction may be positive in:

98

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
a-Yaws. (true) b-Cat scratch fever. (false) c-systemic lupus eryhtematosus. (true) d-Hashimoto's throiditis. (true) e-Sarcoidosis. (false) Comments: The wasserman reaction is a complement fixation test for syphilis but other spirochetes and phospholipidic disorders as malaria ,SLE,Leprosy give false positive resuls. 105-Bromocriptine therapy may cause: a-dyskinesias. (true) b-retroperitoneal fibrosis. (true) c-gynaecomastia. (false) d-hypertension. (true) e-Raynaud's phenomenon. (true) Comments: d-more often causes hypotension, hypertension, MI, seizures, and mental disorders have been reported in postpartum women given bromocriptine for lactation suppression. 106-Human breast milk: a-can be safely used in babies with galactosaemia. (false) b-contains more protein per milliliter than cow's milk. (false) c-contains less fat per milliliter than cow's milk. (false) d-has a relatively high sodium content. (false) e-contains more carbohydrate per milliliter than cow's milk. (true) Comments: Human breast milk is produced under the influence of prolactin, has less calorific value than cow's milk(less protein, more fat and carbohydrate) and low sodium content. Breast milk is not recommended in galactosaemia due to precipitation of hypoglycaemia. 107-Concerning hepatitis E infection: a-it can be transmitted with hepatitis B. (false) b-it is a recognized cause of chronic liver disease. (false) c-Ct scan of the liver with contrast showsdiagnostic appearances. (false) d-the incidence of chronic liver disease is reduced by administration of alpha interferon. (false) e-it does not result in a carrier state. (true) Comments: e-five hepatitis viruses form a heterogenous group causing similar clinical illness. Hepatitis A,C,D,E are all RNA viruses coming from 4 different families and hepatitis B is a DNA virus. Hepatitis A and E cause acute illness with the formercausing most hepatitis in childhood and hepatitis E being very rare. Hepatitis B,C,D cause chronic morbidity and mortality with B causing a third of cases,hepatitis C a fifth of cases, and D is very rare. Hepatitis D can't occur without B as a helper.Hepatitis B can be treated with interferon alpha, which improves liver disease.

108-A dominant R wave in lead V1 is characteristic in:

99

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
a-pulmonary embolus. (false) b-WPW. (true) c-LBBB. (false) d-hyperkalaemia. (false) e-true posterior myocardial infarction. (true) Comments: a- A ightward shift of axis acutely can produce this in a massive PE bu characteristic implies commonly seen, which isn't b- Type A. C+d leftward shift. 109-which of the following statements are true or false: a-familial hypercholesterolaemia is autosomal dominant. (true) b-alpha thalassaemia is autosomal recessive. (true) c-adult polycystic kidney disease is autosomal dominant. (true) d-Hurler syndrome is autosomal recessive. (true) e-sickle cell anaemia is inherited as an autosomal dominant condition. (false) Comments: Alpha thalassaemia, Hurler's syndrome, and SCD are autosomal recessive, AD conditions include achondroplasia,huntington's, FH and APCKD. 110-The following are autosomal dominant: a-neurofibromatosis type 1. (true) b-cystic fibrosis. (false) c-familial polyposis coli. (true) d-Huntington's chorea. (true) e-adult polycystic kidney. (true) Comments: Autosomal dominant disorders include Huntington's, achondroplasia,neurofibromatosis,adult polycystic kidney, polyposis coli. 111-Genetic aniciaption occurs in: a-cystic fibrosis. (false) b-dystrophia myotonica. (true) c-fragile X syndrome. (true) d-Huntington's disease. (true) e-Marfan syndrome. (false) Comments: b-extreme amplifications are not transmitted through the male line. This explains the occurrence of the severe congenital form almost exclusively in the offspring of affected women.

112-Thype 1 insulin dependant diabetes mellitus is associated with a-about a 1:3 positive family history. (false) b-decreased islet cells antibodies with increasing time from diagnosis. (true) c-an 80% concordance among identical twins. (false) d-high plasma glucagon. (true) e-insulin resistance. (false)

100

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
Comments: a-about 1:10 c-this is the figure for type 2 diabetes, type 1 about 40% d-but suppressible with insulin. e-type 2. In type 1 insulin is low or absent rather than high. 113-Common features of pheochromocytoma include: a-panic attacks. (true) b-bradycardia. (false) c-diarrhoea. (true) d-hypoglycaemia. (false) e-hypokalaemia. (false) Comments: Typical features include:paroxysmal panic attacks, sweats, anxiety, tremor,palpitations, hypertension or postural hypotension.Diabetes is a biochemical feature as is hypokalaemia.It is detected by elevated urine free meta adrenaline or normetadrenaline with high sensitivity and specificity. b-reflex bradycardia. d-hyperglycaemia. e-rarely. 114-Low molecular weight heparin: a-exerts its anticoagulant effect by biding with antithrombin. (true) b-inactivates thrombin more readily than unfractionated heparin. (false) c-has fewer chains containing the unique pentasaccharide sequence(the binding site)than unfcationated heparin. (false) d-has a more potent effect on platelets than does unfractionated heparin. (false) e-is excreted in urine. (true) 115-Vancomycin resistant enterococci: a-cause resistant infective diarrhea. (false) b-produce an enzyme that inactivates vancomycin. (false) c-may be found in healthy community not recently hospitalized. (true) d-high dose ampicillin is the treatment of choice. (false) e-are commonly vancomycin dependant. (false) Comments: a-When they cause clinical problems they are usually UTI, bacteraemia, wound infection, neonatal infection, endocarditis. b-they alter peptidoglycan precursors used to build cell walls.vancomycin binds to DalaD-ala but the resistant enterococci have D-ala-D-lac or D-ala terminating precursors. They acquire genes that produce enzymes to change the precursors. c-2% in UK general practice.,28% in belguim.Community reservoir in meat,poultry and cheese. d-only if the MIC of ampicillin is not too high.Evidence exists for its use in E.faecalis endocarditis 20 g/day. e-some strains only explained by that there is an inability to produce cell walls because vancomycin sensitive precursor genes have been turned off and resistant ones only appear in the presence of vancomycin. 116-There is an increased tendency to thrombosis in a-Behcet's disease (true)

101

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
b-Kawasaki's disease. (true) c-Paroxysmal nocturnal haemoglobinuria. (true) d-homocystinuria. (true) e-metastatic malignancy.(true) Comments: Other acquired causes include:CCF,trauma, surgery, myeloproliferative disease, OCP. Other inherited causes:antithrombin 3, protein C & S deficiency or FVL mutation, dysplasminogenaemia,dysfibrinogenaemia and heparin cofactor 2 deficiency. 117- Circulating anticoagulants have been described in: a-SLE. (true) b-Post-partum. (true) c-homocystinuria. (false) d-haemophilia. (true) e-the elderly. (true) Comments: Circulating anticoagulant usually IgG interfere with coagulation reactions. .the main lab feature are prolonged PT and PTT which persists if normal plasma is added a-these are non specific inhibitors which prolong haemostsis by binding to phospholipids,anti factor 8 antibodies may be seen. B+D+E –antifactor 8 antibodies. c-thrombotic tendency. d-haemophilics who had plasma transfusions. 118-A raised iron levels is seen in: a-thalassaemia major. (true) b-polycythaemia rubra vera. (false) c-myelodysplasia. (true) d-haemochromatosis. (true) e-rheumatoid disease. (false) Comments: a,c-iron overload may be seen in repeated transfusions and reduced wih subcutaneous desferioxamine. (iron chelation) and oral vitamin C d-increased iron absorbtion and deposition in various tissues. 119- X-linked inheritance is seen in : a-achondroplasia. (false) b-Huntington's disease. (false) c-G6PD deficiency. (true) d-haemophilia. (true) e-vitamin D resistant rickets. (true) Comments: X linked inherited conditions include; Haemophilia A, colour blindness, G6PD and vitamin D resistant rickets. In X linked dominant where both sexes are equally affected. A,b-autosomal dominant. e- X linked dominant. 120-Increased sweating is seen in: a-acromegaly. (true) b-phaeochromocytoma. (true)

102

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
c-diabetic ketoacidosis. (false) d-hypoadrenalism. (false) e-insulinoma. (true) Comments: Sweats are seen in association with the menopause, acromegaly,phaeochromocytoma, thyrotoxicosis and hypoglycaemia (insulinoma), old TB, lymphoma, brucella. 122-Tetany may occur in: a-osteoporosis. (false) b-thyroid surgery. (true) c-respiratory acidosis. (false) d-hyperventilation. (true) e-untreated hyperparathyroidism. (false) Comments: Tetany occurs in association with low calcium or magnesium, a-osteomalacia. b-by producing iatrogenic hypoparathyroidism. c-respiratory alkalosis would cause low ionized calcium. d-cause respiratory alkalosis. e-this gives hypercalcaemia. 123-When considering drug therapy during pregnancy: a-Methyl dopa is contra indicated in all stages. (false) b-isotretinoin is indication for termination. (true) c-folic acid supplements should be given to patients taking phenytoin. (true) d-heparin cause CNS damage in the fetus if given in 2nd or 3rd trimester. (false) e-thiazide diuretics have been shown to decrease placental perfusion. (true) Comments: a-it is only hypotensive safe in all stages. b-pregnancy is not advised for 2 years after cessation of treatment. d-but warfarin does. 124-A 21 year old nurse who has been nursing a 6 week old child wih congenital rubella for the last week discovers she is pregnant.She does not remember being vaccinated against rubella: a-congenital rubella is not infectious beyond the 1st few days.she can be reassured. (false) b-she should be given attenuated rubella vaccine immediately. (false) c-blood should be taken for serology. (true) d-gammaglobulin injection upsets later serological diagnosis. (false) e-a rising IgM antibody titre is indicative of recent infection. (true) Comments: a-infectious for weeks.This nurse runs the risk of developing rubella infection herself and the process of investigation is 1st to discover if she has IgG antibodies to rubella signifying immunity. IgM suggests recent infection and if she is not immune then she requires treatment with immunoglobulin. 125-Thrombocytopenia is a recognized adverse effect of the following drugs: a-aspirin. (true) b-oxymethalone. (false) c-thiazide diuretics. (true) d-gold. (true)

103

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
e-dapsone. (false) Comments: a-aspirin causes reduced placental function, thrombocytopenia and increased bleeding time. 126-In the T cell response to antigen: a-a process of affinity maturation of the T cell receptor occurs.(false) b-intact antigen is presented in association with self MHC molecules. (false) c-co-operation with other cell types is required for T cell recognition of antigen. (true) d-gamma/delta + T cells respond to antigen presented in association with MHC class 2 molecules. (false) e-interactions of the TcR with an appropriate Ag/MHC complex activates a resting T cell. (false) Comments: a-affinity maturation in an ongoing immune response is a feature of the antibody response. There is no evidence that a similar process occurs in the T cell response. b-MHC molecules present short antigen derived peptides, not the intact antigen. c-T cells recognize antigen only when presented by self MHC molecules on an antigen presenting cell. d-MHC class 2 molecules present antigen to CD4, alpha , beta, + T cells. Most gamma,delta + T cells do not appear to be restricted by self MHC molecules. e-additional costimulatory signals are required to activate resting T cell. Interaction of the TcR of a resting T cell with an appropriate Ag/MHC complex in the absence of costimulatory signals may lead to the induction of anergy. 127-In acute allergic reactions: a-there is an increase in bradykinins. (true) b-T helper cells are involved. (true) c-there is an increase in the products of 5-lipoxygenase pathway. (true) d-gene for allergy located on chromosome 12. (false) e-may be triggered by acute complement activation. (true) Comments: c-leukotrienes. d-chromosome 6. e-anaphylatoxins. 128-Attacks of hypoglycaemia are a recognized complication of: a-Von giereke's disease. (true) b-galactosaemia. (true) c-G6PD deficiency. (false) d-fructosaemia. (true) e-Gaucher's disease. (false) Comments: Hypolycaemia is a feature of glycogen storage disease as Von giereke's disease and Pompe's disease.and also a feature of galactosaemia, fructosaemia. G6PD deficiency causes anaemia, spherocytosis and haemolysis but not hypoglycaemia. Gaucher's diasease is an inherited metabolic disorder in which glucocerebroside accumulate in spleen, liver, lungs, bone marrow and rarely brain.

