AIPGME EXAMINATION ANSWERS & EXPLANATIONS 2008s(CDM ROLLY Le) ae ALCL POT EO Me eC ane ara eS Na tA OY OR constituents of the entire explanatory text and have high probability of being CMR NO LeeLee CL eR CL ortion of text marked “Q” as prefix AOS LEANATOMY 1 Answer is B (Rectus femoris) : BDC II 64; Gray's 41"/849-853; Cunningham's Textbook of Anatomy (original edition) 671; Grant's Method of Anatomy (old Edition ~ 1971)/ 353, Adductor Magnus, Biceps femoris and Pectineus are all examples of composite muscles. The rectus femoris muscle only forms one part of a composite muscle, the Quadriceps femoris (composite of four ‘muscles) but it has not been mentioned as a composite muscle in isolation, Rectus femoris is the single best answer of exclusion ‘Composite Muscles ae Composite Individual Muscles ‘Composite Group of Muscles These include muscles that have different origins (two ‘These include a composite of different individual muscles heads) and different innervations forthe two heads. that function asa single muscle model These muscles are also referred to as Hybrid muscles Examples © Adductor Magnus? © Quadriceps femoris + Biceps Femoris® (This is considered a composite of four individual © Pectineus® muscles namely the rectus femoris, vastus lateralis , * Others all of which work in conjunction ato bring about extension at the knee joint) The existance of more than one nerve to a muscle indicates usually that the muscle is composite - Cunningham's Text-Book of Anatomy (Old edition) Adductor Magnus (Gray's 39/1467) “Adduector magnus is a composite muscle and is doubly innervated by the obturator nerve and the tibial division of sciatic nerve’ - Gray's Biceps Femoris (Gray's 39/1469) ‘Biceps femoris is innervated by the sciatic nerve; the long head through tibial division and the short head through the common peroneal division, which reflects the composite derivation from flexor and extensor musculature’ - Grays Pectineus (BDC II/4*/ 64) “The Pectineus muscle is of double origin and so it also has a double innervation. Its anterior fibres are supplied by the femoral nerve and its posterior fibres by the anterior division of the obturator nerve or the acessory obturator nerve. Such muscles are called Hybrid or composite muscles - BDC The Pectineus supplied by the femoral and obturator nerves belongs to the composite class - Grants Rectus femoris has not been mentioned as a composite muscle in isolation Answer is D (Sternocleidomastoid): Gray's 41"/448-449; Clinically Oriented Anatomy by Moore 5"/32, 263 , Last’s Anatomy 11/262 Digastric muscles refers to muscles with two bellies. Sternomastoid has two heads but it does not have two bellies and hence this muscle cannot be termed as a digastric muscle. Occipitofrontalis (Gray's 39"/ 500, 504) Occipitofrontalis muscle has two bellies (digastric muscle) + Occipital belly of occipitofrontalis and + Frontal belly of occipitofrontalis Omohvotd (Gray's 597538) Omohyoid consists of two bellies united at an angle by an intermediate tendon = _ Inferior belly of omohyoid - Superior belly of omohyoid204» AIPGME EXAMINATION ANSWERS AND EXPLANATIONS - 2008 © Muscle fibres in ligament of Treitz (Gray's 39°/ 1165; Last's Anatomy 11'"/262; Moore 5/263) Muscle fibres within the ligament of Treitz (Suspensary muscle of duodenum) contain two bellies = belly (slip) of skeletal muscle fibres and ~ belly (slip) of smooth muscle fibres. * Sternocleidomastoid: (Gray's 39/536; Moore 5*/ 32) Sternocleidomastoid has two heads of origin but a single belly and hence it cannot be classified as a digastric muscle. Nomenclature of Muscles based on number of heads or bellies (Gray's 39%/114) ‘Number of Heads Number of Bellies Two Heads : Biceps Two Bellies : Digastric Three Heads : Triceps The belly is the fleshy contractile part of a Four Heads : Quadriceps muscle 3. Answer is C (Till Respiratory Bronchioles) : Gray's 41°/968; BDC /6" /277 Bronchial arteries are branches of the descending thoracic aorta, They supply the bronchial wall as for as the respiratory bronchioles. - Grays Blood supply to Bronchopulmonary tissue Samsayeense Broachislieeastar 7) [Bronchial wee dival to the Rapa Orne eter asthe Respiratory Broneiole (Alveolar ducts, Ata, Air Bronchiole saceules,Alveli) Pulmonary vessels) | Pulmonary vessels alone and Bronchial arteries ‘Not supplied by Bronchial Arteries Purmonary pleura Bronchial Artery and Arterial supply of Pulmonary tissues ‘© Bronchial Arteries supply nutrition to the bronchial tree and to the pulmonary tissue ‘© These arteries vary in number, size, and origin but arise from the descending thoracic aorta either directly or indirectly & Right side Left side TR ‘There is one bronchial artery? ‘These are two bronchial arteries®, Arises indirectly? from the descending Arise directly? from the descending thoracic aorta thoracic aorta Either from: ~ Third Posterior Intercosal Artery, or + Upper left bronchial artery ‘+ These bronchial arteries accompany the bronchial tree along with the branches of pulmonary artery. Each Broncho pulmonary segment receives a branch of the bronchial artery ©The bronchial artery supplies the bronchial tree as far as the respiratory bronchiole ‘Segments distal to Respiratory bronchiole je. alveolar ducts, airia, air saccules or alveoli are supplied By branches from pulmonary artery and venis. (and not by branches from bronchial arteries) aAnswer is A (Femoral Nerve) : BDC 11/6"/ 91 |AIPGME EXAMINATION ANSWERS AND EXPLANATIONS - 2008 © 205 The skin overlying the region where a cut down is made to grant access to the great saphenous vein is supplied by the saphenous nerve. The saphenous nerve isa branch of the femoral nerve which is thus the single best answer of choice. ‘Venous cutdown of Great Saphenous Nerve * The Great saphenous vein isthe ideal Jocation® for peripheral venous cut down because ofits superficial and consistent position in both adults and children Itis the most common site® for a cut down ‘+The best location fora cut -down is approximately one finger breadth anterior and superior to medial malleolus * The region around the medial malleous is supplied by the great saphenous nerve (Branch of posterior division of Femoral nerve) ‘© Injury to saphenous nerve (supplied by Femoral nerve) is a known complication of venous cut- down ‘Saphenous nerve Answer is A (Straight tubules — Rete testes -> Efferent tubules) : BDC 11/6/24 The pathway of the sperm from within the testis to the epidydimis proceeds from the seminiferous tubules, to the straight tubules to the rete testes to the efferent tubules and finally from the efferent tubules to the epidydimis, ‘Seminiferous tubules —> straight tubules —> rete testes —> efferent tubule —» Epidydimis Structure of testis and pathway of sperm ‘© Sperms are formed in the seminiferous tubules ‘The glandular part of testes contains 200 — 300 lobules. Each lobule contains highly coiled tubules called seminiferous tubules. The spermatozoa (sperms) are first formed in these seminiferous tubules © — Seminiferous tubules continue into Straight tubules: At the apices of the lobules the seminiferous tubules from all lobules join together and form about 20 to 30 straight tubules ‘These tubules enter the mediastinum of the testis ‘© Straight tubules continue into the Rete testes With the mediastinum of the tests, the straigt tubules anastomose with each other and form a network of tubules called the Rete testes ‘+ Rete testes continues into Efferent ductules Rete testes gives rise to 12 to 30 Efferent ductules which emerge near the upper pole of testes and join the epidydemis, ‘© Efferent ductules continue into the Epidydemis Answer is A (Inferior Mesenteric vein): BDC 11/6%/281: Lasts Anatomy 11"/263, The paraduodenal recess /fossa is present in about 20% of subjects. The inferior mesenteric vein lies in the free edge of the peritonial fold - BDC206 © AIPGME EXAMINATION ANSWERS AND EXPLANATIONS - 2008 A | Duodenal Fossae /Revesses = '* Duodenal fossae are fossae or recesses that are created by folds of peritoneum ‘© These derive their significance by being potential sites of internal hernia that are prone to strangulation ‘© Lies tothe let of the DJ flexure and is orfie looks tothe right (prevent in about 50%) ‘© The inferior mesentric vein lies In the free edge of the (No significant vascular relations) peritoneal fold that forms the fossa (anterior wall) © Significance (present in about 75%) = An incarcerated hernia in this fossa may obstruct and (No significant vascular relation) thrombose the vein Retroduodenal fossa ~ There is danger of dividing the vein during surgery for | | This is the largest duodenal recess (No significant vascular relation) Mesnterico Parietal Fossa of Waldayer (present in 1%) ‘The most usual position of this fossa is in the first part of meso jejunum. The superior mesenteric vessels lie in the fold of peritonium forming this fossa Answer is C (Superior Vesical Artery) : BDC 11/6"/400 The ductus deferens is a thick walled muscular tube which transmits spermatozoa from the epidydimis to the ejaculatory duct. The ductus deferens recieves its blood supply from the artery to ductus deferens which usually arises from the superior vesical artery. Occasionally it may arise from the inferior vesical artery. ~ BDC Internal Iliac Artery oo) ‘Anterior Division Posterior Division 1. Superior Vesical Artery (Gives rise to artery of 1, SHiolumbar artery ductus deferens) 2. Lateral sacral artery (2) 2. Obturator artery 3. Superior gluteal artery 3, Middle rectal artery 4, Inferior vesical artery (Replaced by vaginal artery in females) 5. Inferior gluteal artery 6. Internal pudendal artery 7._Uterine artery (only in females) ‘Superior Vesical Artery and Inferior Vesical Artery are branches of Internal Mac Artery (Anterior Division) Tn females the inferior vesical artery is replaced by the vaginal artery and the uterine an extra branch, Answer is D (Deep Middle Cerebral Vein) : BDC III /6"/463 Deep Middle cerebral veins drain into the basal veins which drain into the Great cerebral veins that terminate in the straight sinus. Deep Middle cerebral veins neither form direct incoming channels nor direct draining channels for the cavernous sinuses. Deep Middle cerebral vein is therefore the single best answer of choice.[AIPGME EXAMINATION ANSWERS AND EXPLANATIONS ~ 2008 © 207 Cavernous Sinus Inoming Channels Draining Channels ‘Superior ophthalmic vein® * Superior Petrosal sinus Inferior ophthalmic vein® (drain into Transverse sinus) (A branch of this vein) * Inferior petrosal sinus * Central vein of Retina® (Grain into Internal Jugular vein) (may drain via superior opthalmic vein) # Emissiary veins® * Superficial middle cerebral vein (drain into pterygoid plexus of veins) # Inferior cerebral vein? # Superior ophthalmic vein® # Sphenoparietal sinus? (Grains into facial vein) * Middle meningeal vein® ‘© Inter cavernous vein® (sinuses) (Frontal and Anterior Trunk) (communicate between the left & right ccavemous sinuses) Frontal and anterior runkof middle meningeal vein Deep fcial vain Side view of the tributaries and communication ofthe cavernous sinu Answer is A (Develop around 8" week of gestation): Gray's 41"/440; Atlas of Vascular Anatomy by Uflacker 2" /71 The diploic veins develop after birth and not during intrauterine life within the diploe of cranial bones. These appear ‘about the fourth year of life and not around the 8" week of gestation. iploe and Diploic Veins © Classic structure of the cranial vault bone in an adult consists of an outer table and inner table of compact bone with an intervening cancellous portion. “This intervening cancellous and vascular portion is called the diploe and corresponds to the cancellous portion of other bones. ‘© The diploe and the tables that are classical in adults, do not develop in intrauterine life and are absent at birth. At birth the cranial vault is unilaminar (one lamina). The tables and diploe (intervening cancellous portion) appears about the fourth year (with maximal differentiation about 35 years) * Diploic veins are veins present within the cranial vault bones that drain the diploe. - These veins present no valves®, - These veins have thin walls and consist only of endothelium surrounded by elastic tissues® = These veins are of considerable size (large) and present dilatations at regular intervals - These channel unite and enlarge once sutures are obliterated = These veins anastomose externally with veins of the pericranium (pericranial veins) and internally with veins of the meninges (meningeal veins) and sinuses of the dura mater (dural sinuses)10. uu. ‘* AIPGME EXAMINATION ANSWERS AND EXPLANATIONS - 2008 = The major diploie veins include: Frontal Anterior temporal (parietal) + Posterior temporal (parietal) Occipital + Numerous small diploic vein tributaries ofthe superior saggital sinus = These veins are liable to inflammation after head injuries and may give rise to pus in the diploe and pye (May give rise to visceral abscesses after head injury) = These veins may be a source of significant bleeding after surgical vault fractures or surgical trephination. Answer is B (Lacrimal bone): BDC 1/1 /6%/240 The lacrimal bone does not form part of the nasal septum ‘Nasal Septum ‘The Nasal septum is the osseo cartilaginous partition between the two halves of the nasal cavity The Vomer ‘The perpendicular plate of. Ethmoid ‘+ Nasal spine of the Frontal bone ‘© Rostrum and rest of the Sphenoid ‘* Nasal crest of the Nasal Bone + Nasal crest of Palatine bone ‘+ Nasal erest of Maxillary bone cartilage Answer is A (Facial Nerve) : BDC III /6"/ 370 Facial nerve does not contain Somatic Efferents General Somatic Efferents # Septal process of the inferior nasal Incisorerest — Vomer Me wall ofthe nasal evity~the nasal septum ‘* Cranial Nerves that supply skeletal muscles of somatic origin contain somatic efferents ‘* These cranial nerves contain Somatic Efferent nuclei that supply these muscles. ‘* Skeletal muscles of somatic origin include the tongue muscles and the muscles that move the eyeball (obliques & Recti) Cranial Nerves Containing Somatic Efferents: (Nerves Hypoglossal Nerve - CN XII Occulomotor nerve - CN Il Trochlear nerve - CN IV Abducent nerve - CN VI Nuclei Hypoglossal nucleus Occulomotor nucleus Trochlear nucleus Abducent nucleus ‘Muscles of somatic origin supplied) Tongue muscles Medial Rectus, Superior Rectus, Inferior Rectus, Inferior Oblique Superior Oblique Lateral Rectus2 13. ‘AIPGME EXAMINATION ANSWERS AND EXPLANATIONS ~2008 © 209 Motor functions of skeletal Motor funetions of mucles Motor function of smooth ] muscles derived from somites | | derrived from branchial arches | | muscles and glands of head and viscera that receive Parasympathetic supply + + + Referred to as Referred to as: Referred to as: ‘Cranial Nerves Cranial nerves a TI (Occulomotor nucleus) V_ (Masticatory nucleus) TH (Edinger westphial nucleus | | 23 IV (Trochear nucleus) VI (Facial nucieus) VII (Superior salivatory nucleus) | |. ‘VI (Abducent nucleus) Ix IX (Inferior salivatory nucleus) 3 XII (Hypoglossal nucleus) x } (Ambiguous nucleus) X (Dorsal motor nucleus) R x iu XI (Spinal acessary nucleus) 2 & = Eacts to Remember 2CN containing Somatic Efferents or General somatic Efferents (SE/GSE) : CNIIII, IV, V1, XII °CN containing Bronchial Efferents or Special Visceral Efferents (BE/SVE) CNY, VUl, IX, X, XT 2CN containing General visceral efjerents (GVE /VE) CNII, VIL, IX, X Answer is B (Pons) : BDC III /6"/390; Neuroanatomy by Handelman (2000)/12 Facial Colticulus is an elevation in the floor of fourth ventricle produced by the abducent nucleus. It lies atthe level of pons Nerve nuclei ‘* The lower 10 cranial nerve (CNII to CN XII) arise from Nuclei within the brainstem ‘* The attachment site of each cranial nerve to the brainstem is a marker to the location of the cranial nerve nuclei within the brainstem (in almost all cases) * Occulomoor (CN) Trigeminal N (CNY) Glossopharyngeal (CN IX) ® Trochlear (CN IV) Abducent N(CN VD) Vagus (CN X) # Facial N(CN VI) Acessary (CN XD) ‘© Vestbulacochlear (CN VII) Hypoglossal (CN XID ‘©The first two cranial nerve nuclei are evaginations of the brainstem itself and these two cranial nerves (CN I and CN ID) do not originate from the brainstem Answer is C (Mesencephalic nucleus of trigeminal nerve) Grays 41"/255-256; Neuroanatomy (BRS) 4/155 Clinical Neuroanatomy (longe) 25/113 The reflex arc of Masseteric reflex involves two nuclei of the trigeminal nerve, namely, the mesencephalic nucleus ‘and the motor nucleus of CNV As Motor nucleus of trigeminal nerve has not been provided in the options, the Mesencephal best answer of choice c nucleus is the single210 © AIPGME EXAMINATION ANSWERS AND EXPLANATIONS - 2008 ‘The masseteric Reflex: Jaw Jerk * The mesenteric reflex isa stretch reflex forthe massetor muscle * Iisa monosynaptic reflex? + Gentle percussion with a reflex hammer generates proprioreceptive impulses inthe first order neurons. ‘+ These proprioreceptive impulses are relayed t0 the mesencephalic nucleus of CN V which sends excitatory projections tothe motor nucleus of CN V. ‘© Efferent impulses ae carried from the motor nucleus of CN V to the masseter muscle and produce the jerk ‘Naleus ofthe aferent lim is the mesencephalic nucleus of CN Nice of he ele ib tenor mes of CH V8 miss run in the nerve CN VE . Thpere (Brisk Jaw Jerk) indicates an upper motor neuron lesion PHYSIOLOGY 14, Answer is A (Histamine) : Skin Immune System by Bos 3/401, Ganong 22™/625; Chaudhuri 6/249; A Guide to Allergies by Ramdass 2007 /141; Goodman and Gillman's 11/405; Katzung 25/258 Lewis Triple Response is caused primarily by the liberation of Histamine and other Related peptides. Axon Reflex contributes only to the ‘Flare’ component of triple response and plays no role in the other two components namely Red Reaction and Wheal. Histamine is the single best answer of choice. According to Lewis in his original description the Triple response was caused by a substance called ‘H substance’ which is identical with histamine or with a compound of Histamine. Lewis Triple Response ‘Charachteristic three part response that develops when a pointed object is drawn firmly2over the skin | Red Reaction Flare Response Wheal | «This manifests inthe form of + This manifests in the form of spreading + This manifests inthe form of | ared line at the point of redness that extends beyond the original __swelling or localized edema contact with the skin (stroke) red line and occupies the same areas as + Results from transient + Results from stimulation of the Axon the red line | localized vasodilation due to reflex that causes vasodilatation ‘+ Results from increased release of histamine and indirectly. capillary permeability due to related mediators at