MAY 2017 (MULTIPLE CHOICE QUESTIONS)

Anatomy 8. Which is attached most anteriorly on the intercondylar area

of tibia (area b/w medial and lateral tibial plateau):
1. Taste sensation from the tongue is/are carried by: a. Anterior cruciate ligament
a. Facial nerve b. Posterior cruciate ligament
b. Glossopharyngeal nerve c. Hypoglossal nerve c. Anterior horn of the lateral meniscus
d. Vagus nerve e. Trigeminal nerve d. Anterior horn of the medial meniscus
2. Which of the following statement(s) is/are true about e. Ligamentum patellae
phrenic nerve except:
a. It is primary motor supply to diaphragm
b. Accessory phrenic nerve joins the phrenic nerve near the Physiology
first rib
c. Formed in front of scalenus medius muscle 9. Congenital adrenal hyperplasia is due to deficiency of
d. It descends posterior to sternocleidomastoid enzyme:
e. Gives sensory supply to central tendon of diaphragm a. 3β-Hydroxysteroid dehydrogenase deficiency

e
3. True statement about shoulder joint: b. 5α Reductase
c. 17α-Hydroxylase deficiency

8/
a. Multipennate acromial fibres of deltoid are powerful
abductor d. 21-Hydroxylase deficiency
b. Axillary nerve injury has no effect on abduction e. Aromatase

h,
c. Musculotendinous cuff stabilizes shoulder joint 10. Which of the following is/are effect of increased 2,3-DPG on
d. Supraspinatus initiates abduction oxygen-hemoglobin dissociation curve:
a. ↑ed affinity of haemoglobin to oxygen
e. Trapezius and serratus anterior act synergistically in
abduction
ar b. ↓ed affinity of haemoglobin to oxygen
4. All are supplied by anterior interosseus nerve except: c. Left shift of oxygen-hemoglobin dissociation curve
ig
a.
Flexor carpi ulnaris b. Brachioradialis d. Right shift of oxygen-hemoglobin dissociation curve
c.
Abductor pollicis brevis d. Flexor pollicis longus e. No change in oxygen-hemoglobin dissociation curve
nd

e.
Flexor digitorum superficialis 11. Oxygen consumption by the heart is determined by:
5. All are true about parotid except: a. Intramyocardial tension
a. 2nd largest salivary gland b. Contractile state of the myo­cardium
ha

b. Stenson’s duct opens into the vestibule of the mouth c. Initial length of the myocardial muscle fiber
opposite 3rd upper molar d. Heart rate
e. Basal oxygen consumption of myocardium
IC

c. Divided into superficial and deep lobes by facial nerve

d. Majority of lymph nodes are embedded in deep lobe 12. True statement about male reproductive physiology:
e. Deep lobe abscess can extend into parapharyngeal space a. Sertoli cells secrete MÜllerian inhibiting substance (MIS)
6. True about epiglottis: b. Inhibin is released by sertoli cell
PG

a. Contains serous gland c. Primary spermatocyte is diploid

b. Contains mucous secreting glands d. LH and FSH are steroidal in nature
c. It is oval shaped e. Inhibin stimulates follicle-stimulating hormone (FSH)
d. Made up of elastic cartilage 13. Insulin causes intracellular shift of which of the following
e. Has bilateral lymphatic supply ion:
7. True about Thyroid gland: a. Na+ b. K+
a.
Thyroid lies in between 2 layers of deep cervical fascia c. Chloride d. Calcium
b.
Berry ligament derived from deep cervical fascia e. Bicarbonate
c.
Left recurrent laryngeal nerve is larger than right recurrent 14. Hypothalmic pituitary axis (HPA) controls all except:
laryngeal nerve a. Thyroid
d.
Superior thyroid artery runs in close relation with superior b. Parathyroid
laryngeal nerve c. Pancreas
e.
The superior parathyroid glands are usually located ventral d. Testis
to the recurrent laryngeal nerve e. Adrenals

Answer Key

1. a, b, d. 2. c. 3. a, c, d. e. 4. a, b, c, e. 5. a, b, d. 6. b, d, e. 7. a, b, c.

d.
8. 9. a, c, d. 10. b, d. 11. All (a, b, c, d, e) 12. a, b, c. 13. b, 14. b, c.
 PGI Chandigarh Self-Assessment & Review: 2017–2013

15. Stress hyperglycemia occurs due to all except: 22. Gluconeogenesis is favoured in fasting state by:
a. Increased level of ACTH a. Activation of pyruvate carboxylase by acetyl CoA
b. Increased level of Cortisol b. Increased conversion of phosphoenol pyruvate to pyruvate
c. Decreased level of norepinephrine by activation of pyruvate kinase
d. Insulin resistance c. Increased fatty acid oxidation in liver
e. Increased level of epinephrine d. Hydrolysis of fructose 1, 6-bisphosphate by fructose 1,
16. Erythropoietin is/are produced by: 6-bisphosphatase
a. Juxtaglomerular cells 23. Which is/are feature(s) of prostaglandins:
b. Interstitial cells of the peri­tubular capillary bed of the a. 20 carbon atom compound
kidneys b. 10 carbon atom compound
c. Pars recta of PCT c. Cyclopentane ring
d. Macula densa d. -OH group at 15th position
e. Mesangial cell e. Trans double bond at 10th position
17. True about carotid sinus: 24. True statement(s) about lipid digestion and absorption:
a. Chemoreceptor a. Micelles play an important role in lipids absorption
b. Present in early part of internal carotid artery b. Absorption of long-chain fatty acids is greatest in the upper
c. Has glomus cells parts of the small intestine

e
d. Barorecptor c. Bile acid has no role in fat absorption

8/
e. Supplied by glossopharyngeal nerve d. Fatty acids after absorption are reesterified to triglycerides
in the enterocytes
25. True statement are:

h,
Biochemistry a. All lipid are fat
b. Linoleic acid is essential fatty acid
18. Mechanisms for regulating enzyme activity is/are:
a. Covalent modification
ar
c. Hydrogenation converts unsaturated fatty acid to saturated
fatty acid
b. Allosteric activation
ig
c. Competitive inhibition
d. Induction of genes for enzyme synthesis
Immunogenetics &
nd

e. Repression of gene for inhibition of enzyme synthesis

19. All are true about glycosaminoglycans except: Molecular Biology
a. Protein associated with glycosaminoglycans is called core
ha

26. Which of the following is/are pyrimidine(s):

proteins
a. Adenine b. Cytosine
b. May be associated with connective tissues
c. Uracil d. Thymine
c. Highly positively charged
IC

e. Guanine
d. Negatively charged
27. True about telomerase:
e. Component of ECM
a. It has reverse transcriptase activity
20. All are true about Hexose monophosphate pathway (HMP)
b. DNA-dependent RNA polymerase
PG

except:
c. Help in DNA replication at end of lagging strand
a. Produce NADPH in oxidative phase of pathway
d. Also called terminal transferase
b. Does not produce ATP
28. True about DNA Gyrase:
c. Occurs in testes, ovaries, placenta and adrenal cortex
a. A type of topoisomerase I
d. Produces ribose 5-phosphate in oxidative phase of pathway
b. A type of topoisomerase II
e. Glucose 6-phosphatase dehydrogenase enzyme is involved
c. Act on circular DNA
21. Not useful in laboratory diagnosis of diabetic ketoacidosis
d. Overcome the problem of supercoils
(DKA):
29. Ultraviolet radiation exposure can causes DNA damage by:
a. Plasma ketones
a. Pyrimidine dimers formation
b. Blood glucose
b. DNA breakage
c. Urine ketones
c. Thymine dimer formation
d. Anion gap
d. Acetylation of DNA
e. Blood pH
e. Methylation of DNA
MCQs

Answer Key
15.
c, 16. b. 17. b, d, e. 18. All 19. c. 20. d. 21. None
22. a, c, d, 23. a, c, d. 24. a, b, d. 25. b, c. 26. b, c, d. 27. a, c, d. 28. b, c, d.

29. a, c,

4
 May  | 2017

30. Post-translation modification of protein includes all except: 37. Newer inclusion in 2015 WHO classification of Squamous
a. Removal of peptide cell carcinoma of lung include(s):
b. 5’ capping a. Clear cell variant
c. Intein splicing b. Papillary cell variant
d. Protein folding c. Adenocarcinoma variant
e. Covalent modification d. Nonkeratinizing variant
31. Which of the following is not true about transcription: e. Lymphoepithelioma-like carcinoma
a. Synthesis of precursors for the large and small ribosomal 38. True about RAS oncogene:
RNAs a. Tyrosine kinase has role in RAS activation
b. Formation of tRNA transcript b. Most common form of oncogene in human tumors
c. RNA polymerase II is responsible for the synthesis of c. It has an intrinsic GTPase activity
precursors for the large ribosomal RNAs d. Mutation may result in carcinomatous growth
d. RNA polymerase I is responsible for the synthesis small e. Belongs to growth factor category of oncogene
ribosomal RNAs 39. Which is/are not tumor suppressor gene(s):
e. Binding of RNA polymerase on DNA a. TP53 b. RB
c. CD95 d. SKT11
32. True about DNA photolyase:
e. RAS
a. Repair damage caused by UV light

e
40. Which of the following dyad of disease and inheritance
b. Found only in human

8/
pattern is/are true:
c. Use visible light
a. Sickle cell anaemia - autosomal recessive
d. Breaks pyrimidine dimer
b. Duchene muscle dystrophy- X-linked dominant

h,
c. Vit D resistant rickets- X-linked dominant
d. Achondroplasia – autosomal dominant
Pathology ar e. Osteogenesis Imperfecta - autosomal recessive
33. PAX5 is/are marker for: 41. True about Autosomal recessive polycystic kidney disease
a. Acute myeloid leukemia (ARPKD)
ig
b. T-cell lymphomas a. Can be diagnosed in utero by USG
c. Anaplastic large cell lymphoma b. Hypertension develops in late stages of the disease
nd

d. Hodgkin’s lymphoma c. May proceed to renal failure before preschool age

e. B-Lymphoblastic lymphoma d. Enlargement of kidney
e. Hematuria is early feature
ha

34. Which of the following is/are associated with synovial cell

sarcoma: 42. Multiple myeloma may be associated with:
a. Translocation (9;22) (q34;q11) a. Fanconi’s syndrome
IC

b. SS18-SSX4 fusion genes b. Amyloidosis

c. Translocation t (X;18) (p11;q11) c. Mixed cryoglobinemia
d. SS18-SSX1 fusion genes d. Cast nephropathy
35. True about Dubin-Johnson syndrome: e. Interstitial nephritis
PG

a. ↑ed conjugated bilirubin 43. True statement about primary myelofibrosis:

b. Usually associated with increased AST and ALT a. Hepatomegaly is the most common manifestation
c. Mutation in Uridine diphosphate-glucuronyltransferase b. Dry tap on bone marrow aspiration
peptide A1 c. Only potentially curative treatment is allogeneic stem cell
d. Decreased biliary excretion of conjugated bilirubin transplantation
e. Autosomal dominant inheritance d. Splenomegaly is almost invariably present
36. Tumor marker for lung adenocarcinoma is/are: e. Myeloblasts may be seen in peripheral blood
a. Positive for cytokeratin 5 44. Which of the following can cause pulmonary embolism:
b. Positive for cytokeratin 7 a. Pregnancy
c. Positive for cytokeratin 20 b. OCP uses
d. Transthyretin (TTR) mutation c. Mitral regurgitation
e. EGFR mutation d. Left ventricular failure
e. Excessive unaccustomed exercise
MCQs

Answer Key
30.
b. 31. c, d. 32. a, c, d. 33. d, e. 34. b, c, d. 35. a, d. 36. b, e.
37. d. 38. a, b, c, d. 39. c, e. 40. a, c, d. 41. a, b, c, d. 42. All (a, b, c, d, e) 43. b, c, d, e.

44. a, b, d, e.

5
 MAY 2017  (ANSWERS & EXPLANATIONS)
Anatomy •• It passes in front of the root of the lung (left phrenic— of left
lung; right phrenic- of right lung).
•• The phernic nerve is a mixed nerve that provides the sole
1. Ans:   a. Facial nerve, b. Glossopharyngeal nerve motor supply to the diaphragm.
d. Vagus nerve •• It also send sensory branches to the pericardium, the
[Ref: BDC 7th/ Vol.III 278-79] mediastinal parietal pleura, and the pleura and peritoneum
“Hypoglossal nerve: It is motor supply to all intrinsic and covering the upper and lower surfaces of the central part of
extrinsic muscle of tongue except palatoglossus (supplied by the diaphragm.
•• “Sensory fibres from the phrenic nerve supply the central
the cranial root of the accessory nerve through the pharyngeal
plexus)- BDC 7th/ Vol.III 278 part of the diaphragm, including the surrounding pleura
Chorda tympani is a branch of facial nerve (BDC 7th/ Vol.IV 71) and peritoneum. The nerve also supplies sensation
Lingual nerve is branch of mandibular division of trigeminal to the mediastinal pleura and the pericardium”-
nerve-Snell 9th/625 teachmeanatomy.info
“The phrenic nerves contain motor, sensory, and sympathetic

e
Table (BDC 7th/ Vol.III 279): Comparison of the parts of the tongue nerve fibers. These nerves provide the only motor supply to
the diaphragm as well as sensation to the central tendon

8/
Anterior two- Posterior one- Posteriormost (except the most peripheral diaphragm, which is supplied by
thirds third part and
intercostal nerves). In the thorax, each phrenic nerve supplies
vallecula
the mediastinal pleura and pericardium”-wiki

h,
Situation Lies in mouth Oropharynx Oropharynx
Phrenic Nerve
cavity ar –– Gray’s 40th/456-57
Structure Contains Contains —
•• The phrenic nerve arises chiefly from the fourth cervical
papillae lymphoid tissue
ventral ramus, but also has contributions from the third and
ig
Function Chewing Deglutition Deglutition fifth.
Sensory •• It is formed at the upper part of the lateral border of
nd

