AIPGME EXAMINATION ANSWERS & EXPLANATIONS 2oOo0GOe ae LA cna statements that have been asked as Oa Lear ee ACM ed examinations over the previous years These are the most important UNL KMN Ma ip a eee een al Ty dd aaa ON mes ew Lan ele a OCLC to pay more attention to the entire portion of text marked “Q” as prefix AO LaeANATOMY. 1 3. Answer is D (Popliteus): Gray's 41°/1397 “The popliteus tendon is intraarticular, being located within the capsule of knee joint. ‘Popliteus arises within the capsule of the knee joint by a strong tendon’-Gray’'s Remember opliteus is regarded as the muscle that unlocks the knee joint at the beginning of flexion of a fully extended knee ®. (Popliteus rotates the tibia medially on the femur or when the tibia is fixed rotates the femur laterally on the tibia). Answer is B (Exophthalmos): Repeat.; Read text below: Stellate ganglion block or damage to stellate ganglion results in Horner's syndrome, Horner’s syndrome is associated with enophthalmos and not exophthalmos. Answer is C (Cut to spinal part of accessory nerve): BDC II1/4* /71,72,198: BDC 1/6/87; Surgical anatomy by Lee MC Gregor 12"/439,438 Over head abduction ie. abduction in the range of 120° to 180° (above head to brush hair) Occurs at the Seapulo thoracic linkage and is aided by upward rotation of Scapulae by the action of trapezius and serratus anterior. Trapezius is supplied by the spinal part ofthe accessory nerve which runs inthe middle ofthe roof of the posterior triangle Inability to raise arm above the level of head following surgical procedure or the posterior triangle suggests the agnosis of injury to spinal part of accessory nerve. Glenohumeral joint (0-120") Initial abduetion Abduetion upto 90° Abduction eel eee (0-150°) 15-90") (90"-120°) scapulothoracie Supraspnatus Dettid Delt (+shor extemal otators) Linkage (Guprascaputar nerve) (Axillary nerve) ‘This ial 30° of Abduction requires the Trapezius humeras tobe externally rotated (spinal acessary nerve) allowing the grater tubercle to pass Serratus Anterior posterior fo acromian (Axillary nerve) __(nerve to serratus anteres) Contents of the posterior triangle (ites Occipital riage’ - Subelavian triangle) Nerves « Spinal acessory nerve Three trunks of brachial ‘+ Four cutaneous branches of cervical plus plexus * Lesser oosipital (C2) Nerve to serratus anterior * Great auricular (C2,C3) (long thoracic, C5, 6,7) + Anterior cutaneous neve of neck (C2,C3)_ « Nerve to suboavius (C5, ~ Supraclavicula nerves (C3, C4) Co) ‘© Muscular branches «© Suprascapular nerve (CS, = Two small branches tothe levator scapulae C6) (c3.c4) - Two smal branches to the trapezius (C3, i) «Nerve to rhomboideus (C5) «+ Upper part ofthe rahi plexus Vessels « Transverse cerviak artery and vein + Third par of subclavian + Occipital artery artery and subclavian vein + Suprascapular artery & vein + Commencement of transverse cervical artery and termination ofthe corresponding vein «Lower par of external jugular vein Lymph Along the posterior border ofthe 1 A few members ofthe nodes sterocleidomasoid, more inthe lower supraclavicular chain pr, the supraclavicular nodes and a few at ‘he upper angle the ociptal nodes5 ‘Scaleneus medius lies deep in the floor of posterior triangle, deep to the prevertebral layer of deep cervical fascia. Its actions include Lateral flexion of cervical spine elevation of first rib and stabilization of neck. Itis not involved in abduction of the arm at all. ‘+ Suprascapular nerve courses the lower part of the posterior triangle (not the middle) and supplies the supraspinatus (and inferior spinatus). Its action includes initiation of abduction and is involved during an incision and drainage 15°, It is unlikely to be injured during an incision and drainage procedure in the middle of posterior triangle and its involvement will not lead to difficulty in overhead abduction. + Spread of infection to shoulder joint or septic arthritis will lead to painful limitation of all movements of the joint and not manifest only with limitation of overhead abduction, Answer is B (Internal maxillary artery): BDC JI1/6"/119 Middle meningeal artery is a branch of the fist part of the maxillary artery® given off in the infratemporal fossa. It enters the middle cranial ‘fossa through the foramen spinosum.2 Maxillary artery: For descriptive purposes the maxillary artery is divided into three parts by the Lateral pterygoid? removal ofthe lateral pterygoid Maxillary Artery (Terminal branch of extemal carotid artery) ————ee_ Horizontal course between neck of Superficial tothe lower head of Lateral Through the two heads of Lateral pterygoid mandible along lower border of Lateral Pterygoid and through the pterygopalatine fissure pterygoid «© Deep temporal + Posterior Superior alveolar # Deep auricular + Prerygoid + Infiaorbital + Anterior tympanic = Mosseterie + Greater Palatine + Middle meningeal © Buccal + Pharyngeal + Acessary meningeal + Artery of pterygoid canal + Inferior alveolar ‘+ Sphenopalane Answer is A (Lower border of L1): Gray's 39/775; BDC IIl/ 6"/ 334; IBS Neuroanatomy 6" /27 ‘Spinal card extends from the upper border of the atlas to the lower border of vertebra LI or the upper border of vertebra L2.’ -BDC I11/309 (4" edition) ‘Spinal cord extends from the upper border of the atlas 10 the junction between the first and second lumbar vertebra’ Grays/AIPGME EXAMINATION ANSWERS AND EXPLANATIONS -2006 + 561 Remember ~ = sae ‘+ Inadults the cord ends at the junction between Ly&L;® a Grly ‘laseen + Inchildren the cord ends at the level of 3! Lumbar cor vertebra (L3) (Surgical anatomy Megregor 12°/405) «The dural sheath ends at level of S; vertebra? + Subdural space ends at level of 8; vertebra + Filum terminale extends from level S; vertebra to coceyx®, + Gervical enlargement of spinal cord extends from C,10T; a Segments lane (Source of spinal nerves which supply the upper limbs) aes ‘+ Lumbar enlargement of spinal cord extends from L, to S;® (Source of spinal nerves to the lower limbs) Com edulis Important vertebral levels in relation to the spinal cord Answer is B (Deep inguinal Lymph nodes): Dutta Gyanecology 4/28; BDC II/6"/390 Lymphatics from the cervix do not drain to the deep inguinal Lymph nodes. Lymphatic drainage from the cervix The lymphatic from the cervix drain into the following Iymph nodes coursing along the uterine veins. Compon ac Pregacral Common iliac © Parametrial group » QO *Intemal iliac group OO tara © Obturator group ¢ itiee + External iliac group @ + Sacral group \\. \xcanal 0 0% Paramateril =0. Subepithelial plexus Inconsistant-— {Secondary Group: + Common iliac group Obturator © Superior Lumbar group Lymphatic drainage of the cervix Note: Lymphatics from all the primary groups drain into the secondary group. Answer is D (Vascular sinuses): TB Singh Histology 4"/185; Harsh Mohan 5/464; Internet references as specified. Vascular sinuses are a component of the red pulp of spleen and not the white pulp. Structure/ Histology of Spleen: www.med.ca/anatomyts/thorax/lymphist htm 1, Capsule (outer covering of connective tissue): The spleen has a capsule which is mainly collagen with some elastin 2. Trabeculae: Septae pass inwards from the capsule providing structural strength to this blood organ 3. White pulp: The white pulp ofthe spleen is formed of a mass of T and B lymphocytes surrounding central arteries. Blood passes outwards from the central arteries to reach the marginal zone surrounding the white pulp. Antigen presenting cells are present in the marginal zone as are macrophages. The T and B lymphocytes respond to the presence of antigens in the perfusing blood. 