AIPGME EXAMINATION ANSWERS & EXPLANATIONS 2005A ATT NRSC NT ah a questions in. various PG. entrance examinations over the previous years. a constituents of the entire explanatory MA a iar PR scan eae ee Me ORT LC ORR Le ee CCRAU mT aSANATOMY 1 2 Answer is C (Flexor carpi radialis): BDC 6"/ol 1/105; Snells 7°/520 The tendon of flexor carpi radialis lies within a split in the flexor retinaculum i.e, between the retinaculum and its deep slip. It thus lies in a separate tunnel or compartment formed between two slips of flexor retinaculum and not within the true carpal tunnel. The true carpal tunnel lies deep to the flexor retinaculum including its deep slip radially. ‘Carpal tunnel: Review "Structures passing through carpal tunnel 1. Median nerve 2. Flexor digitorum superficial tendons 3. Flexor digitorum profundus tendons 4, Flexor pollicis longus tendon ‘Structures pasing superficial to flexor retinaculuch Ulnar nerve Ulnar vessels Palmar cutaneous branch of wnar nerve Palmars longus tendon Palmar cutaneous branch of medi nerve Note in the figure that the tendon of flexor ‘carpi radialis passes between the retinaculum and its deep slip in a separate tunnel and not ‘through the true carpal tunnel. Answer is C (Femoral artery): BDC 6%/ Vol Il/ 45-46 The femoral ring refers to the upper opening of the most medial compartment of the femoral sheath (femoral canal). The femoral artery occupies the lateral compartment and is separated from the femoral ring by an intermediate ‘compartment, occupied by the femoral vein, Boundaries of femoral ring: Tercalbeomh of Aniteriorly by inguinal ligament ontolemor neve Medially by lacunar ligament (concave margin) + Posteriorly by pectinius and covering fascia + Laterally by septum separating it from femoral vein Right femoral sheath and its contents Remember: + Femoral sheath encloses upper 3-4 cm of femoral vessels and is divided into 3 compartments by septa: 2 ‘1 Lateral compartment "| Intermediate compartment + Femoral artery + Femoral vein + Lymph node of cloquet or « Femoral br. of genitofemoral n, Rosenmuller and lymphatics + The medial compartment containing the lymph node is also called as femoral canal,694» _AIPGME EXAMINATION ANSWERS AND EXPLANATIONS - 2005 Answer is A (Upper border of rib): Snells 9/45; other references The neurovascular bundle of each intercostal space is closely related to the lower border of the rib above. To avoid damage to the intercostal nerves and vessels therefore, the needle should be introduced close to the upper border of the lower rib. 4. Answer is C (Median lobe): Snell's 9/277 Benign prostatic hypertrophy is associated ‘eid medan abe oposite with enlargement of the median lobe of the career Prostate, which encroaches within the sphincter vesicae, located at the neck of the bladder. Enlargement of the median lobe results in the formation of a pouch of pooh of stagnant wie stagnant urine behind the urethral orifice etic ae within the bladder. felony dct ‘osteoriobe pg Soggitl section fa prostate that had undergone benign enlargement ofthe ‘median lobe, Noe the Baer pouch filled with stagnant rine behind te prostate Note: (Board Review series Anatomy 4/249) «Median lobe which lies between urethra and the ejaculatory duct is prone to benign hypertrophy. © + Posterior lobe, which lies behind the urethra and below the ejaculatory duct contains glandular tissue and is prone 10 carcinomatous transformation.? 5. Answer is B (Presents a concavity posteriorly): Keith and Moore 4/363; Snells 9"/278; Other references “Prostatic urethra is the widest and most dilatable part of the urethra and is concave anteriorly? Cunningham's Manual 15" yol2223 Prostatic urethra: = It is the widest and the most dilatable part of male urethra ° A + Descends through the prostate closer to the anterior than the posterior surface mae tte © with a gentle curve that is concave anteriorly 2 + _Exils the prostate and becomes continuous with the membranous urethra — across the anterior surface, anterior to the apex ° (not at the apex as ‘mentioned in several texts) + Prostatic ductules from prostatic glands open into the prostatic sinus on the my posterior wall of the prostatic urethra ‘Note in the figure that the prostatic urethra is concave anteriorly Pose and is closer to anterior surface of prostate. =6. 1 The posterior wall or floor of the Prostatic urethra presents the ‘AIPGME EXAMINATION ANSWERS AND EXPLANATIONS 2005 + 695 7 ridge of mucus membrane + Prostatic sinus: Vertical grooves situated, one on each side of the urethral crest. = Colliculus seminalis: is an elevation on the middle ofthe ‘urethral crest. On tis elevation there isa sit like orifice through which the Prostatic uéricle opens into the urethra (Prostatic urcle isa blind sac situated between the median and posterior lobe of prostate and is homologous withthe ‘uterus of vagina of the female &) = Openings of ejaculatory ducts: These are situated on the edge ‘of the mouth ofthe utricle = Opening of Prostatic glands: The posterior glands open into the Prostatic sinuses + 2The widest and most dilatable part of male urethra: Prostatic urethra + ©The narrowest part of the male urethra is: External urethral orifice + ©The narrowest and least dilatable part of male urethra: Membranous urethra (if external urethral orifice is not provided amongst the options) Answer is D (It is separated from the base of bladder by the peritoneum): BDC 6"/vol II/ 373, 400 Vas deferense lies closely opposed to the base of the bladder. There is no intervening layer of peritoneum between the bladder base and vas deferens + Vas deferens ascends from the superior pole of testes into the inguinal canal within the spermatic cord. As the vas deferens emerges from the deep ring it lies lateral to the inferior epigastric artery. (Memo: An indirect inguinal hernia that passes through the deep inguinal ring is characteristically present lateral to the inferior epigastric vessels) + Inthe region of the ischial spine it crosses the ureter and then bends medially reaching the base of the bladder. + The terminal part of the ductus lying behind the base of the bladder is dilated and tortuous and is ‘known as the ampulla, ‘Only Upper part of base covered wy oertoneum Answer is D (Deep inguinal): BDC 6"/vol II/ 390 The uterus does not drain into the deep inguinal lymph nodes Lymphatic dra Fundus and upper part of body + Paraortic gp of nodes . + Partly to superficial inguinal nodes, along the round ligament of uterus Lower part of body External iliac nodes e of uterus: Cervix © External iliac © Internal iliac + Sacral nodes Answer is A (Internal iliac lymph nodes): Gray's 39" 1204; Snel 's 9°/265-268 The internal iliac lymph nodes do not lie in anterior relation to the rectum. When enlarged they may be palpated laterally696 10. ‘+ AIPGME EXAMINATION ANSWERS AND EXPLANATIONS - 2005 ‘The following structures may be palpated on per-rectal examination t Anteriorly Posteriorly, Lateral “Opposite terminal phalyae > Sacrum = Tschial spines * Posterior surface of bladder + Coccyx ‘+ Ischialtuberosities + Seminal vesicles + Anococeygeal body ‘© Contents of ischiorectal fossa + Vas deferentia + Intiliac lymph nodes when ‘Opposite middle phalym enlarged Prostate + _Rectoprostatie fuscia Opposite proximal phalyme * Perineal body ‘© Urogenital diaphragm + Bulb ofpenis Answer is B (Anterior ethmoidal artery): BDC 6"vol 111/210, 101 Anterior ethmoidal artery is a branch of the ophthalmic artery which is a branch of the internal carotid artery = Gray's 399/696 i Branches of extemal carotid artery “Anterior: 1, Superior thyroid artery _ Posterior auricular 2. Lingual artery 3. Facial artery Posterior: = Occipital 1. Occipital artery au 2. Posterior auricular artery ~ ternal juguae vein Medial: 1, Ascending pharyngeal artery Aacering pharyreal ‘Terminal: 1. Maxillary artery 2. Superficial temporal artery Outinw of carats Branches of external carotid at Answer is A (Cavernous sinus): BDC III/ 6"/193 ‘Cavernous sinus lesions may be associated with paralysis of 3", £", S* (opthalmia and maxillary divisions) and 6" nerve on account of its characteristic relations as depicted in the figure 7 Structures in he lateral wall of sinus ftom above downwards @)Occulomotor (HIF) nerve ) Trochlear nerve (IV") ©). Ophthalmic (V,) nerve &) Maxillary (V3) nerve )_Trigeminal ganglion ‘Sertares passing troogh centre of the sinus a) Abducent (VI) nerve b)_ Internal carotid artery. Preepation ‘Nervous symptoms ‘Venous symptoms Marked edema ofthe eyelids, comea and root of nose with Pain in the distribution of Paralysis of extraocular muscles due eXophthalmos due to congestion of orbital veins. Vi& Va to lesion affecting Il, IV & VI cranial nervesWL 2. 13. 14. [AIPGME EXAMINATION ANSWERS AND EXPLANATIONS -2005 » 697 Answer is B (4" cranial nerve): BDC I11"/6"351 Superior oblique is supplied by the IV" cranial nerve. Nerve supply of extraocular muscles Se SD 0(4) LR(6) Remaining (3) Superior Oblique is supplied by IV" The Lateral Rectus (LR) is supplied by ‘The remaining extraocular muscles are all cranial nerve or trochlear nerve the sixth cranial nerve (LR 6) supplied by the I cranial nerve or Occulomotor nerve. Answer is D (Contains postganglionic parasympathetic fibres): BDC vol III/6"/137; Various references Chorda tympai nerve contains preganglionic secretomotor parasympathetic fibres that synapse on cell bodies in the submandibular ganglion. It does not contain post ganglionic parasympathetic fibres. ‘Chorda Tymp: f facial nerve) Course Fibres carried © Iisa branch of the facial nerve + Preganglionic secretomotor parasympathetic fibres: Arise ‘+ Itarises within the facial canal in the vertical part about 6 inthe superior salivatory nucleus and relay in ‘mm above the stylomastoid foramen. submandibular ganglion. Postganglionic fibres from ‘+ Ttenters the middle ear and runs in close relation to tympanic _ submandibular ganglion reach submandibular gland ‘membrane, directly and to sublingual gland via the lingual nerve. ‘+ It leaves the middle ear by passing through the ‘+ Special visceral afferent (SVA) fibres carrying taste ppetrotympanic fissure. sensations from anterior 2/3 of tongue. They relay in the + Itjoins the lingual nerve in the infratemporal fossa. ‘geniculate ganglion and then ascend further Connection ofthe submandibular ganglion Answer is A (Symphysis): Gray's 41°/738 “The sacrococeygeal joint is a ‘symphysis? between the sacral apex and coccygeal base united by a thin Sibrocartilaginous disc.’ - Gray's Answer is D (Replacement of red bone marrow with yellow marrow): Various texts; Gray's 41°/91-93 At the epiphyseal growth plate (physes) new bone ‘Sages during the growth of epiphyseal plate ‘growth occurs by the process of enchondral ossification ie. ossification of proliferating cartilage. + Proliferation of cll! cell division This process sequentially involves proliferation and + Interstitial and appositonal growth hypertrophy of chondrocytes, their calcification and + vascular invasion. Replacement red bone marrow with {Transformation white marrow is not seen, + Cell hypertrophy Calan ori + Chondrolysis + Vascular invasion (vascularization) + seeps Remodeling1698» AIPGME EXAMINATION ANSWERS AND EXPLANATIONS - 2005 15. Answer is A (Interphase): Tortora Principles of Anatomy and Physiology 10/1098; Robbins 7*/ 178; ‘Chandrasoma Taylor 3" 227 “The inactive X can be seen in the interphase nucleus as a darkly staining small mass in contact with the nuclear ‘membrane known as the Barr body or X chromatin’ ~ Robbins ‘Barr body is the inactivated X chromosome. In non dividing interphase cells it remains tightly coiled and can be seen as a dark staining body within the nucleus’ ~ Tortora Principles of Anatomy and Physiology 10? 1098 Barr body: Review ‘What are Barr’ ‘+ When two X chromosomes are present in a cel (asin a normal female) one of them becomes inactivated and condensed on the nuclear membrane and i called the ‘Barr body". This proces is termed as X chromosome lyonization (inactivation) ‘(Significance of Barr bodies + Presence or absence of Barr bodies helps in ascertaining the sex of an individuals = Absence of Barr body indicates that the patient has only one X chromosome (eg. Normal male XY or Turner's syndrome(XO)) ~ Nuclei of cells in females (XX) contain a darkly staining Barr body that isnot present in the nuclei of cells in males. ‘Wentification of Barr bodies * Barr bodies are most easily seen in a smear of squamous epithelial cells obtained by seraping the buccal mucosa ° Barr bodies react differently to histological stains and are best seen as dark staining bodies with in the nucleus of non dividing interphase cells. PHYSIOLOGY 16. Answer is B (Type Il Pneumocytes): Repeat: Ganong 21"/ 658 Surfactant is produced by type I! alveolar epithelial cells ~ Ganong 21°1658 (Alveolar epithelial cells are termed as pneumocytes) Surfactant Review ‘+ The major constituent of surfactant is: Di-palmitoyl-phosphatidyl choline 2 + Surfactant reduces the alveolar surface tension and prevents alveolar collapse ® + prevents pulmonary edema © + Respiratory distress syndrome/ Hyaline membrane disease is produced due to deficiency of surfactant. ical Relevance: Thyroid hormone increases activity of Type I prewmocyies® TRDS is more common with Low Thyroid hormones (Hypothyroidism) ‘Glucocorticoids enhance maturation of surfactant ‘RDS is more common in premature babies (There is an increase in matemal & fetal cortisol near term) Tnsulin inhibits activity of type I pneumocytes ® ‘RDS is common in Diabetic mothers (Fetal hyper-insulinemia occurs in diabetic mothers) + Surfactant Deficiency may also occur with [FOechuson of Main bronchus ® |- Occlusion of Pulmonary artery ® | Long term inhalation of 100% 0, | Cigarette smokers ® 17. Answer is D (Hypoventil *hysiology by Chaudhri 5"/ 143 Arterial oxygen tension may be reduced either from a defect in oxygenation (eg. Type I failure) or ventilation (type II failure). Ibis not reduced in anaemia, CO poisoning or moderate exercise. Reduced arterial oxygen tension Decreased inspiratory Defect in oxygenation Defectin ceeees (0; tension (4 P10;) (VQ mismatch) cg, Living in high altitude 7 Defect in Defectin lung Obstruction Hypoventiation parenchyma vasculature +SCOPD «+ Decreased respiratory + Pheamonia + Right o let drive ftom CNS disorders + ARDS shunts «+ Weakness of respiratory muscles19. 