the point The Axon Reflex may actually be histamine and other related of contact with the skin stimulated by released histamine along mediators with other related peptides Direct vasodilating effect of | { Indirect vasodilatory effect of histamine | | Histamine induced increased ] histamine by stimulating the Axon Reflex permeabil 15. Answer is D (All of the above) : Ganong 22™ /107; Chaudhuri 6% /318 KDT 6"/ 151, 152, 153 Histamine may be present in the mast cells (mast cell histamine) and in other cells as in the gastric mucosa (non mast cell histamine). Histamine increases gastric secretions (H; Receptors) and has been related to arousal, sexual behavior, regulation of secretion of some anterior pituitary hormones, blood pressure, drinking, pain thresholds and in the sensation of itch - Ganong‘AIPGME EXAMINATION ANSWERS AND EXPLANATIONS - 2008 © 217 Histamine ‘© Histamine is an amine synthesized locally from amino acid Histidine? ‘Histamine is mainly found within storage granules of mast cells and basophils but it is also found in other tissues ‘Mast cell histamine ‘Mast cells? and Basophils® Non Mast cell histamine : Gastric mucosa®, Brain ‘© Histamine receptors have been classified into three types — Hi, Hy and Hy, ‘Major Actions of Histainergie 5 Gastric glands Smooth muscles NS (Brain) # Histamine causes marked inerease + Blood vessels. - dilatation Histamine has been related to in gastric acid secretion” Histamine causes marked dilatation® — «Arousal = This direct action on parietal of smal blood vessels * Sexual behavior cells through 7; receptors? « Visceral smooth muscles -consiriction + Blood pressure = Thisis a G-protein coupled? ‘Airway (Bronchoconstition) + Drinking response mediated by Adenylate ‘Uterus + Pain thresholds cyclase activation? and an Intestinal Sensation of itch increase in cd 16. Answer is C (Increases gastric acid secretion) : Ganong 22/462 Gastrin decreases gastric acid secretion — Ganong 22™/ 486 ‘© Secretin is secreted by ‘S" cells of the a Secretin is homologous to glucagon® (Secretin — Glucagon family) 14 of the 27 aminoacids in secretin are same as those in glucagon). Increases the secretion of bicarbonate? by the duct cells of Pancreas and biliary tract (it causes secretion of a watery and alkaline pancreatic juice®) (its action on pancreatic duct cells is Mediated via cAMP®) ‘© It augments the action of CCK® in producing pancreatic secretion of digestive enzymes” © Itdecreases —gastric acid secretion by gastric parietal cells® «ita the contraction of pyloric sphincter® (along with CCK) ‘© Acid (H+) in the lumen of the duodenum® * Products of protein digestion® and fatty acids? in the lumen of duodenum 17. Answer is A (Tropomyosin): Ganong 22™/ 69; Chaudhuri 6" 6/486 In resting muscle tropomyosin covers the sites where myosin heads bind to actin — Ganong Role of Troponin and Tropomvos ‘Tropomyosin a E 5 . ‘Tropomyosin is a long filament like protein ‘Troponin is a complex of three regulatory proteins Tropomyosin covers the sites where myosin heads bind | | Troponin T: (T for Tropomyosin) actin Attaches troponin complex to tropomyosin + Tropomyosin snot alowed to ove fom his positon in| | troponin Troponin binds he oponin complex to Actin ‘the relaxed muscle because troponin binds both: a ‘tropomyosin and actin concomitantly so that tropomyosin | | ‘Troponin C :(C for Ca"*) This is the calcium binding remains serewed with actin troponin - ee ‘Troponin — Tropomvosin complex ‘Together the troponin — tropomyosin complex inhibits the interaction between actin and myosin and ‘constitutes a relavin protein® Role of Calcium (Calcium s released fom the sarcoplasmic Reticuli in response tothe ation potential) ‘This calcium binds to toponic ‘and eases a confirmational change i the Troponin -Tropomyosin = Actin uni? such that tropomyosin now shits poston and myosin ead binding sites of actin Become uncovered212 © AIPGME EXAMINATION ANSWERS AND EXPLANATIONS - 2008 18, 19, 20. Answer is D (Perleean) : Ganong 22nd68 (fig 3.4): Harrison 17” (2683-2684 Perlecan is a large multidomain proteoglycan found in the Extracellular matrix. It is not a sarcolemmal protein. Dystrophin, Sarcoglycan and Dystroglycan are all part of a large complex of sarcolemmal proteins and glycoproteins Sarcolemmal Proteins ‘© Several important proteins and glycoproteins are related to the sarcolemma. Important Proteins Related to Sarcolemma include ee ‘Transmembrane Proteins localized to sarcolemmal proteins the cytoplasmic face of sarcolemma 1. Dystroglycans (f-dystroglycan) : 2 Sarcoglycans (a, f,v,a,6) 4. Dystrophin 3. Caveolin - 3 2. Dysferlin 4. Integrins (B, a) ae ‘+ These sarcolemmal proteins and glycoproteins form three important complexes ‘Sareolemmal proteins and Glycoproteins complexes a el Dystrophin-Dystroglyean — Dysferlin Caveotin complex Integrin complex Sarcoglycan complex * Defect in these sarcolemmal proteins and glycoproteins and their complexes results in selected muscular dystrophies? Answer is A (Factor XIII) : Ganong 22™/ $43; Harrisons 17" /364 Factor XII is also known as fibrin stabilizing factor. Activated factor XII (XIIla) covalently cross links and stabilizes the fibrin clot — Harrison The fibrin is initially a loose mesh of interlacing strands, It is converted into a dense, tight aggregate (Stabilization) by the formation of covalent cross linkages. This reaction is catalyzed by activated factor XI and requires calcium. = Harrison Answer is D (Vascular endothelium is smooth and coated with glycocalyx) :Guyion 11"/ 463 Glycocalyx is an endothelial surface factor which repels clotting factors and platelets, thereby preventing activation of clotting in the normal vascular system ~ Guyton i in the normal Vascular System are? ( ‘© The smoothness" of the endothelial cell surface This prevents contact activation of the intrinsi clotting system? © Layer of Glycocaly on the endothelium Glycocalyx is a mucopolysacharide adsorbed to the surface of endothelial cells. Glycocolyx repels clotting factors and platelets and thereby prevents activation of clotting. © Throml {ulin on the endothelial membrane ‘Thrombomodulin is a protein bound with the endothelial membrane that binds thrombin Binding of thrombin with thrombomodulin prevents clotting by ~ removing thrombin = activating a plasma protein (Protein C) that acts as an anticoagulant by inactivating factor V and VIULa. 2. ‘AIPGME EXAMINATION ANSWERS AND EXPLANATIONS ~ 2008 © 213 Answer is B (Is higher than intraarterial pressure): Ganong 22™/ 590, Medicine for Anaesthetists 4"/ 285 Screening for Diseases by Snow (2004) /135] Blood pressure measured by Sphygmomanometer with a standard cuff tend to overestimate ‘true’ arterial pressures as measured by arterial cannulation, especialy in the elderly and the obese ~ Ganong. Bl ssure Measurement with nometers ‘* Sphygmomanometer isa device that measures blood pressures indirectly. ‘External pressure is applied with a sphygmomanometer cuff to the overlying tissues and the required to occlude the artery is assumed to be equal to the intra arterial pressure. ‘The sphygmomanometer will give accurate readings only if no pressure (zero mm. of mercury) is dissipated in compressing the soft tissues overlying the artery. However in practice, some pressure is always dissipated in compressing the blanket of soft tissues overlying the artery and hence blood pressure measured by the sphygmomanometer are slightly higher than true intra arterial Pressures. «The amount by which the sphygmomanometer overestimates the true blood pressure is influenced by the amount of overlying fat and the compressibility of the vessles. [Overlying Soft tissue Blanket | [ Compressiblity of vessels Size of Cuff. f= Thick overlying soft tissue | J» Vessels that are difficultto | |» Small (Narrow) cuff? leads to falsely blanket leads to ‘compress lead to high blood pressure recordings overestimation of blood ‘overestimation of blood (overestimation) pressure pressure Large (wide) cuff leads to falsely lower |» Obese individuals? havea | |» Elderly individuals® and blood pressure recordings thick blanket of fat which Diabetics may have rigid (under estimation) dissibates cuff pressure. sclerotic vessels that are + If the standard arm cuffs used to Hence Blood pressure is difficult to compress. Blood measure blood pressure in the thigh likely to be overestimated pressure measured in such falsely high blood pressure values will when measured by individuals with be obtained (due to relatively smaller sphygmomanometer and a sphygmomanometer will cuff size and greater soft tissue blanket). standard cuff. result in over estimation of | |. [fthe standard arm cuffs used on the | blood pressure forearm falsely lower blood pressure. | (Pseudohypertension) values may be recorded. | Note ‘More accurate pressure can be recorded in obese individuals by using a wider cuff size® © More accurate pressure can be recorded in the thigh by using a wider cuff size® Answer is D (During Exercise Systole is shortened more than diastole) : Ganong 22™ /566, 603; Chaudhuri 6°/191,202; KDT 6/478 During exercise the diastole is shortened more than the systole ‘The duration of systole is much more fixed than the duration of diastole, and when the heart rate is increased (exercise) diastole is shortened to a much greater degree’ - Ganong 22/566 ic stimulation (Noradrenaline)74 23. 24. ‘© AIPGME EXAMINATION ANSWERS AND EXPLANATIONS - 2008, Control of Heart by thetic (Noradrenaline) and asympathetic (vagus) nerv Force of cardiac contraction Decreased Increased (norropic effec (mainly atria, litle effect on ventricle) Conductivity Decreased Enhanced a Rate of cardiae contraction Decreased (Bradyeardia) Increased (Tachycardia) Vagal Parasympatheti) fibres are distebuted mai and not much tothe ventricles. Thus the major effect of vagal stimulation is to dsereass the hear rate o ate of eadiae contraction (bradycardia). Negave inotropic effect of vagal stimaation i ess pronounced. ‘Sompatheic bres ars distipted to both he atria andthe ventricles. Thus Sympathetic stimulation has a strong eect on both, the heart rate andthe force of era contraction, © Complete de df i erease in the resting heart rate. Efi Densreton fh hark (Ganong 27°60. Chart 9717-202 Node Inirinsie Rhythmic “The normal heart rate at rest in young persons is about 70/minute (Range thmiciy peoween 30- 100/min) ‘Sinuatrial node (SAN) 100/min' Atrio Ventricular node O/min® ‘© The sinuatrial node (SAN) is the normal pacemaker of the heart and MaPenenaint 3. tolan? generates a rhythm of about 100éminute ‘The normal heart rate of about 70/min in a young adult is maintained as a result of autonomic influences on the SAN ‘When both vagal & sympathetic nerves are removed (denervated hear), the sinuatrial node becomes fre from all autonomic (sympathetic & parasympathetic) influences and starts generating its normal rhythm of about 100/min + As the normal resting heart rate is usualy less, about 70/min, complete denervation of the heart would cause an increases inthe heart rate from 7W/nin to 100/min. ‘+ During exercise the diastole is shortened more than systole. Changes in Duration of Systole and Diastole, when heart rate is increased (Exercise), + Exercise is associated with an increase in the heart rate + Cardiac muscle has the unique property of contracting and repolarizing faster when the heart rate is high ‘+ This leads to a decrease in duration of both systole and diastole “However the duration of systole is much more fixed than that of diastolic and when the heart rate is increased (eg. exercise) diastole is shortened to a much greater degree” - Ganong ‘+ This longer duration of diastole enables : ‘Superior coronary blood flow to the cardiac musculature? Superior ventricular filling? Answer is B (Temperature lower than core body temperature): Ganong 22/427 Spermatogenesis requires a temperature considerably lower than that of the interior of the body — Ganong ‘© Spermatogenesis requires a temperature lower than the core body temperature Tesies are normally maintained at a temperature of about 32°C. This lower temperature is maintained by: - air circulating around the testes ~ heat exchange in a counter current fashion between spermatic arteries and veins + Factor which raise scrotal temperature® can impair’ is and lead to infertilit ‘These include: - Ectopic or undescended testes (intraabdominal)? - Wearing of tight scrotal support® ~ Presence of varicocele® ~ Occupations involving exposure to excessive heat, such as men working in blast furnaces Answer is C (The tubes are lined by ciliated epithelium) Guyton 11/1028, 1029; Dutta 6/7, Williams Obstetrics 22/27; Shaw's Gynaecology 14"/ 177, 178. The fallopian tubes are lined by. ted epithelium. + ‘The fallopian tubes are lined by ciliated columnar epithelium. ‘The fallopian tubes are lined by a single layer of columnar cells. Some of them are ciliated and others are secretory. The ciliated cells are most abundant at the fimbriated extremity, elsewhere they are found in discrete patches Williams 22/2725. ‘AIPGME EXAMINATION ANSWERS AND EXPLANATIONS - 2008 © 215 © Thecilia always beat towards the uterus ~ (Guyton) The transport of fertilized ovum through the fallopian tube into the cavity of uterus is effected by: 1. A feeble fluid current in the tube resulting from epethelial secretion and the action of tubal cilia. The cilia ‘always beat towards the uterus, such that the direction of flow is towards the uterine cavity-Guyton, Williams 2. Tubal persistalss, resulting from rhythmic contractions of the tubal musculature ‘© Eertilization of ovum occurs in the fallopian tubes, and not in the uterus (Guyton) Fertilization must occur within a few hours, and no ‘more than 24 hours® after ovulation ‘+ Implantation of the fertilized ovum occurs between 5-7 days af t afte 2A hours) (Guyton) ‘After fertilization has occurred, an additional 3-5 days is normally required for transport of the fertilized ovum through the fallopian tube into the cavity of uterus Implantation occurs at the stage of ‘blastocyst’? Answer is D > A (Massage of foot > Increased with change from supine to standing position) : Guyton 11'%/192; Ganong 22"/ 593, Concepts in Medical Physiology by Seifier (2005)/ 163, 164 Any external factor that causes intermittent compression of lymph vessels (Massage of foot) causes pumping of the lymphatics and improves (increases) the rate of lymph flow. Factors that increase interstitial fluid pressure (change from supine to standing position) also increase the rate of Lymph flow if lymph vessels are functioning normally. Thus both, option A and option D are correct statements. However prolonged standing tends to worsen lymphoedema ‘and hence if we have to pick one single correct answer from amongst the options provided, massage of the foot would probably be the single best answer of choice. Fluid efflux from tissues exceeds the fluid influx across tissue capillaries and constitutes the Intertial fluid Lymph is derived from this interstitial fluid and is returned back to the central circulation (subclavian vein) through iymphatic vessels. + Factors Controlling Rate of Lymph Flow Interstitial Fluid Pressure Lymphatic Pump Suction forces ‘Other Factors ‘Any factor that increases interstitial fluid ‘Any factor that causes intermitten | |e Intrins pressure also inereases Iymph flow compression of lymph vessels causes contractility of pumping of lymphatics and Lymphatic Lymph Flow is thus increased by: improves the rate of ymph flow capillaries + Ted capillary hydrostatic pressure increases rate of + Led plasma colloid osmotic pressure | | Lvsmph slow is thus inreased by. lymph flow + Ted interstitial fluid colloid osmotic | |* Active striated muscle a. — ‘+ Movement of parts of the body nervous system + Ped permeability of capillaries ‘© Pulsation of arteries adjacent to stimulation Deep vein valve incompetence increases the lymphatics through the action ‘venous stasis and impairs the ability of + Compression of tissues by of catecholamines venous end of capillaries to reabsorb objects outside the body on aand fluid. Tis increases the amount of (massage of foot) adrenergic interstitial fluid and enhances the rate of | | « Rhythmic changes of intra receptors Iymph flow abdominal and intra thoracie increases rate of (Edema results once volume of fluid pressure caused by respiration ene q exceeds the capacity of the lymphatics) (suction forces) ym! |216 ‘© AIPGME EXAMINATION ANSWERS AND EXPLANATIONS - 2008 Standing from supine position: Effect on Lymph formation and flow ‘When an individual goes from a supine to standing position water and filtrable substances move from the intravascular space to the interstitial compartment thereby raising the interstitial fluid pressure, “Any factor that increases interstitial fluid pressure also increases lymph flow ~ Guyton 1792 1 This should therefore also enhance or increase the rate of lymph flow When a person stands up from a recumbent position, the amount of lymph production per unit of time may increase upto 40% in the area ofsyprafascial lymph vessel ofthe lower leg ~ old's Textbook of Lymphology (2007) /199 26. Answer is A (Does not change) : Ganong 22" /634 Cerebral blood flow is maintained at constant levels (does not change) in response to moderate exercise ‘Changes in Blood Flow in Response to moderate exercise (Isotonic) Cd creased Decreased ‘Maintained (No change) © Active Skeletal ‘© Inactive Skeletal Muscle ‘© Brain (cerebral) Muscles © Kidney © Skin (cutaneous) © Liver Gastrointesinal tract Other Organ systems 27. Answer is A (Fine Touch) : Ganong 22” /138; Guyton 11/588 Fine touch is transmitied through the Dorsal /Posterior column . ons requiing fine gradients of intensity /high degre of loalizaion ‘+ Fine Pressure (Fine degrees of judgement of pressure intensity) © Vibration Joint Position Sense ‘SGisations Transmitied by Anterolateral Column /Spinothalamic Tract” NaN © Oude Touck® * Crude pressure? © Pain (Pin Prick)? ¢ Temperature? __ “Anterior” Spinothalamic Tract (Ventral) | [Lateral Spinothalamie Tract Crude Touch® Pain (Pin Prick)® Crude Pressure? Temperature? BIOCHEMISTRY 28, Answer is D (HMP Pathway) : Harper 27" /177, 189 Lippincott's 4" / 104, 113, 192 ‘The pentose phosphat pathway or hexose monophosphate shunt (HMP) is an alternate route for the metabolism of glucose, other than glycolysis. It does not lead to formation of ATP - Harper 278/177 No ATP is directly consumed or prduced in the hexose monophosphate shunt (HMP) ~ Lippincott's 4/145‘AIPGME EXAMINATION ANSWERS AND EXPLANATIONS -2008 © 217 ‘ATP Generation from important Metbolie cycles Glycolysis Tricarboxylic Acid Cycle Fatty acid oxidation (ca) Oxidation of fatty acids produces a large eecinea para 12 molecules of ATP per quantity