4, Red pulp: The red pulp is made up of a mesh of leaky sinusoids through which the red cells re squeezed. Many of the cells lining the sinusoids are phagocytic and are able to engulf debris from the blood or fragments of red cells broken by being unable to bend enough to pass through the pores ofthe leaky sinusoids.‘562 © AIPGME EXAMINATION ANSWERS AND EXPLANATIONS - 2006 - White pulp Wed pulp es Consists of lymphatic (olen) nodules Surrounds iymphatc nodules ands intermeshed + Central artery: actually an arteriole, usally has an with he tabeculae eccentric position nthe nodule + Venous sinuses: spaces that conduct blood + Lymphocytes located between cods of lymphocyes plete (ympbati) noduloe + Adjacent blood spaces: contains blood cells ‘Are of densely packed |ymphocytes and macrophages and appears to be arranged in cords caled splenic and cords of Lymphocytes billroth, Germinal center: sphericl-shaped collection of relatively sparse actively diving lymphocytes ‘+ Marginal Zone: Antigen presenting cll Macrophages 8. Answer is C (Oogenesis): /B singh Embryology/ 7"/ 3,14,12; Langman 12"/12-13 Polar are formed during the process of oogenesis. ‘+ Female gonad is the ovary Oogonia or germ cells. + Male gonad is the testes that give rise to ova are contained + Spermatogonia or germ cell that give rise to spermatozoa are found in the sec cords of the testes ‘+ Ova are derived from oogonia and in this process. + Spermatozoa are derived from spermatogonia and in polar bodies are formed. this process no polar bodies are formed. : ‘00c0NNM aa &) &) | centages ofr sremaocomas meron | nts | NN . ay OSs : SECONDARY (=) Q = 2 aes Second 7 \8S =I or 696 oua(*) ai ie {omconah Fearn fary ban Note When the primary Spermatocyte divides, its eytoplasm is equally distributed between the two secondary spermatocytes formed. However, when the primary oocyte divides almost all the cytoplasm goes to the daughter cell which forms the secondary oocyte. The other daughter cell or polar body (first) receives half the chromosomes but ‘almost no cytoplasm. The polar body (first) is thus formed merely to get rid of unwanted chromosomes.‘AIPGME EXAMINATION ANSWERS AND EXPLANATIONS - 2006» 563 PHYSIOLOGY % Answer is A (270 to 285): Harrison 16/252 The normal plasma osmolality is 275 to 290 mosmoV/kg ~ Harrison ‘Osmolality : Harrisons 16°7252 ‘+ The solute or particle concentration of a fluid is known as + Itis expressed as milliosmoles per kilogram of water (mosmoV/kg) + Water crosses cell membranes to achieve osmotic equilibrium, therefore ‘ECF osmolality = ICF osmolality’ + Solutes that are restricted to the ECF or ICF determine the effective osmolality ofthat compartment = Major ECF particles are Na” CI’ and HCO; = Major ICF particles are K” and organic phosphate esters @ «The normal plasma osmolality is 275 to 290 mosmoVkg and is kept within a narrow range by mechanism capable of sensing a I to 2% change in toxicity. ‘osmol ty Answer is C (Layer 4): Ganong 22/161 Afferents from Lateral geniculate body terminate onto the visual cortex, mostly through the magnocellular, and parvocellular pathways. Axons from parvocellular and magnocellular pathway, both terminate in Layer 4 of the visual cortex. The axons from Lateral geniculate nucleus that form the magnocellular pathway end in layer four (4). Many of the ‘axons that form the parvocellular pathway also end in Layer 4. Most of the axons from Lateral geniculate nucleus thus end in Layer 4 of the visual cortex. Some fibres from Lateral geniculate body terminate via the inter laminar pathway. These terminate onto layers ‘2’ & “3 of visual cortex. Understanding the visual pathway from Retina to visual cortex: Retinal ganglion cells. §-——————+ Lateral Geniculate body ———— Visual cortex ‘Retinal alls ‘These are of two kinds + Each Geniculate body contains six well defined | » Each visual cortex has 6 layers layers + Visual cortex receives afferents I 1 « Six layers divide Lateral geniculate body into | from three portions ~ Magnocellular pathway Parvocelular pathway a q + = Interlaminar portion ae [Magnocelhiar [Parvocelular + These pathways mainly terminate Projecttothe | « Projetto the || Jportion portion in Layer 4 but also in layer 28 3 ‘+ Mognocellula | © Parvocelllar || Layers 1,2) [Layers 3,4, —1_ portion of portion of | 5.6) + 1 cl | ea Js Receives |» Rescives [+ Receives enicu ulate : projections | projection | projection body body from M cells| from*P* | from-P" cells + Interlaminar on portion of Lateral Geniculate bod Ganglion cells M (Magno calls) P (Parvo cells) (M cells & P cells) 7] eer Lateral Geniculate body ‘Magnocellular Laminas Interlaminar Region “~~~ Parvocellular Laminas (2 Regions)» (Lamina 1,2) | | Visual Cortex ——> Layer 4 Layers 2,3 Layer 4 (Superficial layer 4c) (BLOBS) (Deep Layer 4c) Function — Movement Colour Shape Location Colour ‘Spatial organization‘564 + AIPGME EXAMINATION ANSWERS AND EXPLANATIONS - 2006 Answer is C (Colour processing) : Ganong 22/161 “Blobs are arranged in a mosaic in visual cortex and are concerned with colour vision’ — Ganong 22/161 ‘+ Layers 2 and 3 of the cortex contain clusters of P cells (Ganglion cells) ‘ells about 0.2 mm in diameter, that unlike neighbouring cells contain a high concentration of the mitchcondrial enzyme ‘cytochrome Inter Laminar Parvocellular portion of oxidase’, Res Lateral Geniculate body ‘+ These clusters have been named as blobs ‘+ They are arranged in a mosaic in the visual | cortex and are concerned with color vision. Layer 2,3 Deep layer 4c (Layer 4) of BLOBS visual cortex Color® Color Answer is B (Colour ision, shape, fine details) : Ganong 22"/161 “The parvocellular pathway from layers 3-6 carries signals for colour vision, textures, shape and fine detail’ — Ganong 22/161 (iateral Geniciate Body nl (ima 1 Layers 1.2 Layers 3,4, 5 & 6 Carries signals for detection Caries signals for color Caries signals concerned with color ‘of movement depth and flicker vision, texture shape and fine vision detail 13. Answer is A (Integrity of Reflex are) : Ganong 22/206 ‘Postural Reflexes not only maintain the body in an upright balanced position but also provide the constant adjustments ‘necessary to maintain a stable postural background for voluntary activity’- Ganong 22™/207 Integrity of the postural reflex arc is therefore the single best answer of choice. 14. Answer is B (Withdrawal Reflex) : Ganong 22/208 Amongst the options provided ‘Withdrawal reflex’ is the single best answer of choice as explained below. ‘The Withdrawal Reflex: ‘The Withdrawal Reflex is a typical polysynaptic reflex that occurs in response to a noxious stimulus The response is flexor muscle contraction and inhibition of extensor muscles so that the part stimulated is withdrawn from the stimulus. Regarding the first reflex response to appear after spinal shock wears off ~ Ganong 22/208 ‘The first reflex response to appear as spinal shock wears off in humans is frequently a slight contraction of the leg flexors, and adductors in response to a noxious stimulus’ ~ Ganong ‘The description of this reflex activity suits a diagnosis of “withdrawal reflex” Withdrawal reflex is therefore the single best answer of choice. 15. Answer is C (GABA-ergic and cholinergic system) : Ganong 22/215 ‘In Huntington's disease, a loss of the intrastriatal GABA ergic and cholinergic neurons occurs’ ~ Ganong 22/215 ‘The loss of GABA ergic pathway to the external pallidum releases inhibition, permitting the hyperkinetic features of the disease to develop, Note: ‘Degeneration of Nigrostriatal dopaminergic system causes Parkinson's disease®.16. 