AIPGME EXAMINATION ANSWERS & EXPLANATIONS 2O004O°” as prefix and / or suffix stands for NACo eC OSTEO an an Paar anne These are the most — important PRU OLLM A Te Ik a e PEM a rc arya mene” RCo med OR i) portion of text marked “Q” as prefix eSANATOMY 1 2 3. Answer is B (Raise the arm above the head on the affected side) : Repeat BDC 1/6"/56, 64 ‘Long thoracic nerve’ is the nerve to serratus anterior. Serratus anterior is supplied by Nerve to serratus anterior or Long scapular nerve (Cs, 4,2) (Branch arising from the roots ®) Actions of Serratus anterior ‘Rotates the scapula so that glenoid cavity ts turned upwards = Helps in raising arm above the head (helped by Trapezius in this action) © }2. Pulls the scapula downwards around chest wall to protect the upper limb = In Pushing and Punching movements (helped by pectoralis minor in this action) © 3. Steadies the scapula during weight carrying [4._Helps in forced inspiration 2 The arm cannot be abducted above the horizontal plane, because the serratus anterior is unable to rotate the sglenoid cavity superiorly to face upwards and allow complete abduction of the arm, above the horizontal Answer is A (Right lung is shorter and wider than left lung) : Gray's 41"/956-57; Repeat Right principal bronchus : Grays ‘+ The right principal bronchus is wider, shorter and more vertical than the left being about 2.5 cm long. ‘+The greater width and the more vertical course of right principal bronchus explain why foreign bodies enter itmmore common that the lef. (Trachea thus directs the foreign body to right lung by branching such that right bronchus becomes more vertical) + Itgives off its first branch, the superior lobar bronchus and then enters the right pulmonary hilum where it divides into a middle and an inferior lobar bronchus (Inferior lobar bronchus is thus the terminal continuation of the principal bronchus) Note : Although right lung is both shorter and wider than the left lung, this is not a cause for an increased likelihood of foreign bodies to lodge in the right lung. Larger & _— 5 Smaller and lighter? ‘+ Shorter & broader? + Larger and narrower? + Has 2 fissures and 3 lobes? ‘+ Has only one fissure and 2 lobes? ‘© Anterior border is straight ‘+ Anterior border is interrupted by the cardiac notch Answer is A (Lateral cutaneous nerve of thigh) : BDC 11/6"/313-314 This question asks about nerves that come in posterior relation, to the kidney Three nerves come in posterior relation to the kidney : 1. Subcostal nerves 2. Miokypogastric nerves 3. Mioinguinal nerves Posterior relation of kidneys : Ty Tie diaphragm 2. The medial and lateral arcuate ligament 3. Psoas major 4, Quadratus lumborum 5. Transversus absominis 6. Subcostal vessels 7. Nerves : subcostal nerves, iliohypogastric nerves, ilioinguinal nerves 8, 12" rib (11" rib to left kidney only)'* AIPGME EXAMINATION ANSWERS AND EXPLANATIONS - 2004 Answer is D (Penile urethra) : Gray's 41°V1263 ‘Lymphatics from the male spongiose (penile) urethra end in the deep inguinal lymph nodes? - Grays + Urethral Lymphatics : = Vessels from the prostatic and membranous urethra in the males and the whole female urethra pass to the internal iliac nodes. (a few may end in external iliac nodes) = Vessels from the male spongiose (penile) urethra accompany those of the glans penis ending in the deep inguinal lymph nodes. (a few may end in superficial nodes) ‘+ Region surrounding the isthmic part of uterine tube is drained along the round ligament to the superficial inguinal nodes. ‘+ Superior to the pectinate line lymphatics from anal canal drain into the intemal iliac lymph nodes. Inferior 10 the pectinate line lymphatics drain into the superficial inguinal nodes. + Big toe drains into superficial nodes. Answer is C (Pampiniform plexus) : Moore's 4" / 202; Snells 9" / 128 The testicular veins emerge from the testes and epidydimis and join to form a venous network, the pampiniform plexus, lying anterior to the ductus deferens and surrounding the testicular artery in the spermatic cord. ampniform pies yeeeular artery vas deren, ym vesses ary of ves. posterior anterior jm enim testis \ tal The pampiniform plexus is part of thermoregulatory system of testes helping to keep this gland at constant temperature.® Answer is B (Atlanto axial joint) : Gray's 41°/736-37; Also see Al / 2003 ‘Movements of cervical spine can be divided into 1, Movements at Atlanto axial joints (C1-C2) 2. Movements at Atlanto occipital joints (Cl-occiput) 3. Movements at other cervical joints (C2-C7) Movements, Atlanto occipital joint Atlanto axial joint Other cervical joints Main movement is flexion with = Movement consists almost exclusively Main movement is of a little lateral flexion and rotation of rotation of axis, flexion and extension ~ The normal range of atlantoaxial rotation is about 29 -54 ° Answer is D (synchondrosis / syneendrosis) : Gray's 41°/96-101; Chaurasiva's general anatomy/51 Costochondral joints are unusual synarthroses where convex tip of cartilage is received by a complementary recess in the tip of the rib - Grays‘AIPGME EXAMINATION ANSWERS AND EXPLANATIONS - 2004 Cartilaginous joints are essentially of the following two types - Primary cartilaginous joint = Synchondrosis/ hyaline cartilaginous joints Bones are united by a plate of hyaline cartilage so + that joint is immovable or strong, Examples 5 Joint between epiphysis and diaphysis of long one ——_ Secondary cartilaginous joint = ‘Symphysis / ibrocartilaginous joint Articular surfaces are covered by a thin layer of hyaline cartilage and united by a disc of fibrocartilage ‘Typically these joints occur in median plane and allow limited movements due to compressible pad of '. Sphenooccipital joint fibrocarilage and occasional fluid felled cavities ‘First chondrostemal joint Examples 4, Costockondral joints + Symphysis pubis ‘+ Manubriosternal joi Intervertebral joint between vertebral bodies Classification of Joints Fibrous joints a Sutures + Shall 1b. Syndesmosis ‘© Inferior tibiofibular joint &. Gomphosis ‘© Tooth in its sockets Cartilaginous joints Primary cartilaginous (or synchondrosis or hyaline + Joint bin epiphysis and diaphysis cartilage joint) ‘© Spheno-occiptal joint ‘+ Istchondrostemal joint © Costochondral joint b. Secondary cartilaginous (or symphyses or ‘© Symphysis pubis ibrocartlaginous joint) ‘© Manubriostemal joint + Intervertebral joint Synovial joints a Plane synovial + Intereapal and intertarsal + Joint bin articular process of vertebra b Hinge + Elbow + Ankle + Interphalangeal & Pivot Trochoid) + Sup. and Inf. radioulnar joint + Median atianto-axial joint 4 Condylar Bicondylar) + Knee joint + Right and left jaw joint e Ellipsoid + Wrist joint ‘+ Metacarpophalangea joint + Atlanto-occipital joint J. Saddle (Sellar) + Ist carpometacarpal joint + Stemoclavicular joint + Caleaneocubiod joint Ball and socket (Splieroid) + Shoulder joint + Hip joint + Talo-calcanconavicular joint Answer is B (It has a rich nerve supply) : Gray's 41°/83, ‘Articular cartilage has no nerves or blood vessels’ ~ Grays 38° /496. Articular hyaline cartilage covers the articular surfaces in synovial joints, providing an extremely smooth, resistant surface, bathed by synovial fluid, allowing almost frictionless movement. Properties of articular cartilage Grays ° 87 The surface of articular cartilage is devoid of perichondrium.? * Articular cartilage has no nerves or blood vessels © (except occasional vascular loops reaching and even penetrating the calcified zone from the osseous side) ‘+ ‘Nutrition is derived from diffusion from three sources: vessels of synovial membrane, synovial fluid and ‘hypochondral vessels in an adjacent medillary cavity + Cells of articular cartilage divide by mitosis + Progressive loss of superficial cells from normal young joint surfaces is probably replaced by cells from deeper surfaces. But this is not confirmed. « _Articular cartilage does not ossify. 2 AIPGMEE 2004 - EXPLANATIONS.828 10. *® AIPGME EXAMINATION ANSWERS AND EXPLANATIONS - 2004 Answer is C (Thymus) : Gray's 41°73 Lymphocytes are concentrated in many sites in the body typically at strategic sites which are liable to infection «or in possible routs tothe spread of infection. The main areas of lymphocyte proliferation can be classed as cither primary or secondary, lymphoid tissue. + Thymus + Lymph nodes + Bone marrow + Spleen These are described as primary lymphoid organs + Lymphoid tissue associated with epithelial surfaces g because of their initial roles in lymphocyte = palatine & nasopharyngeal tonsils ‘generation = payers patches in small intestine = lymphoid nodules in respiratory urogenital systems, skin & Conjunctiva ‘Note that bone marrow serves as a secondary lymphoid tissue as well as primary, because lymphocytes pass back into it, through the circulatory system, to engage in furthur proliferation when needed. Answer is A (Acrocentric) : Molecular genetics by Precid and Strachan /49, 153 SSS Metacentric © Human X chromosome is large submetacentric chromosome with numerous genes. Es Submetacentric SSS Acroceatric © Human ¥ chromosome is a small acrocentric chromosome. —— + Sabiston 16°/1000 Answer is A (Hepatic vein and portal vei Anatomy of hepatic lobes can be elaborated by two systems of segmental nomenclature The system shows more considerations for the hepatic venous drainage and caudate lobe but also applies to the portal anatomy ‘© The planes containing the right, middle and left hepatic veins are called portal scissurae whereas planes containing the portal pedicles are called tie hepatic scissurae. ‘© They divide liver into eight segments. ‘The American system ‘© The general relationship between hepatic veins and portal vein branches is used to | determine the lobar anatomy of the liver ‘© They divided liver into four segments 4 |-AIPGME EXAMINATION ANSWERS AND EXPLANATIONS ~20 PHYSIOLOGY 2 1B. Answer is D (Shift of oxygen dissociation curve to the left) : Ganong 20" / 655 “With acclamatization, 2,3 DPG rises within the RBC and oxygen dissociation curve shifts to right such that ‘oxygen unloading to tissues becomes easier’ ~ Chaudhary. cclamatizatio A person remaining at high altitudes for days, weeks and or years becomes more and more acclamatized to the low pO. so that it causes fewer deleterious effects on the body and it becomes possible forthe person to work hharder without hypoxic effects and to ascend to still higher altitudes. The principle compensatory defence mechanisms in acclimatization involve : 1 ulmonary ventilation (Hyperventilai = Hypoxic stimulation uf central chemoceptors (carotid and aortic) increases alveolar ventilation. + _ Immediate increase in pulmonary ventilation blows off CO;, reduces p PO, and there by increases pH and inhibits the central chemoceptors (respiratory centre). However with acclimatization over 2-5 days, CSF begins to expel bicarbonate ions and this decreases the pH in the fluid surrounding central chemoceptors of respiratory centre thus. stimulating the central chemoceptors of respiratory centre. i ia and increased Hl concentration Increased diffusing capacity Circulatory system: - increased cardiac output ~~ increased capillarity 5. Cellular: increased mitochondria, celular oxidative enzymes Note : Within RBC the 2, 3 DPG rises, which shifts the oxygen dissociation curve to the right, and oxygen unloading to tissues becomes easier. Review : LSS eS 1. Increased 2, 3 DPG cavsed by 1. Decreased 2, 3 DPG caused by ~ Hypoxia ~ High altitude storage of blood in blood bank for long > Exercise - Anemia ~ decreased glycolytic activity = Androgens - Thyroid hormone = Growth hormone 2. Decreased pH 2. Increased pl 3. Increased temperature 3. Decreased temperature 4. Increased pCO, 4, Decteased p CO; Answer is C (80 mm Hg) : Ganong 19" / 636 fig 352; Ganong 20" /645 Observe the following table from Ganong 19" /636 10 BS 0.03, 20 35 0.06 30 37 009 40 15 0.12 50 835 ous 60 89 018 70 92.7 021 80 945 024 90 96.5 027 100 975 030 ‘+ Given concentration of oxygen is in ml /ml and needs to be converted into ml /dl Knowing the fact that 1 dl = 100 ml .0025 ml / ml = 0025 ml 0025 x 100 ml /dl I io0"! = 25 mi/dl From the table a value of dissolved oxygen of 25 ml /dl corresponds to 94.5 % saturation of Hb and 80 mm Hg of PO. Sincerely am not aware of any formula for calculating the above nor do I consider it possible for any of us to remember the table when we set out for our exams, You may look out for a better explanation yourself.14. 