of ATP — Harper bau hycolye molecule of Acetyl CoA —_(The net energy yield from oxidation of one 2moleculesof 8 molecules of molecule of palmitate is 129 ATP —Lippincott) ATP foreach ATP for each molecule of molecule of glucose glucose 29, Answer is B (Muscle) : Harper 27" /142; Chatterjee 7/328; Lippincott 4"/128, 129, 130 Muscle glycogen cannot contribute directly to plasma glucose since muscle lacks glucose 6-phosphatase — Harper Glycogenolysis in Liver and Musel * Breakdown of glycogen into glucose is called glycogenolysis ‘© When glycogen is degraded the primary product is glucose 1- phosphate®, obtained by breaking a (1-4) glycosidic bonds? ‘© This reaction is catalyzed by enzyme ‘phosphorylase’ (Rate limiting and key enzyme in glycogenolysis®) Glycogen phosphorylase (Present in both Muscle and Liver) Phosphoglucomutase (Present in both Liver and Muscle) (Glucose 6 =F) Further =o 00] ‘InLiver (and kidney) a specific enzyme glucose 6— In Muscle, enzyme glucose 6- phosphatase is absent Phos is present ; ‘ Free glucose can therefore not form in muscle directly and This enzyme removes the phosphate (PO, from vi Meee cnabtng te oonaten offrelucse, —Hetee Glycogenolysis in muscle does nt contribue directly to This free glucose is free to diffuse from the hepatic load glucose, cells to extracellular spaces including blood. This glucose 6- P can enter the glycolytic cycle and form Gtycogenolysis in Liver thus contributes directly to pyruvate and lactic acid, Indirectly, lactic acid may go to blood glucose glucose formation in the liver 30. Answer is D (Insulin) : Harper 27" /161, 162, 163 Chatterjea 6"/326, 327 Insulin inhibits the activation of phosphorylase b. It does this by increasing the uptake of glucose, leading t0 increased formation of glucose 6- Phosphate, which is an inhibitor of phosphorylase kinase — Harper Factors maintaining phosphorylase ints active form | [Factors maintaining phosphorylase in its inactive form (phosphorylase a) (phosphorylase b) 2 * cAMP © Insulin © Calcium © Protein phosphatase + ATP + Glucose 6 phosphate218 © AIPGME EXAMINATION ANSWERS AND EXPLANATIONS - 2008 Phosphorvlase enzyme and its regulation ‘* Phosphorylase is the most important and rate limiting enzyme of glycogenolysis® * Phosphorylase enzyme is found in two forms, active (phosphorylase a ) and inactive (phosphorylase b). ‘Active phosphorylase (phosphorylated form) : Phosphorylase a Inactive phosphorylase (dephosphorylated form) : Phosphorylase b ‘© The active form of phosphorylase (phosphorylase a) catalyses the following reaction Glyeogen +, Glycogen, + Glucose 1-P ‘The inactive form of phosphorylase (phosphorylase b) is activated into the active form (phosphorylase a) by a CAMP / calcium dependent enzyme ~ phosphoryl kinase (a) (active) as depicted in the following flow chart. + Novepinepine Epinephrine ° * Glucagon TeAMP Thyroid hormone: CAMP dependent Protein Kinase Calcium ADP Phosphorylase a @ C) (active) 1,0 o ® Protein Phosphoryl kinase (b) Phosphoryl kinase (a) Je G6P<*—[Insutin} ¥ phosphatase (inactive) (Active) arp] ADP p Phosphorylase b ‘ ATP ‘Anactive) 1. CAMP and hormones that increase cyclic AMP ‘concentrations ie... Epinephrine , Norepinephrine Glucagon, Thyroid hormones ‘These activate cyclic AMP dependent protein kinase ‘which intur activates phosphoryl kinase and subsequently converts phosphorylase b to active phosphorylase a 2° Calcium Calcium activates the caleium dependent unit (g subunit) of phosphoryl kinase and subsequently converts phosphorylase b to active phosphorylase a 3. ATP ATP donates the "Pi for required for phosphorylation ‘of phosphorylkinase b and phosphorylase b into their respective active (a) forms 2. Protein 1. Glucose 6 phosphate Glucose 6 phosphate is an inhibitor of phosphorylase kinase rosphatase Protein phosphatase converts active phosphorylase (2) into inactive phosphorylase (b) by dephosphorylation (removing iP). It also dephosphorylates active phosphoryikinase (a) to inactive phosphoryl kinase (b) 3. Insuli Insulin inhibits activation of phosphorylse b. It does this by increasing uptake of glucose leading to increased formation of glucose 6 phosphate which is an inhibitor of phosphorylkinase Insulin also increases Protein Phosphatase activity Answer is D (Chaperones) : Harper 27" / 515, 516, 517, Ganong 22™ /25, 297, Chattarjee 7"/251 Chaperones an proteins that play a role in proper folding of other proteins without themselves being components of ‘the latter - Harper ‘Chaperones: CChaperones are proteins that play a role in the assembly and proper folding of synthesized proteins so that the latter proteins gain biological activity These proteins enable proper folding of other proteins without themselves being components of the latter®32. 33. |AIPGME EXAMINATION ANSWERS AND EXPLANATIONS - 2008 © 219 haperon proteins _ Present in a wide range of species from bacteria to humans, ‘BP (immunoglobulin binding protein) Many are so-called heat shock proteins (HSP) GRP94 (glucose — regulated protein) Some are inducible by conditions that cause unfolding of newly synthesized proteins (eg. clevated temperature and various chemicals) They bind to predominantly hydrophobic regions of unfolded Calnerin Calreticutin and ageregated proteins. They actin part as a quality control or editing mechanism for detecting misfolded or otherwise defective proteins Most chaperones show associated ATPase activity, with ATP or ADP being involved in the protein-chaperone interaction Found in various cellular compartments such as cytosol, mitochondria, and the lumen ofthe endoplasmic reticulum. Proteosomes (Ubiquitin ~ Proteosome pathway) or Endoplasmic Reticulum Associated Degeneration (ERAD) '* Proteosomes® are organelles involved in degradation of misfolded proteins and regulatary enzymes that have short half lives ‘© — Ubiquitin® is a small, highly conserved protein that plays a key role in marking various proteins for furthur degradation in proteosomes (Ubiquitin tags proteins for degradation) ‘© Prior to entering proteosomes most proteins are ubiquinated and are escorted to proteosomes by polyubiqutin — binding proteins | Pathways for Protein degeneration in Eukaryotes [Protein degradation in Lysosomes (Protein degradation in proteosomes ‘* Involves Lysosomal proteases * Invoves by Ubiquitin ~ Proteosome pathway '* This process does not require ATP? ‘+ This process requires ATP (ATP dependent)? Proteases: Proteases are enzymes that catalyse the hydrolysis of proteins into their component amino acids (Harper 27/7) ‘Templates: ‘Template is a strand of DNA which is copied during RNA synthesis. In the double stranded DNA molecule, the genetic information resides in the sequence of nucleotides on one strand called the template strand (Harper 274/312) Answer is A (Golgi bodies): Harper 27" /506, 518 The Golgi apparatus is involved in glycosylation and sorting of proteins — Harper 27%/518 ‘Many studies have shown that the Golgi apparatus plays a major role in sorting of proteins for their correct destinations — Harper 277506 ‘The rough endoplasmic reticulum branch of protein storing. ‘+ Newly synthesized proteins are inserted into the ER membrane or lumen from membrane-bound polyribosomes. + Proteins then pass through the various subcompartments of the Golgi until they reach the Trans - Golgi Network (TGN), the exit side of Golgi. + Inthe TGN, proteins are sorted and seggregated. Answer is C (Enterokinase) : Chatterjee 7"/435; Harper 279/597 Enterokinase is a glycoprotein enzyme that activates trypsin220 © AIPGMEEXAMINATION ANSWERS AND EXPLANATIONS - 2008 oe 3 Trypsin Trypsin isa proteolytic enzyme (proteinase) involved in the digestion of proteins ‘Activators of Trypsin Tnhibitors of trypsin Enterokinase” © Alpha Antiproteinase or Alpha-l Antritrypsin® Caleium® * Di isopropy! fluro phosphate (DFP) Trypsin itself” © Egg white? (Egg white contains water soluble mucoprotein which Trypsin acts nan alka is a potent inhibitor of trypsin) ‘medium ‘+ Human and bovine colostrum ‘+ Raw soyabeans Alpha Antiproteinase is Synonymous with a, Antitrypsin Itis synthesized by hepatocytes and macrophages and is the principal inhibitor of serine proteases in human plasma inhibits trypsin, elastase and certain other proteases by forming complexes with them. Answer is C (Apoprotein CII inhi Harper 27 / 217, 218 Chaterjee 6/383; Apoprotein CII acts as an activator of lipoprotein lipase. It is required as a cofactor for lipoprotein lipase activity its lipoprotein lipase): Li jrotenemia) ‘+ Lipoprotein Lipase is n extracellular enzyme attached to the capillary endothelium of most tissue (Adult Liver does not have this enzyme”) by heparan sulphate ‘Lipoprotein Lipase activated by Apo C Il (and Apo C 1) on circulating lipoprotein particles hydrolyzes the triacyl glycerol contained in these particles to yield fatty acids and glycerol + Patients with a deficiency of Li Apoprotein C II show a dramatic accumulation of chylomicrons in the plasma (bypertriacylglycerolemia) = Type Hyperlipoprotenemia or familial lipoprotein lipase deficiency ‘What ipoproteins / Apoproteins : Review ‘Apoproteins / Apotipoproteins are the protein moieties of Lipoprotiens. The plasma lipoproteins are spherical macromolecular complexes of lipids and specific proteins called apoproteins Functions of Apolipoproteins ® + Lipoprotein Lipase activators: ‘Apo ~ CH (Most important) and Apo — CI + Lipoprotein Lipase inhibitors : Apo Cll, Apo A It + Lecithin - Cholesterol Aeyl Transferase (CAT) Activators: Apo ~ Al + LDL Receptors? ~ Apo B100, ApoE + HDL Receptor® + Apo AI © Remnant Receptor? = ApoE (LDL Receptor related protein) Form part of the structure of lipoproteins B Apoprotin B Structural protein for ehylomlront VLDIs IDls LDL. = Apoprotein A -1 :_ Structural protein for HDL SD ili Eli35. ‘AIPGME EXAMINATION ANSWERS AND EXPLANATIONS - 2008 © 221 Defect in biosynthesis / secretion of Apoppoprotein B results in Abetalipoproteinemia and Homozygous ‘Hypobetalipoprotonemia i.e. absence of chylomicrons, VLDL, IDL and LDL (Malabsorption & Neurological defects) Defect in biosyntsis ‘secretion of Apolipoprotein AL results in virtual absence of plasma HDL. and premature heart disease? Answer is C (II) : Harrisons 17"/ 2419 Type III hyper lipoprotenemia (Familial Dysbetalipoprotenemia or familial broad fi disease) is characterized by mixed hyperlipidemia due to accumulation of ‘remnant’ lipoprotein porticles of VLDL and chylomicrons. ~ Harrisons 17/2419 Apoprotein E present on chylomicron and VLDL remnants is required for their removal via hepatic lipoprotein receptors. Type III hyper lipoprotenemia results from a defect in Apoprotein E as a result of which VLDL and chylomicron remnants are not removed ‘adequately and accumulate in the circulation Frederickson Classification of Hyperlipoproteinemias Laboratory Features (Borin vst Chyomisons LDL LDeand VBL” Chyloicrons VLDL Chylomirons B end VEDL fd VIDE i remnants Tigers tote - ” wore + a Choteser tos pg HO Ra Sa HHT LDL-cholesterol + + + + + + WDLetoleserol +++ + w ¥ + a Plammmperece Lakota Clee Tubid ——Tubid——_Lactescent Clinica ears Xantbomss ewe Tendon, bes None Palmar, None Epi bevenptve Pancreas He o o ° ° os Coronary ° oe ve ” “ erasers espe! o ‘ + * *% a tetra Molecular ict & Genetic nomenlare Moker defects LPLandpo-C-ll LD Leer ApoB-10, Unknown Apel AOA and. ApoA-V and PCSKO, ARH, ABCOS a Chino Unknown BCG Gensticnomeciate FCS FH, FDB,ADH,ARH,——FCHL fa ATG TG Sloeolenia + FCS (lami cylomicranemiasadrome) + FDB Gala defective apoB) {FH Gail ypercholeserotemia) {ARI (atosomalrecesvehypercholesterlemia) © ADH (atasomel dominant hypercholestrolemia) + ECHL Gala combined hyperpidemta) © FDBL familial dsbetalpopretenemia) { FHTG Gamal perrighceridemi). © LPL Aipoproten lipase «Apo apolipoproten)‘222 © AIPGME EXAMINATION ANSWERS AND EXPLANATIONS - 2008 36. Answer is A (ds DNA) : Harper 27" /335, 336, 337 Lippincow 4/406 Okazaki fragments are short segments of DNA synthesized on the lagging strand, during the process of replication of a double stranded DNA (dsDNA) lication of jed DNA Helicase ‘The process of replication of double stranded DNA requires the ds ‘Unwinds ds DNA to provide ss DNA DNA to unwind into single stranded DNA (ssDNA) template as a replication can occur only from a single stranded DNA template (ssDNA template isa step inthe process of replication of dsDNA) Relieves torsional stain that results from helicase mae induced unwinding Formation of replication fork and identification of two strands Single spond binding (leading strand /lagging strand) proteins’ Prevent premature rannealing Initiation of DNA synthesis ofds DNA fo) aR Lagging Stand primase? # RNA Primer is RNA primer in synthesized to prime Initiates synthesized to prime synthesis of new DNA syntheses of synthesis of new DNA new RNA J primer ‘*DNA is then synthesized « DNA is then synthesized in multiple short continuously in $'-3" fragments ~ Okazaki fragments in S'-3" direction by DNA direction by DNA polymerase I? polymerase II? Ueyuesting ‘© RNA primer is then excized by DNA DNA only in polymerase I se ‘© DNA gap between Okazaki fragments is direction? filled by DNA polymerase [° ‘* Remaining nicks are sealed by DNA ligase! Removal of RNA primer and filling of the resulting “gaps” by DNA polymesare I37. 38. AIPGME EXAMINATION ANSWERS AND EXPLANATIONS ~ 2008 * 223 Answer is A (Folic Acid) : Harper 27" /490, 496 ~ Lippincott’s 4/373 Folic acid isa water soluble vitamin. Nine vitamins (Folic acid, cobalamine, ascorbic acid, pyridoxine, thiamine, niacin, riboflavin, biotin and pantothenic acid) are classified as water soluble, whereas four vitamins (Vitamin A, D, E and K) are termed fat soluble-Lippincott 4/373 Classification of Vitamins: + Vitamin A (retinol, B-carotene) as + Vitamin D (cholecalciferol) + Vitamin K (phylloquinones, menaquinones) Ascorbic acd (vitamin C) + Vitamin E (tocopherols) a ato Pro Other See ‘Thiamine (vitamin B,) * Folicacid —» Pyridoxine (vitamin B6) «+ Riboflavin (vitamin B,) ¢ Vitamin By + Niacin (vitamin B,) + Biotin + Pantothenic acid Answer is D (Vitamin k) : Harper 27"/495 Lippincott 4%/389 The principle role of vitamin K is in the post translational modification of various blood clotting factors, in which it serves as a coenzyme in the carboxylation of certain glutamic acid residues present in these proteins ~ Lippincott Role of vita blood coagulation ‘© Vitamin k is required in the hepatic synthesis of prothrombin and blood clotting factors Il, VII, IX and X® ‘These proteins are initially synthesized as inactive precursor molecules The activation of these molecules requires carboxylation of their glutamic acid residues Vitamin K acts as a coenzyme during this carboxylation reaction” COs, Precursors of clotting factors \ Carboxylase 1H, VIL, 1X, ‘Mature clotting factors Il, VII, IX, X (Inactive Glutamyl residues) Vitamin K (Active y-carboxy-glutamyl Gla residues) of _iyiroxyquinone) This reaction requires 0,00, and the hyroxyquinone form of vitamin K? This carboxylation reaction is sensitive to inhibition by dicumarot® and warfarin? Dicumarol isa natural analog of vitamin K Warfarin isa synthetic analog of vitamin K * The carboxylated glutamyl residues (Gla) on mature clotting factors confer on them the capacity to bind Ca”* and to get bound to phospholipid surfaces. These properties enable participation of mature clotting factors in the coagulation cascade ‘© Vitamin K is the only fat soluble vitamin® that functions as a coenzyme? (Lippincott) Vitamin K exists in three forms = Vitamin K,, Kp and Ky Vitamin Ky Phylioquinoney: Normal derry source found n green vegetables Vitamin K; (Menaquinone) : This form is synthesized by intestinal bacteria® Vitumin K; (Menadione) : These ae synthetic compounds? that canbe metabolized vitamin K (phylloguinones)®‘224 © AIPGME EXAMINATION ANSWERS AND EXPLANATIONS - 2008 39. 40. © Funct : : Role in blood Role in synthesis of Role in Oxidative ‘ongsaton atu ining protein Pisepherieon Vitamin K is | | Vitamin K is required for synthesis of two proteins present | | Vitamin K is necessary co- required in in bone; factor in oxidative hepatic synthesis ||- Osteocalcin phosphorvlation® being ofprothrombin | |_ Bone matrix Gla protein. associated with mitochondrial jand blood Treatment of pregnant women with Warfarin is known to lipids cloning, Jacior ‘cause fetal bone abnormalities (fetal warfarin syndrome). 