20. 21. 22, ‘+ Anemic hypoxia: Co pomene % Y + In both anemia and CO poisoning while the total oxygen content is decreased the oxygen tension of arterial blood (P,O;) is unaltered. P.O; is produced due to dissolved O; in the plasma and this remains normal + Moderate exercise: The increased compensatory respiratory drive and perfusion are able to maintain a normal P,O; during moderate exercise. Hypoxemia may however be associated with severe exercise, Answer is D (Bicarbonate): Ganong 21°/ 674; Guyton 10"/ 471 “Transport of carbon dioxide in the form of bicarbonate ions accounts for approximately 70% of the carbon dioxide transported from the tissues to the lungs. Thus this is by far the most important of all methods of transport.’ - Guyton Transport of carbon dioxide: Carbon dioxide is transported in following thre forms Bore TNL PAcording to Guyton ‘ As Bicarbonate 10% 43.8% (43.8 ml/100 ml of blood) As Carbaminocompounds 23% 2.6% (2.6 ml/100 ml of blood) As dissolved CO, ™ 2.6% (2.6 ml/100 ml of blood) Although there isa significant conflict inthe amount by which CO: is transported in various forms between the text in Guyton and Ganong, the most important of all modes of transport is certainly bicarbonate Answer is B (Brain): Ganong 21"/ 599 “The direct vasodilator action of CO; is most pronounced in the skin and brain’- Ganong. As skin is not present amongst the options, brain is the answer of choice. The metabolic changes that produce vasodilation include, in most tissues, decrease in oxygen tension and pH. Increase in CO; tension and osmolality also dilate the vessels. The direct dilator action of CO is most pronounced in the skin and brain - Ganong 21"/ 599 Exposure to high concentrations of CO; is associated with marked cutaneous and cerebral vasodilation, but there is vasoconstriction elsewhere and usually a slow rise in blood pressure ~ Ganong 21"/612 Answer is B (Arterioles): Concise Medical Physiology by Chaudhri 5"/ 198 Arierioles are the major site of resistance to blood flow and are hence often termed as ‘seat of peripheral vascular resistance’. Small changes in their caliber cause large changes in total peripheral resistance and hence on distribution of blood flow. Also called ‘precapillary resistance vessels’, arterioles, help in distribution of blood flow by alteration in their diameter, thereby increasing or decreasing the peripheral resistance to blood flow. Answer is D (Lying to standing change in posture): Ganong 21°/ 575 When a person moves from a supine position to standing position a significant volume of blood pools in the lower extremity because of high compliance of veins and venous return decreases. As a result of decreased venous return the length of ventricular cardiac muscle fibres is decreased and in accordance with ‘Frank-Sterling relationship’ the stroke volume and cardiac output decreases. actors that normally decreas or increase the length of ventricular cardiac musle bres ~ Garona Increased pumping action of skeletal muscles Increased negative intrathoracic pressure > Soooger rl conan ‘+ Increased total blood volume Shona! pericardial pressure + Increased venous tone ‘+ Decreased ventricular compliance Answer is D (Generates impulses at the highest rate): Ganong 21°/ 549; Guyton 10"/ 111 “The sinus node controls the beat of the heart because its rate of discharge is greater than that of any other part of the heart. Therefore the sinus node is the pacemaker of the heart” - Guyton Although the AV node and Purkinje fibres are also capable of generating impulses spontaneously, itis the sinus node which controls the hearts rhythmicity and acts as the pacemaker of the heart.5 2 700 23. 24, 25. © AIPGME EXAMINATION ANSWERS AND EXPLANATIONS - 2005 This is attributed to the fact that the discharge rate ofthe SA node is considerably faster than the natural self excitatory discharge of either the AV node or the Purkinje fibres. Each time the sinus node discharges is impulse is conducted into both, the AV node and Purkinje fibres and discharges their excitable membranes. Then these tissues as well as the sinus node recover and start almost at the same time, but the sinus node discharges again much more rapidly and discharges the AV node & Purkinje fibres again before they can reach their own threshold for self excitation. convoluted tubule): Ganong 21/724; Guyton 10”/ 353 About 80 t0 90 percent of bicarbonate reabsorption occurs in the proximal tubule - Guyton Reabsorption of bicarbonate: [Segment “FT| CHCO; Reabeorted am nine Proximal tubule 80% 10 90% ‘aca Loop of Henle (thick) | 10% i se ns Distal ubule and Remainder oa collecting duct cae aneoeen Answer is A (The bulk of water reabsorption occurs secondary to Na’ reabsorption): Guyton 10"/ 299 “The reabsorption of water is coupled to sodium reabsorption. Changes in sodium reabsorption significantly influence the reabsorption of water.” - Guyton This phenomenon is best evidenced in the proximal tubule where water permeability is high and water is reabsorbed as ‘rapidly as the solutes. With about 65% of water being reabsorbed in the proximal tubule, the bulk of water reabsorption an certainly be said to occur secondary to Na° reabsorption. Reabsorption of water Obligatory reabsorption Facultative reabsorption + Absorption of water in renal tubules independent ofthe + Absorption of water in renal tubules varying in amount depending plasma osmolality (i.e. irespective of water balance) __on variation in plasma osmolality (dependent on response to water + Absorption of water in proximal tubule intake or water deprivation) «Filtered water is reabsorbed isoosmotically and is + Absorption of water in late distal tubule and collecting duct. independent of ADH levels + A amount of water resorbed depends on the serum ADH levels. ‘Segment = NO ADH (in absence of ADH) High ADH (Volume contracted state) ef ‘© Proximal tubule (Obligate 65% of filtered water is reabsorbed 65% of filtered water is reabsorbed reabsorption irespective of water balance) ‘* Late distal tubule and collecting Tubular cells are impermeable to Tubular cells are permeable to water H,0 is duct (Facultative reabsorption) water in absence of ADH (No reabsorbed until the osmolarity of tubular fluid Git seabsorption) equals that of surounding interstial uid Thick ascending limb of loop of Henle, and early distal tubule are both impermeable to water and no reabsorption ‘occurs in these segments irrespective of water balance. Answer is A (ECF volume contraction): Guyton 10"/ 315 The kidney has the ability to form urine that is more concentrated than the plasma. When there is contraction of the ECF volume (water deficit in the body), the urinary concentrating ability of the kidney increases and it forms a ‘concentrated urine with a smaller volume, thereby maintaining homeostasis.26. 2. ‘AIPGME EXAMINATION ANSWERS AND EXPLANATIONS - 2005 = 701 ECF volume contraction /water deficit : L ADH increases the permes * plasma osmolarity tubules and collecting ducts to water L thereby allowing these tubular segments to ‘1 secretion of ADH from posterior pituitary absorb water + 2 Hi larity of renal medulla 1 permeability of late distal tubule & collecti interstitial fluid (eee presence of hyperosmotic Provides the osmotic gradient necessary renal medulla for water reabsorption to occur, in Increased reabsorption of water from the tubular lumen presence of high levels of ADH. L Passage of concentrated urine that is low in volume thereby maintaining homeostasis + Reduction in medullary hyperosmolarity leads to loss of oncotic pressure gradient which essential to produce concentrated urine, Reduction in medullary hyperosmolarity therefore decreases its concentrating ability. ‘+ Increase in RBF and increase in GFR both indicate an adequately filled (or overfilled) vascular system and hence are likely to decrease ADH secretion. This in turn would reduce the permeability of the distal rubule and collecting, ‘duct to water and hence will decrease its concentrating ability. Answer is C (NO): -hninger's Biochemistry 4"/ 434, 860; Ganong 21/90 ‘A suprising ining In the mid-1980's was the role of tri xide (NO) as an important biological messenger’ Lelminger 4°7 360 ‘Nitric oxide (NO) is a short lived messenger that acts by stimulating a guanyl cyclase raising cGMP and stimulating protein kinase G’ — Lehninger 48/434 ‘Gases as Neurotransmitters / Neuromodulators in Nervous system of mammals = [NO, CO - Ganong Answer is C (Layers 1, 4, 6): Neuroanatomy by Inderbir Singh 6"/ 233; Ganong Fibres from the nasal hemiretina of the opposite eye end in Lamina 1, 4, and 6 ~ 1B Singh's Neuroanatomy sniculate body and the relay pathwa + Lateral geniculate body is a relay station on the visual pathway lying just posterior to the optic tract. + Itreceives fibres from the contralateral nasal hemiretina and ipsilateral temporal hemiretina + Grey matter of this body is spit into six laminae. (Fibres from ipsilateral temporal hemiretina Fibres from contralateral nasal hemireting 0) End in lamina 2,3 & 5 End in famina 1,4 & 6 From retin of From ret of ‘ame oe ‘pposte sce Magee Poon ~T Sig for detection Signa for colour vison, fmovemcet depth texture sage nde ‘Eiclertovinal—dealo vou conex30. 31. Answer is A (Color contrast): Ganong 21"/ 163, The parvocellular pathway from layers 3-6, carries signals for color vision, texture, shape and fine detail.- Ganong, Color contrast is thus the single best answer amongst the options provided. (Do refer figures in the previous question) From the lateral geniculate nucleus, a magnocellular pathway and a parvocellular pathway project to the visual cortex. The magnocellular pathway from layers 1 & 2, carries signals, for detection of movement, depth and lickers. The parvocellular pathway, from layers 3-6, carries signals for color vision texture shape and fine detail ~ Ganong Answer is B (HDF): Bijlani 3/271; Lehninger's 4"/ 173 “Itis worth noting that 2, 3 DPG does not combine with Fetal haemoglobin’ ~ Bijlani 3/271 2,3 DPG & Haemoglobin: + 2,3 DPG is present in high concentration in erythrocytes (with adult Hb i. HbA > HbA.) + 2,3 DPG greatly reduces the affinity of haemoglobin to oxygen (There is an inverse relation between binding of oxygen and binding of DPG.) + Because a fetus must extract oxygen from its mothers blood, fetal Hb (HbF) must have a greater affinity for O2 than ‘Maternal Hb. (This means that it must have lesser affinity for 2, 3 DPG than maternal adult Hb) +The fetus thus synthesizes y subunits rather than f subunits forming a3 72 Hb (HDF), This tetramer has much lower affinity for BPG than normal adult Hb as well as HbA.; and correspondingly a higher affinity for O. [HDF causes the axygen-dissociation curve to shift to Left 2 2,3 DPG causes the oxygen- A + BH; (Reduction) (2 transferases: (Catalye wansfer of C-,N, orP’ containing groups 1+ Hexokinase Eg. @ serine hydroxylmethyl transferase which converts serine to glycine + Transaminase A-X+BOASB-X ‘+ Transmethylase | Phosphorylase 3. Hydrotases: Catalyze cleavage of bonds by addition of water Lipases| Eg. Urease cleaves urea to CO; & Ammonia ‘© Alkaline phosphatase AB +H,0-> AH+BOH © Urease Ay Lyases: Catalyze cleavage of C-C, C-S and certain C-N bonds | © Aldolase Eg, Pyruvate decarboxylase cleaves Pyruvate to acetaldehyde + Fumarase AB+X-Y 9 AX+BY Le Histidase 5. Isomerases Catalyze racemerization of optical or geometric isomers + Ketoisomerase Eg. Methylmelonyl CoA converts Methyimelonyl CoA tosuccinyl CoA A— A ‘= _ Phospho hexoseisomerase (interconversion) Catalyze formation of bonds between carbon and O, S, N coupled to hydrolysis of high + Glutamine synthetase succinate energy phosphates thiokinase Eg. Pyruvate carboxylase which converts Pyrwate to oxaloacetate A+B AB38. Answer is C (Enolase): Harper 26"/ 137; Satvanarayanan 2"/ 255 “For blood glucose estimation in the laboratory, fluoride is added to the blood to prevent glycolysis by cells by inhibiting ‘enolase’ so that blood glucose is correctly estimated’ — Satyanarayanan ‘Inthe glycolysis pathway: 2 phosphoglycerate is converted to phosphophenol pyruvate by the enzyme enolase “Bnolase is inhibited by fluoride, a y ; property that can be made use of when it Fluoride is required to prevent glycolysis in blood Enol prior to estimation of glucose’ - Harper. _ |2phosphoglycerate — ron phosphoenolpyruvate + water| is 39. Answer is A (LD-1): Harper 26" 57 Since the heart expresses the H subunit almost exclusively, isoencyme I, (LDH Isoenzyme-l) with four predominates in this tissue — Harper Isoenzymes of Lactate Deh ase: + Lactate dehydrogenase is a tetrameric enzyme and consists of four subunits ‘+ These subunits can occurs in two isoforms ic H isoform (for heart) M isoform (for muscle) + Catalyticaly active tetrameric enzyme Lactate dehydrogenase thus can be represented in the following ways 1, (LDH-1) HHHH 1, (LDH-2) HHHM 1, (LDH-3) HHMM 1, (LDH-4) HMMM “Is (LDH-S) MMMM Isoenzyme LDH-1 (Iy) expresses the ‘H’ subunit almost exclusively and predominates in the ‘Heart’. Isoenzyme LDH-S (Is) expresses the °M’ subunit almost exclusively and predominates in the ‘Liver’. The elevation