15, 16. © AIPGME EXAMINATION ANSWERS AND EXPLANATIONS - 2004 Answer is D (Ther: Edema normally occurs due to increased hydrostatic pressure that pushes fluid out or due to reduced oncotic pressure that fails to pull the fluid. “Acute heart failure is usually predominantly systolic and sudden reduction in cardiac output often results in systemic hypotension without peripheral edema.’ — Harrison 15% / 321 Acute heart failure is thus associated witha fall in hydrostatic pressure and not an increase, and therefore explains lack of peripheral edema. Peripheral edema appears later consequent to fluid retention by the kidney a ‘renal compensation’ in systemic capillary hydrostatic pressure) : Reed text below Answer is B (End of isovolumetric contraction) : Guyton 10/99 Fig: Events of the cardiac cycle for left ventricular function, showing changes in left atrial pressure, left ventricular pressure, aortic pressure, ventricular volume, the electrocardiogram, and the phonocardiogram. The period of isovolumetric contraction is when ventricle contracts as a closed chamber with both the semilunar and AV valves closed. The total period of isovolumetric contraction lasts about .05 sec until the pressure in the left and right ventricle exceeds the pressure in the aorta and the aortic and pulmonary valves open. ‘Note from figure above Beginning of systole AY valves close Sa 2) End of isovolumetric contraction ‘Semilunar valves open End of diastole AY valves close a End of diastasis AY valves ae open and semilunar valves are closed Answer is C (Follicle stimulating hormone): Chaudhry 4° /308 ‘Sertoli cells have receptors for FSH and testosterone’ ~ Chaudry. Role of Sertoli cells 1. Sertoli cells have receptors for FSH and testosterone? After combining with FSH, Sertoli, cells, stimulate the first half of spermatogenesis®. Subsequently testosterone ~ Sertoli cell binding causes development of last half of spermatogenesis. Sertoli cells synthesize androgen binding protein (ABP) Q. The ABP binds with testosterone and causes great concentration of testosterone within the seminiferues tubules. Sertoli ceils produce the blood testes barrier (BTB) Q Sertoli ceils also produce inhibin Sertoli cells also produce activin and Mullerian regression factor Sertoli cells provide nutrition to germ cells. O Testosterone is converted into 5 «dihydrotestosterone by Sertoli cells. Sertoli cells contain aromatose (CYP 19) which is responsible for conversion of androgens to estrogens. & SN aPae17. 19. 20. ‘AIPGME EXAMINATION ANSWERS AND EXPLANATIONS - 2004 831 Answer is C (Aromatase) : Ganong 19" /420 Aromatose is the enzyme that catalyzes the conversion of andostenidone to estrone and conversion of testosterone to estradiol. ‘Adrostenidone Testosterone aa maa Estrone Estradiol Estriol ‘The naturally occurring estrogens are 17 f estradiol, estrone and estriol ‘They are secreted primarily by the granulosa cells of the ovarian follicle, the corpus luteum and the placenta, ‘The biosynthetic pathway involves formation from androgens. ‘They are also formed from aromatization or androstenidione in the circulation. Answer is C (GABA) (Most probably) : Various tests ‘Recent studies suggest that during prepubertal period an inhibitory neuronal system suppresses LHRH release and that during the subsequent maturation of hypothalamus this prepubertal inhibition is removed allowing the adult pattern of pulsatile LHRH release’. In fact gama amino butyric acid (GABA) appears to be an inhibitory neurotransmitter responsible for restricting LHRH release before onset of puberty in female rhesus monkey’ — Endocrine reviews by E. Terasawa &David Fernandez “GnRH neurosecretion has been shown to be under the control of many neurotransmitters and neuropeptides. Among the latter, two amino acids have a predominant action: glutamate which has an excitatory effect and whose levels increase before puberty and GABA which exerts an important inhibitory action or GnRH secretion ‘and whose concentrations diminish at puberty’ — Internet, Answer is D (free form) : Harrisons 15" /2053; Ganong 19" /231 Cleavage of precursor molecule occurs as they are transported and the storage granules in the endings contain ‘free vasopressin’ (or free ADH) ~ Ganong 19/231 Supraoptic nuclei (Hypothalamus) + ADH + Neurphysin Il + Copeptin (Cytosol) + Golgi apparatus + Neurosecretory vesicles + Posterior pituitary oe f + y Free ADH ‘Neurophysin II Copeptin + Released into circulation Answer is D (Glutamate) : Ganong 19" / 101; Ganong 20" / 102 + Glutamate is the main excitatory transmitter in the brain and spinal cord, responsible for upto 75% of ‘excitatory transmission in brain - Ganong if + Excitatory amino acids ~ Anhibitory amino acid Glutamate Glycine Aspartate ‘Gama amino butyric acid (GABA) ‘+ GABA is the major inhibitory mediator inthe braina. 2. | ANSWERS AND EXPLANATIONS - 2004 Answer is C (Increasing the amplitude of action poter janong 20" / $3; 19/70, Action potential follows an all or none law. If sufficient amplitude is reached to produces a response, increasing the amplitude further will not have any effect on the function to follow. 1's responsible for gradit t in the motor neurons) : Frequency of contraction Frequency of discharge in the individual fibre plays a role. Tension developed (summation) during a tetanic contraction is greater than that during individual twitches. Answer is D (Siggaard —Anderson normogram) : Ganong 19" / 703 fig 39.8 Siggard-Anderson normogram : plots the acid — base characteristic of arterial blood and is helpful in clinical situations. PCO; is plotted on the vertical axis and pH on the horizontal axis. ‘+ Vertical line through ph 7.40 : = Any point to left ofthis vertical line indicates acidosis = Any point to right indicates alkalosis. ‘+ Horizontal line through p CO; of 40 mmHg : Position of point above or below this horizontal line defines the effective degree of hypoventilation or hyperver BIOCHEMISTRY 2. Answer is A (AUG codon): Lippincott's biochemistry 2"/395 ‘Shine Dalgarno sequence’ is a sequence of nucleotide bases (5' - UAGGAGG-3') located 6-10 bases upstream of the AUG codon on the mRNA molecule Lippincott. ToS Ribosomal RNA my peat ue SEW UAAGGAGG YA AUG. ‘Shine-Dalgamo sequence 308-Ribosomal subunit,4, 28. Shine Dalgarno sequence is important as a mechanism by which the ribosome recognizes the nucleotide sequence tha is essential for initiation’ of translation (protein synthesis) ‘There are two mechanisms by which ribosome recognizes the nucleotide sequence that initiates translation: 1. Shine - Dalgarno sequence 2. m codon, ‘Shine Dalgarno Sequence: «Isa sequence of nucleotide base (5'-UAGGAGG-3) located 6-10 bases upstream on AUG codon on mRNA ‘molecule in bacteria such as E, coli * The 16 ribosomal RNA component of the 30s ribosomal subunit has @ nucleotide sequence near its 3' end that is complementary to all or part of shine Dalgarno sequence. ‘* Thus the mRNA 5' end and the 3’ end of the 16 S ribosomal RNA can form complementary base pairs thus facilitating the binding and positioning of the mRNA on the 30s ribosomal subunit. Ans, is D (Primer) : Lipponcott 2/374; Chatterjee shinde 5/226 RNA polymerase does not require a primer to initiate transcription while DNA polymerase requires it. RNA polymerase: ‘+ RNA polymerase is the principle enzyme required in process of transcription ‘© Transcription is the process of synthesis of RNA froma DNA template. [RNA polymerase holoenzyme requires the following: Chatterjee Shinde/226 11. Template of double stranded DNA (or occasionally single stranded DNA) [2 Four ribonucleotide triphosphates GTP, ATP, UTP, CTP 3. Mg” or Mn” # Prokaryotes have only one type of RNA polymerase which is responsible for synthesis of mRNA, tRNA and tRNA as well Eukaryotes has at least three different RNA polymerases to synthesize different types of RNA Type I: transcribes ribosome RNA (r RNA) ‘Type Il: transcribes messenger RNA (mRNA) ‘Type III: transcribes transfer RNA (t RNA) Note: “Feature DNAppolymerase RNA polymerase TEE Primer Needed Not needed $ Endonuclease activity Yes No Exonuclease activity ‘Yes No die Answer is A (Introns): Harper 26/253 ‘+ The primary RNA transcripts contain two types of sequences 1. Introns (Imervening sequences): sequences that do not code/contribute to the genetic information ultimately translated into the amino acid sequences of a protein molecule 2. Exons: (Expressed sequences): sequences that code for various amino acids ‘+ This primary transcript undergoes extensive processing which involves cleaving out of the intervening introns (non coding sequence) and splicing (ligation) together of the exons (coding sequences) Thus introns are removed from the primary transcript and exons are ligated together to form mRNA ‘molecule. Answer is C (Reverse transcriptase): NMS Biochemistry 4"/187: Lippincott 2™/407, Harper 25"/407 Reverse transcriptase isan 'RNA dependent DNA polymerase’ that produces double stranded DNA copies of, RNA templates. RNA polymerase Synthesizes RNA form DNA‘834 © AIPGME EXAMINATION ANSWERS AND EXPLANATIONS - 2004 27, Answer is B (Glutamic acid): Harper 26"/362 + Although substitution of one amino acid for another (due to single base changes in structural genes) are capable of inducing unacceptable mutations, (eg. Hemoglobin produced by substitution of valine for glutamic acid at position 6 on f chain), some mutation have no apparent effect. + ‘Tthas been shown that the codon for valine at position 67 of the chain is not identical in all persons who posses a normally functional {chain of Hb.’ - Harper This means that normally functional haemoglobin may have different amino acid at position 67 of chains in place of valine. = When glutamic acid is present at position 67 in place of valine: Hb Milwaukee (Functionally noma) = When aspartic acid is present at position 67 in place of valine: Hb Bristol (Functionally normal) | Acids in place or Valine at position 67 of Bchain 2 Glutamic acid Hb Milwaukee Aspartic acid Hb Bristol Alanine Hb Sydney Thus any of the above amino acids, can be a homologous substitution for valine with no apparent effect and result in functionally normal haemoglobin. 28. Answer is B (A stretch of hydrophobic aminoacids): Harper 26/450 Protein within cell membranes are of two types: ‘A. Integral or trans membrane proteins that span the lipid bilayer B. Peripheral proteins present embedded in either the inner or outer leaflet ofthe lipid bilayer. A. Integral proteins/Transmembrane proteins: ‘They interact with the phospholipids and require the use of detergents for their solubilization. generally span the lipid bilayer® distributed asymmetrically across the lipid bilayer® are usually globular proteins 2 they are amphipathic in nature Integral proteins are amphipathic in nature and contain both hydrophobic and hydrophilic regions. Hydrophiltic regions are located at the ends while the transmembrane region i.e. the region that traverses the core of the bilayer is composed of a stretch of hydrophobic amino acids. B. Peripheral proteins: ‘They do not interact directly with the phospholipids in the bilayer and do not require use of detergents for their release ‘They are weakly bound to the hydrophilic region of specific integral proteins. Hydrophilic ends | ) oti 1 1 ie Hy Hydo- phobic probe pi |roamceaka< poten “SPS bier | | _ 29, Answer is D (Chaperones): Harper 26/507, Chatterjee Shinde 5%/235 ‘Chaperones are proteins that play a role in the assembly or proper folding of other proteins without themselves being components of the latter’ They prevent faulty folding and unproductive interactions of other proteins.30. 