17. Answer is C (Lateral Hypothalamic Area): Ganong 22/238 “The orexins: linking circulatory control with behavior’ (www.une.edu/~ajusvEhmke_03_rev-Orexins pdf) “Orexins are synthesized in neurons located in the lateral hypothalamus’ Ganong 22/238 ‘In the CNS, all the orexinergic neurons have their origin in the lateral hypothalamus from where they project widely to regulate especially wakefulness and paradoxical sleep, appetite and food intake and endocrine and autonomic processes’ = Sciemtific paper published in 2004 (www.pharm.emory edu/thall/Holmavist_ ‘The Orexin System + Orexins (also called hypocretins) were first described in 1998 as the result ofa search for unknown regulatory peptides in the hypothalamus. + Orexins are signal substances both in the central nervous system (CNS) and in the periphery. + The orexin system consists of = Two closely related neuropeptides.orexin A and orexin B, which are produced from a common precursor, and = Two receptors, the orexin receptor type-I (OX1) and orexin receptor type-2 (OX2) ‘+ At most of the projection sites both OXI and OX2 receptors are expressed ‘+ The orexins most often act in an excitatory manner both via putative pre-, post- and extrasynaptic mechanisms JBC_2005.pdt) +All the orexinerpic neurons have they origin inthe ‘+ Orexins and orexinrecepfors have been have been lateral hypothalamus fiom where they project widely found in the gasto-intestinal tract and inthe endocrine + They are believed to regulate: organs. = Wakefuiness and paradoxical sleep, ‘+The prominent peripheral effects seen so far include = Appetite and food intake regulation of gastrointestinal motility and hormone = _ Endocrine and Autonomic processes. production and release, especially in the adrenal gland Note: Mutation in one of the Orexin Receptor Genes has been linked to Narcolepsy Answer is C (Sensing NaC! concentration in the macula densa) : Guyton 1"/323, 324 To perform the function of auto regulation, the kidneys have a feed back mechanism (tubuloglomerular feed back) that links changes in sodium chloride concentration at the macula densa (tubular component) with the control of renal arteriolar resistance. (glomerular component) - Guyton 1 Jomerular feedback + Itis a feedback from the renal tubules, to the glomerulus to regulate the GFR, in an attempt to ensure constant sodium chloride delivery to the distal tubule. + The sensor for this response is macula densa ‘© The macula densa senses the changes in sodium chloride concentration. «The Nat and Cl- enter the macula densa cells via the Na+ - K+ - 2CI- cotransporter. 4 Arterial pressure ~) {Glomerular hydrostatic pressure ¢~ : GFR |} TProximal | NaCl =>! Macula densa NaCl {reabsorption Aton ere : Renin + T Angiotensin IL fo Wag PES : t Fo Maca cea fg) eet x (oy lamina [71 Efferent arteriolar 4 Afferent arteriolar Smoot Oe resistance resistance oe membrane ele Structure of the juntaglomerular, demonstrating its possible __-Macula densa feedback mechanism for autoregulation of glomerular feedback rlein the contol of nephron function hydrostatic pressure and glomerular tiation rate (GFR) during extraceliuartuid 500 0/9) ‘ <— (1300mg) ¥§ a ‘Secretion Reserpton tm (250 mg/day) | | (800 mg/day) Filtration Reabeorpion cas Calm, Abang | (9980 ma/day)¥ _ 1 (9880 mg/day) pace “ATPase ome Feces (900 mg/day) (flag Kidneys Urine rein! stoopton lean (100 mg/day) | Paar cal concataton <= ‘Overview of calcium exchange between different tissue ‘Retivation of vitamin D3 to form 1,25- compartments in a person ingesting 1000 mg of calcium per day. | dihydroxycholecaleiferol and the role of vitamin Note that most of the ingested caleium is normally eliminated in | D in controlling the plasma calcium concentration the feces, although the kidneys have the capacity to excrete large amounts by reducing tubular reabsorption of calcium. 20. Answer is A (Thyroid gland) : KDT 5"/301; Ganong 22/393 Calcitonin is primarily secreted by the parafollicular *C’ cells of the Thyroid gland. ” cells of the thyroid (Ia non mammalian vertebrates the source of calcitonin is the ultimobranchial bodies)® ‘* Calcitonin levels rise in response to rise in plasma Ca" (>9mg/dl) concentration and tend to decrease the serum. calcium level ‘Decrease in serum calcium levels is brought on by = Inhibition of bone resorption by direct inhibition of osteoclasts? ‘© Secreted by the parafollicular Inhibits proximal tubular calcium reabsorption ® and thereby increases calcium excretion Paget's disease of bone? = Post menopausal osteoporosis ® ~ Hypercaleemic states: - Hyperparathyroidism ~ Hypervitaminosis D ~ Osteolytic bone metastasis 21. Answer is A (Leydig cells) : Ganong 22/424, 425 “Between the tubules in the testes are nests of cells containing lipid granules. The ‘Interstitial cells of Leydig’ which secretes testesterone into the blood stream’ ~ Ganong 22/42423, 24. Interstitial cells of Leydig Primitive germ cells toi cells Secretetestesterone® + Secrete Mature into primary = Androgen binding protein® spermatocytes = Inhbin® + MIS? (contain aromatase eypia) + Contribute to blood testes barrier (The spermatids mature into spermatozoa in sertoli cells) ‘Note : « Mature spermatozoa are released from sertoli cells © ‘+ Mature spermatozoa acquire motility during passage in the epid Answer is B (LH) : Ganong 22/438 ‘A surge in LH secretion triggers ovulation’ ~ Ganong 22/438 A surge in LH secretion triggers ovulation and ovulation normally occurs about 9 hours after the peak of the LH surge dat mideycle’. - Ganong Answer is D (Functional hypothalamopituitary axi ): Reference along with text Maternal Glucocorticoids play an important role in production of surfactant and have been implicated to play a regulatory role in development of Hypothalmo pituitary axis. Glucocorticoids also contribute to thymic involution. No study to date has examined the effect of maternal glucocorticoids on thyroid function and thyroid function therefore is the single best answer of exclusion. + Maternal glucocorticoids and thyroid function: No study to date has examined the long-term efjects of maternal glucocorticoids on the thyroid function of the affipring- Maternal-Fetal Glucocorticoid Milieu Programs Hypothalamic-Pituitary-Thyroid Function of Adult Offspring Endocrinology 145(9):4068-4072 (htip:/iendo.endojournals.org/egi/reprint/145/9/4068) + Maternal glucocorticoids and functional hypothalmo-pituitary axis: ‘Glucocorticoids play a key role in the development of a various systems before birth. Glucocorticoids cross the placenta from the mother to the fetus and vice versa and there is evidence that elevated maternal glucocoticoid play a regulatory role in the development and activity of fetal pituitary-adrenal axis’ ‘Maternal-Fetal Glucocorticoid Milieu Programs Hypothalmic-Pituitary-Thyroid Function of Adult Offspring’ Endocrinology 145(9): 4068-4072 (http://endo.endojournals.orgiegi/reprint/145/9/4068) + Glucocorticoids and thymic involution “Glucocorticoids decrease the circulatory lymphocyte count and the size of the lymph nodes and thymus by inhibiting lymphocyte mitotic activity’ ~ Ganong 22/370 + Maternal/Retal glucocorticoids and surfactant ‘Maturation of surfactant in the lungs is accelerated by glucocorticoid hormones. Fetal and maternal cortisol increase near term and the lungs are rich in glucocorticoid receptors- Ganong 22/670 Answer is B (Pancreatic juice) : Guyton 11/794 “Pancreatic juice is essentially alkaline with a pH as high as 8.0 10 8.3 Intestinal Tuice pA Daily seretion of Intestinal Juices Saliva 6.0-7.0 Daily volume (ml) pH Gastric juice 10-35 sere ‘029 Banerji 80-43 ee 2 Brunner’s gland secretion 200, ie intestinal secretion 20025. 