Author: Renu Maurya

Ophthalmia neonatorum

Ophthalmia neonatorum


OPHTHALMIA NEONATORUM

  • Inflammation of the conjunctiva in the first 28 days of life.
  • Also known as Neonatal Conjunctivitis.

TYPES:

Aseptic – 

  • Chemical conjunctivitis mostly
  • Silver nitrate – prophylaxis  of infectious conjunctivitisNot as common anymore because of the use of erythromycin ointment
  • Crede’s method of prophylaxis

Septic-

  • Bacterial, chlamydial (the most common cause), and viral infections are major causes  
  • Acquired by passage through birth canal

ETIOLOGY:

  • Chemical or Microbial
  • Silver nitrate: surface-active chemical, facilitating agglutinate gonococci and inactivating them., toxic to the conjunctiva, potentially causing a sterile neonatal conjunctivitis.
  • Microbial

Chlamydia trachomatis

  • Most common infectious cause
  • 4-10% pregnant women infected
  • Infants whose mothers have untreated chlamydial infections antepartum have a 30% to 40% chance of developing chlamydial neonatal conjunctivitis postpartum.
  • Reservoir- maternal cervix or urethra

Neisseria gonorrhea

  • Ability to penetrate intact epithelial cells, and once inside the cell, they divide rapidly.
  • Most dangerous and virulent infectious cause

Other bacteria

  • Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus viridans, and Staphylococcus epidermidis.
  • Escherichia coli, Klebsiella pneumoniae, Serratia marcescens, and Proteus, Enterobacter, and Pseudomonas species
  • Herpes simplex can cause neonatal keratoconjunctivitis

 CLINICAL FEATURES

  • Main findings are erythema, chemosis & purulent eye discharge
  • Incubation PeriodChemical Conjunctivitis:mild, transient tearing
  • Chemical conjunctivitis (silver nitrate)- 1st day of life- disappear spontaneously in 2-4 days
  • Gonococcal- 3-5 days or later
  • Chlamydial- 5-14 days
  • Other bacteria- longer
  • Herpetic- within 2wks 

Gonococcal: Bilateral purulent conjunctivitis – classical (75%), 

  • More severe (hyperacute conjunctivitis)
  • Chemosis and ulceration – perforation of cornea and endophthalmitis (inflmn. of ocular cavity & adj. structures)
  • Rhinitis, stomatitis, arthritis, meningitis, anorectal infection, septicemia…
  • Conjunctival membrane plus blindness

Chlamydial

  • From Mild hyperemia with scant mucoid discharge
  • Eyelid swelling, chemosis and pseudo membrane formation
  • unilateral or bilateral watery discharge
  • Blindness-rare and slower to develop-b/s of eyelid scarring and pannus (non suppurating inflamed lymph gland)
  • Pneumonitis, pharyngeal and rectal colonization

Other Bacteria

  • Similar findings like edema of eye lids, chemosis and eye discharge.
  • Pseudomonas is rare but can cause accelerated corneal ulceration and perforation; if left untreated endophthalmitis and death can occur.

Herpes simplex

  • Keratoconjunctivitis, generalized herpes simplex, encephalitis (low immunity)
  • Nonspecific lid edema, moderate conjunctival congestion
  • Non-purulent, unilateral or bilateral discharge
  • Geographic ulcers around the skin of the eye are typical

DIAGNOSIS:

  • Gram stain/ Geimsa stain of conjunctival scrapings (rule out Chlamydia…intracellular inclusion bodies)
  • Culture (Thayer-Martin/ chocolate/ blood Agar)
  • Direct immunofluorescent antibody
  • HSV culture if vesicles are present 

TREATMENT:

  • Prophylaxis Medical treatment:Systemic treatment of erythromycin, gentamycin and bacitracin are used for the treatment
  • Antenatal – thorough care of mother and treatment of genital infections when suspected.
  • Cesarean Delivery
  • Natal – Topical 0.5% silver nitrate, 1% tetracycline for gonococcal infection

Treatment prior to laboratory results

  • Topical erythromycin ointment and
  • IV or IM third-generation cephalosporin (ceftriaxone 30-50mg/kg/d IV or IM. Max 125mg)

 Chemical Conjunctivitis

  • Eye is regularly flushed and the eyelids cleaned – symptoms disappear within 1 to 2 days
Exam Question
 
  • Ophthalmia neonatorum is a common causes of childhood blindness
  • Systemic treatment of erythromycin, gentamycin and bacitracin are used for the treatment
  • N gonorrhoeae is the likely organism causing ophthalmia neonatorum on the 3rd day of birth
  • Chlamydial infection is causative organism of Ophthalmia neonatorum
  • Ophthalmia neonatorum is most commonly  caused by Chlamydia trachomatis, Neisseria gonorrhea 
  • Ophthalmia neonatorum is Inflammation of the conjunctiva occurring in an infant less than 30 days old
  • Herpes Simplex Virus II is responsible for causing ophthalmia neonatorum on 5-7th day after birth
Don’t Forget to Solve all the previous Year Question asked on Ophthalmia neonatorum

Ophthalmia neonatorum

OPHTHALMIA NEONATORUM

Q. 1

All of the following are common causes of childhood blindness, EXCEPT:

 A

Congenital rubella

 B

Toxoplasmosis

 C

Ophthalmia neonatorum

 D

Congenital dacryocystitis

Q. 1

All of the following are common causes of childhood blindness, EXCEPT:

 A

Congenital rubella

 B

Toxoplasmosis

 C

Ophthalmia neonatorum

 D

Congenital dacryocystitis

Ans. D

Explanation:

The common causes of childhood blindness that affects the retina are hereditary dystrophies, retinopathy of immaturity and toxoplasmosis. Corneal blindness could be due to vitamin A deficiency, measles and Ophthalmia neonatorum. Congenital rubella affects the lens of the eye. Other congenital conditions and cortical blindness can also attribute to blindness in children.

Ref: Pediatric Retina: Medical and Surgical Approaches, Mary Elizabeth Hartnett, M.D., Page: 318


Q. 2

Which one among the following is not used in opthalmia neonatorum?

 A

Erythromycin

 B

Bacitracin eye ointment

 C

Gentamycin

 D

Local penicillin

Q. 2

Which one among the following is not used in opthalmia neonatorum?

 A

Erythromycin

 B

Bacitracin eye ointment

 C

Gentamycin

 D

Local penicillin

Ans. D

Explanation:

The most common etiologies of ophthalmia neonatorum are chemical conjunctivitis (hyperemia and mucoid discharge during the first 24 hours postpartum) caused by silver nitrate or erythromycin prophylaxis, herpes simplex, Neisseria gonorrhoeae and N. meningitidis, and Chlamydia trachomatis.

 
Systemic treatment of erythromycin, gentamycin and bacitracin are used for the treatment. Topical treatment is not effective. Please note that local preparations of penicillin is barred in India.

Q. 3

Which of the following is the likely organism causing ophthalmia neonatorum on the 3rd day of birth?

 A

N gonorrhoeae

 B

Chlamydia

 C

Streptococcus

 D

Haemophilus influenzae

Q. 3

Which of the following is the likely organism causing ophthalmia neonatorum on the 3rd day of birth?

 A

N gonorrhoeae

 B

Chlamydia

 C

Streptococcus

 D

Haemophilus influenzae

Ans. A

Explanation:

The common causative organisms of ophthalmia neonatorum include Chlamydia trachomatis (most common), Neisseria gonorrhoeae (most threatening), Haemophilus species, Streptococcus species, Staphylococcus aureus, and viruses such as Herpes simplex (HSV). 

The “rule of fives” is a mnemonic for predicting the most likely bacterial etiology of the condition. However, there is considerable overlap in times to onset.
 
0 to 5 days: N gonorrhoeae
5 days to 5 weeks: Chlamydia
5 weeks to 5 years: Streptococcus or Haemophilus influenzae
 
Ref: Levsky M.E., DeFlorio P. (2010). Chapter 2. Ophthalmologic Conditions. In K.J. Knoop, L.B. Stack, A.B. Storrow, R.J. Thurman (Eds), The Atlas of Emergency Medicine, 3e.

Q. 4

Chlamydial infection is a/w

 A

Coronary heart disease

 B

LGV

 C

Ophthalmia neonatorum

 D

All

Q. 4

Chlamydial infection is a/w

 A

Coronary heart disease

 B

LGV

 C

Ophthalmia neonatorum

 D

All

Ans. D

Explanation:

Ans. is ‘a’ i.e., Corononary heart disease; ‘b’ i.e., LGV; ‘c’ i.e., Ophthalmia Neonatorum

.  “Epidemiological studies have demonstrated an association between serologic evidence of C. pneumoniae infection and atherosclerotic disease of the coronary and other arteries.”  

.  “Occasiaonal patients develop endocarditis and C. psittaci infection should be considered in cases of culture-negative endocarditis.”  

.   Pneumonia caused by C. pneumoniae resembles the primary atypical pneumonia of M. pneumoniae.

.  C. trachomatis types D to K can cause ophthalmia neonatorum.

.  C. trachomatis (type LI; L2, L3) causes L.G.V.


Q. 5

Ophthalmia neonatorum is caused by:

 A

Gonorrhoea

 B

H. Irtfluenzae

 C

Chlamydia

 D

a and c

Q. 5

Ophthalmia neonatorum is caused by:

 A

Gonorrhoea

 B

H. Irtfluenzae

 C

Chlamydia

 D

a and c

Ans. D

Explanation:

A i.e. Gonorrhoea; C i.e. Chlamydia


Q. 6

Ophthalmia neonatorum is seen in:

 A

Gonococcus

 B

Chlamydiae

 C

H. influnzae

 D

a and b

Q. 6

Ophthalmia neonatorum is seen in:

 A

Gonococcus

 B

Chlamydiae

 C

H. influnzae

 D

a and b

Ans. D

Explanation:

A i.e. Gonococcus; B i.e. Chlamydia


Q. 7

Which of the following is not given in ophthalmia neonatorum:

 A

Erythromycin locally

 B

Tetracycline 1%

 C

Penicillin locally

 D

Silver nitrate

Q. 7

Which of the following is not given in ophthalmia neonatorum:

 A

Erythromycin locally

 B

Tetracycline 1%

 C

Penicillin locally

 D

Silver nitrate

Ans. D

Explanation:

D i.e. Silver nitrate

  • 1% AgNO3 (Crede’s prophylaxis) used to prevent gonococcal opthalmia in new born is not used now as it leads to opthalmia neonatorum. It is important to note here that 1% AgNO3 is used for prophylaxis of gonococcal opthalmia, and it has got no role in treatment of opthalmia neonatorum. In fact it is a cause of opthalmia neonatorum.
  • If Ophthalmia Neonatorum is confirmed then the treatment is started on the lines of Gonorrhoeal infection and the treatment modified on the microbiological studies and clinical response.

Q. 8

Most common cause of blindness in children in India except:

 A

Malnutrition

 B

Ophthalmia neonatorum

 C

Glaucoma

 D

Congenital dacryocystitis

Q. 8

Most common cause of blindness in children in India except:

 A

Malnutrition

 B

Ophthalmia neonatorum

 C

Glaucoma

 D

Congenital dacryocystitis

Ans. D

Explanation:

D i.e. Congenital dacryocystitis


Q. 9

Ophthalmia neonatorum is:

 A

Inflammation of the conjunctiva occurring in an infant less than 30 days old

 B

Any discharge/watering from the eye in first week of life

 C

Always caused by gonococci

 D

All of the above

Q. 9

Ophthalmia neonatorum is:

 A

Inflammation of the conjunctiva occurring in an infant less than 30 days old

 B

Any discharge/watering from the eye in first week of life

 C

Always caused by gonococci

 D

All of the above

Ans. A

Explanation:

Ans. Inflammation of the conjunctiva occurring in an infant less than 30 days old


Q. 10

Incubation period of gonococcal ophthalmia neonatorum is:

 A

24 hours

 B

5-7 days

 C

7-10 days

 D

None of the above

Q. 10

Incubation period of gonococcal ophthalmia neonatorum is:

 A

24 hours

 B

5-7 days

 C

7-10 days

 D

None of the above

Ans. D

Explanation:

Ans. None of the above


Q. 11

Neonatal conjunctivitis is caused by all except:

 A

Gonococcus

 B

Chlamydia

 C

Aspergillus

 D

Pseudomonas

Q. 11

Neonatal conjunctivitis is caused by all except:

 A

Gonococcus

 B

Chlamydia

 C

Aspergillus

 D

Pseudomonas

Ans. C

Explanation:

Ans. Aspergillus


Q. 12

Most common cause of blindness in children in India except:

 A

Malnutrition

 B

Ophthalmia neonatorum

 C

Glaucoma

 D

Congenital dacryocystitis

Q. 12

Most common cause of blindness in children in India except:

 A

Malnutrition

 B

Ophthalmia neonatorum

 C

Glaucoma

 D

Congenital dacryocystitis

Ans. D

Explanation:

Ans. Congenital dacryocystitis


Q. 13

The following is responsible for causing ophthalmia neonatorum on 5-7th day after birth:

March 2013 (b)

 A

Chemical

 B

Herpes Simplex Virus II

 C

Neisseria gonorrhoea

 D

Chlamydia trachomatis

Q. 13

The following is responsible for causing ophthalmia neonatorum on 5-7th day after birth:

March 2013 (b)

 A

Chemical

 B

Herpes Simplex Virus II

 C

Neisseria gonorrhoea

 D

Chlamydia trachomatis

Ans. B

Explanation:

Ans. B i.e. Herpes simplex virus II

Ophthalmia neonatorum

  • Time frame of signs/ symptoms following birth play an important role in determining the most likely etiology and subsequent proper diagnosis and treatment
  • Within 48 hours: Chemical conjunctivitis (Typically presents within first 24 hours following birth) & Niesseria gonorrhoe
  • 48-72 hours: Staph. aureus, Strepto. Hemolyticus
  • 5-7 days: HSV-II
  • More than 1 week: C. trachomatis (D-K)

Q. 14

Bacteria not causing ophthalmia neonatorum ‑

 A

Chlamydia

 B

Gonococcus

 C

Pseudomonas

 D

Moraxella

Q. 14

Bacteria not causing ophthalmia neonatorum ‑

 A

Chlamydia

 B

Gonococcus

 C

Pseudomonas

 D

Moraxella

Ans. D

Explanation:

Ans. is ‘d’ i.e., Moraxella

Ophthalmia neonatorum

  • Ophthalmia neonatorum, also called neonatal conjunctivitis, is the conjunctivitis in the first month of life. Infection may be acquired during birth from infected birth canal (most common) or after birth. The causative agents are : –
  1. Common organisms are : – Gonococcus, C. trachomatis, Herpes simplex virus. Other organisms are : -Staphylococcus aureus, pneumococcus, Streptococcus, Pseudomonas, Serratia, Klebsiella.
  2. Chemical conjunctivitis : – Caused by use of silver nitrate or antibiotic prophylaxis.


Rickets

Rickets


TYPES:

  • Nutritional Rickets
  • Vitamin D Resistant Rickets
  • X-linked dominant
  • Defect in skeletal ossification
  • Reduced serum phosphorus
  • Vitamin D Dependent Rickets (Type I & Type II)
  • Congenital Rickets

ETIOLOGY:

  • Nutritional rickets: vit D deficiency, Malabsorption
  • Rickets is due to Loss of calcium in urine,Increased mobilisation of calcium from bone
  • Accelerated loss of vit D: Phenytoin, Rifampicin, Barbiturates
  • Impaired hydroxylation in liver and Kidney:
  • Liver disease, Hypoparathyroidism, Renal failure, Renal Tubular Acidosis
  • Vit D Resistant rickets, Fanconi’s syndrome, Wilson’s disease.

CLINICAL FEATURES:

  • Delayed teeth development 
  • Defect in proximal tubular reabsorption is seen in  vitamin D resistant rickets
  • Widening of growth plate
  • Craniosynostosis
  • Scoliosis
  • Triradiate pelvis
  • Wormian bones 
  • Quant’s sign (a T-shaped depression in the occipital bone) 
  • Caries teeth
  • Rickets is seen before closure of growth plates
  • Susceptibility to fractures,weakness and hypotonia, and disturbances in growth
  • Parietal flattening
  • Costochondral junction swelling
  • Frontal bossing develops in the skull
  • Craniotabes: The calvariae are softened
  • Sutures may be widened
  • Genu valgum(knock knee)
  • Wide open fontanelles in infants
  • Rachitic rosary Prominence of the costochondral junctions(in infancy)
  • Harrison’s groove :indentation of the lower ribs at the site of attachment of the diaphragm
  • Knock knee + Coxa Vara
  • Bow legs
  • Pot Belly
  • Hot cross bun sign 
  • Forward projection of sternum (Pectus Carinatum)
  • Caput Quadratum
  • Widening of wrist 
  • Wind swept deformity
  • Lumbar Lordosis
  • Short stature, coxa vara, Kyphoscoliosis
  • Rickets is characterized by defective mineralization of bones
  •  Any child with rickets also has osteomalacia while the reverse is not necessarily true because Osteomalacia is found within the same spectrum of rickets, but occurs in persons of any age group, not only in children.

RADIOGRAPHIC FINDINGS:

  • Thickening and widening of epiphysis 
  • Cupping and fraying of metaphysis 
  • Irregular metaphyseal margins
  • Flaring of anterior ends of ribs
  • Ricketic rosary
  • Bowing of diaphysis

BIOCHEMICAL REACTIONS:

  • Serum calcium: normal or low
  • Serum phosphate: low
  • Alkaline phosphatase: high
  • Hypophosphatasia shows low level of alk. phosphatase 
  • PTH: High
  • Hypophophatemia 

DIAGNOSIS:

Blood tests:

  • Serum calcium may show low levels of calcium, serum phosphorus may be low, and serum alkaline phosphatase may be high.
  • Arterial blood gases may reveal metabolic acidosis

An X-ray or radiograph of an advanced sufferer from rickets tends to present in a classic way:

  • Bow legs (outward curve of long bone of the legs) and a deformed chest. 
  • Changes in the skull also occur causing a distinctive “square headed” appearance. These deformities persist into adult life if not treated. 
  • Long-term consequences include permanent bends or disfiguration of the long bones, and a curved back.
  • The earliest feature of healing in rickets is seen in X ray of growing end of the bones.
Exam Question
  • Defect in proximal tubular reabsorption is seen in  vitamin D resistant rickets
  • Craniotabes, Bow legs & Increase alkaline phosphatase are findings of rickets
  • Rickets in infancy is characterised by Craniotabes,Rachitic rosary, Wide open fontanelles
  • Radiological examination of long bones are investigations showing the earliest evidence for healing in treatment of rickets
  • Flaring of anterior ends of the ribs is characteristically seen in Rickets
  • A child presented with clinical features of rickets but low level of serum alkaline phosphatase is seen in Hypophosphatasia
  •  Any child with rickets also has osteomalacia while the reverse is not necessarily true because Osteomalacia is found within the same spectrum of rickets, but occurs in persons of any age group, not only in children.
  • vitamin D-resistant rickets X-linked dominant showing Defect in skeletal ossification & Reduced serum phosphorus
  • Triradiate pelvis is seen in Rickets
  • Serum marker of rickets is Alkaline phoshpatase 
  • Rickets is due to Loss of calcium in urine,Increased mobilisation of calcium from bone
  • Basic pathology in rickets is Defect in mineralization
  • Cupping of metaphysis & Defective Mineralization is seen in rickets
  • Craniotabes & Widening of wrist are seen in nutritional rickets
  • Bow legs,Pot belly & Craniotabes is seen in Rickets 
  • Most common cause of genu valgum in children is Rickets
  • Wind swept deformity is seen in Rickets
  • Costochondral junction swelling  is seen in Rickets
  • Prominent fontanelle,Hot cross bun sign & Caries teeth is seen in active rickets
  • Cupping of metaphysis,Ricketic rosary are the radiographic feature of rickets
  • Quant’s sign (a T-shaped depression in the occipital bone) may be present in rickets 
  • Hypophophatemia is seen in Rickets
  • Wormian bones are seen in rickets
Don’t Forget to Solve all the previous Year Question asked on Rickets

Rickets

Rickets

Q. 1

What is true of vitamin D resistant rickets?

 A X linked recessive
 B

No End organ resistance to 1, 25(OH)2D2

 C Defect in proximal tubular reabsorption 
 D

Hyperphosphatemia and high 1, 25 (OH)2 D3

Q. 1

What is true of vitamin D resistant rickets?