31. ‘AIPGME EXAMINATION ANSWERS AND EXPLANATIONS 2004» 835 Properties: 1. Present in a wide range of species from bacteria to humans 2. Many are so called ‘Heat shock proteins’ (HSP) 3. Some are inducible by conditions that cause unfolding of newly synthesized proteins (eg. Elevated temperature and various chemicals) |4. They bind to predominantly hydrophobic regions of unfolded or aggregated proteins S. They act in part as a quality control or editing mechanism for detecting misfolded or otherwise defective proteins 16, Most cheperones show associated ATPase activity, with ATP or ADP being involved in the protein ccheperone interaction 7._Found in various cellular compartments such as cytosol, mitochondria and lumen of endoplasmic reticulum. Remaining options: ‘© Proteases are enzymes that hydrolyze proteins ‘+ Proteosomes (eg. 26s component) help in degrading the proteins marked with ubiquitin ‘+ Template is involved in the synthesis of nucleic acids Answer is D (Ubiquitin) : Ganong 21"/299, NMS Biochemistry 4/375 Ubiquitin is a small protein present in eukaryotic cells, that targets many intracellular proteins for degradation, mainly abnormal newly produced proteins - Aged normal proteins ‘The 'C’ terminal residue of ubiquitin becomes covalently attached to lysine residues of proteins that are then degraded via an adenosine triphosphate dependent process. Other options: | Clathrin; © Clathrin is a peripheral membrane protein that helps in endocytosis. The vesicles formed” f uring absorptive pinocytosis are derived from invaginations (pits) that are coated on the cytoplasmic site with a filamentous material known as clathrin. Is a proteolytic enzyme secreted by chief cells of stomach It is used for digestion is found in extracellular matrix. Itis the most abundant glycoprotein present in basement membrane 2 Answer is D (Adenylate eyelase) : Ganong 19/41 © Adenylate cyclase is an enzyme that occurs on the surface of cell membranes © + Itbelongs to the family of cell membrane receptors that are linked to the effecter through one or more GTP activated G-proteins (G-protein coupled receptor) 2 ‘+ Cycle AMP is an important second messenger that is formed from ATP by the action of enzyme adenelyl cyclase. Simiaioy Ae ener Tuer ge ome oe ut A Te y | i 3 wwe (Cypopinam ATP cap == cs ate 4 | 4 ryocope oe ‘Cyclic AMP acts by activating a cyclic nucleotide ~ dependent protein kinase (protein kinase-A) which catalyzes the phosphorylation._ AIPGMEE 2004 - EXPLANATIOI cll 836 32. 33. + AIPGME EXAMINATION ANSWERS AND EXPLANATIONS - 2004 Answer is A (Inosital Triphosp! ite): Ganong 21°/42; NMS biochemistry 4/263 “Inosital triphosphate diffuses to the endoplasmic reticulum, where it triggers the release of calcium into eyloplasm’ — Ganong Inositol triphosphate and diacylglycerol (DAG)both of which are second messengers, are associated with Gy subset of G protein mediated receptors. G, protein | Stimulate Phospholipase C-B Hydrolysis Phosphatidylinositol 4,5 — biphosphate (PIP,) ——— Inositol 1,4,5-triphosphate (IP3) Diacylglycerol (DAG) + + Diffuse in to the cytosol and causes Lipid soluble molecule, diffuse laterally in the the release of calcium ions from membrane and activates protein kinase-C, which is intracellular stores caleium dependent + + Then IP; is inactivated by ‘They are then rapidly inactivated by hydrolysis dephosphorylation Hormones that acts through this receptor ‘> Epinephrine at the a, ~ adrenergic receptor subtype | « Angiotensin * Histamine ~ H) + Prostaglandin -FP, EP,, EP; * Muscarinic - My, Ms + Thromboxane ~ TP + SHT, + Leukotriene + Vasopresin — oxytocin, + Cholecystokinin-Gastrin + Bradykinin-B) + PAF Answer is B (calmodulin) Calmodulin can be defined as a calcium dependent regulatory protein Calmodulin has four calcium binding sites and full occupancy of these sites induces marked conformational changes that allow calmodulin to activate enzymes and ion channels. ‘Calmodulin + Ca‘ —> activated calmodulin -> Activation of enzymes and ion channels Enzymes and proteins regulated by Actin myosin complex of smooth muscles Ca"/ealmodulin + Various microfilament mediated + Adenylate cyclase + processes in non contractile cells # Cat" dependent protein kinases «# including + Ca Mg ATPase = Cell motility + Ca” phospholipid dependent protein kinase = Cell conformation changes * Cyclic nucleotide phosphodiesterase ~ Mitosis «Some eytoskeletal proteins | Granule release © Some ion channels Nitric oxide synthase ~ Endocytosis + Phosphorylase kinase ‘Some receptors34 35. 36. 37. /AIPGME EXAMINATION ANSWERS AND EXPLANATIONS - 2004» 837 Answer is B (VLDL): Harper 26/211 “Feeding of diets high in carbohydrates lead to high rates of lipogenesis and esterification of faty actds and are associated with enhanced synthesis of triacyl glycerol and secretion of VLDL by liver.’- Harper ‘Well fed state (rather than the starved state) Feeding of diets high in carbohydrates (particularly if they contain sucrose or fructose) leading to high rates 2 of lipogenesis and esterification of fatty acids. High levels of circulating free fatty acids. Ingestion of ethanol 5. Presence of high concentration of insulin and low concentration of glucagon which enhance fatty acid synthesis and esterification and inhibit their oxidation, Answer is D (Increased triglyceride and cholesterol levels in serum): - Chatterjee Shinde 5"/Dutta 5°/585 Increased triglyceride and cholesterol levels are best attributed to the metabolic effects of steroidal contraceptives themselves rather than as consequence of decreased vitamin B6 levels. ling metabolic effects of oral contraception on Lipid metabolism, Dutta states ‘Plasma lipids and lipoproteins are increased. Total cholesterol and triglycerides are increased’ "Use of oral contraception is also associated with deficiency of pyridoxine (Vit B6) ~ Dutta Alll other features mentioned in the questions may be attributed to pyridoxine deficiency as described below. + Increased xanthiuric acid exer Pyridoxine acts as a coenzyme for ‘kynurenine kymureninase which converts 3 OH | 4 santhurenie acid kynurenine to 3 OH anthranillie (excreted in urine) acid which ultimately forms 30H kynurenine Y nicotinic acid Bs deficiency + Inpyridoxine deficiency the a substrates are increased and they are converted into xanthurenic acid in extrahepatic tissues which is excreted in urine, 30H anthranilic acid Niacin Decreased Pyridoxal —P is required for conversion of a amino f ketoadipic acid 10 5-ALA an haemoglobin _ important step in heme synthesis level: In B6 deficiency heme synthesis suffers, thus explaining anemia or decreased haemoglobin levels © Neurological Pyridoxine deficiency is associated with peripheral neuropathy seizures in infants and ‘symptoms: abnormal electroencephalograms ~ Harrison's 15463. Answer is D (Selenium): Harrison's 15"/469 Selenium in the form of ‘selenocysteine’ isa component of enzyme glutathione peroxidase. ‘Glutathione peroxidase serve to protect proteins, cell membranes, lipid and nucleic acids from oxidant ‘molecules’ ~ Harrison Answer is B (Brain ischaemia): Harsh Mohan Pathology 4/296: Chatterjee Shinde 5/562 Creatine phosphokinase exists as three isoenzymes in human tissues 1 CPK-1 or CPK-BB: Found in brain 2. CPK-2 or CPK~ MB : Found in Myocardium 3._CPK~3 or__CPK MM: Found in skeletal muscle Thus creatinine phosphokinase | is essentially found in brain and would be increased in brain ischaemia Note: Normally creatine phosphokinase-2 (MB isoenzyme) occurs in very small quantity accounting for as less as 2% of total CK activity of plasma (almost undetectable). Thus elevation of CK-MB isoenzyme is considered specific ‘for myocardial damage.39. 40. Further CKMB also exists in 2 forms CK MBT Exiracardiac form CKMB 2 Cardiac form A ratio of CKMB2: CkMB1 above 1.5 is highly sensitive for the diagnosis of acute Ml after 4-6 hours of onset myocardial ischaemia. Answer is D (Sucrase): Nelson 17" / 1268 ‘The patient in question develops gas and diarrhea following consumption of dairy products. He is thus presenting with features of ‘Lactose intolerance’ which results from deficient action of enzyme However as “lactase” has not been provided as an option, we have to look for another condition that may present in a similar fashion, Sucrase deficiency presents with similar clinical manifestations as elaborated below: - Lactase deficiency Pes ‘Sucrase-isomaltase deficiency ‘© Due to deficiency of enzyme lactase Due to deficiency of enzyme sucrase and isomaltase * Clinical manifestations occur in response to ‘+ Clinical manifestations occur in response toa sucrose or glucose ingestion of lactose, the sugar in milk. polymer containing diet ‘= Presentation is with ‘* Presentation is with = Bloating (gas) = Bloating (gas) = Watery diarrhea = Watery diarrhea = Failure to thrive ~ Failure to thrive ~ Recurrent, vague, abdominal pain Development of gas and diarrhea following a diet of dairy products (sucrose or glucose polymer diet) is: consistent with a diagnosis of sucrase-isomaltase deficiency and this explains the answer Other options Saas cacy eT RNRRTURERNES Scr ORERNRER OR 7 galactosidase deficiency Galactosidosis GMI ganglosidosis “Mucopolysacharidosis IVA: Morguio A | aglucosidase deficiency ‘Type Il Glycogen storage disease ag gs (Acid al, 4 glucosidose deficiency : Pompes disease) =| Answer is B (Tertiary structure) : Homology of Pseudomonas cytochrome C:51 with Eukaryotic Cytochrome C— By Soul B. Needleman, Department of Blochemisiny, Northwestern University School of Medicine “Pseudomonas (bacterial) cytochrome C differs from eukaryotic (human) cytochrome in the total number of amino acid residues, in composition and in the order of residues in the large segment of amino acid sequence’ Comparison of primary protein structure with the predicted tertiary structure revealed that functionally crucial residues fold closely together in 3D space (tertiary structure), even though some of these residues were distant to ‘each other in the primary structure. Tertiary structure of eytochrome C's are highly conserved and explain for functional plausibility. Ans. is B (Secondary structure): Chatterjee Shinde 5"/82 Protein structure is normally described at four levels of organization 1. Primary structure 2. Secondary structure 3. Tertiary structure 4. Quartnery structure Secondary structure is produced from folding or coiling of the peptide chain (primary structure) and production of cross linkages or bonds, mainly the Hydrogen bonds Organization may result in the formation of ache Pleated sheets + Trile et + ehtcaefomedty ncn =f pleted sacred by ier chiniyogn onde * REE Ihetopen bons {Heya pote when drogen bonds are fomed between ETS - helmayeciterlethanded "atom snggenand amie hydopen of wo agjacenchais ceri hanes ~The ajcanchains maybe eter parlor ant pre Proline is never found in a helix® Silk fibroin a protein of silk worm is rich in f pleated sheets ©42. ‘AIPGME EXAMINATION ANSWERS AND EXPLANATIONS - 2004» 839 Ans. is (A) (Level of fructose 1, 6 biphosphate is higher than normal): Harper 26/154, 157 Gluconeogenesis proceeds through the following steps involving fructose 1,6 biphosphate Pyrivate | Fructose 1,6 aren Fructose nuose26 9 [biphosphate |p iphosphaare @ Fructose 6 phosphate _ Glucose ‘+ Fructose 1, 6 biphosphatase is under negative feed back control of fructose 2, 6 biphosphate ‘+ If fructose 1, 6 biphosphatase becomes less sensitive to the negative feed back of fructose 2, 6 biphosphate, its level of activity will increase ‘+ Thus more fructose, 1, 6 biphosphate will be cleaved into fructose 6 phosphate and levels of fructose 1, 6 biphosphate will decrease and be lower than normal + Also cycle will be shifted more towards gluconeogenesis i.e. formation of glucose and pyruvate levels will bbe decreased as they will be utilized for glucose synthesis. + ATP would be generated during breakdown of glucose i.e. during glycolysis and not while generating slucose via the gluconeogenesis pathway. Ans. is B or D (DNA polymerase I or DNA ligase): Harper 26/337;Lippincot 2/374;Chatterjee Shinde 5/224 + Xeroderma pigmentosm is an autosomal recessive genetic disease + The inherited defect seems to involve repair of damaged DNA particularly thymidine dimers ‘Repair of thymidene dimers: Excision repair + AULY. specific ‘endonuclease’ makes a ‘nick’ in the affected DNA strand usually on the S'end of the dimer and the defective segment comes out. + DNA polymerase 1 (DNA pol 1) = Synthesises new DNA strand in 5' to 3 direction with the 3' end of the nicked strand acting as primer and intact complementary strand serving as the template. = _ 5'to 3" exonuclease activity of DNA pol | then removes the damaged sequence + ‘DNA ligase’ lastly seals the gap between the newly synthesized segment and the main chain. + There is marked sensitivity to sunlight. DNA of skin cells is damaged on exposure to sunlight, and the cells are unable to repair the damaged DNA, resulting in excessive accumulation of mutations and skin cancers. ‘Thus xerodermapigmentosum can result from a defect in either ofthe three 1. UV specific endonuclease 2. DNA polymerase | 3. DNA ligase 'The most common form of this disease is caused by the absence of UV ~ specific endonuclease’ - Lipponcott However this has not_been mentioned in the options Both ‘DNA ligase' and ‘DNA polymerase 1' can thus be possible options. ‘None of the books clearly point towards a single enzyme other than endonucleases as the most common.PATHOLOGY 43. 45. Answer is D (Arachidonic acid metabolites): Robbins 9°/84 Lipoxins are the most recent addition to the family of bioactive products generated from arachidonic acid’ = Robbins yxins have a number. fl wwory actions: = inhibit neutrophil chemotaxis and adhesion but stimulate monocyte adhesion = (LXAd stimulates vasodilation and attenuates the action of Leukotiene induced vosoconstrition (May act as ‘endogenous negative regulators of Leukotriene action) Arachidonic acid metabolites include + ae pstgbading’ Leukottienes® = Prostaglandins’ = Lipoxins? Arachidonic acid Prostaglandin G: + Prostaglandin H 5 Lipooxygenase| Leukotrienes LT Ay Prostacyclins | ‘Thromboxanes Az <— LTA > LTB,; Chemotaxis? PGI, TXA: 12 Liposypenase + vasodilatation® |» Vasoconstriction ‘inhibit platelet | Promote platelet aggregation? | aggregation” LTC, > vasoconstriction? Prostaglandins LTD, } ‘bronchospasm? PGDs, PGE, Play LTE, J increased permeability? sodilatation® «* Potentiate edema Answer is D (Thrombin) : Robbins 9°/118 “Thrombin is essentially the culmination of the coagulation cascade and converts the soluble plasma protein fibrinogen into the insoluble fibrillar protein fibrin — It is thus perhaps the most important procoagulant and is formed from factor II or prothrombin.’ Clotting is also controlled by three types of natural anticoagulants. These include tee 9 Proteins C&S° Se , Antithrombin 111)? Seen = Inhibit the activity of = These are two vitamin K > Ttis derived from thrombin and other serine dependent proteins characterized plasminogen and acts by proteases ie. factors IXa, Xa, _by theirability o inactivate factor breaking down fibrin and. la, and XIla Va and Villa, interfering with its = Antithrombin III is activated (Thrombomodulin®: has polymerization bybinding to heparin like anticoagulant properties. It acts ~The resulting fibrin molecules or endothelial cells indirectly. It binds to thrombin, degradation products can (explains clinical usefulness of converting it from a procoagulant to also act as weak administering heparin to an anticoagulant capable of activating anticoagulants ‘minimize thromboses) protein C) Thus while protein C and protein S are natural anticoagulants thrombomodulin has indirect anticoagulant action as explained above. Answer is C (bel -2): Robbins 6/294 ‘bel-2' gene is the first identified antiapoptotic gene that inhibits apoptosis — Robbins 6/294 ‘Over expression of bcl-2 protects lymphocytes from apoptosis and allows them 10 survive for long periods; thus there ba sendy accumulation of B lymphocytes resulting in ymphadenopathy and marrow inflation’ — Robbins 69/29446. 47. 48. 49. Genes that regulate Apoptosis: These genes can be recognized as series of three letter words that begin with v F | Genes that inhibit “Apoptosis’ Genes that favour apoprasis oa bel-2 bax : bel—xL bad bol-xS ‘+ ‘p53 has proapoptotic action (tumor suppressor gene) and this seems to be mediated by upregulation of bax gene! ~ Robbins + 'C-mye induces apoptosis when cells are driven by e-mye activ Robbins Answer is A (Laminin): Robbins 9/21: Repeat ‘Laminin is the most abundant glycoprotein in Basement membranes’ ~ Robbins Answer is D (Trk A expression): Robbins 9/477 The following prognostic factors have been elaborated in Robbins text © Tnfants younger than one year of age have an excellent prognosis regardless of . the stage of neoplasm 3 : ‘Children older than one year of age have a poorer prognosis: g 2. Stage: ‘* Stages III & IV have a poorer prognosis in relation to stage I & Il (in children y older one year of age) = E ‘* Hyper diploid or triploid tumors occur in infants & have a good prognosis 2 ‘+ Near diploid tumors occurring at any age have a poor prognosis i 4. Cytogenetic + Deletions ofthe distal short arm of chromosome | is the most characteristic ‘abnormalities cytogenetic abnormality in neuroblastomas ~ Tumors with chromosome 1 deletions have a worse prognosis = Tumor with chromosome 14 deletions also have a worse prognosis It is associated with worse prognosis Amplification of oncogene 'N-mye amplification tends to occur in advanced stage tumors with chromosome Ip deletions. 6. Trk A gene The differentiation and regression of neuroblastomas appear to be at least partially affected by nerve growth factor and its high affinity receptor Trk ~ A + High levels of expression of the Trk-A gene are associated with a favaurable ‘outcome and almost always occur in tumors lacking n-myc amplification. Answer is A (RET proto oncogene): Harrison's 15%/2081, Robbins 6/1145 + Medullary thyroid carcinoma when associated with multiple endocrine neoplasia type II (men type I), harbours an inherited mutation of the RET gene. - Harrison's + A subset of sporadic medullary thyroid carcinoma contain somatic mutations that activate RET. ~ Harrison's [Note that RET oncogene is also involved in the origin of papillary thyroid carcinoma] Gene Associated condition FAP gene Familial adenomatous polyposis: defect in APC gene (adenomatous polyposis coli gene) also implicated Rb gene Retinoblastoma BRCAI gene Breast cancer Answer is C (46, XXY): Harrison's 15"/2173 The patient in question depicts a hypogonadic male that occurs when there are two or more X chromosomes and one ¥ chromosome, and represents the clinical picture of klinefelter's syndrome (47 XXY) None of the options appear technically correct as an extra X chromosome in the male should increase the total ‘number of chromosomes to 47 and hence 47 XY should be the most appropriate answer. Within the available options however an extra X-chromosome is the most essential aspect and hence the best answer here is 46 XY.842+ AIPGME EXAMINATION ANSWERS AND EXPLANATIONS - 2004 Klinefelter's Syndrome: 47 XXY or 46 X.Y / 47 XXY Mosaicism © Small firm testes: Hyalinization of seminiferous tubules and azoospermia ° Gynaecomastia © Lack of secondary male characters such as deep voice, beard, male distribution of pubic hair £ Distinct body habitus: Elongated body: Abnormally long legs? ° The mean IQ is some what lower than normal but mental retardation is uncommon ° Hypogonadism and infertility®: © Klinefelter’s syndrome is produced by non disjunction during meiotic divisions 50. Answer is A (X-linked Recessive): See text below From the available information in the question a pedigree analysis would appear as follows: Wiothers Brother Start reading theanabsis. Ly © [from here RS o O Ser ‘ce ‘ce + The pedigree analysis reveals the following: = Males only are affected by disease = Females are acting as carriers (sister 1 & sister 2) + The disease is thus likely to be transmitted through the 'X' chromosome in the mother + [tis.a recessive condition and the mother is a carrier, because if it were a dominant condition, the mother ‘would also manifest the disease. So would sister 1 and sister 2 who carry the affection at least on a single X chromosome as is evident by the affection of male children of both sisters. ‘Males having a single X chromosome (XY) manifesta recessive condition as a disease Also note: females with only one chromosome eg Tumer's syndrome can manifest x linked recessive disorders in the same way as males do. 51. Answer is D (Familial hypercholesterolemia): Harrison's 15/2251: Repeat ‘Familial combined Hyperlipidemia’ is transmitted as an autosomal dominant disorder Gstic fibrosis “Autosomal recessive Phenyl ketonuria ‘Autosomal Recessive a-lantitrypsin Autosomal Recessive Sh. Answer is D (Monosomy-1): Wintrobe's 10"/2329 ‘Myelodysplastic syndromes’ are a group of clonal haematopoetic stem cell diseases characterized by dysplasia and ineffective hematopoesis in one or more of the major myeloid stem lines. The cytogenetic abnormalities in Adult myelodysplastic syndromes are ‘Monosomy 7 10-50% Thus monosomy 7 and 5q are the two commonest cytogenetic abnormalities. Although Sq may be commoner ‘than monosomy 7 in some settings, overall monosomy 7 appears more common.