104

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
129-The following are true: a-phaeochromocytoma occurs as part of MEN syndrome type 1. (false) b-elevated alkaline phosphatase is a feature of osteoporosis. (false) c-patients with Down's syndrome have an increased incidence of thyrotoxicosis. (false) d-fertility in Kallaman's syndrome is restored by therapy with GnRH. (false) e-elevated urinary VMA can occur in insulin dependant diabetic patients with hypoglycaemia (true) Comments: a-MEN type 2. Osteoporosis typically associated with no abnormalities of bone except fractures where alkaline phophatase may rise. Down have an increased risk of hypothyroidism. Fertility may be restored in Kallaman's partially by LH and FSH therapy. e-also in association with foods as vanilla, beta blockers and ganglion blockers. 130-a single nuclear sex chromatin body will be found in: a-males with Down syndrome.(false) b-most females with Turner's syndrome. (false) c-males with kleinefelter syndrome. (true) d-females wih adrenogenotal syndrome. (true) e-females wih XXX sex chromosome. (false) Comments: Barr body b-only some the mosaics e-2 131-A karyotype: a-may be prepared from chorionic villi of the fetus. (true) b-helps in the diagnosis of chromosome disorders. (true) c-is made from cells arrested at telophase of mitosis. (false) d-from a patau syndrome a patient shows an extra chromosome number 18. (false) e-helps in the identification of the Philadelphia chromosome in chronic myeloid leukaemia. (true) Comments; Karyotype is the chromosomal composition of cells-normal karyotype is 46XX or XY. Patau syndrome is associated with trisomy of chromosome 13. 132-Trinucleotide repeat sequence are seen in: a-cystic fibrosis. (false) b-Duchenne muscular dystrophy. (false) c-myotonic dystrophy. (true) d-fragile X syndrome. (true) e-Leber's optic atrophy. (false) Comments: Also Huntington's chorea 133-Regarding primary genital herpes: a-has an incubation period of 2 months. (false) b-tender inguinal lymphadenopathy frequently occurs. (true) c-oral acyclovir given within 48 hours reduces duration of symptoms. (true) d-first attack is milder than subsequent attacks. (false)

105

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
e-urinary retention is a recognized feature. (true) Comments: The incubation period of genital herpes is about 2 to 12 days. Temder inguinal lymphadenopathy frequently accompanies the primary attack. Oral acyclovir has been shown to be effective treatment for primary genital herpes infection, reducing the duration of local symptoms and virus shedding. The primary infection is generally much more severe than subsequent attacks. Urinary retension, neuralgia and constipation may all occur due to sacroradiculomyelitits. 134-presenting features of hypothyroidism include: a-deafness. (true) b-menorhagia. (true) c-hirsutism. (true) d-enlarged thyroid gland. (true) e-osteoporosis. (false) Comments: Hirsutism is rarely reported in association with hypothyroidism although hair loss also features. Goitre is a frequent feaure in both Hashimoto's thyroiditis and also iodine deficiency. Other presenting features include ataxia/neuronopathies especially compression neuropathiesand the peaches and cream appearance due to hyper beta carotenaemia. Cognitive impairment, macrocytic anaemia and pleural effusion also feature. 135-In a double blind placebo control clinical trial: a-some of the patients are not treated nor given placebo. (false) b-some of the patients receive a placebo. (true) c-the patients do not know which treatment they receive. (true) d-everybody receives both treatments. (false) e-the clinical assessing in the effects of the treatment does not show which treatment the patient has been given. (true) Comments: a-all are treated identically although some are treated with placebo. c-the patients are blind to the treatment choice. d-that would be a double blind crossover study. e-the clinician is blind to the treatment choice. 136-Recognised features of untreated panhypopituitarism include: a-growth of lanugo hair. (false) b-increased insulin sensitivity. (true) c-pigmentation of mucous membrane. (false) d-extreme emaciation. (false) e-low total serum thyroxine concentration. (true) Comments: A and D-anorexia nervosa. Panhypopituitary patients look pale, have fine wrinkled skin and loss of body hair. c-Addison's. There is low T4 and TSH, low sex hormones and LH/FSH with hypocortisolaemia and low ACTH. GH and IGF-1 are also low. 137-The following factors will lower the ESR: a-polycythaemia. (true) b-macrocytosis. (false) c-sickle cell disease. (true)

106

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
d-DIC. (true) e-female gender. (false) Comments: Large cells, less cells and more proteins increase ESR. d-other protein factors that may reduce ESR include hypofibrinogenaemia, dysfibrinogenaemia, hypogammaglobulinaemia, low molecular weight dextran. 138-Physiologically elevated body temperature is found: a-in the tropics. (true) b-following a large meal. (true) c-with emotional disturbance. (true) d-during part of the menstrual cycle. (true) e-during REM sleep. (false) Comments: Elevation of body temperature is a feature of topical climates ,drugs as ecstasy, ovulation and following a large meal. Falls in temperature are typical of sleep. 139-ADH secretion is inhibited by: a-cold. (true) b-increase blood pressure. (true) c-alcohol. (true) d-decrease body fluid tonicity. (true) e-barbiturates. (false) Comments: ADH secretion is inhibited by dilution, cold, increased blood pressure, alcohol, and tetracyclines. Barbiturates and SSRIs as well as sulphonylureas increase secretion. 140-Polyxystic ovary syndrome is associated with: a-primary amenorrhoea. (true) b-hirsutism. (true) c-increased FSH, decreased LH. (false) d-decreased sex hormone binding globulin. (true) e-increased androgens. (true) Comments: a-usually secondary amenorrhoea occurs but rarely it may be primary. b-a particular problem. c-increase LH and decrease FSH. d-because of decreased synthesis in the liver from the effect of androgens. e-increased production from ovaries and adrenals. 141-adverse effects of carbimazole include: a-cholestatic jaundice. (true) b-agranulocytosis. (true) c-impaired renal function. (false) d-alopecia. (true) e-gynaecomastia. (false) Comments: Rarely agranulocytosis and neutropenia is associated but the most worrying side effect, others are pruritits, rash and alopecia, vasculitis rarely. 142-Acyclovir: a-is effective against CMV. (false)

107

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
b-acts ia viral thymidine cycle. (true) c-treats herpes simplx encephalitits. (true) d-decreases recurrence of genital herpes. (true) e-stops herpetic neuralgia. (false) Comments: a-ganciclovir. Is effective against cmv. b-aciclovir is phosphorylated by this pathway and then competes with deoxyguanosine triphosphate for a position in the viral DNA. c-given IV for 10 days. e-prevents herpetic neuralgia if given at the onset of infection but is ineffective later. 143-Diamorphine elixir for the relief of pain in terminal patients: a-initial sedation typically continuewhile drug is administered. (false) b-analgesia is enhanced if cocaine is added. (false) c-constipation is characteristic sequel of treatment. (true) d-dependance occurs rapidly. (false) e-the same amount of pain relief is produced as when the same dose is given via intramuscular injection. (false) Comments: a-sedation occurring in the first few days typically wears off. b-halucinations also occur. c-an aperients should always be added to the treatment regimen. d-adiction is not a problem. e-an intramuscular injection is 3 times more effective than the same oral dose. 144-The following side effects of drugs are describes in the fetus: a-alcoholism producing microcephaly. (true) b-sulphonylureas produce neural tube defect. (false) c-chloroquine producing corneal opacities. (true) d-hydrocortisone producing cleft palates. (false) e-tetacycline producing phocomelai. (false) Comments: Alcohol excess cause fetal alcohol syndrome with micrognatiha,microcephaly,and small fetus. Sulphonyl ureas may produce marked hyperinsulinism in the fetus with fetal hypoglycaemia.Chloroquine like in adults may cause cataracts and opacification.High dose steroids are safe due to ability of placenta to metabolise cortisol to the inactive cortisone.tetracycline causes dental pigmentation. 145-With regard to calcium metabolism and its control: a-the major stimulant to parathyroid hormone secretion is a fall in the plasma unionized calcium concentration. (false) b-in plasma calcium binding to protein is pH dependant. (true) c-calcitonin secretion may be stimulated by alcohol.(true) d-cholecalciferol is 25-hydroxylated in the liver. (true) e-the average daily absorption of calcium from the diet is 10mmol. (true) Comments: Calcium metabolism is mostly under control of PTH and vitamin D. Calcitonin released from the c cells of the thyroid act to reduce calcium. 146-Antimicrobial agents effective against pseudomonas aeroginosa infections include:

108

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
a-gentamicin. (true) b-flucloxacillin. (false) c-cephalexin. (false) d-carbenicillin. (true) e-metronidazole. (false) Comments: others are ceftazidime, ciprofloxacillin.

147-hyperprolactinaemia may be associated with: a-myxaedaema. (true) b-galactorrhoea. (true) c-brommocriptine therapy. (false) d-chlorpromazine therapy. (true) e-non functioning pituitary tumour. (true) Comments: Hyperprolactinaemia is associated with non functional pituitary tumours due to stalk compression.also found in acromegaly and hypothyroidism. c-dopamine agonist used to treat hyperprolactinaemia. Cholorpromazine like haloperidol,domperidone is a dopamine antagonist and causes hyperprolactinaemia. 148-Side effects of thiazide diuretics include: a-hypercalcaemia.(true) b-acute pancreatitis. (true) c-hperglycaemia. (true) d-cholestatic jaundice. (true) e-necrotizing vasculitis. (true) Comments: Side effects of thiazide include,hyperglycaemia,hyperuricaemia,postural hypotension,impotence,hyponatraemia and hypokalaemia,mild calcium elevation,lipid abnormalities. Skin reactions including pemphigoid and rarely necrotizing vasculitis are recognized. 149-The following are true: A-carbimazole is teratogenic and must be avoided in pregnancy. (false) b-skin rashes due to carbimazole are unlikely to recur if therapy is changed to propylthiouracil.(true) c-relapse in thyrotoxicosis is very rare when carbimazole treatment is continued for 2 years. (false) d-carbimazol is secreted in milk. (true) e-symptomatic hypocalcaemia following subtotal thyroidectomy is generally transient. (true) Comments: Carbimazole is used in treatment of thyrotoxicosis with pregnancy. It is associated with aplasia cutis but this may be more associated with thyrotoxicosis per se than the drugs.thionamides are used in thyrotoxicosis for variable periods form 6 months to 2 years,but irrespective recurrence of thyrotoxicosis following withdrawal is of the order of 70% 150-Hyponatraemia is a recognized complication of: a-carbenoxalone therapy. (false)

109

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
b-major surgery. (true) c-hepato-cellular failure. (true) d-congestive heart failure. (true) e-cerebral contusion. (true) Comments: Hyponatraemia can be classified to hypovolaemic,euvolaemic and hypervolaemic states.the former is due to marked dehydration with excessive salt losses, vomiting, Addison's . The middle typically reflects SIADH. The latter due to conditions as CCF, cirrhosis, nephritic syndrome, myxaeddaema.carbenoxalone causes pseudohyperaldosteronism with hypertension,hypernatrraemia and hypokalaemia.Major surgery,pneumonia,subarachnoid,meningitis and injury as well as drugs can induce SIADH. 151-Hyperprolactinaemia may be found in: a-chronic renal failure. (true) b-testosterone therapy. (false) c-pregnancy. (true) d-chlorpropamide therapy. (false) e-LHRH analogue therapy. (false) Comments: Hyperprolactinaemia is caused by dopamine antagonists as chlorpromazine,haloperidol,metoclopramide,sulpiride.concentrations rise dramatically in pregnancy and are elevated in hypothyroidism, acromegaly, renal failure. 152-Concerning secondary lymphoid follicles: a-the cells of the follicle centre are exclusively B-cells. (false) b-immunoblasts are numerous. (false) c-A mantle zone surrounds the follicle centre. (true) d-centrocytes result from mitotic division of centroblasts. (false) e-antigen presenting cells are present. Comments: a-within lymphoid follicles there are tangible macrophages, follicular dendritic cells and T-lymphocytes.however B-cells predominate. b-the majority of immunoblasts are found outside the follicles. c-the mantle zone consists mainly of small B-lymphocytes surrounding the germinal centre. d-centrocytes develop from stimulated B-cells and are thought to give rise to centroblasts. e-antigen presenting dendritic cells are present within the follicles. 153-Which of these statements regarding carriers is/are correct: a-in classical aemophilia A carriers may show clinical features. (true) b-in duchenne muscular dystrophy carriers never produce affected males, if the husband is normal. (false) c-In cystic fibrosis 2 carriers have a 25% risk of having a child affected with the condition. (true) d-carrier states are seen in achondroplasia. (false) e-certain carrier states can be detected using DNA studies. (true) Comments: The carriers of haemophilia A (females) have 40-50% activity of FVIIIc and so are prone at times of stress to potential increased bleeding-menorrhagia.

110

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
Duchenne muscular dystrophy is an X-linked recessive condition-carriers always are the ones to produce the affected males. Cystic fibrosis is recessive and there would be a 50% chance of having an affected child with 2 parents who are carriers. Achondroplasia is dominant, penetrance may be an issue here rather than carrier status. 154-Turner's syndrome(karyotype 45XO)s associated with : a-abnormal breast development. (true) b-infantile lymphaedaema. (true) c-increased incidence of bone fractures. (true) d-coarctation of the aorta. (true) e-primary aamenorrhoea. (true) Comments: Turner's syndrome is associated with delayed pubertal development, a characteristic phenotype, (short, wide carrying angle, shield chest. )due to primary hypogonadism. C-osteoporosis due to oestrogen deficiency. Hypertension is commoner in this condition an coarctation may be found in up to 10% of cases. 155-The following conditions can cause hyperprolactinaemia: a-oral contraceptives. (false) b-metoclopramide. (true) c-hyperthyroidism. (false) d-craniopharyngioma. (true) e-chronic renal failure. (true) Comments: a-oral contraceptives do not cause hyperprolactinaemia. Dopamine antagonists as metoclopramide and haloperidol and new antipsychotics as otanzapine, produce hyperprolactinaemia. Other drugs as MAOI, methyl dopa, reserpine, phenothiazines, butyrophenones, morphine. Craniopharyngioma (as well as any pituitary tumour.)may produce pituitary stalk compression and hyperprolactinaemia. CRF causes hyperprolactinaemia as the consequences of impaired prolactin excretion. Hypothyroidism not hyperthyroidism produce increased prolactin. 156-Hyperosmolar non-ketotic diabetic coma: a-is unusual in the elderly. (false) b-is rarely associated with a blood sugar › 30 mmol/L. (false) c-may cause focal neurologicall signs. (true) d-causes hyperventilation. (false) e-predispose to thrombosis. (true) Comments: a-commonest in the elderly. b-typically d-not associated with acidosis. e-full anticoagulation is part of the treatment. 157-Insulin: a-interacts with nuclear membrane. (false) b-causes an increased glucose protein transport on the endoplasmic reticulum. (false) c-acts via a similar mechanism as steroid receptors. (false)

111

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
d-can be detected in the lymph. (true) e-is synthesized in the alpha cells of islets of Langerhans. (false) Comments: a-cell surface receptors. Insulin binding to its receptor result in receptor autophosphorylation on tyrosine residues and tyrosine phosphorylation of insulin receptor substrates, (IRS-1,2,3)by the insulin receptor tyrosine kinase e-beta. 158-Recognised causes of body hair loss: A-hypothyroidism. (true) b-anorexia nervosa. (true) c-haemochromatosis. (true) d-Cushing's syndrome. (false) e-sheehan syndrome, (postpartum pituitary nerosis). (true) Comments: a-dry and progressively sparse hair. b-loss of axillary and pubic hair although there is also growth of lanugo hair. c-hpogonadism. d-increased hair/hirsuism. e-any cause of hypopituitarism as iron deficiency, cytotoxic drugs, child birth, (telogen effluvium), OCP, antithyroid drugs, anticoagulants, retinoids. 159-Hypoparathyroidism: a-causes short stature, candidiasis, and impaired nail and dental development in children. (true) b-may be a feature of Crohn's disease. (false) c-when due to an abnormality of PTH receptor is termed pseudo-pseudo hypoparathyroidism. (false) d-biochemically is characterized by increased calcium, increased phosphate and normal alkaline phosphatase. (false) e-positive Chvostek's sign can be treated with intravenous calcium. (true) Comments: a-as part of autoimmune polyendocrine syndrome type 1. b-no association. Reduced calcium and high phosphate typify the condition. c-just pseudo hypoPTH. Pseudo-pseudo hypoPTH is where there are typical physical features as short 4th metacarpal but no biochemical abnormality. Tetany can be treated with IV calcium gluconate.