Lingual (post- Glossopharyn- Internal laryngeal

nerve trematic geal (nerve of branch of vagus scalenus anterior and descends almost vertically across its
branch of 1st 3rd arch) (nerve of 4th anterior surface behind the prevertebral fascia.
arch) arch) •• It descends posterior to sternocleidomastoid, the interior
ha

belly of omohyoid (near its intermediate tendon), the

Sensation of Chorda Glossopharyn- Internal
taste tympani geal including laryngeal branch internal jugular vein, transverse cervical and suprascapular
arteries and, on the left, the thoracic duct.
IC

except the vallate pa- of vagus

circumvallate pillae •• At the root of the neck, it runs anterior to the second part
papillae of the subclavian artery, from which it is separated by the
(pre-trematic scalenus anterior (some accounts state that on the left side
PG

branch of 1st the nerve passes anteriror to the first part of the subclavian
arch) artery), posterior to the subclavian vein.
•• The phrenic nerve enters the thorax by crossing medially in
Develop- Lingual Third arch Fourth arch
ment of swellings which forms which forms front of the internal thoracic artery.
epithelium of 1st arch. large ventral small dorsal part Accessory phrenic nerve
from endo- Tuberculum part of of hypobranchial –– Gray’s 40th/456
derm impar hypobranchial eminence
•• The accessory phrenic nerve is composed of fibres from the
which soon eminence
disappears
fifth cervical ventral ramus which run in a branch of the
nerve to subclavius.
2. Ans:   c.  Formed in front of scalenus medius muscle •• This lies lateral to the phrenic nerve and descends posterior
(occasionally anterior) to the subclavian vein.
[Ref: BDC 7th/ Vol II 363-64; Moore 2nd/105-06; Gray’s 40th/456-57, •• The accessory phrenic nerve usually joins the phrenic
1010; Snell’s 9th/618]
nerve near the first rib, but may not do so until near the
Phrenic Nerve pulmonary hilum or beyond.
–– Snell’s 9th/618, 99 •• The accessory phrenic nerve may be derived from the fourth
•• The phrenic nerve arises from C3-5 nerves of the cervical or sixth cervical ventral rami or from the ansa cervicalis.
plexus.
•• It run vertically downward across the front of the scalenus 3. Ans:  a. Multipennate acromial ...c. Musculotendinous cuff
anterior muscle and enter the thorax by passing in front of ... d. Supraspinatus initiates... e. Trapezius and serratus
the subclavian artery. anterior ...
 May  | 2017

[Ref: BDC 7th/Vol. I 70, 73, 77; Snell 9th/364-65; Essential Anatomy by 5. Ans:   a. 2nd largest salivary gland, b. Stenson’s duct opens
Moore 2nd/484; Gray’s 40th/812] into the vestibule of the mouth..., d. Majority of lymph
“The conventional view is that supraspinatus initiates abduction nodes are embedded in deep lobe
of shoulder and assists deltoid in abduction thereafter. However, [Ref: BDC 7th/ Vol. III 108-13; Snell 9th/630-32; Essential Anatomy by
there is evidence that both supraspinatus and deltoid are involved Moore 2nd/954-55; Gray’s 40th/495-97]
throughout the range of abduction, including the initiation of the “The facial nerve divides the gland into superficial and deep
movement” (Gray’s 40th/812) lobes”- Snell 9th/630
“The multipennate acromial fibres are powerful abductors of “Facial layer is very thick superficially but very thin on the
arm at the shoulder joint from beginning to 900. A multipennate deep side of the parotid gland where parotid abscess can burst
arrangement allows a large number of muscle fibres to be packed to form a parapharyngeal abscess and thence spread to the
into a relatively small volume. As the strength of contraction of a mediastinum”-P.L.Dingra 6th/263
muscle is proportional to the number of muscle fibres present in
it (not on their length), a multipennate muscle is much stronger Parotid Gland
than other muscles having the same volume” (BDC 7th/ Vol. I –– BDC 7th/ Vol. III 108-13
70-71) •• It is the largest of salivary glands.
“Axillary nerve damage: Deltoid is paralyzed, with loss of the •• Stenson’s duct opens into the vestibule of the mouth opposite
power of abduction up to 90° at the shoulder, rounded contour of the crown of the upper second molar teeth

e
shoulder is lost and there is sensory loss over the lower half of the •• “Superficial surface of parotid is covered with a few deep

8/
deltoid in a badge-like area called regimental badge” (BDC 7th/ parotid lymph nodes embedded in the glans”- BDC 7th/
Vol. I 72-73) Vol. III 110
“Musculotendinous cuff of the shoulder or rotator cuff gives •• Facial nerve lies in relation to isthmus of the gland which

h,
strength to the capsule of shoulder joint all around except separates large superficial part from small deep part
inferiorly” (BDC 7th/ Vol. I 74) ar of the gland. Facial nerve divides into two branches—
“Trapezius upper and lower fibres act with serratus anterior to temporofacial and cervicofacial nerve”- BDC 7th/ Vol. III
rotate the scapula forwards round the chest wall thus playing an 111
important role in abduction of the arm beyond 90°” (BDC 7th/
ig
–– Gray’s 40th/495-97
Vol. I 64, 105) •• The paired parotid glands are the largest of the salivary
The deltoid originates in three distinct sets of fibers, often re-
nd

glands.
ferred to as “heads” •• The gland also projects forwards onto the surface of mas-
•• The anterior or clavicular fibers assist Pectoralis Major to seter.
ha

flex the shoulder. •• Lymph nodes occur in the skin overlying the parotid gland
•• The lateral fibers or acromial fibers perform basic shoulder (preauricular nodes) and in the substance of the gland.
abduction when the shoulder is internally rotated, and There are usually 10 lymph nodes present in the gland, the
IC

perform shoulder transverse abduction when the shoulder majority lie in the superficial part of the gland above the
is externally rotated. plane related to the facial nerve. Lymph from the parotid
•• The posterior fibers or spinal fibers assist Latissimus Dorsi gland drains to the upper deep cervical lymph nodes.
PG

to extend the shoulder. Parotid: The parotid lymph nodes are a small group of nodes
located superficially to the parotid gland. They collect lymph
4. Ans:   a. Flexor carpi ulnaris..., b. Brachioradialis, c. Abductor from the nose, the nasal cavity, the external acoustic meatus, the
pollicis brevis, e. Flexor digitorum superficialis tympanic cavity and the lateral borders of the orbit. There are
[Ref: BDC 7th/ Vol. I 114] also parotid lymph nodes deep to the parotid gland that drain
the nasal cavities and the nasopharynx”-teachmeanatomy.info
Anterior interosseous nerve
–– BDC 7th/ Vol. I 114, 110 6. Ans:   b. Contains mucous secreting glands, d. Made up of
•• Branch of median nerve elastic cartilage, e. Has bilateral lymphatic supply
•• Supplies- Flexor pollicis longus, Flexor digitorum [Ref: BDC 7th/ Vol. III 264; Snell’s 8th/ 802; Moore 2nd/628; Gray’s 40th/
profundus (lateral half) and pronator quadratus 577-78, 588; Dhingra 6th/283-85; H and N Cancer by Louis B Harrison
•• Also supplies- distal radioulnar and wrist joints 3rd/368; H and N Surgery by Robert Satalof 1st /693]
Muscles and their Supply
EPIGLOTTIS/EPIGLOTTIC CARTILAGE
“Flexor carpi ulnaris-Ulnar nerve”- BDC 7th/ Vol. I 108
“Flexor digitorum superficialis- median nerve”- BDC 7th/ Vol. –– BDC 7th/ Vol. III 264
I 108 •• The epiglottis is a leaf-shaped structure.
“Abductor pollicis brevis-median nerve”- BDC 7th/ Vol. I 124 •• It is a flap that is made of elastic cartilage tissue covered with
“Brachioradialis-radial nerve”- BDC 7th/ Vol. I 101 a mucous membrane, attached to the entrance of the larynx.
•• The epiglottis is one of nine cartilaginous structures that Answers
&
make up the larynx (voice box). While one is breathing, it Explanations
lies completely within the pharynx. When one is swallowing

19
 PGI Chandigarh Self-Assessment & Review: 2017–2013

it serves as part of the anterior of the larynx. deep cervical fascia. It is thin along the posterior border of
•• The epiglottis has two surfaces, a lingual and a laryngeal the lobes, but thick on the inner surface of the gland where it
surface, related to the oral cavity and the larynx respectively forms a suspensory ligament (of berry), which connects the
•• The entire lingual surface and the apical portion of the lobe to the cricoid cartilage”- BDC 7th/Vol III 145
laryngeal surface (since it is vulnerable to abrasion due to “The course of the recurrent laryngeal nerves on the right and
its relation to the digestive tract) are covered by a stratified left sides is different. The left RLN is longer than the right,
squamous non-keratinized epithelium. because it crosses under the arch of the aorta at the ligamentum
•• The rest of the laryngeal surface on the other hand, which arteriosum. The lower origin and consequently, a longer course
is in relation to the respiratory system, has respiratory of the left RLN makes it more vulnerable to injury than the right
epithelium: pseudostratified, ciliated columnar cells and RLN.”- emedicine.medscape.com; BDC 7th/Vol IV 83
mucus secreting Goblet cells. “Superior thyroid artery: It runs downwards and forwards in
Lymphatic Drainage intimate relation to external laryngeal nerve”- BDC 7th/Vol III
147
–– Gray’s 40th/ 588; Moore 2nd/628
“About 85% of individuals have four parathyroid glands that can
•• The vocal cords, with their firmly bound mucosa and
be found within 1 cm of the junction of the inferior thyroid artery
paucity of lymphatics, provide a clear demarcation between
and the RLN. The superior glands are usually located dorsal to
the upper and lower areas of the larynx.
the RLN, whereas the inferior glands are usually found ventral

e
•• Above the vocal cords, the lymph vessels draining the
to the RLN”-Schwartz 10th/1523-
supraglottic part of the larynx accompany the superior

8/
laryngeal artery, pierce the thyrohyoid membrane, and end 8. Ans:  d. Anterior horn of the medial meniscus
in the upper deep cervical lymph nodes, often bilaterally.
The supraglottic lymphatics also communicate with those at [Ref: BDC 7th/ Vol. II 26-27; Snell’s 8th/470; Gray’s 40th/1397]

h,
the base of the tongue. (Note: Epiglottis is supraglottic part Attachments on the intercondylar area (b/w medial and lateral
of larynx- Dhingra 6th/283) ar tibial plateaus): Attachment from before backward BDC 7th/
•• Below the vocal cords, some of the lymph vessels pass Vol. II 26-27
through the conus elasticus to reach the prelaryngeal 1. Anterior horn of the medial meniscus
ig
(Delphian) and/or pretracheal and paratracheal lymph 2. Anterior cruciate ligament
nodes, while others accompany the inferior laryngeal artery 3. Anterior horn of the lateral meniscus
nd

and join the lower deep cervical nodes. 4. Posterior horn of the lateral meniscus
•• “The supraglottis has extensive bilateral network of 5. Posterior horn of the medial meniscus
lymphatics that result in frequent regional metastases”-H 6. Posterior cruciate ligament
ha

and N Cancer by Louis B Harrison 3rd/368 Intercondylar Area

“Unlike the other two anatomic sites (glottis and subglottis) of
–– Gray’s 40th/1397
the larynx, the supraglottis is formed without midline union
IC

•• The rough-surfaced area between the condylar articular

and consequently has bilateral lymphatic drainage”-H and N
surfaces is narrowest centrally where there is an
Surgery by Robert Satalof 1st /693
intercondylar eminence, the edges of which project slightly
proximally as the lateral and medial intercondylar tubercles.
PG

7. Ans:   a. Thyroid lies in between 2 layers of deep cervical

fascia, b. Berry ligament derived from deep cervical •• The anterior intercondylar area is widest anteriorly.
fascia, c. Left recurrent laryngeal nerve is larger than Anteromedially, anterior to the medial articular surface,
right recurrent laryngeal nerve a depression marks the site of attachment of the anterior
horn of the medial meniscus. Behind this a smooth area
[Ref: L and B 26th/742; Schwartz 10th/1523] receives the anterior cruciate ligament.
Thyroid Gland •• The anterior horn of the lateral meniscus is attached
anterior to the intercondylar eminence, lateral to the
–– Schwartz 10th/1523-25
anterior cruciate ligament.
•• The thyroid gland is enveloped by a loosely connecting
•• The posterior horn of the lateral meniscus is attached to
fascia that is formed from the partition of the deep cervical
the posterior slope of the intercondylar area. The posterior
fascia into anterior and posterior divisions (false capsule)
intercondylar area inclines down and backwards behind the
•• The true capsule of the thyroid is a thin, densely adherent
posterior horn of the lateral meniscus.
fibrous layer that sends out septa that invaginate into the
•• A depression behind the base of the medial intercondylar
gland, forming pseudolobules.
tubercle is for the posterior horn of the medial meniscus.
•• The thyroid capsule is condensed into the posterior
The rest of the area is smooth and provides attachment for
suspensory or Berry’s ligament near the cricoid cartilage
the posterior cruciate ligament, spreading back to a ridge to
and upper tracheal rings.
which the capsule is attached
•• “The false capsule is derived from the pretracheal layer of the
Answers
&
Explanations

20
 May  | 2017

Fig.: (BDC 7th/ Vol. II 26-27): Superior view of the upper end of the right tibia

Physiology

e
8/
9. Ans:  a. 3β-Hydroxysteroid dehydrogenase deficiency, c. 17α-Hydroxylase deficiency, d.21-Hydroxylase deficiency
[Ref: Davison 22nd/782; Harrison 19th/2327-28]

h,
Table (Harrison 19th/2328): Variants of Congenital Adrenal Hyperplasia

Variant Gene
ar
Impact on Steroid Synthesis
21-Hydroxylase deficiency (21OHD) CYP21A2  Glucocorticoid deficiency, mineralocorticoid deficiency, adrenal
ig
androgen excess
11β-Hydroxylase deficiency (11OHD) CYP11B1  Glucocorticoid deficiency, mineralocorticoid excess, adrenal
nd

androgen excess
17α-Hydroxylase deficiency (17OHD) CYP17A1  (Glucocorticoid deficiency), mineralocorticoid excess, androgen
deficiency
ha

3β-Hydroxysteroid dehydrogenase HSD3B2  Glucocorticoid deficiency, (mineralocorticoid deficiency), adrenal

deficiency (3bHSDD) androgen excess
IC

P450 oxidoreductase deficiency POR  Glucocorticoid deficiency, (mineralocorticoid excess), androgen

(ORD) deficiency, skeletal malformations
PG

“Aromatase deficiency and 17α-hydroxylase deficiency are associated with decreased estrogen and elevated gonadotropins and with
hyperandrogenism and hypertension, respectively”-Harrison 19th/337
Testosterone can be converted to the more potent DHT by 5α-reductase, or it can be aromatized to estradiol by CYP19 (aromatase)”-
Harrison 19th/2358

Congenital Adrenal Hyperplasia

–– Harrison 19th/2327-28
•• Congenital adrenal hyperplasia (CAH) is caused by mutations in genes encoding steroidogenic enzymes involved in glucocorticoid
synthesis (CYP21A2, CYP17A1, HSD3B2, CYP11B1) or in the cofactor enzyme P450 oxidoreductase that serves as an electron donor
to CYP21A2 and CYP17A1
•• “The most common enzyme defect is 21-hydroxylase deficiency”-Davison 22nd/782
•• Invariably, patients affected by CAH exhibit glucocorticoid deficiency. Depending on the exact step of enzymatic block, they may also
have excess production of mineralocorticoids or deficient production of sex steroids
•• The diagnosis of CAH is readily established by measurement of the steroids accumulating before the distinct enzymatic block, either
in serum or in urine, preferably by the use of mass spectrometry–based assays
•• Mutations in CYP21A2 are the most prevalent cause of CAH, responsible for 90–95% of cases. 21-Hydroxylase deficiency disrupts
glucocorticoid and mineralocorticoid synthesis
Answers
&
Explanations

21
 PGI Chandigarh Self-Assessment & Review: 2017–2013

some conditions, the BPG mechanism can be important for

adaptation to hypoxia, especially to hypoxia caused by poor
tissue blood flow.
•• Red cell 2,3-DPG concentration is increased in ane­mia and
in a variety of diseases in which there is chronic hypoxia.
This facilitates the delivery of O2 to the tissues by raising
the Po2 at which O2 is released in peripheral capil­laries.
•• In banked blood that is stored, the 2, 3-DPG level falls and
the ability of this blood to release O2 to the tissues is reduced.