in levels of LDH-1 or LDH-S isoenzymes is detected by separating the different oligomers of Lactate dehydrogenase by electrophoresis and assaying their catalytic activity 40, Answer is B (Posttranslational modifications): Harper 25"/ 640, 649 Both vitamin C and vitamin K are required for post translational modifications Vitamin C is required for post ‘translational modification of procollagen polypeptide molecules in collagen synthesis and vitamin K is required for post translational modification of glutamate residues for generation of clotting factors. Note: + Synthesis of clotting factors is helped by vit K but not by vit C + Antioxidant properties are features of vit A, vit E and vit C but not of vit K. + Vitamin C with its involvement in Electron transport Chain may contribute to Microsomal hydroxylation reactions, ‘an action not shared by vitamin K. PATHOLOGY 41. Answer is A (Formation of Amorphous densities in mitochondrial matrix): Robbins 9%/45-46 Formation of amorphous densities in the mitochondrial matrix isa feature of irreversible injury and not reversible injury. ‘Transition to irreversible injury is characterized by swelling and disruption of lysosomes, presence of large amorphous densities in swollen mitochondria, disruption of cellular membranes and profound nuclear changes = Robbins 7/1242. EXAMINATION ANSWERS AND EXPLANATIONS - 2005 aa Early arrangements following depletion of ATP, Persistence of injurious stimulus or excessive injury which the cell can compensate, The cell is capable of causes the cells to pass the threshold of reversibility returning to normaley ifthe injurious stimulus abates and a transition to irreversible state occurs. + t Pathological manifestations of reversible injury Pathological manifestations of ieversible injury ~ Cellular swelling = Presence of large locculent, amorphous densities + Loss of microvilli {in swollen mitochondria (increased calcium influx) + Formation of Cytoplasmic Blebs ‘+ Swelling and disruption of lysosomes. Leakage of + ER swelling: Detachment of ribosomes lysosomal enzymes into cytoplasm and their + Myelin figures activation occurs leading to decreased + Nuclear changes in the form of clumping of nuclear + ‘Nuclear changes chromatin = Pyknosis (Nuclear condensation) Note: ~ _Karyorhexis (Nuclear fragmentation) + Diminished generation of ATP constitutes the eitical = _Karyolysis (Nuclear dissolution) ‘mechanism of cellular injury and occurs in both + Severe damage to plasma membranes reversible and ireversible phases. 1+ Decreased basophilia + Myelin figures? (laminated structures) derived from damaged membranes of organelles and plasma membrane, first appear during the reversible stage (They become more pronounced in irreversibly damaged cells) Ischaemia + Decreased oxidative phosphorylation t Decrenyed ATP + Inhibition of ATP dependent Na*K pump Increased Anaerobic glycolysis Other effects + 4 Detachment of Ribosomes Increased (1) influx of Na" H,O, Ce" (Increased 4 Glycogen Lok + ettarotk) (side emonment) tpi sti L Swelling lumping of macear Lipid deposition ‘chromatin (Nuclear changes) 7 Swelling of organciies ] [+ Collar swelling 1 ER welling 1 Lose af miro + Mitochondrial swing | |“ Formation of blebs Answer is D (Decreased hydrostatic pressure): Robbins 9%/74 With acute inflammation hydrostatic pressure is increased (due to increased blood flow from vasodilation) and at the same time osmotic pressure is reduced because of protein leakage (due to increased permeubility)- Robbins™/S1(f 2-3) ‘Association with Acute inflammation’ Hydrostatic pressure : Increased Colloid osmotic pressure : Decreased Changes ig Acute Inflammation Vascular events Cellular events T. Changes in vessel caliber (vasodilation) T, Margnaton, rolling and adhesion of leucocytes to endothelium TL Changes in vascular flow (stasis) II. Transmigration (diapedesis) across the endothelium IIL, Changes in vascular permeability (nereased 11. Migration in interstitial issues towards a chemotactic stimulus permeabiliy) t T Formation of Cellular Exudate Formation of Fluid Exudates rich in plasma proteins _(The accumulation of neutrophil polymorphs within the extracellular space isthe diagnostic histological feature of acute inflammation‘AIPGME EXAMINATION ANSWERS AND EXPLANATIONS - 2005 + 707 Remember: Cardinal physical characteristic of acute inflammation (celsus) “cardinal Sign “one ise: ERUERE SS Rubor (Redness)® ‘Due to vasodilation of small blood vessels Calor (Heat)? ‘Due to increased blood flow (Hyperaemia) Tumor (Swelling)® ‘Due to accumulation of fluid exudate (mainly) and cellular exudate (to a lesser extent) Dolor (Pain)? Due to stretching and distortion of tissue from inflammatory oedema. (pressure). ‘Also from chemical mediators including bradykinin and prostaglandins Answer is C (Diabetic glomerulosclerosis): Robbins 9/44 Fibrinoid necrosis has not been mentioned as a feature of diabetic glomerulosclerosis Fibrinoid Necrosis: Fibrinoid necrosis isa distinctive morphological pattern of cell injury characterized by L @ ‘Along with 3 molecules of FAS. 4 ‘0000000 00000, Form a binding ste For FAS associated om 00 Death domain ao FADD SOQ meme (FAS associated death domain binds) — 4 = 4 ProCaspase$ > Active Caspase-8 sce ih Sees Executioner Caspases . t nnn cae Apoptosis 1 ‘ — Fig: The extrinsic death (receptorntated) pathway of apoptosis, ilusratad by the evens folowng Fas engagement ‘+ Best known death receptor are the type 1 TNF receptor (TNFR1) and a related protein called Fas (CD95). Answer is A (Fraction of cells in apoptotic pathways): Various texts/ Journals; The Journal of Histochemistry & Cytochemistry: Volume 47(5): 711-717, 1999 In situ DNA nick end-labeling is an in situ method for detecting areas of DNA which are nicked during apoptosis. Terminal deoxynucleotidyl transferase mediated dUTP — biotin Nick end labeling ‘TUNEL! is a method for detecting apoptotic cells that exhibit DNA fragmentation. The biological hallmark of apoptosis is the cleavage of chromosomal DNA that can be detected by in situ DNA nick end-labeling techniques such as TUNEL (TdT-mediated dUTP Nick End Labeling assay )- The Journal of Histochemistry & Cytochemistry Volume 47(3): 711-717, 1999 Apoptosis is typically associated with a multistage process of double stranded DNA fragmentation. The in situ DNA nick end-labeling technique allows detection of fragmented DNA (Gavrieli et al. 1992) : The Journal of Histochemistry & Cytochemistry Volume 47(5): 711-717, 1999 Apoptosis is currently one of the most intensively researched areas of science, and numerous ways exist to measure the process. Among the morphological, biochemical and molecular changes occurring in the dying cells, DNA fragmentation is widely recognized as a hallmark of apoptosis, and its detection is the most common analysis for identifying Apoptosis. In situ detection methods are dependent on the detection of cleaved (nicked) fragments and their labelling Methods that can be used to label DNA breaks (and detect Apoptosis) in various tissues include: + ISEL (insitu end labelling), + TUNEL (terminal deoxynucleotidyl transferase-mediate dUTP nick end labelling) and + ISNT (in situ nick translation) What is in situ DNA Nick End Labeling (TUNEL technique): Apoptosis Assay Methods : Methods for studying ‘apoptosis in individual cells : Apoptosis, Cell Death, and Cell Proliferation Manual47. DNA Nicks «Extensive DNA degradation is a characteristic event, which occurs, in Seer the late stages of Apoptosis. Seevesivriet, «Cleavage of the DNA may yield double-stranded, LMW DNA fragments (mono- and oligonucleosomes) as well as single strand ts breaks (“nicks”) in HMW-DNA. z= + Those DNA strand breaks can be detected by enzymatic labeling of : the free 3"-OH termini with modified nucleotides (X-dUTP,).. Suitable labeling enzymes include terminal deoxynucleotidyl | eran tandems transferase (end labeling) ome End labeling a Terminal deoxynucleotidyl transferase (Ta) is able to label blunt ends of doublestranded DNA breaks independent of a template. The end- labeling method has also been termed TUNEL (TdT-mediated X-dUTP . nick end labeling) Caution: One has to keep in mind that these methods are based on the detection of DNA strand breaks. There are rare situations when apoptosis is induced without DNA degradation. Conversely, extensive DNA degradation, even specific to the internucleosomal linker DNA, may accompany necrosis. Thus, one should always use another independent assay, along with the TUNEL method, to confirm and characterize apoptosis. Answer is C (Cerebral microcirculation): Ganong 21°/ 546 ‘All endothelial cells except those in the cerebral microcirculation produce thrombomodulin, a thrombin protein, ‘and express it on their surface’ - Ganong Note { Syueietrombonpdln“:Thonbynstns cl awe prc thi hombin and conversion activator of protein C (vit K dependent protein) Activated ‘protein C” cleaves factor Va and Villa thus inhibiting coagulation. ‘BH Produce heparin like molecules ® These act by activating antithrombin IL .Secrete plasminogen activators > Suchas tissue plasminogen activator (TPA) Degrade a? ¢ ine “protein §%, a cofactor for ‘protein C” and release PGI; ° ace release nitic oxide ° scious Answer is D (Rb): Robbins 7°/ 300 ‘Tumor suppressor genes’ are genes whose products, down regulate the cell cycle, and thus apply brakes to cellular ‘proliferation. Loss of tumor suppressor genes is associated with several important human tumors. Rb gene is a tumor suppressor gene, loss of which (when both normal copies are lost) is associated with Retinoblastoma (and osteosarcoma). Myc, fos and ras are all examples of protooncogenes and not tumor suppressor genes. “+ Carcinomas of Colon Cell surface + E-cadherin + Carcinoma of stomach + Familial gastric eancer lier aspect of | NF-1 jon of RAS signal Neuroblastomes [Neurofibromatosis type 1 and [plasma membrane transduction and of p21 sarcomas Be cell-cycle inhibitor Cytoskeleton = NF-2 Cytoskeletal stability Schwannomas and_—_—_‘Neurofibromatosistype-2 ‘meningiomas acoustic sehwannomas and H + APCip-catenin + Inhibition of signal Carcinomas of + Familial adenomatous transduction stomach, colon, polyposis colveolon cancer * PTEN + PI kinase signal pancreas; melanoma» Unknown transduction «Endometrial and * Unknown E: » SMAD 2 and “+ TGF-B signal prostate cancers SMAD4 transduction + Colon, Pancreas tumors710» AIPGME EXAMINATION ANSWERS AND EXPLANATIONS - 2005 - Nucleus + RB ‘+ Regulation of cell cycle * Retinoblastoma; + Retinoblastomas, + ps3 *Cellcycle arrest and osteosarcoma osteosarcoma 2 WIL apoptosis in response to. carcinoma of breast, —_« Li-Fraumeni syndrome; «+ pl6 (INKéa) DNA damage colon, lung ‘multiple carcinomas and * BRCA-1 and ‘Nuclear transcription Most human cancers BRCA2 '* Regulation of cell cycle » Wilms tumor + KLF6 by inhibition of '* Pancreatic, breast, and cyclindependent esophageal cancers « Carcinomas of female breast kinases: * Unknown and ovary; carcinomas of + DNA repair + Prostate male breast + Transcription factor + Unknown 48. Answer is B (Increased Requirement of growth factors): Biology of the cell (2003) 357-364 Cultured cells undergoing malignant transformation do not show increased requirement of growth factors. On the contrary they lose the requirement of growth factors. The process of malignant transformation is associated with a stable heritable loss of requirement of cultured cells for growth factors. — Biology of the Cell 2003) 387-364 While the initial cell lines are still fully dependent of hormones and other growth factors for their growth; the subsequent ones that show malignant transformation become fully independent of hormone and growth factors for their growth and also completely lose their otganogenic capacities ~ Biology of the Cell 49. Answer is A (Ames test): Lehninger 4/967; Goodman Gilman's 10"/ 71 ‘Ames test is a simple test developed by Bruce Ames that measures the potential of a given chemical compound to ions in a specialiced bacterial strain (mutagenic carcinogenesis)’ - Lehninger #°/967 To determine whether or not a chemical is potentially carcinogenic to humans two main types of laboratory tests are done Rapid simple bacterial test Prolonged test + Invitro studies like Ames test using salmonella ‘+ These are in vivo studies and consist of feeding laboratory typhimurium animals (mice and ras) the chemical at high doses for the + This ype of study is performed to determine whether or entire life span not a chemical is mutagenic. ‘+ This study ean detect both genotoxic toxins and promoters (many carcinogens are mutagens) ‘+ Autopsies and histopathological examination are performed This type of test can detect genotoxic carcinogens but ‘on each animal to determine the incidence of tumor. ‘ot promoters. The Ames test Histidine free medium plated with a strain of Salmonella typhimurium (Histidine is required for the growth of Salmonella typhimurium) | A strain of Salmonella typhimurium that has @ mutation that inactivates an enzyme of histidine biosynthetic pathway is plated on a histidine - free medi (strain can not synthesize histidine now and tere is no histidine in medium) Only few cells grow To tes the mutagenic potential of carcinogen, the mutagen that promotes back mutation ofthe inactive enzyme (to the active enzyme of histidine synthetic pathway) is inoculated nutrient plates ‘A large number of colonies grow now because the ‘mutagen greatly increases the rate of back mutation and provides histidine via its synthetic pathway‘AIPGME EXAMINATION ANSWERS AND EXPLANATIONS - 2005» 711 50. Answer is D (CEA): Robbins 9/337; Kirk's Manual of Surgery; Harrison 16°V5S1; Biological markers of germ cell testicular tumors include AFP, HCG, Placental alkaline