 A X linked recessive
 B

No End organ resistance to 1, 25(OH)2D2

 C Defect in proximal tubular reabsorption 
 D

Hyperphosphatemia and high 1, 25 (OH)2 D3

Ans. C

Explanation:

Defect in proximal tubular reabsorption REF: Nelson’s 18th ed page 2720

Familial Hypophosphatemia: (Vitamin D-Resistant Rickets, X-Linked Hypophosphatemia)

  • The most commonly encountered non-nutritional form of rickets is familial hypophosphatemia. The usual mode of inheritance is X-linked dominant
  • Pathogenic mechanisms involve defects in the proximal tubular reabsorption of phosphate and in the conversion of 25(OH)D to 1,25(OH)2 D. The latter defect is evidenced by low-normal serum 1,25(OH)2 D levels despite hypophosphatemia and by the finding that further phosphate depletion of subjects with familial hypophosphatemia does not stimulate 1,25 (OH)2 D synthesis as it does in normal subjects
  • Patients have a normal or slightly reduced serum calcium level, a moderately reduced serum phosphate level, elevated alkaline phosphatase activity, and no evidence of secondary hyperparathyroidism. Urinary phosphate excretion is large, despite hypophosphatemia, indicating a defect in renal tubular phosphate

Q. 2

In rickets all are seen EXCEPT:

 A Craniotabes
 B

Increased acid phosphatase

 C Bow legs
 D

Increase alkaline phosphatase

Q. 2

In rickets all are seen EXCEPT:

 A Craniotabes
 B

Increased acid phosphatase

 C Bow legs
 D

Increase alkaline phosphatase

Ans. B

Explanation:

Increased acid phosphatase REF: Nelson Textbook of Paediatrics 17th edition page 186487 “Alkaline phosphatase not acid phosphatase is increased in rickets”

RICKETS is a softening of bones in children due to deficiency or impaired metabolism of vitamin D, magnesium, phosphorus or calcium, potentially leading to fractures and deformity. Types

  • Nutritional Rickets
  • Vitamin D Resistant Rickets
  • Vitamin D Dependent Rickets (Type I & Type II)
  • Congenital Rickets

Signs and symptoms:

  • Bone pain or tenderness
  • Dental problems
  • Muscle weakness (rickety myopathy or “floppy baby syndrome” or “slinky baby” (such that the baby is floppy or slinky-like)
  • Increased tendency for fractures (easily broken bones), especially greenstick fractures
  • Skeletal deformity

            — Toddlers: Bowed legs (genu varum)

            — Older children: Knock-knees (genu valgum) or “windswept knees”

            — Cranial, pelvic, and spinal deformities (such as lumbar lordosis)

  • Growth disturbance
  • Hypocalcaemia (low level of calcium in the blood)
  • Tetany (uncontrolled muscle spasms all over the body)
  • Craniotabes (soft skull)
  • Costochondral swelling (aka “rickety rosary” or “rachitic rosary”)
  • Harrison’s groove
  • Double malleoli sign due to metaphyseal hyperplasia
  • Widening of wrist raises early suspicion, it is due to metaphyseal cartilage hyperplasia. 

Diagnosis:

Blood tests:

Serum calcium may show low levels of calcium, serum phosphorus may be low, and serum alkaline phosphatase may be high.

  • Arterial blood gases may reveal metabolic acidosis
  • An X-ray or radiograph of an advanced sufferer from rickets tends to present in a classic way:

bow legs (outward curve of long bone of the legs) and a deformed chest. Changes in the skull also occur causing a distinctive “square headed” appearance. These deformities persist into adult life if not treated. Long-term consequences include permanent bends or disfiguration of the long bones, and a curved back.


Q. 3

Rickets in infancy is characterised by the following except :

 A

Craniotabes

 B

Rachitic rosary

 C

Wide open fontanelles

 D

Bow legs

Q. 3

Rickets in infancy is characterised by the following except :

 A

Craniotabes

 B

Rachitic rosary

 C

Wide open fontanelles

 D

Bow legs

Ans. D

Explanation:

Bow legs Mel: Ghai Paediatrics 6/e, p 128. Nelson 17/e,p 183; Apley’s 8/e, p 119]

Ghai states – “Long bones of legs get deformed when the child starts bearing weight. Therefore deformities of legs are unusual before the age of 1 year. Anterior bowing of legs, knock knee and coxa vera are the usual deformities.”

  • Clinical manifestation of Rickets:

The main factor responsible for pathogenesis in Rickets: –

  • In rickets the abdomen is protuberant (pot belly) because of marked hypotonia of abdominal wall muscles. Visceral proptosis and lumbar lordosis also occurs in rickets.
  • More Questions on rickets: ?
  • Earliest manifestation of Rickets     Craniotabes
  • Clinical manifestation of Rickets appears at       later half of first year or in T.’d year. (Unusual below the age of 3 months)
  • Questions on Radiological feature of Rickets: ?

– Earliest radiological changes appear in long bones of radius and ulna

– Cupping of inetaphyses

– Large gap b/w epiphyses and metaphyses (widening of the phy.vis i.e. growth plate)

– Irregular metaphyseal margins (ill-defined zone of provisional calcification)

–  Osteopenia


Q. 4

A 8 year old boy is being treated for rickets. Which of the following investigations shows the earliest evidence for healing?

 A

Serum Ca

 B

Serum phosphates

 C

Radiological examination of long bones

 D

Serum ALP

Q. 4

A 8 year old boy is being treated for rickets. Which of the following investigations shows the earliest evidence for healing?

 A

Serum Ca

 B

Serum phosphates

 C

Radiological examination of long bones

 D

Serum ALP

Ans. C

Explanation:

The earliest feature of healing in rickets is seen in X ray of growing end of the bones.


Q. 5

Flaring of anterior ends of the ribs is characteristically seen in:

 A

Neurofibromatosis

 B

Scurvy

 C

Rickets

 D

Hypothyroidism

Q. 5

Flaring of anterior ends of the ribs is characteristically seen in:

 A

Neurofibromatosis

 B

Scurvy

 C

Rickets

 D

Hypothyroidism

Ans. C

Explanation:

Flaring of the anterior ends of the ribs is characteristically seen in rickets.

In children, prior to epiphyseal fusion, vitamin-D deficiency results in growth retardation associated with an expansion of the growth plate known as rickets.

Though flaring of the ribs  can also be seen in scurvy, it is more characteristic of rickets.

Ref: Harrison’s Principle of Internal Medicine, 16th Edition, Page 2247; Abnormal Skeletal Phenotypes: From Simple Signs to Complex Diagnosis By Alessandro Castriota-Scanderbeg, Bruno Dallapiccola, Page 140


Q. 6

A child presented with clinical features of rickets but low level of serum alkaline phosphatase. He has the following condition:

 A

Primary biliary cirrhosis

 B

Hypophosphatasia

 C

Hyperparathyroidism

 D

Benign familial hyperphosphatasemia

Q. 6

A child presented with clinical features of rickets but low level of serum alkaline phosphatase. He has the following condition:

 A

Primary biliary cirrhosis

 B

Hypophosphatasia

 C

Hyperparathyroidism

 D

Benign familial hyperphosphatasemia

Ans. B

Explanation:

Hypophosphatasia is a rare autosomal recessive condition characterized by deficiency of alkaline phosphatase activity in serum, bone, and tissues.

Enzyme deficiency leads to poor skeletal mineralization with clinical and radiographic features similar to rickets.

Diagnosis is made by demonstrating elevated urinary phosphoethanolamine associated with low serum alkaline phosphatase.

Alkaline phosphatases are primarily found in liver, bone, intestines, kidney, and placenta. It increased in,
  • Obstructive hepatobiliary disease
  • Bone disease (physiologic bone growth, Paget disease, osteomalacia, osteogenic sarcoma, bone metastases)
  • Hyperparathyroidism
  • Rickets
  • Benign familial hyperphosphatasemia
  • Pregnancy (third trimester)
  • GI disease (perforated ulcer or bowel infarct)
  • Hepatotoxic drugs
Ref: Zeitler P.S., Travers S.H., Nadeau K., Barker J.M., Kelsey M.M., Kappy M.S. (2012). Chapter 34. Endocrine Disorders. In W.W. Hay, Jr., M.J. Levin, R.R. Deterding, J.J. Ross, J.M. Sondheimer (Eds), CURRENT Diagnosis & Treatment: Pediatrics, 21e.

Q. 7

A 7 year old boy brought with clinical manifestations suggestive of rickets. 

 
Assertion: Any child with rickets also has osteomalacia, while the reverse is not necessarily true.
 
Reason: Osteomalacia is found within the same spectrum of rickets, but occurs in persons of any age group, not only in children.
 A

Both Assertion and Reason are true, and Reason is the correct explanation for Assertion

 B

Both Assertion and Reason are true, and Reason is not the correct explanation for Assertion

 C

Assertion is true, but Reason is false

 D

Assertion is false, but Reason is true

Q. 7

A 7 year old boy brought with clinical manifestations suggestive of rickets. 

 
Assertion: Any child with rickets also has osteomalacia, while the reverse is not necessarily true.
 
Reason: Osteomalacia is found within the same spectrum of rickets, but occurs in persons of any age group, not only in children.
 A

Both Assertion and Reason are true, and Reason is the correct explanation for Assertion

 B

Both Assertion and Reason are true, and Reason is not the correct explanation for Assertion

 C

Assertion is true, but Reason is false

 D

Assertion is false, but Reason is true

Ans. A

Explanation:

Osteomalacia is found within the same spectrum of rickets, affects trabecular bone, and results in undermineralization of osteoid bone. By definition, rickets is found only in children prior to the closure of the growth plates, while osteomalacia occurs in persons of any age.

Ref: Internal Medicine: An Illustrated Radiological Guide By Jarrah Ali Al-Tubaikh, 2010, Page 222.

 


Q. 8

Craniotabes is found in children with the following conditions, EXCEPT:

 A

Rickets

 B

Hydrocephalus

 C

Syphilis

 D

Kernicterus

Q. 8

Craniotabes is found in children with the following conditions, EXCEPT:

 A

Rickets

 B

Hydrocephalus

 C

Syphilis

 D

Kernicterus

Ans. D

Explanation:

Conditions associated with kernicterus are rickets, hydrocephalus, syphilis, cleidocranial disastosis, cretinism, wormian bones and vitamin A excess. Craniotabes is a normal finding upto 6 months.

 

 

 

Craniotabes refers to softening and thinning of bones of the skull. Assessment of craniotabes is done by palpating the scalp firmly along the suture line in the temporoparietal area. This causes cranial bones to feel pliable and soft and on firm palpation an indentation is created.

 

 

 

Ref: Clincal Methods in Paediatrics by ML Kulkarni page 527. Advanced Pediatric Assessment By Ellen M. Chiocca  page 270.

 


Q. 9

All of the following statements are correct about vitamin D-resistant rickets, EXCEPT:

 A

X-linked dominant condition

 B

Defect in skeletal ossification

 C

Reduced serum phosphorus

 D

Reduced serum calcium

Q. 9

All of the following statements are correct about vitamin D-resistant rickets, EXCEPT:

 A

X-linked dominant condition

 B

Defect in skeletal ossification

 C

Reduced serum phosphorus

 D

Reduced serum calcium

Ans. D

Explanation:

Hypophosphatemic rickets (vitamin D–resistant rickets) is an dominant X-linked condition in which vitamin D production and metabolism are normal but renal tubular loss of phosphate interferes with skeletal ossification.

The major manifestations are a mild-to-moderate decrease in stature and bowing of the lower extremities. 

 

 

The medical history usually discloses a parent or sibling with short stature and bowlegs. In addition, serum phosphorus is reduced, and serum calcium is normal. 

 

 

 

Ref: Rab G.T. (2006). Chapter 11. Pediatric Orthopedic Surgery. In H.B. Skinner (Ed), CURRENT Diagnosis & Treatment in Orthopedics, 4e.

 


Q. 10

Triradiate pelvis is seen in :

 A

Rickets

 B

Chondrodystrophy

 C

Osteoporosis

 D

Hyperparathyroidism

Q. 10

Triradiate pelvis is seen in :

 A

Rickets

 B

Chondrodystrophy

 C

Osteoporosis

 D

Hyperparathyroidism

Ans. A

Explanation:

Ans. is a i.e. Rickets

Contracted pelvis is alteration in size and / or shape of pelvis of sufficient degree so as to alter the normal mechanism of labour in an average size baby. It can be a result of malnutrition, diseases or injuries affecting the bone of pelvis or it can be due to any developmental defect.



Q. 11

Serum marker of rickets is –

 A

Acid phosphates

 B

Alkaline phoshpatase

 C

Decreased serum calcium

 D

Urinary posphates

Q. 11

Serum marker of rickets is –

 A

Acid phosphates

 B

Alkaline phoshpatase

 C

Decreased serum calcium

 D

Urinary posphates

Ans. B

Explanation:

Ans. is ‘b’ i.e., Alkaline phosphatase

o Amongst the given options, alkaline phosphatase is best because it is raised in all type of rickets.

o The primary (Basic) investigations in a child of rickets are :‑

  1. Serum calcium
  2. Serum phosphorus
  3. Alkaline phosphatase

o If patient does not respond to calcium and Vit D therapy, secondry investigations are done :‑

  1. Vit D level
  2. Serum PTH
  3. Urinary calcium and phosphorus.

Q. 12

Rickets is due to –

 A

Loss of calcium in urine

 B

Increased mobilisation of calcium from bone

 C

Decreased absorption of calcium

 D

a and b

Q. 12

Rickets is due to –

 A

Loss of calcium in urine

 B

Increased mobilisation of calcium from bone

 C

Decreased absorption of calcium

 D

a and b

Ans. C

Explanation:

Ans. is ‘c’ i.e., Decreased absorption of calcium

Rickets is a metabolic disorder characterized by deficient mineralization of bone.

o Rickets may be due to : –

i)         Vit D deficient —> absorption of calcium (Vit D dependent rickets).

ii)       Increased phosphate excretion due to defective reabsorption —) Vit D resistant rickets.


Q. 13

Basic pathology in rickets-

 A

Defective bone matrix formation

 B

Defect in mineralization

 C

Defect in osteoid formation

 D

All of the above

Q. 13

Basic pathology in rickets-

 A

Defective bone matrix formation

 B

Defect in mineralization

 C

Defect in osteoid formation

 D

All of the above

Ans. B

Explanation:

Ans. is ‘b’ i.e., Defect in mineralization

o To know the pathophysiology of rickets, one should know the structure of bone.

o Bone consists of ‑

1)      Protein matrix i.e. osteoid —–> also known as unmineralized bone.

2)      Mineral phase. principally composed of calcium and phosphate, mostly in the form of hydroxyapatite.

o In rickets osteoid (protein matrix) is formed normally but mineralization of this osteoid does not occur i.e. there is defective mineralization.

o Rickets is a syndrome of diverse etiology characterized by defective mineralization of bone and epiphyseal cartilage (growth plate) of growing bones.


Q. 14

Seen in rickets A/E –

 A

Cupping of metaphysis

 B

Defective Mineralization

 C

Epiphyseal dysgenesis

 D

All

Q. 14

Seen in rickets A/E –

 A

Cupping of metaphysis

 B

Defective Mineralization

 C

Epiphyseal dysgenesis

 D

All

Ans. C

Explanation:

Ans. is ‘c’ i.e., Epiphyseal dysgenesis

o In rickets osteoid (protein matrix) is formed normally but mineralization of this osteoid does not occur i.e. there is defective mineralization.

o Epiphyseal plate (growth plate) has following five zones (moving from epiphysis towards metaphysis) –

i)        Resting zone

ii)       Proliferative zone

iii)      Maturation zone

iv)      Zone of hypertrophy

v)       Zone of provisional calcification

o Normally, capillaries grow from metaphysis to epiphysis via tunnels in the zone of provisional calcification. This ingrowth of capillaries destroy the cartilagenous cells in zone of hypertrophy, thereby limiting the growth of epiphyseal plate.

Changes in Rickets

o In rickets, tunnels are not formed in zone of provisional calcification because there is defective mineralization No capillary ingrowth from metaphysis to epiphysis —> cartilagenous cells continue to proliferate but do not die —> Thickening of growth plate.

o Proliferating cells in growth plate extend beyond the normal width of bone —> widning of growth plate (clinically presents as palpable enlargement at wrist, elbow and ankle, also at costochondral junction -4 rachitic rosary).

o As there is softening of metaphysis, axial pressure pushes the epiphysis into the metaphysis cupping or flaring of metaphysis (In normal bones, metaphysis is rigid so cupping does not occur).

o As there is irregular calcification (mineralization), the edge of the metaphysis loses its sharp border —> fraying of metaphysis.

In subperiosteal region, calcium deposition in the osteoid surrounding the shaft is impaired —> softening and deformity of long bones.


Q. 15

Deficient mineralisation in epiphysical growth cartilage is seen in –

 A

Rickets

 B

Osteomalacia

 C

Scurvy

 D

Hyperparathyroidism

Q. 15

Deficient mineralisation in epiphysical growth cartilage is seen in –

 A

Rickets

 B

Osteomalacia

 C

Scurvy

 D

Hyperparathyroidism

Ans. A

Explanation:

Ans. is ‘a’ i.e., Rickets


Q. 16

A 2-year-old boy has vitamin D resistant rickets. His investigations revealed serum Calcium- 9 mg/ dl, Phosphate- 2.4 mg/d1, alkaline phosphatase- 1041 IU, normal intact parathyroid hormone and bicarbonate 22 mEq/L. Which of the following is the most probable diagnosis –

 A

Distal renal tubular acidosis

 B

Hypophosphatemic rickets

 C

Vitamin D dependent rickets

 D

Hypoparathyroidism

Q. 16

A 2-year-old boy has vitamin D resistant rickets. His investigations revealed serum Calcium- 9 mg/ dl, Phosphate- 2.4 mg/d1, alkaline phosphatase- 1041 IU, normal intact parathyroid hormone and bicarbonate 22 mEq/L. Which of the following is the most probable diagnosis –

 A

Distal renal tubular acidosis

 B

Hypophosphatemic rickets

 C

Vitamin D dependent rickets

 D

Hypoparathyroidism

Ans. B

Explanation:

Ans. is ‘b i.e., Hyphosphatemic rickets

Clues in this question are ‑

1. Normal calcium                                            3. Low phosphate

2. Normal paratharmone                                 4. Elevated alkaline phosphatase

o All these suggest the diagnosis of hypophosphatemic rickets.


Q. 17

A 2 year old boy has vitamin D refractory rickets. Investigations show serum calcium 9 mg/dl. Phosphate 2.4 mg dl, alkaline phosphate 1040 IU. Parathyroid hormone and bicarbonate levels are normal. The most probable diagnosis is ‑

 A

Distal renal tubular acidosis

 B

Hypophosphatemic rickets.

 C

Vitamin D dependent rickets

 D

Proximal renal tubular acidosis

Q. 17

A 2 year old boy has vitamin D refractory rickets. Investigations show serum calcium 9 mg/dl. Phosphate 2.4 mg dl, alkaline phosphate 1040 IU. Parathyroid hormone and bicarbonate levels are normal. The most probable diagnosis is ‑

 A

Distal renal tubular acidosis

 B

Hypophosphatemic rickets.

 C

Vitamin D dependent rickets

 D

Proximal renal tubular acidosis

Ans. B

Explanation:

Ans. is ‘b’ i.e., Hypophosphatemic rickets


Q. 18

True about nutritional rickets –

 A

Craniotabes

 B

Multiple #

 C

Widening of wrist

 D

a and c

Q. 18

True about nutritional rickets –

 A

Craniotabes

 B

Multiple #

 C

Widening of wrist

 D

a and c

Ans. D

Explanation:

Ans. is ‘a’ i.e., Craniotabes, ‘c’ i.e., Widening of wrist

Clinical features of rickets

o Clinical manifestations of rickets are usually manifested by 6 months of age.

o Rickets is unusual below the age of 3 months.

A.Reginal manifestations

1. Skull

 Craniotabes (softening of cranial bones)

o It is the earliest manifestation of rickets.

o Pressure over occipital and parietal bones gives ping pong ball like feel.

               Frontal bossing –> Prominent frontal bones.

               Parietal bossing

               Widned sutures

               Delayed closure of anterior fontanel.

              Caput quadratum or hot cross – bun skull The widned suture & thickening of bone around sutures create a cruciate pattern.

2. Chest

              Rachitic rosary —> Prominent costochondral junction.

              Pectus craniatum (pigeon breast) sternum projects forward.

              Harrison ‘s groove —> A horizontal depression along lower border of chest corresponding to the insertion of diaphram. It occurs due to pulling of the softened ribs by the diaphragm during inspiration.

3. Teeth

               Delayed eruption

               Enamel hypoplasia and dental caries.

4. Spine

               Thoracic kyphosis —> Rachitic Cat back

               Accentuation of lumbar lordosis

               Scoliosis (uncommon)

5. Limbs & joints

               Bone pain & Tenderness —> most common manifestation.

               Coxa vara

               Genu valgus or Genu varus

              Bowing of tibia, femur, radius & ulna

              Widening of wrist, elbow, knee & ankle because of enlargement of ends of long bones.

               Rachitic saber shins

              Sawsage – like enlargements of ends of the phalanges and metacarpals, with regular constrictions corresponding to the joints —> string-of-pearls deformity.

                   Windswept deformity

                  Double malleoli sign —> on palpation of medial malleoli two malleoli are palpable instead of one.

6. Abdomen

             Abdomen becomes protuberant —> Rachitic pot – belly.

              This is because of marked hypotonia of abdominal muscles.

B.Systemic manifestations

                         Growth retardation

                         Apathy, listlessness & irritability

                         Hypotonia and muscle weakness

                         Ligament laxity

                         Tetany, laryngeal stridor and convulsions, when there is hypocalcemia or Alkalosis which predisposes to hypocalcemia.

Note ‑

Deficiency of vitamin D in early infancy may result in bilateral lamellar cataract.


Q. 19

Rickets in infant present as all except-

 A

Cranitabes

 B

Widened Fontanel

 C

Rachitic Rosary

 D

Bow legs

Q. 19

Rickets in infant present as all except-

 A

Cranitabes

 B

Widened Fontanel

 C

Rachitic Rosary

 D

Bow legs

Ans. D

Explanation:

Ans. is ‘d’ i.e., Bow legs

o Long bones of legs gets deformed when the child starts bearing weight. Therefore deformities of legs are unusual before the age of one year.


Q. 20

All of the following are seen in Rickets except –

 A

Bow legs

 B

Gunstock deformity

 C

Pot belly

 D

Craniotabes

Q. 20

All of the following are seen in Rickets except –

 A

Bow legs

 B

Gunstock deformity

 C

Pot belly

 D

Craniotabes

Ans. B

Explanation:

Ans. is ‘b’ i.e., Gustock deformity

o Gunstock deformity is seen in malunited supracondylar fracture of humerus.

Note ‑

o Dont get confuse between option ‘a’ and answer of previous question. In this question the age of the child has not been mentioned. Bow legs can occur, once the child starts walking.