Hb-O2 dissociation curve

Left shifting Right Shifting
•• ↓2, 3-BPG •• ↑2, 3-BPG
•• Alkalosis •• Acidosis
•• Hypothermia •• Hyperthermia

e
•• Foetal Hb •• High altitude

8/
•• Hypocarbia •• Exercise
•• Stored blood •• Hypercarbia

h,
•• Hb Chesapeake •• Anaemia
ar •• Hb Ranier •• Sickle cell anaemia
•• HbM
Fig. (Harrison 19th/2359): Androgen metabolism and actions. SHBG,
sex hormone–binding globulin. •• Diabetic Ketoacidosis
ig
•• Thyroid hormone
10. Ans:  b. ↑ed affinity of haemoglobin to oxygen, d. Right shift
nd

•• Growth hormone
of oxygen-hemoglobin dissociation curve
•• Androgen
[Ref: Ganong 25th/640-41; Guyton 12th/356-57; A K Jain 6th/430]
•• Diseases causing chronic
ha

“All the factors which shift the oxygen-hemoglobin dissociation hypoxia

curve to right, decreases the affinity of haemoglobin for
oxygen, therefore, a higher pO2 is required for Hb to bind a
IC

given amount of oxygen”- A K Jain 6th/430

2,3-DPG and oxygen-hemoglobin dissociation curve Ganong
25th/641
PG

•• 2, 3-DPG is very plentiful in red cells. It is formed from

3-phosphoglyceraldehyde, which is a product of glycolysis
via the Embden-Meyerhof pathway.
•• It is a highly charged anion that binds to the β chains of
deoxyhemoglobin. One mole of deoxyhemoglobin binds 1
mol of 2, 3-DPG.
•• An increase in the concentration of 2,3-DPG shifts the
reaction to the right, causing more O2 to be liberated.
Effect of BPG to Cause Rightward Shift of the Oxygen-
Hemoglobin Dissociation Curve
–– Guyton 12th/357
•• The normal BPG in the blood keeps the oxygen-hemoglobin
dissociation curve shifted slightly to the right all the time.
•• In hypoxic conditions that last longer than a few hours, the
quantity of BPG in the blood increases considerably, thus
shifting the oxygen-hemoglobin dissociation curve even
farther to the right.
Fig.: Shift of the oxygen-hemoglobin dissociation curve to the right
Answers •• This causes oxygen to be released to the tissues at as much
caused by an increase in hydrogen ion concentration (decrease in pH).
&
Explanations
as 10 mm Hg higher tissue oxygen pressure than would BPG, 2,3-biphosphoglycerate.
be the case without this increased BPG. Therefore, under

22
 May  | 2017

11. Ans:  All (a, b, c, d, e) •• The greater the contractility, the more oxygen the
myocardium consumes. Faster, more powerful contractions
[Ref: Ganong 25th/550; Guyton 12th/216-17]
(increased dP/dT) requires more energy.
“Frank-Starling law: The force of muscle contraction is directly •• Increased HR leads to increased myocardial O2 consump-
proportional to the initial length of the muscle fiber, within tion. Heart rate is extremely important in that it influences
physiological limits. In the heart, the initial length is at the end not only supply, but demand as well, as the myocardium is
of diastole”- Guyton 12th/216 perfused during diastole.
“Increasing preload (e.g., ventricular end-diastolic volume) •• In the unanesthetized individual, myocardial consumption
also increases myocardial oxygen consumption; however, the is the main determinant of myocardial supply.
increase is much less than what might be expected because of
the LaPlace relationship”- www.cvphysiology.com 12. Ans:   a. Sertoli cells secrete Mullerian inhibiting substance
(MIS), b. Inhibin is released by sertoli cell, c. Primary
OXYGEN CONSUMPTION BY THE HEART
spermatocyte is diploid
–– Ganong 25th/550
•• Basal O2 consumption by the myocardium is about 2 mL/ [Ref: Ganong 25th/409; Guyton 12th/537; A K Jain 6th/]
100 g/min. O2 consumption by the beating heart is about 9 FSH and LH are peptide in nature- Guyton 12th/537
mL/100 g/min at rest. Increases occur during exercise and “The Sertoli cells secrete androgen-binding protein (ABP),
in a number of different states. inhibin, and Mullerian inhibiting substance (MIS). They

e
•• O2 consumption by the heart is determined primarily by the do not syn­ thesize androgens, but they contain aromatase

8/
intramyocardial tension, the contractile state of the myo­ (CYP19), the enzyme responsible for conversion of androgens
cardium, and the heart rate. to estrogens, and they can produce estrogens. ABP probably
•• Ventricular work per beat corre­lates with O2 consumption. functions to maintain a high, stable supply of androgen in the

h,
The work is the product of stroke volume and mean arterial tubular fluid. Inhibin inhibits follicle-stimulating hormone
pressure in the pulmonary artery or the aorta (for the right ar (FSH) secretion”- Ganong 25th/419
and left ventricle, respectively). Spermatogenesis
•• Because aortic pressure is seven times greater than –– Ganong 25th/418
ig
pulmonary artery pressure, the stroke work of the left •• Spermatogonia, the primitive germ cells next to the basal
ventricle is approximately seven times the stroke work of the lamina of the seminiferous tubules, mature into primary
nd

right. spermatocytes.This process begins during ado­ lescence.

•• In theory, a 25% increase in stroke volume without a change The primary spermatocytes undergo meiotic division,
in arterial pressure should produce the same increase in O2 reducing the number of chromosomes.
ha

consumption as a 25% increase in arterial pressure without •• In this two-stage pro­cess, they divide into secondary
a change in stroke vol­ume. However, for reasons that are spermatocytes and then into spermatids, which contain
incompletely understood, pressure work produces a greater the haploid number of 23 chromo­somes. The spermatids
IC

increase in O2 consump­tion than volume work. mature into spermatozoa (sperm).

•• In other words, an increase in after­load causes a greater
increase in cardiac O2 consumption than does an increase
PG

in preload. This is why angina pectoris due to deficient

delivery of O2 to the myocardium is more com­mon in aortic
stenosis than in aortic regurgitation. In aortic stenosis,
intraventricular pressure must be increased to force blood
through the stenotic valve, whereas in aortic regurgita­tion,
an increase in stroke volume with little change in aortic
impedance occurs.
Chemical Energy Required for Cardiac Contraction:
Oxygen Utilization by the Heart
–– Guyton 12th/204-05
•• Oxygen consumption has also been shown to be nearly
proportional to the tension that occurs in the heart muscle
during contraction multiplied by the duration of time that
the contraction persists, called the tension-time index.
•• Because tension is high when systolic pressure is high,
correspondingly more oxygen is used.
Myocardial O2 Consumption
–– determinants www.openanesthesia.or Answers
Fig.: (Ganong 25th/409): Postulated interrelationships between the &
•• The amount of oxygen consumed is determined by the basal hypothalamus, anterior pituitary, and testes. Solid arrows indicate Explanations
O2 consumption, wall tension, contractility and heart rate. excitatory effects; dashed arrows indicate inhibitory effects

23
 PGI Chandigarh Self-Assessment & Review: 2017–2013

13. Ans:  b. K+
[Ref: Ganong 25th/433-34; Guyton 12th/613; A K Jain 6th/748]

Relation to Potassium
–– Ganong 25th/433-34; Guyton 12th/613
•• Insulin causes K+ to enter cells, with a resultant lowering of the extracellular K+ concentration.
•• Infusions of insulin and glucose significantly lower the plasma K+ level in normal individuals and are very effective for the temporary
relief of hyperkalemia in patients with renal failure.
•• Hypokalemia often develops when patients with diabetic acidosis are treated with insulin.
•• The reason for the intracellular migra­tion of K+ is still uncertain. However, insulin increases the activity of Na, K ATPase in cell
membranes, so that more K+ is pumped into cells.

14. Ans:  b. Parathyroid, c. Pancreas

[Ref: Ganong 25th/308-14; Harrison 19th/401e-2]

e
8/
h,
ar
ig
nd
ha
IC
PG

Answers
& Fig.: (Harrison 19th/401e-2): Diagram of pituitary axes. Hypothalamic hormones regulate anterior pituitary trophic hormones that in turn
Explanations determine target gland secretion. Peripheral hormones feedback to regulate hypothalamic and pituitary hormones.

24
 May  | 2017

Hypophysiotropic Hormones Function Afferents from Integrating

–– Ganong 25th/314 Areas
•• There are six established hypothalamic releasing and Growth hormones Unknown receptors Periventricular
inhibiting hormones: corticotropin-releasing hormone via somatostatin and nucleus,
(CRH); thyrotropin-releasing hormone (TRH); GRH arcuate nucleus
growth hormone–releasing hormone (GRH); growth
hormone–inhibiting hormone (GIH, now generally called 15. Ans:   c. Decreased level of norepinephrine
somatostatin); luteinizing hormone–releasing hormone
(LHRH, now generally known as gonadotropin-releasing [Ref: Ganong 25th/364; Guyton 12th/598,556; Schwartz 9th/17-20; A K
Jain 6th/606; L and B 26th/4-9; CSDT 11th/103-05]
hormone [GnRH]); and prolactin-inhibiting hormone
(PIH). Hormone which increases blood sugar level: epinephrine,
•• In addi­ tion, hypothalamic extracts contain prolactin- glucagon, GH, cortisol”- A K Jain 6th/606
ity, and a prolactin-releasing hormone
releasing activ­ “Following injury, neural impulses carried via spinothalamic
(PRH) has been postulated to exist. pathways activate the brain stem and thalamic and cortical
•• GnRH stimulates the secretion of FSH as well as that of LH, centers, which stimulate the hypothalamus. Hypothalamic
and it seems unlikely that a separate FSH-releasing hor­ stimulation triggers combined neural and endocrine discharges.
mone exists. Norepinephrine is released from sympathetic nerve endings,

e
epinephrine from the adrenal medulla, aldosterone from the
Table ( Ganong 25th/309): Summary of principal hypothalamic

8/
adrenal cortex, ADH from the posterior pituitary, glucagon
regulatory mechanisms from the pancreas, and ACTH, TSH, and growth hormone from
Function Afferents from Integrating
the anterior pituitary. These hormones produce secondary

h,
Areas elevations of cortisol, thyroid hormone, and somatomedins”-
CSDT 11th/104
Neuroendocrine control of:
ar Mediators of the Metabolic Response to Injury
Catecholamines Limbic areas concerned Dorsal and
with emotion posterior –– L and B 26th/4-9
ig
hypothalamus •• The classical neuroendocrine pathways of the stress
response consist of afferent nociceptive neurones, the
nd

Vasopressin Osmoreceptors, “volume Supraoptic and

spinal cord, thalamus, hypothalamus and pituitary .
receptors”, others paraventricular
nuclei •• Corticotrophinreleasing factor (CRF) released from the
hypothalamus increases adrenocorticotrophic hormone
ha

Oxytocin Touch receptors in breast, Supraoptic and (ACTH) release from the anterior pituitary.
uterus, genitalia paraventricular
•• ACTH then acts on the adrenal to increase the secretion
nuclei
of cortisol. Hypothalamic activation of the sympathetic
IC

Thyroid-stimulating Temperature receptors in Paraventricular nervous system causes release of adrenalin and also
hormone infants, perhaps others nuclei and stimulates release of glucagon.
(thyrotropin, TSH) neighboring
•• There are, however, many other players, including alterations
PG

via TRH areas

in insulin release and sensitivity, hypersecretion of prolactin
Adranocoriticotropic Limbic system (emotional Paraventricular and growth hormone (GH) in the presence of low circulatory
hormone (ACTH) and stimuli); reticular nuclei insulin-like growth factor-1 (IGF-1) and inactivation of
β -lipotropin (β-LPH) formation (“systemic” peripheral thyroid hormones and gonadal function.
via CRH stimuli); Hypothalamic
•• Of note, GH has direct lipolytic, insulin-antagonising and
and anterior pituitary cells
sensitive to circulating proinflammatory properties
blood cortisol level; Insulin Resistance
suprachiasmatic nuclei –– L and B 26th/9
(diurnal rhythm)
•• Following surgery or trauma, postoperative hyperglycae-
Follicle-stimulating Hypothalamic cells Preoptic area; mia develops as a result of increased glucose production
hormone (FSH) and sensitive to estrogens, other areas combined with decreased glucose uptake in peripheral
luteinizing hormone eyes, touch receptors in tissues. Decreased glucose uptake is a result of insulin re-
(LH) via GnRH skin and genitalia or reflex sistance which is transiently induced within the stressed
ovulating species
patient.
Prolactin via PIH and Touch receptors in Arcuate •• Suggested mechanisms for this phenomenon include the
PRH breasts, other unknown nucleus; action of proinflammatory cytokines and the decreased
receptors other areas responsiveness of insulin-regulated glucose transporter
(hypothalamus
proteins. The degree of insulin resistance is proportional to Answers
inhibits &
secretion) the magnitude of the injurious process. Explanations

25
 PGI Chandigarh Self-Assessment & Review: 2017–2013

e
8/
h,
ar
ig
Fig.: (L and B 26th/5): The integrated response to surgical injury
nd

(first 24-48hr)
Insulin
ha

–– Schwartz 9th/20
•• Hyperglycemia and insulin resistance are hallmarks of injury and critical illness due to the catabolic effects of circulating mediators,
including catecholamines, cortisol, glucagon, and GH. The increase in these circulating proglycemic factors, particularly epinephrine,
IC

induces glycogenolysis, lipolysis, and increased lactate production independent of available oxygen in a process that is termed “aerobic
glycolysis.”
•• Although there is an increase in insulin production at the same time, severe stress is frequently associated with insulin resistance,
PG

leading to decreased glucose uptake in the liver and the periphery contributing to acute hyperglycemia.
Catecholamines
–– Schwartz 9th/20
•• The hypermetabolic state observed following severe injury is attributed to activation of the adrenergic system. Both norepinephrine
(NE) and epinephrine (EPI) are increased three- to fourfold in plasma immediately following injury, with elevations lasting 24 to 48
hours before returning toward baseline levels.
•• In the liver, EPI promotes glycogenolysis, gluconeogenesis, lipolysis, and ketogenesis. It also causes decreased insulin release, but
increases glucagon secretion. Peripherally, EPI increases lipolysis in adipose tissues and induces insulin resistance in skeletal muscle.
These collectively manifest as stress-induced hyperglycemia, not unlike the effects of cortisol on blood sugar.