26. ~_AIPGME EXAMINATION AN Answer is D (The cerebral arterial pressure rises) : Ganong “Negative ‘’ causes increased cardiac output, a rise in cerebral arterial pressure, intense congestion of the head and neck vessels, ecchymosis around the eves, severe throbbing head pain and eventually mental confusion (red out)’ — Ganong 22°/632 gravity on the earths surface mae: (Black outs) Isthe force due to acceleration acting in the long + axis of body from head to foot + During exposure to postive “g’ blood is thrown . into lower part of the body, and consequently there is decrease in cerebral arterial pressure. [Positive ‘g” creates a tendency for + Decreased cardiac output . + Decreased cerebral arterial pressure : + Black out and unconsciousness : During exposure to positive ‘g” mn are multiplied during acceleration or deceleration, + Force acting on the body as a result of acceleration is commonly expressed in ‘g’ units, 1°g” being the force of Negative ‘g" (Red outs) [Negative ‘g’ creates a tendency for 22/632 Is the force due to acceleration acting in the long. axis of body in opposite direction. During exposure to negative ‘g’ blood pools into the upper part ofthe body, and consequently there is an increase in cerebral arterial pressure. Increased cardiac output Increased cerebral arterial pressure ~ intense congestion of head / neck vessels - echymosis around eyes, - severe throbbing head ache “Red out” and mental confusion + Arterial pressure in the head is reduced, but so are venous pressure and intracranial pressure and this reduces the decrease in arterial blood flow that would otherwise occur. + Cardiac output is maintained for atime because blood is drawn from the pulmonary venous reservoir and because the force of cardiac contractions is increased. ‘+ Ataccelerations more than ‘Sg’ however vision fails (black outs) and unconsciousness follows almost immediately. Answer is D (Piloerection) : Guyton 11"/895 Piloerection is not important in human beings. (Guyton) ‘Piloerection means hairs ‘standing on end. Sympathetic stimulation causes the arrector pili muscles attached to the hair follicles to contract which brings the hairs to an upright stance. This is not important in human beings but in lower animals, ypright protections of hairs allows them 0 entrap a thick layers of “insulator air’ next tothe skin, $0 that transfer of heat to the surroundings is greatly depressed" Guyton 11°7895 ‘Temperature Increasing Mechanisms (When the body is 100 cold) ‘+ Vasoconstriction of skin blood vessels (stimulation of posterior hypothalamic sympathetic centers) ‘ Increase in Thermogenesis (Heat production) ~ Enhanced shivering. ~ Thyroxine secretion ~ Sympathetic excitation of heat production + Pilocrection : (conserve heat) = Not important in human beings = Important in lower animals ‘Temperature Decreasing Mechanisms (When the body’is too hot) ++ Vasodilatation of skin blood vessels inhibition of posterior hypothalamic sympathetic centres) + Decrease in Thermogenesis (Heat production) = Inhibition of shivering = Inhibition of chemical thermogenesis ‘+ Sweating : (Heat loss) = Evaporative heat lossBIOCHEMISTRY 27. 28. 29. D EXPLANATIONS - 2006 Answer is a (Oxidase): Robbins 7/60; Chatterjea Shinde 6/18 The electron transport chain system responsible for the respiratory burst is ‘NADPH oxidase’ (on oxidase enzyme) —Chatterjea 6"/18 The biochemical mechanism of microbial killing and degradation following phogoeytosis is called ‘respiratory burst This is accomplished largely by oxygen dependent mechanisms. “The generation of reactive oxygen intermediates is due to rapid activation of an oxidase (NADPH oxidase)’-Robbins Answer is C (of the acidic p of vesicle): Chatterjea Shinde 6/19; Lippincott 3/230 The low pH breaks the linkage between receptor ~macromolecule (ligand) complex ~Chatterjea 6/19 Endosomes and their role in receptor mediated Absorptive Pinoeytosis: + These are transient cellular structures involved in the transport of macromolecules from the exterior of cells to its interior. + They do not contain hydrolytic enzymes, are Tess dense than lysosomes and have an internal pH of 5.0, + Endosomes receive the receptor. by fusing with the ‘coated vesicles” (Coated vesicles consist of Receptors, Ligand (macromolecule) and a layer of clathrin protein) + On fusion, the coated vesicles discharge their ‘macromolecules into the interior of endosomes. +The low pH within the endosome, breaks the linkage between receptor-macromolecule complex and releases the receptor, the macromolecule, clathrin, and membrane fragments. and complex Answer is C (Brown adipose tissue): Harper 26"/217. Brown adipose tissue is a specialized tissue for promoting thermogenesis. Oxidation and phosphorylation are not coupled in mitochondria of this tissue. Thus oxidation in this tissue produces mainly ‘heat’ and only a little free energy is trapped in ATP-Harper Answer is B (Chylomicrons): Lippincott 3¥/230,225 Lipoproteins may be differentiated on the basis of their lipid & protein compositions. The lipoproteins containing the largest percentage of triacylglycerol are Chylomicrons (90%) Chylomicron. VLDL LDL. HDL Triacylglycerol 90% 60% 8% 5% Protein % 5% 20% 40% Phospholipids 3% 15% 2% 30% Cholesteral & Cesters 5% 20% 50% 25%31. 32. ipoproteins = Chylomicrons - VLDL - LDL = HDL. lic | Neutral Lipi Surrounding shett = Triacylglycerol ~ Proteins = Cholesterol and chlolesterol (Apolipoproteins) ‘esters. = Phospholipids eS) Approximate size and density of serum lipoproteins. Each family of ipoproteins exhibits a range of sizes and densities; this figure ‘shows typical values [Note: The width of the rings approximates the amount of each component) Answer is C (valine): Harper 26%/15 Isoleucine is an aminoacid with an aliphatic side chain. Amongst the options provided valine is the only other amino acid with an aliphatic side chain and is the answer of choice here. Substitution of isoleucine with valine in a protein sequence is an example of a homologous or conservative substitution, Answer is D (Quartenary structure): Harper 26"/34 Polypeptide chains arranged as homodimers or heterodimers constitute an example of quartenary structure. Quartenary structure: This defines the polypeptide composition and spatial relationship between subunits of proteins that are assembled from more than one polypeptide units. Homodimers Heterodimers ‘Contain two copies of same polypeptide chain ‘Contain different polypeptide subunits Represented as X> Represented as a 8 Remember # Sequence of amino acids» The folding of short (3-30) sional confermation ofa single ina single polypeptide Contiguous segments ofa single polypeptide chain chain polypeptide chain into geometrically > Domains ordered units ‘+ Teetiary structure indicates in three dimensional = Alpha helix space how secondary structure features helices, ~ Beta sheet sheets, loops and bends assemble to form domains + Loops & bends and how these domains relate spatially to one ‘Insufficient to performa + Insufficient to perform a particular another. particular chemical or chemical or physical task. + Sutticient to perform a particular chemical & physical tsk physical task34 Answer is A (Randomly : Most probable answer of exclusion ) : Several internet sites and most standard textbooks. Extensively searched, but no direct reference or explanation available: Inference from various references summarized. ‘Most variations in aminoacid sequence of eytochrome c affect the primary structure in a way not to affect the secondary and tertiary structures which are more important for function. The amino acids that cannot be replaced without a major ‘modification of the enzymic properties of the cyiochrome c are not altered. Thus the amino acids at locations that determine the secondary structure of protein (loops , helix or strands ) are preserved while aminoacids that do not contribute to the determination of secondary and tertiary structure are preferentially altered. These alterations are likely to be distributed randomly as they result from point mutations on the responsible gene and this isthe single best answer of exclusion here. Also note that it isthe tertiary