112

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)

‫د‬

‫ر‬: Pharmacology [left] Pharmacology The following antibiotics are usually effective against pseudomonas aeruginosa: 1 F Cephradine. A F Amoxicillin. B T Carbenicillin. C T Gentamicin. D F Trimethoprim. E √ The following antibiotics act on bacterial cell walls: 2 T Penicillin A T Ceftazidime B F Metronidazole C F Clindamycin D F Gentamicin E Comment: Metranidazole inhibit nucleic acid synthesis. Clindamycin and gentamycin inhibit protein synthesis. listeria monocytogenes: 3 T Can grow at 6c. A F Is gut commensal B F Is a gram-negative bacillus C F Infection is best treated with benzylpenicillin D T Is a cause of septicaemia in neonates E Metronidazole: 4 T Is effective against giardia lamblia A T Is effective when administered per rectum B F Should not be administered intravenously C T Is usually effective against entamoeba histolytica D T Interferes with ethanol metabolism E Metronidazole: 5 F Is a folic acid antagonist A F Is ineffective when given per rectum B F Should not be administered intravenously C T Is effective against Entamoeba histolytica D T Interferes with ethanol metabolism E Gentamicin: 6 T Is ineffective systemically when given by mouth A F Is metabolized prior to excretion by the kidney B T May cause damage to the eighth cranial nerve C

113

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
T Is a bacteriostatic drug D T Toxicity is potentiated by frusemide E Co-trimoxazole: 7 T Contains two different drugs. A T Inhibits folic acid synthesis. B T Potentiates the action of warfarin. C F Is bacteriostatic D T Displaces methotrexate from protein binding sites. E Comments 2: Combination of sulphonamide and trimethorpim, with synergistic bactericidal effect through inhibition of folic acid synthesis. It potentiates the effects of warfarin (like erythromycin, isoniazid) and the sulphonamide component can displace methotrexate from its plasma protein binding site.+ The following substances are sympathomimetic amines: 8 T Amphetamines A T Ephedrine B F Histamine C T Isoprenaline D F Chlorpromazine E Sympathomimetic drugs in therapeuticc doses: 9 T Cause tachycardia A F Cause hypotension B F Cause a decrease in cardiac output C T Cause arrhythmias in association with hydrocarbon anaesthetics D F Are contraindicated in thyrotoxicosis E Comments 2: Beta-sympathomimetic drugs in therapeutic doses causes a direct inotropic and chronotropic effect on the heart. There is little or no effect on the mean blood pressure because the increase in blood pressure resulting from increased heart rate and contractility is counteracted by the decrease in total peripheral resistance due to vasodilation in blood vessels perfusing skeletal muscle. Arrhythmias can occur in large doses – tachycardia is commonly associated with their use. Beta-sympathomimetic drugs are not contraindicated in thyrotoxicosis but may produce an increase in heart rate eg you can use beta agonists to treat asthma in a patient with thyrotoxicosis.

The following drugs are beta-sympathomimetic agonists: 10 T Adrenaline A T Noradrenaline B F Phenylephrine C T Ritodrine hydrochloride D F Oxprenolol hydrochloride E Comment: Phenylephrine is α– agonist

Beta sympathomimetic drugs may: 11 F Cause bronchospasm A T Reduce the frequency of uterine contractions B

114

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
F Cause heart block C T Reduce diastolic blood pressure D T Increase blood glucose concentration E Comments 2: These drugs have the following effects vasodilation, bronchial relaxation, intestinal and genitourinary wall relaxation, cardiac stimulation, renin release, glycogenolysis, gluconeogenesis, lipolysis.

The following are beta-mimetic effects 12 F Constriction of bronchioles A T Increased heart rate B F A decrease in the force of cardiac contraction C F Constriction of arterioles in the skin D T Increased glycogenolysis in skeletal muscle E The following agents are bronchodilators: 13 T Salbutamol A F Atenolol B F Prostaglandin F2α C F Morphine D T Prednisolone E The following drugs can cause bronchoconstriction: 14 T Propranolol A F Atropine B T Morphine C F Ritordine D T Aspirin E Comments 2: These bronchoconstrictors act in the following manner - Porpanolol by being a beta blocker and Morphine causes histamine release. Aspirin induced bronchoconstriction is thought to be due to shunting of arachidonic acid into the lipooxygenase pathway or removal of cyclooxygenase product which prevent bronchospasm. Ritodrine is a beta symphatomimetic and atropine is an anticholinergic agent that causes broncodilation.

Ventilation is increased due to stimulation of central receptors by 15 T Nikethamide A T Hypoxia B T Doxapram C F Phenobarbitone D F Salbutamol E The following drugs stimulate myometrial contractility: 16 T Vasopressin A F Nifedipine B F Hydralazine hydrochloride C

115

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
F Salbutamol D F Indomethacin E The following statements describe the action of drugs on the myometrium: 17 T Ergometrine stimulates sympathetic alpha receptors. A F Indomethacin inhibits contractions by blocking prostaglandin receptors. B F Prostaglandin E1 is a stimulant of isolated uterine tissue in vitro. C T Oxytocin requires ionised calcium as a co-factor. D F Magnesium sulphate is a myometrial stimulant. E The following are features of Ergometrine maleate: 18 F It is inactive when administered orally A F The onset of action after intravenous injection occurs in approximately 5 minutes. B T Transient hypertension may occur after its administration C T Parenteral administration may result in vomiting D F Its use is contraindicated in patients with migraine E The following agents inhibit uterine activity: 19 T Magnesium sulphate A T Ritodrine hydrochloride B F Oxprenolol hydrochloride C Fenoterol hydrobromide D T Indomethacin E Recognised unwanted effects of prostaglandin E include 20 F Water retention A F Increased uterine contractility B T Increased small bowel peristalsis C T Flushing of the skin D T Vomiting E Concerning heparins: 21 T Heparin is synthesized in the lungs A T Antithrombin III is necessary for standard heparins to exert their anticoagulant effect B T Factor X is inhibited by low-molecular-weight heparins C T Low-molecular-weight heparins have a longer half-life than standard heparins D T Penicillins potentiate the action of low-molecular-weight heparins E The following statements about drug interactions are correct: 22 T Antacids decrease intestinal absorption of tetracycline. A F The effects of warfarin are potentiated by combined oral contraceptives. B F The action of heparin is opposed by vitamin K C T Alcohol metabolism is impaired by metronidazole D F The effects of bromocriptine are potentiated by chlorpromazine. E The following statements about anticoagulants are correct: 23 T Heparin inhibits the action of thrombin A F The action of heparin is antagonized by vitamin k B T Heparin increases antithrrombin III activity C F The effects of coumarin anticoagulants are decreased by metronidazole D

116

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
T Warfarin is greater than 80%protein-bound in plasma E Aspirin: 24 T Inhibits cyclooxegenase. A F Is the treatment of choice in childhood fever. B T Is contraindicated in gout. C T Should be avoided by women in anticoagulant therapy. D T Has little anti –platelet activity when given in low dosage. E Propanolol: 25 F Is a selective beta adrenergic blocking agent A F Is not secreted in breast milk B T Given in pregnancy slows the maternal heart rate C T Causes bad dreams D T Antagonises the tocolytic effect of salbutamol E The following anti-hypertensive agents are correctly paired with their mode of action: 26 T Captopril : angiotensin –converting enzyme inhibition A T Phentolamine : alpha adrenoceptor blockade B F Methyldopa : ganglion blockade C F Hydralazine hydrochloride : angiotensin II inhibition D T Sodium nitroprusside: vasodilatation E The following drugs are potassium sparing diuretics: 27 T Amiloride hydrochloride A T Triameterene B T Spironolactone C F Chlorothiazide D F Frusemide E Hypokalaemia may be caused by: 28 T Bendrofluazide A F Digoxin B F Spironolactone C T Carbenoxolone D F amiloride E Comments 2: Carbenoxolone may cause hypokalaemic hypertension like liquorice through inhibition of 11beta hydroxysteroid dehydrogenase (11bHSD). Bendroflumethiazide is a thiazide diuretic and promotes potassium excretion. Amiloride, like spironolactone is a potassium sparing diuretic and causes hyperkalaemia. Digoxin toxicity is exacerbated by hypokalaemia but it does not cause hypokalaemia.

The following substances exert their diuretic actions upon the distal convoluted tubule: 29 T Bendrofluaside A F Fusemide B F Bumetanide C F Mannitol D F Alcohol E Fluid retention may be caused by the administration of: 30

117

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
F Spironolactone A F Chlorothiazide B T Diethylstilboestrol C T Carbenoxolone D T Prednisolone E Parenteral administration of atropine in therapeutic doses to a normal person causes: 31 T Impaired visual accommodation. A F Diarrhoea. B F Constriction of the bronchi. C T An increase in heart rate. D T A reduction in bronchial secretions. E Subcutaneous atropine injection characteristically produces 32 T An increase in heart rate A F An increase in salivation B F Constriction of the pupil C F A hypnotic effect D T Decreased bronchiolar secretion. E The following drugs have anti-cholinergic effects: 33 T Propantheline bromide. A F Carbachol. B F Distigmine bromide. C T Benzhexol. D T Atropine. E Comment: Carbachol- Nicotinic Agonists. Benzhexol - used in Parkinson‘s disease and is MUSCARINIC ANTAGONISTS. Atropine is MUSCARINIC ANTAGONISTS. Propantheline bromide is ANTI-MUSCARINIC DRUGS FOR URINARY FREQUENCY, ENURESIS AND URGE INCONTINENCE.

The following have an antiemetic action: 34 T Hyoscine hydrobromide A F Morphine sulphate B T Chlorpropamide C T Promethazine hydrochloride D T Perphenazine E Comments 2: Hyoscine is an alkaloid, Promethazine is an antihistamine, Perphenazine is an antipsychotic and all 3 have antiemetic properties. The sulphonyl urea chloropropramide may have antiemetic properties and has thus been marked as true. Morphine has an emetic action.

The following statements are true: 35 F Suxamethonium is non-depolarising muscle relaxant. A F Huxamethonium is a ganglion blocker. B T Tubocurarine is reversed by neostigmine C F Streptomycin is absorbed from the gastrointestinal tract D F Thiopentone can be given intramuscularly. E

118

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
The following stimulate peristalsis in the large bowel: 36 F Opiates A T Liquid paraffin B F Suxamethonium chloride C T Neostigmine D T Senna glycoside E Treatment with morphine: 37 T Causes respiratory depression A F Increases gastric motility B T Causes side effects which may be reversed by naloxone C T Increases the secretion of antidiuretic hormone D F Causes papillary dilatation E

Treatment with morphine: 38 T Causes respiratory depression A F Increases gastric motility B T Causes side effects, all of which may be reversed C T Increases the secretion of anti-diuretic hormone D F Causes papillary dilatation E The following statements about morphine are true: 39 T All of its pharmacological actions are reversed by naloxone A T It is transferred into breast milk B F It does not cross the placenta in significant quantites C F Its analgesic effects last about 1 hour D F It causes papillary dilatation E Neostigmine in therapeutic doses: 40 F Acts for several days A T Inhibits hydrolysis of acetylcholine B F Causes paralytic ileus C F Reverses the action of carbachol D T Relieves the effects of myasthenia E Lignocaine used as a local anaesthetic: 41 T Cause tachycardia if given as systemic injection A F Has a longer lasting action than bupivicaine B F Is used in combination with adrenaline for ring block C F Causes vasoconstriction D T Is a week base E Comments 2: Lidocaine may cause tachycardia and rise in blood pressure on IV administration. Bupivicaine has a longer lasting action than lidocaine. Adenaline is a vasoconstrictor and cannot be used in

119

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
organs with end-arteries. Local anaesthetics cause vasodilataion. All local anaesthetics are weak bases.

Halothane produces: 42 T Cardiac arrhythmias A F Explosive mixtures with air B T Liver damage if given repeatedly C T Myometrial relaxation D F Bronchial irritation E Thiopentone sodium administered intravenously: 43 F Is a potent muscle relaxant A F Is predominantly excreted by the kidney B T Binds to protein C T Is fat soluble D T Crosses the placenta E Oestrogen therapy raises the plasma concentrations of: 44 T Thyroxine binding globulin. A F Free cortisol. B T Transferring. C F Albumin. D F Folate. E The following compounds are predominantly progestogens: 45 F Buserelin A T Dydrogesterone B T Norethisterone C T 17 α -hydroxyprogesterone D F Androstenedione E The effectiveness of a combined oral contraceptive may be reduced by: 46 F Bromocriptine A T Phenytoin B T Rifampicin C T Ampicillin D F Sodium valproate E Clomifene citrate: 47 F Is an anti-androgen A T Does not stimulate ovulation directly B T Can produce visual disturbances C T Is generally prescribed throughout the proliferative phase of the menstrual cycle D T In the treatment of an ovulation, increases the risk of multiple pregnancy E Cyproterone acetate 48 F Is an oestrogen A F Is used for the treatment of amenorrhea B T Bind to androgen receptors C F Increases libido D T Inhibits spermatogensis E

120

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
The following are cytotoxic alkylating agents 49 T Cyclophosphamide A F Mercaptopuracil B T Chloroambucil C F Fluorouracil D F Methotrexate E The following drugs may cause enlargement of the fetal thyroid gland: 50 F Methyldopa A F Thyroxine B T Carbimazole C F Propranolol D T Propylthiouracil E The following substances lower the blood glucose concentration: 51 F Adrenaline A T Chlorpropamide B F Chlorothiazide C T Metformin D F Thyroxine E The following drugs and side effects are associated: 52 T Carbenoxolone : sodium retention A F Chlorothiazide: hypoglycaemia B F Salbutamol: bronchospasm C T Clonidine: rebound hypertension D T Phenytoin: folate deficiency E The following drugs and side effects are associated: 53 T Methyldopa:depression A F Paracetamol: thromboembolism B T Indomethacin:peptic ulcer C T Prednisolone :osteoporosis D F Ritodrine:hypoglycaemia E The following substances increase the serum uric acid concentration: 54 F Colchicine A T Cholorothiazide B F Allopurinol C F Probenecid D F Phenylbutazone E The therapeutic effect of the first drug is enhanced by the second drug: 55 F Phenytoin: ethinyloestradiol A F Bromocriptine: metoclopramide B T Penicillin: probenecid C T Ritodrine: dexamethasone D F Warfarin: phenobarbitone E The following factors enhance the transplacental passage of drugs: 56 T Lipid solubility A

121

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
F A high degree of ionic dissociation B F High molecular weight C F Protein binding D F Uterine contractions E The following drugs diminish detrusor contractions: 57 T Atropine. A F Carbachol. B T Propantheline. C T Nifedipine. D F Distigmine. E Comments 2: Atropine has anticholinergic effects. Carbachol causes the detrusor muscle to contract. Propantheline has antimuscarinic and ganglionic-blocking effects Nifedipine – calcium antagonist - Influx of extracellular calcium is important for detrusor muscle contractions and this can be blocked by calcium antagonists. Distigmine does not have any effect on detrusor contractility.