phosphatase, placental lactogen and LDH. HCG, AFP and LDH are widely used clinically and have proved to be valuable in the diagnosis ‘and management of testicular cancer. CEA is an oncofetal antigen and may be used as a tumor marker in adenocarcinoma of colon, pancreas, lung, breast & ovary. It is however not used as marker for Germ cell tumors. ‘Tumor Markers for Germ Cell Tumors Alpha fetoprotein HCG ‘Others Non seminomatous germ ail] | Nonseminomatous gem cell wos] | EDA tumors: May be seen in 10% of seminomas Placental Alkaline phosphatase “Tumor Markers Cancer ‘Non.Neoplastic Conditions Hormones Human chooni gonadotropin - Gestational wophobastic disease, Pregnancy F sondl gem cel unor ~ Medullary cancer of the thyroid 8 peer totenines = Pheocromecytona Rg Oncofetat Antigens [Alphafeoprotin ~ Heats carcinoma, gonadal Cts Reais ‘germ cel mor ne f ‘Carcinoembryonic antigen. ‘= Adenocarcinomas of the colon, en 7 = enone fic coon, _yeptis hemolytic anemia, ay tes = Enzymes Prostatic acid phosphatase = Prostate cancer Prostatitis, prostatic hypertrophy Neuron-specif enolase ~ Smal cell cance ofthe hn, soa eurbistoma Lactate dchydogenase ae Hepat, hemolytic anemia, many thers Tumor Associated Proteins Prostatic-specific antigen = Prostate cancer Prostatitis, prostatic hypertrophy eocioannunepia > Mysora tn MOUS epuny ca-i25 Ovarian cancer, some mmphoras etapa pesmane ca199 ~ Colon, pancreas breast cancer p30 ~ Hodgkin's disease, snuplastc large cell Imphoma (oo2s = Hairy cel eke adult cl leukemnia/lymphoma 1. Answer is C (Congo Red): Robbins 7"/259 “To differentiate amyloid from other hyaline deposits (eg. Collagen and fibrin), a variety of histochemical techniques are used, of which the most widely used is Congo Red” — Robbins 7/259 Identification of Amyloid Amyloid is a pathological proteinaceous substance deposited between cells in various tissues and organs of the body Ss + + t + Histochemical staining with Under Light Microscopy Under electron X-Ray Crystallography “Congo Red’? ‘and standard tissue stains microscopy and Infra red + J Y Spectroscopy Amyloid is stained with congo Red and Amyloid appears as an Amyloid is een as + observed under ‘amorphous eosinophilic © made up lergely of Demonstrates hyaline extracellular non branching® characteristic ‘f tT substance that with filaments of pleated ° sheet Ondinarylight ‘Polarizing ight Progressive accumulation indefinite length conformation’ Pink orred® Green encroaches on and colour is imparted birefringence of Produces pressure atrophy tottissue deposits stained amyloid is °Fadjacent cells? observed? (Dramatic & specific)2 s g ¥ = g 2 53. IE EXAMINATION ANSWERS AND EXPLANATIONS - 2005 Answer is B (Familial Amyloidotic Neuropathy): Robbins 7"/ 260 Transthyretin is a normal serum protein that binds and transports thyroxine and retinol (trans-thy-retin). A mutant ‘form of transthyretin is deposited in a group of genetically determined disorders referred to as familial amyloid polyneuropathies’ ~ Robbins Familial Mediterranean fever: is associated with ‘AA’: Amyloid associated protein + Dialysis associated amyloidosis: is associated with fy microglobulin + Prion associated amyloidosis: is associated with misfolded prion protein (PrPsc) Amyloidosis: Review Amyloid is a pathological proteinaceous substance deposited between cells in various tissues and organs of the body in variety of clinical settings. Amyloid with different chemical natures is deposited in different ciinical settings ‘The most important amyloid proteins and their relevant clinical scenarious include ‘This is derived from plasma cells? and contains It isa unique non immunoglobulin protein synthesized by immunoglobulin light chains. Reticuloendothelial cells of Liver & It is associated with Secondary Itis associated with Primary amyloidosis ® amyloidosis & reactive systemic amyloidosis ® + Immunocyte dyscrasias with amyloidosis such as Multiple « Chronic Inflammatory conditions: ‘myeloma ® = Tuberculosis, @ + Other monoclonal B-cells proliferation, ~ Bronchiectasis, @ = Osteomyelitis 2 + Connective Tissue Disorders: + Rheumatoid Arthritis ° (most common), = Ankylosing spondylitis, @ = 1° Biliary cirthosis © © Non immune derived rumours: ~ Renal cell carcinoma, © = Hodgkins Lymphoma ® oid proteins and their relevant clinical settings ° Brmicroglobulin By Amyloid Transthyretin Calcitonin Islet amyloid Atrial natriuretic factor (ABam) protein (AB) (ATTR) associated peptide (AIAPP) associated amyloid amyloid (A eal) (ANF) ‘Type + Isolated atrial Answer is A (Pyrin): Robbins 8/251 “The gene for Familial Mediterranean fever has been cloned and its product is called pyrin, (for its relation to fever) = Robbins 7"/ 261. 1 Mediterran Fever ‘* Most common ‘familial form of amyloidosis + ® Autosomal Recessive inheritance '» Febrile disorder characterized by + Responsible gene has been cloned and its product is called — Attacks of fever ‘pyrin’. Aithough its exact function is obscure pyrin has been — Tllammation of serosal surices including _-uBREted to be responsible for regulation of acute Fnlemmaton of sero surics including finan, by hibit the anton of netophi «+ Encountered largely in individuals of Medteranean _* © Attyloid fibril protein is made up of A protein. Scion. nv of Amenian Spars evs and Antic origin r Answer is B (REAL Classification) : Robbins 9/588; AJC Cancer staging Handbook In 1994, a group of hematopathologists, oncologists and molecular biologists came together (International Lymphoma Study Group) and introduced a new classification, called the ‘Revised European-American Classification of Lymphoid Neoplasms (REAL). WHO has now reviewed and updated the real classification resulting in inclusion of additional rare entities.55. 1S - 2005 L.Precursor B-cell Neoplasm TV. Peripheral T-Cell and NK-Cell Neoplasms Precursor lymphoblastic leukemi/Iymphoma “T-cell prolymphocytic leukemia Ni Large granulat lymphocytic leukemia ‘Chronic Iymphocyticleukeria/small lymphocytic Mycosis famgodes/Sezary syndrome iymmphoma B-cell prolymphocytic leukenia Lymphoplasmaeytic lymphoma Splenic and nodal marginal zone lymphomas Extranodal marginal zone lymphomas Mantle cel Iympoma Follicular lymphoma Marginal zone lymphoma Hairy cel! leukemia Plasmacytoma plasma cell myeloma Diffuse large B-cell lymphoma Burkt lymphoma ‘Precursor-T lymphoblastic leukemia/Iymphoma Peripheral large cell lymphoma, unspecified Anaplastic large cell lymphoma Enteropathy-associated T-cell lymphoma Hepatosplenic 6 T-cell lymphoma ‘Adult T-cell leukemia/lymphoma NK/T-cell lymphoma, nasal type [NK cell leukemia Y¥. Hodgkins Lymphoma ‘Classial subtypes = Nodular sclerosis = Mixed cellularity = Lymphocyte-rich - Lymphocyte depletion ‘Lymphocyte predominance ° 78 Answer is A (Lymphocyte predominance): Robbins 9/607; Harrisons 16"/ 655. The lymphocyte predominance variant is also known as Nodular Lymphocyte predominant Hodgkin's Disease. The nodular pattern is due to the presence of expanded B cell follicles. ‘Nodular Lymphocyte Predominance Hodgkin's Disease is now recognized as an entity entirely distinct from classical Hodgkin’s disease’ ~ Harrisons 16"/ 655 i AIPGMEE 2005 - EXPLANATIONS | In Accordance with REAL (WHO) classification, Hodgkin's disease is now classified into: - Robbins Glasses sibiypes a ymphoeyte predominance + Nodular selerosis Tn Iymphoeyie predominance Hodgkins L, the Reed + Mixed eelulrty Sternberg cells havea characteristic B-cell + Lymphocyte rich ‘immunophenotype distinct fom that of classical Hodgkins. + Lymphocyte depletion In the ‘classical subtypes’ the Reed-Stemberg cells have a similar immunophenotype and are therefore clumbed together as ‘classical’ forms of Hodgkins L. Answer is D (Tartrate resistant acid phosphatase posi Wintrobe's ty is typically seen in hairy cell leukaemi: 11°/2468, 2470, 2471 Hairy cells in hairy cell leukaemia (HCL) are associated with an isoenzyme of alkaline phosphatase inthe cytoplasm which unlike other isoenzymes is resistant to tartorate ie. Tartorate Resistant Acid phosphatase. TRAP stain is positive in HCL and usually negative or only weakly positive in other disorders ~ Wintrobo's 11" 2468, 470, 2471 + Mycloperoxidas sudan Black: Chandrasoma Taylor 3“/ 417 Blasts of ALL are typically Sudan black positive Blasts of AML are typically myeloperoxidase negative + Leucocyte alkaline phosphatase & CML: Although LAP scores are characteristically low in CML, they are increased when CML transforms into blast crisis. “LAP scores are often increased when CML transforms to blast crisis or accelerated phase’ -Winirobe’s 11"/2243 Confusing Memo: Leucocyte alkaline phosphatase is decreased in ‘CML (Chronic myeloid leukaemia) + PNA (Paroxysmal noctumal haemoglobinuria) + Tartarate resistant acid phosphatase (TRAP) score: Hairy cells of HCL contain acid phosphatase isoenzymes 5 in their cytoplasm. This isoenzyme unlike other acid phosphatase isoenzyme is not inhibited by tartarate and is termed as “Tartorate Resistant Acid phosphatase o TRAP’.57. EXAMINATION ANSWERS AND EXPLANATIONS -2005 “TRAP is an important tool in differential diagnosis of HCI although it is not pathognomic for the condition.” The testis positive in 95% of cases of HCI and usually negative or weakly positive in other disorders, z aba oe! B-CLL small ype mpm . Lympbopismacyidymphome NA Mantle cell Iymphoma, 2 Follicle center cell Iymphoma 2 Malt lymphoma : {Splenic marginal zone lymphoma He Hairy cell leukemia + Plasmacytoma Nia B-CLL: B chronic lymphocytic leukemia; TRAP: Tartare resistant acid phosphate Answer is D (A diffuse proliferation of medium to large lymphoid cells with high mitotic rate): British Journal of Haematology, 125, 294-317, 2004 Blackwell Publishing Lid; New Biologic Indicators of Prognosis in Chronic Lymphocytic Leukemia: Vol. 18, No. 2, April 2004; William G. Finn, M.D. MLabs Hematology Laboratory; Wintrobe's Haematology 11" 2438; Robbins 7"/ 673 The patient in question is a case of Chronic lymphocytic leukemia as indicated by the characteristic clinical picture and immunophenotypic characteristics. (Typically, CLL cells express CDS, CD19, CD23 and show absence of CD79B, CD22 and FMC?) Histopathological examination in a case of ypical CLL shows diffuse effacement of lymphocyte architecture by small to medium sized lymphocyes with clumped chromatin, indistinct or absent nucleoli and scanty cytoplasm. The round lymphocytes may give way focally top paler areas consisting of larger round ces (prolymphocytes). These paler areas are often referred to as proliferation centers and when present are pathognomic for CLLISLL. They contain relatively large number of mitotically active cells. Thus, a diffuse proliferation of medium to large lymphoid cells with high mitotic rate is consistent with a histopathological picture of CLL and hence is the single best answer here. Clinical picture Histology ‘Consistent with diffuse proliferation + = [EL] > of lymphoid celts with high mitotic Immunophenotype Lymph node biopsy [rate why Cu Clinical picture & Laboratory parameters Immunophenotype ~+ Weakness together with cervical lymph node + Positive for CDS, CD 19 & CD 23 enlargement & splenomegaly + Typically CCL cells express CD 5, CD 19, CD + Increased total leucocyte count with 80% mature 23 & show absence of CD 79 B, CD 22. & TM 67 lymphoid cells (BIOH, 124, 294-317, 2004) + Ane! Conaition smi CDS CD10 CD11e CDI9! "CD30" eD22! [eDzs" "CDs! "CDAS" COTS! (CIOS! TENET Chroniclymphocytic Dim ++ eo Dime leukemia Waldenstrom ee ee ee ee ee smacroglobulinemia Prolymphocytic Ht leukemia Hairy Cell Leukemia, H+ = HE HR HS ee Hairy Cell Leukemia HHH variant Spleniclymphoma wih + HHT we ‘illous lymphocytes Marginal one Beech = +} = tk Hat ymphoma Mantle cell lymphoma H+ HHH HHH aa Follcuariympboma Hea sig: surface membrane immunoglobulin‘AIPGME EXAMINATION ANSWERS AND EXPLANATIONS - 2005» 715 ‘Why “diffuse proliferation of medium to large lymphoid cells with high mitotic rate” was opted as the Histological characteristic of CLL in lymph node. + ~+ Lymph node architecture is diffusely effaced by small lymphocytes 6-12 years, in diameter containing round to slighty irregular nuclei with condensed chromatin and seant cytoplasm (Although Robbins mentions 6-12 mm diameter nuclei as small, many texts considered these as small fo medium sized nuclei) + These cells are mixed with variable number of larger cells called prolymphocytes in many cases prolymphocytes ‘gather together focally to form lose ageregates referred to as proliferation centres, so called because they contain relatively large number of mitotically active cells. When present proliferation centres are pathognomic of CLUSLI. Thus, although an option stating ‘diffuse proliferation of small to medium Iymphoid cells with variable number of large cells with a high mitotic rate’ wound have been more correct, nevertheless. With the available options, option D is the single best answer. Answer is D (Inv (16) is often detected in the blasts and the eosinophils): This isa case of ALL with hypereosinophillic syndrome. Inv (16) is associated with AML and not ALL, and therefore represents the incorrect statement amongst the option. ‘Wonder why such questions are set at all: This questions has been taken from a case report published in “Annals jouranal of Haematology’, authored by the faculty at AHIMS, who believed tat ‘the case represents the first report of the coexistance of granular ALL and hypereosinophillic syndrome’. Is difficult to understand what the faculty of the examination section at AIMS ‘expects out of undergraduates. Personally I believe that such questions are a mockery atthe tremendous efforts each candidates ‘puts up in preparation leading to the examinations Abstract Title: Granular acute lymphoblastic leukemia with hypereosinophilic syndrome. Journal Source: Ann Hematol. 