16. Ans:  b. Interstitial cells of the peri­tubular capillary bed of the kidneys
[Ref: Ganong 25th/706; Guyton 12th/461; A K Jain 6th/68]
The juxtaglomerular apparatus (JGA) consists of three types of cells: A K Jain 6th/68
•• the macula densa, a part of the distal convoluted tubule of the same nephron
•• juxtaglomerular cells, (also known as granular cells) which secrete renin
•• mesangial cells or lacis cell: supporting cell

Answers
&
Explanations

26
 May  | 2017

Erythropoietin
–– Ganong 25th/706
•• In adults, about 85% of the erythropoietin comes from the kidneys and 15% from the liver. Both these organs contain the mRNA
for erythropoietin.
•• Erythropoietin can also be extracted from the spleen and salivary glands, but these tis­sues do not contain its mRNA and consequently
do not appear to manufacture the hormone. When renal mass is reduced in adults by kidney disease or nephrectomy, the liver cannot
compensate and anemia develops.
•• Erythropoietin is produced by interstitial cells in the peri­tubular capillary bed of the kidneys and by perivenous hepa­tocytes in the
liver.
•• It is also produced in the brain, where it exerts a protective effect against excitotoxic damage triggered by hypoxia; and in the uterus
and oviducts, where it is induced by estrogen and appears to mediate estrogen-dependent angiogenesis.
PCT is divided into two parts: pars convolute and pars recta- A K Jain 6th/504

17. Ans:  b. Present in early part of internal carotid arterym, d. Barorecptor, e. Supplied by glossopharyngel nerve
[Ref: Ganong 25th/658; Guyton 12th/251-52; A K Jain 6th/327-29; Guyton 40th/447]
“Carotid bodies and aortic bodies are chemorecptor”- A K Jain 6th/331-32

e
“Each carotid and aortic body (glomus) contains islands of two types of cell, type I (glomus) and type II cells”- Ganong 25th/658

8/
Carotid Sinus
–– A K Jain 6th/327-29
It is dilated area at initial part of internal carotid artery just superior to the bifurcation of the internal carotid and external carotid at the

h,
level of the superior border of thyroid cartilage
Barorecptor
Supplied by carotid sinus nerve (branch of glossopharyngeal nerve)
ar
ig
nd
ha
IC
PG

Fig.: (A K Jain 6th/329): Systemic arterial barorecptors (location and innervation)

Answers
&
Explanations

27
 PGI Chandigarh Self-Assessment & Review: 2017–2013

Biochemistry •• In addition, some enzymes with specialized regulatory

functions respond to allosteric effectors or covalent
modification, or they show altered rates of enzyme synthesis
18. Ans:  All (a, b, c, d, e) (or degradation) when physiologic conditions are changed.
[Ref: Harper 30th/ 89-94; Lippincott 6th/62-64; Vasudevan 5th/42-50; •• Regulation of allosteric enzymes
Shinde 7th/119-20; Satyanarayan 4th/100] •• Regulation of enzymes by covalent modification
•• Induction and repression of enzyme synthesis:The
Table ( Lippincott 6th/64): Mechanisms for regulating enzyme regulatory mechanisms described above modify the activity
activity of existing enzyme molecules. However, cells can also
regulate the amount of enzyme present by altering the
Regulator Typical Results Time required for
rate of enzyme degradation or, more typically, the rate of
Event Effector change
enzyme synthesis. The increase (induction) or decrease
Substrate Substrate Change in Immediate (repression) of enzyme synthesis leads to an alteration in
inhibition velocity (vo) the total population of active sites.
Product Reaction Change in Immediate
inhibition product Vmax and / 19. Ans:  c. Highly positively charged
or K0.5
[Ref: Harper 30th/634-36; Lippincott 6th/ 157-60; Shinde 7th/;

e
Allosteric Pathway end Change in Immediate Satyanarayan 4th/22,281]

8/
control product Vmax and/
“Hyaluronic acid is present in connective tissues, tendon, synovial
or Km
fluid and vitreous fluid”-Vasudevan 5th/69
Covalent Another Change in Immediate to

h,
Glycosaminoglycans (GAGs)/Mucopolysaccharides
modification enzyme Vmax and / minutes
or Km ar –– Lippincott 6th/ 157-60
•• They are large complexes of negatively charged hetero-
Synthesis or Hormone or Change in Hours to days
degradation metabolite the amount polysaccharide chains. They are generally associated with
a small amount of protein, forming proteoglycans, which
ig
of enzyme of enzyme
typically consist of over 95% carbohydrate. [Note: This is in
“Allosteric regulation may be either allosteric activation or comparison to the glyco proteins, which consist primarily of
nd

allosteric inhibition”- Vasudevan 5th/48 protein with a small amount of carbohydrate.]

“In case of inhibition, the inhibitors acts on the enzyme activity •• They have the special ability to bind large amounts of
water, thereby producing the gel-like matrix that forms the
ha

directly. On the contrary, repression acts at the gene level and

number of enzyme molecule is reduced in presence of repressor basis of the body’s ground substance, which, along with
molecule”- Vasudevan 5th/49-50 fibrous structural proteins such as collagen and elastin,
IC

“Induction is turning ‘on’ the switch of the gene. Repression is and adhesive proteins such as fibronectin, make up the
turning ‘off ’ the gene expression”- Vasudevan 5th/444 extracellular matrix (ECM).
•• The viscous, lubricating properties of mucous secretions
Factor Influencing Enzyme Activity
also result from the presence of glycosaminoglycans,
PG

–– Shinde 7th/119-20; Vasudevan 5th/42-50 which led to the original naming of these compounds as
•• Enzyme concentration mucopolysaccharides.
•• Product concentration
•• Substrate concentration Table ( Harper 30th/638): Some Functions of Glycosaminoglycans
•• Activators and coenzymes and Proteoglycans
•• Inhibitors (competitive, non-competitive and allosteric
•• Act as structural components of the ECM
inhibition)
•• Have specific interactions with collagen, elastin, fibronectin,
•• Repressor or depressor
laminin, and other proteins such as growth factors
•• Time •• As polyanions, bind polycations and cations
•• pH •• Contribute to the characteristic turgor of various tissues
•• Temperature •• Act as sieves in the ECM
•• Covalent modification •• Facilitate cell migration (HA)
Regulation of Enzyme Activity •• Have role in compressibility of cartilage in weight-bearing (HA,CS)
•• Play role in corneal transparency (KS I and DS)
–– Lippincott 6th/62-64 •• Have structural role in sclera (DS)
•• The regulation of the reaction velocity of enzymes is •• Act as anticoagulant (heparin)
essential if an organism is to coordinate its numerous •• Are components of plasma membranes, where they may act as
metabolic processes. receptors and participate in cell adhesion and cell-cell interactions
Answers •• The rates of most enzymes are responsive to changes in (e.g., HS)
&
substrate concentration •• Determine charge selectiveness of renal glomerulus (HS)
Explanations
•• Are components of synaptic and other vesicles (eg, HS)

28
 May  | 2017

The Glycosaminoglycans Found in Proteoglycans are 21. Ans:  None

Built up of Repeating Disaccharides
[Ref: Harrison 19th/ 2417-18; Davidson 22nd /812-13; Lippincott
–– Harper 30th/634-35 6th/339, 345]
•• Proteoglycans are proteins that contain covalently linked
All are useful in diagnosis of diabetic ketoacidosis (DKA)
glycosaminoglycans (GAGs).
•• At least 30 have been characterized and given names such Table (Harrison 19th/2417): Laboratory Values in Diabetic
as syndecan, betaglycan, serglycin, perlecan, aggrecan, Ketoacidosis (DKA) and Hyperglycemic Hyperosmolar State
versican, decorin, biglycan, and fibromodulin. (HHS) (Representative Ranges at Presentation)
•• The proteins bound covalently to glycosaminoglycans are
called “core proteins.” DKA HHS
•• Proteoglycans vary in tissue distribution, nature of the core Chloride Normal Normal
protein, attached glycosaminoglycans, and their function; Phosphate Normal Normal
they have proved difficult to isolate and characterize
Creatinine Slightly ↑ Moderately ↑
•• There are at least seven GAGs: hyaluronic acid
(hyaluronan), chondroitin sulfate, keratan sulfates I and Osmolality (mOsm/ 300–320 330–380
II, heparin, heparan sulfate, and dermatan sulfate. mL)
Plasma ketones ++++ +/–

e
20. Ans:  d. Produces ribose 5-phosphate in oxidative phase of
Serum bicarbonate, <15 meq/L Normal to slightly

8/
pathway
meq/L ↓
[Ref: Harper 30th/ 196-200; Lippincott 6th/145-45; Satyanarayan Arterial pH 6.8–7.3 >7.3
4th/270-71]

h,
Glucose, mmol/L 13.9–33.3 33.3–66.6
Hexose Monophosphate Pathway (HMP) or HMP shunt ar Sodium, meq/L 125–135 135–145
–– Satyanarayan 4th/270-71
Potassium Normal to ↑ Normal
•• This is an alternative pathway to glycolysis and TCA cycle for
ig
the oxidation of glucose Magnesium Normal Normal
•• The sequence of reactions of HMP shunt is divided into 2 Arterial PCO2, mmHg 20–30 Normal
nd

phases- oxidative and non-oxidative

Anion gap [Na– (Cl + ↑ Normal to slightly
•• Oxidative phase:NADPH is produced
HCO3)] ↑
•• Non-oxidative: ribose 5-phosphate
Glucose (mg/dl) 250–600 600–1200
ha

•• The first reaction (occur in oxidative phase) catalysed by

G6PD is most regulatory in the HMP shunt Diabetic Ketoacidosis (DKA)–Investigations
Hexose Monophosphate Pathway (HMP) – – D a v i d s o n 2 2 nd / 8 1 2 – 1 3
IC

–– Lippincott 6th/145 The following are important but should not delay the institution
•• Also called as pentose phosphate pathway or 6-phosphoglu- of intravenous fluid and insulin replacement:
conate pathway •• Venous blood: for urea and electrolytes, glucose and
PG

•• It occurs in the cytosol of the cell. bicarbonate (severe acidosis is indicated by a venous plasma
•• It includes two, irreversible oxidative reactions, followed by bicarbonate < 12 mmol/L).
a series of reversible sugar–phosphate interconversions •• Urine or blood analysis for ketones
•• No ATP is directly consumed or produced in the cycle. •• ECG.
•• Carbon 1 of glucose 6-phosphate is released as CO2, and •• Infection screen: full blood count, blood and urine culture,
two NADPH are produced for each glucose 6-phosphate C-reactive protein, chest X-ray. Although leucocytosis
molecule entering the oxidative part of the pathway. invariably occurs in DKA, this represents a stress response
•• The pathway provides a major portion of the body’s and does not necessarily indicate infection.
NADPH, which functions as a biochemical reductant. Diabetic Ketoacidosis (DKA)
•• It also produces ribose 5-phosphate, required for the
– Harrison 19th/ 2417-18
–
biosynthesis of nucleotides
•• DKA is characterized by hyperglycemia, ketosis, and
•• This portion of the pathway is particularly important in the
liver, lactating mammary glands, and adipose, which are metabolic acidosis (increased anion gap) along with a
active in the NADPH-dependent biosynthesis of fatty acids, number of secondary metabolic derangements
•• Leukocytosis, hypertriglyceridemia, and hyperlipoprotein-
in the testes, ovaries, placenta and adrenal cortex, which
are active in the NADPH-dependent biosynthesis of steroid emia are commonly found as well
hormones, and in erythrocytes, which require NADPH to •• Ketosis results from a marked increase in free fatty acid
keep glutathione reduced release from adipocytes, with a resulting shift toward ketone
body synthesis in the liver. Answers
&
Explanations

29
 PGI Chandigarh Self-Assessment & Review: 2017–2013

•• Reduced insulin levels, in combination with elevations in catecholamines and growth hormone, increase lipolysis and the release
of free fatty acids.
•• Increased lactic acid production also contributes to the acidosis. The increased free fatty acids increase triglyceride and VLDL
production.