Q. 21

Most common cause of genu valgum in children is ‑

 A

Osteoarthritis

 B

Rickets

 C

Paget disease

 D

Rheumatoid arthritis

Q. 21

Most common cause of genu valgum in children is ‑

 A

Osteoarthritis

 B

Rickets

 C

Paget disease

 D

Rheumatoid arthritis

Ans. B

Explanation:

Ans. is ‘b’ i.e., Rickets

o Genu valgum (also known as knock knee) is a condition where knees are abnormally approximated and ankles are abnormally divergent.

o It is caused due to softening of bones or damage to lateral Femoral epiphysis

Out of given options ‑

o Most common cause in children is Rickets.

o Other diseases given in option are seen in elderly.


Q. 22

Wind swept deformity is seen in‑

 A

Scurvy

 B

Rickets

 C

Achondroplasia

 D

Osteoporosis

Q. 22

Wind swept deformity is seen in‑

 A

Scurvy

 B

Rickets

 C

Achondroplasia

 D

Osteoporosis

Ans. B

Explanation:

Ans. is ‘b’ i.e., Rickets

Windswept deformity

o A valgus deformity of one in association of varus deformity of other knee is known as windswept deformity.

Causes of windswept deformity

o Rickets              

o Physeal osteochondromatosis      

o Hereditary dysplasia (epiphyseal dysplasia) of bone.


Q. 23

True about vit – D deficiency rickets –

 A

Vit. D3 given at a dose of 50-150 mg/day

 B

X-ray knee joint is diagnostic

 C

Rickety rosary is tender

 D

All

Q. 23

True about vit – D deficiency rickets –

 A

Vit. D3 given at a dose of 50-150 mg/day

 B

X-ray knee joint is diagnostic

 C

Rickety rosary is tender

 D

All

Ans. B

Explanation:

Ans. is ‘b’ i.e., X-ray knee joint is diagnostic

Treatment of Vit D deficiency rickets

o There are two startgies for administration of vitamin D ‑

A) Startgy 1 (stoss regimen)

               6 lac IU (15,000 g or 15 mg) Vit D3 is administered every 2 weekly.

               At every follow up monitoring is done by X-rays and blood investigations.

               Once healing is started, children are further put on 400 IU or 10 g of vitamin B3 per day.

B) Startgy 2

               2,000 – 5,000 IU (50 – 125 g) of vit D3 is given every day for 4-6 weeks.

Radiological changes of Rickets

o Earliest radiological changes are seen around the wrist, i.e. at lower end of radius & ulna.

o Later on, similar changes may also be seen around knee, elbow & ankle.

o X-ray findings are –

             Cupping & flaring of metaphysis

             Large gap between epiphysis and metaphysis because of widening of physis (growth plate).

             Fraying of metaphysis due to irregular calcification at metaphyseal margins.

             Generalized osteopenia

             Cortical thinning

             Coarse & fuzzy trabeculation

            White line of calcification (frenkels line) at physeal region —> It is the first radiological sign of healing and appears after administration of Vit D.

About other options

o Rachitic rosary is nontender (in contrast rosary of scurvy, i.e. scorbutic rosary is tender).

o Softening of ribs impairs air movement and predisposes patient to chest infection (pneumonia) and atelectasis. o Hyponatremia may be seen in rickets due to renal tubular acidosis (not in Vit D deficiency rickets).


Q. 24

Earlier manifestation of Rickets is-

 A

Craniotabes

 B

Rachitic rosary

 C

Harrison groove

 D

Pigeon chest

Q. 24

Earlier manifestation of Rickets is-

 A

Craniotabes

 B

Rachitic rosary

 C

Harrison groove

 D

Pigeon chest

Ans. A

Explanation:

Ans. is `a’ i.e., Craniotabes

Craniotobes is the earliest manifestation of Rickets.


Q. 25

Splaying and Cupping of the metaphysis is seen in –

 A

Rickets

 B

Scurvy

 C

Paget’s disease

 D

Lead poisoning

Q. 25

Splaying and Cupping of the metaphysis is seen in –

 A

Rickets

 B

Scurvy

 C

Paget’s disease

 D

Lead poisoning

Ans. A

Explanation:

Ans. is ‘a’ i.e., Rickets


Q. 26

Costochondral junction swelling are seen in –

 A

Scurvy

 B

Rickets

 C

Chondrodystrophy

 D

All of the above

Q. 26

Costochondral junction swelling are seen in –

 A

Scurvy

 B

Rickets

 C

Chondrodystrophy

 D

All of the above

Ans. D

Explanation:

Ans. is ‘d’ i.e., All of the above


Q. 27

Which of the following is not a sign of active rickets?

 A

Prominent fontanelle

 B

Hot cross bun sign

 C

Saddle nose

 D

Caries teeth

Q. 27

Which of the following is not a sign of active rickets?

 A

Prominent fontanelle

 B

Hot cross bun sign

 C

Saddle nose

 D

Caries teeth

Ans. C

Explanation:

Ans. is ‘c’ i.e., Saddle nose

o Saddle nose is not seen in rickets


Q. 28

Bulging anterior fontanel is/are seen in-

 A

Rickets

 B

CMV infection

 C

Scurvy

 D

a and b

Q. 28

Bulging anterior fontanel is/are seen in-

 A

Rickets

 B

CMV infection

 C

Scurvy

 D

a and b

Ans. D

Explanation:

Ans. is ‘a’ i.e., Rickets; ‘b’ i.e., CMV infection

Bulging anterior fontanel

o The fontanel is normally flat or slightly depressed relative to the frontal and parietal bones and is pulsatile. o Bulging fontanel is a reliable sign of raised ICT during infancy.

o The pulsations may disappear when fontanel becomes tense due to marked elevation of ICT.


Q. 29

Radiological features of rickets include:

 A

Narrowing of epiphysis

 B

Cupping of metaphysis

 C

Ricketic rosary

 D

b and c

Q. 29

Radiological features of rickets include:

 A

Narrowing of epiphysis

 B

Cupping of metaphysis

 C

Ricketic rosary

 D

b and c

Ans. D

Explanation:

B, C i.e. Cupping of metaphysis, Ricketic rosary

 Radiological features of bone

Rickets

 Metaphysis: indistinct, frayed, splaying, and cupping of marginQ. Patchy sclerosis in case of intermittent dietary deficiency

  • Widened epiphysis with hazed cortical margin
  • Generalized reduction in bone density
  • Looser’s zone (less common)
  • Severe cases show Genu valgum, bow legs, thoracic kyphosis, pigeon chest, ricketic rosaryQ, skull bossing, cox vera.
Scurvy
  • Metaphysis: Frankel’s while line, trumerfeld lucent zone, Pelikan’s spur due to fracture.
  • Wimberger’s sign (small epiphysis surrounded by sclerotic rim)
  • Subperiosteal hemorrhage with periosteal elevation
  • Ground glass appearance of bone with pencil thin cortex.



Q. 30

Splaying and cupping of the’metaphysis is seen in :

 A

Rickets

 B

Scurvy

 C

Paget’s disease

 D

Lead poisoning

Q. 30

Splaying and cupping of the’metaphysis is seen in :

 A

Rickets

 B

Scurvy

 C

Paget’s disease

 D

Lead poisoning

Ans. A

Explanation:

A i.e. Rickets


Q. 31

Flaring of anterior ends of the ribs is characteristically seen in

 A

Neurofibromatosis

 B

Scurvy

 C

Rickets

 D

Hypothyroidism

Q. 31

Flaring of anterior ends of the ribs is characteristically seen in

 A

Neurofibromatosis

 B

Scurvy

 C

Rickets

 D

Hypothyroidism

Ans. C

Explanation:

C i.e. Rickets

  • Flaring of anterior ends of rib is charcteristically seen in ricketsQ and beaded ribs are found in osteogenesis imperfectaQ.
  • Other causes of multiple anterior rib flaring are – achondroplasia, scurvy, thanatophoric dysplasia & normal variants.

Q. 32

Quant’s sign (a T-shaped depression in the occipital bone) may be present in –

 A

Down’s syndrome

 B

Head injury

 C

Rickets

 D

Scurvy

Q. 32

Quant’s sign (a T-shaped depression in the occipital bone) may be present in –

 A

Down’s syndrome

 B

Head injury

 C

Rickets

 D

Scurvy

Ans. C

Explanation:

Ans. is ‘c’ i.e., Rickets 


Q. 33

Hypophophatemia is seen in:

 A

Pseudohypoparathyroidism

 B

CRF

 C

Rickets

 D

Respiratory acidosis

Q. 33

Hypophophatemia is seen in:

 A

Pseudohypoparathyroidism

 B

CRF

 C

Rickets

 D

Respiratory acidosis

Ans. C

Explanation:

Answer is C (Ricket’s)

Hypophosphatemia may be seen in X-linked Hypophoaphatemic Rickets and in Hyperparathyroidism. Causes of Hypophosphatemia:

 

I. Reduced renal tubular phosphate reabsorption

A. PTH/PTFIrP – dependant

I. Primary hyperparathyroidism

  1. Secondary hyperparathyroidism
  2. Vitamin D deficiency/resistance
  3. Calcium starvation/malabsorption
  4. Bartter syndrome

II. Autosomal recessive renal hypercalciuria with hypomagnesemia

B. PTH/PTHrP independent

1. Genetic hypophosphatemia

  1. X-linked hypophophatemic rickets
  2. Dent disease
  3. Autosomal dominant hypophophatemic rickets
  4. Fanconi syndrome(s)
  5. Cystinosis
  6. Wilson disease
  7. McCune-Albright syndrome (fibrous dysplasia)
  8. Idiopathic hypercalciuria (absorptive subtype)
  9. Hereditary hypophosphatemia with hypercalciuria (Bedouins)

2. Tumor-induced osteomalacia

D. Impaired intestinal phosphate absorption

  1. Aluminium-containing antacids
  2. Sevalamer


3. Other systemic disorders

  1. Poorly controlled diabetes mellitus
  2. Alcoholism
  3. Hyperaldosteronism
  4. Hypomagnesemia
  5. Amyloidosis
  6. Hemolytic uremic syndrome
  7. Renal transplantation or partial liver resection
  8. Rewarming or induced hyperthermia

4. Drugs or toxins

  1. Ethanol
  2. Acetazolamide, other diuretics
  3. High-dose estrogens or glucocorticoids
  4. Heavy metals (lead, cadmium)
  5. Toluene, N-methyl formamide
  6. Cisplatin, ifosfamide, foscarnet, rapamycin
  7. Calcitonin, pamidronate

III. Shifts of extracellular phosphate into cells

  1. Intravenous glucose
  2. Insulin therapy of prolonged hyperglycemia or diabetic ketoacidosis
  3. Catecholamines (epinephrine, dopamine, albuterol)
  4. Acute respiratory alkalosis
  5. Gram negative sepsis, toxic shock syndrome
  6. Recovery from starvation or acidosis
  7. Rapid cellular proliferation
    1. Leukemic blast crisis
    2. Intensive erythropoietin, other CSF therapy

IV. Accelerated net bone formation

  1. Following parathyroidectomy
  2. Treatment of Vitamin D deficiency, Paget disease
  3. Osteoblstic metastases

Q. 34

True about rickets:

 A

Hyperphosphatemia

 B

Hypophosphatemia

 C

Hypophosphaturia

 D

Decreased alkaline phosphatase

Q. 34

True about rickets:

 A

Hyperphosphatemia

 B

Hypophosphatemia

 C

Hypophosphaturia

 D

Decreased alkaline phosphatase

Ans. B

Explanation:

Answer : B.) Hypophosphatemia.

Rickets

  • Failure of osteoid calcification (rickets) in children is because of a disruption in the pathway of either vitamin D or phosphate metabolism.
  • Types of rickets include the following:
    • Nutritional rickets
    • Congenital rickets
    • Rickets of prematurity
    • Vitamin D resistance (type I and type II)
    • Neoplastic rickets
    • Hypophosphatemic rickets
    • Drug-induced rickets.
  • Low phosphate and high alkaline phosphatase levels characterize most of the disorders

Q. 35

Alkaline phosphatase is elevated in all, EXCEPT:

 A

Rickets

 B

Osteomalacia

 C

Hypoparathyroidism

 D

Hypophosphatemia

Q. 35

Alkaline phosphatase is elevated in all, EXCEPT:

 A

Rickets

 B

Osteomalacia

 C

Hypoparathyroidism

 D

Hypophosphatemia

Ans. C

Explanation:

Answer is C (Hypoparathyroidism) :

Raised alkaline phosphatase levels are associated with hyperparathyroidism and not with hypoparathyroidi.sm. Serum alkaline phosphatase levels may be raised in hyperparathyroidism depending upon degree of involvement of bone. Q


Q. 36

Rachitic rosary is a feature of:              

March 2013 (c)

 A

Rickets

 B

Scurvy

 C

Osteomalacia

 D

Osteoporosis

Q. 36

Rachitic rosary is a feature of:              

March 2013 (c)

 A

Rickets

 B

Scurvy

 C

Osteomalacia

 D

Osteoporosis

Ans. A

Explanation:

Ans. A i.e. Rickets

Rickets

  • Pathology: Defective mineralization of osteoid/ bones & cartilage
  • Features:

–        Craniotabes,

–        Wide open fontanelle,

–        Rachitic rosary (Enlargement of costochondral junction)

  • X-ray appearances:

–        Widening & thickening of epiphysis,

Cupping & fraying of metaphysis


Q. 37

All of the following are seen in rickets except:

September 2009

 A

Frenkels line

 B

Widening of epiphysis- diaphysis distance

 C

Cupping and splaying of metaphysis

 D

Rarefaction

Q. 37

All of the following are seen in rickets except:

September 2009

 A

Frenkels line

 B

Widening of epiphysis- diaphysis distance

 C

Cupping and splaying of metaphysis

 D

Rarefaction

Ans. A

Explanation:

Ans. A: Frenkels Line

In rickets, the skeletal effects are due to lack of calcification of osteoid.

The first changes of rickets appear in rapidly growing distal ends of ulna & radius (wrist & knee are commonly involved due to more use).

Rarefaction of provisional zone of calcification with widening of epiphysis- diaphysis distance is first to appear. The most obvious change are at ‘metaphysis’- where rapid growth is occurring.

First change to appear is a ‘loss of normal zone of provisional calcification’ adjacent to metaphysis.

This begins as an indistinctness of the metaphyseal margin, progressing to a ‘frayed’ appearance with widening of the growth plate, due to lack of calcification of metaphyseal bone.

Weight bearing & stress on uncalcified bone gives rise to ‘splaying’ Sr ‘cupping’ of metaphysis.

A similar but less marked effect occurs in subperiosteal layer, which may cause lack of distinctness of cortical margin.

Eventually a generalized reduction in bone density is seen.

In the epiphysis – there may be some haziness of cortical margin.

Thus all findings in Rickets occur due to failure of calcification & abnormal demineralization

i. Skull changes

–        Pronounced calvarial demineralization

–        Basilar Invagination

–        Indistinct sutural margin

–        Delayed tooth eruption Premature craniostenosis

–        Craniotabes

–        Calvarial thickening following treatment

ii. Spine changes

–       Scoliosis

–        Biconcave vertebral bodies

–        Triradiatic pelvis.


Q. 38

All of the following are true about rickets except:

March 2010

 A

Craniotabes

 B

Rachitic rosary

 C

knock-knees

 D

Hypertonia

Q. 38

All of the following are true about rickets except:

March 2010

 A

Craniotabes

 B

Rachitic rosary

 C

knock-knees

 D

Hypertonia

Ans. D

Explanation:

Ans. D: Hypertonia

The history in patients with rickets may include the following:

  • Generalized muscular hypotonia of an unknown mechanism is observed in most patients with clinical (as opposed to biochemical and radiographic) signs of rickets.
  • Craniotabes manifests early in infants with vitamin D deficiency, although this feature may be normal in infants, especially for those born prematurely.
  • If rickets occurs at a later age, thickening of the skull develops. This produces frontal bossing and delays the closure of the anterior fontanelle.

In the long bones, laying down of uncalcified osteoid at the metaphases leads to spreading of those areas, producing knobby deformity, which is visualized on radiography as cupping and flaring of the metaphyses.

  • Weight bearing produces deformities such as bowlegs and knock-knees.
  • In the chest, knobby deformities results in the rachitic rosary along the costochondral junctions. The weakened ribs pulled by muscles also produce flaring over the diaphragm, which is known as Harrison groove. The sternum may be pulled into a pigeon-breast deformity.

In more severe instances in children older than 2 years, vertebral softening leads to kyphoscoliosis. The ends of the long bones demonstrate that same knobby thickening. At the ankle, palpation of the tibial malleolus gives the impression of a double epiphysis (Marfan sign). Because the softened long bones may bend, they may fracture one side of the cortex (i.e., greenstick fracture).


Q. 39

Which of the following is the radiological features of rickets:  

 A

Frenkel line

 B

Narrowing of epiphysis

 C

Metaphyseal cupping and splaying

 D

Pelikan spur

Q. 39

Which of the following is the radiological features of rickets:  

 A

Frenkel line

 B

Narrowing of epiphysis

 C

Metaphyseal cupping and splaying

 D

Pelikan spur

Ans. C

Explanation:

Q. 40

Which of the following is not a radiological feature of rickets: 

March 2010

 A

Metaphyseal cupping

 B

Physeal widening

 C

Frenkel’s line

 D

Triradiate pelvis

Q. 40

Which of the following is not a radiological feature of rickets: 

March 2010

 A

Metaphyseal cupping

 B

Physeal widening

 C

Frenkel’s line

 D

Triradiate pelvis

Ans. C

Explanation:

Ans. C: Frenkel’s Line


Q. 41

Hypocalcemia with hypophosphatemia is seen in:

September 2006

 A

Crush injury

 B

Rhabdomyolysis

 C

Vitamin D dependent rickets-II

 D

Renal failure

Q. 41

Hypocalcemia with hypophosphatemia is seen in:

September 2006

 A

Crush injury

 B

Rhabdomyolysis

 C

Vitamin D dependent rickets-II

 D

Renal failure

Ans. C

Explanation:

Ans. C: Vitamin D dependent rickets-II

In rhabdomyolysis due to crush injury, hypocalcemia and hyperphosphatemia may occur. Severe intravascular hemolysis may lead to a similar syndrome.

Hyperphosphatemia alters calcium and phosphate ion solubility products, and calcium deposition in soft tissue may occur. The lower circulating concentrations of 1, 25 (OH)2D may further aggravate the hypocalcemia by impairing intestinal absorption of calcium.

Hyperphosphatemic-induced hypocalcemia inhibits vitamin D synthesis and results in an increase in PTH secretion. Secondary hyperparathyroidism from long-term hyperphosphatemia is usually associated with renal insufficiency. Treatment should be directed towards the hyperphosphatemia in order to correct the hypocalcemia.

Hypophosphatemia is more severe than hypocalcemia in vitamin D deficiency states because of the increased secretion of PTH, which is only partly active in elevating blood calcium but is capable of phosphaturia.


Q. 42

Vitamin D deficiency is manifested as:

September 2005

 A

Scurvy

 B

Night blindness

 C

Beri-Beri

 D

Rickets

Q. 42

Vitamin D deficiency is manifested as:

September 2005

 A

Scurvy

 B

Night blindness

 C

Beri-Beri

 D

Rickets

Ans. D

Explanation:

Ans. D: Rickets

Rickets, a childhood disease characterized by impeded growth, and deformity, of the long bones which can be caused by calcium or phosphorus deficiency as well as a lack of vitamin D.

The dietary risk factors for rickets include abstaining from animal foods.

Vitamin D deficiency remains the main cause of rickets among young infants in most countries, because breast milk is low in vitamin D and social customs and climatic conditions can prevent adequate UVB exposure.

Osteomalacia, occurs exclusively in adults and is characterized by proximal muscle weakness and bone fragility.


Q. 43

Fraying at the ends of long bones is seen in:

 A

Rickets

 B

Scurvy

 C

Osteogenesis imperfecta

 D

Congenital syphilis

Q. 43

Fraying at the ends of long bones is seen in:

 A

Rickets

 B

Scurvy

 C

Osteogenesis imperfecta

 D

Congenital syphilis

Ans. A

Explanation:

Ans. Rickets


Q. 44

The radiological changes in Rickets are:

 A

Narrowing or absence of the normal zone of provisional calcification

 B

Fracture of the bone

 C

Epiphysis smaller than normal and have characteristic thin pencil line cortex

 D

Bowing of the bone

Q. 44

The radiological changes in Rickets are:

 A

Narrowing or absence of the normal zone of provisional calcification

 B

Fracture of the bone

 C

Epiphysis smaller than normal and have characteristic thin pencil line cortex

 D

Bowing of the bone

Ans. A

Explanation:

Ans. Narrowing or absence of the normal zone of provisional calcification


Q. 45

The earliest evidence of Rickets is seen by:

 A

Radiological examination of growing end of bone

 B

S. alkaline phosphatase level

 C

S. calcium level

 D

S. phosphorus level

Q. 45

The earliest evidence of Rickets is seen by:

 A

Radiological examination of growing end of bone

 B

S. alkaline phosphatase level

 C

S. calcium level

 D

S. phosphorus level

Ans. A

Explanation:

Ans. Radiological examination of growing end of bone


Q. 46

 Fraying of anterior ends of ribs is seen in

 A

Scurvy

 B

Rickets

 C

Down syndrome

 D

Osteoporosis

Q. 46

 Fraying of anterior ends of ribs is seen in

 A

Scurvy

 B

Rickets

 C

Down syndrome

 D

Osteoporosis

Ans. B

Explanation:

Ans. Rickets


Q. 47

Ricketsial disease with positive Weil-Felix reaction by only OX-19 ‑

 A

Epidemic typhus

 B

Scrub thphus

 C

Trench fever

 D

Q-fever

Q. 47

Ricketsial disease with positive Weil-Felix reaction by only OX-19 ‑

 A

Epidemic typhus

 B

Scrub thphus

 C

Trench fever

 D

Q-fever

Ans. A

Explanation:

Ans. is ‘a’ i.e., Epidemic typhus

Weil felix reaction

  • This reaction is an agglutination test in which sera are tested for agglutinins to 0 antigens of certain nonmotile proteus strains OX – 19, OX – 2 and OX – K.
  • The basis of the test is the sharing of an alkali – stable carbohydrate antigen by some rickettsiae and by certain strains of proteus, P. vulgaris OX – 19 and OX – 2 and P. mirabilis OX – K.
  • The test is usually done as a tube agglutination, though rapid slide agglutination methods have been employed for screening.