1, Vi, IX and X°) | This may be explained by deficiency of vitamin K secondary | | Dicumarol2, an antagonist of to warfarin use, which inturn leads to bone abnormalities | | vitamin kis known to act as due to defective synthesis of bone calcium binding proteins. | |@n uncoupler of oxidative phosphorylation Answer is A (lonised): Chatterjea 7" /875, Harrisons 17" /286 Ionized calcium isthe physiologically active form of calcium ~ Chatterjea 7/875 Total Calcium eed Tonized calcium Protein bound calcium (Ditfusible calcium) (Non diffusible calcium) + About 50% of total calcium is ionized ‘+ Remaining 50% of total calcium is bound, mainly to * Ionized calcium is the physiologically albumin, active form of calcium + Protein bound calcium is not physiologically active Facts to Remember®: Normal level of plasma calcium is 9 ~ 11 mg/dl The frst step in diagnostic evaluation of hyper or hypocalcemia is to ensure that the alteration in serum calcium level is not due to abnormal albumin concentration’ ‘When serum albumin concentration is reduced, the concentration of ionized, free or active calcium is increased and hence serum calcium values need to be ‘corrected’ ‘Corrected’ calcium level calculations require measurement of total calcium and albumin and subsequent application of a mathematical correction. Corrected calclum concentration is calculated by adding 0.8 mg/dl (0.2mM) to the total ‘calcium level for every decrement in serum albumin of 1.0 g/dl, below the reference value of 4.1g/dl of albumin, and conversely for elevation in serum albumin® - Harrison Answer is C (Simple Diffusion) : Harper 27"/424, 108, 433, Ganong 22™/31 Absence of charge over molecules (Uncharged / Neutral molecules) favours their transport by simple diffusion. ‘Small neutral molecules are usually transported freely across plasma membranes by simple diffusion. Diffusion is the single best answer amongst the options provided. ‘Transport of Neutral / Uncharged Molecules ‘Small Neutral (Uncharged) Molecules Large Neutral (Uncharged) Molecules © Free Diffusion ‘© Channel Proteins (Simple diffusion) (Simple Diffusion) ‘© Carrier Proteins (Facilitated diffusion or Active transport) ‘Some selected small uncharged molecules may be transported through channels or pores‘AIPGME EXAMINATION ANSWERS AND EXPLANATIONS - 2008 #225 [actors Favouring Transport of Molecules via Simple Diffusion Charge 2 Absence of charge (Neutrality) favours transport by Simple diffusion © Size Small size favours transport by Simpe diffusion ‘© Polarity Absence of polarity (Non Polar nature) favours transport by Simple diffusion © Hydrophobicity Lipid solubiliy/Hydrophobicity favours transport by Simple diffusion (Lipid Solubitiy) PATHOLOGY 41, Answer is B (NADPH Oxidase) : Robbins 9" /47-48 Oxygen dependent killing is largely mediated through Reactive Oxygen Intermediates (ROD). The generation of reactive oxygen intermediates is due to the rapid activation of an oxidase, NADPH oxidase ~ Robbins Catalase, superoxide dismutase and Glutathione peroxidase are radical scavenging enzymes that prevent oxygen ‘mediated injury. nD killing of infectious agents and necrotic cells crronsou ing i gue ome + Oxygen dependent killing is largely mediated through the generation of ie od Reactive oxygen intermediates® — ‘+ The most important enzyme involved in generation of reactive oxygen won ta ec, intermediates is NADPH oxidase. <= + NADPH oxidase leads directly to the generation of superoxide anion and a 7 | indirectly to the generation of Hydrogen peroxide (H, O;), Hydroxylation tora fe (OH) and hypochlorite (HOCI), with the help of Myeloperoxidase enzyme oa oA ‘within azurophilic granules of neutrophills. Sa Radical generating Reactive oxygen we Radical scavenging enzymes enzymes intermediates (Protective) ‘NADPH oxidase (Most ‘Superoxide anion (>) Catalase important) Hydrogen per oxide (H:0:) ' Superoxide dismutase Xanthine oxidase (In some cells) Hydroxyl radical (OH) Glutathione peroxidase [NADPH + Myeloperoxidase Hypochlorite (HOCI) Hydrogen peroxide - Myeloperoxidase — Halide system: Most efficient bactericidal system + The most efficient bacterecidal system mediating oxygen dependent killing is HO;~ MPO Halide system in neutrophils? © This system requires NADPH oxidase, Myeloperoxidase and halide ions® = NADPH oxidase system generates H;0> = Mycloperoxidase within azurophilic granules of phagocytes in presence of halide & ions converts H3O3 into HOC. = HOC is the potent antimicrobial agent that destroys microbes by halogenation and for oxidation - 42. Answer is D (Direct effect of injuring agent): Robbins 9 /74; Pathology by Holliman 4/22 Delayed prolonged leakage is believed to be caused either by the direct effect of injurious agent or by cytokine ‘mediated endothelial retraction. Itis not casued by cytokine mediated vasodilatation and cytokine mediated endothelial retraction is not provided in the options. Direct effect of injuring agent is therefore the single best answer of choice “The mechanism of delayed prolonged leakage is unclear. It may result from the direct effect of injurious agent leading 10 delayed endothelial cell damage (perhaps by apoptosis) or the effect of cytokines causing endothelial retraction’ Robbins226 AIPGME EXAMINATION ANSWERS AND EXPLANATIONS - 2008 43. Patterns of Altered Permeabilit Increased vascular permeability” is the hallmark of Acute inflammation Increased permeability in acute inflammation may occur in three patterns ‘Delayed Prolonged Leakage Immediate sustained leakage +* Occurs in response to mild injuries * Occurs in response to moderate injuries ‘* Occurs in response to severe + Permeability (Leakage) begins * Permeability (Leakage) begins after 2- 12 injury Immediately after exposure to hours and lasts for several hours or even days. ¢ Permeability (Leakage) begins mediators and is usually reversible ‘immediately after injury and is and short lived oF transient (15 to sustained ata high level for 30 minutes) + Affects venules as well as capillaries several hours until the damaged « Affects venules alone. Capillaries vessels are thrombosed or and arterioles remain unaffected © Caused by physical injuries such as thermal repaired + Caused by chemical mediators injury, X-Ray or UV radiation and certain Affecis venules, capillaries and such as histamine, bradykinin bacterial toxins arterioles Jeukotrenes and substance P © Caused by direct endothelial # Mechanism not clear. damage due to severely injurious © Mechanism: Believed to result from direct efect ofthe stimuli such as in burs or Gaps in the endothelial lining ‘injurious agent leading to delayed endothelial _ severe neorotizing / lytic from endothelial contraction cell damage (pethaps by apoptosis) may be bacterial infections caused by cytokine mediated endothelial © Mechanism: retraction which is usually delayed (in Direct endothelial injury ‘comparison to endothelial contraction caused _resultin in endothelial cell by histamine et) necrosis and detachment Fact to remember: The most common pattern of increased permeability is Immediate Transient leakage® Answer is A (Causes Pain) : Robbins 9" /39 Bradykinin increases vascular permeability, causes contraction of smooth muscles (bronchoconstriction), dilatation ‘of blood vessels and pain - Robbins 7/65 Bradykini ‘© Increased Vascular ‘© Vasodilatation Permeability © Contraction of smooth muscles © Pain (bronchoconstriction) Role of Mediators in Different Reactions of Inflammation, Tncreased vascular permeability Vasoactive amines? (C3a and C5a (through liberaing amines) © Bradykinin® Leukotrienes Cy Dy EX PAFe Substance Pe Noe Oxygen metabolites? ‘Chemotaxis, leukocyte recruitment and Ca activation Leukotriene BE : Chemokines? IL-1, TNF Bacterial products? Fever IL-1 (and 1L6)® TNEe Prostaglandins Ee Prostaglandins? E- Bradykinin® Tissue damage ‘Neutrophil and macrophage lysosomal enzymes® Oxygen metabolites? Nitric oxide®45. [AIPGME EXAMINATION ANSWERS AND EXPLANATIONS - 2008 © 227 Answer is C (T-cells): Current Occupational and Environmental Medicine 3" /193; Tumor Immunology by Parmiani and Lotze (2002) /48; Biotherapy by Rieger 2™ /48 ‘Antigen presenting cells include Macrophages, Dendritic cells in lymphoid tissue, Langerhans cells in the skin, Kupffer cells in the liver, Microglia cells in the nervous system and B lymphocytes? = Current Occupational and Environmental Medicine 3rd /193 (The CMDT series of books by Lange publications) ‘Antigen Presenting cells * Monocyte? - Macrophages? © Dendritic cells® in Lymphoid tissue Activated = Kupfer cells® in liver * Langerhans celis® in the skin B Lymphocytes? = Microglia® in nervous system ~ Alveolar macrophages in lungs = Splenic macrophages Other References to support B lymphocytes (Exact lines quoted) “Antigens are processed by specialized Antigen — Presenting — cells (APC) eg Dendritic cells, monocytes, B-cells’. ~ Tumor Immunology (2002) /48 “The best defined Antigen presenting cells are Dendritic cells, Macrophages and Activated B lymphocytes’. —Biotherapy 2"/48 ‘Three types of cells of bone marrow origin are now established as MHC — class I! expressing Antigen Presenting cells. These are B lymphocytes, Macrophages and dendritic cells’ — Clinical Oral Science (1997)/250 ‘Tivmphoeytes are not Antigen Presenting cells T cells ean only recognize an already processed antigen displayed by an antigen presenting cell. For any cell to function ‘as an Antigen presenting cell it should have the ability to internalize the antigenic substance / protein by phagocytosis / pinocytosis, process the endocytosed antigenic structure and then display the antigenic fragments of the native protein ‘on its surface. T cells do not have the ability to internalize and process such native antigens, and hence they can not act as antigenic presenting cells. T cells however perform the critical step of recognizing such processed antigens on the surface of APC’s Answer is A (8, Microglobulin) ; Robbins 7/260, 261 Repeat (AI ~2007) Patients on long term hemodialysis for renal failure develop amyloidosis due o deposition of f, microglobulin (Robbins) ‘The most important amyloid proteins and their relevant clinical scenarious include: ‘This is derived from plasma cells and contains Itis a unique non immunoglobulin protein synthesized by {immunoglobulin ight chains. Reticuloendothelal cells of Liver & It is associated with Secondary It's associated with Primary amyloidosis © amyloidosis & reactive systemic amyloidosis ® + Immunocyte dyscrasias with amyloidosis such as * Chronic Inflammatory conditions: Maltiple myeloma ® ~ Tuberculosis, @ ‘+ Other monoclonal B-cells proliferation. ~ Bronchiectasis,® Osteomyelitis 2 + Connective Tissue Disorders ~ Rheumatoid Anhits ° (most common), = Ankylosing spondylitis, = 1PBilliary cirhosis ® + Non immune derived tumours = Renal cll carcinoma, ® = Hodgkins Lymphoma &228 © AIPGME EXAMINATION ANSWERS AND EXPLANATIONS - 2008 Br Transthyretin Islet amyloid Atrial natriuretic factor mlcroglobulin protein (AB) (ATTR) associated peptide (ALAPP) associated amyloid (Bam) isloid (A cal) (ANF) is@ « Senile cerebral’ « Familial ‘* Medullary CA # Type I ++ Isolated atrial amyloidosis ‘associated — + Alzheimer's? amyloidotic Thyroid? diabetes® + Misfolded prion protein disease neuropathies? (PsPse) Prion disease ; «Systemic senile : camyloidosis® 46. Answer is D (sis): Robbins 8% 281; Devita 6"/13, ‘sis? oncogene is a growth factor. The protooncogene ‘sis’ encodes the ( B chain of) Platelet Derived Growth Factor (PDGF) - Robbins 7" /293 ‘mye, jun and fos oncogene are all nuclear regulatory proteins. Selected Oncogenes with their Modes of Action + erb (EGFR) Brotsin tyosine kinases |» fins (CSF-1 Receptor) | + rer (Receptor for Neurotrophic factor) + kit (Receptor for stem cel factor) + ros (Insulin receptor) rine “Threonine 1 erb A (Related 19 kinases thyroid hormone ras proteins (H, KN) receptor) (953 antagonist) CDK4 (Cyclin dependent kinases) PDGF (Platelet derived Growih factor), FOF (FibroBlast Growth actor), EGFR (Epidermal Growth Factor Receptor) 47. Answer is D (Wild type is associated with tumors) : Harrisons 17"/ 499, 500; Devita's Principle and Practices of Oncology 6"/19; Robbins 7"/ 302, Harsh Mohan 5/216, 217. Wild type of pss gene refers to the Normal (Non-mutated) form of ps; gene. The wild type of pss gene (Normal /Non- mutated) is a tumor supressor gene that maintains the genetic integrity of cells and prevents the development of tumors. Itis the mutated form of pss gene (and not the wild type) that is associated with tumors (Devita 6" /19) Gene (Guardian of the Genome) (Molecular policeman ‘The pss Gene is located on the short arm (p) of chromosome 17° (17p 13.) © The pss gene derrives its name from its apparent molecular mass (It is a $3 k D, protein)? ‘Normal (Wild type) «The Normal ps; gene (Wild type) functions as a tumor supressor gene® and functions as a critical gatekeeper against the development of cancer (Molecular policemen / Guardian of the genome®) ‘© The psy gene is located in the nucleus and functions as a nuclear transcription factor? ‘* Two major functions of ps gene are, A. Inblocking mitotic activity : pss gene inhibits cyclins and cyclin dependent kinases (CDK) and prevents the cell to enter G, phase transiently®. This allows the normal cell to repair the DNA domage B. Inpromoting Apoptosis”: psy gene acts together with another anti-oncogene (RB gene) and identifies the genes that have damaged DNA which cannot be repaired by in built system. Ps; gene directs such cells to Apoptosis® by activating apoptosis inducing BAX Genes, and thus brings the defective cells to an end. This process operates in the cell cycle at G, and Gz phase before the cell enters the S or M phase48. 49, Mutant P53 gene (Mutant pss gene) ‘AIPGME EXAMINATION ANSWERS AND EXPLANATIONS - 2008 © Most pss mutations are acquired in somatic cells and affect both psy alleles. = Some psy mutations (less common) may be inherited in the germ line, These mutations usually affect a single allele (Such individuals are said to have ps type Li Fraumeni® syndrome and have a 25 fold greater chance of developing a malignant tumor by the age of 50 years than the general population) (Inheritance of one mutant pss allele predisposes individuals to develop malignant tumors because only one additional ‘hit is needed to inactivate the second normal 29 The wild type of pss gene may undergo mutations that inactivate or alter the normal function of p® gene llele ~ “Second hit phenomenon’) ‘© Mutations in both alleles of ps; (Homozygous loss of ps, activity) can give rise to several human cancers “Most common genetic alteration found in human cancer (>50%) is on acquired mutation in p gene® (Harrison) ‘Tris likely that all kuman cancers have genetic alterations that inactivate the Rb and p53 tumor supressor pathway. * Presence of mutant ps; genes in tumor cells predicts a poor response to radiotherapy and chemotherapy? (poor prognostic factor)® Tumors expressing mutant pss gene are more resistant? to radiation therapy and chemotherapy than tumors with wild type pss Harrison) Answer is A (Melanoma) ; Harrisons 16" /563, 439, Harrisons 17"/615 HMB ~ 45 is an immunohistological marker for Melanoma ‘© —S—100 (90% of Melanomas are positive for S - 100) *__ HMB ~ 45 (HMB ~ 45 is more specific but less sensitive than S ~100) ‘Miscellaneous Tumor Markers : (Harrisons) Tumor Markers [Cancer Gestational trophoblastic disease, Human chorionic gonadotropin sonadal germ cell tumor Calcitonin Medullary cancer ofthe thyroid | Catscholamines Pheochromocytoma ‘Antigens | Cancer rs Alphafetoproein Hepatocellular carcinoma, gonodal | germ cell tumor | Carcinoembryonic antigen | Adenocarcinoma ofthe colon, | pancreas, lng, breast, ovary [Eieymes (Cancer ae Prostatic acid phosphatase | Prostate cancer [Neuron specific enolase | Small ell eancer ofthe lung, neuroblastoma Lactate dehydrogenase Lymphoma, Ewing’s sarcoma imor-ASsoclated Proveins | Cancer = Prostate ~ specific antigen ‘Monoclonal immunoglobulin CA~ 125 IcA- 19-9 CD30 cps Prostate cancer Myeloma Ovarian cance, some lymphomas Colon, pancreatic, breast cancer Hodgkin's disease, anaplastic large cll lymphoma Hairy cell eukemia, adult T cll leukemia /Iymphoma PSA / prostatic acid phosphatase Placena alkaline phosphatase Gross esti Hid protein Factor Vil ‘Thyroid transcription factor ~ 1 (rte=1) Actine myosin filaments Calretinn, Mesothelin |Chromogranin, Synaptophysin Neuron specific enolase [BRST 1 Progesterone & Estrogen Receptors [cDx2 Answer is A (t x; 18) : Robbins 8" / 1233, Harrisons 16% /563 Cancer Lymphoid neoplasm Hodgkin's disease Carcinoma Lymphoid neoplasm [Neuroendocrine tumor, Melanoma Breast, sweat gland Kaposi’s sarcoma, angissreoma Lung adenocarcinoma, thyroid Rhabdornyosarcoma Neuroendocrine tuners Carcinoma Melanoma Bladder cancer Mesotielioma "Neuroendocrine tumours Breast cancer| Breast cancer| Gastrointestinal eancer ‘Most synovial sarcomas show a charachteristic chromosomal translocation t (x; 18) - Robbins 7/1323AIPGMEE 2008 - EXPLANATIONS. 230 © AIPGME EXAMINATION ANSWERS AND EXPLANATIONS - 2008 female ssa Facts to Remember : Harrisons 16"/ 563; 645 Devita's 6"/ 1844, 2412 111322) wing's Sarcoma Family * Classical Ewing's Sarcoma + Peripheral neuectodermal Tumor (PNET) = Askin’s Tumor 1(12;22) Clear Cell Sarcoma ‘Malignant Melanoma of Soft tissues e 141216) Myroidlposarcoma 1aiB Alveolar Rhabdomosarcoma RIED 0x: 18) Synovial cell sarcoma Cytogenetic Markers ies) Mantle Cell Lymphoma (14; 18) Follicular Lymphoma 814) 184] Burki'sExmphoma (8 cell ALL) 1118) MALT Lymphoma uals 15) CLL/ Small mphocytic Lyomphoma 49:2) Precursor B cell ALL (Pre-B- ALL) Chron Myeloid Levbaemia (CML) ease) ‘Acute Promyclocytic Leukaemia (AML M3) 18:21) “eae NicloblateLesacnta th motration ASS 5 50. Answer is A (CD15 and CD30) : Robbins 7/688, Harrisons / 16" /655 The tumor cells in Hodgkins Lymphoma are characteristically positive for CD15 and CD30 and negative for CD45. Robbins 7/688 Lymphocyte predominance Hodgkins Lymphoma is the only histological subtype that does not express CD15 and CD30, This subtype expresses CD45 and is often considered as an entirely distinct category from classical Hodgkin's disease (Harrisons) (HAGEL ¥mphionia”—— Tmmunopheno type "Nodular Sclerosis DIS +, CD30+ EBV -Ve Lacuna cells? (Occasional RS-cels) ee eD1s +, cD30+ HELV CONTERIS Cie eal Sirnis [Lymphocyte depletion DIS +, CD30+ EBV +Ve2 Reticular variant? (Frequent R-S cells) Pinon coh ern a re TH “| CD30- EBV — eS 51, Answer is A (Retinoblastoma) : Khurana 4" /281: Robbins 8/1365 Rosettes are characteristic in retinoblastomas. Microscopic features of well differentiated Retinoblastomas include, Flexor ~ Wintersteiner Rosettes (characteristic of Retinoblastomas), Homer -Wright Rosettes (characteristic of neuroblastoma & medulloblastoma) Pseudorosettes and fleurette formation. Rosettes: Review (‘Neuropathology for the Neuroradiologists’: Pathology Review by Wippold and Perry)52. /AIPGME EXAMINATION ANSWERS AND EXPLANATIONS ~ 2008 ¢ 231 What are rosettes? Rosettes are pathological findings characterized by a halo or spoke whee! arrangement of cells surrounding acentral core or hub. What is the significance of rosettes” The presence of primary rosettes often suggests a given diagnosis (charachteristic finding), however this finding alone is not considered absolutely specific or pathognomic for one specific tumor type Common type of rosettes? Fleaner Winterstelner Homer Wright ‘True Epeniymal Perivascalar Rosettes Rosettes wowette pocuteroeties + Anal ofcels surounds a + Aaloofeellssuroundss © Ahuloofeells _* All of cells surounds a blood ves largely empty central hub ceniral hub that contains a surrounds an empty _* The term ‘pseudo’ is used because the but small eoplasmic meshwork of fibres area central structure is not formed from the extensions from cells (Neutrophil rich centre) tumor itself, and represents a nonneo project In the men plastic eletent CS oS, 2 wwe SO) x ao ee é oe Se Flexner Wintersteiner Homer Wright rosettes are Truc Ependymal rosettes Pseudorosettes are not considered rosetes are characteristic of om NEM ‘mechancterisicof characteristic of any particular Retinoblastomas® Renan and Ependymomas ‘These may be seen in Medulloblastomas = Ependymomas Meuioem = Means = Medullobsoras Medulolastomas Meekeos + Primitive Neuroectoderma tumors Pineoblastomas Tumors (PNET) ~ Central Neurocytoma, - Pineoblastomas = Gliablastomas = Retinoblastoma Retinoblastomas * Monomorphous pilomyxoid asteetenae ‘Summary of rosette patterns and associated tumors Homer Wright rosette ‘Neuroblastoma, medulloblastoma, primitive neuroectodermal tumor, pineoblastoma (Flexner-Wintersteiner rosette Retinoblastoma, pineoblastoma, medulloblastoma 4@ True ependymal rosette Ependymoma -ular pseudorosette Ependymoma, medulloblastoma, primitive 4 neuroectodermal tumor, central neurocytoma, ‘ glioblastoma, monomorphous pilomyxoid astrocytomas | Pineocytomatous rosette Pineocytoma (Neurocytic rosette Central neurocytoma | Answer is D (Hyaline Arteriosclerosis) : Robbins 9/490; Harsh Mohan 5"/ 711, 712, 713 Hyaline arteriosclerosis