The following drug combinations have been shown to interact to produce the stated effects: 58 T Ampicillin enhances the anticoagulant action of warfarin. A T Aciclovir diminishes the effect of oral contraceptives. B F Cimetidine inhibits the metabolism of phenytoin. C T Aspirin diminishes the action of ritodrine. D F Tamoxifen increases the anticoagulant effect of warfarin. E Comment: Oestrogens (including tamoxifen) are pro-thrombotic and antagonise warfarin effects *. Anti-viral agents - nevirapine, nelfinavir, ritonavir - induce hepatic enzymes *.

The following cytotoxic drugs are correctly classified: 59 F Methotrexate: alkylating agent A T Cyclophosphomide: alkylating agent B F Vinblastine: antimetabolite C T Mercaptopurine: antimetabolite D F Fluoruracil: antibiotic E The following drugs should be avoided in renal impairment: 60 T Cephalothin A T Cisplatin B F Norethisterone C F Dopamine D T Gentamycin E [/left]

PATHOLOGY AND IMMUNOLOGY MCQS 85 STEM 27 √ Metastatic calcification may be seen in the following conditions: 1

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DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
F Old pulmonary tuberculosis. A √ F Degenerationg leiomyomata. B T Multiple myeloma. C T Hyperparathyroidism. D T Sarcoidosis. E Comment Metastatic calcification is the deposition of calcium salts in normal tissues and always reflects some derangement in calcium metabolism (hypercalcemia). Hypercalcemia causes by: 1\ increase secretion of parathyroid hormone. 2\ destruction of bone (Paget disease, immobilization, multiple myeloma and leukemia. 3\ vitamin D intoxication and sarcoidosis. 4\ renal failure. TISSUE CALCIFICATION ***** • DYSTROPHIC - calcium deposition in tissues in the presence of normal plasma calcium and phosphate levels • Occurs in old infarcts, fat necrosis, site of dead parasites, previous TB granulomas, scarred heart valves • METASTATIC *- occurs in normal tissues in the presence of hypercalcaemia • Associated with hyperparathyroidism, hypervitaminosis D, sarciodosis, milk-alkali syndrome, bone metastases associated with malignant disease and multiple myeloma √ Metastasis to lymph nodes are commonly associated with: 2 F Fibrosarcoma. A √ T Malignant melanoma. B F Medullablastoma. C T Seminoma of the testis. D F Basal cell carcinoma of the skin. E Comment 2: Lymph node metastases are frequent in lymphomas and carcinomas but are less typical of sarcomas. BCC seldom metastasizes, whereas fibrosarcoma would metastasise more commonly to specific organs. Medulloblastoma seldom metastasizes beyond the brain. Seminoma may metastasize first to the para-aortic lymph nodes. √ Early blood-borne dissemination is characteristic feature of: 3 F Carcinoma of the endometrium. A T Osteosarcoma. B F Basal cell carcinoma. C F Carcinoma of the cervix. D T Choriocarcinoma. E A metaplastic process is involved in the histogenesis of the following tumors: 4 F Squamous cell carcinoma of the vulva. A T Squamous cell carcinoma of the bronchus. B F Scirrhous carcinoma of the breast. C T Squamous cell carcinoma of the cervix. D T Adenocarcinoma of the oesophagus. E Comment: METAPLASIA ***** • Reversible change in which one adult cell type is replaced by another adult cell type • May be an adaptive response, for instance, squamous metaplasia in the respiratory tract in response to chronic irritation • In smokers, the normal ciliated columnar epithelium is often replaced by focal areas of stratified squamous epithelium

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DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
• The influences that cause metaplasia, if persistent, may induce malignant transformatio n in metaplastic epithelium - thus the commonest form of cancer in the respiratory tract is squamous cell carcinoma * • In patients with persistent oesophageal reflux, the distal oesophagus may become lined with columnar secretory epithelium instead of stratified squamous epithelium – Barrett‘s oesophagus. This may undergo malignant transformation into an adenocarcinoma * • In the ovary, the coelomic epithelium can undergo metaplasia into serous, mucinous or endometroid types which undergo malignant transformation into serous, mucinous or endometroid adenocarcinomas* • Metaplasia may also occur in mesenchymal cells, for instance, bone being formed in areas of soft tissue injury A metaplastic process is involved in the histogenesis of the following tumors: 5 F Squamous cell carcinoma of the vulva. A T Squamous cell carcinoma of the bronchus. B F Scirrhous carcinoma of the breast. C T Squamous cell carcinoma of the cervix. D F Adenocarcinoma of the ovary. E Comments 2: A metaplastic process may be found preceding the development of many overt carcinomas, particularly cervical, carcinoma of the oesophagus and gastric (Barrett's Oesophagus) and bronchial carcinoma. Comment: METAPLASIA ***** • Reversible change in which one adult cell type is replaced by another adult cell type • May be an adaptive response, for instance, squamous metaplasia in the respiratory tract in response to chronic irritation • In smokers, the normal ciliated columnar epithelium is often replaced by focal areas of stratified squamous epithelium • The influences that cause metaplasia, if persistent, may induce malignant transformation in metaplastic epithelium - thus the commonest form of cancer in the respiratory tract is squamous cell carcinoma * • In patients with persistent oesophageal reflux, the distal oesophagus may become lined with columnar secretory epithelium instead of stratified squamous epithelium – Barrett‘s oesophagus. This may undergo malignant transformation into an adenocarcinoma * • In the ovary, the coelomic epithelium can undergo metaplasia into serous, mucinous or endometroid types which undergo malignant transformation into serous, mucinous or endometroid adenocarcinomas* • Metaplasia may also occur in mesenchymal cells, for instance, bone being formed in areas of soft tissue injury √ The following agents are correctly paired with the named tumors: 6 F Androgenic steroids: vaginal clear cell adenocarcinoma. A T Aflatoxins: liver cell carcinoma. B F β-naphthylamine: bronchial carcinoma. C √ T Asbestos: peritoneal mesothelioma. D T Vinyl chloride: hepatic angiosarcoma. E Comment Clear cell carcinoma is associated with synthetic steroid (diethylstilbestrol). β -naphthylamine causes bladder cancer. CARCINOGENIC CHEMICALS *****

124

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
• Include synthetic and natural compounds • May act directly or require metabolic conversion in vivo to produce the ultimate carcinogen • Most carcinogens are metabolised by cytochrome P-450 dependent enzymes 1) Direct-acting alkylating agents: used for chemotherapy and treatment of auto-immune disorders. Drugs like cyclophosphamide increase the risk of induced cancer 2) Polycyclic aromatic hydrocarbons - cause a wide range of cancers including skin cancer, sarcomas and organ-specific cancers. The ultimate carcinogen is dihydrodiol epoxide 3) Aromatic amines and Azo dyes - mainly affect the liver where the ultimate carcinogen is formed by P450 dependent enzymes. Beta-naphthylamine is the exception - associated with increased risk of BLADDER cancer in workers in aniline dye and rubber industries * 4) Aflatoxin B1 *- naturally occurring, produced by some strains of Aspergillus flavus which grows in poorly stored grains and peanuts. Causes hepatocellular carcinoma following activation in the liver to produce dihydrodiol epoxide 5) Nitrosamines and amides may be involved in gastric cancer 6) Asbestos - *bronchial carcinoma, mesothelioma and GI cancers 7) Vinyl chloride - 8hemangiosarcoma of the liver Inhaled chromium and nickel - lung cancer 9) Arsenic - skin cancer Growth of the following tumors is hormone dependent: 7 F Squamous cell carcinoma of the cervix. A T Breast adenocarcinoma. B T Uterine leiomyoma. C T Prostatic adenocarcinoma. D F Testicular carcinoma. E Comment: HORMONE-DEPENDENT TUMOURS ***** • Endometrial adenocarcinoma - oestrogen • Breast cancer - oestrogens and progestogens • Prostate cancer - androgens • Some melanomas - oestrogen • Fibroids - oestrogen Uterine fibroids: 8 T Are defined histologically as fibromyxomas. A T Arise from endometrial stroma. B T May be associated with polycythaemia. C F Predispose to endometrial hyperplasia. D F Are liable to sarcomatous change in about 5% of cases. E Comment Sarcomatous change in 0.2%. may be associated with polycythaemia , iron deficiency anaemia is more common as a result of menorrhagia. Not pre-malignant. UTERINE LEIOMYOMAS (FIBROIDS) ***** • Benign tumours of the uterine smooth muscle • Not encapsulated but the compressed surrounding myometrium may give a capsulated appearance • May be sessile or pedunculated • May be sub-serosal (sub-peritoneal), intramural or sub-mucosal (immediately beneath the endometrium) • Sub-serosal fibroids may become attached to the omentum or pelvic peritoneum, forming parasitic leiomyomas

125

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
• Present with an irregularly enlarged uterus and are a recognised cause of menorrhagia. Other symptoms include abdominal discomfort, frequency of micturiction, dysmenorrhoea • Histologically consist of bundles of smooth muscle fibres with varying degrees of fibrous connective tissue * • Oestrogen sensitive. Atrophy after the menopause and increase in size during pregnancy and may obstruct labour • May undergo calcification, hyaline degeneration, torsion, & infarction. Red degeneration typically occurs in association with pregnancy • Not pre-malignant * • May be associated with polycythaemia *although iron deficiency anaemia is more common as a result of menorrhagia

√ The following pairs indicate correct pathological association: 9 T Epstein-Barr virus: Burkett's lymphoma. A T Peutiz-Jeghers syndrome: intestinal carcinoma. B F Wood dust: pleural mesothelioma. C F Progestagens: endometrial carcinoma. D T Aniline dyes: bladder carcinoma. E Comment Wood dust causes nasal sinuses The following tumors produce characteristic blood markers: 10 F Clear cell carcinoma. A T Choriocarcinoma. B F Osteogenic sarcoma. C T Yolk sac tumor. D F Transitional cell tumor. E Comment: TUMOUR MARKERS ***** Hormones • Human chorionic gonadotrophin - trophoblastic tumours, non-seminomatous testicular tumours * • Calcitonin - medullary carcinoma of the thyroid • Catecholamines and metabolites - phaeochromocytoma Onco-fetal antigens • Alpha-fetoprotein - hepatocellular carcinoma, non-seminomatous germ cell tumours of testis, ovarian endodermal sinus / yolk sac tumour * • Carcino-embryonic antigen - carcinoma of the colon, pancreas, lung, stomach, breast Enzymes • Prostatic acid phosphatase - prostatic carcinoma. • Neuron-specific enolase - small cell carcinoma of the lung, neuroblastoma Specific proteins • Immunoglobulins - multiple myeloma • Prostate specific antigen - prostate cancer Glycoproteins • CA-125 - ovarian cancer *

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DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
√ Concerning the adrenal gland: 11 F The cortex is derived from neural crest cells. A F The zona fasciculate secretes aldosterone. B T Cortical adenomas may cause Cushing syndrome. C T Neuroblastomas arise in the medulla. D T Addison's disease may result from autoimmune destruction of the cortex. E √ In tumors of bone: 12 √ F Primary malignancy is more common than secondary malignancy. A F Osteoma rarely present in skull bones. B T Osteosarcoma is associated with paget's disease of bone. C T Lymph node metastases are unusual. D T Simple bone cysts have a strong tendency to recur. E Comment The commonest tumor in bone is secondary carcinoma. The commonest sites are the proximal bones: the skull, spine, pelvis and the proximal ends of humerus and femur. TUMOURS ***** • The commonest malignant tumour in bone is a secondary deposit * • In adults, malignant primary bone tumours are more common than benign tumours. Osteosarcoma is commonest, followed by chondrosarcoma and Ewing's tumour. The peak incidence of osteosarcoma is the second decade* • In the first decade of life, only 15-20% of primary bone tumours are malignant • Patients with retinoblastoma have a 500 fold increased risk of osteosarcoma. Risk also increased in Paget's disease of bone. * • All osteosarcomas are aggressive tumours and metastasise rapidly via the bloodstream to the lungs. Lymph node involvement is unusual * • Osteomas are sessile tumours composed of sclerotic, well-formed bone projecting out from cortical surfaces, most often of skull and facial bones. Often protrude into one of the air sinuses *. Only need to be excised if they cause obstruction or pose a cosmetic problem. The following are premalignant conditions: 13 F Diverticular disease of the large bowel. A T Ulcerative colitis. B T Pulmonary asbestosis. C T Paget's disease of the bone. D F Condylomata lata of the vulva. E Comment HPV, HSV infections, vulvar dysplasia, low socioeconomic class and history of vulvar dystrophies are associated with increased incidence of vulvar carcinoma. Vulvar condylomas are not precancerous. Pre-neoplastic conditions • Neurofibromatosis - autosomal dominant, gliomas of the brain and optic nerve, acoustic neuromas, meningioma, phaeochromocytoma • Tuberous sclerosis - autosomal dominant, glial tumours, harmatomas • Xeroderma pigmentosa -autosomal recessive, basal and squamous cell carcinoma of the skin, malignant melanoma • Fanconi‘s anaemia - autosomal recessive, acute leukaemias • Ataxia telangiectasia - autosomal recessive, acute leukaemia, lymphoma and breast cancer in females ACQUIRED PRE-NEOPLASTIC CONDITIONS **** • Endometrial hyperplasia, especially atypical hyperplasia

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DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
• • • • • • • • • • • Cervical intra-epithelial neoplasia * Vulval intra-epithelial neoplasia Bronchial squamous metaplasia Pulmonary asbestosis * Cirrhosis of the liver * Chronic atrophic gastritis Chronic ulcerative colitis * Solar keratosis of the skin Leukoplakia of the oral cavity, penis and vulva Paget's disease of bone Pulmonary asbestosis