Q. 48

Genu valgum deformity is seen in all except ‑

 A

Rickets

 B

Bone Dysplasia

 C

Rheumatoid arthritis

 D

Medial compartment osteoarthritis

Q. 48

Genu valgum deformity is seen in all except ‑

 A

Rickets

 B

Bone Dysplasia

 C

Rheumatoid arthritis

 D

Medial compartment osteoarthritis

Ans. D

Explanation:

Ans. is ‘d’ i.e., Medial compartment osteoarthritis

Genu valgum (knock knee)

Genu valgum is a condition in which the lower legs are positioned at an outward angle with abnormal approximation of knees and abnormally divergent ankles. Genu valgum is a condition in which the knees touch, but the ankles do not touch. Normally, a child is born with genu varum. Therefore, neonates and infants normally have genu varum. When the infant begins to stand and walk, the lower limb straighten and this physiological genu varus disappear at around years of age. The leg become straight. Then, between the age of 2-3 years genu valgum starts developing gradually with maximum genu – valgum of 12° at the age of 31/4 years. Finally genu-valgum spontaneously get corrected by the age of 7 years to that of normal adult genu valgum of 7 – 8°. So upto 7 years, exagerated genu valgum is physiological. If this exaggerated genu valgum persists after 8 years, then it is pathological genu valgum.


Q. 49

Genu valgum deformity is seen in all except ‑

 A

Rickets

 B

Bone Dysplasia

 C

Rheumatoid arthritis

 D

Medial compartment osteoarthritis

Q. 49

Genu valgum deformity is seen in all except ‑

 A

Rickets

 B

Bone Dysplasia

 C

Rheumatoid arthritis

 D

Medial compartment osteoarthritis

Ans. D

Explanation:

Ans. is ‘d’ i.e., Medial compartment osteoarthritis


Q. 50

Wormian bones are seen in all except ‑

 A

Fibrous dysplasia

 B

Osteogenesis inperfecta

 C

Cretinism

 D

Rickets

Q. 50

Wormian bones are seen in all except ‑

 A

Fibrous dysplasia

 B

Osteogenesis inperfecta

 C

Cretinism

 D

Rickets

Ans. A

Explanation:

Ans. is ‘a’ i.e., Fibrous dysplasia

Wormian bones

  • Wormian bones are extra bone pieces that occur within a suture in the cranium.
  • These are irregular isolated bones which appear in addition to the usual centers of ossification of the cranium.
  • They occur most frequently in the course of the lambdoid suture.
  • Causes of wormian bones (Mnemonic – PORKCHOPS)
  1. Pyknodysostosis
  2. Osteogenesis imperfecta
  3. Rickets
  4. Kinky hair syndrome
  5. Cleidocranial dysostosis
  6. Hypothyroidism (cretinism) / Hypophosphatasia
  • Otopalatodigital syndrome
  • Progeria
  1. Syndrome of Downs
  • Wormian bone appears radiographically as islands of ossification in the skull in nonossified membranous bone.
  • To be diagnostic value, the wormian bones should be 4 mm by 6 mm in size, 10 in number and arranged in a mosaic pattern.
  • Wormian bones are not present in normal skull.

Q. 51

Which among the following are the causes of the condition of the lower limbs as shown in photograph below ? 

 A

Osteomalacia.

 B

Rickets.

 C

An injury to the growth area of the tibia bone.

 D

All of the above.

Q. 51

Which among the following are the causes of the condition of the lower limbs as shown in photograph below ? 

 A

Osteomalacia.

 B

Rickets.

 C

An injury to the growth area of the tibia bone.

 D

All of the above.

Ans. D

Explanation:

 The condition of the lower limbs as shown in photograph above represents Knock knees (Genu valgum).

Knock knees are angular deformities at the knee, in which the head of the deformity points inward. A standing child whose knees touch, but whose ankles do not, is usually said to have knock knees. During early childhood, knock knees are a part of normal growth and development.

CAUSES-

Knock knees are usually part of the normal growth and development of the lower extremities

.•   Some cases, especially in a child who’s 6 or older, may be a sign of an underlying bone disease, such as osteomalacia or rickets. 

•   Obesity can contribute to knock knees—or can cause gait (walking) problems that resemble, but aren’t actually, knock knees. 

•   The condition can occasionally result from an injury to the growth area of the shin bone (tibia), which may result  in just one knocked knee.


Q. 52

Diagnose the underlying metabolic disorder as seen in the  X-ray wrist below? 

 A

Scurvy.

 B

Rickets.

 C

Osteomalacia.

 D

Osteoporosis.

Q. 52

Diagnose the underlying metabolic disorder as seen in the  X-ray wrist below? 

 A

Scurvy.

 B

Rickets.

 C

Osteomalacia.

 D

Osteoporosis.

Ans. B

Explanation:

The underlying metabolic disorder as seen in the  X-ray wrist above represents Rickets (Appearance, cupping,Fraying,Splaying).

Rickets is a disease of growing bone that is unique to children and adolescents. It is caused by a failure of osteoid to calcify in a growing person.



Glutathione

Glutathione

Q. 1

Which of the following statements concerning glutathione is true? 

 A

Glutathione Reductase is a selenium-containing enzyme that scavenges free radicals

 B

Serves as a vehicle for the transport of amino acids into some cells

 C

Peroxidase is used to maintain hemoglobin in the reduced state

 D

Is present in most if not all cells in trace quantities

Q. 1

Which of the following statements concerning glutathione is true? 

 A

Glutathione Reductase is a selenium-containing enzyme that scavenges free radicals

 B

Serves as a vehicle for the transport of amino acids into some cells

 C

Peroxidase is used to maintain hemoglobin in the reduced state

 D

Is present in most if not all cells in trace quantities

Ans. B

Explanation:

Glutathione is a tripeptide, 7- glutamylcysteinylglycine, present in high concentration in all cells. The ‘y-glutamyl cycle is used by some cells to transport amino acids across the cell membrane. A membrane-associated enzyme, y-glutamyl transpeptidase forms peptide bonds between the glutamyl moiety of glutathione and the amino acid to be transported into the cell. The glutamyl-aniino acid is split off from the cysteinylglycine part of the molecule as both are brought into the cell. The transported amino acid is then split from the glutamyl moiety, depositing the free amino acid on the cytosolic side of the membrane. 5-Oxyproline is produced from the glutamyl moiety, which has to be replaced or resynthesized, as does the glutathione. This process uses 3 adenosine triphosphates (ATPs), but is very active in some tissues, such as the kidney. Glutathione reductase is the enzyme used to protect the red cell from oxidative stress and to reduce methemoglobin. Glutathione peroxidase is the selenium containing enzyme used to scavenge free radicals and peroxides.
Glutathione is present in all cells in relatively large amounts, attesting to its importance in metabolism. Glutathione S-transferase is a liver enzyme used in detoxification reactions. It forms a glutathione complex with the compound to be detoxified. There is no such enzyme as glutathione transaminase.


Q. 2

All are true about glutathione except:

 A

It is a tripeptide

 B

It converts hemoglobin to methemoglobin

 C

It conjugates xenobiotics

 D

It is co-factor of various enzymes

Q. 2

All are true about glutathione except:

 A

It is a tripeptide

 B

It converts hemoglobin to methemoglobin

 C

It conjugates xenobiotics

 D

It is co-factor of various enzymes

Ans. B

Explanation:

it converts hemoglobin to methemoglobin [Ref: Harper 26/e, p 166, 169, 629; Various websites]

Glutathione prevents oxidation of hemoglobin to methemoglobin.

The heme group of hemoglobin contains iron in the ferrous state. Hemoglobin can accept and transport oxygen only when the iron atom is in its ferrous form. When hemoglobin becomes oxidized, it is converted to the ferric state (Fe3+) or methemoglobin. Methemoglobin is unable to transfer oxygen. Glutathione prevents this oxidation. Glutathione

  • Glutathione is a tripeptide of glutamic acid, cysteine, and glycine. The molecule has a sulfhydryl (-SH) or thiol group on the cysteine, which accounts for its strong electron-donating character.
  • It exists in two forms: reduced glutathione or GSH. In the reduced state, the thiol group of cysteine is able to donate a reducing equivalent (Fr+ e) to other unstable molecules, such as reactive oxygen species. In donating an electron, glutathione itself becomes reactive, but readily reacts with another reactive glutathione to form glutathione disulfide (GSSG) or oxidized glutathione. GSH can be regenerated from GSSG by the enzyme glutathione reductase.
  • While all cells in the human body are capable of synthesizing glutathione, liver glutathione synthesis has been shown to be essential. The liver is the largest GSH reservoir.
  • Because of its reducing property, reduced glutathione has potent antioxidant action.
  • Functions:

a. GSH is an extremely important cell protectant. It directly reduces reactive hydroxyl free radicals, other oxygen-centered free radicals, and radical centers on DNA and other biomolecules

b. GSH is the essential cofactor for many enzymes which require thiol-reducing equivalents, and helps keep redox­sensitive active sites on enzymes in the necessary reduced state. GSH is used as a cofactor by

(1)   multiple peroxidase enzymes, to detoxify peroxides generated from oxygen radical attack on biological molecules;

(2)  transhydrogenases, to reduce oxidized centers on DNA, proteins, and other biomolecules; and

(3)  glutathione S-transferases (GST) to conjugate GSH with endogenous substances (e.g., estrogens) and to exogenous electrophiles (e.g., arene oxides, unsaturated carbonyls, organic halides), and diverse xenobiotics.

c. GSH is a primary protectant of skin, lens, cornea, and retina against radiation damage, and the biochemical foundation of P450 detoxication in the liver, kidneys, lungs, intestinal epithelia, and other organs.

d. GSH acts as a carrier in transport of certain amino acids across membranes in the kidney.

e. Glutathione (GSH) participates in leukotriene synthesis


Q. 3

Glutathione reductase contains the following prosthetic group:

 A

FAD

 B

NAD

 C

ATP

 D

None of the above

Q. 3

Glutathione reductase contains the following prosthetic group:

 A

FAD

 B

NAD

 C

ATP

 D

None of the above

Ans. A

Explanation:

Glutathione reductase contains a flavoprotein containing FAD. Reduced glutathione removes H2O2 in a reaction catalyzed by glutathione peroxidase, an enzyme that contains the selenium analogue of cysteine (selenocysteine) at the active site. 
         
Ref: Harper 28th edition, chapter 21.

Q. 4

Glutathione reductase contains the following metal:

 A

Selenium

 B

Magnesium

 C

Manganese

 D

Calcium

Q. 4

Glutathione reductase contains the following metal:

 A

Selenium

 B

Magnesium

 C

Manganese

 D

Calcium

Ans. A

Explanation:

In red blood cells the pentose phosphate pathway provides NADPH for the reduction of oxidized glutathione catalyzed by glutathione reductase, a flavoprotein containing FAD. Reduced glutathione removes H2O2 in a reaction catalyzed by glutathione peroxidase, an enzyme that contains the selenium analogue of cysteine (selenocysteine) at the active site (Figure 21–3). The reaction is important, since accumulation of H2O2 may decrease the life span of the erythrocyte by causing oxidative damage to the cell membrane, leading to hemolysis
         
Ref: Harper 28th edition, chapter 21.

 


Q. 5

All are true about glutathione except:

 A

It converts Hemoglobin to Methemoglobin

 B

It scavenges free radicals & superoxide enzymes

 C

It acts as a cofactor for some enzyme

 D

Causes sulfate conjugation

Q. 5

All are true about glutathione except:

 A

It converts Hemoglobin to Methemoglobin

 B

It scavenges free radicals & superoxide enzymes

 C

It acts as a cofactor for some enzyme

 D

Causes sulfate conjugation

Ans. A

Explanation:

A i.e. It converts hemoglobin to methemoglobin


Q. 6

Which of the following act as antioxidants:

 A

Glutathione peroxidase

 B

Vit. C

 C

Selenium

 D

All

Q. 6

Which of the following act as antioxidants:

 A

Glutathione peroxidase

 B

Vit. C

 C

Selenium

 D

All

Ans. D

Explanation:

 All Correct – A,B & C


Q. 7

True about Glutathione reductase:

 A

Sulphur containing enzyme

 B

Important in methemoglobinemia

 C

Free radical scavenger

 D

All

Q. 7

True about Glutathione reductase:

 A

Sulphur containing enzyme

 B

Important in methemoglobinemia

 C

Free radical scavenger

 D

All

Ans. C

Explanation:

C i.e. Free radical scavanger


Q. 8

Selenium is co-factor for :

 A

Glutathione peroxidase

 B

Glutathione reductase

 C

Glutathione synthetase

 D

Glutathione dehydrogenase

Q. 8

Selenium is co-factor for :

 A

Glutathione peroxidase

 B

Glutathione reductase

 C

Glutathione synthetase

 D

Glutathione dehydrogenase

Ans. A

Explanation:

Q. 9

Which of the following is true about glutathione?

 A

Contain sulfhydral group

 B

Forms met Hb from Hb

 C

It does not detoxity superoxide radicals

 D

All

Q. 9

Which of the following is true about glutathione?

 A

Contain sulfhydral group

 B

Forms met Hb from Hb

 C

It does not detoxity superoxide radicals

 D

All

Ans. A

Explanation:

Q. 10

In glutathione, which amino acid is the reducing agent?

 A

Glutamic acid

 B

Glycine

 C

Cysteine

 D

Alanine

Q. 10

In glutathione, which amino acid is the reducing agent?

 A

Glutamic acid

 B

Glycine

 C

Cysteine

 D

Alanine

Ans. C

Explanation:

Q. 11

Regarding glutathione which of the following is/are true:

 A

It helps in absorption of certain amino acids

 B

It inactivates some enzymes

 C

It helps in membrane transport

 D

All

Q. 11

Regarding glutathione which of the following is/are true:

 A

It helps in absorption of certain amino acids

 B

It inactivates some enzymes

 C

It helps in membrane transport

 D

All

Ans. C

Explanation:

Ans:C.)It helps in membrane transport.

GLUTATHIONE:

  • Glutathione is a tripeptide made up of glutamate, cysteine and glycine (T-glutamyl-cysteinyl-glycine).
  • Glutathione is present in all mammalian cells except neurons.
  • The sulphydryl (-SH) group of cysteine residue is the reactive portion of glutathione which can undergo oxidation and reduction.
  • Thus, glutathione may exist as the reduced (G-SH) or oxidized form (G-S-S-G) and can play a role in some oxidation-reduction reactions.
  • In oxidized form two molecules of glutathione are linked by disulfide bond.
  • Cysteine in glutathione act as reducing agent 

FUNCTIONS : –

  • It helps in keeping some enzyme in active state by preventing the oxidation of sulphydryl (-SH) group of enzyme.
  • It helps in detoxification of H2O2 by reducing it. Superoxide anion (O2) first converted to H2O2 by superoxide dismutase. 
  • Glutathione helps in membrane transport
  • H2O2 is then reduced to H2O2 by glutathione perioxidase, a reaction requires reduced glutathione. Thus, glutathione scavenges free radicals and superoxide anion.
  • It helps in detoxification of xenobiotics by their conjugation (conjugation reaction).
  • Reduced form of glutathione (GSH) with a free sulphydryl (-SH) group serves as a redox buffer, regulating redox state of the cell.
  • Reduced glutathione is essential for maintaining the normal structure of RBCs and for keeping hemoglobin iron in ferrous state (prevents formation of methemoglobin).
  • It is involved in the transport of amino acids across the cell membane of kidney and intestine.

Q. 12

Glutathione is:   

 A

Dipeptide

 B

Oligopeptide

 C

Tripeptide

 D

Polypeptide

Q. 12

Glutathione is:   

 A

Dipeptide

 B

Oligopeptide

 C

Tripeptide

 D

Polypeptide

Ans. C

Explanation:

 

Glutathione (GSH) is a tripeptide.

It contains an unusual peptide linkage between the amine group of cysteine and the carboxyl group of the glutamate side chain.

Glutathione, anantioxidant, helps protect cells from reactive oxygen species such as free radicals and peroxides. Glutathione is not an essential nutrient since it can be synthesized from the amino acids L-cysteine, L-glutamic acid and glycine.


Q. 13

Glutathione consists of cysteine plus glutamate plus ‑

 A

Leucine

 B

Lysine

 C

Glycine

 D

Valine

Q. 13

Glutathione consists of cysteine plus glutamate plus ‑

 A

Leucine

 B

Lysine

 C

Glycine

 D

Valine

Ans. C

Explanation:

Ans. is ‘c’ i.e., Glycine

Glutathione

Glutathione is a tripeptide made up of glutamate, cysteine and glycine (T-glutamyl-cysteinyl-glycine).

Glutathione is present in all mammalian cells except neurons.

The sulphydryl (-SH) group of cysteine residue is the reactive portion of glutathione which can undergo oxidation and reduction.

Thus, glutathione may exist as the reduced (G-SH) or oxidized form (G-S-S-G) and can play a role in some oxidation-reduction reactions.

In oxidized form two molecules of glutathione are linked by disulfide bond.

Glutathione has following function : –

i) It helps in keeping some enzyme in active state by preventing the oxidation of sulphydryl (-SH) group of enzyme.

ii) It helps in detoxification of H2O2 by reducing it. Superoxide anion (O2) first converted to H2O2 by superoxide dismutase. H2O2 is then reduced to H2O2 by glutathione perioxidase, a reaction requires reduced glutathione. Thus, glutathione scavenges free radicals and superoxide anion.

iii) It helps in detoxification of xenobiotics by their conjugation (conjugation reaction).

iv) Reduced form of glutathione (GSH) with a free sulphydryl (-SH) group serves as a redox buffer, regulating redox state of the cell.

v) Reduced glutathione is essential for maintaining the normal structure of RBCs and for keeping hemoglobin iron in ferrous state (prevents formation of methemoglobin).

vi) It is involved in the transport of amino acids across the cell membane of kidney and intestine.


Q. 14

Glutathione is maintained in reduced state by the help of ‑

 A

HMP shunt

 B

Glycogenesis

 C

Uronic acid pathway

 D

Transamination

Q. 14

Glutathione is maintained in reduced state by the help of ‑

 A

HMP shunt

 B

Glycogenesis

 C

Uronic acid pathway

 D

Transamination

Ans. A

Explanation:

Ans. is ‘a’ i.e., HMP shunt

Oxidized glutathione is reduced by the help of NADPH, which is generated by NADPH.


Q. 15

Molybdenum is present in which enzyme ‑

 A

Cytochrome oxidase

 B

Xanthine oxidase

 C

Glutathione peroxidase

 D

Urease

Q. 15

Molybdenum is present in which enzyme ‑

 A

Cytochrome oxidase

 B

Xanthine oxidase

 C

Glutathione peroxidase

 D

Urease

Ans. B

Explanation:

 Ans:B.)Xanthine Oxidase.

Molybdenum containing enzymes include: xanthine oxidase and closely related enzymes (the molybdenum-containing hydroxylases), sulphite oxidase and nitrate reductase. 



Apoptosis

Apoptosis


APOPTOSIS

  • Programmed cell death.
  • Self-initiated & energy-dependent process.
  • Eliminates irreparable & damaged cells.

CAUSES OF APOPTOSIS

PHYSIOLOGICAL 

  • Natural phenomena
  • Embryogenesis
  • Involution of hormone-dependent tissues (examples are endometrium & prostate )  
  • Ageing.
  • Cell death in proliferating cell population (eg: interstitial epithelium).
  • Deletion of harmful self-reacting lymphocytes (mechanism to prevent autoimmunity).

PATHOLOGICAL

  • DNA damage due to radiation
  • Cytotoxic anticancer drugs
  • Extremes of temperature
  • Accumalation of misfolded protein 
  • Cell injury in certain infections as in HIV
  • Pathological atrophy of glands after ductal obstruction.
  • Tumor cell death.

MORPHOLOGICAL FEATURES:

  • Cell shrinkage – 
  • Earliest change
  • Due to damage to cytoskeletal proteins.

Chromatin condensation (pyknosis)/nuclear compaction 

  • Most characteristic feature.

Convolution of cell membrane 

  • Leading to formation of cytoplasmic blebs (although cell membrane remains intact).

Formation of apoptotic bodies:

  • Membrane-bound spherical bodies containing compacted organelles with/without nuclear fragments.
  • Examples- Civatte bodies, kamino bodies, councilman bodies (as in viral hepatitis).
  • Does not elicit any inflammatory response.
  • Due to intact cell membrane.

Ultimately phagocytosis of these bodies. 

MECHANISM OF APOPTOSIS

  • Caspase acivates endonuclease  (neuronal apoptosis lacks caspases,  thus activation of AIF)
  • Endonuclease damages DNA 
  • Chromatin clumping 

INITIATION PHASE

  • Consists of two pathways –

Intrinsic/Mitochondrial Pathway

  • Major mechanism.
  • Cellular stress/injury activates stress sensors (BH3 proteins).