2000 May;79(5)272-4. ‘Authors: Jain P, Kumar R, Gujral S, Kumar A, Singh A, Jain Y, Dubey S, Anand M, Arya LS. ‘A four-year-old boy presented with marked peripheral blood eosinophilia (absolute cosinophil count of $4 x 10(9)/1), features of bypereosinophilic syndrome, and acute lymphoblastic leukemia (ALL-L2), the latter characterized by the presence of granular bass. Blasts were negative for myeloperoxidase, non-specific esterase, acid phosphatase, periodic-acid Schiff tain, and toluidine blue. They exhibited an early pre-B immunophenotype (TaT, CD19, CD10, CD20 and CD22 positive) and stained negative for T (CD7, CD2, CDS and CD3) and myeloid markers (MPO, CD33 and CD13). Chromosomal analysis revealed a normal karyotype. To the best of our knowledge, this case represents the frst report of the coexistence of granular ALL and hypereosinophilic {syndrome do not have the permission to elaborate the entire case report therefore, I shall be citing the relevant text, only, however, I do recommend each one of you to read the entire article as this question has also been asked in AIIMS/2004 with different options and may as well be twisted and repeated in future. yhy ALU) ‘+ Blasts were negative for myeloperoxidase and non specific esterase ‘Type ‘Myeloperoxidase Suidan black AML - - ALL + + Presence of positive immunological markers CD 19, CD 20, CD 22 indicate a Ball Lineage ALL, (CimmunoTogical markers for Beell Lineage ALL; CD19, CD20, CD22, CD79a, CD22, eCD 79a ] iy Hypereosinophillic Syndrome! Option A Explanati Idiopathic hypereosinophillic syndrome is a rare condition characterized by extremely high levels of peripheral ‘blood eosinophil counts. (80% of (70 x 10°) Leucocytes were eosinophils in this patient) Clinical picture of dry cough, dyspnea, wheezing etc is further suggestive of HES. ‘+ This is differentiated from eosinophillic leukaemia by the absence of eosinophilic blast cells. (Text from case report: for option A) -xplanations to options: Text from ort + ‘In contrast to myeloproliferative disorders where Eosinophils are part of the Neoplastic clone, eosinophilia in patients with ALL is believed to be a reactive process.’ ~ Case report + ‘A normal karyotype has been observed in 45% of patients of ALL/Eo and ¢ (5:14) rearrangement has been documented in same of them.’ ~ Case report + ‘The child was treated with MCP-841 protocol of NC2 (prednisolone, L-asparginine, vincristine and daunarubicin) and was in remission after 4 weeks of chemotherapy. However, the peripheral blood eosinophils and the ‘pulmonary symptoms normalized 6 weeks after attaining remission. — Case report3 i ; 2 60. 61. Answer is B (A diagnosis of plasma cell leukemia Wintrobe's haematology 11"/ 2620, 2593 ‘Plasma cell leukaemia” by definition is characterized by more than 20% plasma cells in the peripheral blood. The patient in question has 14% plasma blasts in peripheral blood and thus does not classify as a plasma cell leukaemia. + More than 20% plasma cells in the peripheral blood © Absolute plasma cell count of more than 2 x 10°/L. [gD Myeloma (Winirobe's 11"/ 2592) a 4+ Accounts for approximately 2% of all eases of myeloma + Presence of Monoclonal IgD inthe serum usally indicates IgD myeloma + Present with a small bond or no evident M-spike on serum protein electrophoresis. + Higher incidence of renal insufficiency, Amnyloidoss and proteinuria than IgG /IgA myeloma. + Higher incidence of Extramedullary involvement and inferior survival rates. Monoclonal gammopathy of undetermined significance + Serum monoclonal protein () <3 gil + Nosnemia, renal failure, or hypercalcemia + Bone lesions absent on radiographic bone survey + Bone marrow < 10% plasma cells. Smoldering multiple myeloma ‘+ Serum monoclonal protein (23 gil) or 2 20% marrow plasma eels or ageregates on biopsy, or both + Noanemia, renal fa iypercalcemia attributable to myeloma Multiple myeloma | + Monoclonal protein presents in serum or urine a ‘+ 2 10% marrow plasma cells on biopsy of histologic evidence of plasmacytoma + Plusoae or more more ofthe following = Anemia ~ _Lytic lesions or osteoporosis and 230% plasma cells in marrow = Bone marrow plasms cel labeling index >1% = Renal insufficiency = Hypercalcemia Criteria for diagnosis of Monoclonal Gammopathy of Undetermined Signicance, Smoldering Muliple Myeloma and Maulple Myeloma, According to Kyle and Greipp-Wintrobes. Answer is C (Rheumatic carditis): Robbins 9°/558; (Repeat) Aschoff bodies are characteristic focal inflammatory lesions of acute rheumatic fever found in any of the three layers of the heart. Aschoff bodies: + Aschoff bodies are focal inflammatory lesions seen during acute rheumatic fever ‘+ They consist of foci of swollen eosinophilic collagen surrounded by ~ Lymphocytes (primarily T cells) = Occasional plasma cells = Aschoff giant cells (macrophages of rheumatic fever) = Antitschkow cells (Antischkow cells are modified macrophages with abundant cytoplasm and central round to ovoid nuclei in which the chromatin is disposed in the central, slender wavy ribbon like pattern ~ caterpillar cells) + During acute RF, Aschoff bodies may be found in any of the three layers of the heart ~ pericardium, myocardium and endocardium. Answer is B (Predominance of alveolar exudate): Robbins 9"/707 Viral pneumonias are an example of ‘atypical pneumonias’ and are characterized by inflammatory reaction predominantly restricted within the walls of alveoli within the intertitium. The alveoli may be free from exudates Robbins. The alveolar septa are widened and edematous and usually have a mononuclear inflammatory infiltrate. Alveoli may be free from exudates but in many patients there is accumulation of intraalveolar proteinaceous matrial®, a cellular exudates and characteristically pink hyaline membranes. These changes reflect alveolar damage similar to that seen diffusely in ARDS.62. ‘Air Space Peoumonia (Typical Pneumonia) Interstitial Pneumonia (Atypical Paeiimoni)/ ONO Exudate in alveoli ie, consolidation ‘No exudate, alveoli are air filed ie, no consolidation — (flat i interstitium) : (Mnttrate i primarily af ieutrophills (PMN). "Tnfltrate is primarily lymphatic) a ‘Agents responsible are extracellular Agents responsible ae intracellular PoE) ‘Cough is productive of purulent sputum ‘Chest X-ray shows alveolar pattem ‘Chest X-ray shows interstitial pattern ay Answer is D (Kleibsella pneumoniae): Chandrasoma Taylor 3/516; Harrison 16%/882 [Keibsella pneumonia present as typical ‘ir space’ pneumonia with cough productive of purulent sputum. “Purulent sputum production and ‘airspace’ diseases X Ray ve typical’ ~ Harrison 16%882 1, Mycoplasma pneumonias 2. Viral pueumonias ~ Influenza -RSV. = Adenovirus Rhinovirus = Rubeola - Varicilla = Corona virus 3. Chlamydia pneumonia 4, Coxiella bumetti jeumocystis carinit ‘Corona virus is an infrequent cause of pneumonia, ‘SARS associated corona virus (SARS-CoV) caused epidemic of pneumonia from Nov 2002 10 July 2003 - Harrison Answer is D (Benign Nephrosclerosis): Robbins 7°/ 992, 1006; Repeat; CMDT 2005 / 893 ‘In gross appearance kidneys (in benign nephrosclerosis) are either normal or moderately reduced in size. The loss ‘of mass is due mainly to cortical scarring and shrinking.’ — Robbins ‘Gross renal size in other disorders Amyloidosis Rapidly progresivecrescentric Diabetes meltus glomerulonephrits CCharacteristiclly kidney ‘Kidneys are enlarged and pal often “The most common lesion is dtfse size tends o be ether _withpetichal aemorhageson the _glomerulosclerosis but nodular glomeruloscleross normal or increased cortical surfaces" ~ Robbins */977 is (Kimmelsiel- Wilson) is palhognomic. The “Robbins 7/992 Kidneys in these patients are usually enlarged as & result of cellular hypertrophy and proliferation. — MDT 2005/ 893, Answer is A (Thrombotic microangiopathy): Robbins 9"/941 Hemolytic syndrome is classically included in the spectrum of Thrombotic microangiopathies. “The term Thrombotic microangiopathy encompasses a spectrum of clinical syndromes that include TTP and HUS’. = Robbins 7/612 ‘The pathogenesis of Classical Childhood Hemolytic uraemic syndrome involves both thrombosis and vasoconstriction, resulting in characteristic microangiopathy (Thrombotic Microangiopathy)'-Robbins 7/1010 ‘Thrombotic microangiopathies: These represent a group of disorders that are characterized morphologically by thrombosis in capillaries and arterioles throughout the body and clinically by microangiopathic hemolytic anemia, thrombocytopenia and in certain conditions renal failure. ‘Widespread formation of Hiyaline thrombi comprised primarily of platelet aggregates inthe microcirculation f — —7T Consumption of platelets Hemolytic anemia resulting from trauma to Organ dysfunction depending on the + red cells from obstruction of vascular bed involvement Thrombocytopenia microvasculature by intravascular thrombi 4 + Renal failure in HUS Microangiopathie hemolytic anemia Neurological dysfunction in TTP ‘Note that the term encompasses a spectrum of clinical syndromes that includes TTP & HUS. DIC is not included While DIC and Thrombotic microangiopathies share several features such as microvascular occlusion and microangiopathic hemolytic anemia, they are pathologically distinct ~ Robbins 7" 653718 6s. 66. © AIPGME EXAMINATION ANSWERS AND EXPLANATIONS - 2005 Answer is D (Chronic alcoholism): References mentioned below ‘Alcoholic liver disease (ALD) is the most frequent secondary faty liver disease. Secondary faty liver can also occur in chronic Viral hepatitis C (HCV), chronic viral hepatitis B (HBV), chronic autoimmune hepatitis (AIH), and Wilson's disease’ -wew.medicinenet.comifat i Thus although fatty liver may be seen secondary to all the options mentioned in the question chronic alcohoticm being the most common cause is the single best answer here. Causes of Fatty Liver (www.cnn.com/HEALTHMibrary/DS100577.himl) ‘Alcoholic Fatty Liver Disease ‘Non-Aloholi Fatty Liver Disease (NAFLD) ‘Alcoholic liver disease isthe most common cause for This condition is associated with many risk factors (including fatty liver disease chronic infection with hepatitis Cor B and Wilsons disease) Non-Alcoholic Fatty Liver Disease (NAFLD) (NASH) ‘Although the cause of nonalcoholic fatty liver disease is unclear, the condition is associated with many risk factors. ‘Overweight and obesity Diabetes Hyperlipidemia Abdominal surgery Chronic infection with hepatitis C or B Medication Miscellaneous conditions ~ Wilson's disease, a hereditary condition that affects copper levels; = Weber-Christian disease, which effects nutrient absorption = Abetalipoproteinemia, a rare congenital disorder that affects the ability to digest fat = Inherited metabolic disorder; galactosemia storage diseases. Review: Causes of Fatty Liver (Hepatic steosis): Harrison 16/870 ‘Macrovesicular (large fat droplets in hepatocytes) ~ Alcohol, alcoholic liver disease ~ Total parenteral nutition, jejunilelal bypass ~ Insulin resistance ~ Rapid weightloss ~ Syndrome X (obesity, diabetes, hyperplyceridemia, _~ Drugs, “eg. methotrexatem aspirin, vitamin A, glucocorticoids, hypertension) amiodarone, calcium channel blocker and synthetic estrogen, = Lipodystrophy nucleoside analogues (ddl, AZT) * Dysbetalipoproteinemias ~ Inflammatory bowel disease ~ Protein-calorie malnutrition, starvation Microvasicular (small fat droplets in hepatocytes) ~ Reye’s syndrome = Drugs, eg. valproic sickness = Acute fatty lover of pregnancy ~ Drugs, eg. valproic aid, tetracycline, nucleoside analogues = Jamaican vomiting sickness ~ Environmental hepatotoxins (eg. phosphorus, petrochemicals) Answer is D (Bridging fibrosis): Ackerman Surgical Pathology 9"/ 959; Harsh Mohan 5"/ 650; API 7/621 Fibrosis in noncirrhotic portal fibrosis is confined to portal and periportal region. Fibrosis bridging one portal tract to another (bridging fibrosis) is not seen. Non cirrhotie portal fibrosis (NCPF): Hepatoportal sclerosis: Non cirrhotic portal fibrosis is primarily a vascular disorder of the liver characterized by fibrous intimal thickening of the portal vein or its branches in patients with non cirrhotic portal hypertension. “Histological features f + ‘Vascular changes Fibrosis + Hallmark ofthe disease is chrombosivcleross ofthe portal vein» Vascular changes are accompanied by portal branches. and periportal fibrosis of varying extent. ‘+The portal vein is dilated with sclerosis ofthe walls and in autopsy thrombin in medium or small portal vein branches with accompanying areas of ischaemic necrosis have been reported. ‘+ Aberrant Intrahepatic vessels may be present in the periportal area, ‘hich correspond to dilated terminal poral vein branches or venules. These are often termed as “megasinusuoids” or periportal angiomatosis Both vascular changes (thrombosis, ischaemia) and fibrosis are certain to be associated with some nonspecific inflammatory infiltrates (although not mentioned directly).Bridging fibrosis is the single best answer of exclusion. (Bridging fibrosis represents more extensive “fibrosis bridging one portal tract to another ‘and has not been mentioned as a feature)6. Note: There is divided opinion on whether nodular regenerative hyperp ‘regenerative activity is characteristically absent Harsh Mohan) degree may be present (Ackermann, API) Answer is B (25%): Repeat; Harrison's 16/2235 In accordance with an autosomal dominant inheritance pattern the chances of having an anaffected baby are 25%. asia is an autosomal dor + Let ‘a’ represent the normal allele and A represent the act asia is present or not According to some texts nodular According to some, nodilar regenerative hyperplasia fo some hhondroplasic allele. Given that both parents have