structure which is most important for function and hence itis the most conserved parameter. Some changes in the secondary structure (helix ,loop or strands ) may be seen as a result of random changes in the polypeptide sequence of amino acids. These changes may affect the ‘helical regions’ or the ‘loops? or the ‘strands’ randomly and should not be confined to only the helical regions , the loops or the strands. ‘The following text has been directly quoted from some of the references: + The cytochrome ¢ from different species essentially has similar function ‘+ Function of a protein largely depends on its tertiary structure.As the function of cytochrome c is largely preserved ‘the functional structure ie, the Tertiary structure is essentially similar .A large number of papers also quote similarity in secondary structure (loops ,helix and strands) of eytochrome c in different species “The polypeptide chains of different vertebrate cytochrome c molecules are all of about the same length (104 amino acid residues) and arrange themselves into similar secondary and tertiary structures’. - ‘The Evolutionary Significance Of The Species Variation In Cytochrome C Structure” (hitp://wwrw.asa3.org/ASA/PSCF/1968/JASA6-68%20Mills html) + The comparison of the amino acid sequence of cytochrome ¢ from different species shows many variations and ‘many invariant regions in the primary structure ie.in the polypeptide chain, Statistical considerations indicate that no matter how many species of cytochrome ¢ were examined, 27 to 29 invariant residues would remain. These represent the amino acids that cannot be replaced without a major modification of the enzymic properties of the cytochrome c.There are certain similarities in all vertebrate cytochrome ¢ structures, ¢.g., in having cysteine residues at positions 14 and 17 and in having an eleven amino acid invariant chain from position 70 through position 80. In vertebrate cytochrome e molecules, there are 77 positions (cut of 104) which possess identical amino acid residues. When yeast cytochrome c is compared with vertebrate cytochrome c, there are 58 positions with identical amino acid residues + Comparison of all the various cytochrome ¢ molecules indicates a strict homology in structure; the closer the taxonomic relationship between two species, the greater the similarity in structure. Answer is B (Ligand binding residues): Lehninger 4/160. Harper 26"/362 Function in biochemistry revolves around a reversible protein ligand interaction. A molecule bound reversibly by a protein is called a ‘Ligand’. A ligand binds ata site on the protein called the ‘binding Site’, which is complementary to ligand in size, charge and hydrophobic or hydrophillic character. As long as the ligand binding residues are preserved to allow interaction between the ligand and the binding sites the function will essentially be preserved. + Amino acid sequence alterations are compatible will 0 functionally normal haemoglobin: (Acceptable missense ‘mutations) «eg. Haemoglobin Hikari has been found in atleast two families of Japanese people. This haemoglobin has asparginine substituted for lysine at position 61 in IL B chain. (change in AA sequence). This replacement of specific lysine with arginine apparently does not alter the normal function of the B chain in these individuals. Harper ‘+ Aslong as the domains / Ligand receptors are preserved, a variation in Structure is still compatible with normal function. + Environmental changes do not explain why only a few out of 300 variants of human globin gene are incompatible will function.35. 36. 37. Answer is B (Fibrous proteins): Harper 26"/38 Proteins responsible for maintaining the structural strength of cells (i.e. cytoskeleton) and tissues include collagens, keratin and myosin ete. These proteins are classified as fibrous proteins. ‘Collagen is the most abundant of the fibrous proteins. Other prominent fibrous proteins include keratin and myosin. These proteins represent a primary source of structural strength for cells (the cytoskeleton) and tissues’-Harper 26/38 Answer is D (Histidine): Lippincot 3/261 Methionine, Valine, Isoleucine and Threonine are the four aminoacids that form succinyl- CoA. Histidine forms a ketoglutarate and not Succinyl CoA. Catabolism of carbon skeletons of Aminoacids: "AA that form Oxaloacetite Sa * Asparginine (Aspartate) [AA That form acketoglutarate a + Glutamine + Proline Answer is A (Alani Lippicott 3/250 The amino acid used primarily by muscle, for transport of ammonia to liver is alanine. Most other tissues however use glutamine. ‘Transport of ammonia to Liver Ammonia is transported to Liver from peripheral tissue for its ultimate conversion to urea. ‘Two mechanisms are available in humans for this transport + ‘Mechanism found in Most tissue ‘Mechanism in Muscle | | Uses Glutamine Uses Alanine —_ Os LIVER ak we (Urea synthes Alanine ‘Ammotransf Pyruvate39. | ANSWERS AND EXPLANATIONS - 2006 Answer is C (q and p arms): Robbins 7"/171; Internet links as provided below The short arm of chromosome is desingated as ‘p’ (for petit) and the long arm is refered to as ‘q’ (the next letter of alphabet): Robbins 7"/171 Chromosomes Nomenclature: Karyotype nomenclature: inttp://www-ring-chromosome-20.org/what_are_chromosomes.aspx Karyotype is an actual photograph of the chromosomes from one cell. + Every cell of the human body has 46 chromosomes + 46 chromosomes occur as 23 pairs. + Chromosomes are laid out in pairs, from largest (#1) to smallest (#22) The last pair are called the sex chromosomes labeled X or Y. Female have two X chromosomes (XX), and males have an X and a Y chromosome (XY). + Each chromosomes has a p and q arm; P (petit) isthe short arm and q (next latter in the alphabet) isthe long arm When a karyotype is made the q arm is always put on the bottom and the p on the top. ‘The arms are separated by a region known as the centromere Chromosomes have characteristic banding pattems created by trypsin and Giemsa The chromosomes need to be stained in order to see them with a microscope. When stained the chromosomes look like strings with light and dark “bands’. Each chromosome arm is defined further by numbering the bands, the higher the number, the further that area is from the centromere. . ABBREVIATIONS \ lp ‘Short arm SNyetl sp ae 1 2 a a 6 + additional chromosome a - missing chromosome fr 2d Cor Se 4 c Taleaton Hu sy del deletion gu 8 oo7 ‘dup duplication * 8 ne Y der derivative Answer is A (Uncondensed): Harper 26th/316 hitp:/www.infobiogen.fr/services/chromeancer/Deep/ChromatinDeep. html; hitp:/www.bookrags.com/sceinces/gemetics/euchromatin-wog.html; bitp://www.bookrags.com/sciences /geneties/euchromatin-wog. html Heterochromatin stains more strongly and is a more condensed chromatin. Euchromatin stains weakly and is more ‘open (less condensed). Euchromatin remains dispersed (uncondensed) during interphase, when RNA transcription occurs www.eme maricopa.eduifaculty/farabee/bookGENCTRL htm! Based on microscopic observation, chromatin has been divided into two distinct domains, heterochromatin and euchromatin. Hetrochromatin was defined as a structure that does not alter in its condensation throughout the cell eycle whereas euchromatin is decondensed during interphase [ Heitz, 1928 # I] - http://www. nfobiogen.fr/services/chromcancer/Deep/ChromatinDeep html When the cell cycle is at the phase known as interphase, chromosomes present two types of chromatin under a light microcope: a highly condensed portion, known as heterochromatin, and less condensed one, termed euchromatin. Euchromatin is the is the dispersed portion of chromatin that is transcribtionally active during interphase in other words,euchromatin contains genes capable of transcribing genetic information into proteins that are necessary during interphase for young cells’ maturation, metabolic functions, or DIVA repair. http://www. bookrags.com/sciences/genetics/euchromatin=og. html40. 