Acts by 2 ways:

  • Activation of PRO-APOPTOTIC PROTEINS (BAX,BAK,p53).
  • Inactivation of ANTI-APOPTOTIC PROTEINS (Bcl-2, MCL-1) on outer membrane of mitochondria.
  • In turn results in increased mitochondrial permeability.
  • “Cytochrome c” leaks out to cytoplasm.
  • Leakage of “SMAC /DIABLO” into cytoplasm.
  • It binds to APOPTOSIS activating factor 1.
  • Inhibits ANTI -APOPTOTIC IAP – Physiological inhibitor of apoptosis.

Forms apoptosome complex.

  • Triggers CASPASE 9 activation 

Extrinsic (Death Receptor-Initiated) Pathway

  • Initiated by receptor-ligand interactions
  • Responsible for elimination of self-reactive lymphocytes and damage by cytotoxic T lymphocytes
  • Death receptors 
  • eg: Type1 TNF receptors & FAS (= CD95)
  • FAS (receptor) + FAS-L (ligand)
  • Trimerisation occurs and activation of adaptor protein
  • Activation of CASPASE 8 &10 (in humans).
  • CD 95 –Marker of extrinsic pathway of Apoptosis.

EXECUTION PHASE:

  • Initially caspases will activate,
  • Executioner caspases: caspase-3 and caspase-7
  • Disrupt cytoskeleton & leads to cell fragmentation.
  • Finally phagocytosed by macrophages 

DYSREGULATED APOPTOSIS

  • Defective apoptosis and increased cell survival – autoimmune diseases
  • Increased apoptosis and excessive cell death
  • Neurodegenerative diseases
  • Ischemic injury (MI, stroke)
  • Viral infections

IDENTIFICATION OF APOPTOSIS

  • Staining of chromatin condensation.
  • Flow cytometry –Most commonly used method for detecting apoptosis.
  • To visualize rapid cell shrinkage.
  • DNA changes detected by in situ techniques or by gel electrophoresis.

Agarose gel electrophoresis:

  • Endonucleases induced inter-nucleated damage – Appearing as “Step-ladder pattern”.

Annexin V Assay:

  • Classical technique for detecting apoptosis.

Annexin V – 

  • Calcium-dependent phospholipid-binding protein.
  • Has high affinity for phophatidylserine (PS), plasma membrane phospholipid.

Earliest features: 

  • Translocation of PS from inner to outer leaflet of plasma membrane —> exposing PS to external environment.
  • Annexin V binds to this exposed PS.
  • Thus, identifies cells at earlier stage of apoptosis (When compared to assays based on DNA fragmentation.
Exam Question
 
  • Inflammation is absent in Apoptosis.
  • Annexin V is a marker of Apoptosis.
  • Cell shrinkage, Chromosomal breakage, Clumping of chromatin, nuclear condensation and fragmentation, Intact cell membrane, Cytoplasmic eosiophilia is seen in Apoptosis
  • Councilman Bodies, Graft versus host disease, Menstrual cycle, Pathological atrophy following duct obstruction are examples of apoptosis.
  • Cytochrome C has a direct role in Apoptosis.
  • Memory cells doesn’t undergo apoptosis due to presence of Nerve growth factor.
  • Organelle that plays a pivotal role in apoptosis is mitochondria.
  • Apoptosis is inhibited by bcl-2.
  • In apoptosis, Apaf-1 is activated by release of Cytochrome c from mitochondria.
  • The most characteristic feature of apoptosis is condensation of nuclear chromatin which corresponds to nuclear compaction (pyknosis) on light microscopy.
  • Intact cell membrane is also a characteristic feature of Apoptosis .
  • Cysteinyl aspartate specific proteases (Caspases) is involved in Apoptosis.
  • Considerable apoptosis may occur in tissues before it becomes apparent in histology.
  • Apoptotic cells appear round mass of the intensely eosinophilic cytoplasm with dense nuclear chromatin fragments.
  • Macrophages phagocytose the apoptotic cells and degrade them.
  • The normal cellular counterparts of oncogenes are important for inhibition of Apoptosis.
  • Peripheral aggregation of chromatin characterizes Apoptosis.
  • Chemotherapeutic drugs can cause both necrosis and apoptosis.
  • CD 95 is a marker of extrinsic pathway of Apoptosis.
  • Caspases is activated for nuclear fragmentation in apoptosis.
  • Ladder pattern of DNA electrophoresis in apoptosis is caused by the action of endonuclease enzyme.
  • Internucleosomal cleavage of DNA is characteristic of Apoptosis.
  • Phosphatidyl serine has important role in Apoptosis.
  • Starting point of apoptosis for programme cell death is activation of caspases.
  • Apoptosis is self-initiated.
  • Apoptosis is the hallmark of programmed cell death.
  • CD 95 induces apoptosis when it engaged by fas ligand system.
  • BCL-2 is the gene for apoptosis.
  • The lymphocytopenia seen a few hours after administration of a large dose of prednisone to a patient with lymphocytic leukemia is due tomassive lymphocytic Apoptosis.
  • Ubiquitin is required for Apoptosis.
  • Inducers of apoptosis are growth factor withdrawal, detachment from matrix, glucocorticoids, cytotoxic drugs & immune cytolysis.
  • The earliest change seen in apoptosis is Cell shrinkage.
  • Execution caspases of apoptosis are Caspase 3 & 7.
Don’t Forget to Solve all the previous Year Question asked on Apoptosis

Apoptosis

Apoptosis

Q. 1

Apoptosis can occur by change in hormone levels in the ovarian cycle. When there is no fertilization of the ovum, the endometrial cells die because :

 A

The involution of corpus luteum causes estradiol and progesterone levels to fall dramatically

 B

LH levels rise after ovulation

 C

Estradiol levels are not involved in the LH surge phenomenon

 D

Estradiol inhibits the induction of the progesterone receptor in the endometrium

Q. 1

Apoptosis can occur by change in hormone levels in the ovarian cycle. When there is no fertilization of the ovum, the endometrial cells die because :

 A

The involution of corpus luteum causes estradiol and progesterone levels to fall dramatically

 B

LH levels rise after ovulation

 C

Estradiol levels are not involved in the LH surge phenomenon

 D

Estradiol inhibits the induction of the progesterone receptor in the endometrium

Ans. A

Explanation:

Ans. is a i.e. The involutlon of corpus luteum causea estradlol and progesterone levels to fall dramatlcally

“The withdrawl of estrogen and progesterone initiates important endometrial events, vasoconstriction, the process of apoptosis, fissue loss and tinally menstruation.”

In the first half of the secretory phase, acid phosphatase and potent lytic enzymes are confined to lysosomes. Their release is inhibited by progesterone stabilisation of the lysosomal membranes. With the involution of corpus luteum, levels of estrogen and progesterone fall, the lysosomalmembranes are not maintained and enzymes are released which cause apoptosis of the endometrial cells.


Q. 2

True about Apoptosis all EXCEPT:

 A Annexin 5 is marker
 B

Inflammation is present

 C Cell shrinkage
 D

Clumping of chromatin

Q. 2

True about Apoptosis all EXCEPT:

 A Annexin 5 is marker
 B

Inflammation is present

 C Cell shrinkage
 D

Clumping of chromatin

Ans. B

Explanation:

Inflammation is present REF: Robbin’s 7th edition, p. 21, 27, and 31

Indirect repeat from June 2008 & June 2009

See APPENDIX-27 for “APOPTOSIS VS NECROSIS”


Q. 3 True about Apoptosis is? 
 A

Requires energy

 B Cell self-initiated
 C Swelling of cytoplasm
 D Loss of membrane integrity
Q. 3 True about Apoptosis is? 
 A

Requires energy

 B Cell self-initiated
 C Swelling of cytoplasm
 D Loss of membrane integrity
Ans. B

Explanation:

Cell self-initiated REF: Robbin’s 7th edition, p. 21, 27, and 31

Repeat from June 2008

See APPENDIX-27 for “APOPTOSIS VS NECROSIS”


Q. 4

Example of Apoptosis is?

 A Councilman Bodies
 B Gamma Gandy Body
 C Russell bodies
 D

None

Q. 4

Example of Apoptosis is?

 A Councilman Bodies
 B Gamma Gandy Body
 C Russell bodies
 D

None

Ans. A

Explanation:

Councilman Bodies REF: Cell proliferation & apoptosis by David Hughes, H. Mehmet Page 211 Repeat in December 2009

See APPENDIX-25 for “FEW IMPORTANT BODIES IN MEDICAL SCIENCE”


Q. 5

Memory cells doesn’t undergo apoptosis due to presence of which growth factor:

 A

Platelet derived growth factor

 B

Nerve growth factor

 C

Insulin like growth factor

 D

Fibroblast growth factor

Q. 5

Memory cells doesn’t undergo apoptosis due to presence of which growth factor:

 A

Platelet derived growth factor

 B

Nerve growth factor

 C

Insulin like growth factor

 D

Fibroblast growth factor

Ans. B

Explanation:

Nerve growth factor [Ref: http://www.jbc.org/content/276/42/39027.full]

Survival of memory B lymphocytes is tightly linked to the integrity of the Bel-2 protein and is regulated by a nerve growth factor (NGF) autocrine circuit.

Nerve growth factor inhibits apoptosis in memory B lymphocytes via inactivation of p38 MAPK, prevention of Bcl-2 phosphorylation, and cytrochrome c release.

NGF is a classical survival factor, essential for a large number of cell types, including neurons, keratinocytes, and memory B lymphocytes.


Q. 6

Annexin V is a marker of ‑

 A

Apoptosis

 B

Necrosis

 C

Artherosclerosis

 D

Inflammation

Q. 6

Annexin V is a marker of ‑

 A

Apoptosis

 B

Necrosis

 C

Artherosclerosis

 D

Inflammation

Ans. A

Explanation:

Apoptosis [Ref: www.clonetech.com]

  • Annexin V assays provides simple and effective method to detect apoptosis at a very early stage.
  • This assay makes advantage of the fact that phosphatidylserine (PS) is translocated from the inner (cytoplasmic) leaflet of the plasma membrane to
  • the outer (cell surface) leaflet soon after the induction of apoptosis and that the annexin V protein has strong specific affinity for phosphatidyl serine.
  • Phosphatidyl serine on the outer leaflet is available to bind labelled annexin V providing the basis for a simple staining assay.
  • All of the annexin proteins share the property of binding calcium and phospholipids.
  • Annexin V is a cause of syndrome called antiphospholipid antibody syndrome.
  • Annexin V normally forms a shield around certain phospholipid molecules that blocks their entry into coagulation (clotting) reactions.
  • In the antiphospholipid antibody syndrome; the formation of the shield is disrupted by the abnormal antibodies. Without the shield, there is an increased quantity of phospholipid molecules on cell membranes speeding up coagulation reactions and causing the abnormal blood clotting characteristic of antiphospholipid antibody syndrome.

Q. 7

True about Apoptosis are all except :

 A >Inflammation is present
 B >Chromosomal brekage
 C >Clumping of chromatin
 D >Cell shrinkage
Q. 7

True about Apoptosis are all except :

 A >Inflammation is present
 B >Chromosomal brekage
 C >Clumping of chromatin
 D >Cell shrinkage
Ans. A

Explanation:

inflammation is present [Ref. Robbins 7th/e p 31, 271

  • At early stage of apoptosis dying cells secrete soluble factors that recruit phagocytes.
  • Apoptotic cells express phosplzatidylserine in the outer layers of their plasma membrane. Some times thrombospondin is also expressed on the surface of apoptotic bodies.
  • These alterations permit the early recognition of dead cells by the macrophages, resulting in phagocytosis without the release of proinflammatory cellular components.
  • In this way apoptotic response disposes of cells with minimal compromise to the surrounding tissue.
  • The process of phagocytosis of apoptotic cells is so efficient that dead cells disappear without leaving a trace and inflammation is virtually absent.
  • Thus apoptosis is fundamentally different from necrosis which is characterized by loss of membrane integrity enzymatic digestion of cells and frequently a host reaction.
  • In case of apoptosis, the cell membrane remains intact.
  • The two most striking features of apoptosis are:
  • 1.1n contrast to necrosis it does not elicit inflammation
  • 2. Considerable apoptosis may occur in tissues before it becomes apparent in histological section (because it occurs very rapidly).

Morphological changes in apoptosis

1. Cell shrinkage

  • This is the earliest change.
  • It is due to damage of cytoskeletal proteins that provide structural support to the cell.

2. Chromatic Condensation (Pyknosis)

  • This is due to breakdown and clumping of chromatin.
  • This is most characteristic feature of apoptosis

3.Formation of cytoplasimic blebs and apoptotic bodies —> End stage is characterised by bleb formation.

4. Chromosomal DNA fragmentation

  • It is due to activity of endoneuclease and caspases.

5.Phagocytosis of apoptotic cells and bodies by adjacent macrophages or healthy parenchymal cells.

In histological sections apoptotic cell appears as round or oval mass of intensely eosinophilic cytoplasm with dens nucleus chromatin fragments.

Note :

  • Cell shrinkage and fragmentation allow the cells to be efficiently phagocytosed without release of proinflammatory cellular component.

Q. 8 Which of the following has a Direct role in Apoptosis.
 A NO
 B Adenyl cyclise
 C C AMP
 D Cytochrome C
Q. 8 Which of the following has a Direct role in Apoptosis.
 A NO
 B Adenyl cyclise
 C C AMP
 D Cytochrome C
Ans. D

Explanation:

Cytochrome C


Q. 9 Example of Apoptosis is:
 A Council man bodies
 B Gamma Gandy body
 C Russel body
 D None of the above
Q. 9 Example of Apoptosis is:
 A Council man bodies
 B Gamma Gandy body
 C Russel body
 D None of the above
Ans. A

Explanation:

Council man bodies


Q. 10

Organelle that plays a pivotal role in apoptosis:

 A End plasmic reticulum
 B Golgi complex
 C Mitochondria
 D Nucleus
Q. 10

Organelle that plays a pivotal role in apoptosis:

 A End plasmic reticulum
 B Golgi complex
 C Mitochondria
 D Nucleus
Ans. C

Explanation:

Mitochondria


Q. 11 Apoptosis is inhibited by:
 A bcl-2
 B p53
 C ras
 D c-myc
Q. 11 Apoptosis is inhibited by:
 A bcl-2
 B p53
 C ras
 D c-myc
Ans. A

Explanation:

bcl-2


Q. 12

Which of the following has a direct role in apoptosis?

 A

Nitric oxide

 B

Adenylcyclase

 C

cAMP

 D

Cytochrome C

Q. 12

Which of the following has a direct role in apoptosis?

 A

Nitric oxide

 B

Adenylcyclase

 C

cAMP

 D

Cytochrome C

Ans. D

Explanation:

Cytochrome c is involved in initiation of apoptosis. Upon release of cytochrome c to the cytoplasm, the protein binds apoptotic protease activating factor-1 (Apaf-1).


Q. 13

In apoptosis, Apaf-1 is activated by release of which of the following substances from the mitochondria?

 A

Bcl-2

 B

Bax

 C

Bcl-XL

 D

Cytochrome C

Q. 13

In apoptosis, Apaf-1 is activated by release of which of the following substances from the mitochondria?

 A

Bcl-2

 B

Bax

 C

Bcl-XL

 D

Cytochrome C

Ans. D

Explanation:

Apoptotic signals cause increased permeability of outer mitochondrial membrane, which inturn releases the apoptotic trigger cytochrome c from the mitochondria to cytosol.
Cytochrome c is located between the inner and outer mitochondrial membrane.
Its release preceds the morphologic changes of apoptosis, showing that it occur early, consistent with regulatory function.
When cytochrome c is released from the mitochondria, it binds to Apaf 1 and activates it, triggering an initiator caspase and sets in motion the proteolytic events that kill the cell.
 
Ref: Robbins Pathologic Basis of Disease, 6th Edition, Pages 21- 22; Elements of Human Cancer  By Geoffrey M. Cooper, Page 190; Manual of Cable Osteosyntheses: History, Technical Basis  By Reiner Labitzke, Page 289; Recombinant Human Erythropoietin (rhEPO) in Clinical Oncology  By Mohammad Resa Nowrousian, Page 25

 


Q. 14

Which of the following organelles plays a pivotal role in Apoptosis?

 A

Mitochondria

 B

Endoplasmic Reticulum

 C

Nucleus

 D

Golgi Apparatus

Q. 14

Which of the following organelles plays a pivotal role in Apoptosis?

 A

Mitochondria

 B

Endoplasmic Reticulum

 C

Nucleus

 D

Golgi Apparatus

Ans. A

Explanation:

Mitochondria is the organelle which plays a pivotal role in apoptosis.

Ref: Robbins pathologic basis of disease 6th edn/page 21.


Q. 15

The characteristic feature of apoptosis on light microscopy is:

 A

Cellular swelling

 B

Nuclear compaction

 C

Intact cell membrane

 D

Cytoplasmic eosinophlia

Q. 15

The characteristic feature of apoptosis on light microscopy is:

 A

Cellular swelling

 B

Nuclear compaction

 C

Intact cell membrane

 D

Cytoplasmic eosinophlia

Ans. B

Explanation:

Characteristic apoptotic feature include cell membrane blebbing, Cell shrinkage, chromatin condensation (nuclear compaction) and DNA fragmentation.
Out of all the options given nuclear compaction only fits into the characteristic features on light microscopy.
 
Ref: Cell Apoptosis Research Advances By Carter R. Kettleworth, Nova Publishers, 2007, Page 147; Robbins Basic Pathology, 7th Edition, Page 27.

Q. 16

All of the following are features of Apoptosis, except:

 A

Cellular swelling

 B

Nuclear compaction

 C

Intact cell membrane

 D

Cytoplasmic eosiophilia

Q. 16

All of the following are features of Apoptosis, except:

 A

Cellular swelling

 B

Nuclear compaction

 C

Intact cell membrane

 D

Cytoplasmic eosiophilia

Ans. A

Explanation:

Characteristic apoptotic feature include cell membrane blebbing, Cell shrinkage, chromatin condensation (nuclear compaction) and DNA fragmentation.
As it can be seen cell shrinkage and not cellular swelling in seen in apoptosis.
 
Ref: Cell Apoptosis Research Advances By Carter R. Kettleworth, Nova Publishers, 2007, Page 147; Robbins Basic Pathology, 7th Edition, Page 27All of the following are features of Apoptosis, except.

Q. 17

Which of the following organelles plays a pivotal role in Apoptosis:

 A

Mitochondria

 B

Endoplasmic Reticulum

 C

Nucleus

 D

Golgi Apparatus

Q. 17

Which of the following organelles plays a pivotal role in Apoptosis:

 A

Mitochondria

 B

Endoplasmic Reticulum

 C

Nucleus

 D

Golgi Apparatus

Ans. A

Explanation:

Initiation of apoptosis occurs through two different pathways, intrinsic mitochondria pathway and extrinsic death receptor mediated pathway. Mitochondria plays active role in apoptosis.

Ref: Tanley L. Robbins, Ramzi S. Cotran, (2012) , Chapter 1, “Cell Injury”, In the book, “Pocket Companion to Robbins and Cotran Pathologic Basis of Disease”, 8th Edition, USA, Page 27; Robbin’s Basic Pathology, 7th Edition, Pages 28, 29; Essential of Apoptosis (2003), Page 245


Q. 18

Annexin V is associated with which of the following?

 A

Necrosis

 B

Apoptosis

 C

Atherosclerosis

 D

Inflammation

Q. 18

Annexin V is associated with which of the following?

 A

Necrosis

 B

Apoptosis

 C

Atherosclerosis

 D

Inflammation

Ans. B

Explanation:

Annexin V is a calcium-dependent phospholipid binding protein that has a high affinity for the phophatidylserine (PS), a plasma membrane phospholipid.

One of the earliest features of apoptosis is the translocation of PS from the inner to the outer leaflet of the plasma membrane, thereby exposing PS to the external environment.

Annexin V binds to PS exposed on the cell surface and identifies cells at an earlier stage of apoptosis than assays based on DNA fragmentation. 

The Annexin V Assay, a classical technique for detecting apoptosis, is the most commonly used method for detecting apoptosis by flow cytometry.


Q. 19

True about cysteinyl aspartate specific proteases (Caspases) is?

 A

Involved in apoptosis

 B

Cause necrosis

 C

Involved in pain pathway

 D

Are cytokines inhibitor

Q. 19

True about cysteinyl aspartate specific proteases (Caspases) is?

 A

Involved in apoptosis

 B

Cause necrosis

 C

Involved in pain pathway

 D

Are cytokines inhibitor

Ans. A

Explanation:

Caspases ( cysteinyl aspartate specific proteases) are the effector proteins in the apoptotic cascade of cell death. 

Human caspases are classified into two groups:

  • Those related to apoptosis: caspases 2,3,6,7,8,9,10.
  • Those related to apoptosis: caspases 1, 4, 5 and 11.

Q. 20

Which of the following pathological process is associated with ‘Annexin V’?

 A

Apoptosis

 B

Necrosis

 C

Atherosclerosis

 D

Inflammation

Q. 20

Which of the following pathological process is associated with ‘Annexin V’?

 A

Apoptosis

 B

Necrosis

 C

Atherosclerosis

 D

Inflammation

Ans. A

Explanation:

Identifying apoptotic cells:
  • Staining of chromatin condensation
  • Flow cytometry to visualize rapid cell shrinkage
  • DNA changes detected by in situ techniques or by gel electrophoresis
  • Annexin V as marker for apoptotic cell membrane having phosphatidylserine on the cell exterior
Ref: Essential Pathology By Harsh Mohan, 2005, Page 38.

Q. 21

In which of the following pathological processes caspases are involved in?

 A

Apoptosis

 B

Fatty change

 C

Hydropic degeneration

 D

Collagen hyalinosis

Q. 21

In which of the following pathological processes caspases are involved in?