‘AIPGME EXAMINATION ANSWERS AND EXPLANATIONS - 2004 © 843 Answer is B (Results from an expansion of Neoplastic T lymphocytes): Repeat: Harrison's 15%/725; Robbins 9°/604 Hairy cell leukemia isa ‘B' cell neoplasm and is characterized by expansion of neoplasticB cells (not T = Iymphocytes) Hairy cell leukemia Hairy cell leukemia is a rare but distinctive form of chronic B cell leukemia that derives its name from the appearance of fine ‘hair like projections’? on the leukaemic cells (large B cells) © Characteristic ‘Presence of tartrate resistant acid phosphatase "TRAP" © in neoplastic B cells «cytochemical feature: + Cellular features! ‘+ Hairy cells express the pan B cell markers CD 19 and CD 20 and monocyte ee Markers? associated antigen CD I ‘+ Plasma cell associated antigen (PCA-1) is also present - Robbins iS ‘+ Expression of CD 25, 1L.2 and specific adhesion molecules ~ Harrison 14/695 ge * Clinica features ‘+ Present predominantly in the older age group > 40 years? Zz result largely fram + Massive splenomegaly® (hepatomegaly is less common) 2 infiltration of bone + Lymphadenopathy & ‘marrow liver and spleen» Pancytopenia® “ + Recurrent infections + Treatment? * Curent treatment of choice i with purine analogues ~Cladrbine® s + Other drugs used S = Pentostotin® 3 = Inerferon a® | + Splenectomy used tobe the standard treatment earlier Answer is C (Absolute Lymphocyte count < 600/l): Kelly's textbook 4/1693 Oncology texts The following seven adverse prognostic factors were described for advanced Hodgkin's disease by on international group in 1998: T. Male gender la. Age> 45 years 3. Stage IV disease la. Haemoglobin < 10.5e/Al IS. Leucoeytosis with WBC> 15,000 [6. Lymphocytopenia with either one or both ofthe criteria: ‘8. Absolute lymphocyte count < 600/41 Lymphocytes < 8% of WBC 7._A Serum albumin level < g/dl Answer is B (Necrotic myofibres with presence of neutrophils): Robbins 9/544 The patient in question succumbed to myocardial infarction after about 28 hours of the attack. Characteristic morphological changes evolve in the heart of patients with MI depending on duration since the attack. After twenty four hours of the attack light microscope shows coagulative necrosis of myofibrils with loss of ‘nuclei and striations along with an interstitial infiltrate of neutrophils. Reversible Injury - (Oto tr None None’ Relaxation of myofibrils; E slycogen loss; mitochondrial swelling Irreversible injury Bosh None Usually none; variable waviness of Sarcolemumal disruption; fibres at border ‘mitochondrial amorphous densities 12h Occasionally dark Beginning coagulation necrosis; mottling edema; hemorrhage 1224 hr Dark mottling Ongoing coagulation necrosis; pyknosis of nucle: myocyte | hypereosinophilia; marginal contraction band necro neutrophilic infiltrate- EXPLANATIONS 244 87. /AIPGME EXAMINATION ANSWERS AND EXPLANATIONS - 2004 13 days ‘Mottling with yellow- Coagulation necrosis, with loss of : tan infaret center ‘nuclei and striations; interstitial infiltrate of neutrophils 3-7 days Hypermic border: Beginnig disintegration of dead central yellow-tan myofibers, with dying neutrophils, softening carly phagocytosis of dead cells by ‘macrophages at infarct border 7-10 days Maximally yellow an Well-leveloped phagocytosis of dead and soft, with depressed els; early formation of fibrovascular red-tan margins ‘granulation tissue at margins 10-14 days Red-gray depressed ——_‘Well-established granulation tissue infarct borders with new blood vessels and collagen deposition 2-8 wks Gray-white scar, Increased collagen deposition, with progressive from border decreased cellularity toward core of infarct Answer is A (Post streptococcal glomerulonephritis): Harrison's Although all conditions mentioned in the question are associated with low compliment levels ‘persistently depressed levels' are not seen in post streptococcal glomerulonephrits. In post streptococcal glomerulonephritis: serum C; levels are depressed within 2 weeks, however these usually return to normal levels within 6 t0 8 weeks Persistently depressed levels after this period should suggest another cause such as presence of C; nephritic factor (Membranoproliferative glomenulonephritis) - Harrison Differential diagnosis of Nephritic syndromes based on complement levels Se ‘Low complement levels i Normal complement levels (immune complex glonerulonephritis) ‘+ Anti GBM disease: Good posture’s syndrome ‘* Idiopathic proliferative glomerulonephritis ‘+ Pauci immune glomenulonephritis ‘© Crescentric glomenelonephritis > Wegeners granulomatoses ‘* Membranoproliferative glomerulonephritis = Microscopic polyarteritis nodosa ‘© Lupus nephritis «Immune complex mediated © Cryoglobulinemia = IgA Nephropathy ‘© Bacterial endocarditis + Henoch schonlein purpura © Shunt nephritis = Fibrillary Glomerulonephritis ‘+ Post infectious glomerulonephritis (post streptococcal) Answer is C (Diarrhea associated hemolytic uremic syndrome): Refer previous question Lupus Nephritis, post streptococcal glomerulonephritis and membrano proliferative glomerulonephritis are all associated with low complement levels as depicted in the table in the previous question. Hemolytic uraemie syndrome is characterized by microangiopathic hemolytic anemia, thrombocytopenia and renal failure due to microangiopathy. Depress 9Jement levels are not seen and laboratory feat Thrombocytopenia Normal tests of coagulation with exception of elevated fibrin degradation products Microangiopathic hemolytic anemia: striking red blood cell fragmentation on peripheral blood smear LDH elevation, out of proportion to degree of hemolysis Still searching for a convincing answer Answer is C (Verrucuous carcinoma): Ackerman's surgical pathology 8/235 ‘Verrucuous carcinomas also referred to as giant condyloma accuminatum or Buschke-Lowenstein tumor are ‘considered an intermediate lesion between candyloma acumination and invasive squammous cell carcinoma, It is important to distinguish verrucuous carcinoma from squammous cell carcinomas as these tend to remain localized and are cured by wide excision, however they may undergo malignant transformation to invasive ‘squammous cell carcinomas,[AIPGME EXAMINATION ANSWERS AND EXPLANATIONS - 2004 © 845 Features of verrucuous carcinomas + Prediliction for males > 50 years + Predisposed in tobacco users, poor oral hygiene ES ee + Large ‘+ Cytological features of malignancy are absent or minimal and rare + Soft + Epithelium is thickened and thrown into papillary folds + Wart like lesions/ + The folds project both above and below the level of surrounding mucosa and crypt papillomatous like surface grooves exhibit marked, prekeratin plugging (hyperkeratosis ? ) + Fungation may be + The rete projections are broad, bulbous and relatively smooth bordered and there present may be chronic inflammatory infiltrate in the subjacent lamina propria, + The deep border of epithelial projections is ‘pushing’ and not infiltrative, The patient in question is an elderly male (70 years) with a chronic history of tobacco use. + Gross features of a large’, ‘soft’, papillary’ lesion that has undergone ‘fungation’ are all consistent with the diagnoses of verrucuous carcinoma. Benign appearing ‘papillomatoses' with ‘hyperkaratosis" further supports the diagnosis. Contiguous structures may be involved as the tumor grows. Tumor of the buccal mucoses can grow become {fixed to the periostium of mandible and with continued growth may eventually destroy the periostium and directly invade the mandible — Oral cancer by Jofin, P. Shah/132, Answer is D (Vascular endothelium is smooth and coated with glycocalyx): Ref.: Gray's Anatomy 38° /1456 "The luminal surface of the endothelium is relatively smooth and the membrane is coated by a prominent Glycocalyx. The glycocalyx is highly charged, polysaccharide rich felt of glycoprotein anchored to the cell ‘membrane. Because of the high charge density the glycocalyx may contribute to the non-thrombogenic properties of the surface of the intact endothelium." - Grays MICROBIOLOGY 61. 62. Answer is B (It needs a carrier to induce immune response): Ananthnaryanan 9°/87 Hapten is defined as a molecule which is incapable of inducing antibody formation by itself but can react specifically with antibodies. i.e itis a substance which is not immunogenic but reacts with specific antibodies. © A hapten becomes immunogenic on combining with a larger molecule called carrier . ~~ Ananthnarayan 6"/75, Greenwood 14/131 ‘© Hapten — protein complexes are T cell dependent antigens, so these produce immunological memory and require preliminary processing by macrophages. Remember ‘Antigens can be classified functionally into t ‘Complete antigens® (immunogens) Hapten® Je Substances which are able to generate an ‘© Substances that are able to a react with immune response by themselves and produce a antibodies but are unable to stimulate their specific and observable reaction with the production directly antibody so produced Epitope: Site on an antigen recognized by an antibody tis the smallest unit of antigenecity and is also called ‘antigenic determinant’ @ Paratope®: The part of the antibody or T cell receptor that interacts with the epitope 2 Answer is A (0157 : H7) : Repeat: Harrison's 15%/954 Entorotoxigenic E. coli (ETEC) Shiga toxin producing E. coli. (STEC)/enterohaemorrhagic E. Coli Enteropathogenic E. coli Enteroinvasive E. coli Entero aggregative E. coli Diffusely adherent E. coli apaEnRe846 65. [AIPGME EXAMINATION ANSWERS AND EXPLANATIONS - 2004 + The Shiga toxin producing E. coli or Enterohaemorthagic E. coli have been associated with severe disease in the form of fatal haemorthagic colitis. + Although a number of serotypes have been associated with haemorrhagic colitis due to ‘enterohaemorchagic E. coli, the serotype 0157 : H7"is the most prominent’ — Harrison Note: Haemorrhagic/Hemolstic uremic syndrome is also associated with EHEC and the ‘0157 : H7’ serotype. Answer is B (Shiga toxin): Harrison's 15"/976 ‘Shiga toxin is compos ide subunit The frst: TLocated on the larger A subnit is an N-glycosidose that hydrolyzes adenine from specific sites of ribosomal RNA of the mammalian 60s ribosomal subunit, irreversibly inhibiting protein synthesis. The second. | isa binding site onthe B subunit that recognizes glycolipids of target cell membranes (glycolipid Gb 3). ‘Toxins that act by inhibiting protein synthesis 1. Shiga toxin® 2. Diphtheria toxin® 3.__Pseudomonas toxin® Answer is B (P-pili): Ananthnarayanan 9°/277; Medical microbiology by Greenwood 14/324 P-pilli are pyelonephritis associated pilli that are found an uropathic strains of E. coli and may play a role in Pathogeneses of UTI. They play no role in attachment of diarrheogenic E. coli to receptors in GIT and hence a vaccine against them would play no role in prevention of diarrhea from E coli. Many members of family enterobactiraceae posess fimbriae (type 1) that facilitate their adhesion to a wide range of human and animal cells. Such adhesions favour pathogenecity. A vaccine developed against such fimbnae that mediate adhesion, of E. coli to cell receptors in the gastrointestinal tract, would potentially reduce their pathogenecity, and help in prevention of diarrhea from E coli /Pavtimbrae’ ‘Action/source = 1. K88-~ enterowxigenic ‘© K-88 is found in strains causing enteritis in pigs 2K 99 E.coli from animals ‘ K 99s found in trains causing enteritis in calves and lambs 3. Colonizaion factor antigen (CFA) © Found in enterotoxigenic E.coli of human origin 4cs2 ‘Found in enterotoxigenic Ecol of human origin $. Pfimbria Found in uropathogenic E cli important in urinary tact infection P fimbrae bind specifically to the P blood group substances on human erythrocytes and uroepethelial cells. Answer is C (vibrio parahemolyticus): Ananthnarayanan 7/312, 287, 308,202 ‘No enterotoxin has been identified with vibrio parahemolyticus. The vibrio is believed to cause enteritis by invasion of the intestinal epethelium' — Anantinarayanan 6°/292 Toxins elabor 1. Vibrio parahemolyticus 2. Vibrio cholerae ‘No enterotoxin has been identified Causes enters by invasion of intestinal epethelium Produce cholera enterotoxin or cholera toxin (CT)? ‘Similar to heat labile toxin of E.coli (LT) but more® patent in biological activity Consists of one A and SB subunits A subunit (active) causes prolonged activation of celular adenylate cyclase and accumulation of cAMP B subunit (Binding) attaches othe GM, ganglioside receptor on the surface of intestinal epithelial eels 3. Shigella ‘Shigella dysenteriae ype I forms an exotoxin (example of exotoxin produced by gram negative becilli) * Cytotoxic activity appearsto be same as for verotoxin-I (shiga like toxin of E coi) of VTEC (associated with HUS) Produces a prefered exotoxin called ‘enterotoxin, which is responsible for manifestations of food poisoning. + Sixtypesie A,B,C, C.D & E have been identified. + Type F (seventh type) is the toxic shock syndrome