Adenocarcinoma of the large bowel: 14 √ T Most common originates in the ascending colon. A T May develop as a single polyp. B T May show signet ring features histologically. C F Characteristically metastasis to the liver before the lymph nodes. D T Is a recognized complication of long-standing ulcerative colitis. E Comment: MALIGNANT COLONIC TUMOURS ***** • 60-70% located in the rectum and sigmoid colon. However, the incidence of carcinoma of the right colon is increasing * • Over 95% are adenocarcinomas * • May arise from a single polyp of from multiple polyps in patients with familial polyposis coli * • Associated with dietary factors such as low vegetable fibre, high fat and high refined carbohydrate content. Oestrogen and NSAIDs may be protective • Peak incidence in the 7th decade. Male : female = 2 : 1 • May be fungating, ulcerating or infiltrating. Right sided tumours tend to be fungating but because of the wide diameter of the caecum, rarely cause obstruction while left sided tumours tend to be infiltrating and cause annular constriction of the bowel • Spread is to regional lymph nodes. Haematogenous spread to liver, lungs and brain is late * • Associated with increased levels of CEA (Carcino-embryonic antigen) in 19-40% of patients. Mucinous carcinomas produce mucin which may accumulate within the cells, pushing the nucleus to one side and giving the cell a signet ring appearance * May be the primary in a woman with a Kruken The following statements relate to embryonic tumors: 15 F An ovarian teratoma is usually malignant. A F A nephroblastoma may be benign. B T A neuroblastoma can arise in the adrenal medulla. C F A hamartoma is usually malignant. D T Choriocarcinoma may arise in a teratoma. E Comment: GERM CELL TUMOURS • 15-20% of all primary ovarian tumours • May be benign (mature terratomas, gonadoblastoma) or malignant TERRATOMAS • Result from the differentiation of germ cell tumours into embryonic tissue MATURE TERRATOMA - DERMOID CYST ***** • Tissues are microscopically similar to those seen in adult tissue

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DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
• Benign • Most are cystic. The mature cystic terratoma or dermoid cyst accounts for 15 -20% of all ovarian neoplasms • Large thick walled cyst with hair and sebaceous material. Typically lined by stratified squamous epithelium. May contain teeth, cartilage, thyroid tissue or respiratory epithelium • Malignant change supervenes in 1% of dermoid cysts and is usually a squamous cell carcinoma IMMATURE TERRATOMA ***** • Make up ~5% of all terratomas. Contain immature tissue of either ectodermal, mesodermal or endodermal origin with immature neural tissue being the most common • Only germ cell tumour for which histological grade is of prognostic significance • Contra-lateral ovary contains mature terratoma in 10-15% of cases OVARIAN CHORIOCARCINOMA ***** • Usually a secondary from a uterine tumour • Primary ovarian choriocarcinoma is rare and develops from germ cells • Solid tumours, typically unilateral with cytotrophoblasts and syncytiotrophoblasts on histological examination. Produce HCG HAMARTOMAS • Local malformations in which normal cells are present in abnormal proportions - such as moles. • Usually present from birth and growth is not progressive • Neither malignant nor pre-malignant. √ The following tumors are correctly paired with likely causative agents: 16 F Angiocarcinoma of the liver: vinyl chloride. A F Carcinoma of the colon: dietary fiber. B T Hepatoma: aflatoxins. C F Carcinoma of the bronchus: coal dust. D T Carcinoma of the bladder: beta naphthylamine. E Comment: CARCINOGENIC CHEMICALS ***** • Include synthetic and natural compounds • May act directly or require metabolic conversion in vivo to produce the ultimate carcinogen • Most carcinogens are metabolised by cytochrome P-450 dependent enzymes 1) Direct-acting alkylating agents: used for chemotherapy and treatment of auto-immune disorders. Drugs like cyclophosphamide increase the risk of induced cancer 2) Polycyclic aromatic hydrocarbons - cause a wide range of cancers including skin cancer, sarcomas and organ-specific cancers. The ultimate carcinogen is dihydrodiol epoxide 3) Aromatic amines and Azo dyes - mainly affect the liver where the ultimate carcinogen is formed by P450 dependent enzymes. Beta-naphthylamine is the exception - associated with increased risk of BLADDER cancer in workers in aniline dye and rubber industries * 4) Aflatoxin B1 *- naturally occurring, produced by some strains of Aspergillus flavus which grows in poorly stored grains and peanuts. Causes hepatocellular carcinoma following activation in the liver to produce dihydrodiol epoxide 5) Nitrosamines and amides may be involved in gastric cancer 6) Asbestos - *bronchial carcinoma, mesothelioma and GI cancers 7) Vinyl chloride - hemangiosarcoma of the liver Inhaled chromium and nickel - lung cancer 9) Arsenic - skin cancer Adenocarcinoma is the commonest type of primary malignant tumor to occur in the: 17 F Bladder. A

129

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
F T T F Lung. B Oesophagus. C Fallopian tube. D Testis. E

Carcinoma in situ in epithelium (intraepithelial neoplasia) is characterized by: 18 T Increased mitotic activity. A T Loss of polarity. B F Increased adhesiveness to the underling stroma. C T Pyknosis. D T Increased thickness of the epithelium. E Comment: CERVICAL INTRA-EPITHELIAL NEOPLASIA **** • Histological diagnosis made following cervical biopsy. The abnormality originates at the squamo-columnar junction • Pre-malignant although CIN I and probably CIN II regresses spontaneously • Associated with HPV 16, 18, 31, 33 * • Atypical cells are characterised by: 1) Loss of cell polarity 2) Loss of maturation 3) Increased nuclear : cytoplasmic ratio with nuclear and cytoplasmic pleomorphism 4) Increased number of mitotic figures and the presence of abnormal mitotic figures • CIN I - dysplastic cells are confined to the lower third of the epithelium • CIN II - dysplastic cells are confined to the lower two thirds of the epithelium • CIN III - the entire thickness of the epithelium is involved √ The parathyroid glands: 19 F Originate from the pharyngeal cleft ectoderm. A T Secrete parathyroid hormone via the chief cells. B F Secrete calcitonin via the oxyphil cells. C T May become hyperplastic in the presence of intestinal malabsorption. D T May develop adenomas in association with islet cell tumours of the pancreas. E √ The following conditions may lead to hydronephrosis: 20 F Mercury poisoning. A T Cervical carcinoma. B T Renal calculi. C F Renal vein thrombosis. D T Posterior urethral valves. E Acquired diverticular disease of the colon: 21 T Is present in at least 15% of Caucasians over the age of 50 years. A T Is due to a congenital abnormality of the bowel wall. B T Is associated with increased intra-luminal pressure. C F Is associated with muscular thickening. D T May result in intestinal obstruction. E Comment: DIVERTICULAR DISEASE ***** • Saccular out-pouchings of the colon that develop in the recto-sigmoid with advancing age. Herniations of the mucosa and sub-mucosa at points of muscular weakness * • Asymptomatic in the majority of cases • Commoner in developed countries. Rare in those < 30 years old. Present in over 50% of those aged over 60 years *

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DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
• Arises as a result of increased intra-luminal pressure (constipation, low fibre diet) and foci of muscular weakness in the colonic wall * • 95% located in the sigmoid colon. There is hypertrophy of the musculature*of the affected segment and the taeniae coli are more prominient with 0.5-1cm flask-like out-pouchings at their margins. The walls of the diverticula are composed of flattened mucosa, compressed submucosa and thin or absent muscularis. • Complications include acute inflammation, abscess formation, fistulas and strictures with obstruction following recurrent inflammation • Not pre-malignant Obstruction of the lower end of the common bile duct is suggested by: 22 T An elevated serum conjugated bilirubin concertration. A F A reduced serum alkaline phosphatase concentration. B T The presence of urobilinogen in the urine. C √ T Increased conjugated bilirubin in the urine. D √ T A reduced serum cholesterol concentration. E Apoptosis: 23 F Causes necrotic cell death. A T Is involved in embryonic remodeling. B F Releases pro-inflammatory mediators. C T Is characterized by condensation of nuclear chromatin. D T Is associated with endonuclease activity. E Comment: APOPTOSIS ***** • Programmed cell death * • Affects single cells surrounded by unaffected viable cells • Characterised with shrinkage of cell volume and chromatin condensation • Energy dependent process * • Endonucleases *are activated and break down chromatin. Cytosolic proteins are cross-linked, converting the cell into a shrunken shell with intense basophilic staining • Apoptotic cells are phagocytosed by macrophages, forming apoptotic bodies -secondary lysosomes containing cellular debris • Not associated with inflammation * • Occurs during organogenesis - mechanism by which fingers / toes are separated * • May be pathological and occur in irradiated or atrophic tissue and following exposure to cytotoxic T cells. • May be prominent in malignant tissue. Neutrophil polymorphs at the site of inflammation are capable of the following: 24 T Phagocytes. A T Production of oxygen free radicals. B F Replication. C F Fusion to form giant cells. D F Antibody production. E Chemical mediators concerned in the production of an inflammatory response include: 25 T 5-hydroxytryptamine. A F Aldosterone. B F Glucocorticoids. C

131

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
T Bradykinin. D T Leukotrienes. E Comment: The chemical mediators of acute inflammation include ***** • Vaso-active amines - histamine and serotonine • Plasma proteases - kinin system (bradykinin & kallikrein), complement system • Coagulation -fibrinolytic system • Arachidonic acid metabolites - prostaglandins and leukotrienes • Lysosomal components • Cytokines • Growth factors such as EGF, FGF • Platelet activating factor • Oxygen free radicals Granulomatous inflammation occurs in: 26 F Lobar pneumonia. A T Pulmonary tuberculosis. B T Sarcoidosis. C F Staphylococcal. D F Temporal arteritis. E Comment: • Granulomatous inflammation occurs in: * 1) TB and leprosy 2) Syphilis - gumma 3) Cat scratch disease 4) Schistosomiasis 5) Cryptococcus and coccidiodes infections 6) Sarcoidosis 7) Silicosis and berylliosis Granulation tissue contains the following: 27 F Elastin fibres. A T Inflammatory cells. B T Capillaries. C √ F Epithelioid cells. D T Fibroblasts. E Comment: • Granulation tissue formation: * Granulation tissue consists of inflammatory cells, fibroblasts and new vasculature in a hydrated matrix of glycoproteins, collagen and glycosaminoglycans. Its formation begins within 3-5 days after wounding and overlaps with the preceding inflammatory phase. Wound contraction and neovascularisation occur at this stage. Contraction is maximal between 5 and 15 days after wounding and is mediated to a great extent by the myofibroblast and its specialized connections with the surrounding extracellular matrix The following cells may be phagocytic: 28 T Neutrophils. A T Kupffer cells. B T Monocyte cells. C T Hofbauer cells. D

132

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
F Plasma cells. E White cell migration from blood vessels in areas of inflammation involves: 29 T Cell migration occurring between endothelial cells. A T A passive loss of fluid blood elements. B F Cell migration independent of endothelial cell motion. C T Initial emigration of polymorphonuclear neutrophils. D F More polymorphs than monocytes after 2 days. E In acute tubular necrosis of the kidney: 30 T The lesion is reversible. A F The kidney is small. B T 25% of deaths occur in the diuretic phase. C F The distal convoluted tubules are mainly affected in mercury poisoning. D T Proteinaceous casts are found in the collecting ducts. E Comment: ACUTE TUBULAR NECROSIS (ATN) ***** • Major cause of acute reversible renal failure • Associated with destruction of tubular epithelial cells • Two types: 1) Ischaemic or tubulorrhectic - associated with hypotension, severe renal hypoperfusion and ischaemia: ante / post-partum haemorrhage or septic shock. Pigmented ATN is a form of ischaemic ATN associated with massive haemoglobinuria or myoglobinuria * 2) Nephrotoxic - toxic agents that direct damage the tubes including gentamicin, cephalosporins, contrast media, cyclosporine; lead, mercury and arsenic poisoning, organic solvents like carbon tetrachloride, methyl alcohol, ethylene glycol and other poisons like mushrooms, insecticides and herbicides. Injury is most obvious in the proximal convoluted tubule * • There is focal tubular necrosis at multiple points with skip areas in between and tubular occlusion with casts • The straight portion of the proximal tubule and the thick ascending limb of the loop of Henle are most commonly affected • Eosinophilic hyaline casts and pigmented granular casts are common and contain Tamm Horsfall protein* (a specific glycoprotein normally secreted by tubular epithelial cells), haemoglobin, myoglobin and other plasma proteins. There is usually evidence of epithelial regeneration • The disorder progresses through initiation, maintenance and recovery phases. • Initiation phase is dominated by the underlying injury • Maintenance phase characterised by sustained oliguria, salt and water retention, electrolyte imbalance and increased serum urea and creatinine • Recovery phase - increased urine out-put with eventual polyuria and loss of fluid and salt. Risk of hypokalaemia. There is increased vulnerability to infection • Up to 50% of patients with ATN may not have oliguria and may have increased urine out put. The development of tissue necrosis: 31 F Can be identified by light microscopy within 1 hour of myocardial infarction. A T Is recognized by the presence of karyorrhexis. B F Is of colliguative type in the kidney. C T Occurs in tertiary syphilis. D T Is associated with rupture of lysosomes. E

133

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
Comment: NECROSIS ***** • Death of cells or tissues which are still part of living organisms • Caused by anoxia = infarction • May be caused by infection, extremes of temperature, chemicals • Rapid freezing and the use of cryoprotectants prevents the formation of ice crystals in tissues, minimising cellular damage and preventing necrosis • Microscopically characterised by cytoplasmic eosinophilia. Some nuclei undergo dissolution (karyolysis), break-up into distinct fragments (karyorrhexis) or shrink and appear as densely staining masses (pyknosis) * • There is vacoulisation of the mitochondria, swelling of lysosomes and development of amorhous densities in the mitochondrial matrix. These changes are visible in the myocardium as early as 30-60min after ischaemia • However, unmistakable light microscopic changes characteristic of cell death do not occur in the myocardium until 10-12h after total ischaemia * • Using routine staining, coagulative necrosis is not detectable in the myocardium for the first 4-8h * • The lysosomes eventually rupture and their enzymes leak into the cytoplasm* • Coagulative necrosis - thromboplastin deposition results in dead tissue becoming swollen and firm with bright eosinophylic staining - occurs typically in the heart / kidneys/stromal malignancies * • Colliquative necrosis - associated with autolysis with eventual cyst formation - typically occurs in the brain * • Necrosis associated with bacterial infection and polymorphonuclear cell infiltration forms an abscess • Caseation - typically occurs in TB infection * • Necrosis + bacterial infection = gangrene: colliquative necrosis forms wet gangrene while coagulative necrosis forms dry gangrene • Fat necrosis occurs in breast tissue after trauma. Also occurs in pancreatitis due to release of lipase into the abdomen Wound healing is delayed by: 32 F Insulin. A √ F Ultraviolet light. B T Zinc deficiency. C T Low temperature. D T Glucocorticosteroids. E Comment: Wound healing is impaired by: ***** • Local factors: • Infection • Surgical technique - crushing of tissue with blunt instruments impairs healing. Excessive tension at wound edges impairs healing • Ischaemia - foreign bodies, infection or strangulating tissue • Haematoma • Foreign body reaction - wounds with foreign bodies are characterised by low pH and low pO2 and these impair healing • Topical medications and dressings - Occlusive or semi-occlusive dressings promote faster reepithelization. They may also alter certain aspects of dermal repair. They also provide the moist environment needed for optimal wound repair, they may also help to prevent bacterial invasion and wound infection