4. ‘AIPGME EXAMINATION ANSWERS AND EXPLANATIONS - 2006» 575 Answer is C (Short sequence (2-5) repeat DNA): Robbins 7"/307; Harrisons 16!/449; Harper 26/322 ‘Microsatellites are tandem repeats of one to six nucleotides scattered throughout the genome’ —Robbins 7/307. What Are Microsatellites: hp://oneweb.utc.edu/~Margaret-Kovach/microsat. html “Microsatellites’ are defined as loci (or regions within DNA sequences) where short sequences of DNA (nucleotides; ‘adenine- A, thiamine- T, guanine- G, eytosine- C) are repeated in tandem arrays. This means that the sequences are repeated one right after the other. The lengths of sequences used most often are di-, tr-, or tetra-nucleotides. What microsatellites useful ‘> They-can be used for DNA fingerprinting: Used in forensic and paternity/parentage work ‘At the same location within the genomic DNA the number of times the sequence (eg.AC) is repeated often varies between individuals, within population, and/or between species. So one population may commonly have 13 AC's (dinucleotide repeat sequence) repeated in a row while another population has 18 AC’s repeated at the same location within the genomic DNA. + Predicting the progression of disease, Microsatellites are acutely prone to replication errors that result in expansions and contractions of repeat unit (repeat length variability) because of misalignment of the template and daughter strands, Variability of microsatellite repeat lengths leads to Genomic instability and, plays a role in the progression of disease, presumably by gene inactivation DNA mismatch repair (MMR) enzymes maintain genomic stability by removing replication errors from DNA. Defective DNA mismatch repair (MMR) enzymes in association with microsatellite instability (MSI) are thus, {mplicated in the progression of several diseases and cancers. Examples includes = Fragile syndrome = Huntington’s chorea = Myotonic dystroply ~ Spinobulbar muscular atrophy = Kennedy's - Hereditary non polyposis colon cancer + Provides clue to Genetic bases of disease. ‘The association ofa specific polymorphism in affected family members and the lack of this association in unaffected members may be the first clue about genetic bases ofa disease. Answer is A (Closed Cireular): http://phylo.gen.lu.se/Research_Thesis_X_Xiu html; Itp:/www.cmgs.org/BPG/Guidelines/2004/Mitochondrial?%20DNA%20Testing htm ‘Mammalian mitochondrial DNA (mtDNA) is a closed-circular double-helix molecule which contains two rRNA _genes, 13 protein-coding genes, and 22 1RNA genes - hup://phylo.gen.lu.se/Research_Thesis_X_Xuhtml Mitochondrial DNA (mtDNA) is a small (1 6. Skb), closed-circular molecule of DNA that exhibits a strict maternal transmission and is present within cells in multiple copies - ‘htp://www.cmgs.org/BPG/Guidelines/2004/Mitochondrial%20DNA%20Testing. htm Significance of Mitochondrial D! * Mitochondrial DNA is the only non-chromosomal DNA in human cells? DNA in humans may be found either in the Nucleus (Nuclear DNA) or in the Mitochondria (Organelle DNA) + Mitochondrial DNA,is always maternally inherited. © Mitochondrial and nuclear DNA are located in different places in the cell. During fertilization, the sperm and egg cell nuclei fuse to form an embryo. The egg cel is very lange compared to the sperm, so although the cells' nuclei fuse, the rest ofthe cell mass in the embryo comes from the egg only. Nuclear DNA is therefore co-inherited but the ‘mitochondrial DNA, which is located outside of the nucleus, is always maternally inherited because all ‘mitochondria ina foetus and later adult are derived from the mitochondria in the mother’s egg. All children from affected mother will inherit the disease but it will not be transmitted from an affected father to his children.- Harrison's 16"/374576» AIPGME EXAMINATION ANSWERS AND EXPLANATIONS - 2006 ted Mitoc Disease/Syndrome eS MELAS syndrome: mytochondtrial myopathy with encephalopathy, lactic acidosis and stroke + Leber's optic atrophy: hereditary optical neuropathy «+ Keams-Sayre syndrome (KSS) ophthalmoplegia, pigmental degeneration ofthe retina, cardiomyopathy GHIMERRF syndrome: myoctonie epilepsy and ragged red fibres ‘© Maternally inherited myopathy and cardiomyopathy (MMC) (HiNearogenic muscular weakness with ataxia and retinitis pigmentosa (NARP) # Progressive extemal ophthalmoplegia (CEOP) (Pearson drome (PEAR): bone marrow and pancreatic failure ‘Autosomal dominant inherited mitochondrial myopathy with mitochondrial deletion (ADMIMY) 42. Answer is B (tDNA): Harper 26/356 The t-RNA’s contain many modifications of the standard bases A,U,G, and C, including methylation, reduction, deamination and rearranged Glycasidic bonds- Harper 26"/356. 43. Answer is C (Specifically recognizes the promoter site): Lippincott 3/415 The o subunit (sigma factor) enables RNA polymerase to recognize promoter regions on the DNA-Lippincott 3/415 Pr .NA poly + RNA polymerase is a multisubunit enzyme, that synthesizes all of the RNA in prokaryotes (except RNA primers needed for DNA replication which are synthesized by RNA primase) ‘+ Itis made up of 2 a subunits, 1 subunit, 1p” subunit and 16 subunit (Holoenzyme). The 2c subunits together with 1 and 1” subunit constitute the core: ¥ + Core units (core enzyme) ‘sub unit (2a.8,,) Responsible for synthesis of RNA from S'end i.e, Enables the RNA polymerase to recognize promoter S'-> 3 RNA Polymerase activity region on DNA 44. Answer is A (5°GTACG CTTAA’ The complementary sequence is 3’ AATICGCATG 5" or 5' GTACGCTTAA 3° + Base pairing rules = Adenine (A) is always paired with Thiamine (T) - Cytosine (C) is always paired with Guanine (G) + Complementary sequence of ays proceeds from 3 Thu STTAAGCGTACS ippincott 3°/395 | Complements SY AATTCGCATGS’ This can also be rewritten in 5-3" as the following: S'GTACGCTT AA3"4s. 46. CHARGAFF'S RULES: In any sample of DNA ‘+ Amount of Adenine (A) equals amount of Thymine (T) + Amount of Guanine (G) equals amount of Cytosine (C) ‘+ Total amount of Purines equals total amount of Pyrimidines. Answer is C (DNA Polymerase III): Lelminger 4"/961 Lippincott 3"/401,402,403 Lagging strand synthesis is accomplished in short Okazaki fragments. First an RNA primer is synthesized by primase and DNA polymerase III, then binds to the RNA primer and adds deoxyribonucleotides (polymerization)’ = Lehninger 4/961 Okazaki fragments are short segments of DNA synthesized on the lagging strand, during the process of DNA replication. Synthesis of Okazaki fragments involves polymerization of deoxyribonucleotide residues along the single stranded template. This polymerization function is accomplished by DNA polymerase III. (ip Ep 4 rive clone by DA poiymerase mun another Removal of RNA primer and filling of the resulting “gaps” by DNA polymesare [ DNA Replicatign (Elongation) Leading stand Logging stand RNA primer (made by primase) RNA primer (made by Primase) L 4 (synthesis of RNA primes) DNA chain made by DNA polymerase II DNA made by DNA polymerase HIE (Addition of Deoxyribonucleoties or polymerization) {in short Okazaki fragment) (in an antiparallel fashion) Excision of RNA primer by DNA polymerase I DNA gap filled by DNA polymerase | Remaining nuclei sealed by DNA ligase, Answer is B (Somatic): Lippincott 3/405; Ganong 22"/20 Somatic cells do not have the telomerase enzyme. ‘Without the transcriptase and related enzymes known collectively as ‘telomerase’ somatic cells lose DNA as they divide 40-50 times and then become senescent and undergo apoptosis'- Harper 26"/20. ‘Telomerase and Eukaryotic DNA Rep! Shor repeats of DNA that characterize the ends