toxin (TSST)‘AIPGME EXAMINATION ANSWERS AND EXPLANATIONS - 2004 = 847 Answer is C (Bacillus anthracis): Ananthnarayanan 9"/245-248 Presence of a characteristic ‘pustule' with demonstration of gram positive bacilli in chains and a characteristic M’ Fadyean's reaction is diagnostic of Bacillus Anthracis, Bacillus Anthracts,- Review ; ‘Gram positive™ = Aerobic? Sporing [spores are formed in culture or in soil but never in animal body during life] ° bacilli arranged in short chains, the entire chain being surrounded by a polypeptide capsule® chain of bacilli presents a bamboo stick appearance? M. Fadyean's reaction®: When blood films containing anthrax bacilli are stained with polychrome methylene blue for a few seconds and examined under microscope, an amorphous, purplish material is noted around the bacilli. This represents the capsular material and is characteristic of anthrax bacilli This is called M. Fadyean's reaction and is employed for presumptive diagnosis of anthrax in animals, Cultural characteristics Frosted glass appearance® on agar plates Inverted fir tree appearance? on gelatin stab culture Medusa head appearance? String of pear''s reaction: differentiates bacillus anthracis from B. cereus and other aerobic bacilli, Pathogenecity/Presentation: ‘Anthrax is a zoonosis, primarily a disease of cattle and sheep and less often of horses and swine. Human disease is contracted from animals and it may be Cutaneous anthrax Pulmonary anthrax Intestinal (Hide porters disease) (Wool sorter's disease) anthrax ‘Characterized by presence of a ‘malignant pustule * This isa « Rare ‘* A central necrotic lesion® covered by a black eschar haemorrhagic ‘* Generally resolves spontaneously® pneumonia with a ‘* Used to be caused by shaving brushes made of animal hair? high fatality rate and occasionally by mechanical transmission by insect bite? Answer is A (Standard Agglutination test): Most probably: Read text below ‘The ‘key word? in the question appears to be ‘chronic’, We are to suggest atest that would not be helpful in diagnosing chronic brucellosis of four years duration, Standard Agglutination Test: This is a tube agglutination test, in which: Equal volumes of serial dilutions of the patients serum (antibodies) + (is mixed with) Standardized antigen (a killed suspension of a standard strain of Br. abortus) | incubated at 37°C for 24 hours or 50°C for 18 hours Titre of 160 or more is considered significant The agglutination test identifies mainly the IgM antibodies ~ Ananmarayanan In brucelleses both IgM and IgG antibodies appear in 7-10 days after the onset of clinical infection. As disease progresses, IgM antibodies decline, while IgG antibodies persist or increase in titre. In chronic infections IgM may ofien be absent and only IgG can be demonstrated. Considering the fact that the standard agglutination test identifies mainly the IgM antibodies, this testis usually positive in acute infection but may only be weakly positive or even negative in chronic cases. A negative agglutination test in a chronic case thus does not exclude a diagnosis of brucellosis, ‘* The complement fixation test is more useful in chronic cases as it detects IgG antibodies also ‘* The coombs test is more reliable than the standard agglutination test as it obviates the blocking effect and. detects incomplete antibodies as wellAnswer is D (Gas is invariably present in the muscle compartments): Ananthnarayanan 9/257 * Gas gangrene can be defined as rapidly-spreading edematous myonecrosis characterized by presence of ‘gas within fascial planes (muscle compartments) '* The most important agents responsible for gas gangrene belong to the clostridia species but clostridium botulinum has not been implicated in gas gangrene. Gas producing clostridia # Clostridium species are = Gram positive = Anaerobic = Spore forming = Bacilli ‘© Pathologicalclinical features in gas gangrene are attributed to release of soluble exotoxins and not endotoxins. All clostridia owe their pathogenecity to elaboration of such soluble exotoxins that destroy tissue and blood cells. Answer is A (Listera monocytogenes): Ananthnarayanan 9"/395: Harrison's 15"/915-917 -ra monocvto; classified as 2 miscellaneous bacteria that is: © small - = coccoid® gram positive? © bacillus? © tendency to occur in chains? ‘+ aerobic or microaerophillic Ithas a characteristic slow, tumbling motility? when grown at 25°C (non motile at 37°C) This is because peritrichous flagellae are produced by the bacillus optimally at 20°C to 30°C but only scantily or not at all at 37°C. ‘* _It grown on ordinary media within a temperature range of 1" to 45°C° © Itisan intracellular pathogen®, a characteristic consistent with its prediliction of causing illness in persons with deficient cell mediated immunity © Itis the only gram positive bacteria with endotoxin® (LPS) Listerosis in humans may present in several forms 7] Pregnancy associated listerosis ‘CNS infection: Meningitis Miscellaneous ‘a meningoencephalitis, # May occur during any stage of pregnancy» Particularly affected are Abscesses ‘© Maternal illness consists of fever, myalgia _neonates and persons over Conjunctivitis, malaise, backache and abdominal 40 years of age complaints ‘¢ Trans placental spread results in abortions * Pneumonia intrauterine fetal deaths and stil births ‘© Endocarditis * Septicemia70. nL. n B. Answer is C (chocolate agar with isovitale X): Ananthnarayan 9"/331 ‘The presentation of patient is consistent with the diagnosis of ‘chancroid! or ‘soft sore’ which presents as a tender ‘non indurated irregular ulcer on the genital ‘Agent factors: ‘Haemophillus ducrei Short ovoid bacillus or cocobacillus with a tendency to occur in ‘end to end pais’ or ‘short chains’. Gram negative (but may appear gram positive and show bipolar staining) May be arranged in small groups or whorls or in parallel chains giving a ‘school of fish' or ‘rail road track’ appearance. Cultur ‘© On chocolate agar, enriched with isovitale X and fetal calf serum, and containing vancomycin as a selective agent, H duerei forms small gray translucent colonies. Other media include: Fresh clotted rabbit blood Choriono allantoic membrane of chick embryo Note: * Thayer martin medium is used for gonococei 2 * Tellurite blood agar is used for diptheria ® ‘© Blood agar with factor II & X are also used for Haemophilus species such as H. influenzae °, but these have not been mentioned for H. ducrei Answer is C (Polymerase chain reaction): Harrison's 15/1079 "Amplification assays such as ligase chains reactions and polymerase chain reactions are now the most sensitive chlomydial diagnostic methods available” —Harrison 1. Cell culture techniques ‘Low and variable sensitivity (60 to 80%) 2. Direct immunofluorescent antibody test | « 70-85% sensitive and quiet specific 3. Enzyme lented immuno sertant assay ‘© 60-80% sensitive (ELISA) 4. Ligase chains reaction and PCR © Most sensitive chlamydial diagnostic methods available Answer is D (Multiple myeloma): Repeat Harrison's 15/1110, Ananthnarayan 9°/475 EB virus has been implicated in the following conditions: © Infectious mononucleosis ‘+ Lymphoproliferative syndrome (X-linked-Dunean's © GBsyndrome syndrome) © Acute transverse myeliis © CNS lymphoma © Peripheral neuritis © Tonsillar carcinoma © Aplastic anemia © Gastric carcinoma * Chronic fatigue syndrome © Leiomyosarcoma © Burkit’s Lymphoma © Thymoma '* Hodgkin's disease (mixed cellularity) ‘© Oral hairy leukoplakia in HIV adults 2 Tell lymphoma © _ Nasopharyngeal carcinoma Answer is D (Detection of viral haemagglutination inhibiting antibodies in a single serum specimen): Harrison's 15"/1091, Urology manual for medical students Diagnosis requires demonstration of viral haemagglutination inhibiting antibodies in at least two samples. One single serum specimen is not sufficient. Hacmagelutination inhibition test: Many viruses agglutinate erythrocytes by virtue of presence of haemagglutinin proteins on their surface ‘+ This reaction may be specifically inhibited by immune or convalescent sera which contains antibodies to the «haemagglutinin proteins ‘+ Hacmagglutination inhibition assays measure this ability of serum antibodies to inhibit virus induced agglutination of erythrocytes.850 74. 75. 16. ‘AIPGME EXAMINATION ANSWERS AND EXPLANATIONS - 2004 Diagnosis ‘+ Diagnosis requires demonstration of viral haemagglutination inhibiting antibodies in at least two samples. ~ First in the acute serum (collected early in the acute phase of disease) = Second during convalescence (convalescent serum taken 14-21 days later) ‘* Serological diagnosis is based on demonstration ofa greater than four fold inerease in IgG antibody ‘concentration (antibodies inhibiting haemagglutination) in the convalescent serum in comparison to the acute serum ‘+ Assingle serum specimen showing inhibition of viral haemagglutination is not considered diagnostic because such inhibition may also be caused by the presence of certain ‘non specific inhibitors’ that prevent agglutination of erythrocytes by viruses. Such non specific inhibitiors may be lipids and lipoproteins ete and are found frequently in serum, saliva, urine and milk ete Answer is C (There is a single serotype causing infection) Ananthnarayanan 9/486, Park 17°/ ‘© The causative agent of poliomyelitis is the polio virus which has three serotypes 1, 2 and 3, Most outbreaks of paraljtie polio are due to type — Ivins? Sa Type Ul virs is the most effective antigen ‘Feacooral route 7 Is the main route of spread in developing countries Droplet infection i ‘May occur in the acute phase of disease. (more important in developed countries) ‘© Clinical spectrum: “napparent ben fed Spee AT RANT Ue re Tere ea ET ‘Abert pls Salas gua Pipta ae Tea _ «mild sel lining lines and dlagasis cannot be made clnicaly Paralytic polio + Less than 1% of cases ® PSE ‘* Herd immunity results even if only approximately 66% of community is immunized. Intestinal infection stimulates the production of IgA secretory antibodies. The vaccine progeny is excreted in the feces and secondary spread occurs to household contacts. Non immunized persons are thus immunized providing herd immunity. Answer is C (Hepatitis E): Repeat: Ananthnarayanan 9°/550; Harrison's 15/1933 ‘A unique feature of hepatitis E virus is the clinical severity and high case fatality rate of 20-40% in pregnant women, especially in the last trimester of pregnancy’ - Ananthnarayan " Hepatitis E can be complicated by fatal fulminant hepatitis in 1-2% of all cases and in upto 20% of cases ‘occurring in pregnant women’ — Harrison 15/173. Answer is D (Hemorrhagic fever): Ref: Ananthnarayan 9°/491 © Entervirus type 70 causes acute hemorthagic conjunctivitis but itis not responsible for hemorrhagic fever, which is caused by Hantavirus (haemorrhagic fever with renal syndrome) Enteroviruses Polioviruses type 1-3 Coxsackievirus Echoviruses type 1-34 Meningitis __Enteroviruses type 68-72 Type A Type B ‘Type 1-24 Type 1-6 1. Herpangina 1. Epidemic pleurodynia (Bornholm disease) 2. Aseptic meningitis 2. Myocarditis and pericarditis 3. Epidemic fever with maculopapular or vesicular 3. Juvenile diabetes rashes 4. Spastic paralysis (Hand, foot and mouth disease) 5. Pancreatitis, hepatitis, encephalitis 4. Respiratory infections # Entero virus type 68 —> pneumonia and bronchitis Entero virus type 71 —> meningitis and encephalitis. ‘© Entero virus type 72 —> Hepatitis virus type A (Heparna virus)‘NPGME EXAMINATION ANSWERS AND EXPLANATIONS -2004 © 1. Answer is C (kyanasur forest diseases is transmitted by Ticks): Park 17" Repeat © KFD is transmitted by ‘Hard ticks Disease transmitted by Ticks: Ward tks (Sc © Tick typhus? Q Fever ® © Tick paralysis? Relapsing fever ° © Tularemia® ‘© Viral haemorrhagic fever®: kyanasur forest disease ‘© Human babesiosis ° ‘© Dengue is transmitted by acdes and not by cules, Diseases transmitted by mosquitoes Culex | ‘© Bancroftian filariasis © Japanese encephalitis : © West Nile fever 4 © Viral arthritis = Aedes ‘Monsonoides © Yellow fever? © Malayan (Brugian) filariasis j © Dengue® © Chikangunya © Dengue haemorrhagic fever? | © Chikangunya fever® + Chikangunya haemorrhagic fever ® © Rift valley fever ® Yellow fever is not found in India ‘© Four different serotypes of Dengue virus exist (not one) PHARMACOLOGY 7B. Answer is A (is excreted mainly by the kidney): KDT 7/29 (Nom ionized drugs Tonized drugs ‘+ Non ionized drugs are lipid soluble + Lonized drugs are lipid insoluble + Rapidly absorbed from stomach and» Poorly absorbed from stomach and intestine intestines + Poorly pass across placenta + Rapidly pass across placenta + Highly ionized drugs or polar drugs are not + Reabsorbed by renal tubules after reabsorbed by the tubules and hence are {filtration and hence net excretion by easily excreted. Kidney is less sma protein bindi + Acidic drugs bind to plasma albumin while basic drugs bind to «acid glycoprotein + Extent of binding depends on the individual compound and no generalization can be made with reference to its ionization. 