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DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
• Low temperature: *The relatively low tissue temperature in the distal aspects of the upper and lower extremities (a reduction of 1-1.5C [2-3F] from normal core body temperature) is responsible for slower healing of wounds at these sites • Systemic factors • Metabolism*: Abnormal carbohydrate and fat metabolism slows wound repair. Glucose may be unavailable or fail to enter cell properly. Insulin deficiency leads to suppress collagen deposition in the wound • Protein deficiency may occur after major trauma or during sepsis. Fibroplasia and matrix formation are delayed, wound remodelling is impaired. Protein deficiency may lead to an increased risk of infection • Vitamins: Vitamin A deficiency associated with slowed re-epithelization, decreased collagen synthesis and stability and an increased risk of infection. • Vitamin C (Ascorbic acid) is an essential cofactor during collagen biosynthesis. In scurvy, the collagen formed is unhydroxylated, relatively unstable - wound healing is poor • Vitamin K deficiency results in a deficiency in the production of vitamin K dependent clotting factors - bleeding diathesis, hematoma formation and poor wound healing • Trace elements and minerals - Required as cofactors for various enzymes during wound healing. • Zinc deficiency* important clinically, as it is a constituent of multiple important metalloenzymes including collagenase and DNA and RNA polymerases. Its deficiency results in impaired immune responses, decreased protein and collagen synthesis, decreased lysyl oxidase activity and interfere with vitamin A transport • Wound healing impaired in the elderly. Mechanism behind lack of scarring in fetal wounds unknown • Systemic conditions Hereditary Ehlers-Danlos syndrome Coagulation disorders Hemophilia, Von Willebrand‘s disease, Factor XIII deficiency Vascular disorders Congestive heart failure, Atherosclerosis, Vasculitis Venous stasis Lymphoedema Metabolic Chronic renal failure Diabetes mellitus Malnutrition Cushing‘s syndrome Hyperthyroidism Others Chronic pulmonary disease Chronic liver disease (cirrhosis) Malignancy Myelofibrosis and other chronic hematologic disorders associated with thrombocytopenia Drugs ***** Glucocorticoids Anticoagulants Antineoplastic drugs Cyclosporin A Colchicine Penicillamine

135

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
** Ultraviolet light improves wound healing *

In healing by primary intention, the following events occur: 33 F Formation of fibrin-free haematoma. A T An acute inflammatory reaction. B F Migration of epithelial cells within 6 hours. C T Phagocytosis. D T Invasion by capillary buds within three days. E Comment: HEALING BY PRIMARY INTENTION ***** • Wound associated with minimal loss of tissue and is without significant bacterial contamination • The incision space is immediately filled with blood clot containing fibrin and blood cells * • Dehydration of the clot forms a scab that seals the wound from the environment. • Vascular and inflammatory phase:* An initial 5-10 minutes period of vasoconstriction is followed by more persistent vasodilatation. Within 24h: neutrophils appear at the margins of the incision. Their prime function is the phagocytosis and killing of contaminant bacteria. By day 3, neutrophils have largely been replaced by macrophages. They become activated and release proteases and vasoactive peptides as well as growth and chemotactic factors for fibroblasts and endothelial cells. • Re-epithelisation: *Within 24-48h, spurs of epithelial cells from the edges grow along the cut margins of the dermis and beneath the surface of the scab to fuse in the mid-line forming a continuous thin epithelial layer. Proliferation is maximal at 48 to 72 hours after wounding and is reflected by a 17 fold increase in mitosis and epithelial hyperplasia at the wound edges • Granulation tissue formation: * Granulation tissue consists of inflammatory cells, fibroblasts and new vasculature in a hydrated matrix of glycoproteins, collagen and glycosaminoglycans. Its formation begins within 3-5 days after wounding and overlaps with the preceding inflammatory phase. Wound contraction and neovascularisation occur at this stage. Contraction is maximal between 5 and 15 days after wounding and is mediated to a great extent by the myofibroblast and its specialized connections with the surrounding extracellular matrix • Fibroplasia and matrix formation: * Collagen deposition begins by day 3 but is initially vertically oriented and do not bridge the wound. By day 5, collagen fibres are more abundant and begin to bridge the incision. Fibroblasts and epithelial cells proliferate and by day 5, the epidermis recovers its normal thickness with surface keratinisation • Matrix and collagen remodelling: * During the second week, there is continuous accumulation of collagen and proliferation of fibroblasts and there is regression of vascular channels with blanching. Type I collagen becomes the major collagen present in the remodelled scar, reversing the earlier type III collagen predominance. The process of remodelling may continue for up to a year and maximal tensile strength is regained. Collagen: 34 F Has a double helical structure. A T Shows a regular banding pattern on electron microscopy. B T Is not formed normally in the absence of ascorbic acid. C F Is not found within basement membranes. D T Synthesis is inhibited by glucocorticoids. E Comment

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FRCS(Ed), FRCS (Ir), FRCS(Glas)
Trihelical structure. Concerning cells: 35 √ F Glycosylation takes place in the smooth endoplasmic reticulum. A T Low density Lipoproteins attach to cell membrane receptors. B F Glycoproteins are present on the cytosol surface of the plasma membrane. C T Centrioles are composed of tubulin. D T Nuclear heterochromatin is genetically inactive. E √ The following tissues are capable of cellular regeneration: 36 F Spinal cord. A T Liver. B T Epidermis. C F Myocardium. D T Bone marrow. E Comment 2: Skin and bone marrow are particularly active in cellular turnover and capable of regeneration. The liver is also capable of regeneration as is often seen in cirrhosis with regenerating nodules amongst the cirrhotic tissue. Myocardium nor spinal cord do not regenerate. The following provide conclusive evidence of pregnancy in uterine curettings: 37 F Decidua compacta. A F Arias-stella changes in endometrial glands. B F Spiral arterioles. C F Plasma cell infiltration. D T Chorionic villi. E Comment: THE ARIAS-STELLA REACTION ***** • Secondary to a direct effect of progesterone on the endometrium * • Endometrial epithelial cells become increasingly vacuolated and thrown into pseudo -papillary folds giving a hyper-secretory impression • There is evidence of decidualisation around spiral arteries and under the surface of the epithelium • Complete decidualisation is however, not evident until pregnancy is well established • The cell nuclei are pleomorphic and there is glandular hyperplasia, intra-nuclear cytoplasmic invaginations which may resemble viral inclusions • The Arias-Stella occurs in normal intra-uterine pregnancy, ectopic pregnancy, progestogen therapy and can also occur in the endocervix * • The presence of chorionic villi on endometrial currettings provide conclusive evidence of an intra-uterine pregnancy * In anaphylactic shock in humans: 38 T IGE is a mediator. A T There is degranulation of mast cells. B F Complement is required. C T Histamine release occurs. D F The principle response is in the gastrointestinal tract. E Comments 2: Anaphylaxis is a type I hypersensitivity reaction and occurs within minutes or hours. As well as bronchoconstriction, vasodilatation and circulatory collapse with pharyngeal swelling with

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DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
possible airway obstruction, anaphylaxis may be associated with urticaria and pruritis. Comment: IMMEDIATE (TYPE I) HYPERSENSITIVITY ***** • Rapid IgE and mast cell dependent vascular and smooth muscle reaction that is usually followed by an inflammatory reaction in an individual who has been previously exposed to an antigen (sensitized) * • Antigen binds to IgE on mast cells, cross-linking receptors and inducing mast cell degranulation * • Released mast cell granules contain histamine, heparin, neutral proteases and cytokines typical of TH2 responses - IL-3 and IL-4 * • Cyclo-oxygenase and lipoxygenase are also activated with the production of vasodilator prostaglandins, leukotrienes and thromboxanes * • In the skin is characterized by a wheal and flare reaction * • The result is increased capillary permeability, smooth muscle contraction and this manifests as wheezing, oedema, hypotension - this is the acute phase and occurs within minutes * • The latent phase peaks after 3-5 hours and is caused by cytokine mediated inflammatory infiltration by neutrophils and eosinophils - this is responsible for tissue damage that occurs after repeated episodes of immediate hypersensitivity * • Typical disease processes include asthma, hay fever, drug and insect bite induced anaphylaxis, penicillin allergy, food allergy, atopic dermatitis * _________________

PATHOLOGY AND IMMUNOLOGY ‫ طرف من‬mandible ‫ ف براي ر ال س بت ف ي‬12, 2011 5:41 pm Amyloid: 39 F Is predominantly intracellular. A T Contains fibrils. B F Is enzymatic. C T Can be found in nerve tissue. D T Deposits occur with chronic sepsis. E Comment: AMYLOIDOSIS ***** • Process characterised by extracellular* tissue deposits of amyloid in one or many organs Amyloid is characterised by • Homogenous pink extracellular material on H & E staining • Orange colour by light microscopy and green birefringence by polarising microscopy in sections stained with Congo red • Fine non-branching 7.5 - 10nm on electron microscopy • Beta-pleated sheet *structure of fibrils by x-ray diffraction Amyloid deposition may be either a primary (idiopathic) or secondary to some other condition and may be localized to one specific site or generalized throughout the body (systemic) • Primary amyloidosis tends to involve mesodermal tissues, most frequently affecting peripheral nerves, skin, tongue, joints, heart, and liver while secondary amyloidosis mainly affects parenchymatous organs, such as spleen, kidneys, liver, and adrenals. • Systemic forms of amyloid are derived from circulating protein precursors by conversion from soluble into insoluble (fibrillar) form.

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DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
Classification • Based upon the tissue distribution (local or systemic), the absence or presence of preexisting disease (primary or secondary), and the chemical type of amyloid protein fibril. Classification Disease association Amyloid precursor Systemic amyloidosis Primary / secondary

Multiple myeloma* Immunoglobulin lambda / kappa chain Secondary Chronic inflammation* TB, rheumatoid, lung abscess, chronic pyelonephritis, chronic osteomyelitis Non-immunoglobulin amyloid associated protein Secondary Hodgkin's disease Non-immunoglobulin amyloid associated protein Secondary Chronic renal failure / dialysis Beta-2-microglobulin Localised amyloidosis Medullary carcinoma of thyroid* Calcitonin Senile cardiac amyloidosis Transthyretin Senile cerebral amyloidosis, Alzheimer‘s disease* Amyloid precursor protein

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DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
Amyloidosis Related to Monoclonal Ig Light Chains - usually lambda chain produced by abnormal clones of Ig-secreting plasma cells (B cells) * • Amyloidosis occurs in about 5-10% of patients who have pre-existing or coexisting multiple myeloma. * • Amyloidosis associated with Inflammatory or Infectious Diseases * - deposits have a systemic distribution and contain AA (amyloid-associated) fibrils which are related to the nonimmunoglobulin AA protein and its serum protein precursor (SAA), an acute phase reactant synthesized by hepatic cells. Associated with rheumatoid arthritis (5-10% of rheumatoid patients) and also dermatomyositis, scleroderma, Crohn‘s disease, ulcerative colitis, chronic pyelonephritis, chronic osteomyelitis • Reactive-type amyloidosis may also occur in association with cancer, such as Hodgkin's disease and renal cell carcinoma. • Endocrine-related - *Localized amyloid deposits are associated with hormones produced by certain endocrine tumours and endocrine glands, such as medullary carcinoma of the thyroid gland (procalcitonin), islet cell tumors of the pancreas, and the islets of Langerhans (islet associated polypeptide, IAPP) in patients with type II diabetes mellitus. • Age-related. Amyloid deposits of transthyretin occur in the heart of elderly patients with senile cardiac amyloidosis. • Beta amyloid protein is deposited in the cerebral blood vessels and plaques of patients with senile cerebral amyloidosis and Alzheimer's disease * • Organs extensively infiltrated by amyloid are enlarged and have a pale, waxy appearance and tough consistency. • The iodine test for amyloid is done by applying iodine solution to the washed cut surface of the organ: amyloid typically stains mahogany-brown, and this changes to blue ( a "starch-like" reaction) after the application of dilute sulphuric acid. SYMPTOMS & SIGNS • Nonspecific, determined by organ or system affected, and often obscured by the underlying disease. • Nephrotic syndrome is the most striking early manifestation with anasarca, hypoproteinemia, and massive proteinuria. • Hepatic amyloidosis - hepatomegaly but rarely jaundice. Liver function test usually normal • Cardiac amyloidosis - cardiomegaly, intractable heart failure, or any common arrhythmia. • GI amyloid - oesophageal motility abnormalities, gastric atony, motility abnormalities of the small and large intestine, malabsorption, bleeding, or pseudo-obstruction. Macroglossia is common in primary and myeloma-related amyloidoses. • A firm, symmetric, nontender goiter resembling Hashimoto's or Riedel's struma may result from amyloidosis of the thyroid gland. TREATMENT • Treat underlying condition Amyloid deposition is part of the pathological process in the following diseases: 40 √ F Medullary carcinoma of the thyroid. A T Plasmacytoma. B √ F Diabetes mellitus. C T Chronic pyelonephritis. D F Bronchial asthma. E In tissue pigmentation, the following are associated: 41 F Kernicterus and conjugated bilirubin. A T Addison's disease and increased cutaneous melanin. B

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DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
F Melanosis coli and bile pigments. C T Wilson's disease and copper deposition in the cornea. D T Corpusluteum and carotenoids. E In sarcoidosis: 42 F Lesions are confined to the lung. A F The Mantoux test is strongly positive. B T Caseation is not present. C T The lesions contain giant cells. D F The Kveim test is a useful adjunct to diagnosis. E Comment: SARCOIDOSIS ***** • Multi-system granulomatous disorder * • Affects young adults (peak incidence 30-40years) and presents with bilateral hilar lymphadenopathy, pulmonary infiltration, skin and eye lesions • Wide-spread non-caseating granulomas with epitheloid cells * • Differential diagnosis is berylliosis • Common in USA and more severe in Blacks than Whites • There is depressed cell-mediated reactivity to tuberculin - negative in 80% of patients • Lymphopaenia is present - T-lymphocytes low, B-lymphocytes normal • Commonest cause of erythema nodosum • Eyes - anterior uveitis and kerrato-conjunctivitis sicca • Hypercalcaemia in 10% due to increased circulating 1, 25 dihydroxyD3. Increased risk of calculi • CNS involvement rare but may cause severe disease • Arthralgia, hepato-splenomegaly and cardiac involvement • Serum levels of angiotensin converting enzyme are elevated • Raised ESR with normochromic, normocytic anaemia • The Kveim test is of very limited value and is very rarely used for diagnosis. CT / CXR and biopsy / bronchial lavage are used.