 A

Apoptosis

 B

Fatty change

 C

Hydropic degeneration

 D

Collagen hyalinosis

Ans. A

Explanation:

Apoptosis can be initiated by external signals that have features in common with those used by ligands such as TNF- or by an internal pathway activated by DNA damage, improperly folded proteins, or withdrawal of cell survival factors.
Regardless of the mode of initiation, the apoptotic program is carried out by a large family of cysteineproteases termed caspases.
The caspases are highly specific cytoplasmic proteases that are inactive in normal cells but become activated by apoptotic signals.
 
Ref: Blumenthal D.K., Garrison J.C. (2011). Chapter 3. Pharmacodynamics: Molecular Mechanisms of Drug Action. In L.L. Brunton, B.A. Chabner, B.C. Knollmann (Eds), Goodman & Gilman’s The Pharmacological Basis of Therapeutics, 12e.

Q. 22

Which of the following cell organelle is mainly involved during apoptosis?

 A

Nucleus

 B

Mitochondria

 C

Endoplasmic reticulum

 D

Golgi complex

Q. 22

Which of the following cell organelle is mainly involved during apoptosis?

 A

Nucleus

 B

Mitochondria

 C

Endoplasmic reticulum

 D

Golgi complex

Ans. B

Explanation:

Loss of mitochondrial function is seen during apoptosis.
Mitochondrial membrane integrity is not maintained, causing the end of normal activity and release of cytochrome c into the cytoplasm where it activates proteolytic enzymes called caspases.
The initial caspases activate a cascade of other caspases, resulting in protein degradation throughout the cell.
 
Ref: Mescher A.L. (2010). Chapter 3. The Cell Nucleus. In A.L. Mescher (Ed), Junqueira’s Basic Histology: Text & Atlas, 12e.

Q. 23

All of the following statements regarding apoptosis are TRUE, EXCEPT:

 A

Considerable apoptosis may occur in tissues before it becomes apparent in histology

 B

Apoptotic cells appear round mass of the intensely eosinophilic cytoplasm with dense nuclear chromatin fragments

 C

Apoptosis of cells induce inflammatory reaction

 D

Macrophages phagocytose the apoptotic cells and degrade them.

Q. 23

All of the following statements regarding apoptosis are TRUE, EXCEPT:

 A

Considerable apoptosis may occur in tissues before it becomes apparent in histology

 B

Apoptotic cells appear round mass of the intensely eosinophilic cytoplasm with dense nuclear chromatin fragments

 C

Apoptosis of cells induce inflammatory reaction

 D

Macrophages phagocytose the apoptotic cells and degrade them.

Ans. C

Explanation:

Apoptosis refers to preprogrammed natural or physiological cell death. It occurs without any inflammatory reaction. 
 
Features of apoptosis are:
  • Death occur by shrinkage
  • It affects isolated cells
  • It is a gene initiated process, and DNA fragments are small and regular
Histologic features:
  • Cell shrinkage
  • Nuclear condensation and fragmentation
  • Membrane budding
  • Buds includes cell organelles
  • Buds detach to form apoptotic bodies
  • Phagocytosis of the apoptotic bodies occur
Ref: Textbook of Pathology  By Datta page 48.

Q. 24

The normal cellular counterparts of oncogenes are important for the following functions, except:

 A

Promotion of cell cycle progression

 B

Inhibition of apoptosis

 C

Promotion of DNA repair

 D

Promotion of nuclear transcription

Q. 24

The normal cellular counterparts of oncogenes are important for the following functions, except:

 A

Promotion of cell cycle progression

 B

Inhibition of apoptosis

 C

Promotion of DNA repair

 D

Promotion of nuclear transcription

Ans. C

Explanation:

Oncogenes may function by inactivation of DNA repair genes, but not by promotion of DNA repair.

Ref: Robbin’s Illustrated Pathology, 7th Edition, Pages 293, 295; Oncogenes By Geoffrey M. Cooper, 1995, Preview.


Q. 25

A gastric biopsy is performed on a patient with suspected graft-versus-host disease following bone marrow transplantation. The biopsy demonstrates many isolated dying epithelial cells in crypts showing fragmented, hyperchromatic nuclei and small discrete blebs containing both cytoplasm and nuclear fragments. The biopsy demonstrates which of the following?

 A

Apoptosis

 B

Caseous neurosis

 C

Coagulative necrosis

 D

Gangrenous necrosis

Q. 25

A gastric biopsy is performed on a patient with suspected graft-versus-host disease following bone marrow transplantation. The biopsy demonstrates many isolated dying epithelial cells in crypts showing fragmented, hyperchromatic nuclei and small discrete blebs containing both cytoplasm and nuclear fragments. The biopsy demonstrates which of the following?

 A

Apoptosis

 B

Caseous neurosis

 C

Coagulative necrosis

 D

Gangrenous necrosis

Ans. A

Explanation:

The changes described are those of apoptosis, which is a form of programmed cell death.

Apoptosis can be seen in a variety of settings.

In this case, it is occurring in the context of graft-versus-host disease, which is mediated by CD8+ and CD4+ cells.

Apoptosis also occurs during embryogenesis, during hormone-dependent involution in the adult (eg, during menstruation), during rapid proliferation of cell populations (eg, intestinal crypt epithelia), and in the immune system (e.g., in developing thymus).

It can also occur after duct obstruction in organs such as pancreas and during some viral diseases.

The hallmark of this programmed method of cell death is the fragmentation of the cell with formation of cytoplasmic blebs and apoptotic bodies that are phagocytized by other healthy cells.
 
Caseous necrosis, such as is seen in tuberculosis, shows necrotic, amorphous granular debris surrounded by a granulomatous response.
 
Coagulative necrosis, such as is seen in myocardial infarction, shows coagulated, anuclear cell “ghosts.”
 
Gangrenous necrosis is a commonly used surgical term (eg, in diabetic feet) that does not have a precise pathologic counterpart.
 
Ref: Jan B.V., Lowry S.F. (2010). Chapter 2. Systemic Response to Injury and Metabolic Support. In F.C. Brunicardi, D.K. Andersen, T.R. Billiar, D.L. Dunn, J.G. Hunter, J.B. Matthews, R.E. Pollock (Eds), Schwartz’s Principles of Surgery, 9e.

Q. 26

Which of the following features characterizes apoptosis but not necrosis?

 A

Disaggregation of polyribosomes

 B

Eosinophilia

 C

Inflammation

 D

Peripheral aggregation of chromatin

Q. 26

Which of the following features characterizes apoptosis but not necrosis?

 A

Disaggregation of polyribosomes

 B

Eosinophilia

 C

Inflammation

 D

Peripheral aggregation of chromatin

Ans. D

Explanation:

Apoptosis is a form of cell death that serves to eliminate unwanted cells during development, maintain cell numbers in intact organs or tissues, and eliminate immune cells after an immune response has faded.

Apoptosis also occurs in response to noxious agents and in the aging process.

The process is the result of execution of an internal program mediated by the expression of a number of different genes.

In the process of apoptosis, cells shrink and cytoplasmic organelles become more densely packed.

Cytoplasmic blebs may form, and apoptotic bodies (membrane-bound cellular fragments) can be produced.

The most characteristic feature of apoptosis is a distinctive peripheral aggregation of chromatin, sometimes accompanied by breaking up of the nucleus into several fragments. In necrosis, the chromatin may become more pale (karyolysis), or form irregular clumps, and the nucleus itself may shrink into a dense pyknotic body.
 
Disaggregation of polyribosomes is characteristic of the initial stages of cellular injury and necrosis.
 
Eosinophilia characterizes both apoptosis and necrosis. Inflammation is typically absent in apoptosis, in contrast to necrosis.
 
Ref: Jan B.V., Lowry S.F. (2010). Chapter 2. Systemic Response to Injury and Metabolic Support. In F.C. Brunicardi, D.K. Andersen, T.R. Billiar, D.L. Dunn, J.G. Hunter, J.B. Matthews, R.E. Pollock (Eds), Schwartz’s Principles of Surgery, 9e.

Q. 27

Which of the following growth factor maintain the neurons by reducing apoptosis therefore the memory cells does not undergo apoptosis?

 A

Platelet derived growth factor

 B

Nerve growth factor

 C

Insulin like growth factor

 D

Fibroblast growth factor

Q. 27

Which of the following growth factor maintain the neurons by reducing apoptosis therefore the memory cells does not undergo apoptosis?

 A

Platelet derived growth factor

 B

Nerve growth factor

 C

Insulin like growth factor

 D

Fibroblast growth factor

Ans. B

Explanation:

The first neurotrophin to be characterized was nerve growth factor (NGF), a protein growth factor that is necessary for the growth and maintenance of sympathetic neurons and some sensory neurons. 

NGF is picked up by neurons and is transported in retrograde fashion from the endings of the neurons to their cell bodies. It is also present in the brain and appears to be responsible for the growth and maintenance of cholinergic neurons in the basal forebrain and the striatum. 
There is evidence that the maintenance of neurons by NGF is due to a reduction in apoptosis.
 
Ref: Barrett K.E., Barman S.M., Boitano S., Brooks H.L. (2012). Chapter 4. Excitable Tissue: Nerve. In K.E. Barrett, S.M. Barman, S. Boitano, H.L. Brooks (Eds), Ganong’s Review of Medical Physiology, 24e.

Q. 28

Cytosolic Cytochrome C mediates

 A

Apoptosis

 B

Electron transport

 C

Krebs cycle

 D

Glycolysis

Q. 28

Cytosolic Cytochrome C mediates

 A

Apoptosis

 B

Electron transport

 C

Krebs cycle

 D

Glycolysis

Ans. A

Explanation:

A i.e. Apoptosis

Cytochrome C has two very opposite roles. Within the mitochondrial membrane it serves as electron carrier in oxidative phosphorylation. But when it leaks out into cytosol it combines with Apaf I and activates caspase-9 to mediate apoptosisQ. This dual functioning is known as moonlighting.


Q. 29

Mitochondria is involved in all of the following, except:

 A

ATP production

 B

Apoptosis

 C

Tricarboxylic acid cycle

 D

Fatty acid biosynthesis

Q. 29

Mitochondria is involved in all of the following, except:

 A

ATP production

 B

Apoptosis

 C

Tricarboxylic acid cycle

 D

Fatty acid biosynthesis

Ans. D

Explanation:

D i.e. Fatty acid biosynthesis


Q. 30

Memory cell in immune system are long lived and escape apoptosis because of:

 A

Insulin like growth factor

 B

Fibroblast growth factor (FGF)

 C

Platelet derived growth factor

 D

Nerve growth factor

Q. 30

Memory cell in immune system are long lived and escape apoptosis because of:

 A

Insulin like growth factor

 B

Fibroblast growth factor (FGF)

 C

Platelet derived growth factor

 D

Nerve growth factor

Ans. D

Explanation:

D i.e. Nerve growth factor

  • Nerve growth factor inhibits apoptosis in memory B cellsQ via inactivation of p38 MAPK, prevention of antiapoptotic factor Bcl-2 phosphorylation (i.e. maintaining its integrity) & cytochrome c release
  • Although other growth factors like FGF, PDGF and IGF can also prolong the survival, it is the nerve growth factor that is most important in immortalization of memory cells.

Growth factor —> activate P13 kinase —> activate Akt —> inactivates procaspase 9 & inhibit Fast synthesis


Q. 31

Chemotherapeutic drugs can cause‑

 A

Only necrosis

 B

Only apoptosis

 C

Both necrosis and apoptosis

 D

Anoikis

Q. 31

Chemotherapeutic drugs can cause‑

 A

Only necrosis

 B

Only apoptosis

 C

Both necrosis and apoptosis

 D

Anoikis

Ans. C

Explanation:

Ans. is ‘c’ i.e., Both necrosis and apoptosis

o Injurious stimuli, e.g., radiation, cytotoxic anticancer durgs, heat and hypoxia, can induce apoptosis if the insult is mild, but large doses of same stimuli result in necrotic cell death.


Q. 32

True about apoptosis is all, except –

 A

Considerable apoptosis may occur in tissues before it becomes apparent in histology

 B

Apoptotic cells appear round mass of the intensely eosinophillic cytoplasm with dense nuclear chromatin fragments

 C

Apoptosis of cells induce inflammatory reaction

 D

Macrophages phagocytose the apoptotic cells and degrade them.

Q. 32

True about apoptosis is all, except –

 A

Considerable apoptosis may occur in tissues before it becomes apparent in histology

 B

Apoptotic cells appear round mass of the intensely eosinophillic cytoplasm with dense nuclear chromatin fragments

 C

Apoptosis of cells induce inflammatory reaction

 D

Macrophages phagocytose the apoptotic cells and degrade them.

Ans. C

Explanation:

Ans. is ‘c’ i.e., Apoptosis of cells induce Inflammatory reaction

oThe two most striking features of apoptosis are:

1.   In contrast to necrosis it does not elicit inflammation

2.   Considerable apoptosis may occur in tissues before it becomes apparent in histological section (because it occurs very rapidly).

Morphological changes in apoptosis

  1. Cell shrinkage

o This is the earliest change.

o It is due to damage of cytoskeletal proteins that provide structural support to the cell.

  1. Chromatic Condensation (Pyknosis)

o This is due to breakdown and clumping of chromatin.

o This is most characteristic feature of apoptosis

  1. Formation of cytoplasimic blebs and apoptotic bodies -4 End stage is characterised by bleb formation.
  2. Chromosomal DNA fragmentation

o It is due to activity of endoneuclease and caspases.

  1. Phagocytosis of apoptotic cells and bodies by adjacent macrophages or healthy parenchymal cells. In histological sections apoptotic cell appears as round or oval mass of intensely eosinophilic cytoplasm with dens nucleus chromatin fragments.

Note :

o Cell shrinkage and fragmentation allow the cells to be efficienccy phagocytosed without release of proinflammatory cellular component.


Q. 33

Characteristic feature of apoptosis –

 A

Cell membrane intact

 B

Cytoplasmic eosinophilia

 C

Nuclear moulding

 D

Cell swelling

Q. 33

Characteristic feature of apoptosis –

 A

Cell membrane intact

 B

Cytoplasmic eosinophilia

 C

Nuclear moulding

 D

Cell swelling

Ans. A

Explanation:

Ans. is ‘a’ i.e., Cell membrane intact

o No option is exactly correct in this question, as chromatin condensation is the most characteristic feature of apoptosis.

o But, we have to choose one option anyways.

o Amongst the given options two features are seen in apoptosis : ‑

Option a         –>           Cell membrane intact

Option b         —->        Cytoplasmic eosinophilia

o Cytoplasmic eosinophilia is not characteristic feature of apoptosis; cytoplasmic eosinophilia is also seen in necrosis. o On the other hand Intact cell membrane is a striking feature of apoptosis and it differentiates apoptosis from necrosis

 

(in which cell membrane is damaged)

o Most characteristic feature of apoptosis o Earliest change of apoptosis

o End stage of apoptosis

o Most striking feature of apoptosis

 

  -> Chromatin condensation (Pyknosis)

–    Cell shrinkage

—> Formation of cytoplasmic blebs & apoptotic bodies.

–  Absence of inflammation.


Q. 34

The characteristic feature of apoptosis on light microscopy is –

 A

Cellular swelling

 B

Nuclear compaction

 C

Intact cell membrane

 D

Cytoplasmic eosinophlia

Q. 34

The characteristic feature of apoptosis on light microscopy is –

 A

Cellular swelling

 B

Nuclear compaction

 C

Intact cell membrane

 D

Cytoplasmic eosinophlia

Ans. B

Explanation:

Ans. is ‘b’ i.e., Nuclear compaction

o The most characteristic feature of apoptosis is condensation of nuclear chromatin which corresponds to nuclear compaction (pyknosis) on light microscopy.


Q. 35

True about Apoptosis are all except‑

 A

Inflammation is present

 B

Chromosomal brekage

 C

Clumping of chromatin

 D

Cell shrinkage

Q. 35

True about Apoptosis are all except‑

 A

Inflammation is present

 B

Chromosomal brekage

 C

Clumping of chromatin

 D

Cell shrinkage

Ans. A

Explanation:

Ans. is ‘a’ i.e. inflammation is present

  • In apoptosis there is no inflammation. Why is it so ? Lets see.
  • In apoptosis the cell membrane remains intact, so that intracellular contents do not leak out to induce inflammatory response.
  • The most efficient mechanism that prevent inflammation is phagocytosis of apoptotic cells or apoptotic body by macrophage without release of proinflammatory cellular components.

Mechanism of phagocytosis of apoptotic cell

o Normally phosphatidyl serine is located on the inner (cytosolic) surface of plasma membrane.

o In apoptotic cell this phosphatidylserine is translocated to the outer (extracellular) surface of plasma membrane by scrumplase.

  • Some times thrombospondin is also expressed on the surface of apoptosis bodies.
  • These alterations permit the early recognition of apoptotic cells by macrophages, resulting in phagocytosis without the release of proinflammatory cellular components.

o The process of apoptotic cells is so efficient that dead cells disappear without leaving a trace and inflammation is virtually absent.

In Contrast, there is inflammation in necrosis

  • In necrosis there is disruption of cell membrane —> cellular components leak out and induce inflammatory response. Processes of disposal of cellular debris whose results do not damage the organism, differentiate apoptosis from necrosis.

Differtiating features of apoptosis and necrosis

Apoptosis                                                                        

o Death of a single cell

o Cell size decreases (Shrinkage)

o Plasma membrane intact

o Lysosomal and other organelles remain intact o Cellular contents do not leak out

o Adjacent inflammation absent

o In early stage require protein synthesis o Active process : – Energy dependent

o May be pathological or physiological

Necrosis

o Death of many contiguous cells (usually) o Increased cell size (swelling)

o Disruption of plasma membrane

o Lysosomal breakdown with release of hydrolases o Cellular contents leak out.

o Adjacent inflammation persent.

o Protein synthesis

o Passive process : – Not energy dependent

o Always pathological


Q. 36

All of the following are features of apoptosis, except‑

 A

Cellular swelling

 B

Nuclear compaction

 C

Intact cell membrane

 D

Cytoplasmic eosiophilia

Q. 36

All of the following are features of apoptosis, except‑

 A

Cellular swelling

 B

Nuclear compaction

 C

Intact cell membrane

 D

Cytoplasmic eosiophilia

Ans. A

Explanation:

Ans. is ‘a’ i.e., Cellular swelling

o Apoptosis is associated with cellular shrinkage (reduced cell size) and not cellular swelling.


Q. 37

Example of Apoptosis is?

 A

Councilman Bodies

 B

Gamma Gandy Body

 C

Russell bodies

 D

None

Q. 37

Example of Apoptosis is?

 A

Councilman Bodies

 B

Gamma Gandy Body

 C

Russell bodies

 D

None

Ans. A

Explanation:

Ans. is ‘a’ i.e., Councilman bodies

Apoptotic body

o One of the murphological hallmark of apoptosis is the apoptotic body which is eosinophilic and may contain some karryorhectic nuclear bebris.

  • It is a result of shrinkage of cytoplasm and nuclear disruption.
  • First there is surface blebbing and margination of chromatin which is followed by cell shrinkage and breakup into smaller apoptotic bodies.

o These apoptotic bodies are taken up by surrounding cells and digested.

o Since the process was seen for a long time before the mechanism was understood, apoptotic bodies in particular situations attracted specific names:

i)        Civatte bodies or colloid bodies in lichen planus.

ii)      Kamino bodies in melanocytic lesions

iii)    Councilman bodies in acute viral hepatitis

iv)     Tingible bodies (founds in macrophages) in lymphoma

v)       Sunburn cells

vi)     Satellite dyskeratotic cells

vii)   Eosinophilic globules


Q. 38

Which of the following organelles plays a pivotal role in apoptosis?

 A

Mitochondria

 B

Endoplasmic reticulum

 C

Nucleus

 D

Golgi apparatus

Q. 38

Which of the following organelles plays a pivotal role in apoptosis?

 A

Mitochondria

 B

Endoplasmic reticulum

 C

Nucleus

 D

Golgi apparatus

Ans. A

Explanation:

Ans. is ‘a’ i.e. Mitochondria

o Mitochondria are the most important organelles involved in apoptosis initiation and regulation. Significant changes can be observed in mitochondrial physiology and morphology during apoptosis.


Q. 39

Cytosolic cytochrome C plays an important function in –

 A

Apoptosis

 B

Cell necrosis

 C

Electron transport chain

 D

Cell division

Q. 39

Cytosolic cytochrome C plays an important function in –

 A

Apoptosis

 B

Cell necrosis

 C

Electron transport chain

 D

Cell division

Ans. A

Explanation:

Ans. is ‘a’ i.e. Apoptosis

Mechanism ofApoptosis

o Apoptosis is induced by a cascade of molecular events that may be initiated in distinct ways but culminate in the activation of caspases.

o Caspases are central to the pathogenesis of apoptosis

o The process of apoptosis is divided into two phases

i)        Initiation phase —> During this phase caspases become catalytically active

ii)      Execution phase —> During this phase caspases act to cause cell death.


Q. 40

CD 95 is a marker of –

 A

Intrinsic pathway of apoptosis

 B

Extrinsic pathway of apoptosis

 C

Monocyte

 D

Leucocyte

Q. 40

CD 95 is a marker of –

 A

Intrinsic pathway of apoptosis

 B

Extrinsic pathway of apoptosis

 C

Monocyte

 D

Leucocyte

Ans. B

Explanation:

Ans. is ‘b’ i.e. Extrinsic pathway of apoptosis

o CD 95 is a marker of extrinsic pathway of apoptosis.


Q. 41

In apoptosis, Apaf-1 is activated by release of which of the following substances from the mitochondria ?