1”. Answer is D (phase IV): Goodman Gillman 10/60 ‘As depicted in the flow chart below, ‘phase 4 of clinical testing is a phase of post marketing surveillance and is undertaken on the basis of result of phase 1, 2 and 3. This phase occurs only after *FDA Safety Review’, \DA submission’ and finally ‘NDA approval’ and hence does not require ethical clearance.ai. PRECLINICAL TESTING Satis in vir Avimal os 1590 Testing Tem Leng avenge 26 eu) Tem FDA aay J ssi Review nt (CLINICAL TESTING Who? Nonna volunteers, special populations {Genl and hepatic inpairoea) Why? Safty, blalogial effets, metabolism, ‘ints, drug interactions. By whom? Cina! pharmacolois PHASE 2 Wo? selcted pation Why? Thrapettic efficacy. dose rang, iets, metaboli| By whoo? Cine pharmacologsts and selina ives 2.1ayears f iE 1 : wwerage 5.6 years) i Ib ‘Who? Lage sample of selected patient Wy? Safely and efficacy ‘By whan? Cina veto ¢ NDA subi 2 mont -7 years (average 26 yeu) Jom NDA Approved ‘POSTMARKETING SURVEILLANCE PHASE ‘Who? Patients given drug for therapy Why? Adverse reactions, patterns of drug utlization, additional indications iscovered Answer D (Erectile dysfunction): Principles of anatomy & Physiology by Tartora 10"/580 Erection is mediated via prarasympathetic stimuli, while ejaculation is under control of sympathomimetic agents. Thus sympathomimetic agents will not help in erectile dysfunction, Sympathomimetic agents such as ‘a1 adrenergic agonists! may be useful in reversing priaprism. ‘Other functions: ‘© Hypo tension; a, adrenergic agonists cause vasoconstriction is skeletal muscle arterioles and are thus useful in conditions of inadequate perfusion to vital organs. ‘© Hypertension; Centrally acting sympathomimetic agents suchas clonidine (ay adrenergic agonist are used for treatment of hypertension © Heart disease: agonist action (sympathomimetic cause increased hear rate and force of atrial and venticular contractions. Answer is C (Renal dysfunction is not a contraindication for their use): - KDT 7"/275-76; Katzumg 708 Biguanides are contraindicated in patients with renal disease, alcoholism, hepatic disease or conditions predisposing to tissue anoxia such as chronic cardiopulmonary dysfunction, because of an increased risk of lactic acidosis induced by biguanides drugs in these diseases. Biguanides: Oral hypoglycemic agents Biguanides are orl hypoglycemic agents that do nota by increasing insulin release? and cause litle or no Aypogtvcemia® ‘Mechanism of action: They donot stimulate pancreatic cells to cause insulin release. Probable mechanism for bbypoglycemic actions include = suppress hepatic gluconeogenesis® and glucose output from iver®: major action ~ inhibit intestinal absorption of glucose” ~ promote peripheral uilizaton of glucose by enhancing anaerobic glycolysis ~ enhance binding of insulin to its receptors and stimulate insulin mediated glucose disposal ‘Adverse effects: Hypoglycemia is nota complication (Little or no hypoglycemia)® + Lactic acidosis is most serious complication® + Abdominal discomfort, anorexia, nausea, mild diarrhea and tiredness are frequent Use + May be used alone + Biguanides re also indicated for use in combination with suflonylureas and thiazolidinediones in type 2 diabetes mellitus {in whom oral monotherapy is ineffective.[AIPGME EXAMINATION ANSWERS AND EXPLANATIONS - 2004 * 853 Answer is C (Hypoglycemia is a serious and common side effect): KDT 7”/277; Katzung 9"/710, Harrison's 15"/2132 Prominent adverse effects of «glucosidase inhibitors include, flatutence, diarrhea, and abdominal pain and result from the appearance of undigested carbohydrates in the colon that is then fermented into short chain {fatty acids producing gas. Hypoglycemia is not a side effect when a glucosidase inhibitors are used alone (monotherapy) Hypoglycemia may occur with concurrent treatment with sulfonylurias. Thus hypoglycemia is certainly not a common side effect. Alpha glucosidase inhibitors: acarbose: Miglital ‘These are a class of oral glucose lowering agents that reduce post prandial hyperglycemia by delaying glucose absorption. Action: + Complex starches, oligosacharides and diasacharrides must be broken down into individual monosaccharides before being absorbed in the duodenum and upper jejunum. + This action i facilitated by "a glucosidase’ enzymes that are attached tothe brush border of the intestinal cells. + + Digestion and absorbtion of such agents is thus decreased with o. glucosidase inhibitors and post prandial hyperglycemia is reduced without increasing insulin levels. Use: * They are FDA approved for use in individuals with type-2 diabetes as monotherapy and incombination with sulfonylureas ~ Kateung + These agents are unique as they reduce post prondial glucose rise even in individuals with type-I diabetes rellitus Adverse effect 1 Major adverse effects include flatulence, diarrhea and abdominal distension/pain: This results from appearance of undigested carbohydrates, inthe colon that is then fermented into short chain fatty acids releasing gas. 2.Hypoglycemia: Not a problem with monotherapy May occur with concurrent use sulfonylureas. Contraindications: These agents are contraindicated in patients with inflammatory bowel disease, or any intestinal condition that could be worsened by gas and distension + Should not be used in patients with renal impairment «Should be used with caution in presence of hepatic disease. Answer is D (Flutamide): KDT 7"/302; Katzung 9/916; Harrison's 15"/538 Flutamide is a non steroidal drug having specific antiandrogenic, but no other hormonal activity. ‘Actio + It's active metabolite competitively blocks androgen action on accessory sex organs as well as on pituitary ~ inereases LH secretion by blocking feed back inhibition + Plasma testesterone levels increase in males which par flutamide ly over come the direct antiandrogenic action of Use: Palliative effect may occur in advanced prostatic carcinoma. Has been tried in female hirsutism along with oral contraceptives Side effects: ‘Gynaecomastia + Breast tenderness + Liver damage «Nausea & Hot flushes (Bone marrow depression has not been mentioned as aside effect) + Daunarubicin, Doxorubicin and chlarambucil are all known agents for bone marrow depression.854 84. 85. 86. 87. ‘AIPGME EXAMINATION ANSWERS AND EXPLANATIONS - 2004 Answer is C (Reduces incidence of venous thrombosis) KDT 7/314 ‘The only serious concern with raloxifen use isa three fold increase in the risk of deep vein thrombosis and pulmonary embolism’ — KDT5%/280 Raloxifen : review Raloxifen isa recently introduced selective estrogen receptor modulator (SERM) ‘Mechanism of action: Partial agonist in Antagonist action in Bone > Endometrium Cardiovascular system = _ Breast, ‘+ Ithas high affinity for both ER cand ER Bp + Ithas a distinet DNA target: ‘Raloxifene response element (RRE) Actions: 1. Prevents bone loss in post menopausal women : (BMD may even increase 0.9 to 3.4% over years) 2. Reduces the risk of vertebral fractures to half: (but not that of long bones except ankle) 3. Reduces LDL cholesterol. There is no increase in HDL or tryglyceride levels. Tt may have atherogenic potential 4, Reduces risk of breast cancer (by 65%) (protection was confined to Estrogen receptor positive breast cancer) ‘+ Raloxifen does not stimulate endometrial proliferation and there is no increase in risk of endometrial carcinoma ‘+ Raloxifen does not relieve vasomotor symptoms of menopause. Rather hot flushes may be induced in some ‘women. ‘+ Raloxifen isan effective alternative to HRT for prevention and treatment of osteoporosis in post menopausal ‘women. It has no use in men, effec 1, Hot flushes and leg cramps are generally mild and occasional vaginal bleeding may be seen 2. Increase in risk of deep vein thrombosis and pulmonary embolism. Answer is D (Buspirone): KDT 7"/466 Buspirone is the first azopirone — newer antianxiety drug which differs from benzodiazepines in that it does not interact with GABA-BZD receptor chloride channel complex — KDT Answer is B (Digoxin): Harrison's 15"/1295 ‘Ifin the presence of AF, the ventricular rhythm because regular and slow (eg. 30-60 bpm), complete heart block is suggested and if ventricular rhythm is regular and rapid (eg 2 100 bpm), «tachycardia arsing in the AV junction or ventricle should be suspected. Digitalis is intoxication is a common cause of both henomenon.'- Harrisons Above patient has following complaints = Rheumatic mitral stenosis ~ Atrial fibrillation The patient in question has atrial fibrillation and while on treatment for fast ventricular rate, develops a regular and slow pulse of 64/min, thus suggesting a complete heart block, secondary to digoxin administration. Answer is D (Systemic Lupus erythematosis): KDT 7/533 ‘Amiadorone' is an ‘iodine’ containing” long acting antiarrythmic belong to class III°, "APD is prolonged” (Action potential duration) ERP is prolonged ° (Effective refractory period) ‘Conduction is slowed ® (oral does have minimal effect on cardiac contractility and BP) Use: Used inesistant ease of VT and recurrent VF Used in resistant eases of AF when other drugs have filed Adverse effects 1. Teinerferes with thyroid function: Both hypothyroidism and Hyperthyroidism may be seen (inhibits peripheral conversion of T, to T;°) Cardiac depressant action®: seen not on oral dose but on Lv injection fall in BP and myocardial depression occurs Peripheral neuropathy? Pulmonary alveolitis and fibrosis” Photosensitization® ‘Comeal microdeposits®90. on. ‘AIPGME EXAMINATION ANSWERS AND EXPLANATIONS -2004 © 855 Answer is D (Sucralfate inhibits aborption of ranitidine): KDT 7"/649, 656; Katzung 9"/1043 + Sucralfate polymerizes at pH < 4 by cross linking of molecules, assumes a sticky gel like consistency, and then preferentially and strongly adheres to ulcer base, where it precipitates surface proteins and acts as a physical barrier preventing acid, pepsin and bile from coming in contact with the ulcer base. + Normally ranitidine would increase the gastric pH (lower acidity) and prevent action of sucralfate by preventing its polymenzation which occurs at pH values < 4, Ranitidine however does not lower the gastric pH (does not Tacidity) and hence options C is incorrect. + Sucralfate also has been shown to adsorb many drugs and thereby it interferes with their absorption. Absorption of tetracyclines, fluoroquinolones, H receptor antagonists, phenytoin, digoxin are some of them, Here inhibition of absorption of ranitidine as a result of its adsorbtion on sucralfate isthe best reason to explain the incorrectness of the combination. Answer is D (Domperidone blocks levodopa induced emesis and it’s therape potential): KDT 7"/666, 429 ‘When domperidone is administered with levodopa or bromocriptine, it counter acts their dose limiting emetic action, without affecting the therapeutic effect in Parkinsonism’ - KDT Levodopa isa prodrug, inactive by itself but is the immediate precursor of the transmitter dopamine. Interactions: 1. Pyridoxine abolishes the therapeutic effect by enhancing peripheral decarboxylation of levodpa. ? Less levodpoa is thus available to cross BBB, to be converted ito dopamine in dopaminergic neurons in CNS 2. Phenothiazones, butyrophenones, and metoclopramide’ reverse therapeutic effect by blocking DA. receptors. 