of chromosomes ae called slomer. ‘+ Telomeres are thought to regulate how many times an individual cell can divide ‘* Telomeric sequences shorten and may be lost as a result of DNA replication or by the attack of nucleases. Critical shortening of the telomers are linked to cellular aging &death, # Telomerases are special reverse transcriptase enzymes that sythesize these short repeats of DNA (telomers) and thus prevent or protect cellular aging & death| ANSWERS AND EXPLANATIONS - 2006 Thus 7. (Cells with telomerase Activity Cells without telomerase activity ‘Do not undergo cellular aging and death (apoptosis) as ‘Undergo cellular aging and death (apoptosis) after telomers are constantly resynthesized by the reverse 40-60 replications when the telomers become transcriptase enzyme telomerase” critically short or are gone. Examples include cells that do not age such as : Examples includes somatic cells - (Harper) + Germ line cells (germinal) - (Lippincott) = Cancer cells (Tumor) - (Lippincott) = Hoemopoetic cells Answer is C (Reading frame changes down stream to the mutant site): Harper 26/361, 363,364. Reading frame changes in the mRNA, all the way down stream to the mutant site is a feature of ‘frame shift ‘mutations’. It is not seen in single base substitution mutations. Mutations Base Substitution Mutations Frame shift mutations + Involves changes to a single base (point mutation) ‘+ Involves change to a single base but no substitution and substitution of the base with another base. May be seen as May be seen as: Delection Transitions: Pyrimidine changed to pyrimidine = Insertion Transversion: Purine to Pyrimidine or vice versa © The resulting mRNA shows a major alteration. + The resulting mRNA will show a change only at a downstream to the mutant site, because the point complementary to a base change at the translating machinery does not recognize that a base oresponding locus. was missing i UG WG AL MELA aN LAL A LNG Nm Fae Mar Ae-Sa-On-e-Cy-TeSa-SSTOP TiO UA UU ALG GEL LE AN AG. Pein Mele Se-Ch-Lp-Gy-Tyt-Se-Se-STOP tome Sassen Example (eon rie. UG UNG ALD CL LAX UL 3 Pale MeraleseeCn- ig OpTe~Se-Se-STOP Gabi Effects Effect 1. Silent mutation: Change in base in mRNA on third Garbled translation of the mRNA all the way distal nucleotide of a codon usually causes no detectable to the single nucleotide deletion. effect because of digeneracy of the code. (changes one codon for an amino acid into another codon for 2. Premature termination may occur if reading of the that same amino acid) message results in appearance of a nonsense codon. 2. Missense effect: AAifferent amino acid is incorporated at the corresponding site in the protein molecule. (codon for one amino acid is changed into codon for another amino acid) 3. Nonsense effect ‘Annon sense codon can appear that would then result in premature termination of peptide chain and only a fragment of the intended protein will be produced (codon for one amino acid is changed into translation termination codon)48, 49. AIPGME EXAMINATION ANSWERS AND EXP! Answer is D (Northern blot analysis): Harrisons 16°/365, 378, 595 Definitive diagnosis of a point mutation in the beta globin gene requires DNA analysis. Northern blot testis a technique used to study the RNA, rather than DNA and hence is the answer of exclusion. Polymerase chain reaction, DNA Sequencing and southern blot testing are rapid methods for DNA analysis, and can all be used to detect the point mutation in the globin gens. Polymerase chain reaction with allele Specific oligonucleotide hybridization and DNA sequencing “The advent of polymerase chain reaction (PCR), allele specific oligonucleotide hybridization and automated DNA sequencing has made it possible to identify globin gene mutations in a few days’ ~Harrisons 16/595 Southern blot analysis: hrp://www.uel,ac.uk/~uebhiow/b24 techniques html “The southern blot technique is a fast way of analyzing a small number of DNA fragments, for instance the sickle cell ‘mutation. Before PCR and cheap fast sequencing became available, the southern blot was the universal workhorse Northern blot analysis: htp://en.wikipedia.org/wiki/Northern_blot The northern blot isa technique used in molecular biology research to study gene expression. It takes its name from the similarity of the procedure to the Southern blot procedure, named for biologist Edwin Southern, used to study DNA, with the key difference that RNA, rather than DNA, is the substance being analyzed The northern blot is a technique to analyze RNA rather than DNA. This is thus the answer of exclusion. Answer is B (Homoeystine Methyl transferase ): Lippincott 3/373 Chetterjea Shinde 6"/181 Vitamin B > is required as a coenzyme to homocystine methyl transferase invotved in the synthesis of methionine ym homocystine. Ni-Methyltetrahydrofolate _Tetrahydrofolate Homocysting, ——— "ethionine Vitamin B,;(Methyl-cobalamine) Biologically active forms of vitamin B,2are called as ‘cobamide coenzymes’ and act as coenzymes with several enzymes for various metabolic reactions. These include 1. Isomerization of methyl malonyl co-A to succinyl CoA® Vitamin B,» (Deoxyadenosyl cobalamine) Methyl malonyl CoA ——————+ Suceinyl CoA. Methyl malonyl CoA mutase 2. Methylation of Homocystine to methionine® Vitamin Biz Methyl cobalamine Homocysteine. ———————+ Methionine (requires methyl tetrahydrofolate Homocysteine methyl transferase ‘Asa methyl cartier) 3. Methylation of pyrimidine ring to form thymine. 4, Conversion of ribonucleotides to deoxyribonucleotides in DNA synthesis Vitamin Bi: Ribonucleotides. + Deoxyribonucleotides Reductase 5. Required for metabolism of diols: Vitamin By> Ethylene glycol ——————+ Acetaldihyde. 6. In Bacteria for interconversion of glutamate and methyl aspartate . Vitamin B,» Glutamic acid ——————+ f Methyl aspartate50. ‘© AIPGME EXAMINATION ANSWERS AND EXPLANATIONS - 2006 Answer is D (Hexokinase): Harper's Biochemistry 23/496 (old edition) Hexokinase is not regulated by calcium/calmodulin, Enzy! calcium/calmodulin = Adenylate cycalse® © Guanylateeyelase® ‘© Cad dependent protein kinase © NAD kinase © Cad+/Mg2+ ATPase * Phospholipase A2 ‘© Ca2+/phospholipid-dependent protein kinase + Phosphoprotein phosphatase 2B ‘© Cyclic nucleotide phosphodiesterase + Pyruvate carboxylase ‘+ Glycerol-3-phosphate dehydrogenase ‘+ Pyruvate dehydrogenase Glycogen synthase? = Pyruvate kinase Answer is D (Presence of Ser-His-Asp catalytic triad at the active site): www.rpc.msoe.edu/lib/sp pdf: worw.users.ren.comikimball. ma.ultranet/BiologyPages/S Series/Serine_Proteases.him; wrw.ebicac.uk/interpra/potm/2003_S/Pagel htm . itive site of serine proteases contain ‘residues are often referred to as the catalytic triad, Ciara Elastase and iTypaie ‘are the three serine proteases that function essentially as enzymes. Each of these enzymes contain the ‘catalytic triad within their active sites but differ with respect to their target cleavage sites.