 A

Bel – 2

 B

Bax

 C

Bcl – XL

 D

Cytochrome C

Q. 41

In apoptosis, Apaf-1 is activated by release of which of the following substances from the mitochondria ?

 A

Bel – 2

 B

Bax

 C

Bcl – XL

 D

Cytochrome C

Ans. D

Explanation:

Ans is ‘d’ i.e., Cytochrome C

Apoptosis is induced by a cascade of molecular events all of which culminate in the activation of caspases. ‘In the cytosol cytochrome C binds to a protein called Apaf I (Apoptosis activating factor – 1) and the complex activates caspase 9’


Q. 42

In apoptosis, cytochrome C acts through –

 A

Apaf 1

 B

Bcl-2

 C

FADD

 D

TNF

Q. 42

In apoptosis, cytochrome C acts through –

 A

Apaf 1

 B

Bcl-2

 C

FADD

 D

TNF

Ans. A

Explanation:

Ans. is ‘a’ i.e., Apaf 1

o One of these proteins is cytochrome c, well known for its role in mitochondrial respiration. In the cytosol, cytochrome C binds to a protein called Apaf-1 (apoptosis activating factor-1), and the complex activates caspase-9. (Bc1-2 and Bcl-x may also directly inhibit Apaf-1 activation, and their loss from cells may permit activation of Apaf-1).


Q. 43

Which is activated for nuclear fragmentation in apoptosis –

 A

Caspases

 B

Apaf – 1

 C

Oxygen free radicals

 D

All

Q. 43

Which is activated for nuclear fragmentation in apoptosis –

 A

Caspases

 B

Apaf – 1

 C

Oxygen free radicals

 D

All

Ans. A

Explanation:

Ans is ‘a’ i.e., Caspases

o Caspases and endonuclease cause chromatin fragmentation in apoptosis.

o They are inactive, so first they should be activated.

o Cytochrome ‘c’ binds with Apaf-1 and this complex activates caspases.

o Caspases cause fragmentation of chromatin and also activate endonuclease.

About option ‘b’

o Though Apaf-1 helps in activation of caspases, it has no role in chromatin framentation and It does not have two seprate forms active or inactive. It just forms complex with cytochrome ‘C’ to activate caspases.


Q. 44

In apoptosis which is/are involved –

 A

Apaf-1

 B

Bc12

 C

Caspases

 D

All

Q. 44

In apoptosis which is/are involved –

 A

Apaf-1

 B

Bc12

 C

Caspases

 D

All

Ans. D

Explanation:

Ans. is ‘a’ i.e., Apaf-1; ‘b’ i.e., BCl2; ‘c’ i.e., Caspases


Q. 45

Caspases are involved in –

 A

Apoptosis

 B

Cell signaling

 C

Pinocytosis

 D

Cell injury

Q. 45

Caspases are involved in –

 A

Apoptosis

 B

Cell signaling

 C

Pinocytosis

 D

Cell injury

Ans. A

Explanation:

Ans. is ‘a’ i.e., Apoptosis


Q. 46

Ladder pattern of DNA electrophoresis in apoptosis is caused by the action of the following enzyme

 A

Endonuclease

 B

Transglutaminase

 C

DNAse

 D

Caspase

Q. 46

Ladder pattern of DNA electrophoresis in apoptosis is caused by the action of the following enzyme

 A

Endonuclease

 B

Transglutaminase

 C

DNAse

 D

Caspase

Ans. A

Explanation:

Ans. is ‘a’ i.e., Endonuclease

o Apoptosis progresses quickly and its products are quickly removed, making it difficult to detect or visualize.

o During karryorrhexis endonuclease activation leaves short DNA fragments, regularly spaced in size.

o This gives a characteristic laddered appearance on agar gel electrophoresis. o This ladderd patteren is characteristic but not specific for apoptosis. o It may be seen in necrosis also.


Q. 47

Internucleosomal cleavage of DNA is characteristic of-

 A

Reversible cell injury

 B

Irreversible cell injury

 C

Necrosis

 D

Apoptosis

Q. 47

Internucleosomal cleavage of DNA is characteristic of-

 A

Reversible cell injury

 B

Irreversible cell injury

 C

Necrosis

 D

Apoptosis

Ans. D

Explanation:

Ans. is ‘d’ i.e., Apoptosis

o In apoptosis first there is breakdown of DNA into large 50-300- kilobase pieces.

o Subsequently these DNA pieces undergogo internucleosomal cleavage to yield oligonucleosomes in multiples of 180-200 base pairs.

o These Oligonucleosomes fragments are visualized by agarose gel electrophoresis as DNA ladders. o The internucleosomal cleavage is brought about by Cal+ and Mg2+ dependent endonucleases. Note: Internucleosomal DNA cleavage is not specific for Apoptosis. (can be seen in necrosis too)


Q. 48

True about apoptosis –

 A

Increase in lysosomal enzyme

 B

Increase in caspases

 C

Phosphatidyl serine has important role

 D

b and c

Q. 48

True about apoptosis –

 A

Increase in lysosomal enzyme

 B

Increase in caspases

 C

Phosphatidyl serine has important role

 D

b and c

Ans. D

Explanation:

Ans. is ‘b’ i.e., Increase in caspases,’c’i.e., Phosphatidylserine has important role

o The process of apoptosis is often accompanied by generation of reactive oxygen species, which bring about rapid oxidation of the fatty acids in phosphatidylserine before this lipid is externalized.

o Indeed, it is now apparent that only molecular species of phosphatidylserine with an oxidatively truncated sn-2 acyl group that incorporates terminal gamma-hydroxyl (or oxo)- alpha, beta,-unsaturated acyl moieties are recognised by scavenger receptors in macrophages as a prerequisite for engulfment of apoptotic cells.

o Phosphatidylserine is a phospholipid component, usually kept on the inner-leaflet (the cytosolic side) of cell membranes by an enzyme called filppase. When a cell undergoes apoptotic cell death phosphatidylserine is no longer restricted to the cytosolic part of the membrane, but becomes exposed on the surface of the cell.

o “During normal embryogenesis, programmed cell death is performed by apoptosis and autophagy. CASPASES and ICE are intracellular proteases whose function is to digest cells during the apoptotic cascade, whereas P53,

MDM-2, BCL-2 & BAX act as transcription factor. Decreased apoptosis can result in abnormal structures like webbed digits (cutaneous syndactly) that result when the interdigital skin webs are not absorbed.”–Potter’s pathology of the fetus, infant & child 3rd/e pg 33.

o The apoptotic cell exhibit a characteristic breakdown of DNA into large 50 to 500 Kb pieces. Subsequently, there is internucleosomal cleavage of DNA into oligonucleosomes by Ca2+ and Mg2+ dependent endonuclease.


Q. 49

True about apoptosis-

 A

Migration of Leukocytes

 B

End products are phagocytosed by macrophage

 C

Intranuclear fragmentation of DNA

 D

All

Q. 49

True about apoptosis-

 A

Migration of Leukocytes

 B

End products are phagocytosed by macrophage

 C

Intranuclear fragmentation of DNA

 D

All

Ans. D

Explanation:

Ans. is ‘b’ i.e., End products are phagocytosed by macrophage; ‘c’ i.e., Intranuclear fragmentation of DNA

o As there is no inflammation in apoptosis —> there is no leukocyte migration.

Apoptotic cells or apoptotic bodies (end products) are phagocytosed by macrophages.

o Endonuclease causes double stranded breaks of nuclear DNA. The nucleus itself may break up producing two or more fragments.

o Activation of caspases is central to the pathogenesis of apoptosis.

o Following are the method to identify the apoptopic cells :

          Staining of chromatin condension by haematoxylin, Feulgen and acridine orange.

         Flow cytometry to visualise rapid cell shrinkage.

         DNA changes in situ technique or by electrophoresis.

         Annexin Vas a marker of apoptotic cell.


Q. 50

Starting point of apoptosis for programme cell death is –

 A

Activation of endonuclease

 B

Release of enzyme

 C

Accumulation of calcium

 D

None

Q. 50

Starting point of apoptosis for programme cell death is –

 A

Activation of endonuclease

 B

Release of enzyme

 C

Accumulation of calcium

 D

None

Ans. D

Explanation:

Ans. is ‘None’

o Activation of caspases (not endonuclease) is central in the pathogenesis of apoptosis.

“A family of proteins known as caspases are typically activated in the early state of apoptosis – Anderson.”

o After activation of caspases, they (caspases) activate endonuclease.

For one answer go ahead with option ‘a’, because amongst the given option only activation of endonuclease is related to pathogenesis of apoptosis.


Q. 51

Annexin Visa marker of

 A

Apoptosis

 B

Necrosis

 C

Artherosclerosis

 D

Inflammation

Q. 51

Annexin Visa marker of

 A

Apoptosis

 B

Necrosis

 C

Artherosclerosis

 D

Inflammation

Ans. A

Explanation:

Ans. is ‘a’ i.e., Apoptosis

o Annexin V assays provides simple and effective method to detect apoptosis at a very early stage.

o This assay makes advantage of the fact that phosphatidylserine (PS) is translocated from the inner (cytoplasmic)

leaflet of the plasma membrane to the outer (cell surface) leaflet soon after the induction of apoptosis and that the

annexin V protein has strong specific affinity for phosphatidyl serine.

o Phosphatidyl serine on the outer leaflet is available to bind labelled annexin V providing the basis for a simple staining assay.

o All of the annexin proteins share the property of binding calcium and phospholipids.

o Annexin V is a cause of syndrome called antiphospholipid antibody syndrome.

o Annexin V normally forms a shield around certain phospholipid molecules that blocks their entry into coagulation (clotting) reactions.

o In the antiphospholipid antibody syndrome; the formation of the shield is disrupted by the abnormal antibodies. Without the shield, there is an increased quantity of phospholipid molecules on cell membranes speeding up coagulation reactions and causing the abnormal blood clotting characteristic of antiphospholipid antibody syndrome.


Q. 52

Which of the following has a direct role in apoptosis?

 A

Nitric oxide

 B

Adenylcyclase

 C

cAMP

 D

Cytochrome C

Q. 52

Which of the following has a direct role in apoptosis?

 A

Nitric oxide

 B

Adenylcyclase

 C

cAMP

 D

Cytochrome C

Ans. D

Explanation:

Ans. is ‘d’ i.e., Cytochrome C

 o Amongst the given options, cytochromome C is involved in apoptosis.


Q. 53

Annexin V is associated with?         

 A

Necrosis

 B

Apoptosis

 C

Atherosclerosis

 D

Inflammation

Q. 53

Annexin V is associated with?         

 A

Necrosis

 B

Apoptosis

 C

Atherosclerosis

 D

Inflammation

Ans. B

Explanation:

Ans. is ‘b’ i.e., Apoptosis


Q. 54

True about Caspases is?

 A

Involved in apoptosis

 B

Cause necrosis

 C

Involved in pain pathway

 D

Are cytokines inhibitor

Q. 54

True about Caspases is?

 A

Involved in apoptosis

 B

Cause necrosis

 C

Involved in pain pathway

 D

Are cytokines inhibitor

Ans. A

Explanation:

Ans is ‘a’ i.e., Involved in apoptosis

o Apoptosis is induced by a cascade of molecular events all of which culminate in the activation of caspases. ‘In the cytosol cytochrome C binds to a protein called Apaf I (Apoptosis activating factor – 1) and the complex activates caspase 9’


Q. 55

True about Apoptosis all EXCEPT –

 A

Annexin 5 is marker

 B

Inflammation is present

 C

Cell shrinkage

 D

Clumping of chromatin

Q. 55

True about Apoptosis all EXCEPT –

 A

Annexin 5 is marker

 B

Inflammation is present

 C

Cell shrinkage

 D

Clumping of chromatin

Ans. B

Explanation:

Ans. is ‘b’ i.e., Inflammation is present

o The two most striking features of apoptosis are:

1.1n contrast to necrosis it does not elicit inflammation

2. Considerable apoptosis may occur in tissues before it becomes apparent in histological section (because it occurs very rapidly).



Q. 56

Annexin V is a marker of –

 A

Apoptosis

 B

Necrosis

 C

Artherosclerosis

 D

Inflammation

Q. 56

Annexin V is a marker of –

 A

Apoptosis

 B

Necrosis

 C

Artherosclerosis

 D

Inflammation

Ans. A

Explanation:

Ans. is ‘a’ i.e., Apoptosis


Q. 57

True about Apoptosis is?

 A

Requires energy

 B

Cell self-initiated

 C

Swelling of cytoplasm

 D

a and b

Q. 57

True about Apoptosis is?

 A

Requires energy

 B

Cell self-initiated

 C

Swelling of cytoplasm

 D

a and b

Ans. D

Explanation:

Ans. is ‘a’ i.e., Requires energy ‘b’ i.e., Cell self-initiated

Apoptoisis is an active process, which requires energy (in contrast to necrosis which is passive and does not require energy.

o Most of the time, apoptosis is self induced in cells to combat DNA damage, i.e., physiological (In contrast to necrosis which is always pathological and induced by pathological stimuli e.g., ischemia, hypoxia, poisons, hypothermia etc.)



Q. 58

Organelle that plays a pivotal role in apoptosis ‑

 A

Endoplasmic reticulum

 B

Golgi complex

 C

Mitochondria

 D

Nucleus

Q. 58

Organelle that plays a pivotal role in apoptosis ‑

 A

Endoplasmic reticulum

 B

Golgi complex

 C

Mitochondria

 D

Nucleus

Ans. C

Explanation:

Ans. is ‘c’ i.e. Mitochondria

o Mitochondria are the most important organelles involved in apoptosis initiation and regulation. Significant changes can be observed in mitochondrial physiology and morphology during apoptosis.


Q. 59

Apoptosis is inhibited by –

 A

RAS

 B

N-myC

 C

BC1-2

 D

All

Q. 59

Apoptosis is inhibited by –

 A

RAS

 B

N-myC

 C

BC1-2

 D

All

Ans. C

Explanation:

Ans. is ‘c’ i.e. Bcl-2


Q. 60

Which of the following is the hallmark of programmed cell death ?

 A

Apoptosis

 B

Coagulation necrosis

 C

Fibrinoid necrosis

 D

Liquefaction necrosis

Q. 60

Which of the following is the hallmark of programmed cell death ?

 A

Apoptosis

 B

Coagulation necrosis

 C

Fibrinoid necrosis

 D

Liquefaction necrosis

Ans. A

Explanation:

Ans. is ‘a’ i.e., Apoptosis


Q. 61

The following are example of apoptosis except‑

 A

Graft versus host disease

 B

Menstrual cycle

 C

Pathological atrophy following duct obstruction

 D

None

Q. 61

The following are example of apoptosis except‑

 A

Graft versus host disease

 B

Menstrual cycle

 C

Pathological atrophy following duct obstruction

 D

None

Ans. D

Explanation:

Ans. is ‘None’


Q. 62

CD – 95 in apoptosis; the death receptors initiated through –

 A

Induces apoptosis when it engaged by fas ligand system

 B

Cytochrom C binds to a protein Apoptosis activating (Apaf -1) factor – 1

 C

Apoptosis may be initiated by caspase activation

 D

Apoptosis mediated through DNA damage

Q. 62

CD – 95 in apoptosis; the death receptors initiated through –

 A

Induces apoptosis when it engaged by fas ligand system

 B

Cytochrom C binds to a protein Apoptosis activating (Apaf -1) factor – 1

 C

Apoptosis may be initiated by caspase activation

 D

Apoptosis mediated through DNA damage

Ans. A

Explanation:

Ans. is ‘a’ i.e., Induces apoptosis when it engaged by fas ligand system


Q. 63

The gene for apoptosis is –

 A

BCI-2

 B

BRAC

 C

RET

 D

All

Q. 63

The gene for apoptosis is –

 A

BCI-2

 B

BRAC

 C

RET

 D

All

Ans. A

Explanation:

Ans. is ‘a’ i.e., BCL -2


Q. 64

The process of programmed gene directed cell death characterized by cell-shrinkage, nuclear condensation and fragmentation is known as

 A

Necrosis

 B

Chromatolysis

 C

Pyknosis

 D

Apoptosis

Q. 64

The process of programmed gene directed cell death characterized by cell-shrinkage, nuclear condensation and fragmentation is known as

 A

Necrosis

 B

Chromatolysis

 C

Pyknosis

 D

Apoptosis

Ans. D

Explanation:

Ans. is ‘d’ i.e., Apoptosis


Q. 65

One of the following is an apoptosis inhibitor gene-

 A

p53

 B

Bc1-2

 C

Rb

 D

c-Myc

Q. 65

One of the following is an apoptosis inhibitor gene-

 A

p53

 B

Bc1-2

 C

Rb

 D

c-Myc

Ans. B

Explanation:

Ans. is ‘b’ i.e., BCI-2


Q. 66

CD-95 has a major role in –

 A

Apoptosis

 B

Cell necrosis

 C

Interferon activation

 D

Proteolysis

Q. 66

CD-95 has a major role in –

 A

Apoptosis

 B

Cell necrosis

 C

Interferon activation

 D

Proteolysis

Ans. A

Explanation:

Ans. is ‘a’ i.e., Apoptosis

Function of Human Leucocyte surface antigen CD-95 is to mediate apoptosis.


Q. 67

The lymphocytopenia seen a few hours after administration of a large dose of prednisone to a patient with lymphocytic leukemia is due to ‑

 A

massive lymphocytic apoptosis

 B

Bone marrow depression .

 C

Activation of cytotoxic cells

 D

Stimulation of natural killer cell activity

Q. 67

The lymphocytopenia seen a few hours after administration of a large dose of prednisone to a patient with lymphocytic leukemia is due to ‑

 A

massive lymphocytic apoptosis

 B

Bone marrow depression .

 C

Activation of cytotoxic cells

 D

Stimulation of natural killer cell activity

Ans. A

Explanation:

Ans. is ‘a’ i.e., Massive lymphocytic apoptosis

o Glucocorticoid induce programmed cell death (apoptosis) in lymphoid malignancies.


Q. 68

Apoptosis means:        

September 2005

 A

Regeneration of cells after injury

 B

Reperfusion injury of the cells

 C

Programmed internal cell death

 D

Uncontrolled multiplication of cells

Q. 68

Apoptosis means:        

September 2005

 A

Regeneration of cells after injury

 B

Reperfusion injury of the cells

 C

Programmed internal cell death

 D

Uncontrolled multiplication of cells

Ans. C

Explanation:

Ans. C: Programmed internal cell death

Apoptosis is defined as a process of programmed cell death (PCD) that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death.

These changes include blebbing, loss of cell membrane asymmetry and attachment, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation.

Apoptosis differs from necrosis, in which the cellular debris can damage the organism.

  • Apoptosis in physiological conditions:

– During embryogenesis

– Involution of hormone-dependent tissues upon hormone withdrawl, such as endometrial cell breakdown during menstrual cycle, ovarian follicular atresia in menopause etc.

– Cell loss in proliferating cell populations, such as immature lymphocytes in the bone marrow. Elimination of potentially harmful self-reactive lymphocytes


Q. 69

Following are the examples of apoptosis except:

September 2008

 A

Graft versus host disease

 B

Menstrual cycle

 C

Pathological atrophy following duct obstruction

 D

Tumour necrosis

Q. 69

Following are the examples of apoptosis except:

September 2008

 A

Graft versus host disease

 B

Menstrual cycle

 C

Pathological atrophy following duct obstruction

 D

Tumour necrosis

Ans. D

Explanation:

Ans. D: Tumour necrosis


Q. 70

True regarding ubiquitin is:      

September 2009

 A

Required for apoptosis

 B

It is found throughout the cell

 C

Found only in eukaryotes

 D

All of the above

Q. 70

True regarding ubiquitin is:      

September 2009

 A

Required for apoptosis

 B

It is found throughout the cell

 C

Found only in eukaryotes

 D

All of the above

Ans. D

Explanation:

Ans. D: All of the above

Ubiquitin (Ub) is a small protein that is composed of 76 amino acids.

This protein is found only in eukaryotic organisms and is not found in either eubacteria or archaebacteria. Ub is a heat-stable protein that folds up into a compact globular structure.

It is found throughout the cell (thus, giving rise to its name) and can exist either in free form or as part of a complex with other proteins.

Single Ub molecules can be conjugated to the lysine of these proteins, or more commonly, Ub-chains can be attached. Ub is involved in many cell processes.

Ub is conjugated to the protein cyclin during the G1 phase of mitosis and thus plays an important role in regulating the cell cycle.

Ub conjugation is also involved in DNA repair, embryogenesis, the regulation of transcription, and apoptosis (programmed cell death).


Q. 71

Which of the following induces apoptosis in a cell?

 A

Oleic acid

 B

Glucocorticoids

 C

Isoprenoids

 D

Myristic acid

Q. 71

Which of the following induces apoptosis in a cell?

 A

Oleic acid

 B

Glucocorticoids

 C

Isoprenoids

 D

Myristic acid

Ans. B

Explanation:

 

Glucocorticoids induce apoptosis in a cell.

Inducers of apoptosis are growth factor withdrawal, detachment from matrix, glucocorticoids, cytotoxic drugs and immune cytolysis.


Q. 72

The earliest change seen in apoptosis is ‑

 A

Cell shrinkage

 B

Pyknosis

 C

Formation of apoptotic bodies

 D

Fragmentation of cells

Q. 72

The earliest change seen in apoptosis is ‑

 A

Cell shrinkage

 B

Pyknosis

 C

Formation of apoptotic bodies

 D

Fragmentation of cells

Ans. A

Explanation:

Ans. is ‘a’ i.e., Cell shrinkage

Morphological changes in apoptosis

  • Features of apoptosis are :‑

1) Cell shrinkage : It is the earliest changes. It is due to damage to cytoskeletal proteins.

2) Chromatin condensation (pyknosis)/nuclear compaction : It is the most characteristic feature.