3. The antidopaminergic domperidone blocks levodopa induced nausea and vomiting without abolishing its antiparkinsonian effect, because domperidone does not cross the blood brain barrier. 2 4, Reserpine abolishes levodopa action by preventing entry of DA into synaptic vesicles. ® 5. Nonselective MAO inhibitors: prevent degradation of peripherally synthesized DA and NA ~ hypertensive crisis may occur. ® AIPGMEE 2004 - EXPLANA al 6.__Atropine and other anticholinergic drugs have additive anti parkinsonion action®. Answer is C (Cisapride) : Harrison's 15/434 Cisapride is metabolized by the hepatic 'eytochrome p-450 CYP 344 enzyme’. When coadministered with drugs that inhibit this enzyme such as ketoconozola, fluconazole, macrolide antibiotics and HIV protease inhibitor significant increase in serum levels of cisapride may occur that may lead to QT prolongation on the ECG and serious cardiac complications — Katzung 9"/1046 Drugs causing prolonged QT interval/Torsades de pointes Amiodarone 10. Disopiranide 19. Prosanamide 2 amitipyine® 1, Doxepia 20. Quinine 3. Astemizole 12, Enythromein® 21, Resperidone 4 Beprdil 13, Haloperidl® | 22. sottot 5. Chlorpromazine 14, butlde 23. Terfenaine? 6 Cisapride® 15. Imipramine? 24, ‘Trimethoprim-sulfmethoxazole 7. Clomipanine 16. Mapoiline 25, ‘Theoridazene 8 Desipramine 17. Penamidine 26. Thiothinene 9. _Dipheny hydramine 18,_Probucal | 27. Teioperazene [This is an exhaustitive list, and has been placed here only for reference purpose] Answer is A (Supra spinal analgesia): Katzung 9"/498 This is one of the controversial/confusing types, with different texts suggesting different answers. Personally believe in referring a standard text, that leads us some where towards a simple best option rather than another standard text, that confuses the issue. It is for this reason that I have selected Katzung to base my answer on.‘Swpraspinal and spinal analgesia Sedation Inhibition of respiration (Respiratory depression) Modulation of hormone and newrotransmiter release Supraspinal and spinal analgesia ‘Modulation of hormone and neurotra Supraspinal and spinal analgesia Psychomimetic effects Slowed Gl transi Although KDT also attributes respiratory depression and reduced gimotilty to delta receptors the fact that they have not been mentioned in Katzung indicate these to be minor functions with 5 receptors if at all Hence supra spinal analgesia here is the answer of choice. 92, Answer is A (Head injury): KDT 7/474; Goodman and Gillman 10%/591 ions Of Mo T._ Head injury : morphine is contraindicated in patients with head injury (KD). Reasons are - a. By retaining CO; it increases intracranial tension which will add to that caused by head injury itself. b. Even therapeutic doses can cause marked respiratory depression in these patients. ©. Vomiting, miosis, and altered mentation produce by morphine interfere with assessment of progress in head injury cases. 2. Branchial asthma : Morphine can precipitate an attack by its histamine releasing action. 3. Hypothyroidism, liver and kidney disease patients are more sensitive to morphine 4, Infants and elderly are more susceptible to the respiratory depressant action of morphine. 5. It is dangerous in patients with respiratory insufficiency (Emphysema, pulmonary fibrosis, corpulmonale), sudden deaths have occurred. 6. Hypotensive states and hypovolemia exagerate fallin BP due to morphine. 7. Undiagnosed acute abdominal pain —> morphine can aggravate certain conditions e.g., diverticulitis, biliary colie, pancreatitis. E 8. Elderly male -> chances of urinary retention are high. me 9. Unstable personalities ~» are liable to continue its use and become addicted. + Morphine should thus not be used in cases of head injury and bronchial asthma both. However as the text uses the term ‘contraindicated in association with head injury, we select this as a better answer from the options provided and draw the following inference to justify answer. = Morphine is contraindicated in patients with head injury ~ Morphine should be avoided in patients with bronchial asthma as it has the potential to exacerbate or precipitate an attack. + Patients with hypothyroidism are more sensitive to effects or morphine. This however does not contribute 4s a contraindication to its use and a dose reduction may probably be all that is required for these. 93. Answer is A (Sulfasalazine is absorbed well from GIT): KDT 7/683, 706; Katzung 9"/591 + Sulfasalazine is poorly absorbed from the gastrointestinal tract. Sulfosalazine is a compound of sulfapyridine and S-aminosalicylicacid. Only 10-20% of orally administered sulfasalazine is absorbed. Itis split up in the intestine to release sulfapyridine and 5-ASA. Sulfapyridine is well absorbed while 5-amino salicylic acid remains unabsorbed. ‘+ Sulfonamides can precipitate in urine specially at neutral or acid pH producing crystalluria, hematuria or even obstruction Crystalluria is treated by administration of sodium bicarbonate to alkalize the urine and fluids to maintain adequate hydration. + Kernincters may be precipitated in new bor specially if premature by displacement of bilirubin from plasma protein bending sites and more permeable blood brain barrier. + Sulfonamides are primarily bacteriostatic ‘They inhibit both gram positive and gram negative bacteria, nocardia, chlamydia trachomatis, and some protozoa.96. AIPGME EXAMINATION ANSWERS AND EXPLANATIONS - 2004 © 857 Answer is C (Ampicillin and chloramphenical) KDT 7/741; Goodman & Gillman 10/1164 ‘Combination ofa bactericidal with a bacteriostatic drug may be synergistic or antagonistic depending upon the ‘organism. ‘+ Ifthe organism is highly sensitive to cidal agent, antogonism may be seen: = Pocumosoedt > Penicilin-+ Teraeyeline #Poeumocoesi - Penicilin + Chloramphenical © Group A steplcocsi ~ Pesiilin + Eythromyein 2 Bali - Nalidixi aid + Nitroirantoin + Itthe organism has fow sensitivity to the cidal agent, synergisin may be seen: + Actinomyeosis - Penicilin + Salfonamide # Brucellosis - Seplomycin + Tetracycline # Kpmeumonese - streptomycin + chloramphenical + Leprosy - Refampin + Dapsone Thus the combination of penicillin and chloramphenicol is antagonistic in nature for organisms such as ‘Pneumococii. Other options: ‘ Vancomycin and Amikacin: Combination increases risk of renal and otoxicity, but is not antagor Caphellexin and Gentamycin: Combination increases risk of renal toxicity but is not antagonistic * Ciprofloxacin and piperacillin: combination is mutually synergistic and used in various hospital acquired infections. Answer is B (Trovofloxacin): Goodman Gillman 10/1182 Kalzung 9/779 + Fluoroquinolones that are excreted primarily by non renal mechanism and for which adjustment is not ‘needed in renal pathology include : I. Nalidixie acid 2. Grepotioxacin 3. Trovafloxacin 4, Pefloxacin Fluroquinolones that are primarily excreted by renal mechanisms and for which dose adjustment is needed include: Sparfloxacin has 50% renal and 50% fecal route of excretion and hence dose adjustment may be required in renal pathology Answer is D (Cefoperazone): Goodman Gillman 10"V/1174 “Firstciice 7/7 Yseeond choice ‘Antipscudomonal penicillin + quinolone Antipscudomonal pencillin + ‘+ Antipseudomonal cephalosporin aminoglycoside ‘+ Imipenum or Meropenem ‘+ Aztreonam + aminoglycoside Drugs for pseudomonas include : 2 1, Antipseudomonal Cephalosporins = Ceftazidime + Cefaperazone (-cephalosporin excreted in bile therefore not given with probenacid®). + Other Id gen. CS. (but these are not dependable) 2. Antipeudomonal pencillins: * Carobxy penicillins: e.g. Carbeneillin and Ticarcillins. + Ureidopencillins __: e.g. Azlocilline, Mezlocilline, piperacillin.97. 98, 100. 101. 3. Imipenem : [tis the most broad spectrum B lactam antibiotic® (active against pseudomonas)? 4, Aztreonam : It is a B lactam antibiotic with only one lactam ring i.e. monobactam. 5. Quinolones : e.g, Ciprofloxacin 6. Aminoglycosides : Gentamycin, tobramycin and amikacin are used for gram -ve infections. 7. Polypeptides like Polymyxin B and Colistin may be used. Colistn is more potent in pseudomonas Remember + Vancomycin does not act on pseudomonas ° + Bacitracin does not act on pseudomonas Answer is C (Streptomycin): KDT 7°70 ‘Streptomycin is an aminoglycoside antibiotic contraindicated in pregnancy due to risk of foetal ototoxicity. Answer is A (Tobramyein): KDT 7/744; 770 Second line drugs in treatment of tuberculosis include 1. Thiocetazone 1 2. PAS 2. Ofloxacin 3. Ethionamide 3. Clarithromycin 4. Cycloserine 4. Azithromycin 5. Kanamycin 5. Rifabutin| 6 Amikacin 7. Capreomyein ane Tobramycin bas activity similar to gentamycin, but is 2-4 times more active against pseudomonas and proteus. It has not been mentioned to be affective against M. tuberculosis. Answer is C (Taxol): KDT 7°/865; CMDT 2003/1613 + Taxol is the brand name for paclitaxel and is classified an 'antimicrotubule agent’ It is indicated for metastatic ovarian and breast cancers but is not a hormonal agent. + Aromatase inhibitors (eg. Anastrazole, letrozole) and inactivators (exenestase) block peripheral conversion of adrenal androgens into estrogens and have been shown to be atleast as effective as or more effective than tamoxifen for metastatic hormone receptor expressing breast cancer. + Tamoxifen is a selective oestrogen receptor modulator (SERM) and is useful in estrogen receptor expressing breast cancer. Answer is B or A (Doxorubicin or Adriamycin) : Oxford textbook of oncology Devita’s tex’ 24/ 2511, 2525 ‘+ Doxarubicin (adriamycin) has been shown to be an effective agent against leiomyosarcomas arising in the uterus. ‘+ The best responses in cases of soft tissue tumors have been observed with doxarubicin (adriamycin) and ifsofamide (not in option) Itis certainly not possible to chose between Doxorubicin and adriamycin as adriamycin is infact a trade name for doxarubicin itself. Doxirubicin would perhaps be the ‘pick! if we were to choose one. Answer is B (Cyclosporine): KDT 7°/915 Interactions of | e with other dri INH? + INH produces a pyridoxine deficiency state ‘+ INH reacts with pyridoxine to form hydrazone and inhibit generation of pyridoxal phosphate ‘* Due to formation of hydrazones the renal excretion of pyridoxine compounds is increased Thus INH produces a pyridoxine deficiency state 2, Levodops + Pyridoxine abolishes the therapeutic effet of dopamine in bri + Pyridoxine promotes formation of dopamine from levodopa in peripheral tissues, thus reducing its availabilty in brain and abolishing its therapeutic effect in parkinsonism. 3, Hydralazine: ‘These drugs interfere with pyridoxine uilization and action {also eycloserne & pincllamine) 4.0cP° + Reduce pyridoxal levels in some women |S.d-dooxy pyridoxine « Is a vit, By antagonist