22. Ans:   a. Activation of pyruvate carboxylase by acetye CoA, c. Increased fatty acid oxidation in liver, d. Hydrolysis of fructose
1,6-bisphosphate by fructose 1,6-bisphosphatase
[Ref: Satyanarayan 4th/ 258-63; Harper 30th/188; Lippincott 6th/117-123; Shinde 7th/347]
“Acetyl CoA promotes gluconeogenesis: During starvation-due to excessive lipolysis in adipose tissue, acetyl CoA accumulates in liver.
Acetyl CoA allosterically activates pyruvate carboxylase resulting in enhanced glucose production”- Satyanarayan 4th/ 263
Reactions Unique to Gluconeogenesis
–– Lippincott 6th/118-123
•• Seven glycolytic reactions are reversible and are used in the synthesis of glucose from lactate or pyruvate. However, three of the
reactions are irreversible and must be circumvented by four alternate reactions that energetically favor the synthesis of glucose. These
reactions, unique to gluconeogenesis, are described below.
A. Carboxylation of pyruvate: The first “roadblock” to overcome in the synthesis of glucose from pyruvate is the irreversible

e
conversion in glycolysis of PEP to pyruvate by pyruvate kinase. In gluconeogenesis, pyruvate is first carboxylated by pyruvate

8/
carboxylase to OAA, which is then converted to PEP by the action of PEP- carboxykinase
B. Transport of oxaloacetate to the cytosol: OAA must be converted to PEP for gluconeogenesis to continue. The enzyme
that catalyzes this conversion is found in both the mitochondria and the cytosol in humans. The PEP that is generated in the

h,
mitochondria is transported to the cytosol by a specific transporter, whereas that generated in the cytosol requires the transport
of OAA from the mitochondria to the cytosol. However, OAA is unable to directly cross the inner mitochondrial membrane; it
ar
must first be reduced to malate by mitochondrial malate dehydro genase. Malate can be transported from the mitochondria to the
cytosol, where it is reoxidized to oxaloacetate by cytosolic malate dehydrogenase as NAD+ is reduced . The NADH produced is
used in the reduction of 1,3-BPG to glyceraldehyde 3-phosphate, a step common to both glycolysis and gluconeogenesis.
ig
C. Decarboxylation of cytosolic oxaloacetate: Oxaloacetate is decarboxylated and phosphorylated to PEP in the cytosol by PEP-
carboxykinase. The reaction is driven by hydrolysis of guanosine triphosphate. The combined actions of pyruvate carboxylase and
nd

PEPcarboxy kinase provide an energetically favorable pathway from pyruvate to PEP. Then, PEP is acted on by the reactions of
glycolysis running in the reverse direction until it becomes fructose 1,6-bisphosphate
ha

D. Dephosphorylation of fructose 1,6-bisphosphate: Hydrolysis of fructose 1,6-bisphosphate by fructose 1,6-bisphosphatase by-

passes the irreversible phosphofructokinase-1 reaction, and provides an energetically favorable pathway for the formation of fruc-
tose 6-phosphate. This reaction is an important regulatory site of gluconeogenesis.
IC

Table (Harper 30th/188):  Regulatory and Adaptive Enzymes Associated with Carbohydrate Metabolism.

  Activity in        
PG

  Carbohydrate Fasting Inducer Repressor Activator Inhibitor

Feeding and
Diabetes
Glycogenolysis, glycolysis, and pyruvate oxidation 
Glycogen synthase ↑ ↓     Insulin, glucose Glucagon
6-phosphate
Hexokinase         Glucose 6-phosphate
Glucokinase ↑ ↓ Insulin Glucagon    
Phosphofructokinase-1 ↑ ↓ Insulin Glucagon 5'AMP, fructose Citrate, ATP, glucagon
6-phosphate,
fructose
2,6-bisphosphate, Pi
Pyruvate kinase ↑ ↓ Insulin, fructose Glucagon Fructose ATP, alanine,
1,6-bisphosphate, glucagon,
insulin norepinephrine
Pyruvate dehydrogenase ↑ ↓     CoA, NAD+, insulin, Acetyl CoA, NADH,
Answers ADP, pyruvate ATP (fatty acids,
&   ketone bodies)
Explanations

30
 May  | 2017

  Activity in        
  Carbohydrate Fasting Inducer Repressor Activator Inhibitor
Feeding and
Diabetes
Gluconeogenesis

Pyruvate carboxylase ↓ ↑ Glucocorticoids, Insulin Acetyl CoA ADP

glucagon,
epinephrine
Phosphoenolpyruvate ↓ ↑ Glucocorticoids, Insulin Glucagon  
carboxykinase glucagon,
epinephrine
Glucose 6-phosphatase ↓ ↑ Glucocorticoids, Insulin    
glucagon,
epinephrine

e
8/
h,
ar
ig
nd
ha
IC
PG

Fig.: (Lippincott 6th/123): Key concept map for gluconeogenesis

Answers
&
Explanations

31
 PGI Chandigarh Self-Assessment & Review: 2017–2013

23. Ans:  a. 20 carbon atom compound, c. Cyclopentane ring, unmodified and are actively transported into the portal
d. -OH group at 15th position blood. They circulate as free (unesterified) fatty acids. The
fatty acids containing more than 10–12 carbon atoms are
[Ref: Harper 30th/ 239-40; Lippincott 6th/ 213-15; Vasudevan 5th/167;
Shinde 7th/64-65; Satyanarayan 4th/644]
too insoluble for this. They are reesterified to triglycerides
in the enterocytes.
Prostaglandins (PG) •• In addition, some of the absorbed cholesterol is esterified.
–– Shinde 7th/64-65; Vasudevan 5th/167 The triglycerides and cholesterol esters are then coated with
•• All naturally occurring PG are 20C fatty acids containing a a layer of protein, cholesterol, and phospholipid to form
cyclopentane ring (formed by carbon atom 8 to 12) chylomi­crons. These leave the cell and enter the lymphatics,
•• All PGs have following salient structural features: -OH group because they are too large to pass through the junctions
at 15 position and trans double bond at 13 position between capil­lary endothelial cells
•• Absorption of long-chain fatty acids is greatest in the upper
Prostaglandins and Related Compounds
parts of the small intestine, but appreciable amounts are
–– Lippincott 6th/ 213-15 also absorbed in the ileum.
•• Prostaglandins, and the related compounds thromboxanes
and leukotrienes, are collectively known as eicosanoids to Absorption of Lipids by Intestinal Mucosal Cells
reflect their origin from polyunsaturated fatty acids with 20 (Enterocytes)

e
carbons. –– Lippincott 6th/176
•• They are extremely potent compounds that elicit a wide •• Free fatty acids, free cholesterol, and 2-monoacylglycerol

8/
range of responses, both physiologic (inflammatory are the primary products of lipid digestion in the jejunum.
response) and pathologic (hypersensitivity). These, plus bile salts and fat-soluble vitamins (A, D, E, and
K), form mixed micelles

h,
24. Ans:  a. Micelles play an important role in lipids absorption, •• Mixed micelles are, therefore, soluble in the aqueous
b. Absorption of long-chain fatty acids is greatest in ar environment of the intestinal lumen.
the upper parts of the small intestine, d. Fatty acids •• Short- and medium chain length fatty acids do not require
after absorption are reesterified to triglycerides in the the assistance of mixed micelles for absorption by the
ig
enterocytes intestinal mucosa.
[Ref: Ganong 25th/481-83; Harper 30th/253-54; Guyton 12th/421-23;
nd

Lippincott 6th/176]

Fat Digestion
ha

– – G a n o n g 2 5 th/ 4 8 1 - 8 2
•• Most fat digestion therefore begins in the duodenum,
pancreatic lipase being one of the most important enzymes
IC

involved.
•• This enzyme hydrolyzes the 1- and 3-bonds of the
triglycerides (triacylglycerols) with relative ease but acts
PG

on the 2-bonds at a very low rate, so the principal prod­

ucts of its action are free fatty acids and 2-monoglycerides
(2-monoacylglycerols).
•• Fats are relatively insoluble, which limits their ability to cross
the unstirred layer and reach the surface of the mucosal cells.
However, they are finely emulsified in the small intestine by
the detergent action of bile acids, phosphatidylcholine, and
monoglycerides.
•• When the concentration of bile acids in the intestine is
high, as it is after contraction of the gallbladder, lipids and
bile acids interact spontaneously to form micelles.
•• Micellar formation further solubilizes the lipids and
provides a mechanism for their transport to the enterocytes.
•• The micelles play an important role in keeping lipids in
solution and trans­porting them to the brush border of the
intestinal epithelial cells, where they are absorbed.
Fat Absorption
Answers – – G a n o n g 2 5 th/ 4 8 2 - 8 3
&
Explanations •• Fatty acids containing less than 10–12 carbon atoms are Fig.: Lippincott 6th/ 174
water-soluble enough that they pass through the enterocyte

32
 May  | 2017

25. Ans:  b. Linoleic acid is essential fatty acid, c. Hydrogenation •• Telomerase is an RNA-dependent DNA polymerase,
converts unsaturated fatty acid to saturated fatty acid meaning an enzyme that can make DNA using RNA as a
template.
[Ref: Harper 30th/ 211-15; Lippincott 6th/181-82; Satyanarayan 4th/28-29]
•• It help in DNA replication at telomere (end of lagging
“During process of hydrogenation, unsaturated fatty acids are strand)
converted into saturated acids and EFA content is drastically
Telomerase
reduced”-Park 24th/650
Classification of lipids: (1) Simple lipids- Fats and oils –– Satynarayan 4th/530-31
(Triacylglycerols). The difference b/w fat and oil is only •• Telomerase, also called terminal transferase, is a
physical; (2) Complex (or compound) lipid; (3) Derived lipids; (4) ribonucleoprotein that adds a species-dependent telomere
Miscellaneous lipids”- Satyanarayan 4th/28-29 repeat sequence to the 3' end of telomeres.
•• A telomere is a region of repetitive sequences at each end of
Fatty Acids
eukaryotic chromosomes in most eukaryotes
–– Harper 30th/ 211-15 “Telomerase: This complex contains a protein that acts as a
•• Fatty acids occur in the body mainly as esters in natural fats reverse transcriptase, and a short piece of RNA that acts as a
and oils, but are found in the unesterified form as free fatty template. The CA-rich RNA template base-pairs with the GT-
acids, a transport form in the plasma. Fatty acids that occur rich, single-stranded 3'-end of telomeric DNA . The reverse
in natural fats usually contain an even number of carbon

e
transcriptase uses the RNA template to synthesize DNA in the
atoms. usual 5'→3' direction, extending the already longer 3'-end.

8/
•• The chain may be saturated (containing no double bonds) Telomerase then translocates to the newly synthesized end,
or unsaturated (containing one or more double bonds) and the process is repeated. Once the GT-rich strand has been
–– Lippincott 6th/181-82 lengthened, primase can use it as a template to synthesize an

h,
•• Fatty acid chains may contain no double bonds—that is, RNA primer. The RNA primer is extended by DNA polymerase,
be saturated— or contain one or more double bonds—that ar and the primer is removed”- Lippincott 6th /408
is, be mono- or polyunsaturated. When double bonds are “Telomeres: Structures at the ends of chromosome that contain
present, they are nearly always in the cis rather than in the multiple repeats of specific hexanucleotide DNA sequences.
ig
trans configuration. The telomeres of normal cells shorten on repeated cell division,
•• Essential fatty acids Two fatty acids are dietary essentials which may result in cell death. The enzyme telomerase replicates
nd

in humans because of our inability to synthesize them: telomeres and is often expressed in cancer cells, helping them to
linoleic acid and α-linolenic acid. Plants provide us with evade cell death. Telomerase is usually not detected in normal
the essential fatty acids. [Note: Arachidonic acid becomes somatic cells”-Harper 30th/745
ha

essential if linoleic acid is deficient in the diet.]

28. Ans:  b. A type of topoisomerase II, c. Act on circular DNA,
d. Overcome the problem of supercoils
Immunogenetics &
IC

[Ref: Lippincott 6th /401; Satyanarayan 4th/528]

Molecular Biology
Gyrase
PG

–– Satyanarayan 4th/528
26. Ans:   b. Cytosine, c. Uracil, d. Thymine
•• Bacteria contain a specific type II topoisomerase namely
[Ref: Harper 30th /360; Lippincott 6th /291-92] gyrase
“Both DNA and RNA contain the same purine bases: •• This enzyme cuts and reseals the circular DNA (of bacteria)
adenine (A) and guanine (G). Both DNA and RNA contain and thus overcome the problem of supercoils
the pyrimidine cytosine (C), but they differ in their second Type II DNA Topoisomerases
pyrimidine base: DNA contains thymine (T), whereas RNA –– Lippincott 6th /401
contains uracil (U). T and U differ in that only T has a methyl •• These enzymes bind tightly to the DNA double helix and
group” (Lippincott 6th /291) make transient breaks in both strands. The enzyme then
causes a second stretch of the DNA double helix to pass
27. Ans:  a. It has reverse trans..., c. Help in DNA replication at
through the break and, finally, reseals the break. As a result,
end..., d. Also called terminal transferase
both negative and positive supercoils can be relieved by this
[Ref: Harper 30th/745; Lippincott 6th /408; Satynarayan 4th/530-31; ATP-requiring process.
Vasudevan 5th/421-22] •• Type II DNA topoisomerases are also required in both
Telomerase prokaryotes and eukaryotes for the separation of interlocked
molecules of DNA following chromosomal replication.
–– www.khanacademy.org
•• DNA gyrase, a Type II topoisomerase found in bacteria and
•• Some cells have the ability to reverse telomere shortening
plants, has the unusual property of being able to introduce Answers
by expressing telomerase, an enzyme that extends the negative supercoils into relaxed circular DNA using energy &
telomeres of chromosomes. from the hydrolysis of ATP. This facilitates the future
Explanations

33
 PGI Chandigarh Self-Assessment & Review: 2017–2013

replication of DNA because the negative supercoils neutralize the positive supercoils introduced during opening of the double helix.
It also aids in the transient strand separation required during transcription
–– Lippincott 6th /401
•• These enzymes reversibly cut one strand of the double helix. They have both nuclease (strand-cutting) and ligase (strand-resealing)
activities. They do not require ATP, but rather appear to store the energy from the phosphodiester bond they cleave, reusing the
energy to reseal the strand.
•• Each time a transient “nick” is created in one DNA strand, the intact DNA strand is passed through the break before it is resealed, thus
relieving (“relaxing”) accumulated supercoils.
•• Type I topoisomerases relax negative supercoils (that is, those that contain fewer turns of the helix than relaxed DNA) in E. coli, and
both negative and positive supercoils (that is, those that contain fewer or more turns of the helix than relaxed DNA) in eukaryotic
cells.