isa feature of Benign Nephrosclerosis assciated with benign phase of Hypertension. It is not 4 feature of Malignant Hypertension,232 © AIPGME EXAMINATION ANSWERS AND EXPLANATIONS - 2008 ‘Benign Nephrosclerosis This tem is used to describe the changes in kidney associated with benign phase of hypertension Gross © Kidney size is either normal” or may be moderately reduced” © Grain leather appearance? : The cortical surface has a fine even granularity | Microscopic (Vascular Changes & Parenchymal Changes) © Hyaline Arteriosclerosis ° ‘Narrowing of the lumens of arterioles and small arteries caused by thickening and hyalnization of the walls © Fibroelastic Hyperplasia®: in the intima (intimal thickenning®), duplication of elastic lamina and hypertrophy of the ‘media’ ‘+ Parenchymal changes (due to ischaemic) Variable degree of Atrophy of parenchyma due to ischaemia | Malignant Nephro: slerosis This term is used to describe the changes in kidney associated with malignant or accelerated hypertension Gross © Kidney size is variable? May be smaller in size (when superimposed on benign nephrosclerosis) or Larger in size (enlarged)° than normal (patients ‘who develop malignant hypertension in pure form) © Flea bitten appearance®: The cortical surface may show multiple small peticheal haemorrhages? from rupture of arterioles ‘or glomerular capillaries. Microscopic (Vascular Changes & Parenchymal Changes) 11) + Fibrinoid necrosis of arterioles® (Necrotizing carterioliis®) ‘The vessel wall shows fibrinoid necrosis. Represents an acute event and necrosis is usually ‘not accompanied by intense inflammation + Hyperplastic intimal sclerosis® / Onion ~ Skinning Concentric laminae of proliferated smooth muscle cells, collagen and basement membrane (producing intimal thickenning) ‘* Parenchymal changes (due to ischaernia) Variable degree of atrophy of paranchyma due to ischaemia. Infarction necrosis distal to abnormal vessels may be seen Answer is D (Alports syndrome): Robbins 9/913; Harrison 17"/1785 Alports syndrome is not associated with Rapidly Progressive Glomerulonephritis or Crescentric Glomerulonephritis “Harrison 17° /1785 Rapid jJomerulonephritis (RPGN) / Crescentric Glomerulonephritis Crescentric Glomerulonephritis isa histopathological diagnosis based upon the presence of ‘crescents’ in most of the Glomeruli. This type of histopathological picture (crescents) is seen in cases of Rapidly Progressive Glomerulonephritis (RPGN) and hence RPGN and Crescentric Glomerulo-nephrtis are often used synonymous. Causes of Crescenteric Glomerulonephritis (RPGN [ype I RPGN (Anti - GBM Antibody) ee ‘© Idiopathic Anti Glomerular Basement membrane disease # Good pasture's Syndrome ‘Dope RPGN (immune Compiex) 2 Idiopathic Acute Post Streptococcal Glomerulonephritis (PSGN) Lupus Glomerulonephritis (SLE) Henoch Schonlein Purpura (HSP) IgA Nephropathy Membranoproliferative Glomerulonephritis (Harrisons 17" / 1785) Cryoglobulinemia (Harrision 17"/ 1785) Post infectious (After subacute Bacterial Endocarditis) Glomerulonephritis Wegener's granulomatosis, 2 Microscopie polyangitis Churg ~ Strauss syndrome58. ‘AIPGME EXAMINATION ANSWERS AND EXPLANATIONS - 2008 * 233 Renal disease in Alport’s syndrome (Harrisons 17" /1794) Patients with Alport’s syndrome develop thinning and splitting of Glomerular basement membrane®, and chronic glomerulosclerosis®, leading to renal failure. (Clinically present with hematuria & proteinuria) Rapidly progressive Glomerulonephritis or crescentric glomerulonephritis is not associated with Alport’s syndrome. Harrisons 18° /2344; Chandrasoma Taylor 3" /708 Mesangiocapillary Glomerulonephrits is the other name for Membranoproliferative glomerulonephritis. Itis a type of proliferative Glomerulonephritis. (Harrisons 17” /1789) Answer is B (Mesangiocapillary Glomerulonephi Proliferative changes in Glomerulonephritis (Refer: Chandrsoma Taylor 3"! /702, 708) ‘* Glomerulus contains Endothelial cells, Epethelial cells, and Mesangial cells. Any of the three cell types may undergo proliferation in different types of Proliferativ Glomerulonephritis. ‘© Proliferative changes are not to Membranoproliferative and Mesangioproliferative Glomerulonephritis, bbut may be seen in several other forms of Glomerulonephritis Glomerulonephritis and Proliferative changes el ‘Glomerulonephritis without proliferative changes Glomerulonephritis with proliferative changes “Glomerulonephritis | Proliferative changes [[Glomerulonephritis Proliferative changes ‘Minimal change Disease | - (Absent) Post streptococcal GN + (Crescent) Membranous = (Absent) “Antbasement membrane disease | + (Crescents) Glomerulonephritis (Good — pasture’s syndrome) Diabetic Nephropathy ~ (Absent), ‘IgA Nephropathy (Berger's) + (Mesangial) Amploidosis = (Absen!) Henoch Schonlein Purpura __| + (Mesangial) Focal segmental + Variants with protiferaive | | Mesangioproliferative GN + (Mesangial) Glomeruloscerosis | lesions have heen described | | Membranoproliterative GN | + (Endothelial & including cellular lesions with | | (Mesangiocapilary GN) Mesangial) ‘endocapillary hyperceliutarity- | | Focal Glomerulonephits + Focal) (Harrisons) ‘Secondary Glomerulonephritis | + Variable SLE/PAN Note : Crescents represent proliferation of epethelial cells Answer is C (Nephrin): Robbin's 7"/981, 983, 984 ““A mutation in the Nephrin gene causes a hereditary form of congenital Nephrotic syndrome (Finnish type) with ‘minimal change glomerular morphology”- Robbins 7"/981 + Nephrin is a key component of the slit diaphragm «+ Itis a zipper like structure between podocyte foot processes that might control glomerular permeability + The Nephrin gene maps to chromosome 19q13 and is termed as NPHS1 + Several type of Mutations of the NPHSI gene have been identified and they give rise to congenital nephritic syndrome of the Finnish type. No ‘+ ‘Podocin’ has also been recognized as a component of the slit diaphragm. ‘+ Podocin is encoded by a gene termed as NPHS 2 and maps to chromosome 1425-31 ‘+ Mutation in the podocin gene or NPHS2 lead to an autosomal recessive form of focal segmental glomerulosclerosis.234 © AIPGME EXAMINATION ANSWERS AND EXPLANATIONS - 2008 56. Answer is C (Fibromatosis) : Robbins 8° /1251 Fundamentals of Diagnostic Radiology by Brant & Helms 3/542, Pediatric Hematology by Arceci Hann and Smith 3”! (/373, Nelson's 18/2148 (Askin Tumors) Fibromatosis can be defined as a group of conditions associated with either benign tumors (desmoid tumors) or tumor like conditions (eg peyronie’s disease). These conditions represent benign lesions and are not malignant. Askin Tumors, Chloromas and Plasmacytomas are all Malignant tumors Askin Tumor : (Differentic is in Orthopedic Oncology by Greenspan 2" 323; Nelsons 18"/2146) Askin tumor is a rare malignant neoplasm arising from the chest wall of children and young adults ‘© These tumors arise from primitive neurectodermal rests in the chest wall and are grouped into the Ewing’s sarcoma family of tumors (Ewing’s sarcoma along with PNET (Primitive Neurectodermal Tumors) and Askin tumor) ‘These lesions are very aggressive and associated with a high mortality rate Ch lary Leukaemia or Granulocytic sarcoma) © Chloromas can be described as extramedullary masses of leukaemic cells that are commonly seen in patients with Acute Myeloid Leukemia, (AML) * They represent malignant tumors and are also called granulocytic sarcomas ~The most common site of chloromas is the Orbit / Periorbital region® = They are also frequently noted in the skin® = They may involve the spinal cord and may present with symptoms of cord compression® = They ate most commonly seen with M, and Ms AML® but may also be seen with M, and Mz subtypes Plasmacytomas (Harrisons 17” /704) . Plasmacytomas are malignant tumors of plasma cells. ‘+ They are best described as variants of Multiple Myeloma and usually occur in two forms: Solitary Bone Plasmacytoma: Single Lytic bone lesion without marrow plasmacytosis, Extramedullary Plasmacytomas: Usually involve the submucosal lymphoid tissue of the nasopharynx or paranasal sinuses without marrow plasmacytosis ‘M component in < 30% of cases® ae Associated Median survival 2 10 years® Affect younger individuals? Eibromatosis + Fibromatosis represent a group of fibrous benign tumors or tumor like conditions and are classified into superficial & deep fibromatosis. Fibromatosis are not malignant lesions © These are better described as tumor like lesions Deep fibromatoses represent a group of fibrous rather than true tumors. tumors that are benign but locally aggressive ‘© These conditions include a group of fibrous ‘They do not metastasize and hence are not tissue lesions that are more bothersome than considered malignant despite their locally serious aggressive nature - Palmar fibromatoses (Depuytren contracture) © ‘They may however recur after surgical excision ~ Plantar fibromatoses (due to their locally infiltrative nature) = Penile fibromatoses (Peyronie's disease) ‘+ Example includes Desmoid tumors 57, Answer is A (Genomic imprinting): Harrisons 16"/ 375; Robbins 9"/ 17258. /AIPGME EXAMINATION ANSWERS AND EXPLANATIONS - 2008 © 235 The phenomenon referred to as genomic imprinting leads to preferential expression of an allele depending on its ‘parental origin — Harrison 16%/ 375 ‘Genomic imprinting Imprinting refers to selective inactivation of a gene or set of genes on either the ‘maternal chromosome or the paternal chromosome 7 Maternal genomic imprinting Paternal genomic imprinting Inactivation of maternal allele ie. inactivation of Inactivation of gene on paternal allele i.e. inactivation of a ‘a gene on maternal chromosome gene on paternal chromosome ‘Thus the only functional alleles are now provided by either the paternal or maternal chromosomes (ie. only ‘one parent) Y Deletion of the only functional allele results in genetic syndromes + Prader Willi syndrome: deletion on paternally derived chromosome® + Angelman syndrome: deletion on maternally derived chromosome? | Prader WilliSvndrome || Angleman Willi Syndrome. Maternal Patera Maternal Patemal Prader Will Angelman gene gene Gesomic ‘inpiting imprinted imprinted Active (aac) Active Prader Goativ) Angelman radet Wil Willi gene Angelman gene gene ome ‘The only functional gene ‘The only functional gene is provided bythe is provided bythe paternal chromosome paternal chromosome Deletion on paternal Deletion on pateral chromosome chromosome imprinted imprinted inactive) Ainative Jeeted inactive water Deke intve mater agenan gos Prader Wit Prader Willi gene “Angelman cima gs a! “| Prader Willi Syndrome Angelman Syndrome ‘+ Deletion occurs exclusively on paternal + Deletion occurs exclusively on maternal chromosome 15, chromosome 15 (deletion of tand q 12 in long arm of chromosome 15) = Features 2 Features = Diminished fal activity — Hypotonia = Hypotonia? — Mental retardation = Obesity? - Seizures = Mental retardation Ataxia = Shor stature — Inappropriate laughter (Happy puppets) = _Hypogonadotropic hypogonadism Answer is A > D (Antibody) > (Glycoprotien): Harrisons 17” /2155, Davidsons 20/1074 A Rheumatoid factor is an antibody (auto-antibody) of any immunoglobulin class directed against a specific region of the Fe fragment of human IgG. - Davidson Rheu236 60. ‘© AIPGME EXAMINATION ANSWERS AND EXPLANATIONS - 2008, * A Rheumatoid Factors is an antibody (auto-antibody) of any immunoglobulin class (directed against Fe fragment of human IgG) © Rheumatoid factor in Rheumatoid Arthritis belongs to the IgM class ° (directed against Fc fragment of IgG)? (IgM Rheumatoid factor is positive in about 80% of patients with Rheumatoid arthritis (Harrisons 17"/2155) Q ‘© Antibodies are glycoproteins and immunoglobulins are also glycoproteins © A Rheumatoid factor is an antibody and because antibodies are glycoproteins, it would not be incorrect to say that Rheumatoid Factors are glycoproteins. If Antibody / Auto- antibody is not provided amongst the options Glycoprotein would be the best correct answer, Answer is B (Occurs when donor cells are immunocompromised) : Robbins 9/236, Harrisons 17/715, 716 Graft versus host disease occurs when immunologically competent donor cells (not immunocompromised donor cells) are transplanted into immunologically crippled (immunocompromised) hosts and the transferred cells recognize host cells as alloantigens, (Robbins 17"/ 222) Graft Versus Host Disease (GVHD) ‘© The Graft Versus Host Disease (GVHD) was first recognized in animal studies on mice, when it was termed Runt disease, (Blood' by Handin, Lux, Stossel 2"/2133) ‘+ Graft versus Host Disease may occur in any situation in which Immunocompetent cells or their precursors are transplanted into Immunosupressed recipients Graft versus Host disease occurs because the immunocompetent T-cells present in the donors recognize the HLA. antigens in the host as ‘foreign’ and react against them. * GVH disease occurs most commonly in the setting of allogenic bone marrow transplantation, but may also follow transplantation of solid organs rich in lymphoid cells (eg Liver) or after transfusion of unirradiated blood ‘within 3 months posttransplant or persisting beyond 3 months post transplant * GVHD most commonly presents with changes in Skin, Gut or Liver disease® PER eS 0A eR Ol Rash Elevated Bilirubin Persstant Anorexia Exythroderma Elevated ASTALT Persistant Diarrhoea Desquamation & Bullae Elevated Alkaline phosphatase Both * Diagnosis usually requires Biopsy from Skin, Liver or Gut (endoscopic)? Answer is C (Binds to the cleft in the MHC II Molecule): Harissons 18"/2671-72; Essentials of Clinical Immunology 4"/ 40, 41; Immunology by 1°/ 88, 90 The Cleft in the MHC I molecule represents the Antigen binding groove where conventional peptide antigens or ‘simple? antigens are presented. Superantigens do not bind to the cleft or the antigen binding groove in the MHC II ‘molecule. They bind ata site which is distinct from the cleft and located on the lateral side of the cleft. ‘Superantigens ‘© Super-antigens are protein molecules produced by some bacteria and viruses that do not require to be processed tracellularly by Antigen presenting cells before they activate the T cells. ‘Simple Antigens (Conventional antigens) are first processed by Antigen presenting cells and ‘the processed antigens are then presented on the surface of the APC. These processed antigens are presented in the Antigen binding groove (cleft) of the MHC II molecules. The T cell Receptors om the surface of T cells ean only recognize peptide antigens that are displayed on the antigen binding groove of the MHC.61. |AIPGME EXAMINATION ANSWERS AND EXPLANATIONS - 2008 «237 © They bind directly to MHC of APC and T cells at a site distinct [waperameyen from the cleft or antigen binding groove. This is possible because superantigens have two binding sites. One binding site is for the class If MHC molecules found on the surface —se ‘of APC, and the other binding site is found outside the Antigen ete binding site on the T cell Receptor. Binding of superantigen to re MHC I of APC and T cell causes T cell activation. ed cosa Te ‘* Because the superantigen does not bind to the specific antigen binding site on the TCR, super-antigens select all T celts (carrying a particular T cell Receptor V i gene) regardless of the T cell antigen specificity. This widespread T cell activation results in massive release of inflammatory cytokines and hence clinical ‘manifestations of hypotension and shock are often associated istinguishing features between Simple antigens and Super-antigens = ees ar + Need tobe processed intracellularly by APC before they» Do not need to be processed intracellularly can activate the T cells * Bind to MHC class 11 molecule in the Antigen binding © Bind to MHC class IL molecule directly to the lateral groove or cleft (groove of the af hetrodimer) portion Antigen binding groove or cleft Bind to the Tcells.at the T cell Receptor region (TCR) ‘Bind to the T cel in the lateral portion of the T cell (V region of the TCR a and f chains) Receptor (Lateral portion of TCR 8 chain) + Stimulation of T cells is dependent on the antigenic * Stimulation of Tceltsis independent of T cell antigenic specificity of T cells (Only those T cells that have the T ‘specificity Al cells cerying a particular T cell Receptor V cell Receptor (TCR) appropriate to the MHC antigen B gene are stimulated regardless ofthe T cell antigenic complex are stimulated ~ specific) specifciyy ‘© Stimulate smaller number of T cells ‘Stimulate larger number of T cells (Activate about 1 in 10,000 T cells) (Activate about 1 in $0 T cells) ‘+ The release of inflammatory eytokines is less marked «The release of inflammatory cytokines is massive/marked. (monokines / Lymphokines) (monokines & lymphokines) This is often associated with hypotension & shock. © Examples include + Examples include ‘Normal cell mediated immune reactions Toxic shock syndrome (Staphylococcal, Streptococcal, Clostridial, Yersinial) Role of super antigens is also been investigated for Kawasaki disease (No organism yet identified but superantigen association is ‘based on eytokine profile) Answer is B (Asbestosis) : Robbins 9"/691; Chandrasoma Taylor 3/541 Ferruginous bodies are most commonly seen in Asbestosis ~ Chandrasoma Taylor 3/541 Ferruginous bo + These bodies represent foreign inorganic or organic fibres coated by complexes of iron and glycoproteins (fibre + iron — glycoprotein coat). + While ferruginous bodies are most commonly seen in Asbestosis they are not diagnostic because a similar iron — glycoprotien coat may form on any other type of inhaled fibre. ‘+ Ferruginous bodies are best seen in sections that have been stained for iron with prussian blue ‘+ Microscopically Ferruginous bodies give a shish kebab appearance®. ‘A thin central asbestos fibre (5- 10 1 mlong) encased in an iron containing glycoprotein coat which is brown and typically beaded (like a shish kebab) ts to Remember Schaumann's bodies and Asteroid bodies are seen in sarcoidosis” Russell bodies (cytoplasmic) and Dutcher bodies (nuclear) are seen in Multiple Myeloma? Psammona bodies may be seen in Meningiomas, Papillary Carcinoma Thyroid, Serous Cystadeno Carcinoma of Ovary, and Renal cell carcinoma Pick’s bodies® are sen in Fronto temporal dementia (Pick’s disease) Paschen bodies® and Gunari bodies® are seen in Small Pox or Vaccinia Negri bodies® are seen in Rabies238 © AIPGME EXAMINATION ANSWERS AND EXPLANATIONS - 2008 ‘Mooser’s bodies® are seen in Endemic Typhus fever (Caused by Rick Hsia typhi) Miyagawa’s bodies® are seen in infection with Chlamydia Trachomalis Lafora bodies® are seen in Familial Myoclonic Epilepsy. Donovan bodies® are seen in infection with Calymmatobacterium granulomatis CCivatte bodies? are seen Lichen Planus Call - Exner