achondroplasia, the most favourable inheritance would be : Aa ‘Aa | eaeeeeneeeeeneneeeeeneeeenl t + + AA Aa Aa a Affected Affected Affected __Not affected ‘+ 3 out of 4 children would be affected or 75% of children will be affected ++ 1 out of 4 ie, 25% children will be unaffected. Note: We have chosen only a heterozygous state in both parents as the question is asking about the most favourable Answer is D (X Linked Recessive): Read text below Presentation of disease only amongst males identifies the. ‘outcome possible. If both parents are homozygous 0% children will be unaffected. disorder as sex (X) linked. Because carrier mothers are not ‘manifesting the disease, yet their sons do, the disorder can only be recessive. The disorder is thus X-linked recessive. Males (Father) XY_ Females (mother) XX. Foe have oly ne X-dionosnmes ote nai ve to rocco = A daughter always inherits father's X- = A daughter always inherits one X chromosome ‘chromosomes = A son always inherits one X chromosome «_Roamnevernbris b's X-tromoomes + + ‘© Father to son transmission never occurs in an + Daughters of an affected male are obligate Sond Seo caste manera «Males luays enon th plese bese «Females maybe hmyge rete g0 thopleve ely one X choosy td he Iderpas be pose depen soir bean sagen Eel domi © rent ea toni a @ OO —4 eee a 6am O& eee Ct I I o ® XY} X Mutant allele . . HR &Answer is A (Genomic imprinting): Harrisons 16/375; Robbins 9"/172 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 ofa gene or set of genes on either the matemal chromosome or the paternal chromosome + Inactivation of matemal allele ie. inactivation of Inactivation of gene on paternal allele i. inactivation of a a gene on maternal chromosome gene on paternal chromosome Thus the only functional alleles are now provided by either the patemal or maternal chromosomes (ie. only cone parent) + 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? ‘Angleman Willi Syndrome Maternal —Patemal Prader Willi Angelman gene gene Getomic ‘printing imprinted imprinted an (inactive) ‘Active Prader (inactive) ‘Angelman Prader Will Will gene Angelman ene gene gene ‘The only functional gene ‘The only functional gene is provided by the is provided by the ‘paternal chromosome pateral chromosome Deletion on paternal Deletion on patemal chromosome chromosome imprinted imprinted (inactive) (inactive) Deleted inactive ‘maternal Deleted inactive smatemal 7 Prader Willi Prader Willi gene Angelman ame gene | gene | Prader Willi Syndrome ‘Angelman Syndrome + Deletion occurs exclusively on paternal + Deletion occurs exclusively on maternal chromosome 15 (deletion of band q | chromosome 15 Jong arm of chromosome 15) = Features: [+ Features: ~ Diminished fetal activity —Hypotonia ~ Hypotonia ® Mental retardation Obesity? = Seizures ~ Mental retardation Ataxia = Short stature Inappropriate laughter (Happy puppets) = __Hypogonadotropic hypogonadism‘AIPGME EXAMINATION ANSWERS AND EXPLANATIONS -2005 © 721 Answer is B (Receptor mediated endocytosis): Ganong 2/*/ 29; Lehninger's biochemistry 4"/ 1074 Clathrinis a protein, accumulation of which is associated with receptor mediated endocytosis = Lehninger's biochemistry 4%/ 1074 Receptor mediated endocytosis: Review ‘ Clathrin mediated endocytosis is a specialized, receptor mediated endocytosis ‘+ Endocytosis occurs at membrane indentations called ‘pits’ where endocytic receptors are concentrated. ‘+ These ‘pts’ are coated on their cytosolic side with a lattice of protein called ‘clathrin’ ‘© The clathrin lattice grows as more receptors are occupied by target proteins and is removed by ‘uncoating enzymes only after endocytosis has occurred, ‘+ Examples of clathrin mediated endocytosis include ~ Internalization of nerve growth factor = Internalization of low density lipoproteins (LDL) ‘71. Answer is A (Intermediate filaments): Ganong 21”/ 13; Robbins 7%/ 34 Intermediate filaments form a flexible scaffolding for the cells that organizes the cytoplasm and resists forces applied 10 the cell (resist external pressure). These are however not involved in cellular or flagella movements. ( Microtubules [intermediate filaments + Composed of Actin, Myosin | |« These are hollow slender tibes + These provide flexible and ther regulatory proteins. rade up of protein called ‘abulin’ | | intracellular scaffolding that (Mainly actin with litle + Microtubules are a dynamic portion | | helps resist extemal pressure myosin) of cell skeleton and constitute + These include: > These are essential for various | | structure lke: a.Keratins stages of leucocyte movement || a,Cilia b.Neuro filaments ‘Sapien eee ofsuch || Spindles ¢.Desmin ere ¢. Processes (dendrites) of neurons || 4. Viamentin .Centrioles .Glial cells + (Defects in organization of ‘microtubules causes ~ inhibit sperm + Certain types of cell injury lead to accumulation of rmolitity (& cause sterility) - inhibit | | intracellular intermediate ciliary molitty of resp. epithelium) || filaments + Microtubules like micro ligaments = Mallory body are essential for leucocyte ~ Neurofibritory longus migration & phagocytosis MICROBIOLOGY 72. Answer is A (ADP ribosylation of G-regulatory protein): Harrisons 16"/910, 911 Active subunit of cholera toxin upregulates adenyl cyclase activity by causing irreversible ADP ribosylation of GTP binding regulatory protein of adenyl cyclase. Activity of adenyl cyclase is increased, absorption NaCl is inhibited, and GTPase is not activated. Action of cholera toxin : Pathogenesis + Active subunit of cholera toxin is the Ay subunit + The specific target of this subunit isthe GTP binding regulatory component of adenyl cycalse (G-regulatory protein of adenyl cyclase)2B. 4. "AIPGME EXAMINATION ANSWERS AND EXPLANATIONS -2005 “Active subunit of chotera toxin (A) Inreversibly transfers ADP ribose to G-regulatory component of adenyleyclase ADP Rebosylation of G. regulatory prov of Adel ple Upregulation or increased activity of adenyl cyclase Inacio ceumulation of hgh evels of cAMP Inhibition of absorption of Na” in villi Activation of CI’ secretion in crypts cells Lo Sodium chloride accumulates in intestinal lumen (absorbtion of NaCl) ® ‘Water moves passively into lumen because of increased osmolality in intestinal lumen (due to NaCl) + Watery diarrhea Review Cholera enterotoxin consists of two subunits a v + A subunit (Active) B subunit (Binding subunit) (Monomeric) (Pentameric) + Serves as the active enzymatic subunit? + Serves asthe binding unit? + It is transported into the cytosol with help of B subunit + Binds to receptors on the surface of + Itthen breaks into two subunits A, and A> of which Ay is epithelial cells and makes the delivery of the active unit the active A unit possible to the £ v cytoplasmic target (GM; ganglioside, a A, ‘A; (not active) glycoprotein on surface of jejunal + Toxic effects are produced + Binds the active epithelial cells acts as the toxin receptor by Ay subunit by causing ‘component Ay to the i.e. B subunit binds GM, ganglioside prolonged activation of Binding protein or the B receptor? cellular adenyl cyclase and subunit, accumulation of CAMP. Answer is A (V. cholera): Ananthnarayanan 9/311; Greenwood 16"/ 296 Vibios that have high requirement of sodium chloride are known as halophillic vibrios. Halophillic vibrios that have been shown 10 cause human disease include V. parahaemolyticus, V alginolyticus and V. vulnificus. Vibrios cholerae are non halophilic vibrios. Classification of Vibrios based upon salt tolerance. ‘Non Fialophilic vibros alophillic vibrios Vibrios that are able to grow in media without Vibrios that do not grow in media without added salt added salt (Halophillic vibrios) + Vibrio cholera + V.parahaemolyties + V.Alginolyticus ‘Saltcon ¥en | Vibrio cholerae 0% + : 5 ulifiens Answer is D (Gas gangrene producing strains of C. perfringes produce heat resistant spores): Harrisons 16°/ 847; Ananthnarayanan 9"/253-255 The gas gangrene producing strains of C. perfringens are not resistant 10 heat. + ‘C.perfringens is encapsulated and non motile and rarely sporulates in artificial media. The spores can usually be destroyed by boiling? ~ Harrisons 16°/845 Note that while spores of gas producing strains of C. perfringens are destroyed within S minutes by boiling, those of the food poisoning strains of type A’ and certain ‘type C’ strains resist boiling for 1-3 hours. (Ananthnarayanan)15. 16. + Clostridium perfringens ‘type A’ is the predominant agent causing gas gangrene ~ Ananthnarayanan 7/252 “Some 80% of eases are caused by C. perfringens while C. novyi, C. septicum and C. histolyticum cause most of the remaining’ ~ Harrisons + Cl. perfringens is a normal inhabitant of the large intestine of human beings and animals, 1s found in the faeces ‘and it contaminates the skin ofthe perineum, buttocks and thighs. Ananthnarayanan 7/249 ‘+ “The Cl. perfringens is one of the most prolific of toxin producing bacteria forming at least 12 distinet toxins. The alpha toxin is produced by all types of Cl. perfringens and most adbundantly by type A strains. This is the most {important toxin biologically and is responsible for the profound toxaemia of gas gangrene.” ~ Ananthnarayanan 7"/ 250, 281 Answer is C (Enteroinvasive E, coli produces a disease similar to Salmonellosis): Repeat Enteroinvasive E. coli produce disease similar to shigellosis and not similar to salmonellosis About 5 types of wve been identified Enteropathogenic E.coli EnterotoxigenicE. colt Enteroinvasive Enteroadhesive E. Coli + Bacili act by intimately araching (no + Bacilli act by producing enterotoxin] + Bacilli act by invasion invasion) to cup like projection ofthe + A strain may produce either Labile inthis aspect they resemble enterocyte membrane toxin or Suble toxin ‘Shigeltay Disruption of brush border microvilli ‘Mainly affect infants and children» Afectall age sroups + Affect both Children and Adults Usual epidemics + Endemie in developing countries | + Sporadic May be sporadic hhea-genic E.coli + Cause Traveler's diarrhea ® + Detected by tests = Sereny test ® = Penetration of He-La and HEP-2 cells| [= ot Enterohemorthagic / Verotoxigenic E. Enteroaggregated E. coli ‘+ Actby producing verotoxin (primary target of Form heat stable enterotoxin EASTI and cause vverotoxin being vascular endothelium ®) shortening of vill, hemorthagie necrosis with mild edema and mononuclear infiltration of submucosa ‘© Affects both children and adults ‘© Sporadic and outbreaks © Causes HUS + Associated with persistent diarrhea in developing Lab diagnosis can be made by demonstration of ‘countries. bacilli or VT directly in feces or in culture ‘© Most VTEC strains belong to 0157: H7® + So named because they appear ageregated in a stacked brick formation on HEP-2 cell lines. Answer is A (Leptospirosis): Harrisons 16%/ ; Greenwood 16"/ 356 Leptospires are bacteria belonging to the family of spirochaetes. They are associated with the three"R’s: + Rats: Rodents especially Rats are the most important reservoirs - Greenwood + Rice fields: “Farm workers now represents the group at greatest risk’. Thus farm workers in rice fields constitute an important risk group. Leptospirosis is more common in farm workers that it is in sever workers + Rains: ‘Human are infected when Leptospires in water contaminated by urine of carrier animals enters the body through cuts or abrasions.” Such transmission is thus increased in the rainy season. Leptospirosis: Review Leptospirosis is @ zoonosis. Rodents especially ras, are the most important reservoirs. Transmission of leptospires may follow direct contact with urine, blood of tissues from an infected animal or exposure to a contaminated environment. ‘+ Leptospires are spirochetes and causative agents for WEIL’s disease named ‘Ietohemorrhagicus fever" + Leptospires are found in the urine or rats, dogs and other wild animals, Rodents especially rats being the most important reservoirs. ‘Transmission: Human beings are infected when leptospires in water contaminated but urine of carrier animals enters the body through cuts or abrasions or through intact mucosa of mouth, nose or conjunLeptospires (Weil's Syndrome) Ietero- igicus fever Hepato renal damage Bleeding diasthesis ere E e Purpuric hemorrhages ? lure Albuminuria? Remember: ERA Die a Syphilis ° : Bejel 2 Yaws? Pinta? “Lyme disese® Relapsing = Weil's disease 2 7. ): Ananthnarayan 9°/399; Javete 23/273 Culture of campylobactor jejuni is best under microaerophillic conditions with 0, tension lowered to 5% and carbon dioxide raised to 10%. Incubation of primary plates should be at 42° Thus although option B is not entirely wrong, option A is better and the single best answer here Cam view Morphology Oe aa Soo a Gram negative rods ® # Comma shaped ° (‘Gullwing” shaped rods) + Motile with a single polar flagellum (Darting or tumbling motility on dark field / phase contrast measuring) ° + Non sporing ° Culture (avetz) © Selective media are needed (¢.g. Skirrow's medium) + Incubation must be in a miroaerophilic environment = Oxygen tension shouldbe lowered 1 5% = COsshould be added to up 0 10% + Incubation of primary plates shouldbe at 42°C. (although C. jejuni grows well at 36.37% incubation at 42°C prevents row of most ofthe other bacteria present in the faces thus simplifying the deification of C. jejuni) Biochemical reactions (that have been asked) ‘+ C. jejuni and other campylobactors pathogenic for humans are both catalase andl oxidase positive ° Pathogenesis & clnieal manifestations: + Campylobactr jejuni are a common cause of human bacterial diathel disease 4 Acquired by orl route from food or drink. Clinically presen with acute onset ramp abdominal pin, rose dines, tht maybe grosly bloody, headache, malaise and fever + Usually set tim ‘Treatment © Most cases resolve