29. Ans:  a. Pyrimidine dimers formation, c. Thymine dimer formation

[Ref: Harper 30th /761; Lippincott 6th /412]

Ultraviolet Radiation can be Extremely Damaging

–– Harper 30th /761

e
•• Absorption of this short wavelength, high-energy light can cause the rupture of covalent bonds in proteins, DNA, and RNA; the

8/
formation of thymine dimers in DNA
Repair of Damage caused by Ultraviolet (UV) Light

h,
–– Lippincott 6th /412
•• Exposure of a cell to UV light can result in the covalent joining of two adjacent pyrimidines (usually thymines), producing a dimer.
These thymine dimers prevent DNA polymerase from replicating the DNA strand beyond the site of dimer formation. Thymine
ar
dimers are excised in bacteria by UvrABC proteins in a process known as nucleotide excision repair.
•• A related pathway involving XP (xeroderma pigmentosum) proteins is present in humans.
ig
1. Recognition and excision of dimers by UV-specific endonuclease: First, a UV-specific endonuclease (called uvrABC excinuclease)
recognizes the dimer, and cleaves the damaged strand on both the 5'-side and 3'-side of the dimer. A short oligonucleotide
nd

containing the dimer is released, leaving a gap in the DNA strand that formerly contained the dimer. This gap is filled in using the
same process described previously.
2. UV radiation and cancer: Pyrimidine dimers can be formed in the skin cells of humans exposed to unfiltered sunlight. In the rare
ha

genetic disease xeroderma pigmentosum (XP), the cells cannot repair the damaged DNA, resulting in extensive accumulation of
mutations and, consequently, early and numerous skin cancers.
“Certain DNA sequences are particularly susceptible to mutagenesis. Successive pyrimidine residues (e.g., T-T or C-C) are subject to
IC

the formation of ultraviolet light–induced photoadducts. If these pyrimidine dimers are not repaired by the nucleotide excision repair
pathway, mutations will be introduced after DNA synthesis.”-Harriosn 19th/432-33
PG

30. Ans:  b. 5’ capping

[Ref: Satyanarayan 4th/561-62; Harper 30th /426; Lippincott 6th / 443-44]

Answers
&
Explanations Fig.: (Satyanarayan 4th/561): An outline of Post-translation modification of proteins

34
 May  | 2017

CO-AND POST-TRANSLATIONAL MODIFICATION OF Transcription: The binding of the enzyme RNA polymerase
POLYPEPTIDE CHAINS to DNA is the prerequisite for the transcription to start. The
–– Lippincott 6th / 443-44 specific region on DNA where the enzyme binds in known as
•• Many polypeptide chains are covalently modified, promotor region”- Satyanarayan 4th/544
either while they are still attached to the ribosome Genes
(cotranslational) or after their synthesis has been completed –– Harrison 19th/427-28
(posttranslational). These modifications may include •• A gene is a functional unit that is regulated by transcription
removal of part of the translated sequence, or the covalent and encodes an RNA product, which is most commonly,
addition of one or more chemical groups required for but not always, translated into a protein that exerts activity
protein activity. within or outside the cell.
•• Some types of posttranslational modifications are : •• Historically, genes were identified because they conferred
A. Trimming: Many proteins destined for secretion from specific traits that are transmitted from one generation
the cell are initially made as large, precursor molecules to the next. Increasingly, they are characterized based on
that are not functionally active. Portions of the protein expression in various tissues (transcriptome).
chain must be removed by specialized endoproteases, •• The number of genes greatly underestimates the complexity
resulting in the release of an active molecule. of genetic expression, because single genes can generate
B. Covalent attachments: Proteins may be activated or

e
multiple spliced messenger RNA (mRNA) products
inactivated by the covalent attachment of a variety of (isoforms), which are translated into proteins that are

8/
chemical groups. subject to complex posttranslational modification such as
C. Protein folding: Proteins must fold to assume their phosphorylation.
functional state. Folding can be spontaneous (as a result •• Exons refer to the portion of genes that are eventually

h,
of the primary structure), or facilitated by proteins spliced together to form mRNA.
known as “chaperones” ar •• Introns refer to the spacing regions between the exons
D. Protein degradation: Proteins that are defective, for that are spliced out of precursor RNAs during RNA
example, misfolded, or destined for rapid turnover are processing.
ig
often marked for destruction by ubiquitination— the
attachment of chains of a small, highly 32. Ans:  a. Repair damage caused by UV light, c. Use visible
nd

conserved protein, called ubiquitin light, d. Breaks pyrimidine dimer

Post-transcriptional Modifications [Ref: www.pnas.org; www.ncbi.nlm.nih.gov]
–– Vasudevan 5th/426
ha

Photolyases
•• Poly-A tailing
•• 5’ capping –– www.ncbi.nlm.nih.gov
•• Methylation Photolyases are DNA repair enzymes that repair damage
IC

•• Removal of introns caused by exposure to ultraviolet light.

•• Spicing of exons (connect together) This enzyme requires visible light, preferentially from the
•• Endonuclease cleavage violet/blue end of the spectrum, and the mechanism known as
PG

photoreactivation.
31. Ans:   c. RNA polymerase II is responsible for the synthesis
of precursors for the large ribosomal RNAs, d. RNA Photolyase is a phylogenetically old enzyme which is present
polymerase I is responsible for the synthesis small and functional in many species, from the bacteria to the fungi
ribosomal RNAs to plants and to the animals.
Photolyase is particularly important in repairing UV induced
[Ref: Harrison 19th/427-28; Satyanarayan 4th/546, 566-68]
damage in plants. The photolyase mechanism is no longer
“The RNA copies of the active protein coding genes represent working in humans and other placental mammals who instead
transcriptome. Thus transcriptome is initial product of gene rely on the less efficient nucleotide excision repair mechanism.
expression which directs the protein synthesis”- Satyanarayan
Photolyases bind complementary DNA strands and break
4th/543
certain types of pyrimidine dimers that arise when a pair of
RNA Polymerase in Eukaryotes thymine or cytosine bases on the same strand of DNA become
–– Satyanarayan 4th/546 covalently linked.
•• RNA polymerase I is responsible for the synthesis of Photolyases have a high affinity for these lesions and reversibly
precursors for the large ribosomal RNAs bind and convert them back to the original bases.
•• RNA polymerase II synthesizes the precursors for mRNAs
–– www.pnas.org
and small nuclear RNAs
•• DNA photolyases are highly efficient light-driven DNA
•• RNA polymerase II participates in the formation of tRNAs
repair enzymes which revert the genome-damaging effects Answers
and small ribosomal RNAs &
caused by ultraviolet (UV) radiation. Explanations

35
 PGI Chandigarh Self-Assessment & Review: 2017–2013

•• These enzymes occur in almost all living organisms exposed –– Devita 8th /chap 51
to sunlight, the only exception being placental mammals
Table ( Harrison 19th/699): Cytogenetic Translocation and
like humans and mice. Their catalytic mechanism employs
Associated Oncogenes Often seen in Lymphoid
the light-driven injection of an electron onto the DNA
Malignancies
lesion to trigger the cleavage of cyclobutane- pyrimidine
dimers. Disease Cytogenetic Oncogene
Abnormality
CLL/small lymphocytic t (14; 15 ( (q32; –
Pathology lymphoma q13)

MALT lymphoma t (11; 18) (q21; API2/MALT, BCL–10

33. Ans:   d. Hodgkin’s lymphoma, e. B-Lymphoblastic
q21)
lymphoma
Precursor B-cell acute t (9; 22) (q34; q11) BCR/ABL
[Ref: Robbins 9th (SAE)/590; Harrison 19th/699]
lymphoid leukemia or variant AF4, MLLI
“A high fraction of B-ALLs have loss-of-function mutations in t (4; 11) (q21; q23) TEL, AMLI
genes that are required for B-cell development, such as PAX5, t (12; 21)
E2A, and EBF, or a balanced t (12; 21) involving the genes ETV6

e
and RUNX1”- Robbins 9th (SAE)/590 Precursor acute t (9; 22) BCR, ABL
lymphoid leukemia t (1; 19) E2A, PBX

8/
“The Reed-Sternberg cells in nodular sclerosis and other
t (17; 19) HLF, E2A
“classical” HL subtypes have a characteristic immunophenotype; t (5; 14) HOXI IL2, CTIP2
they are positive for PAX5 (a B-cell transcription factor), CD15,

h,
and CD30, and negative for other B-cell markers, T-cell markers, Mantle cell lymphoma t (11; 14) (q13; BCL-I, lgH
and CD45 (leukocyte common antigen)”-Robbins 9th (SAE)/608 ar q32)
“PAX5 has been reported as being frequently altered in both Follicular lymphoma t (14; 18) (q32; BCL-2, lgH
childhood and adult B-ALL. PAX5 mutation was also reported q21)
in both Hodgkin lymphoma and non-Hodgkin lymphoma”-
ig
www.hindawi.com Diffuse large cell t (3; -) (q27; -)a BCL-6
lymphoma t (17; -) (p13; -)a P53
nd

“PAX-5, a transcription factor expressed throughout B-cell

maturation, is detected in most B-cell neoplasms including Burkitt’s lymphoma, t (8; -) (q24; -) a C-MYC
those that lack expression of mature B-cell markers, such as Burkitt’s leukermia
ha

classical Hodgkin lymphoma (cHL), B-lymphoblastic leukemia

and B-cell lymphomas following rituximab therapy. The lack of CD30+ anaplastic large t (2; 5) (p23; q35) ALK, NPM
PAX-5 expression in most CD30-positive non-hematopoietic cell lymphoma
IC

malignancies (embryonal carcinoma and seminoma) and Lymphoplasmacytoid t (9; 14) (p13; q32) PAX5, lgH
T-cell lymphomas, such as anaplastic large cell lymphoma lymphoma
(ALCL), suggests that the absence of PAX-5 may be used to
PG

confirm non-B-cell lineage”-www.ncbi.nlm.nih.gov 34. Ans:  b. SS18-SSX4 fusion genes, c. Translocation t (X; 18)
“Pax5, or B-cell-specific activator protein, is mostly expressed (p11; q11), d. SS18-SSX1 fusion genes
in B lymphocytes and B-cell lymphomas, although recent
data have shown expression in the developing central nervous [Ref: Robbins 9th (SAE)/1223-24; Harshmohan 7th/861; Harrison
system, some neuroendocrine tumors, and occasional myeloid 19th/119e-1]
leukemias. Pax5 staining is positive in most Hodgkin and “Chronic myelogenous leukemia (CML): Translocation
B-cell non-Hodgkin lymphomas, and also precursor B-cell involving (9; 22) (q34; q11)”- Robbins 9th (SAE)/317
lymphoblastic neoplasms. Plasma cell neoplasms, multiple “Ninety percent of synovial sarcomas contain a characteristic
myeloma, and plasmablastic lymphomas typically are chromosomal translocation t (X; 18) (p11; q11) involving a
negative. T-cell lymphomas are, to date, consistently negative. nuclear transcription factor on chromosome 18 called SYT and
Recently, Pax5 expression has been described in the majority of two breakpoints on X.
small cell carcinomas and Merkel cell carcinomas”-www.ncbi. Patients with translocations to the second X breakpoint (SSX2)
nlm.nih.gov may have longer survival than those with translocations
“Lymphoplascytid lymphoma is associated with PAX 5 involving SSX1”-Harrison 19th/119e-1
oncogene”- Harrison 19th/699 (Table) “Most synovial sarcomas show a characteristic chromosomal
translocation t (x; 18) (p11; q11) producing SS18-SSX1, -SSX2
“t (9; 14) (p13; PAX5 (BSAP)/ Lymphoplasmacytic lymphoma, or -SSX-4 fusion genes that encodes chimeric transcription
q32) IgH: plasma cell myeloma” factors”- Robbins 9th (SAE)/1223-24
Answers
&
Explanations

36
 May  | 2017

Table (MD Anderson Manual of Medical Oncology/Chap 33): Cytogenetic Translocation and Other Abnormalities in Sarcoma

Tumor Cytogenetic Abnormality Gene Product

Synovial sarcoma T(X; 18)(p11; q11) SYT-SSX

35. Ans:  a. ↑ed conjugated bilirubin, d. Decreased biliary excretion of conjugated bilirubin
[Ref: Robbins 9th (SAE)/854; Harrison 19th/2003-04]

Dubin-Johnson Syndrome (DJS)

–– Harrison 19th/2003-04
•• This benign, relatively rare disorder is characterized by low-grade, predominantly conjugated hyperbilirubinemia.
•• Total bilirubin concentrations are typically between 34 and 85 μmol/L (2 and 5 mg/dL) but on occasion can be in the normal range
or as high as 340–430 μmol/L (20–25 mg/dL) and can fluctuate widely in any given patient.
•• Because the hyperbilirubinemia is due to a predominant rise in conjugated bilirubin, bilirubinuria is characteristically present. Aside
from elevated serum bilirubin levels, other routine laboratory tests are normal.
•• Physical examination is usually normal except for jaundice, although an occasional patient may have hepatosplenomegaly.

e
•• Routine liver function tests, including serum alkaline phosphatase and transaminase activities are usually normal.
•• Several different mutations in the MRP2 gene produce the Dubin-Johnson phenotype, which has an autosomal recessive pattern of

8/
inheritance.
•• MRP2 is play a important role in the biliary excretion of conjugated bilirubin
•• Patients with DJS also have a diagnostic abnormality in urinary coproporphyrin excretion. There are two naturally occurring

h,
coproporphyrin isomers, I and III. Normally, ∼75% of the coproporphyrin in urine is isomer III. In urine from DJS patients, total
coproporphyrin content is normal, but >80% is isomer I. ar
“Isolated bilirubin rise (other LFTs normal), normal ultrasound, urobilinogen present, conjugated bilirubin rise”- Davidson 22nd/938
(Flow chart)
ig
Table (Robbins 9th (SAE)/854 ): Hereditary Hyperbilirubinemias
nd

Disorder Inheritance Defects in Bilirubin Metabolism Liver Clinical Course

Pathology
ha

Unconjugated Hyperbilirubinemia

Crigler-Najjar syndrome type I Autosomal recessive Absent UGT1A1 activity None Fatal in neonatal
IC

period

Crigler-Najjar syndrome type II Autosomal dominant with Decreased UGT1A1 activity None Generally mild,
PG

variable penetrance occasional

kernicterus

Gilbert syndrome Autosomal recessive Decreased UGT1A1 activity None Innocuous

Conjugated Hyperbilirubinemia

Dubin-Johnson syndrome Autosomal recessive Impaired biliary excretion of bilirubin Pigmented Innocuous
glucuronldes due to mutation in cytoplasmic
canallcular multidrug resistance protein globules
2 (MRP2)

Rotor syndrome Autosomal recessive Decreased hepatic uptake and storage? None Innocuous
Decreased biliary excretion?