bodies® are seen Ovarian Granulosa Cell Tumors Aschoff bodies® are seen in Rheumatic Carditis Tuffstone bodies® are seen in Metachromatic leukodystrophy 62, Answer is D (Metalloproteinses) : Robbins 8"/ 105 “Degradation of collagen and other ECM proteins is achieved by a family of Matrix. Metallo proteinases (MMP) which are dependent on Zinc ions for their activity’ ~ Robbins / 110 Basement membrane is a component of ECM and largely consists of collagen (Type IV). Matrix: Metaloproteins MMP9 and MMP? are collagenases that cleave type IV collagen of epithelial and vascular basement membranes’ ~ Robbins / 312 jasement Membrane and Matrix Metalloprotein (MMI Basement membrane consists of a network of amorphous Non fibrillar collagen (mostly type 1V)® Laminin, heparan sulphate, proteoglycans and other glycoproteins, (Robbins / 103) “Matrix metalloproteinases (MMP) is a family of enzymes which includes more than 20 members These include enzyme that are involved in degradationof Basement Mebrane such as: + MMP 2 & 9, Gelatinases/Collagenases) which degrade amorphous collagen and fibronectin (Basement Membrane) + MMP 3, 10 & 11 (Stromelysins) which degrade proteoglycans, laminin, fibronetin and amorphous collagens (Basement membrane components) MICROBIOLOGY 63. Answer is B (Prions) : ‘Antisepsis, Disinfection and Sterelization' by Mc Donnell 1“ (2007)/33, Prions are most resistant organisms to antiseptics. Prions Serie, Creuzfeldt-Jakob disease, Chronie Wasting Disease Baceral spores Bacillus, Costidium Protzoal oocysts ‘Gryposporiium "| Feimintheges “Ascaris, Entrobins ~ [ Mycobacteria ‘Mycobacterium wubureulosis (other myeobaeteria) | Small nonenveloped vines | Polio vin, parvoviruses, papilloma virus Protozoal ats Giardia, Acanthamoeba Fungal spores “Aspergillus, Penicillin Gram negative bacteria Pseudomonas, Providencia, Escherchia Vegetative fingi and algae ‘Asperillus, Tichophyton, Candida, Calomierons Vegetative nelminths & protozoa | Ascaris, Cryposporidium. Giardia Large nonenveloped viruses ‘Adenoviruses, rota viruses ‘Gram: postive bacteria Siaphyfococeus, Sweploeoccus, Enterococcus Enveloped vinses | Human immunodeficiency virus, hepatitis B virus, hemes simplex virus | 64, Answer is C (Most Enterococci are sensitive to Peni }: Ananthnarayanan 9/217 Enterococcii are frequently resistant to Penicillin © Enterococci are frequently resistant to penicillin, (Ananthanarayan 7/212) Enterococcal strains resistant to penicillin occur frequently - Ananthnarayana 7"/212 Enterococci are more resistant to Penicillin than other streptococci. Resistance o Penicillin may occur either due to B lactamase production or due to altered Penicillin binding proteins Enterococeii may also be resistant to Aminoglycosides, Cephalosporins, Monobactems, and Vancomycin®‘AIPGME EXAMINATION ANSWERS AND EXPLANATIONS =2008 © 239 ‘* Micrococci are oxidase positive (Ananthanarayanan 7"/200, 201) Micrococci are gram positive cocci which occur mostly in pair, tetrads or irregular clusters Micrococci are Aerobic® Oxidase positive ® Catalase positive ® Oxidase positive nature fferentiate mien staphylococci ‘Hugh and Leifson’s oxidation — fermentation test (Laboratory test) Micrococci show oxidative pattern while staphylococci show: fermentative pattern® ‘* Pneumococci are capsulated. (Ananthanarayanan 7"/217) Pheumococci posess a type specific polysacharide capsule. This is the most important antigen? of the pheumococeus. The capsule may be demonstrated as a clear halo in India Ink preparation ‘© Non Motile® © Bile soluble’ + Non sporing® © Optochin © Capsulated® (Specific polysaccharide capsule) sensitive? ‘© Smail slightly elongate cocci Catalase (flame shaped®, Lanccolate® appearance) Negative? © Arragned in pairs (Diplococci)® Oxidase G positive Negative ‘* Staphylococcus saprophyticus may cause UTI (Ananthnarayanan 7"/200) Staph saprophyticus belongs to the group of coagulase negative® staphylococci ‘They constitute major components of the normal flora? ‘+ They are normally non pathogenic but may cause disease + Urinary tract infection particularly in sexually active young women is characteristic (Men are infected much less common) They are usually sensitive to common antibiotics? Answer is A (Capsular Hyaluranie acid): Ananthnarayanan 9/212 Capsular Hyaluronic acid from streptococcus pyogenes cross-reacts with human synovial fluid. Antigenic eross reactions betwe s & Human Tissues Various structural components of streptococcus pyogenes exhibit antigenic cross reactions with different tissues of the ‘human body ‘These cross reactions are believed to account for some of the manifestations of streptococcal diseases where the tissue have been damaged by immunological manifestations (eg Rheumatic fever) Capsular Hyaluronic Acid Synovial fluid Cell Wall protein Myocardium Group A carbohydrate Cardiac Valves Cytoplasmic Membrane Antigen Vascular Intima Peptidoglycans ‘Skin Answer is C (It is universally susceptible to penicillin): Ananthnarayanan 9"/217; Jawetz 23% /243; Harrisons 179/889 Enterococci are not universally susceptible to penicillin. They may be resistant to penicillin. Resistance to penicillin may occur either due to lactamase production or due to altered penicillin binding proteins - Harrisons 17" (889 They are more resistant to penicillin G than streptococcii — Jawetz 23/243 ‘Strains resistant to penicillin occur frequently ~ Ananthnarayanan 7" /212240 © AIPGME EXAMINATION ANSWERS AND EXPLANATIONS - 2008 67. ‘The enterococci posess the Group D (Lancefield) c I wall specific antigen and therefore are often class Lancefield Group D streptococcii® sd as ‘© There are atleast 12species of enterococci, but Emerococcus fecalis and Enterococcus faecium are the most ‘common [Enterococcus fecalis : Most common® (causes 85-90% of infections) [Enterococcus faecium = Second most common® (causes 5-10% of infections) ‘© Enterococei are part of normal enieric flora? (Present in intestine, genital tract and saliva) Enterococci are amongst she most frequent causes of nosocomial infections particularly inthe Inensive care Units Endocarditis Intra abdominal abscess® Peritonitis” Meningitis in neonates The most common mode of transmission of enterococci is on the hands of hospital personnel? (May occasionally be transmitted on medical devices) Enterococci are frequently resistant to Antibiotics Major problem with enterococci is that they can be highly resistant to antibiotics? ‘* Enterococii may be resistant to Aminoglycosides (Streptomycin > Gentamycin), Cephalosporins, Penicillins, and even Vancomycin, and other antibiotics. = Most wide spread resistance is seen with streptomycin® (Harrison) = Strains resistant to penicillin occur frequently? (Ananthanarayanan) = Vancomycin resistant enterococci have become common® (Harrison) Answer is D (Produces 01 Lipopolysaccharide): Ananthnarayanan 9"/306; Jawetz 23/270; Harrisons 168/909, 910 ¥. cholerae 0139 does not produce the O1 Lipopolysacharide and does not have all the genes necessary to make this antigen’ ~ Jawet: . V. cholerae 0139 biotype was first isolated from a cholera out break in Chennai (Madras) as a novel strain of V- cholerae and was then termed as a Non 01 V. cholerae. (This strain subsequently spread via the coast of Bay of Bengal reaching Bangladesh designated as V-cholerae 0139 Bengal) . Clinical manifestations and epidemiological features of the disease caused by V. cholerae 0139 Bengal are indistinguishable from those of the O1 cholera — Harrison . V. cholerae 0139 does not produce the 01 Lipopolysacharide. V. cholerae 0139 is very similar to V. cholerae 01 Eltor biotype, but there are certain differences? [Wichilerae 0139 Bengal Nel eee YE ‘+ Novel O antigen that does not produce O1 1 Lipopolysaccharide is produce ipopolysaccharide — Jawetz -apsulated? + Non capsulated? . cholerae 0139 makes a polysacharide capsule like *V. cholerae O1 does not make a capsule other non O1 V. cholerae strains’-Jawetz Immunity to V. cholerae O1 ElTor is not protective against the V, cholerae 0139 biotype® + All vibrio cholerae possess a common flagellar H antigen + Vibrio cholerae possess different Lipopolysaccharide O antigens which forms the basis of classification./AIPGME EXAMINATION ANSWERS AND EXPLANATIONS ~ 2008 ¢ 241 Those that agelutinate Ol antisera are called OI V. cholerae and those that do not are called Non Ol V. cholerae. + V. cholerae O1 are distinguished into two biotypes * Classical and E1~Tor. Each biotype is further divided into three serotypes ‘Inaba’, ‘Ogawa’ and ‘Hikojima’ + Non V. cholerae O1 are broadly subgrouped into 0/39 V. Cholerae strains that have been associated with epidemic cholera and Non 01 /Non 0139 V. cholerae that are not known to cause epidemics or pandemics of cholera. Vibrio cholerae (common H Antigen) O1V. cholerae Non—O1 Vibriocholerae (Agglutinate in 01 antiserum) (Do not agglutinate in O1 antiserum) Classical El Tor =a i 1 i ‘Non known to cause Ogawa Inaba Hikolima Epidemic and : Pandemic cholera | | Epidemic/Pandemic cholera Sones Gees Chloera like diarrhea Epidemic and Pandemic cholera Bibs deatee) a Rarely extraintestinal infection (a) Answer is A (Usually associated with CMV infection): Washingion manual of Pulmonary Medicine (2006) 104 Harriosns 16%/ 1194, 1195; Jawetz 24"/ 648, 649; ‘Pneumocystic Pneumonia’ by Wolzer & Cushion 34418; CT sean ofthe body by Mathias /362 Pneumocystis Jiroveci may be associated with CMV infection but itis not usually associated with CMV infection. ‘Pheumocystis Jiroveci is the new nomenclature for human infection with Pneumocystic carini (which is now used for organisms found in rats) Pneumocystis infection in Humans : P. diroveci Pneumocystis infection in Rats: P. Carini Pneumoevstie Jirovecii dis immunosupression ‘Pneumocystis Jiroveci does not cause disease in the absence of immuno supression’ Jawetz 24°'/648 Note Pneumocystic Jiroveci may infect immunocompetent hosts but the disease (pncumocystis pneumonia) occurs only when the host is immunosupressed ‘Most individuals are infected in early childhood But pneumonia occurs in immunocompromised patients only either due 10 reactivation or new wie “Acquired Immunodeficier ase (eg AIDS) * Patients Recieving /mmunosupressive therapy (especially Glucocorticoids) for cancer, organ transplantation etc * Children with primary immunodeficiency diseases ‘+ Premature malnourished infants (immunodeficient) Pneumocystic Pneumonia : Diagnosis Diagnosis of Pneumocystic Pneumonia is based on specific identification of organism in respiratory specimen with appropriate histological staining + Pneumocystis infection is usuall sed by sputum examination ‘Sputum samples should always be obtained by induction (with hypertonic saline) Routine sputum specimen is often inadequate (Washington manual of Pulmonary medicine) + BAL forms the mainstay of diagnosis for Pneumoeystic Pneumonia Iorganisms are not seen on induced sputum examination a Bronchoalveolar lavage specimen should be obtained. BAL forms the mainstay of diagnosis for Pneumocystic Pneumonia - Harrisons 16°242+ AIPGME EXAMINATION ANSWERS AND EXPLANATIONS - 2008 Poremocyte orsmona Suspected Chest Radiograph Reiouar or gma opctin L Sputum by Induction (reve) Negative Bronchoscopy with BAL oc Treat Observe Treat ‘* Pneumocystic Pneumonia and CMV infection (‘Pneumocystic Pneumonia’ by Wolzer & Cushion 3418) ‘Several studies have indicated that CMV is a risk factor for Pneumocystis Pneumonia in Renal transplant patients These is however no convincing evidence to show a direct effect of the CMV virion on Pneumocystis’ ‘Thuswe conclude Pheumocystic may be associated with CMV infection but ina few selected cases and special circumstances lke Renal tansplantation. CMV isnot usually associated with pneumocystic pneumonia. ‘+ Pneumocystis Pneumonia and Pneumatocele Pneumocystic Pneumonia may be associated with pneumotocele formation but Pneumatoceles are not associated in all cases of Pneumocystic pneumonia Sa ier Ooms er oneticad + Peumocystc® ++ Post traumatic (Laceration ) 1s After treatment of metastasis (rafe) 68. (b) Answer is B (Usually diagnosed by Sputum examination) : Refer previous question Pneumocystis Jirovect is usually diagnosed by sputum examination. This is the single best answer of choice amongst the options provided. ‘© Pneumocystic infection is usually diagnosed by sputum examinatio neumoeystic infection is Bronchoscopy with BAL Sputum examination is the initial procedure of choice to confirm the presence of Pneumocystic Jiroveci infection mainstay of diagnosis for P. Jirovect infection is usually diagnosed by histopathological staining of an induced sputum specimen But 4 BUT ‘Sputum examination is not the mainstay of diagnosis of P. Jiroveci infection. Fibreoptic Bronchoscopy with BAL which is more sensitive than sputum examination remains the mainstay of | Pneumocystis diagnosis — Harrison 17"/1195 '* Pneumocystis infection may occur in healthy individuals but disease due to Pneumocystic infection does not ‘occur in the absence of Immunosupression “Serological endence suggests that most individuals are infected in early childhood” — Jawetz 24°/648 “Most healthy children have been exposed to the organism by 3 to 4 years of age’ — Harrisons 16/1194 BuT 4 BUT ‘In the absence of immunosupression P. Jiroveci does not casue disease’ ~ Jawetz 24th/ 648 ‘© Pneumocystic Jiroveci infection may be associated with CMV infection and may present with Pneumatocele ‘(Not always) (Refer previous question)/AIPGME EXAMINATION ANSWERS AND EXPLANATIONS - 2008 ¢ 243 Remember : Facts: Confusing state * Pneumocystis infection is usually diagnosed by sputum examination. : True © Pneumocystis infection is usually diagnosed by routine sputum examination 2 False Routine sputum specimen are often inadequate. Sputum samples should be obtained bby induction with hypertonic saline - Washington Manual ‘© Sputum examination is the mainstay of diagnosis for Pneumocystis 2 False Bronchoscopy with BAL is the mainstay of diagnosis — Harrison ‘© Pneumocystis infects only the immunocompromised host False ‘Most healthy individuals are infected with pneumocystis in early childhood — Jawetz © Pneumocystic pneumonia occurs only in the immunocompromised host True P. Jiroveci does not cause disease in the absence of immunsupression ~ Jawetz Answer is A (They are infectious proteins): Ananthnarayanan 9%/557; Harrisons 16/2495; Jawetz 24/581 Prions are infectious proteins devoid of any nucleic acid - Harrisons Prions and Prion associated diseases ‘+ Prions are infectious proteins devoid of any nucleic acid (RNA or DNA)® (Prions are the only known infectious agents that are devoid of nucleic acid®) ‘© Prion diseases result from the accumulation of the abnormal prion protein ‘Pr P“'@ * Prions are most resistant to physical and chemical agents such as heat, irradiation and formaline®. ‘©The diseases caused by Prions include diseases in human & animals Prion diseases Human Animals + Creutsfeldt Jakob disease® + Scrapie (sheep) ® * Gerstmann — Straussier Scheinker ‘+ Bovine Spongiform Encephalopathy (cattle) 2 disease? «| Mink Encephalopathy (Mink) ® + Faral Familial Insomnia® + Chronic Wasting Disease (Mule, Deer, Elk) ® © Kun ‘+ Feline Spongiform Encephalopathy ( Cats) 2 ‘+ Prion Diseases share several distinguishing hallmarks ‘The disease is confined to the Nervous system® (Although agent may be recoverable from other organs) The basic features are Neurodegeneration and Spongiform® changes ‘* Amyloid plaques may be present * Ch illness is preceded by a long incubation period® (months to decades) Onset of clinical illness is followed by chronic progressive disease® (weeks to years) The disease is always fatal® with no known cases of remission® or recovery '* The host shows no inflammatory response and no immune response® ~ Agents do not appear to be antigenic? - No production of interferon is elicited = There is no effect on host B cell or T cell function = _Immunosupression of the host has no effected on pathogenesis‘244 © AIPGMEEXAMINATION ANSWERS AND EXPLANATIONS - 2008 70. Answer is A (Bird Flu Virus): Molecular Medicine by Trent 3"/209,210; Clinical Infectious Disease by Schlossberg (2008) /1290 HSN1 is the Avian Flue Influenza A virus, also called the Bird Flu virus New A virus ‘+ The Influenza A viruses undergo constant antigenic variations, (Antigenic shift or Antigenic drift) ‘+ Because of these antigenic variations immunity to the influenza virus is partial and temporary ‘+ Antigenic variations mainly involve the two external glycoproteins of the virus, Haemoglutinin (H) and Neuraminidase (N) ‘+ Antigenic ‘Shifts’ result from genetic reassortments and produce immunologically novel strains of the influenza virus. These novel strains occur sporadically and herald longer epidemics & pandemics The ‘HSNT’ strain is one such novel strain found in human infections, that was previously known fo cause luenca out breaks only in birds — Avian Flu virus (First isolated in 1997 from China) The HSN1 avian flue is a particularly virulent type of infection that causes wide spread organ damage and death rapidly Other strains causing outbrakes of bird flu include, H7 N3, HSN2, H7N2, H2N2 © Important animal to human and human to human out breaks that have been recorded recently include. HSNI > 1997 and 2004 ©The range of Influenza A glycoproteins in human HON2 1999 include HIN2 2003 (Also 2002) ‘Species Haemaeglutinin -Neuraminidase HINT 2003 ‘Humans | Hl -H3, HS, H7, H9 | NI, N2,N7 71. Answer is C (Ankylostoma): Harrisons 16/1257, 1271 Biliary obstruction may be seen in infection with Clonorchis, Fasciola and Ascaris. It has not been mentioned in infections with Ankylostoma duodenale, which is the single best answer of choice. “In individuals with chronic infection bile duct obstruction and biliary cirrhosis are infrequently demonstrated. Ascaris (1160/1257) “A large worm can enter and ocelude the biliary tree’. Ankylostoma Biliary obstruction has not been mentained even as a rare manifestation in ankylostoma infections (Hook worm) Facts to Remember Biliary (Hepatic) Flukes include ‘Cholangio-carcinoma® has been reported with ‘© Clonorchis (Sinensis) * Clonorchis Sinensis® © Opithorchis® (Viverrini, Felineus) © Opithorchs Viverrini® + Fasciola (Hepatica, Gigantica) PHARMACOLOGY 72. Answer is A (Therapeutic Efficacy) : Katzung 10/69, 70, 71 Goodman & Gillman 10"/60 Phase I1 in clinical drug trials is done to study the drug kinetics and metabolism and to establish its Therapeutic Efficacy and Dose range2B. ‘AIPGME EXAMINATION ANSWERS AND EXPLANATIONS - 2008 © 245 Phase 1 Phase re (Open label/Non Blind) —_(Single ‘Double Blind). \ Normal volunteers Selected patients — Patients given drug for Special populations (renal patient therapy and hepatic impairment) Why)” Human Pharmacology.