without antimicrobial therapy (self limiting disease) {+ Enjthromycin is otherwise the antibiotic of choice and subsides in a period of 5-8 days. 78. Answer is A (Itis caused by Burkholderia mallei): Harrisons 16"/ 895; Greenwood 16"/ 286 Melioidosis is caused by Burkholderia pseudomallei and not by Burkholderia mallei. B. mallei is the causative agent ‘for ‘glanders’ a potentially fatal disease of horses, mules or donkeys. Melioidosis: Review It is a devastating tropical infection of animals and humans that is endemic in eastern Asia and Northem Australia, Burkholderia pseudomallel isa five living saprophyte normally found in sol, ponds, and rice paddies and on produce from endemic areas./AIPGME EXAMINATION ANSWERS AND EXPLANATIONS - 2005» 725 ‘Clinical manifestations: ‘Virtually every organ can be affected and hence meliodosis has been called the “great, ———_—__—_______ | Y ¥ t + Acute pulmonary Localized skin infection Suppurative parottis in Others ions with ulceration or abscess ehildren + Liver/splenic abscess Mild bronchitis to ‘with lymphangits and + Septic arthritis Sdeasive necrotizing ——‘yanphadenitis + Osteomyelitis pneumonia. + CNS + Genitourinary infection respiratory tract illness, parotitis, lymphadenitis, unsusual skin or subcutaneous lesion or has a chest suggesting tuberculosis inthe absence of sputum associated tubercle baci (Eecirpa entertained when a febrile patient who has been in an endemic area presents with a) Diagnosis: we ‘Microscopy Culture Serology ~ Bipolar stained gram negative bacilli Cultured from sputum, urine, pus, ELISA ~ Aerobic ‘or blood on selective media + PCR = Motile + Indirect haemagglutination (Treatment: ‘+ Intravenous Ceftazidine is the drug of choice for severe melioidosis~ Greenwood ‘+ Carbapenems: Imipenem or meropenem are other agents of choice (Harrisons) 79. Answer is C (Streptococcus pyogenes): Jawetz 23/313, 295; Ananthnarayanan 9/209, 290, 227, 401 Neisseria meningitides, salmonella typhi and Legionella pneumophilia are all known to survive intracellularly. Streptococcus pyogenes is the single best answer of exclusion here. Intracellular nature Legionella pneumophilia Neisseria menin Salmonella typhil “L. pneumophila readily enters and ‘Neisseria typically are found “The ability to resist intracellular Killing sg70ws within human alveolar associated with or inside and to multiply within polymorphs and ‘macrophages and monocytes and is polymorphonuclear cell” -Jawetz macrophages is a measure oftheir not effectively killed by 23°/295 Virulence’. — Anandhnarayan 23% 295 polymorphonuclear leukocytes.'~ _“Meningococciare invaiably found wets 237/313 in the spinal fuid both fee and within the leucocytes’ — Ananthnarayan 79/223 80. Answer is C (Cryptococcus neoformans): Harrisons 16/1116 ‘Cryptococcus neoformans is the leading infectious cause of meningitis in patients with AIDS?-Harrisont 6/116 Also Remember: “Toxoplasmosis is the most common space occupying lesion in HIV infected patients’ - CMDT 2005/1281 81. Answer is B (Gram negative organisms): Ananthnarayan 6"/ 588; Harrison 16"/ 1539 ‘Nosocomial pneumonias are common in immunocompromised patients and are characterized by colorization of the nasopharynx by “Gram negative bacilli’ followed by trickling of upper airway secretions into lower airways, resulting in pneumonia’ — API 7/304 ‘Ina national survey in United States, 64% of all microorganisms isolated from the lungs of patients with nosocomial pneumonias were gram negative bacilli’ ~ Harrison 16"/ 1539. Remember: S. aureus (gram positive cocci) is the most common cause of nosocomial pneumonia in the United States - Harrison 16/1539 Thus while overall gram negative bacilli are the most common of cumulative agents for nosocomial pneumonias, Staph aureus is the most common individual etiological agent. 82. Answer is A (It cannot be eradicated by antimicrobial agents): Ananthnarayanan 7"; References alongside726 + AIPGME EXAMINATION ANSWERS AND EXPLANATIONS - 2005 Although antimicrobials can diminish the number of microorganisms, itis unlikely to remove them completely. Even if complete removal occurs, it is only temporary and the remove flora is rapidly replenished and hence the transient removal cannot be termed ‘eradication’, + The normal microbial flora are more or less constant for each species and are broadly divided into residents and transients. The former constitute a constant population which cannot be completely removed permanently’ ~ Ananthnarayanan 7/599 + The number of superficial microorganisms may be diminished by vigrous daily snubbing with soap containing hexachlorophene or other disinfectants, but the flora is rapidly replenished.’ - Jawetz 23" 197 + Although acidic pH is responsible for keeping the number of microorganisms to a minimum, they are not absent in the stomach. “The stomach’s acidity keeps the number of microorganisms at a minimum (10°-10°/ g of contents) unless ‘obstruction at the pylorus favours the proliferation of gram positive cocci and bacilli” — Jawete 23 198 “Because of low pH of stomach, it is virtually sterile except soon after eating” — Anantimarayanan 7%/ 601 ‘Although text from Ananthnarayan does confuse the issue, in view of the elaborate text from Jawetz (10'-10'/g of contents) and the term ‘virtually’ added before sterile in Ananthnaravanan it is probably not correct to say that ‘microorganisms are absent in the stomach, The flora in the small bronchitis different from the flora of the trachea. ‘Wii the small bronchi (& alveoli) are seri, the flora in the ache is simitar ota in the pharynx and mouth Anantinarayanan 7/600 + Flora does not establish after neonatal period, but may even be present since birth “The mouth of infant is not sterile at birth’ “Within 12 hours of birth, alpha hemolytic streptococci are found in the upper respiratory tract; and become dominant organisms of the oropharynx and remain so for life.” “Intestinal flora is established within 4-12 hrs of birth, partly from below and partly by invasion from above.” ~ Ananthnarayan 7/600 83, Answer is D (Community acquired pneumonia): Ananthnarayan 99/416, 419; Repeat Community acquired pneumonia results from C. pneumoniae and not C. trachomatis. C. trachomatis is associated with infant pneumonia and not community acquired pneumonia. Diseases caused by Chlamydia + t 1 (Gilani wachonatis] Gham Petal Cilaaydla Peeamanise Many serotypes Only one sewiype Pritacois Cocanantysoqied petra eg. acute respiratory disease Serotype A,B, Ba, C Serotype D, FG. WLS. ‘Serotype Ly, Uy by Endemic blinding trachoma | |* Inclusion conjunctivitis Tymphogranuloma Venerum { Enders Minding ocho’ | |* (peonatal & adel) + Genital chlamydiasis | + Infant pneumonia 84. Answer is D (The group specific antigen is respor Sawwetz 23° 358 le for the production of complement fixing antibodies): “Chlamydia posess shared group (genus) specific antigens. These are heat stable lipopolysaccharides. Antibodies to these genus specific antigens can be detected by complement fixation’ — Jawetz + The heat stable genus (group) specific antigen is common to all chlamydia, This isa lipopolysacharide resembling the LPS of gram negative bacilli. Ths is present in all stages of developmental cycle and can be detected by complement fixation test, (It does not differentiate C. pneumonias infections from infection with C. psittai or C. trachomatis, but identifies that infection is by a member of the chlamydia group) + Chlamydia pneumoniae has only one serotype. “There are at least 15 serotypes of C. trachomatis, several serovars of C. psittaci can be demonstrated, Only one serovar of C. trachomatis has been described’ ~ Jawets 23% 358 + C.pneumoniae produces intracytoplasmic inclusions that lack glycogen. — Jawetz 23° 359 C. pneumoniae produces round dense, glycogen negative inclusions that are sulfonamide resistant. + There is mo known animal reservoir of C. pneumoniae, Transmission is presumed to from person to person, predominantly by the air bome route,85. 86. 87. AIPGME EXAMINATION ANSWERS AND EXPLANATIONS - 2005 * 727 | aaa “Ctrachomatis ——C pneumoniae C psittaci Inclusion morphology Round, vacuolar Round dense Large, variable shape, dense ‘Gbyeogen in inclusions Yes No No Elementary body morphology Round Pear-shaped, round Round [Susceptible to sulfonamides Yes No No DNA homology to C < 10% 100% <10% ‘pneumoniae (Plasmid Yes No Yes Serovars 15, 1 24 ‘Natural Host ‘Humans ‘Humans Birds Person to person other to infant Airborne person to person Airborne bird excreta to humans rea Pneumonia, bronchitis, Psittacosis, pneumonia, fever of ‘Pharyngitis, sinusitis unexplained origin Answer is C (High OX-K): ttnnenan 10:4 Harrisons 16"/ 1004 The presence of fever and headache along with an erythematous lesion and lymphadenopathy suggest a diagnosis serub ‘typhus, Humans encounter scrub typhus when they enter ‘typhus islands’ i.e. vegetation between forests and clearings. The disease assumes great importance in military medicine especially during jungle warfare serological diagnosis of scrub typhus is by the ‘Weil-Felix reaction. OX-K agglutins are found only in scrub typhus and hence are diagnostic in the given clinical setting. Disease ‘Agglutination pattern with Ox19 ox2 Ox typhus a + : Brill-Zinsser disease Usually negative or week positive : Endemic typhus a + : Tickborne spotted fever + + ‘Scrub typhus : - +H Weil-Felix reaction in rickettsial diseases Footnote: Note that OX K agglutinins are positive only in scrub typhus. Answer is D (Chemically defined media): Ananthnarayanan 9/434 “As viruses are obligate intracellular parasites they cannot be grown on any inanimate culture medium.’ = Ananthnarayanan Chemically defined media are inanimate media and virus cannot be grown on them. “Methods employed for cultivation isolation of viruses may include + ‘issue culture/ cell culture Embryonated eggs Animal inoculation + Most important method for cultivation of ‘+ Embryonated egg provides several «Earliest method for viruses sites for cultivation of viruses cultivation of viruses + Tissues provide the cellular environment that is = Inoculation on CAM essential for growth of these obligate (chorioallantoie membrane) the most widely employed intracellular parasites = Inoculation into amniotic sac animals in virology + Types include * Inoculation into allantoic evity + Growth of virus may be + Organ culture + Yolk sac inoculation indicated by death, disease Call culture or visible lesion. = _Explant culture _ Infant suckling mice are Answer is A (Transduction): Ananthnarayanan 9°/59, 60 The transfer of a portion of DNA from one bacterium to another by a bacteriophage (virus) is known as transduction. Bacteriophages are viruses that parasitise bacteria and consist of nucleic acid care and a pri (Transformation? ‘Transduction’ Conjugation ~~ ‘© This isthe transfer of genetic material through the agency of free DNA ® (May involve taking up of soluble DNA with host DNA and codes new species through the cell wall) ‘© This has been studied mainly in: - BPH - Bacillus? + Hemophillus? ~ Pneumococcus ® «Transfer of genetic clements after actual + Trasfer ofa portion of DNA from one bacterium tothe other by means of a physical contact bacteriophage ° between a “male” + This has been proposed as donor bacterium and a method of genetic female recipient e.g. engineering ? and in transfer of episomes ‘treatment of some inbome and plasmids such as ‘errors or metabolism. those for resistance @ “Lysogenie conversion® 7) + In lysogenic conversion the phage DNA itsels the new _genetic clement “ as it ‘becomes integrated withthe ‘bacterial host DNA with which it mulplies and is transfered to daughter cll, ‘eg, diptheriae ° corynibactrium78 90. on. ‘© AIPGME EXAMINATION ANSWERS AND EXPLANATIONS - 2005 Answer is B (Reverse transcriptase - PCR): Greenwood 16"/ 532 “Both direct and indirect diagnostic methods are available to make a laboratory diagnosis of HIV infection. Of these the most important sensitive assay is reverse transcriptase PCR for viral nucleic acid, which can detect a single copy of RNA or proviral DNA from infected cells.’ ~ Greenwood 16"/ 532. Answer is D (Trichnella spiralis): Harrisons 16/1253, 1273, 1218, 1217 Trichnella spiralis is one of the smallest nematodes, and man is an accidental host. Trichnella spiralis resides in striated muscles of the body, especially those that are constantly active and are poor in glycogen content. It is not a neuroparasite and is not found in the brain at any time during its life cycle. It does not produce any neurological ‘manifestations. Neuroparasitis nature amongst other options EB ‘Teenia sollum ‘Acanthomoeba aes, q Harrisons 16%/ 1273 Harrisons 16*/ 1218 Harrisons 1¢ + Acts as a neuroparasite by way of + These are fee living amoeba and are ‘+ These ae fee living amoeba and are cysticercosis, which results from associated with neurological manifestation associated with neurological ingestion of T. sollum eggs. ‘+ ‘Granulomatous Amoebic encephalitis’ is manifestations. ‘+ Neurocysticercosisis a ‘ manifestation ofits neuroparasitic “Primary amoebic meningoencephalitis’ is manifestation ofits neuroparasitic mature. ‘a manifestation of its neuroparastic nature + “Infection usually reaches the CNS. nature, + “Cysticerci can be found anywhere _-hematogenously from a primary focus in “Infection reaches the CNS following bbut are most commonly detected in the brain, skeletal muscle, subcutaneous tissue or eye.’ ~ Harrisons 16°/ 1273 the sinuses, skin or lungs. inthe CNS, ‘onset is insidious and the syndrome often ‘mimics a space occupying lesion, Altered ‘mental status, headache, stiff neck may be accompanied by focal findings such as ‘cranial n. palsies ataxia and hemiparesis.” = Harrisons 16"/ 1218 Answer is A (Giardia lambia): Harrisons 16"/ 1249, 1257 aspiration of water contaminated with ‘trophozoites or cysts or the inhalation of contaminated dust leading to invasion of olfactor neuroepithelium. CNS ‘manifestations include headache, fever, ‘meningism, cranial nerve palsies, seizures and coma.’ — Harrisons 16/1217 Giardia lambia is a protozoal parasite that inhabits the small intestine of humans and other mammals. Clinical ‘manifestations are seen in some but not all infected patients, and the mechanism by which Giardia produces alteration of small bowel function is not clear. Disease manifestations of giardiasis range from asymptomatic carriage to fulminant diarrhea and malabsorption. The lactose intolerance and significant malabsorption are clinical signs of the loss of brush border enzyme activities. In chronically infected symptomatic patients, the histopathological findings including flattened villi and clinical manifestations resemble those of tropical sprue and gluten sensitive enteropathy. Gastrointestinal manifestations Giazaiasig Hlookworms sear © Most infected patients are ‘Ancylostoma duodenal ¢ Adult worms in small intestine asymptomatic Necotor Americanus ae usually asymptomatic ¢ Symptomatic patients present» Most Hookworm infections are + In heavy infection particularly in with diarthea and ‘asymptomatic children a large bolus of ‘malabsorption? © Gastrointestinal manifestations entangled worms can cause include epigestie pain, inflammatory = Pain iambea, and other symptoms but + Small bowel perforation ‘malabsorption syndrome is not = Intussusception ‘associated (The major consequence of | ~_Volvulus ete. chronic hookworm infection is ‘+ Malabsorption syndrome is not progressive iron def. anemia) ‘associated Answer is B (India Ink preparation): Greenwood 16"/ 583. . neoformans is best demonstrated in CSF by direct microscopy. The capsule is seen as a clear halo around the ‘yeast cells in unstained wet preparations of CSF mixed with a drop of India ink or nigrosine. Methamine silver stain ‘would be the best choice for a tissue sample.92. [AIPGME EXAMINATION ANSWERS AND EXPLANATIONS - 2005 * 729 Laboratory diagnosis of C. neoformans Direct microscopy Serology Culture + Unstained wet preparations «The most useful serological test is LPA test Cryptococcus can be easily of CSF mixed with a drop of for detection of Lipopolysacharide antigen of cuitured from the CSF, on India ink or nigrosine ‘eyptococcus. This is highly sensitivity and _sabaroud's agar. demonstrate the capsule of specific, for diagnosis and gives better results C. neoferman's is ‘Cuneoformans as a clear than direct microscopy and culture. distinguished from other halo. Remember yeasts by: + Stain such as alcian blue» Tests for serum antibody are positive in less + ability to grow at 37°C and mucicarmine® stain the than 50% of proven cases of cryptococcal and assimilate inositol® capsular material and enable meningitis, since antibodies are neutralized + ability to hydrolyse urea ® identification of organism ‘rapidly, by the large amount of capsular + lack of fermentative and differentiation from antigen released during evolution of infection ability ® Hocapsulatum and (antibodies are not protective). Antibodies Bdermatides. may subsequently reappear, in patients after successful treatment, ‘Remember: Cryptococcus neoformans isthe only pathogenic yeast & It isa round or ovoid budding cell with a prominant polysacharide capsule @ thas four serotypes A,B,C and D.? Most infections are caused by serotypes A and D ®, which are commonly found in the excreta of wild and domestics birds e.g. pigeons.® Answer is A (IgG-1): Harrisons 16%/ 1922; Ananthnarayanan 9"/96-97 1G is the major serum Immunoglobulin (80% of serum Ig) and occurs in four subclasses. The four IgG subclasses are numbered in order of their level in serum, IgG, being found in greatest amount and IgGq the least — Harrison eG: IgGz 1G Wea IgM 1p we 15.85% TAS 5-10 03 0.019 (Least (Commonest)? concentration)? 150 160 950 175 190 (Lightest) 2 (Heaviest) 2 a Monomer ° Monomer, Pentamer? — Monomer Monomer Dimer G,GGs, Gy? (four Al, Ar None None None ij subclasses) (to subclasses) 2 5. Serumhalflife 23 (Maxhalflie)? 6 5 2.5 (Shortest)? (days) ‘Complement Classical °(G;,G;, G3) Alternate? Classical? Altemate® None. aa Alternate (G0) Confusion: Note: (Harrisons should be the preferred text) + According to Harrisons tet, IgG fixes complement by both clasical and alternate pathway, while according to Ananthnarayanal 1gG fzes complement only by the classical pathway + According to Ananthnarayanan IgD & IgM have two subclasses each while according to Harrison's they have no subclasses.IPGMEE 2005 - EXPLANA’ 730 + AIPGME EXAMINATION ANSWERS AND EXPLANATIONS - 2005 93. Answer is D (IgE): Amanthnarayanan 9/162 Type I hypersensitivity is also termed as Anaphylactic, IgE or reagin dependent hypersensitivity. Cytotrophic IgE antibodies are fixed on the surface of mast cells and basophils is sensitized individuals. When the antigen binds these cell fixed IgE antibodies, release of pharmacologically active substance occurs which produces the clinical reaction, Includes. Includes: ‘+ Local: Bezema, Hay fever, Asthma (Atopy).® «Complement mediated lysis. ‘Systemic: Anaphylaxis ‘Antibody dependent cell mediated toxicity (formerly classified as type 1).2 ‘+ Changes in cellular function (former type V).° = Increased function: Grave's disease? = Decreased function: M, Gravis? Phagocytosis.?. Examples based on type LHS ®: Examples incades: . Tenhiad Smith phenomenon:2 This is + Those with Ag on RBC. tnapiylsin pine is , gon «Piston (sms Ruse? Bll msn raion? : Demonstrate ht gk ishomesytotopic i.e, > Nemosicanenia eg with LM. nd mycopl a + Thos wih Agon Nestopis: Aalto ‘© Casoni’s test: Immediate type (IgE) H.S. + Those with Ag on platelets: eg, ITP.2 ‘Those with Ag on basement membrane: Goodpasture’s? ‘Type IIT Immune complex (IgM & IgG) 98 pete hypersensitivity (cellular immunity) a Includes Incas ‘© Local: Arthus reaction.? © Tuberculin test. ‘Systemic: Serum sickness.? Lepromin test. Examples: Contact dermatitis? = Shick’s test? ‘= Post streptococcal G.N.& Detected by RAJI Assay.? Jones-Mote reaction (cutaneous basophilic hypersensitivity). Graft rejection (chronic).2 94, Answer is D (Isograft): Ananthnarayanan 9/183 The graft in question, is from a genetically related member of the same species and hence is an Isograft. ‘Terminology of grafts: ‘Autograft Autogenous or autogenie graft ae shame oe et Sereeeteoet ie Genetically unrelated member of same species Allogeneic graf, Formerly called homograft 95. Answer is A (Severe combined immunodeficiency): Harrison 16/1942 “Patient with severe combined Immunodeficiency Disease (SCID) are deficient in an enzyme involved in purine ‘metabolism, adenosine deaminase (ADA), due to mutation in ADA gene’ ~ Harrison The most common cause of autosomal recessive severe combined immunodeficiency disease (SCID) isthe deficiency of the enzyme adenosine deaminase (ADA). Severe combined immunodeficiency: ‘* Defect lies in lymphoid stem cells, resulting in bot ~ Failure of T cells? ~ Failure of B eels? Most common form of inheritance is autosomal recessive, Deficiency of ADA leads to accumulation of deoxyadenosine & its derivatives, which are particularly toxic to immature lymphocytes, especially those of T lineage, and this may account forthe marked decrease in T lymphocyte numbers in severe cases. ‘+ Status of adenosine deaminase (ADA) in amniotic cel is helpful in prenatal diagnosis.2‘AIPGME EXAMINATION ANSWERS AND EXPLANATIONS - 2005» 731 PHARMACOLOGY 96. 97. Answer is A (is excreted mainly by the kidney): Repeat A highty ionized drug being lipid insoluble, is not reabsorbed by the tubules and is easily excreted by the kidneys a ‘+ Non ionized drugs are lipid soluble ‘+ Tonized drugs are lipid insoluble + Rapidly absorbed from stomach and intestines ‘+ Poorly absorbed from stomach and intestine + Rapidly pass across placenta + Poorly pass across placenta + Reabsorbed by renal ubules afte filtration and hence + Highly ionized drugs or polar drugs are not reabsorbed by net excretion by kidney is less the tubules and hence ae easily exereted. Plasma protein binding: ‘+ Acidic drugs bind to plasma albumin while basic drugs bind to a acid glycoprotein ‘+ Extent of binding depends on the individual compound and no generalization can be made with reference to its nization. Answer is D (Thyroxine): Ganong 21"/ 327; KDT 7°/245-252; Repeat Thyroid hormones have receptors in the nuclei and not on the surface of cells. “Thyroid hormones enter cells and binds to thyroid receptors (TR) in the nuclei” ~ Ganong Hormones and their target cells Hormones acting at cell surface Hormones acting t intracellular Receptors (Cell membrane Receptors) 1 Through cAMP second messenger g t ~ Adrenaline + TSH [ Gyioplasmic receptors Tniranuclear receptors + Glucagon + FSH (steroidal hormones) “Thyroid hormones cuneate * Glucocorticoids + Thyroxine «© Vasopressin (V3) + Mineralocorticoids . “ippahme ACTH 2 Atop Tetons releasing hormones + Estrogens | Through IP;/DAG second messenger |_| « Progestins Vasopressin (V;) + Caleitiol + Oxytocin “Through Tyrosine kinase second messenger « Insulin + Grow hormone + Prolactin Answer is C (It should be expected in anyone receiving > Smg, prednisone daily): References mentioned below Hypothalmo-pituitary axis and the adrenal gland should be suspected in ‘any person who has received > 20-25 mg/day hydrocortisone or equivalent for longer than 2-3 weeks ~ KDT 20 mg equivalent for Hydrocortisone is 5 mg of prednisolone and hence adrenal suppression should be expected in anyone receiving > 5 mg prednisolone daily. Equivalent doses: KDT rable 19.1/260 ‘Prednisolone Methylprednisole’Triametholone Paramethasone Dexamethasone Betamethasone 20mg 25mg Smg 4mg 4mg 2mg 75mg. 75mg, “Suppression of hypothalmo pituitary adrenal (HPA) axis occurs depending both on duration and dose of therapy. In time adrenal cortex atrophies and stoppage of exogenous steroid precipitated a withdrawal syndrome’ - KDT $"/265 “Any patient who has received > 20-25 mg/day hydrocortisone or equivalent for longer than 2-3 weeks should be put on scheme of gradual withdrawl’ — KDT$*/265 Prednisolone is 4 times more potent than hydrocortisone and therefore S mg prednisone is equivalent to 20 mg. Hydrocortisone. ‘Thus, suppression of HPA should be expected in any patient who has received > Smg prednisolone/day for more than 2- 3 weeks. Adrenal suppression may be associated with inhaled steroids also. “The increased systemic absorption that accompanies larger doses of inhaled steroids has been reported to produce adrenal suppression’ — Harrion 16%/1514EXAMINATION ANSWERS AND EXPLANATIONS - 2005 ‘Following cessation the stress responses may take even one year or longer to normalize. (Although it may normalize in 8 weeks. This statement can not be generalized and hence cannot be picked as the answer). “Many patients recover from corticosteroid induced HPA suppression with in several weeks to months. However in ‘some individuals, the time of recovery can be one year or longer.’ ~ Goodman & Gillman 10/1666 99, Answer is C (Adenosine Receptors): Goodman Gillman 10"/ 744; Katzung 9°/ 326 Theophylline is a competitive antagonist at adenosine receptors ~ Goodman & Gillman Effects produced by adenosine are antagonized by theophylline which blocks cell surface adenosine receptors ~ Kateung ‘Mechanism of Action of Methylxanthines (Theophylline) ‘These have two major modes of action Inhibition of PDEs ° Inhibition of cell surface receptors for adenosine (eystie nucleotide phosphodiesterase enzymes) v 4 ‘Adenosine ean act on surface receptors for adenosine and produce PDE’s catalyze breakdown of CAMP & cGMP. Thus a variety of effets such as broncho construction in asthmatics. inhibition rises concentration of cAMP & cGMP _ These effects are antagonized by theophylline which blocks the thereby increasing the signal transduction and action cell surface receptors for adenosine 100. Answer is C (Neostigmine): KDT 7°/109; Goodman Gillman 10”/ 1023; Katzung 9"/ 1045 Acetylcholine is the immediate principal modulator of gastric smooth muscle contractility and hence gastric motility. Anticholinesterase inhibitors (Neostigmine) inhibit the degradation of ACH by cholinesterase, thereby allowing ACH to ‘accumulate and enhance gastrointestinal motility. “The acetyl cholinesterase inhibitor neostigmine can enhance gastric, small intestine and colonic emptying. Intravenous neostigmine (2 mg) has enjoyed a resurgence in clinical usage for the treatment of hospitalized patients of acute colonic pseudo-obstruction resulting in prompt colonic evacuation of flatus and faeces in the majority of Patients’ — Katzung Muscarinic receptor activation Increased availability of Bethanecol and others Acetylehoinesterase [Neostigmine and others acetylcholine ink Dopamine receptor Benzimidazole derivatives Domperidone Dopamine (D,) receptor antagonism antagonists Serotonin (5-H) receptor Substituted benzamides Capri (Renzapride, ST receptor activation; modulation acopride,eabspide) 5-H, receptor antagonism; Metoclopramide S-HT, receptor activation; Dopamine (D3) receptor antagomisn (EMotitin-tikeagents® —___Macrlides i Eytrompein Moti eceptorctivation 101. Answer is B (Metoclopramide): KDT 7°664 Metoclopramide offers protection from gastric aspiration syndrome in patients with reflux by enhancing the tone of LES and speeding gastric emptying. ‘Metoclopramide isa prokinetic drug that speeds up gastric emptying by increasing gastric peristasis while relaxing the pylorus and first part off duodenum. It also increases the lower esophageal sphincter tone and opposes ‘gastroesophageal reflux. -KDT