UGT1A1, Uridine diphosphate –glucuronyttransferese family, peptide A1

Answers
&
Explanations

37
 PGI Chandigarh Self-Assessment & Review: 2017–2013

36. Ans:  b. Positive for cytokeratin 7, e. EGFR mutation

[Ref: Robbins 9th (SAE)/714; Harrison 19th/507-09]

Fig.: (Harriosn 19th/102e-2): Approach to cytokeratin (CK7 and CK20) markers used in adenocarcinoma of unknown primary
“Transthyretin (TTR): Single amino acid substitution mutation in structure of TTR result in variant form of protein which is responsible for

e
amyloidosis (Familial amyloid polyneuropathies, senile cardiac amyloidosis)”-Harshmohan 7th/68

8/
“The epithelioid type of mesothelioma consists of cuboidal, columnar, or flattened cells forming tubular or papillary structures
resembling adenocarcinoma. Immunohistochemical stains are very helpful in differentiating it from pulmonary adenocarcinoma. Most
mesotheliomas show strong positivity for keratin proteins, calretinin, Wilms tumor 1 (WT-1), cytokeratin 5/6, and D2-40”-Robbins

h,
9th (SAE)/724
Table (Harrison 19th/507): Driver Mutations in Non-Small-Cell Lung Cancer (NSCLC)
ar
Gene Alteration Frequency in Typical Histology
ig
NSCLC
AKT1 Mutation 1% Adenocarcinoma, squamous
nd

ALK Rearrangement 3–7% Adenocarcinoma

BRAF Mutation 1–3% Adenocarcinoma
ha

DDR2 Mutation ~4% Squamous

EGFR Mutation 10–35% Adenocarcinoma
IC

EGFR1 Amplification ~20% Squamous

HER2 Mutation 2–4% Adenocarcinoma
KRAS Mutation 15–25% Adenocarcinoma
PG

MEK1 Mutation 1% Adenocarcinoma

MET Amplification 2–4% Adenocarcinoma
NRAS Mutation 1% Adenocarcinoma
PIK3CA Mutation 1–3% Squamous
PTEN Mutation 4–8% Squamous

Lung Carcinoma
–– Harrison 19th/508-09
•• Lung cancer cells harbor multiple chromosomal abnormalities, including mutations, amplifications, insertions, deletions, and
translocations.
•• One of the earliest sets of oncogenes found to be aberrant was the MYC family of transcription factors (MYC, MYCN, and MYCL).
MYC is most frequently activated via gene amplification or transcriptional dysregulation in both SCLC and NSCLC.
•• Adenocarcinomas driver mutations involves EGFR, which belongs to the ERBB (HER) family of protooncogenes, including EGFR
(ERBB1), HER2/neu (ERBB2), HER3 (ERBB3), and HER4 (ERBB4).
•• Additional examples of driver mutations in lung adenocarcinoma include the GTPase KRAS, the serine-threonine kinase BRAF, and
Answers the lipid kinase PIK3CA.
& •• More recently, more subsets of lung adenocarcinoma have been identifed as defined by the presence of specific chromsomal
Explanations
rearrangements resulting in the abberant activation of the TKs ALK, ROS1, and RET.

38
 May  | 2017

•• Although driver mutations have mostly been found Classification,

in adenocarinomas, three potential molecular targets  Restricting the diagnosis of large cell carcinoma only
recently have been identified in squamous cell lung to resected tumors that lack any clear morphologic
carcinomas: FGFR1 amplification, DDR2 mutations, and or immunohistochemical differentiation with
PIK3CA mutations/PTEN loss. Together, these potentially reclassification of the remaining former large cell
“actionable” defects occur in up to 50% of squamous carcinoma subtypes into different categories,
carcinomas.  Re-classifying squamous cell carcinomas into kerati-
•• A large number of tumor-suppressor genes have also been nizing, nonkeratinizing and basaloid subtypes with the
identified that are inactivated during the pathogenesis nonkeratinizing tumors requiring immunohistochemis-
of lung cancer. These include TP53, RB1, RASSF1A, try proof of squamous differentiation,
CDKN2A/B, LKB1 (STK11), and FHIT. Nearly 90% of  Grouping ofneuroendocrine tumors together in one
SCLCs harbor mutations in TP53 and RB1. category,
“Adenocarcinoma of lung is marked by oncogenic gain-of-  Adding nuclear protein intestis (NUT) carcinoma to a
function mutations involving components of growth factor category of other and unclassified tumors,
receptor signaling pathways. These include gain-of-function  Changing the term sclerosing hemangioma to sclerosing
mutations in multiple genes encoding receptor tyrosine kinases, pneumocytoma and moving this tumor to the adenoma
including EGFR, ALK, ROS, MET, and RET, which are all also category,

e
mutated in other forms of cancer”-Robbins 9th (SAE)/714  Changing the name hamartomato “pulmonary

8/
hamartoma,”
37. Ans:  d. Nonkeratinizing variant  Creating a group of PEComatous tumors that include (a)
[Ref: Robbins 9th (SAE)/714; www.sciencedirect.com/scienc] lymphangioleiomyomatosis (LAM), (b) PEComa, benign

h,
(with clear cell tumor as a variant), and (c) PEComa,
Clear and papillary cell variant are type of squamous cell
malignant,
carcinoma in old classification (not included in 2015 WHO ar  Introducing the entity pulmonary myxoid sarcoma with
classification)
an EWSR1–CREB1 translocation,
Lymphoepithelioma-like carcinoma is classified as neuroen-
Adding the entities myoepithelioma and myoepithelial
ig

docrine tumors (Other and Unclassified carcinomas) in 2015
carcinomas which can showEWSR1 gene
WHO classification of lung tumour”- www.sciencedirect.com/
rearrangements,
nd

scienc
 Recognition of usefulness of WWTR1–CAMTA1 fusions
in diagnosis of epithelioid hemangioendotheliomas
2015 World Health Organization (WHO) Classification of AddingErdheim–Chester disease to the lymphoprolifer-
ha


Tumors of the Lung, Pleura, Thymus and Heart ative tumors,1 and
•• This classification is published in 2015  A new group of tumors of ectopic origin was created to
•• This follows previous WHO Classifications of Lung Tumors
IC

include germ cell tumors,

in 1967 and 1981, of Lung and Pleural Tumors in 1999 and intrapulmonary thymoma, melanoma and meningioma.
Tumors of the Lung, Pleura, Thymus and Heart in 2004.
•• Compared with the 2004 WHO Classification, there are TABLE: 2015 WHO Classification of Lung Tumors (Partial list-only
PG

multiple major changes for the common lung cancers most squamous and adenocarcinoma)
of which follow the 2011 lung adenocarcinoma classification
Squamous Keratinizing squamous cell carcinomae;
sponsored by the International Association for the Study
cell Nonkeratinizing squamous cell carcinomae;
of Lung Cancer (IASLC), American Thoracic Society carcinoma Basaloid squamous cell carcinomae; Preinvasive
(ATS), and European Respiratory Society (ERS), which has lesion- Squamous cell carcinoma in situ
essentially been adopted with only minor changes.
•• The most significant changes in this edition compared
Adenocarci- Lepidic adenocarcinomae; Acinar
noma adenocarcinoma; Papillary
with 2004 involve:
adenocarcinoma;  Micropapillary
 Use of immunohistochemistry throughout the adenocarcinomae; Solid adenocarcinoma;
classification including for resected lung cancers, Invasive mucinous adenocarcinomae- Mixed
 A new emphasis on genetic studies, in particular invasive mucinous and nonmucinous
integration of molecular testing to help personalize adenocarcinoma; nonmucinous adenocarcinoma;
treatment strategies for advanced lung cancer patients, Fetal adenocarcinoma;  Enteric
 A new classification for small biopsies and cytology as adenocarcinomae;  Minimally invasive
proposed by the 2011 IASLC/ATS/ERS Classification adenocarcinomae- Nonmucinous and Mucinous;
with a different approach to classification of resected Preinvasive lesions- Atypical adenomatous
lung cancers, hyperplasia and Adenocarcinoma in situe
(mucinous and nonmucinous)
 A completely different approach to lung adenocarcinoma
Answers
as proposed by the 2011 IASLC/ATS/ERS Note-e: New terms changed or entities added since 2004 WHO &
Explanations
Classification

39
 PGI Chandigarh Self-Assessment & Review: 2017–2013

Table ( Robbins 9th (SAE)/714): Histologic Classification of •• Activation of RAS is transient because RAS has an intrinsic
Malignant Epithelial Lung Tumors (Old classification-2004) GTPase activity that is accelerated by GTPase-activating
proteins (GAPs), which bind to the active RAS and augment
Tumor Classification its GTPase activity by more than 1000-fold, thereby
Squamous cell carcinoma: Papillary, clear cell, small cell, basaloid terminating signal transduction. Thus, GAPs prevent
uncontrolled RAS activity.
Small-cell carcinoma: Combined small-cell carcinoma
Adenocarcinoma: Minimally invasive adenocarcinoma Table ( Robbins 9th (SAE)/284): Selected Oncogene, their mode of
(nonmucinous, mucinous) activation and associated Human tumors
Lepidic, Acinar; papillary, solid (according to predominant pattern)
Mucinous adenocarcinoma Category Proto- Mode of Ac- Associated Hu-
Onco- tivation in man Tumor
Large-cell carcinoma: Large-cell neuroendocrine carcinoma gene Tumor
Adenosquamous carcinoma Growth Factors
Carcinomas with pleomorphic, sarcomatoid, or sarcomatous PDGF- chain PDGFB Overexpression Astrocytoma
elements Fibroblast HST1 Overexpression Osteosarcoma
Carcinoid tumor: Typical, atypical growth factors FGF3 Amplification Stomach cancer
Bladder cancer

e
Carcinomas of salivary gland type
Breast cancer

8/
Melanoma
38. Ans:  a. Tyrosine kinase has role in RAS activation, TGF- TGFA Overexpression Astrocytomas
b. Most common form of oncogene in human tumors,
HGF HGF Overexpression Hepatocellular car-

h,
c. It has an intrinsic GTPase activity, cinomas
d. Mutation may result in carcinomatous growth ar Thyroid cancer
[Ref: Robbins 9th (SAE)/284; Harshmohan 7th/203-04] Growth Factor Receptors
RAS Oncogene EGF-receptor ERBB1 Mutation Adenocarcinoma
ig
family (EGFR) Amplification of lung
–– Harshmohan 7th/203-04 ERBB2 Breast carcinoma
•• This is the most common form of oncogene in human
nd

(HER)
tumors, the abnormality being induced by point mutation in FMS-like tyros- FLT3 Point mutation Leukemia
RAS gene ine kinase 3
•• About a third of all human tumors carry mutated RAS
ha

Receptor for RET Point mutation Multiple endocrine

gene, seen in examples such as carcinoma colon, lung and neurotrophic neoplasia 2A and B,
pancreas factors familial medullary
•• Normally, the inactive form of RAS protein is GDP-bound
IC

thyroid carcinomas
while the activated form is bound to GTP. PDGF receptor PDGFRB Overexpres- Gliomas, leukemias
RAS Mutationsn sion, transloca-
PG

–– Robbins 9th (SAE)/286 tion

•• Point mutations of RAS family genes constitute the most Receptor for KIT Point mutation Gastrointestinal
common type of abnormality involving proto-oncogenes KIT ligand stromal tumors,
in human tumors. seminomas, leuke-
•• Approximately 15% to 20% of all human tumors express mias
mutated RAS proteins, but in some types of cancers the ALK receptor ALK Translocation, Adenocarcinoma of
frequency of RAS mutations is much higher. fusion gene lung, certain lym-
•• RAS proteins are members of a family of membrane- formation phomas
associated small G proteins that bind guanosine nucleotides Neuroblastoma
(guanosine triphosphate [GTP] and guanosine diphosphate Proteins Involved in Signal Transduction
[GDP]), similar to the larger trimolecular G proteins.
•• They normally flip back and forth between an excited GTP-binding KRAS Point mutation Colon, lung and
signal-transmitting state in which they are bound to GTP (G) proteins HRAS Point mutation pancreatic tumors
and a quiescent state in which they are bound to GDP. NRAS Point mutation Bladder and kidney
GNAO Point mutation tumors
•• Stimulation of receptor tyrosine kinases by growth
GNAS Point mutation Melanomas, hema-
factors leads to exchange of GDP for GTP and subsequent
tologic malignan-
conformational changes that generate active RAS, which cies
in turn stimulates both the MAPK and PI3K/AKT arms Uveal melanoma
Answers
of the receptor tyrosine kinase signaling pathway. These Pituitary adenoma,
& downstream kinases phosphorylate and activate a number other endocrine
Explanations
of cytoplasmic effectors as well as several transcription tumors
factors that turn on genes that support rapid cell growth.

40
 May  | 2017

e
8/
h,
ar
ig
Fig. (Robbins 9th (SAE)/285): Growth factor signaling pathways in cancer. Growth factor receptors, RAS, PI3K, MYC, and D cyclins are
nd

oncoproteins that are activated by mutations in various cancers. GAPs apply brakes to RAS activation, and PTEN serves the same function for PI3K.