& Therapeutic Exploration & "Therapeutic confirmation "Post marketing Safety Dseranging ‘and comparison ‘suneillance Safety, biological effects, Therapeutic efficacy, dose Confirm safety and efficacy Adverse reactions, metabolism, kinetics, dug range, kinetics, metabolism Establish value of drug in patterns of drug interactions relation to existing therapy —tilization, additional Heel cod BE Rea ieaa aaa Bs eae Ethical Approval is not required for phase IV of clinical testing®. PRECLINICAL TESTING Studies in vio Animal Short 1.5 yeas Testing Tom Long Goceage 26 eam) Term FDA30day Safety Review Who? Nomal volunteers, pil popsltions (ronal and hepatic impairment Wy? Sty, lel efit metabolism nets, ru ineratons. 5y whom Clink pharmaco Piast Who! sect patints 1 ‘Why? Therapeutic efficacy, dose range, |{ ‘Bnet, metabolism i By whom? Cie pharmacalogssand ff] ‘ial vets 4 3 i i aaa CUIICALTESTING [12 z 20 years (verge 56 yeas) ‘Who? Large sample of selected patient Why? Safely and efficacy By whom? Cla investigator: NDA Submision 2 months -7 yes (Areage 26 yea) = NDA Approved POSTMARKETING SURVEILLANCE mas PHASES Who? Patients given drug for therapy patterns of drug tional indications ‘By whom? All physicians. Answer is A (Safety): KDT 9/55; Lippincott's Pharmacology 3 /33 Therapeutic index is a measure of a drug’s safety - Lippincott's /KDT ‘Therapeutic index + Therapeutic index of a drug isthe ratio of the [Therapeutic index (TD)= 22% dose that produces toxicity to the dose that EDSO luces a clinically desired or effect population ‘© The therapeutic index is a measure of a drug's ED 50 Dose that produces a desired effect in half the safety population ‘© A llarge value indicates that there is a wide ‘margin between doses that are effective and doses that are toxic.246 © AIPGME EXAMINATION ANSWERS AND EXPLANATIONS - 2008 Therapeutic Range Therapeutic Range refers to the range that binds the dose which produces the minimal therapeutic effect and the dose that produces maximal acceptable adverse effect * Therapeutic range is also a measure of the — drug's safety + A wider therapeutic range indicates a ‘safer’ drug Answer is C (Potency) : KDT 9"/57; Katzung 10"/28 The concentration of drug that produces fifty percent of that drug's maximum effect is called ECSO or EDSO. This is a measure of the potency of that drug Potency of a drug ‘© Potency of drug refers to the amount (dose) of a drug needed to produce a certain therapeutic effect. ‘© Itis measured by plotting the Dose Response curve (DRC) for the concerned drug and the desired therapeutic effect. © Potency is then defined as the concentration (ECS0) or dose(EDS0) of a drug required to produce 50% of that drugs Percentage of maximal effect ‘maximal therapeutic effect. © The position of *ED50° on the dose axis of DRC determines its potency. © The furthur right ward the EDS0 is located the lower is its oe ss The ECS0 is the concentration of the drug that produces a response equal to fifty percent of the ‘maximal response. (Potency ) The smaller the EC50 the more potent the drug. Drug A is more potent then Drug B Efficacy of a drug Ene (A) ‘© Efficacy ofa drug is refers to the maximal response that can i —= Eaux (Drug A) be elicited by that drug 3 * This is also measured by plotting the dose response curve i (DRC) for the concerned drug and the desired therapeutic Response | & effect 3 ‘© Efficacy is then defined as the maximal response achieved by 3 that drug on the response axis (upper limit of the DRC) and is 3 indicated as Emax = © The height of the DRC curve de fficacy. een permeate Emax is the maximum response produced by the ‘© The lower the height (limit) ofthe curve the lower is its ‘drug (efficacy). efficacy (Emax) The larger the Emax the higher the efficacy. Drug A has higher efficacy than Drug B.5. ‘AIPGME EXAMINATION ANSWERS AND EXPLANATIONS ~ 2008 « .eview of questions on potency and efficacy of dru 7 other and efficacies of dru Drug B is less potent but equally efficacious as Drug A. Drug C is less potent and less efficacious than Drug B. Drug D is more potent than Drug A, B & C but less efficacious than drugs A & B and equally efficacious as Drug ive to each Percentage of maximal effect Answer is B (Reactivation of Cholinesterase) : KDT 9°/111 Pralidoxime is a cholinesterase reactivator used in anticholinesterase poisoning - KDT 6/105 Anticholinesterase Poisoning and Pralidoxime ‘+ Anticholinesterases are agents which inhibit the enzyme cholinesterase (Cholinesterase is responsible for removing ACH by hydrolysis) ‘© Anticholinesterases thus protect ACH from hydrolysis and produce cholinergic effects ‘© _Anticholinesterase poisoning results from excessive exposure to these anticholinesterases and clinical manifestations include effects of cholinergic stimulation Anticholinesterases Dyflos Echothiophate Parathion, Malathion Diazenon Tabum Sarin Somun # Physostigmine © Neostigmene © Pyridostigmine # Edrophonium + Rivastigmine * Galontamine Irreversible © Carbaryl (sevin) ‘+ _Propoxur (Baygon) ‘© Specific Antidotes to Anticholinesterase poisoning include Atropine & Cholinesterase Reactivators (Pralidoxime) Le Atropine Atropine serves as an antidote for anticholinesterase poisoning with both organophasphates and ‘carbamates Atropine however does not reverse the peripheral muscular paralysis? in Anti CHE poisoning which isa nicotinic action es Cholinesterase Reactivators (Pralidoximey) + These serve as Antidotes, but only to anticholinesterase poisoning ‘with organophosphates? + These are ineffective as antidotes to anticholinesterase poisoning with carbamates? Infact ‘oximes’ (pralidoxime) are contraindicated in anticholinsterase poisoning due to carbamates® as these do not reactivate the carbamylated enzyme and may infact worsen the condition due to a weak anti- CHE activity of their ownAIPGMEE 2008 - EXPLANATIONS 248 © AIPGME EXAMINATION ANSWERS AND EXPLANATIONS - 2008 16. 71. Answer is B (Urinary Retention): KD 9"/ 13-116 Ipratropium bromide is an anticholinergic agent. Anlicholinergic agents promote urinary retention and hence are contraindicated in cases of urinary retention, Although Ipratropium bromide is poorly absorbed into the circulation and its systemic effect (including urinary retention) are not prominent, it should still not be used when urinary retention is an obvious presentation. Urinary retention isthe single best answer amongst the options provided. mucus and hence is not contraindicated in peptic ulcer disease ds apg tere any masked be on Blood area Cause bronchodilation®, Lacrimal secrition® Tachycardia |_| stimulant action specially in patients with May cause Dry eye® Used for ~ Stimulates many COPDY and Asthma treatment of ‘medullary centres GIT (Oral cavity 3 (vagal, vasomotor, Relieve smooth muscle spasm®™ | || Sativa secretion® They are more effective in COPD than bronchial asthma’ Bronchial Asthma! They are better suited for regular prophylactic use than for control of an acute attack copp® Inhaled, spium are the bronchodilators of choice in COPD wxore*222) ‘© These agents are not absorbed (poorly absorbed) from the lungs and GIT and hence systemic anticholinergic side effects are rare.78. 1. |AIPGME EXAMINATION ANSWERS AND EXPLANATIONS - 2008 * 249 Answer is D (Tiotropium) : Katzung 10/15 KDT 9"/117; The Overactive Bladder by kredger (2007) /127 Tiotropium is an anticholinergic used as an inhalational drug in asthma and COPD. Itis poorty absorbed from the lungs and GIT and systemic effects including relaxant effects on the bladder are ‘minimal. Tiotropium bromide has not been used for urinary disorders. Oxybutynin, Tolterodine and Darifenacin and are vesicoselective (Bladder selective) antimuscaranic agents with high selectivity for m3 receptors and may be used to relieve bladder spasm (urinary spasm) after urologic procedures. Oxybutynin (Ditropan) Tolterodine (Betrol) Flavoxate (Urispas) Darifenacin Solifenacin Trospiuun isan unselectve antagonist thai has also been approved Atropine has also been used, but it causes other anticholinergic side effects Dicylomine and Imipramine may also be used as they have strong antimuscaranie actions. Propantheline has also been used. Anticholinergics for urinary disorders ‘©The human urinary bladder predominantly shows M2 and M3 muscaranic receptors ‘* The M3 subtype mediates direct contraction of the bladder (The M2 subtype acts indirectly by inhibiting relaxation by Non epinephrine & Epinephrine) Selective M3 receptor antagonists (Anticholinergics with selectivity for M3 receptors) may thus be used to relieve urinary disorders such as Bladder spasms (Bladder spasm is common after urological procedures like TURP) Urinary urgency / incontinance Answer is C (Ischaemic Heart Disease) : Katzung 10*/274; KDT 9"/176 Ergotamine is a vosoconstrictive agent (used most commonly for aborting migraine headaches. Vasoconstriction induced by Ergotomine is usually severe and prolonged and difficult to reverse. They are therefore contraindicated in Ischaemic Heart Disease Ergotamine Obstructive Vascular Disease 1. Migraine (Major indication) | | Ergotamine / dihydroergotamine = Ischaemic heart disease 2. Postpartum Haemorthage Ergonovine (Ergometrine) - Peripheral Vascular Diasease (May be used) Dihydroergotoxine itraindications (Relative) [ses of other Ergot alkaloids | | Bromocriptine ‘* Pregnancy Hyperprolactine ISD © Hypertension (Bromocritine) Methyl sergide ‘© Liver and kidney disease + Senile cerebral insufficiency Sepsis (Dihydroergotoxine) There is no evidence that ordinary » Postpartum Haemorrhage use of ergotamine for migraine in (Ergonovine) . Ppregrancy is hazardous, However + Diagnosis of variant angina ‘most clinicians counsel restraint in (Ergonovine) the use of ergot drivatives by | pregnant patients (Katzung) _ Answer is B (Binds estrogen receptors and prevents negative feedback at hypothalamus) ; KDT 9/312 Clomiphene citrate binds to both Estrogen receptors (ER a and fi) and acts as a pure estrogen antogonist, in all human tissues. It induces Gn secretion in women by Blocking estrogenic feedback inhibition of pituitary. This increases the amount of LH and FSH released at each secretory pulse ~ KDT 6"/303250 2008 - EXPLANATIONS pa 82. ‘© AIPGME EXAMINATION ANSWERS AND EXPLANATIONS - 2008 reat _— . marae © Clomiphine citrate is classified as an Antiestrogen® Mechanism of Action Betis © Pure estrogen antagonist at Estrogen Receptors (ER a and ERB )® ‘© Blocks estrogenic feed back inhibition of pitutary® © Induces gonadotrophin secretion® and the amount of LH/FSH released at each secretory pulse + Promotes ovulation® Use z ‘© Induction of ovulation for anovular infertility® (chief use) ‘+ May be used to aid in vitro fertilization (causes synchronous maturation of several ova) ‘+ May be used to promote spermatogenesis and testesterone secretion in males may be used for male infertility? Adverse effects ‘© Polycystic ovaries? © Hotflushes® — * ~— May increase risk of ovarian tumors ‘© Multiple pregnancy? Gastric upset. Vertigo /Allergic dermatitis Answer is A (Diazepam antagonist) : KDT 9"/ 401;(Repeat) Katzume 10/354 Flumazenit is an antagonist for Benzodiazepines (Diazepam). It is an antagonist at the Benzodiazepine binding site on the GABA receptors. It competes with Benzodiazepine agonists as well as inverse agonists and reverses their depressent or stimulant effects respectively ‘Agonists GABA Receptors lL. Tnverse Agonists Benzodiazipines i (BZD binding site) eg Beta carbolines Facilitate GABA actions and| {| ve -ve}} Impede GABA actions and produce CNS depressant produce CNS stimulant actions Flumazenil actions Competitive antagonist for Agonists and Inverse Agonists J+ Reverses CNS depressant action of Agonists” + Reverses CNS stimulant action of Inverse agonists® Answer is A (Risperidone): KDT 9"/440-446 Risperidone is an antipsychotic drug and is not used as an antianxieety agent. Selective Serotonin Reuptake Inhibitor (SSRL) are antidepressant agents but they are effectively used in many types of severe generalized anxiety disorder (including OCD, Panic attack and Phobias) Buspirone and Clonazepam (BZD) are classified as Antianxiety drugs. Benzodiazepines Azapirones ‘Sedative Anthistaminie Beta Blockers + Diazepam Buspirone Hydroxyzine + Chlordiazepoxide Gepizone Propancol + Oxazepam Isapirone | + Lorazepam Selective Serotonin Reuptake Inhibitors | + Alprazolam [SSRI are effective in Obsessive Compulsive disorders (OCD), phobias, Soca wih ponand man pps ofseee ominent antiepileptic ‘generalized anxiety disorders - KDT H howev neg action. It may however be | used as an antianxiety agent.‘AIPGME EXAMINATION ANSWERS AND EXPLANATIONS ~ 2008 251 83. Answer is C (Tetracycline) : KDT 9/689; Repeat Tetracyclines act by inhibiting protein synthesis. They do not inhibit cell wall synthsis Cephalosporins® (includes cefotetan) Cyeloserine? Vancomycin? Bacitracin® 84. Answer is A (Piperacillin KDT 9/724; Ref: Q-88 (Al -2006); Q 96 (AI -2004) Piperaceltin is an antipseudomonal penicillin belonging to the group of ureidopenicillins Oxycillin and Nafeillin are penicillinase resistant penicillin active against pencillinase producing bacteria. They are however narrow spectrum penicillins, with activity primarily limited to Gram positive bacteria. They are not active ‘against pseudomones Amoxgcillin is an extended spectrum penicillin with activity against many Gram negative bacteria but it is mot active ‘against pseudomonas. Ey Narrow spectrum penicillins Extended spectrum penicillins Activity is limited primarily to Gram positive Activity is extended to include Gram negative bacteria bacteria as well ‘Spectrum include: ‘Spectrum include: ‘Most gram positive bacteria ‘Most Gram positive bacteria ‘Most gram negative bacteria are Many Gram negative bacteria not susceptible? (Non Pseudomonal) ® Depending on whether the gram negative spectrum includes co—__| pseudomonas, these may be Sait PSG further classified as follows. susceptible Resistant “Extended spectrum Extended spectrum Penicillin G Methicillin penicillins not active penicillin active against Penicillin V Cloxacillin against Pseudomonas Pseudomonas Oxacillin (Non Pseudomonal) (Pseudomonal) Dicloxacillin Flucloxacillin + Ampiciltin + Carboxypenicillins Nafeillin + Amoxyillin ~ Carbencillin ~ Tiearcillin ‘+ Ureido penicillins ~ Piperacillin = Meclocillin 85. Answer is A (Can be given orally) : KDI 9/718 Penicillin G is acid labile and is destroyed by gastric acid. It can only be used parentrally and not by the oral route. ‘+ Penicillin G can not be given orally Penicillin G is acid labile and is destroyed by gastric acid® Iris not available for oral administration © Penicillin G can be is either intravenously or ‘cer ‘© Procaine Penicillin G ‘Crystalline Penicillin G or ‘+ Benzathine Penicillin G Sodium Penicillin G (These penicillins release PnG slowly atthe site of injection)252. © AIPGME EXAMINATION ANSWERS AND EXPLANATIONS - 2008 86. Orally administered / Acid Resistant Penicllin similar to penicillin G is Penicllin V° or Phenoxymethyl penicillin (differs from PnG only in that itis acid stable) ‘+ Penicillin G is primarily active against gram positive bacteri PnG has a narrow spectrum of acti - Itis primarily active against Gram positive bacteria® (Cocii® and Bacill®) - Itis usually inactive against Gram negative bacili' = Gram negative cocii are however usually sensitive® (Meningococet® & Gonococi®) = Bacteriodes fragilis is resistant? * Mycobacterium TB is resistan®® - Rickettsia, chlamydia, protozoa, fungi, viruses are totally insensitive to PnG® ‘+ Penicillin G is a 8 Lactam antibiotic and mechanism of action involves interference with the synthesis of, bacterial cell wall. Pencillin G is sensitive to penicillinase or B Lactamase and | Lactamase producing bacteria inactivate PnG by ‘opening the 8 Lactam ring. ‘© Probenecid given along with PnG increases its duration of action PnG is primarily excreted via the kidney by tubular secretion (90%) Probenecid tends to block the tubular secretion of PnG This results in higher and longer lasting plasma concentrations and increased duration of action. (a) Answer is A (Resistance is produced as a result of alteration in Penicillin Binding Proteins): Katzung 10"/727 ‘Methicillin Resistent Staph Aureus by Catterkey (1992) /22-25 Schaechter’s Mechanism of Microbial Disease 4"/60 Essentials of Diagnostic Microbiology by Shimeld & Rodgers (1999)/109; Current Critical Care Diagnosis & Treatment (CCCDT) 2/426 Altered target Penicillin Binding Proteins (PBP) are the basis of Methicillin resistance in staphylococcii (MRSA) ~ Katzung Resistance to methicillin occurs due to altered Penicillin Binding Proteins (PBP-2A). This is transmitted via the MeC A gene. Mec A gene is a chromosomal gene (not a plasmid). Expression of Resistance is enhanced by lowering temperatures to 535°C. Most common mec! in Resistance to Antibacte nts Yes ‘Hydrolysis of s Lactam ring by i-lactamase he No Aeron n Pence a ea fechanism of Microbial disease 4"%60 Resistance in MRSA results from altered Pencillin Binding Protein ~2 (PBP-- (Intrinsic Resistance due to PBP-2A and MeC-A gene) + Penicillin binding Proteins (PBP) are integral cell wall proteins that catalyze various reactions in cell wall synthesis + Beta Lactam antibiotics (Methicillin) bind to the enzymatic sites on these PBP and thereby disrupt bacterial cell wall synthesis (Mechanism of action) + Methicillin Resistant strains of Staph, aureus (MRSA) escape Methicillin by synthesizing an extra PBP called PBP 2A which carries out the functions of those PBP’s that are inactivated by methicillin PBP-2A is also a Penicillin binding protein but itis only bound at extremely high concentrations of methicillin (or other # lactam antibiotics) which lie well above the therapeutic range. Hence PBP-2A is not inactivated at therapeutic doses. «+ PBP-2 production is encoded on a gene called MeC A gene ‘+ MeC A gene transmits resistance chromosomally (and not via plasmids)86. [AIPGME EXAMINATION ANSWERS AND EXPLANATIONS - 2008 © 253 Possible mechanism (Border line Methicillin Resistance) ‘Hyperproduction of Beta Lactamase (Beta lactamase production is encoded by plasmids-plasmid mediated) ‘Hyperproduction of Beta lactamase can lead to Borderline Methicillin Resistance but this should not be confused with true methicillin Resistance’ ~ Essentials of Diagnostic Microbiology by Shimeld & Rodgers (1999)/109 sistance is enhanc ‘the te ‘of incubation to less th ier than. which is used routinely) Although most MRSA are easy to identify by conventional susceptibility testing, some isolates (heteroresistance) with low level resistance may be difficult to identify. Such samples require special conditions of incubation that enhance phenolypic expression of resi Factors which enhance phenotypic expression OF ‘National commitiee for Clinical Laboratory Standards Resistance in MRSA (NCCLS) Guidelines * Reduced Temperature of incubation (<35°C Guidelines for susceptibility testine in MRSA. rather than 38°C 10 37°C) Prolonged incubation (>24 hours) fe 2s ome nee Increasing the amount of inoculum * Use a salt supplemented medium ‘© Addition of sodium chloride (2-4%) to the solid © Temperature of incubation no higher than 35° susceptibility medium (b) Answer is C (Resistance is primarily mediated via plasmids) Resistance is not primarily mediated via plasmids Resistance is primarily mediated via chromosomal MeC-A gene which codes for altered PBP ~ 2A. Borderline resistance to methicillin may be produced as a result of hyper production of Beta Lactamases, but this is not the ‘Primary mechanism, Low resistance to MRSA (heteroresistance) may be missed at 37°C and temperature of incubation ‘no higher than 35°C is recommended - Refer previous question for references Answer is D (Are not known to be teratogenic): KDT 9/736; Katzung 10/748 Tetracyclins are known to have teratogenic effects. Tetracycline use during pregnancy may cause dental enamel dysplasia and bony deformities in the child ‘Tetracveline and its use in pregnane ih * Tetracyclines should not be used in pregnancy, lactation and in children © Tetracycline have chelating property and therefore can bind to calcium deposited in newly formed Bone & Teeth Effect on Teeth Effect on Bone mA Deposited on fetal teeth (deciduous teeth) Deposited in bone, itcan cause bony leading to fluoresence, brown discolouration, deformities and growth supression ‘enamel dysplasia and illformed teeth that are (Teratogenic effect) ‘more susceptible o caries (Teratogenic effect) ‘Prolonged use in children < 8 years of age may result in similar changes as described above and hence Tetracyclines are considered contraindicated for use in young children (< 8years) rr damage (May precipitate Acute hepatic Necrosis in pregnancy)’ * Kidney damage (May produce Fanconi syndrome®) (Tetracycline which does not enhance renal failure® ~ Doxycycline) ‘Vestibular Toxicity (Transient, ataxia, vertigo, nystagmus) 2 Phototoxicity (sunburn like rash)? Teeth damage (Discolouration, enamel dysplasia) ® Bene damage (Growth supression & deformities) ® Diabetes insipidus (Demeclocycline antagonizes ADH action & causes diabetes insipidus.? (Has been used therapeutically for Syndrome of Inappropriate ADH secretion ®) © Antianabolic effect‘254 © AIPGME EXAMINATION ANSWERS AND EXPLANATIONS - 2008, 89. 