In cystic fibrosis, abnormalities are seen in the: 43 T Pancreas. A T Salivary glands. B T Brain. C F Kidneys. D T Ileum. E The following are consequence of pulmonary embolism: 44 T Pulmonary infarction. A T Fibrinous pleurisy. B T Right ventricular hypertrophy. C T Sudden death. D T Haemoptysis. E Comment: PULMONARY EMBOLISM (PE) ***** • An embolus is a detached intravascular solid, liquid or gas which is carried by blood to a site distant from its site of origin • PE is one of the commonest preventable causes of death in hospital patients, especially following pregnancy or pelvic surgery • Over 95% of all PE arise from thrombi in large veins of the lower limbs - popliteal, femoral,

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DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
iliac veins • Venous thrombosis is only identified in 20-70% of patients with confirmed PE. A patient who survives a PE has a 30% risk of developing another one • 60-80% of PE are clinically silent • Obstruction of > 60% of the pulmonary vasculature causes sudden death, acute right heart failure (acute cor pulmonale) or cardiovascular collapse * • Obstruction of small pulmonary arteries which function as end arteries causes pulmonary infarction • Obstruction of larger branches which are not end arteries causes pulmonary haemorrhage as the bronchial circulation maintains tissue viability. Patients present with SOB and / or haemoptysis but rarely pleurytic chest pain as the pleura is not involved * • Multiple emboli lead to pulmonary hypertension with right ventricular hypertrophy * • Only 10% of PE cause infarction which is typically haemorrhagic. The infracted area is wedge shaped with the apex pointing towards the lung hilum. The pleural surface is covered by a fibrinous exudates * Features of disseminated intravascular coagulation include: 45 F Thrombocythaemia. A T Petechiae. B T Haemorrhage. C F Reduced circulating fibrin degradation products. D T Small-vessel thrombosis. E Comment: DISSEMINATED INTRA-VASCULAR COAGULATION ***** • Acute, sub-acute or chronic thrombo-haemorrhagic disorder secondary to a variety of diseases • Coagulation system is activated, leading to the formation of micro -thrombi * • There is consumption of platelets and clotting factors and secondary activation of fibrinolysis with increased concentration of fibrin degradation products * • May therefore present with signs / symptoms of tissue ischaemia secondary to thrombi or haemorrhage * • There is thrombocytopaenia, decreased fibrinogen concentration, increased concentration of fibrin degradation products, evidence of red cell fragmentation on blood film and haemoglobinuria in severe cases. Hyperbilirubinaemia is unconjugated * • Associated with; 1) Obstetric complications such as placental abruption, pre-eclampsia, amniotic fluid embolism, fetal death in-utero, septic miscarriage 2) Infection - gram negative septicaemia, malaria, meningococcal septicaemia 3) Massive tissue injury including burns and extensive surgery 4) Malignant disease - carcinoma of the pancreas, prostate, lung

The following are adverse effects of blood transfusion: 46 T Hypothermia. A √ T Haemoglobinuria. B T Hypocalcaemia. C F Hypocalaemia. D F Thrombocytosis. E The following cause platelet aggregation: 47 T ADP(adenosine diphosphate). A F Prostacyclin. B

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DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
√ F Serotonin. C F Antithrombin III. D T Thromboxane A2. E Comments 2: 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. However, because they have no nucleus they are unable to produce new proteins and therefore aspirin and other drug effect function for the remainder of the platelet lifespan. Platelet life span is approximately 9-10 days in normal individuals. Platelets are capable of producing Nitric oxide, prostaglandins and thromboxane, but not the vasoconstrictor prostacyclin.

Stored blood which is to be used for transfusion: 48 T Is kept at -4 C. A F Must be used within 1 week. B F Is tested for complement content before transfusion. C F May be used for platelet replacement. D T Contains an acid anticoagulant. E Platelets: 49 T Are approximately 50 micrometers in diameter. A T Contain myosin. B T Release a growth factor. C T Are formed from myeloblasts. D F Are prevented from aggregating by thromboxane A2. E Comment: PLATELETS ***** • Attach to sites of endothelial injury, where sub-endothelial elements, particularly fibrillar collagen are exposed. Von Willebrand‘s factor is necessary for adhesion * • Secretion - platelets release the contents of their granules: alpha granules contain fibrinogen, fibronectin, platelet-derived growth factor, anti-heparin and cationic proteins. Dense bodies contain ADP, ionised calcium, histamine, adrenaline and serotonine * • Aggregation - formation of platelet-platelet inter adherence promoted by the formation of thromboxane A2 which is also a vasoconstrictor. Activated platelets also produce ADP which is a platelet activator. The platelet aggregate forma the primary haemostatic plug. * • Platelet activation also results in thrombin formation, a powerful platelet agonist and activates the clotting system. A secondary haemostatic plug is formed

In the pathogenesis of thrombosis: 50 F Prostacyclin induces platelet aggregation. A T Platelets synthesis thromboxane A2. B T Thromboxane A2 induces vasoconstriction. C T Contact with subendothelial collagen causes platelet aggregation. D F Thrombin inhibits platelet aggregation. E Comment: THROMBOSIS Three influences pre-dispose to thrombosis 1) Endothelial injury 2) Alterations in normal blood flow - turbulence or stasis 3) Alterations in the blood - hypercoagulability

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DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
• A thrombus is formed by the interaction of the vessel wall; blood cells particularly platelets and clotting factors. A blood clot only involves the clotting system • Thrombi formed within rapidly moving arterial and cardiac circulations are composed largely of fibrin and platelets and differ from blood clots • Vascular injury results in a brief period of vasoconstriction which may reduce / stop blood loss in small vessels • Injury to endothelial cells exposes highly thrombogenic sub-endothelial connective tissue to which platelets adhere and become activated - occurs within minutes: primary haemostasis * • Tissue factors and platelet factors released at the site of injury activate the clotting system forming fibrin The following factors present on the normal endothelium prevent thrombus formation: 1) Thrombomodulin - binds thrombin and converts it into an activator of protein C, a plasma protein which is a potent anti-coagulant * 2) Protein S synthesised by the endothelial cells is a cofactor for the anti-coagulant activities of protein C * 3) Heparin-like molecules on endothelial cells accentuate the effects of anti-thrombin III, a plasma protein which binds and inactivated thrombin and other clotting factors such as XII a, XIa, Xa, IXa 4) Conversion of ADP (potent platelet activator) to adenine nucleotide by endothelial cells 5) Production of prostacyclin (PGI2), potent inhibitor of platelet aggregation and a vasodilator * 6) Tissue plasminogen activator - promotes fibrinolytic activity. Comments 2: Prostacyclin is thought to have a role in inhibiting platelet aggregation. TBX A2 is synthesized by platelets and its effects are to induce vasoconstriction and procoagulant. Other factors mediating platelet aggregation include contact with the subendothelium, thrombin, fibrin, exposed collagen etc.

Complications of myocardial infarction include: 51 T Fibrous pericarditis. A F Aortic aneurysm. B T Ventricular mural thrombi. C F Coronary atherosclerosis. D T Ventricular aneurysm. E Comment: • Complications of acute MI include: ***** a) Sudden death b) Arrhythmias c) Mitral incompetence following infarction +/- rupture of a papillary muscle d) Fibrinous or fibrinohaemorrhagic pericarditis - develops on day 2-3. May be localised or generalised e) Mural thrombosis with risk of peripheral embolism f) Ventricular aneurysm g) Myocardial rupture causing cardiac tamponade or left-to-right shunt

Osteoporosis is associated with: 52 √ F An increase in uncalcified bone matrix. A F Prolonged oestrogen therapy. B T Long term heparin treatment. C T Bone fractures. D

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DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
F Irregularity of epiphyseal plates. E Comment: OSTEOPOROSIS ***** • Reduction in bone mass sufficient to render bone fragile and liable to fracture • Peak bone mass attained at the age of ~ 30 years • Rate of bone loss thereafter is greater in women because bone loss increases significantly after the menopause - 'senile osteoporosis' • Bone loss also occurs secondary to increased corticosteroid exposure (exogenous / endogenous), hypogonadism, thyrotoxicosis, pregnancy, hypo-pituitarism, mal-nutrition, malabsorption, chronic heparin therapy, prolonged weightlessness * • The condition is systemic, although the vertebrae, femoral neck and metacarpals are more affected than the skull and mid-shaft of long bones * • Additional target sites are the distal radius, proximal humerus, proximal tibia and pelvis • Resorption begins at the cortico-endosteal surface, resulting in enlargement of the medullary cavity and thinning of the cortex • Cancellous bone is also affected and trabeculae may be completely resorbed • The blood concentration of calcium / phosphate remains normal

Osteoporosis is associated with: 53 √ F An increase in uncalcified bone matrix (osteoid tissue). A F Prolonged oestrogen therapy. B T A normal histological bone structure. C T Bone fractures. D F Irregularity of epiphyseal plates. E The following are causes of hypokalaemia: 54 F Angiotensin-converting enzyme(ACE) inhibitors. A F Addison's disease. B T Diarrhea. C F Digoxin overdose. D √ T Metabolic alkalosis. E Osteomalacia is characterized by: 55 F Mineralization of the periosteum. A T Deposition of uncalcified bone matrix. B F Normal osteoblastic activity. C T Increased capillary fragility. D F Normal calcification of bone. E Comment: RICKETS & OSTEOMALACIA ***** • Rickets occurs in children while osteomalacia occurs in adults • Caused by vitamin D deficiency * • Dietary deficiency, inadequate exposure to sun light, malabsorption, derangements in vitamin D metabolism (for instance, chronic renal failure), end-organ resistance or hereditary abnormalities of vitamin D metabolism • There is a failure in bone mineralization resulting in excess un-mineralised matrix and abnormally wide osteoid seams * • Rickets results in skeletal deformity with defective mineralization of the epiphyseal cartilage necessary to control cartilaginous growth while in the adult, there is a pre-disposition to fracture *

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DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
Rickets is characterized by the following: 56 F Mineralization of the periosteum. A T Deposition of uncalcified osteoid. B T Abnormal osteoblastic activity. C T Increased capillary fragility. D √ T Overgrowth of cartilage. E Tetany may occur as a complication of: 57 F Osteoporosis. A F Hypercapnia. B F Respiratory acidosis. C F Peripheral neuropathy. D F Untreated hyperparathyroidism. E Immunology Tissue macrophages: 58 T Are found in the placental villous stroma. A F Express HLA class I but not HLA class II surface antigens. B T Have a role in protection against intracellular pathogens. C T Are phagocytic. D F Are derived from circulating plasma cells. E Natural killer (NK) cells: 59 T Are related to B cells. A T Have large granular lymphocyte morphology. B T Have receptors for HLA class I molecules. C F Are present in large numbers in decidua during the first trimester. D F Express CD3 (cluster differentiation antigen 3) on their surface. E Comment: NATURAL KILLER (NK) CELLS ***** • NK cells a group of cytolytic lymphocytes, distinct from B-lymphocytes and T-lymphocytes, that participate in both innate immunity and adaptive immunity* • Lack B-cell receptors (surface immunoglobulins) and T-cell receptors (TCR / CD3) * • Express receptors for the Fc portion of some IgG antibodies * • Large granular lymphocytes - make up 10% of lymphocytes in blood and peripheral lymphoid tissues and about 2% of lymphocytes in peripheral blood * • Specialized to kill certain types of target cells, especially cells infected with virus or malignant cells * Features of NK Cells • NK cells do not express surface immunoglobulins or TCR/CD3 on their surface. The surface markers that best characterize NK cells are CD2+,CD3-, CD4-, and CD56+ * • NK receptors are polymorphic so that the repertoire of NK receptors differs from person to person. • The first NK cell receptor, called the killer-activating receptor recognises stress-induced molecules. This interaction sends a positive signal which enables the NK cell to kill the cell to which it has bound unless the second receptor cancels that signal. • This second receptor, called the killer-inhibitory receptor (KIR), recognises MHC-I molecules which are usually present on all nucleated human cells. • If MHC-I molecules are expressed on the cell, the killer-inhibitory receptor sends a negative

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DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
signal that overrides the kill signal and prevents the NK cell from killing that cell • This ensures that NK cells are not activated by normal host cells • Viruses often suppress class I MHC expression in cells they infect, the virus-infected cell becomes susceptible to killing by NK cells. • Malignant cells have reduced or no class I MHC expression and are susceptible to killing by NK cells. • NK cells kill cells to which antibody molecules have attached through a process called antibody-dependent cytotoxicity • The killing is done by the exocytosis of granules containing perforin and granzymes. • Pre-programmed to recognise their targets and have no need to develop into a clone of identical cells. • Secrete cytokines such as IFN-γ and TNF-α *

Plasma cells: 60 T Are increased in myeloma. A F Are characteristic of acute infection. B F Are phagocytic. C T Synthesis immunoglobulins. D T Are derived from B lymphocytes. E Comment: LYMPHOCYTES ***** • Make up 20-45% of total leukocyte count • Only immune cells with specific receptors for antigens • Count is increased in viral infections, toxoplasmosis, brucellosis, and whooping cough • Count is decreased in uraemia, Legionnaires disease, corticosteroid treatment, chemotherapy and radiotherapy and HIV infection • Characterised by their differential expression of CD (cluster of differentiation) antigens. • Following stimulation by antigen, some lymphocytes differentiate into memory cells which are capable of mounting a rapid response if the same antigen is later encountered • Most lymphocytes are located in secondary lymphoid tissues - lymph nodes, the white pulp of the spleen, the gut- and bronchial-associated lymphoid tissues. • The part of the B cell receptor that binds antigen is surface immunoglobulin* • Subsequent B cell proliferation and maturation generates plasma cells that secrete this immunoglobulin * • In contrast to B cell receptors, T cell receptors do not bind free antigen. The antigen must be processed into small peptides by antigen presenting cells and these antigen derived peptides are displayed on the antigen presenting cell surface in the clefts of molecules called major histocompatibility molecules (MHC) * • There are three main types of T cells * 1) T helper cells that facilitate B cell responses to antigen 2) T inflammatory cells that facilitate macrophages in the eradication of intracellular infection 3) Cytotoxic T cells that recognise and destroy virus infected cells. B-LYMPHOCYTES ***** • Mature in the bone marrow. Develop into antibody producing plasma cells. Only immune cells capable of antibody production * • Have membrane-bound immunoglobulins which act as antigen receptors * • Plasma cells migrate to the bone marrow where they produce small quantities of antibodies for long periods of time after the initial infection has been cleared • B-cell receptors bind soluble antigens • The bound antigen molecules are engulfed into the B cell by receptor-mediated endocytosis. *

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DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
• The antigen is digested into fragments which are then displayed at the cell surface nestled inside a class II histocompatibility molecule. * • Helper T cells with complementary TCRs bind the B cell and secretelymphokines that * 1) Stimulate the B cell to enter the cell cycle and develop, by repeated mitosis, into aclone of cells with identical BCRs; 2) Switch from synthesizing their BCRs as integral membrane proteins to a soluble version; 3) Differentiate into plasma cells that secrete immunoglobulins.