39. Ans:  c. CD95 e. RAS

ha

[Ref: Robbins 9th (SAE)/291; Harshmohan 7th/205]

RAS is an proto-oncogene- Harshmohan 7th/203
IC

CD95 (Fas) is a death receptor that has a role in apoptosis- Robbins 9th (SAE)/56
Table ( Robbins 9th (SAE)/291): Selected Tumor Suppressor Genes and Associated Familial Syndromes and Cancers, Sorted by Cancer Hallmarks
PG

Gene Protein Function Familial Syndromes Sporadic Cancers

Inhibitors of Mitogenic Signaling Pathways
APC Adenomatous polyposis Inhibitor of WNT signaling Familial colonic polyps and Carcinomas of stomach, colon,
cdi protein carcinomas pancreas; melanoma
NF1 Neurofibromin-1 Inhibitor of RAS/MAPK Neurofibromatosis type 1 Neuroblastoma, juvenile
signaling (neurofibromas and malignant myeloid leukemia
peripheral nerve sheath tumors)
NF2 Merlin Cytoskeletal stability, Neurofibromatosis type 2 (acoustic Schwannoma, meningioma
Hippo pathway signaling schwannoma and meningioma)
PTCH Patched Inhibitor of Hedgehog Gorlin syndrome (basal cell Basal cell carcinoma
signaling carcinoma, medulloblastoma, several medulloblastoma
benign tumors)
PTEN Phosphatase and tensin Inhibitor of Pl3K/AKT Cowden syndrome (variety of benign Diverse cancers, particularly
homologue signaling skin, Gl, and CNS prowths; breast, carcinomas and lymphoid
endometrial, and thyroid carcinoma) tumors
SMAD2, SMAD2, SMAD4 Component of the Juvenile polyposis Frequently mutated (along
SMAD4 TGF signaling pathway, with other components of
repressors of MYC and the TGF signaling pathway) Answers
CDK4 expression, inducers in colonic and pancreatic &
Explanations
of CDK inhibitor expression carcinoma

41
 PGI Chandigarh Self-Assessment & Review: 2017–2013

Gene Protein Function Familial Syndromes Sporadic Cancers

Inhibitors of Cell Cycle progression
RB Retinoblastoma (RB) Inhibitor of G1/S Familial retinoblastoma syndrome Retinoblastoma; osteosarcoma
protein transition during cell cycle (retinoblastoma, osteosarcoma, carcinomas of breast, colon,
progression other sarcomas) lung
CDKN2A P16/INK4a and p14/ARF P16: Negative regulator of Familial melanoma Pancreatic, breast, and
cyclin-dependent kinases; esophageal carcinoma,
p14, indirect activator of melanoma, certain leukemias
p53
Inhibitors of “Pro-growth” Programs of Metabolism and Anglogenesis
VHL Von Hip pel Lindau (VHL) Inhibitor of hypoxia- Von Hippel Lindau syndrome (cere Renal cell carcinoma
protein induced transcription bellar hemangioblastoma, retinal
factors (e.g., HIF1) angioma, renal cell carcinoma)
STK11 Liver kinase B1 (LKB1) or Activator of AMPK family Peutz-Jeghers syndrome (Gl polyps, Diverse carcinomas (5%-20% of
STK11 of kinases; suppresses cell Gl cancers, pancreatic carcinoma and cases, depending on type)

e
growth when cell nutrient other carcinomas)
and energy levels and low

8/
SDHB, Succinate dehydrogenase TCA cycle, oxidative Familial paraganglioma, familial Paraganglioma
SDHD complex subunits B and D phosphorylation pheochromocytoma

h,
Inhibitors of Invasion and metastasis
CDH1 E-cadherin Cell adhesion, inhibition of Familial gastric cancer
ar Gastric carcinoma, lobular
cell motility breast carcinoma
Enablers of Genomic Stability
ig
TP53 P53 protein Cell cycle arrest and Li-Fraumeni syndrome (diverse Most human cancers
apoptosis in response to cancers)
nd

DNA damage
DNA Repair Factors
ha

BRCA1, Breast cancer-1 and breast Repair of double-stranded Familial breast and ovarian Rare
BRCA2 cancer-2 (BRCA1 and breaks in DNA carcinoma; carcinomas of male
BRCA2) breast; chronic lymphocytic leukemia
(BRCA2)
IC

MSH2, MSH1, MLH1, MSH6 DNA mismatch repair Hereditary nonpolyposis colon Colonic and endometrial
MLH1, carcinoma carcinoma
MSH6
PG

Unknown Mechanisms
WT1 Wilms tumor-1 (WT1) Transcription factor Familial Wilms tumor Wilms tumor, certain
leukemias
MEN1 Menin Transcription factor Multiple endocrine neoplasia-1 Pituitary, parathyroid, and
(MEN 1; pituitary, parathyroid, and pancreatic endocrine tumors
pancreatic endocrine tumors)

40. Ans:  a. Sickle cell anaemia - autosomal recessive, c. Vit D resistant rickets- X-linked dominant, d. Achondroplasia – autosomal
dominant
[Ref: Robbins 9th (SAE)/141-42]
Mendelian Disorders
–– Robbins 9th (SAE)/141-42
•• Sickle cell anaemia - autosomal recessive
•• Duchene muscle dystrophy- X-linked recessive
•• Vit D resistant rickets- X-linked dominant
Answers
& •• Achondroplasia – autosomal dominant
Explanations •• Osteogenesis Imperfecta - autosomal dominant

42
 May  | 2017

41. Ans:  a. Can be diagnosed in utero by USG, b. Hypertension develops in late stages of the disease, c. May proceed to renal failure
before preschool age, d. Enlargement of kidney
[Ref: Robbins 9th (SAE)/945,947-48; Harshmohan 7th/645; Harrison 19th/1853; O.P.Ghai 8th/507; CMDT 2016/914]
“ARPKD: The age at presentation may be perinatal, neonatal, infantile or juvenile, but frequently serious manifestations are present at birth
and result in death from renal failure in early childhood”- Harshmohan 7th/645
AUTOSOMAL RECESSIVE POLYCYSTIC KIDNEY DISEASE
–– O.P.Ghai 8th/507
•• Affected children usually present in the neonatal period with oliguria, respiratory insufficiency and palpable kidney
•• It is sometimes diagnosed in in young children presenting with hypertension, renal insufficiency or enlarged kidney, or with portal
hypertension due to associated congenital hepatic fibrosis
AUTOSOMAL RECESSIVE POLYCYSTIC KIDNEY DISEASE
–– Harrison 19th/1853
•• Classic ARPKD is generally diagnosed in utero or within the neonatal period and characterized by greatly enlarged echogenic
kidneys in diseased fetuses.
•• Some patients are diagnosed after the neonatal stage and form the older group. Morbidity and mortality in this group often involve

e
systemic hypertension, progressive renal insufficiency, and liver manifestations.
•• Some patients with the diagnosis of ARPKD at 1 year of age with nephromegaly exhibit slowly declining renal function over 20 years

8/
with only minimally enlarged kidneys at ESRD and markedly atrophic kidneys following renal transplantation. The slow progression
of renal disease is likely due to increasing fibrosis rather than the development of cysts.
•• Systemic hypertension is common in all ARPKD patients, even those with normal renal function.

h,
•• Diagnosis :Ultrasonography, CT, and MRI all can be used for diagnosis. Ultrasonography reveals large, echogenic kidneys with poor
corticomedullary differentiation. The diagnosis can be made in utero after 24 weeks of gestation in severe cases.
ar
Table ( Robbins 9th (SAE)/945): Summary of Renal Cystic Diseases (Partial list)
ig
Disease Inheritance Pathologic Features Clinical Features of Typical outcome
Complications
nd

Adult polycystic kidney Autosomal dominant Large multicystic kidneys, liver Hematuria, flank pain, Chronic renal failure
disease cysts, berry aneurysms urinary tract infection, beginning at age 40-60
ha

renal stones, hypertension years

Childhood polycystic kidney Autosomal recessive Enlarged, cystic kidneys at birth Hepatic fibrosis Variable, death in
disease infancy or childhood
IC

42. Ans:  All (a, b, c, d, e)

[Ref: Robbins 9th (SAE)/937; Harrison 19th/714; Harshmohan 7th/363]
PG

Type I cryoglobulinemia is composed of a single mono-clonal Ig, usually IgM. Type I cryoglobulinemia accounts for 10% to 15% of
people with cryoglobulinemia. It is mainly found in patients with lymphoproliferative disorders (immunocytoma/Waldenström
macroglobulinemia, multiple myeloma)”-asheducationbook.hematologylibrary.org
Light-Chain Cast Nephropathy (“Myeloma Kidney”)
–– Robbins 9th (SAE)/937
Overt renal insufficiency occurs in half of those with multiple myeloma and related lymphoplasmacytic disorders. Several factors
contribute to renal damage:
•• Bence-Jones proteinuria and cast nephropathy: The main cause of renal dysfunction is related to Bence-Jones (light-chain)
proteinuria, and correlates with the degree of proteinuria. Bence-Jones proteins combine with the urinary glycoprotein (Tamm-
Horsfall protein) under acidic conditions to form large, histologically distinct tubular casts that obstruct the tubular lumens and
induce a characteristic inflammatory reaction (lightchain cast nephropathy).
•• Amyloidosis of AL type, formed from free light chains (usually of λ type), which occurs in 6% to 24% of individuals with myeloma.
•• Light-chain deposition disease: In some patients, light chains (usually of κ type) deposit in GBMs and mesangium in nonfibrillar
forms, causing a glomerulopathy, and in tubular basement membranes, which may cause tubulointerstitial nephritis.
•• Hypercalcemia and hyperuricemia are often present in these patients.
“Multiple myeloma: With the increase in the amount of light chains presented to the tubule, the tubular cells become overloaded with
these proteins, and tubular damage results either directly from light chain toxic effects or indirectly from the release of intracellular
lysosomal enzymes. The earliest manifestation of this tubular damage is the adult Fanconi’s syndrome (a type 2 proximal renal tubular Answers
&
acidosis), with loss of glucose and amino acids, as well as defects in the ability of the kidney to acidify and concentrate the urine”-Harrison Explanations
19th/714; Nelson 20th/2530

43
 PGI Chandigarh Self-Assessment & Review: 2017–2013

43. Ans:  
b. Dry tap on bone marrow aspiration, c. Only Venous thromboembolism (VTE) is a disease that includes
potentially curative treatment is allogeneic stem cell both deep vein thrombosis (DVT) and pulmonary embolism
transplantation, d. Splenomegaly is almost invariably (PE)”- www.clevelandclinicmeded.com
present, e. Myeloblasts may be seen in peripheral blood
Table (L and B 26th/914): Risk factors for venous thromboembolism
[Ref: Robbins 9th (SAE)/620-21; Harshmohan 7th/339-40;
Harrison 19th/674-76; Davidson 22nd/] Patient factors Disease or surgical procedure
“Primary myelofibrosis: On examination, splenomegaly •• Age •• Trauma or surgery, especially
is almost invariably present and is commonly massive. The •• Obesity of pelvis, hip and lower limb
liver is enlarged in more than 50% of cases. Nucleated red •• Varicose veins •• Malignancy, especially pelvic,
blood cells are present and the myeloid series is shifted, with •• Immobility and abdominal metastatic
immature forms including a small percentage of promyelocytes •• Pregnancy •• Heart failure
•• Puerperium •• Recent myocardial infarction
or myeloblasts. Splenectomy is not routinely performed but
•• High-dose oestrogen therapy •• Paralysis of lower limb (s)
is indicated for medication-refractory splenic enlargement •• Previous deep vein infection
causing recurrent painful episodes, severe thrombocytopenia, thrombosis or pulmonary •• Inflammatory bowel disease
or an unacceptable transfusion requirement The only embolism •• Nephrotic syndrome
potentially curative option for this disease is allogeneic stem •• Thrombophilia •• Polycythaemia

e
cell transplantation in selected patients, especially those with a •• Paraproteinaemia
matched sibling donor”- CMDT 2016/518-19 •• Paroxysmal nocturnal

8/
“Primary myelofibrosis:Massive splenomegaly produce haemoglobinuria antibody or
abdominal discomfort, pain and discomfort. Hepatomegaly is lupus anticoagulant
present in half the cases. Bone marrow aspiration is generally •• Behçet’s disease

h,
•• Homocystinaemia
unsuccessful and yields ‘dry tap’. Peripheral blood smear shows
bizarre red cell shapes, tear drop poikilocytes, basophilic stippling,
ar Recurrent pulmonary emboli, sometimes with infarction, are
nucleated red cells, immature leucocytes (i.e. leucoerythroblastic an important cause of morbidity and mortality late in the course
reaction), basophilia and giant platelet forms”- Harshmohan of mitral stenosis”- Harrison 19th/1540,Davidson 22nd/616
ig
7th/340 Risk Factors for Venous Thromboembolism
Primary myelofibrosis or Chronic PMF or idiopathic myelo- –– (Schwartz 10th/918)
nd

fibrosis or agnogenic myeloid metaplasia, or myelofibrosis

Acquired
with myeloid metaplasia) Harrison 19th/674-76
•• Advanced age
•• No signs or symptoms are specific for PMF. Many patients
ha

•• Hospitalization/immobilization
are asymptomatic at presentation, and the disease is usually
•• Hormone replacement therapy and oral contraceptive use
detected by the discovery of splenic enlargement and/or •• Pregnancy and puerperium
abnormal blood counts during a routine examination.
IC

•• Prior venous thromboembolism

•• A blood smear will show the characteristic features of •• Malignancy
extramedullary hematopoiesis: teardrop-shaped red cells, •• Major surgery
nucleated red cells, myelocytes, and promyelocytes; •• Obesity
PG

myeloblasts may also be present. •• Nephrotic syndrome

•• Mild hepatomegaly may accompany the splenomegaly but •• Trauma or spinal cord injury
is unusual in the absence of splenic enlargement •• Long-haul travel (>6 hours)
•• Marrow is usually inaspirable due to the myelofibrosis •• Varicose veins
•• For unexplained reasons, splenectomy increases the risk of •• Antiphospholipid antibody syndrome
blastic transformation. Splenic irradiation is best •• Myeloproliferative disease
•• Allogeneic bone marrow transplantation is the only cura- •• Polycythemia
tive treatment for PMF Inherited
•• Factor V Leiden
44. Ans:  a. Pregnancy, b. OCP uses, d. Left ventricular failure, •• Prothrombin 20210A
e. Excessive unaccustomed exercise •• Antithrombin deficiency
[Ref: Robbins 9th (SAE)/127; Harshmohan 7th/106; L and B •• Protein C deficiency
26th/914; Schwartz 10th/918; Davidson 22nd/721] •• Protein S deficiency
•• Factor XI elevation
“Pulmonary embolism is 7-10 times more common in OCP
•• Dysfibrinogenemia
user than in nonusers in first year of use”-Shaw’s Gynae 16th/274
“Stress or fatigue fracture: occur mainly in lower limb Mixed Etiology
after excessive or unaccustomed exercise. Fat embolism is a •• Homocysteinemia
Answers complication of Stress fracture”- Applied Basic Science for Basic •• Factor VII, VIII, IX, XI elevation
&
Surgical Training by Andrew T. Raftery 2008/394 •• Hyperfibrinogenemia
Explanations
•• Activated protein C resistance without factor V Leiden

44