90. Increased intracranial pressure (noted in some infants) Hypersensitivity ‘Superinfection : -Tetracyelines are the most common antibiotics responsible for superinfection? = Intestinal superinfection with candida albicans is most prominent © - Pseudomemiranous colitis may occur + Imitative effects: (Not dose related) = Initative diarrhea (also, nausea, vomiting) = Iritative esophageal ulceration and epigastic pain = _ Pain on intramuscular injection & thrombophlebitis of injected vein Answer is D (Doxycycline): KDT 9"/735, 736 Doxycycline is metabolized and excreted via the liver in bile, It is not excreted via the kidney and is not considered Nephrotoxic ‘All tetracyclines except doxycycline accumulate and enhance renal failure’ - KDT 6""/ 713 ‘+ Aminogivcosides (Gentamycin and Strepte Alll Aminoglycosides are considered nephrotoxic (KDT 6/721) ‘Note Streptomycin is the least nephrotoxic aminoglycoside antibiotic. (but it is nephrotoxic) Nephrotoxicity caused by aminoglycosides is essentially reversible® (provided the drug is promptly discontinued) + Totracvelines ‘All tetracyclines are nephrotoxic except Doxycycline (KDT 6"/713) © Polvmixin B Polymyxins have high systemic toxicity when used parentrally. Systemic toxicity includes marked kidney damage (Nephrotoxicity) - KDT 6°/734 Answer is A (Erythromycin): Park 18/104, Park 19"/106, Harrison 17/893. The options for chemoprophylaxis of diphtheria include. Erythromycin (7-10 days oral course) or Benzathine Penicillin G (single intramucular dose) ‘Chemoprophylaxis for Diphtheris ‘© Close contacts of dephtheria cases should undergo throat cultures to determine whether they are carriers. ‘* After samples for throat cultures are obtained, antimicrobial prophylaxis should be considered for all close contacts ‘even those who are culture negative? Options include * Oral course of Erythromycin for 7-10 days © One dose of LM Benzathine Penicilline G (1.2 Million units for person > 6 years; 600,000 units for children <6 years) ‘Chemoprophylaxis for common diseases (Park 19°/106) Powel “Tetracycline? oF Furazolidone (for household contacts) NNN Bacterial Conjunctivitis Erythromycin ophthalmic ointment Diptheria Erythromycin® (Also initiate first dose of vaccine) Influenza A Amantadine® (for contacts suffering from chronic diseases), Meningococcal meningitis ‘Sulphadiazine® (for house-hold and close community contacts), (Also initiate immunization against serogroups A & C) Pneumonic Plague Tetracycline® Answer is A (Amikacin): Harrisons 179/959. Amikacin is not used in the treatment of Enteric fever. Ciprofloxacin is the drug of choice for Enteric fever, Cotrimaxazole is an alternative agent for treatment of Enteric “fever and Ceftriaxone is used for treatment of multidrug resistant enteric fevera1. 92. ‘AIPGME EXAMINATION ANSWERS AND EXPLANATIONS 2008 © 255 © Amoxyeillin (second line) © Chloramphenicol © Cotrimaxazole Azithromycin * Ceftriaxone * Ciprofloxacin (DOO) © Azithromycin © Amoxyeillin (second choice) « © Chloromphenicol * — Cotrimaxazole Answer is B (Procaine Penicillin G) : Harrison's 16%/983 ; Harrison's 17/1044 Procaine Penicillin G is the alternative agent of choice and the single best answer amongst the options provided. Ceftriaxone (or other third generation cephalosporins) + Ciprofloxacin Ceftriaxone © Azithromycin é 3 The drug of choice for treatment of Neurosyphillis is Acqueous or Crystalline Penicillin G. | Patients with confirmed Penicilin Allergy tent infected with HIV: a EINE pincer ARE Primary, Secondary or Penicillin G benzathine Tetracycline hydrochloride or doxycyetine Early latent Late latent (or uncertain duration) Ev F after Lumbar puncture Evaluate CSF after Lumbar puncture peciomncie. oF CSE normal: Penicilin G benzathine CSF normal and patient not infected with HIV: ee CCSE abnormal: Treat as neurosyphilis Tetracycline hydrochloride (CSF normal and Desensitization and treatment with penicillin if compliance cannot be ensured CSF abnormal: Treat as neurosyphils ‘Neurosyphils Aqueous peniclilin G or Desensitization and treatment with penicillin (asymptomatic or symptomatic) Aqueous penicillin G Procaine plus probenecid ‘Syphilis in pregnancy ‘According to stage Desensitization and treatment with penicillin Answer is D (Clofazimine) : KDT 9'/781-782, 787; Kateung 10/772, 779 Clofazimine is not an antifungal drug. It Mycobacterium Tuberculosis (Katzung) in antibacterial drug active against Mycobacterium Leprae and “Antifungal Drugs T T T 1 + Griesofulvin + Miconazole * Oriconazole + Ketoconazole (Systemic) Antibiotics Antimetabolites Azoles Allylamines Other Topical Agents Polyenes Flucytosine (SFC) Triazoles (systemic) + Terbinafine + Tolnftate + Amphoterecin B + Fluconazole + Natifne + Undecylenic acid + Nystatin + Itraconazole + Ciclopiroxolamine + Hamycin + Vonconazole + Quinodochlor + Natamycin (Pimaricin) Imidazoles (Topical) + Benzoic acid + Clotrimazole + Butenafine Heterocyclic Benzofuran + Econazole + Sodium Thiosulphate256 © AIPGME EXAMINATION ANSWERS AND EXPLANATIONS - 2008 93. 95. Answer is A (Bleomycin): KDT 9°/898, 689; Katzung 10" /895 Bleomycin is a small peptide (glycopeptide) antibiotic with potent antineoplastic activity (katzung /KDT) Bleomycin is a small peptide (glycopeptide) with antineoplastic activi Doxorubicin is an ‘anthracycline’ with antineoplastic activity L-Asparginase is an enzyme with antineoplastic activity (enzymes are proteins) Yalinomycin is a Depsipeptide antibiotic but no clinical application has yet been described for valinomycin (Experimental drug) (Reference Dictionary of Antibiotics and Related substances) Glycopeptide Antibiotics Polymyxin B Colistin Bacitracin Tyrothricin Answer is D (Stabilization of tubules) : KDT 9°/865-866 Paclitaxel acts by Stabilization of microtubules. ‘Mechanism of action of Taxanes (Paclitaxel / Docetaxel) ‘© Tubulin isa protein found in microtubules within cells, ‘+ Paclitaxel emhaces polymerization of tubulin which results in the stabilization of microtubules ‘© This stability in tum results in inhibition of normal dynamic reorganization of the microtubular network which is, essential for vital interphase and mitotic functions ‘© Taxanes thus exert their anticancer actions by acting as mitotic inhibitors ‘Anticancer drugs that act as mitotic inhibitors” include Vinca Alkaloids and Taxanes |Amticancer drugs that act by inkibition of microtubules (tubulin): Vince Alkaloids (Vincristine/Vinblastin) © |Anticancer drugs that act by stabilization of microtubules (tubulin): Taxanes (Paclitaxel /Docataxel)® Answer is A (Methotrexate): KDT 9"/611; Lippincott’sPharmacology 3/458 Leucoverin or Folinic cid is used with Methotrexate to counteract its toxicity Methotrexate Toxicity : Mechanism ter Reducing Methotrexate toxicity: ‘ton (Leucoverin Rescue ‘¢ Methotrexate exerts its antineoplastic { and immuno — suptessant action by acting as an antagonist to Folic acid (DHFRase) the enzyme that converts folic acid into its active coenzyme ‘The cells can be rescued by two Mechanisms This requires a thousand {oem tetatiydrofoate (FE) fold excess ofthe natural # FHS isan essential coenzyme substrate Dihydrofolate required for de novo purine synthesis (FH2) (Not practical) (Adenine, Guanine, Thymidine) and amino acid interconversions (Methionine / Serine) [Required for one Carbon transfer reactions] This requires administration This leads to depressed DNA, RNA of Folinic acid or and protein synthesis and ultimately Teucoverin (NS Formyl to cel death, (Mechanism of action) ‘Leucovorin rescue FH) (Cirrovorum factor) Tey. netnone96. 97. /AIPGME EXAMINATION ANSWERS AND EXPLANATIONS - 2008 ¢ 257 Answer is B (Hirsuitism): Harrisons 17/1987 Tacrolimus does not cause hirsuitism or gingival hyperplasia - Harrison's 17"/ 1987 Tacrolimus and Cyclosporine # Tacrolimus (FK506) is a macrolide lactone antibiotic that is isolated from a Japanese fungus streptomyces tsukubaensis and has immunosupressant properties. ‘© Ithas the same mechanism of action as cyclosporin but is chemically different ‘Chemically a macrolide lactone antibiotic ‘© Chemically different “Mechanism of action same as cyclosporin © Caleineurin inhibitor Cateineurin inhibitor ‘* More potent action than cyclosporin * Less potent (10-100 times more potent) ‘© Oral absorption of Tacrolimus is more predictable than, ral absorption less predictable AIPGMEE 2008 - EXPLANATI cyclosporine * Primarily used for prevention & treatment of Graft ‘¢ Primarily used for prevention and treatment of rejection Initially used for ‘rescue’ therapy for patients in _graft rejection. ‘whom rejection occurred despite the use of cyclosporine Still continues to be the most commonly used (Now tacrolimus is beginning to replace cyclosporine for _—_drug for prevention and treatment of graft primary immunosupression in many transplant centres) rejections (but trend is shifting towards use of tacrolimus) ‘© Overall more toxie than eyclosp © Overall ess toxic than tacrolimus = More Nephrotoxie (Dose it ‘Less Nephrotoxic (Dose limiting toxicity) - More Neurotoxic = Less neurotoxic (Tremor, Seizures, Hallucinations & Coma) ~ More likely to precipitate Diabetes ~ Less likely 10 precipitate Diabetes = More likely to cause Alopecia / Diarrhea ~ Less likely 10 cause Alopecia / Diarrhea Certain adverse effects are less prominent /absent Certain adverse effects are more = Hirsuitism (Absent according to H17th) Prominent 00 = Gum Hyperplasia (Absent; H-17") > Hirsuitism = Hypertension = Gum Hyperplasia = Hypertension Answer is B (Imiquimod): Katzung 10/816, 817, 996 Imiquimod is an immunomodulator shown to be effective in the treatment of external genital and perianal warts, — Katzung 10/816 ‘© Imiquimod is an immune response modifier or immunomodulator agent ‘© Ithas been approved forthe treatment of : + External genital and perianal warts in adults? + Actinic keratosis on the face & scalp + Superficial Basal cell carcnoma on trunk neck & extremities ‘+ The mechanism of action is unknown but is thought to be due to ~ Stimulation of peripheral mononuclear cells to release IFN = Stimulation of macrophages to release IL-1, IL-6, IL-8 and TNF-a ‘© Iisavailable as an agent for Topical Application (Percutaneous absorption is minimal) Adverse side effects consist mainly of local inflammatory reactions including pruritis, erythema and superficial erosions258. © AIPGME EXAMINATION ANSWERS AND EXPLANATIONS - 2008 98. Answer is A (Cytochrome oxidase) : Godman & Gillman 11/44; Harper 27633 Cytochrome oxidase is not mentioned as an enzyme in the metabolism of xenobiotics, Cytochrome P450 and Hydroxylation reactions are involved in Phase ~1 metabolic reactions while Methylation forms Part of phase Il reactions during metabolism of xenobiotics. ‘Xenobiotics and Their Metabolism * Xenobiotics refer to all compounds that are foreign to the body. These include a variety of compounds such as drugs, ‘chemical carcinogens, insecticides ete. ‘* These compounds are usually metabolized in the human body before being excreted ‘© Several different enzymes (atleast 30) catalyze reactions involved in the metabolism of these xenobiotics + The purpose of metabolism is to increase their water solubility (polarity) and thus enhance their excretion from the body ‘+ The metabolsm of Xenobioties is best described in two phase ‘© Inphase I the xenobiotics undergoes their first ‘metabolic biochemical reactions © The major reaction is Hydroxylation. ‘Hydroxylation is catalyzed by members of a ‘group of enzymes called monooxygenases or cytochrome P450's * Hydroxylation may terminate the action ofthe xenobiotic or the metabolized xenobiotic may enter phase II of metabolism ‘© Inphase II the hydroxylated or other compounds produced in phase I are converted into various polar ‘metabolites ‘+ The major reactions in phase II metabolism include = Conjugation (with glucoronic acid, sulphate, acetate, glutathione or certain amino acids) and - Methylation ‘+ These reactions tend to increase the polarity or ‘water solubility of xenobiotics to aid in their excretion from the body. [BiSiobiotic Metabotizing Enzymes Enzymes Reactions Phase I “oxygenases” Reactions Cytochrome P450s (P450 or CYP) Flavin —containing monoxygenases (FMO) Epoxide hydrolases (mEH. sEH) Phase 2 ‘transferases’ Sulfotransferases (SULT) ‘UDP - glucuronosyltransferases (UGT) Glutathione ~ S-transferases (GST) 1N-acetyltransferases (NAT) ‘Methyltransferase (MT) Other enzymes Alcohol dehydrogenases Aldehyde dehydrogenases NADPH -quinone oxidoreductase (NQO) FORENSIC Hydroxylation® / C and O oxidation, dealkylation, others N, Sand P oxidation Hydrolysis® of epoxides Reactions Addition of sulfate (Sulfation) Addition of glucuronic acid (Glucuroindation) Addition of glutathione (Glutathione Conjugation Addition of acetyl group (Acetylation) Addition of Methyl group (Methylation) Reactions Reduction of alcohols Reduction of aldehydes Reduction of quinines 99. Answer is D (Throttling) : Reddy 27/312, 229, 315, 317, 318, Parikh 6 /3.57, 3.40-3.62 Suffocation is a form of asphyxia where death occurs primarily due to mechanical obstruction to the passage of air into respiratory tract other than constriction of neck or drowning Throttling involves compression of neck by human hands, and is a form of strangulation (and not suffocation) Death from throtling occurs due to occlusion of carotid arteries. Occlusion of airways plays a minor role. — Reddy 27/312.|AIPGME EXAMINATION ANSWERS AND EXPLANATIONS - 2008 259 Hanging Hanging is a form of death that results from constriction of neck by a ligature and suspension of the body. The weight of the body acts as the constricting force. ‘Asphyxial Deaths a Suffocation Strangulation ‘Strangulation is a form of asphyxia that result from constriction of neck by any ‘means without suspending Asphyxia Hlanging is not a form of strangulation (Complete weight ofthe body is not essential Weight of the head alone may be sufficient) Suffocation is a form of deprivation of oxygen in the ‘environment or from Drowning Drowning is a form of Asphyxia in which access of air into the lungs that results from the body obstruction of air passages prevented by by means other than submersion of the ‘Sirangulation does not | constriction of neck or body in water or include hanging drowning other fluid medium mae (Complete ‘Strangulation Suffocation does not submersion is not "+ Ligature Strangilation + Throtting (Manual include drowning or constriction of neck necessary, sufficient fluid to cover the strangulation with hands) + Mugging Suffocation is sufficient to cause + Garrotting + Smothering drowning) + Bansdola + Gagging + Choking + Overlaying + Burking Traumatic Asphyxi nostrils and mouth 100. Answer is A (Strangulation) : Reddy 27/311, Parikh 6"/ 3.53 Bruising of neck muscles, fracture of thyroid cartilage and hyoid bone are more common in Strangulation than in Hanging. Strangulation is the single best answer of choice Ligature Mark "Abrasions and ecchymoses {about the edges of ligature mark) Bruising of Neck Muscles ‘Neck ‘Subcutaneous tissues ‘Hyoid bone fracture Thyroid cartilage fracture Larynx and Trachea Emphysematous bullae ‘Carotid arteries Face Signs of asphyxia Tongue (Saliva Bleeding from nose, mouth & ears ([Seminal fui at glans 5 = Itis oblique Does not completely encircle the neck; Usually seen high up in the neck between the chin and larynx, ‘The base is pale, hard & parchment-like Not common Less common Stretched and elongated White, hard & glistening under the mark [Not present on the surface ofthe lungs Damage may be seen Usually pale & petchiae are not common Extemnal signs less marked ‘Swelling and protrusion is less marked Often runs out of mouth ‘Not common More common eiliGa SRO Itis transverse, Usually completely encircling the neck Usually seen below the thyroid cartilage ‘The base is soft and reddish, Common More common [Not stretched or elongated Ecchymosed under the mark ‘May occur (Not rare in manual Strangulation/ Throttling) ‘More common Fracture may be found Very common on the surface of the lungs Damage is rare Congested, livid and marked with petechiae External signs well marked ‘Swelling and protrusion is more marked. Absent Common Less common