- www.rpc.msue.edu + Thev are activated by proteolytic activation and not autocatalytic activation. They are secreted by the pancreas as inactive zymogens into small intestine- and became active through proteolytic cleavage events, either in a subcellular compartment or in an extracellular space where they are required for digestion. + Pancreatic trypsin inhibitor is serine protease inhibitor only for trypsin and not for other serine protease enzymes such as chymotrypsin or elastase. Serine proteases enzymes tightly bind the respective protease inhibitors instead of normal substrates. Pancreatic trypsin inhibitor Alpha-I antichymotrypsin Alpha-I antitrypsin ‘oup of the peptide bond that is to be cleaved (and not essentially the = Chymotrypsin Pepide bond nex to aromate residues Phenyalanne, Tyrosine Tryptophan) Trypsin Peptide bond next to basic residues (Lysine or Arginine) Blastase Peptide bonds next to Hydrophobic residues (Alanine) For more information on serine protease, browse through the following free internet resources. www.rpe.msoe.edulib/pl_pdf www.ebi.ac.uk/interpro{potm/2003_S/Pagel. htm swvew.users.ren.comijkimball. ma.ultranetBiologyPages/S/Series/Serine Proteases. html PATHOLOGY 52. Answer is C (Promotion of DNA repair): Robbins 9" /283-285- www lungcancerbooksandnewslettercom/what_is_eancer him Oncogenes may function by inactivation of DNA repair genes, but not by promotion of DNA repair. Promotion of DNA repair is protective from oncogenesis and is hence the answer of exclusion. + Oncogenesis and DNA repair: (Inactivation of DNA repair genes leads to oncogenesis) = Cancer generally involves multiple incidents of DNA damage. ~ Inactivation of DNA repair genes allow build up of genetic mistakes with each succeeding round of cell division. ~ This ‘genetic instability’ may lead to oncogenesis. + Apoptosis: (Inhibition of apoptosis leads to oncogenesis) ~ Apoptosis or programmed cell death is an inherent method of protection against development of cancer ~ Inhibition of apoptosis by oncogenes promotes cancers + Cellevele progression: (Enhanced cell cycle progression leads to oncogenesis) ~ Cell eycle isa highly ordered sequence of events that lead to cell growth and divi - Innormal cells ‘Cell Cycle Control genes” control the progression of cells through cell division cycles. ~ Deregulation of signals controlling the progression of cell through cell division cycles leads to oncogenesis. + Nuclear transcription (Factors causing enhanced nuclear transcription cause oncogenesis. ‘Transcriptional factors enter the nucleus bind the DNA and cause proliferation and oncogenesis53. 55. ‘AIPGME EXAMINATION ANSWERS AND EXPLANATIONS -2006* 581 Answer is C (Intestinal metaplasia): Harrison 16"/525 “The risk of tumor development is greatly increased in patients in whom mucosal inflammation progresses to ‘multifocal mucosal atrophy and intestinal metaplasia”- Robbins ‘Serial endoscopic examinations of the stomach in patients with atrophic gastritis have documented replacement of the usual gastric mucosa by intestinal type cells. This process of intestinal metaplasia may lead to cellular atypia and ‘eventual neoplasia.’ - Harrison 1. Long term ingestion of high concentration of nitrates in dried smoke and salted foods. ° 2. Loss of gastric acidity atrophic gastrtis® = partial gastrectomy (peptic ulcer surgery) ® = pernicious anemia® 3. Infection with H. pylori? 4. Imestinal metaplasia ® 5. Gatric ulcer & polyps - No association has been found between deodonal ulcer and gastric cancer) 6. Menetrier’s disease” : extreme hypertrophy of gastric rugal folds. 7. Blood group A® 8. Cigarette smoking, Dust ingestion, Ingestion of spirits, Genetic factors have also been implicated. Answer is D (Fundus): Sleisenger & Fordtrans text book of Gastrointestinal disease 7/813 Pernicious anemia is associated with autoimmune atrophic gastritis affecting the fundic glands. Intestinal metaplasia (premalignant for gastric carcinoma),is charachterstically seen in this area of atrophic gastritis .Atrophic glands with extensive intestinal metaplasia are most charachteristically confined to the fundus in patients with pernicious anaemia, “Diffuse corporal Atrophic gastritis (DCAG) is an autoimmune destruction of fundic glands. It isthe pathologic process in patients with pernicious anemia, It is exhibits achlorhydria or hydrochlorhydria, hypergastrenemia, antral G cell hyperplasia, circulating parietal cell and intrinsic factor antibodies.” Answers A (Parotid salivary gland): Robbins 98747 Most acinic cell tumors arise in the parotid - Robbins ‘Uncommon Composed of Most arise inthe parotid. The remainder arise in submandibular May'be bilateral, tumors cells resembling glands. Rarely involve the major glands. (because they have only a and multicentric representing 2% —thenormal serous seant number of serous cells) 103% of salivary acinar cells of aS Sry sland tumors salivary glands Pa ta vis ate Answer is D (The number of mitoses per high power field): Robbins 7°/1090 The most important criterion for distinction of leiomyosarcoma from leiomyoma (malignant transformation) is the ‘number of mitoses present. ‘The distinction of Leiomyosarcoma from Leiomyom: + Itis based on the combination of = Degree of nuclear atypia = Mitotic index = Zonal Necrosis + The most important single criteria is the number of nuclear mitoses present With or without Nuclear atypia Tn presence of nuclear atypia or (independent of nuclear atypia) large cells ‘The presence of ten or more mitoses per ten Ifthe tumor contains nuclear atypia or large high power (x400) fields indicates malignancy __epethelioid cells, five mitoses per ten high power ‘with or without cellular atypism fields are sulfcient to justify a diagnosis of malignancy582+ _AIPGME EXAMINATION ANSWERS AND EXPLANATIONS - 2006 Answer is D (Comedo DCIS): Robbins 9° /1057 DCIS most frequently presents as mammographic calcifications. Less typically DCIS may present as a vaguely palpable mass. This is most likely with comedo carcinomas, eriductal fibrosis and chronic inflammation are common and extensive lesions are sometimes palpable as an area of vague nodularity’~ Marphological characteristics of comedocarcinoma as described in Robbin’s 7"/1139 Ductal carcinoma in situ oV!_, ‘Comedo carcinomas ‘Non comedo careinomas ‘Mentioned to be palpable as an area of vague ‘Not mentioned to be palpable as as area of nodularity nodularity Answer is A (CD 45 RO) + hitp.//e-immunohistochemistry.info/webjan06/Granulocytic_sarcoma.htm; woew.urme.rochester.edu/smd/Rad /neurocases/Neurocase79.htm Granulocytic sarcoma is an extramedullary mass of the myeloid (granulocytic) lineage. Lysozyme, CD43 and ‘Myeloperoxidase are all positive markers for Granulocytic sarcoma. CD45 RO is a T cell lymphoma marker and is usually negative. Note: A few case reports have reported a positive CD45 RO in i ee granulocytic sarcomas, However from the options provided CD45RO is Lysozyme 100% definitely the single best answer of choice pe B58 80% CD4SRO is a T cell marker and is usually negative in granulocytic sarcomas however it has been reported as positive in a few case reports. The positivity with CD45RO has lead to misdiagnoses as T cell NHL, but this is likely to be less of a problem as CD3 becomes the first line T cell marker. ‘© Granulocytic sarcoma is an extramedullary mass composed of a collection of granulocytic cells. It is also known as chloroma or Extra-medullary myeloid tumour. + Occurs primarily in 3-8% of all patients with acute/chronic myelogenous leukemia, but can also arise in patients ‘with other myeloproliferative disorders, such as myelofibrosis with myeloid metaplasia, hypereosinophilic syndrome, polyeythemia vera, and acute lymphoblastic leukemia + Granulocytic sarcomas may develop during the course of, or as a presenting sign of, myelogenous leukemia, + These tumors often occur in multiples and can involve any part of the body Differential Diagnosis, i + The main differential is large cell non-Hodgkin's lymphoma + PNET | Prognosis i ‘+ Most patients presenting with granulocytic sarcoma will eventually develop AML. However, a proportion of patient, treated with appropriate chemotherapy at presentation, will not develop leukaemia, 59. Answer is A (CD 23): Robbins 7" /683; hup://www -medicine.com/meditopic1358.him Mantle cells lymphomas are usually CD23 negative. They are positive for CDS & CD20 and CD 43. ‘Mantle cell Iymphomas express CD19, CD20. It is usually CDS positive and CD23 negative which can help to distinguish it from chronic Lymphocytic leukemia/small lymphocytic lymphoma ~ Robbins