Lymphocytes in healthy: 61 F Form about 2% of the white cell count. A √ T Play an essential role in cell mediated immunity. B T Can change into plasma cells. C T Have proportionately more nuclear material than cytoplasm. D F Have a life span of about 30 days. E Comment: LYMPHOCYTES ***** • Make up 20-45% of total leukocyte count • Only immune cells with specific receptors for antigens • Count is increased in viral infections, toxoplasmosis, brucellosis, and whooping cough • Count is decreased in uraemia, Legionnaires disease, corticosteroid treatment, chemotherapy and radiotherapy and HIV infection • Characterised by their differential expression of CD (cluster of differentiation) antigens • Following stimulation by antigen, some lymphocytes differentiate into memory cells which are capable of mounting a rapid response if the same antigen is later encountered • Most lymphocytes are located in secondary lymphoid tissues - lymph nodes, the white pulp of the spleen, the gut- and bronchial-associated lymphoid tissues. • The part of the B cell receptor that binds antigen is surface immunoglobulin* • Subsequent B cell proliferation and maturation generates plasma cells that secrete this immunoglobulin * • In contrast to B cell receptors, T cell receptors do not bind free antigen. The antigen must be processed into small peptides by antigen presenting cells and these antigen derived peptides are displayed on the antigen presenting cell surface in the clefts of molecules called major histocompatibility molecules (MHC) * • There are three main types of T cells * 1) T helper cells that facilitate B cell responses to antigen 2) T inflammatory cells that facilitate macrophages in the eradication of intracellular infection 3) Cytotoxic T cells that recognise and destroy virus infected cells. B-LYMPHOCYTES ***** • Mature in the bone marrow. Develop into antibody producing plasma cells. Only immune cells capable of antibody production * • Have membrane-bound immunoglobulins which act as antigen receptors * • Plasma cells migrate to the bone marrow where they produce small quantities of antibodies for long periods of time after the initial infection has been cleared • B-cell receptors bind soluble antigens • The bound antigen molecules are engulfed into the B cell by receptor-mediated endocytosis. * • The antigen is digested into fragments which are then displayed at the cell surface nestled inside a class II histocompatibility molecule. * • Helper T cells with complementary TCRs bind the B cell and secretelymphokines that * 1) Stimulate the B cell to enter the cell cycle and develop, by repeated mitosis, into aclone of cells with identical BCRs;

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DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
2) Switch from synthesizing their BCRs as integral membrane proteins to a soluble version; 3) Differentiate into plasma cells that secrete immunoglobulins.

B lymphocytes: 62 √ F Produce tumor necrosis factor. A F Produce complement. B T Produce antibodies. C √ F Contribute to delayed hypersensitivity. D T Produce IgE. E T lymphocytes: 63 T Differentiate in the thymus. A T Are involved in the generation of both cell-mediated and immoral Immune responses. B T Are the predominant lymphoid population in decidua. C T Are the predominant lymphoid population in peripheral blood. D F Are the major cell type in the germinal centers of lymph nodes. E Comment: T-LYMPHOCYTES ***** • Mature in the thymus gland * • Can only recognise peptide antigens that are bound to MHC molecules on specialised antigen-presenting cells - MHC-restricted * • CD4 positive T-cells are helper T-cells - help B cells produce antibodies and help phagocytes destroy ingested organisms * • CD8 positive T-cells are cytotoxic T-cells - capable of killing host cells infected with intracellular organisms * • Na-ve T-cells have antigen receptors but do not perform the functions required to eliminate the antigen. CD8+ T cells • CD8+ T cells bind that are part of class I histocompatibility molecules. Almost all the cells of the body express class I molecules • The best understood CD8+ T cells are cytotoxic T lymphocytes - secrete molecules that destroy the cell to which they have bound. • The role of the CD8+ T cells is to monitor all the cells of the body, ready to destroy any that express foreign antigen fragments in their class I molecules. CD4+ T cells • CD4+ T cells bind epitopes that are part of class II histocompatibility molecules. Only specialized antigen-presenting cells express class II molecules • Essential for both the cell mediated and antibody-mediated branches of the immune system • Bind to antigen presented by antigen-presenting cells and release lymphokines that attract other cells to the area. • Bind to antigen presented by B cells, resulting in the development of clones of plasma cells secreting antibodies against the antigenic material. The following are recognized function of T lymphocytes: 64 F Antibody production. A T Cell-mediated immunity. B T Immune suppression. C √ F Phagocytosis. D

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DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
T Cytokine production. E The following are recognized function of T lymphocytes: 65 F Antibody production. A T Cell-mediated immunity. B T Immune suppression. C √ F Phagocytosis. D T Lymphokine production. E Immunodeficiency states may be associated with: 66 T Viral infection of T lymphocytes. A T B cell lymphomas. B T Glucocorticoid administration. C F Haemolytic disease of the newborn. D T Hodgkin's lymphoma. E Immunodeficiency states may be associated with: 67 T Viral infection of T lymphocytes. A T B cell lymphomas. B T Glucocorticoid administration. C F Haemolytic disease of the newborn. D T Untreated Hodgkin‘s lymphoma. E Concerning immunoglobulins: 68 T IgG contains tow heavy chains. A √ T IgM is produced before IgG in the immune response. B F IgE is the principal immunoglobulin secreted by mucous membranes. C F IgA is the principal immunoglobulin involved in allergic reactions. D √ T IgA is secreted in breast milk. E Human immunoglobulin M (IGM): 69 F Has a molecular weight of 150 000 Daltons. A T Contain J chains. B F Crosses the placenta readily. C F Fixes complement by the alternative pathway. D F Is a dimmer in external secretions. E Comment: IgM ***** • One type, pentamer - ten antigen binding sites * • Half-life in serum = 5 days. • Activates complement and serves as naive B-cell receptor * • First immunoglobulin to be synthesised during B-cell maturation * • Molecular weight 970kDa, makes up 5-10% of immunoglobulins * • Does NOT bind to mast cells, neutrophils or macrophages * • Does not cross the placenta - the presence of IgM in fetal blood indicates fetal infection and fetal antibody production *

Concerning immunoglobulin in pregnancy: 70 F Maternal IgM is responsible for rhesus isoimmunisation in the fetus. A F IgA concentration in cord blood is higher than that in maternal blood. B F IgE crosses the placenta readily. C

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DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
T IgG crosses the placenta readily. D F Fetal IgM is dimeric. E Immunoglobulin M: 71 F Fixes complement by the alternative pathway. A F Crosses the placenta readily. B √ F Fixes to mast cells. C T Is produced by plasma cells. D F Is smaller than immunoglobulin E. E Comment: IgM ***** • One type, pentamer - ten antigen binding sites * • Half-life in serum = 5 days. • Activates complement and serves as naive B-cell receptor * • First immunoglobulin to be synthesised during B-cell maturation * • Molecular weight 970kDa, makes up 5-10% of immunoglobulins * • Does NOT bind to mast cells, neutrophils or macrophages * • Does not cross the placenta - the presence of IgM in fetal blood indicates fetal infection and fetal antibody production *

The following are examples of type-III hypersensitivity (immune-complex) disease: 72 F Autoimmune haemolytic anaemia. A T Systemic lupus erythematosus. B T Glomerulonephritis. C F Tuberculosis. D F Sarcoidosis. E Comment: IMMUNE COMPLEX MEDIATED (TYPE III) HYPERSENSITIVITY ***** • Caused by immune complex deposition in the blood vessels or tissues * • These complexes activate macrophages, activate complement and cause the extracellular release of neutrophil granules and tissue damage * • The inflammatory response is characterised by the Arthus reaction which is characterised by a neutrophilic infiltration and immunoglobulin + complement deposition * • The inciting antigen may be -self- or -non-self- from infectious organisms • Disease processes include * 1) Polyarteritis nodosa and SLE 2) Farmer's lung - occurring in patients sensitized to thermophilic actinomycetes; pigeonfancier's disease - these disorders are generally known as extrinsic allergic alveolitis 3) Post-streptococcal glomerulonephritis 4) Jarisch-Herxheimer reaction+

Type III hypersensitivity: 73 F Is mediated by specifically-sensitized T lymphocytes. A F Causes myasthenia gravis. B T Occurs in systemic lupus erythematosus. C T Is a recognized cause of glomerulonephritis. D F May cause allergic asthma. E Type III (immune complex-related) hypersensitivity is: 74 T Damage localized to a particular cell type. A

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DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
√ F Decreased vascular permeability. B T Microthrombus formation. C T Complement activation. D F Mediation by IgE antibodies. E The major histocompatibility complex (MHC): 75 F Resides on chromosome 11. A T Is composed of human leukocyte antigen (HLA) genes. B F Codes for three classes of antigens. C F Will be identical in dizygotic twins. D F Codes for blood group antigens. E Comment: THE MAJOR HISTOCOMPATIBILITY COMPLEX • Made up of membrane bound proteins on antigen presenting cells that display peptide antigens for recognition by T-cells * • Play a central role in graft rejection * • Human MHC molecules are called human leukocyte antigens (HLA) * • MHC genes are highly polymorphic - there are many different alleles present in different individuals. No two individuals in an outbred population have identical MHC genes or molecules (except identical twins) * • Human MHC located on chromosome 6 * • Variations in MHC genes are not due to DNA recombinations • There are two sets of highly polymorphic HLA genes called class I and class II genes • The MHC also contains several non-polymorphic genes, some involved in antigen presentation and others with unknown functions • Inherited in an autosomal co-dominant fashion * • Class I molecules are expressed by all nucleated cells while class II molecules are expressed by professional antigen-presenting cells only (dendritic cells, macrophages and B-lymphocytes) * • Each MHC molecule can only present one antigen at a time, but is capable of presenting many different peptides. The binding of peptides to MHC molecules is a low affinity, low specificity interaction. Bound peptides are displayed for several days to enable recognition by T-cells • Antigenic peptides are acquired during the synthesis and assembly of MHC molecules in the cytoplasm - class I molecules display peptides acquired from cytosolic proteins while class II molecules acquire peptides from intracellular vesicles • MHC molecules cannot discriminate between self and non-self peptides • MHC molecules cannot present non-peptide antigens

Antibodies play an important part in the development of: 76 T Phagocytosis. A F The Mantoux response. B T Erythroblastosis fetalis. C F Hyperemesis gravidarum. D T Anaphylaxis. E Antibodies: 77 T Are proteins. A F Are formed in the fetus before 12 weeks of intrauterine life. B F Have an average molecular weight of around 10 000 Daltons. C T Of the rhesus type are genetically transmitted. D

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DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
T Are produce of the ribosomes of plasma cells. E The biological effects of complement in the human include: 78 T Opsonisation. A T Cell membrane lysis. B F Participation in the blood coagulation process. C F Promotion of sperm motility. D F Prevention of immune rejection of trophoblast. E Autoantibodies are found in: 79 T Systemic lupus erythematosus. A T Rheumatoid arthritis. B T Pernicious anaemia. C F Bronchial asthma. D T Chronic active hepatitis. E The following cells are correctly paired with their products: 80 T Endothelial cell: factor VIII related antigen. A T Plasma cell: IgG. B T Salivary gland epithelial cell: amylase. C F Mast cell: IgA. D T Decidual stromal cell: prolactin. E In uncomplicated homozygous beta thalassaemia there is: 81 T Hypochromasia. A F A reductionin haemoglobin A2. B T An increase in haemogobin F. C F Megaloblastic erythropoiesis. D F Red cell sickling. E In uncomplicated homozygous beta thalassaemia there is: 82 T Hypochromatasia. A F A reduction in haemoglobin A2. B T An increase in haemoglobin F. C T No depletion of iron stores. D F The presence of megaloblasts in bone marrow. E In beta thalassaemia: 83 F The erythrocytes will sickle at low oxygen tension. A F A homozygous fetus is usually anemic. B F Stainable iron stores in the marrow are usually decreased. C T Target cells may be found in the peripheral blood. D F Erythrocyte survival time is increased. E Characteristic features of addisonian pernicious anemia include: 84 F Leucocytosis. A F Inheritance as an autosomal dominant trait. B F A raised mean corpuscular haemoglobin concentration. C T An increased incidence of gastric neoplasia. D T An increased incidence of primary hypothyroidism. E Steps involved in the identification of restriction fragment length polymorphisms (RFLP) include: 85

153

DR. SYED KARIM SHAH SHIRAZI
FRCS(Ed), FRCS (Ir), FRCS(Glas)
F T T T F Western blotting. A Restriction enzyme digestion. B Southern blotting. C Agarose gel electrophoresis. D Thin layer chromatography. E

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