3) Formation of cytoplasmic blebs : It is the end stage of apoptosis.

4) Cytoplasmic eosinophilia.

5) Chromosomal DNA fragmentation : It is due to activity of endonuclease and caspases.

6) Formation of apoptotic bodies : These are membrane bound round masses of eosinophilic cytoplasm with tightly packed orgaelles which may contain nuclear debries. Important examples of apoptotic bodies are civatte bodies, kamino bodies, councilman bodies, Tingible bodies, sunburn cells, satellite dyskeratotic cells, and eosinophilic globules.

7) Phagocytosis of apoptotic cells and bodies by adjacent macrophages or healthy parenchymal cells.

8) Considerable apoptosis may occur before it becomes apparent on histological section.

Two very important differentiating features from necrosis are :‑

A) Absence of inflammation.

B) Intact cell membrane.


Q. 73

True about Apoptosis are all except-

 A

Inflammation is present

 B

Chromosomal breakage

 C

Clumping of chromatin

 D

Cell shrinkage

Q. 73

True about Apoptosis are all except-

 A

Inflammation is present

 B

Chromosomal breakage

 C

Clumping of chromatin

 D

Cell shrinkage

Ans. A

Explanation:

Ans. is ‘a’ i.e.,, Inflammation is present

The two most striking features of apoptosis are:

  • In contrast to necrosis it does not elicit inflammation
  • Considerable apoptosis may occur in tissues before it becomes apparent in histological section (because it occurs very rapidly).

Q. 74

Not true about apoptosis ‑

 A

Increase in lysosomal enzyme

 B

Increase in caspases

 C

Phosphatidyl serine has important role

 D

Internucleosomal cleavage of nucleus

Q. 74

Not true about apoptosis ‑

 A

Increase in lysosomal enzyme

 B

Increase in caspases

 C

Phosphatidyl serine has important role

 D

Internucleosomal cleavage of nucleus

Ans. A

Explanation:

Ans. is ‘a’ i.e., Increase in lysosomal enzyme

Apoptosis

  • Caspases are central to the pathogenesis of apoptosis.
  • The lysis in apoptosis is caused due to action of caspase.
  • Mitochondrias are the most important organelles involved in initiation and regulation of apoptosis.
  • Hallmark of apoptosis is permeability of the mitochondrial membrane.
  • Normally phosphatidyl serine is located on the inner cytosolic surface of plasma membrane
  • In apoptotic cell this phosphatidyl serine is translocated to the outer (extracellular) surface of plasma membrane.
  • Lysosome and other organelles remain intact.

Q. 75

Caspases are involved in ‑

 A

Apoptosis

 B

Pinocytosis

 C

Cell signaling

 D

Cell injury

Q. 75

Caspases are involved in ‑

 A

Apoptosis

 B

Pinocytosis

 C

Cell signaling

 D

Cell injury

Ans. A

Explanation:

Ans. is ‘a’ i.e., Apoptosis

Caspases and endonuclease cause chromatin fragmentation in apoptosis.

They are inactive, so first they should be activated.

Cytochrome ‘c’ binds with Apaf-1 and this complex activates caspases.

Caspases cause fragmentation of chromatin and also activate endonuclease.

About option ‘b’

Though Apaf- I helps in activation of caspases, it has no role in chromatin fragmentation and It does not have two seprate forms active or inactive. It just forms complex with cytochrome ‘C’ to activate caspases.

Neet Points about Apoptosis

  • Mitochondrion is the critical organelle required for apoptosis.
  • Chromatin condensation is the most characteristic feature.
  • Cell shrinkage is seen.
  • Gel electrophoresis demonstrates ‘step ladder pattern’. Annexin V is the marker for apoptosis.
  • CD 95 is the molecular marker for apoptosis.

Q. 76

Execution caspases of apoptosis are ‑

 A

Caspase 1 & 3

 B

Caspase 3 & 5

 C

Caspase 1 & 5

 D

Caspase 3 & 7

Q. 76

Execution caspases of apoptosis are ‑

 A

Caspase 1 & 3

 B

Caspase 3 & 5

 C

Caspase 1 & 5

 D

Caspase 3 & 7

Ans. D

Explanation:

Ans. is ‘d’ i.e., Caspase 3 & 7


Q. 77

Annexin V is a marker for ‑

 A

Apoptosis

 B

Necrosis

 C

Atherosclerosis

 D

Inflammation

Q. 77

Annexin V is a marker for ‑

 A

Apoptosis

 B

Necrosis

 C

Atherosclerosis

 D

Inflammation

Ans. A

Explanation:

Ans. is ‘a’ i.e., Apoptosis

Annexin V assays provides simple and effective method to detect apoptosis at a very early stage.


Q. 78

Characteristic feature of apoptosis on light microscopy is ‑

 A

Cellular swelling

 B

Nuclear compaction

 C

Intact cell membrane

 D

Cytoplasmic eosinophilia

Q. 78

Characteristic feature of apoptosis on light microscopy is ‑

 A

Cellular swelling

 B

Nuclear compaction

 C

Intact cell membrane

 D

Cytoplasmic eosinophilia

Ans. C

Explanation:

Ans. is ‘c’ i.e., Intact cell membrane

No option is exactly correct in this question, as chromatin condensation is the most characteristic feature of apoptosis.

But, we have to choose one option anyways.


Q. 79

CD 95 is a marker of

 A

Intrinsic pathway of apoptosis

 B

Extrinsic pathway of apoptosis

 C

Monocyte

 D

Leucocyte

Q. 79

CD 95 is a marker of

 A

Intrinsic pathway of apoptosis

 B

Extrinsic pathway of apoptosis

 C

Monocyte

 D

Leucocyte

Ans. B

Explanation:

Ans. b. Extrinsic pathway of apoptosis

Apoptosis

Secondary to Intracellular or Internal Signals

  • Mediated by mitochondria°
  • Mitochondria are the most important organelles involved in initiation and regulation° of apoptosis secondary to intracellular signals° indicating that cell death should occur

Secondary to Extracellular or External Signals

  • Mediated by cell surface death receptors (CSDR) ° CSDR are members of the TNF-receptor family°.
  • The best known death receptors are the type 1 TNF receptor° (TNFR1) and a related protein called Fas (CD-95)°.

Q. 80

Which of the following induces apoptosis in a cell?

 A

Glucocorticoids

 B

Isoprenoids

 C

Myristic acid

 D

Oleic acid

Q. 80

Which of the following induces apoptosis in a cell?

 A

Glucocorticoids

 B

Isoprenoids

 C

Myristic acid

 D

Oleic acid

Ans. A

Explanation:

Ans. a. Glucocorticoids



Asbestosis

Asbestosis


ASBESTOS RELATED DISEASES

INTRODUCTION

  • Asbestos is a family of proinflammatory crystalline hydrated silicates that are associated with pulmonary fibrosis, carcinoma, mesothelioma, and other cancers.
  • There are two distinct geometric forms of asbestos:
  • Serpentine chrysolite – most of the asbestos used in industry
  • Amphibole (crocidolite)
  • Both serpentine and amphibole can cause all asbestos related diseases except for mesothelioma, which is usually associated with amphibole (crocidolite).
  • Aspect (length-to-diameter) ratio decides carcinogenicity. Amosite & crocidolite are relatively malignant, whereas anthophyllite, chrysotile and tremolite are benign
  • Asbestos exposure may occur in asbestos industry, ship building & textile .

ASBESTOS RELATED DISEASES CONSIST OF :

  • Lower lobe fibrosis
  • Localized fibrous plaques which may be calcified.
  • Diffuse pleural fibrosis.
  • Pleural effusion.
  • Pseudotumor(Round Atelactasis)
  • Parenchymal interstitial fibrosis (asbestosis).
  • Lung carcinoma → Most common neoplasm associated with asbestos exposure.
  • Asbestosis and smoking act synergistically to cause lung cancer
  • Mesothelioma of pleura and peritoneum → most specific neoplasm associated with asbestos exposure.
  • Predilection for Lower Zone
  • (Whole lung may be involved with predominant lower zone involvement)
  • Ascites.
  • Laryngeal and other extrapulmonary neoplasms including colon cancer

INVESTIGATIONS IN A CASE OF ASBESTOS RELATED DISEASES

  • Chest x-ray often reveals hyperinflation of the normal parenchyma leading to “honeycombing.”
  • Asbetosis may present with thickening or calcification along the parietal pleura, particularly along the lower lung fields, the diaphragm, and the cardiac border(Shaggy heart) on x ray.
  • HRCT (investigation of choice) shows subpleural pulmonary arcade, pleural based nodular irragularities, parenchymal bands & septal lines.
  • Round atelectasis occurs mostly in peripheral, lower, dorsal (posterior) lobes adjacent to visceral pleura and presents with Comet taiVVaccum cleaner/ Crow’s feet sign and Swiss cheese air bronchogram.
  • Histology:
  • Ferruginous bodies represent foreign inorganic or organic fibers coated by complexes of iron and glycoproteins.
  • While ferruginous bodies are most commonly seen in asbestosis they are not diagnostic because it may be seen in other type ofpneunoconiosis.
  • When asbestos fiber is coated by iron and glycoprotein, this ferruginous body is called asbestos body-characteristic of asbestosis.
  • Ferruginous bodies are best seen in section that have stained for iron with prussion blue.
  • Microscopically ferruginous bodies give a Shikh Kebab appearance.
  • Asbestos bodies seen in sputum.

CHARACTERISTICS OF ASBESTOS RELATED DISEASES

  •  The disease does not usually appear until 5-10 years of exposure.
  • Once established, the disease is progressive even after removal of the worker from contact.
  • It is a notifiable disease under Factory’s act 1948 and Indian Mines act 1952 in India along with silicosis, byssinosis etc
Exam Question
 
  • Asbestosis is asssociated with lung cancer and Ascites.
  • Asbestosis is associated with extensive pleural thickening and calcification especially involving the diaphragmatic pleura.
  • Ferruginous bodies are commonly seen in Asbestosis.
  • Asbestosis is associated with  the following pulmonary manifestations: Mesotheliomas ,Pneumoconiosis,Calcified pleural plaques , Diffuse pulmonary interstitial fibrosis,Progression of lesion even after stopping exposure to asbestos ,Honeycombing,Basal peribronchial fibrosis, Asbestos bodies in sputum,Nodular lesions involving lower lobe.
  • There are six types of asbestos; one is serpentine (chrysotile) and five are fibrous amphiboles (amosite, crocidolite, anthophyllite, tremolite, and actinolite).
  • The most likely diagnosis in a 35 year old roofer presenting with complain of dyspnea and chronic dry cough and Chest x-ray revealing pulmonary hyperinflation with “honeycombing” and calcified parietal pleural plaques is Asbestosis. 
  • The probable diagnosis in a 48 years old man, resident  near a textile mill presenting  with respiratory symptoms, X Ray chest showing – fine reticular nodular pattern in lower zone with loss of clarity of diaphragm & cardiac shadows and the presence of small pleural effusion is Asbestosis.
  • Asbestosis does not usually appear until 5-10 years of exposure.
  • Asbestosis may be associated with peritoneal Mesothelioma.
  • Asbestosis and smoking act synergistically to cause lung cancer.
  • Asbestosis is a notifiable disease under Factory’s act 1948 in India.
  • Asbestosis causes shaggy heart borders.
Don’t Forget to Solve all the previous Year Question asked on Asbestosis

Asbestosis

Asbestosis

Q. 1 Which will develop into lung cancer:
 A Asbestosis
 B Silicosis
 C Byssinosis
 D Benzene exposure
Q. 1 Which will develop into lung cancer:
 A Asbestosis
 B Silicosis
 C Byssinosis
 D Benzene exposure
Ans. A

Explanation:

Asbestosis


Q. 2

Which one of the following condition is associated with extensive pleural thickening and calcification especially involving the diaphragmatic pleura?

 A

Coal worker’s pneumoconiosis

 B

Asbestosis

 C

Silicosis

 D

Siderosis

Q. 2

Which one of the following condition is associated with extensive pleural thickening and calcification especially involving the diaphragmatic pleura?

 A

Coal worker’s pneumoconiosis

 B

Asbestosis

 C

Silicosis

 D

Siderosis

Ans. B

Explanation:

Extensive pleural thickening and calcification especially involving the diaphragmatic pleura are classical features of Asbestosis.

Exposure to asbestos can result in extensive pleural thickening, calcification, effusion, and malignant neoplasm of lung and pleura.

Pleural fibrosis associated with asbestos fiber inhalation result in diffuse pleural thickening or focal plaque formation bilaterally, and is the most frequent manifestation of asbestos exposure.

Pleural calcification occuring especially along the diaphragmatic surface of pleura is also pathognomonic of prior asbestos exposure

Ref: Computed Body Tomography with MRI Correlation, Volume 1 By Joseph K. T. Lee, 4th Edition, Pages 489-90; Handbook of Medical-Surgical Nursing By Lippincott Williams and Wilkins, Page 194; Asbestos : Mixed Dust and Fela Issues, Page 110.

Q. 3

Ferruginous bodies are commonly seen in:

 A

Silicosis

 B

Asbestosis

 C

Bagassosis

 D

Byssinosis

Q. 3

Ferruginous bodies are commonly seen in:

 A

Silicosis

 B

Asbestosis

 C

Bagassosis

 D

Byssinosis

Ans. B

Explanation:

Inorganic particles may become coated with iron containing proteinaceous material, these bodies are called ferruginous bodies.

They mimic asbestos bodies and can be seen in patient with asbestosis but is not specific hence asbestosis is the best answer.

Ferruginous bodies are most commonly seen in Asbestosis.
 
Ref: Robbin’s Illustrated Pathology, 7th Edition, Page 736 ; Concise Pathology By Chandrasoma P, Taylor C, 3rd Edition, Page 541

Q. 4

Asbestosis is associated with all of the following pulmonary manifestations, EXCEPT:

 A

Mesotheliomas

 B

Diffuse alveolar damage

 C

Calcified pleural plaques

 D

Diffuse pulmonary interstitial fibrosis

Q. 4

Asbestosis is associated with all of the following pulmonary manifestations, EXCEPT:

 A

Mesotheliomas

 B

Diffuse alveolar damage

 C

Calcified pleural plaques

 D

Diffuse pulmonary interstitial fibrosis

Ans. B

Explanation:

Occupational exposure to asbestos result in:

?  Pleural effusion
?  Mesotheliomas
?  Bronchogenic carcinoma
?  Parenchymal interstitial fibrosis (asbestosis)
?  Localized fibrous plaques or rarely diffuse fibrosis
?  Laryngeal and other extrapulmonary neoplasms including colon cancer
 
Ref: Robbins Pathologic Basis of Disease, 6th Edition, Pages 732-4

Q. 5

Asbestosis of the lung is associated with all of the following features, EXCEPT:

 A

Mesothelioma

 B

Progression of lesion even after stopping exposure to asbestos.

 C

Nodular lesions involving upper lobe

 D

Asbestos bodies in sputum

Q. 5

Asbestosis of the lung is associated with all of the following features, EXCEPT:

 A

Mesothelioma

 B

Progression of lesion even after stopping exposure to asbestos.

 C

Nodular lesions involving upper lobe

 D

Asbestos bodies in sputum

Ans. C

Explanation:

Lesions of asbestosis in the lung involves thickening or calcification along the parietal pleura particularly along the lower lung fields, the diaphragm, and the cardiac border.

As the disease progress, linear opacities seen initially in the lower lung lobes and then it spreads to the middle and upper lung fields. 

 
Asbestosis develops in workers involved in the production of asbestos products, shipbuilding and construction trades, including pipe fitters and boilermakers. 
 
Lung cancer is the most common cancer associated with asbestos exposure.
Its exposure is associated with the development of both pleural and peritoneal mesothelioma.
Mesotheliomas are not associated with smoking. 
 
Ref: Harrison’s Principles of Internal Medicine, 18e chapter 256 By John R. Balmes.

Q. 6

Match the following
Asbestosis :
 A

Sugar cane factory

 B

Amphibole fibres

 C

Cotton fibres

 D

Coal mines

Q. 6

Match the following
Asbestosis :
 A

Sugar cane factory

 B

Amphibole fibres

 C

Cotton fibres

 D

Coal mines

Ans. B

Explanation:

Asbestosis is a diffuse interstitial fibrosing disease of the lung that is directly related to the intensity and duration of exposure.
There are six types of asbestos; one is serpentine (chrysotile) and five are fibrous amphiboles (amosite, crocidolite, anthophyllite, tremolite, and actinolite). Usually, moderate to severe exposure has taken place for at least 10 years before the disease becomes manifest, and it may occur after exposure to any of the asbestiform fiber types. 
 
The mechanisms by which asbestos fibers induce lung fibrosis is oxidative injury due to the generation of reactive oxygen species by the transition metals on the surface of the fibers as well as from cells engaged in phagocytosis.
 
Ref: Speizer F.E. (2012). Chapter 256. Occupational and Environmental Lung Disease. In D.L. Longo, A.S. Fauci, D.L. Kasper, S.L. Hauser, J.L. Jameson, J. Loscalzo (Eds), Harrison’s Principles of Internal Medicine, 18e.

Q. 7

Extensive pleural thickening and calcification especially involving the diaphragmatic pleura are classical features of:

 A

Coal worker’s pneumoconiosis

 B

Asbestosis

 C

Silicosis

 D

Siderosis

Q. 7

Extensive pleural thickening and calcification especially involving the diaphragmatic pleura are classical features of:

 A

Coal worker’s pneumoconiosis

 B

Asbestosis

 C

Silicosis

 D

Siderosis

Ans. B

Explanation:

Thickening or calcification along the parietal pleura, particularly along the lower lung fields, the diaphragm, and the cardiac border is a characteristic finding in asbestosis.

Coal worker’s pneumoconiosis is manifested by the appearance on the chest radiograph of nodules ranging from 1 cm in diameter to the size of an entire lobe, generally confined to the upper half of the lungs

Silicosis is characterised by the chest radiographic finding of small rounded opacities in the upper lobes. Calcification of hilar nodes may occur in as many as 20% of cases and produces a characteristic “eggshell” pattern.

Sidertosis is a nonspecific term of deposition of iron in tissue.

Ref: Harrisons principles of internal medicine, 18th edition, Page: 2123


Q. 8

The lung disease associated with mesothelioma is:

 A

Silicosis

 B

Asbestosis

 C

Bagassosis

 D

Anthracosis

Q. 8

The lung disease associated with mesothelioma is:

 A

Silicosis

 B

Asbestosis

 C

Bagassosis

 D

Anthracosis

Ans. B

Explanation:

The most important factor for the development of mesothelioma is exposure to asbestos primarily the amphiboles crocidolite and amosite.
 
Asbestos: is a naturally occurring group of fibres. There are two subgroups;
  • Serpentine group: consist of chrysotile 
  • Amphiboles group: crocidolite, amosite, tremolite, anthophyllite and actinolite
There are four main diseases associated with inhalation of asbestos fibres.
  • Mesothelioma – a form of cancer mainly affecting the mesothelial cells.
  • Asbestos related lung cancer
  • Asbestosis – a non-malignant scarring of the lung tissue a form of pneumoconiasis.
  • Non malignant pleural disease (diffuse pleural thickening and pleural plaques)
PathophysiologyThere are 4 principal processes by which asbestos affects the pleura
 
1. The fibers irritate the pleura, thereby inducing scarring or a more malignant process
2. The fibers may pierce the mitotic spindle of cells, thereby disrupting mitosis leading to chromosomal damage
3. They also induce the generation of iron-related reactive oxygen species (ROS) causing DNA damage
4. Asbestos also induces phosphorylation of the mitogen-activated protein (MAP) kinases which increases the expression of early-response proto-oncogenes.
 
Ref: Asbestos: Risk Assessment, Epidemiology, and Health Effects, edited by Samuel P. Hammar, Ronald F. Dodson, Page 314

Q. 9

A 35 year old roofer presents to his primary care physician complaining of dyspnea and chronic dry cough. Chest x-ray reveals pulmonary hyperinflation with “honeycombing” and calcified parietal pleural plaques. The most likely diagnosis is?

 A

Anthracosis

 B

Asbestosis

 C

Berylliosis

 D

Byssinosis

Q. 9

A 35 year old roofer presents to his primary care physician complaining of dyspnea and chronic dry cough. Chest x-ray reveals pulmonary hyperinflation with “honeycombing” and calcified parietal pleural plaques. The most likely diagnosis is?

 A

Anthracosis

 B

Asbestosis

 C

Berylliosis

 D

Byssinosis

Ans. B

Explanation:

Asbestosis is a disease caused by a family of fibrous silicates commonly found in shipyards, insulation, and roofing industries. Many years after exposure, patients complain of dyspnea and chronic dry cough, along with recurrent respiratory infections (especially viral) and weight loss. Classic pathological findings include lower lobe interstitial fibrosis with septal wall widening, worse near the periphery of the lung. Chest x-ray often reveals hyperinflation of the normal parenchyma leading to “honeycombing.” Calcified parietal pleural plaques are also commonly present. Secondary bronchiectasis may complicate the picture.
 
Anthracosis is due to the inhalation of carbonaceous particles by city dwellers, cigarette smokers, and miners. Deposition of carbon dust can be seen as black pigment in lung parenchyma, pleura, and lymph nodes. When isolated, it is not associated with systemic disease.
 
Berylliosis is due to heavy exposure to airborne beryllium or its salts. Because of its high tensile strength and resistance to heat and fatigue, beryllium is used in the
electronic, ceramic, aerospace, and nuclear energy industries. Disease due to beryllium probably represents a type IV hypersensitivity reaction, with noncaseating granuloma formation and eventual fibrosis. There is increased risk of bronchogenic carcinoma.
 
Byssinosis is a type of hypersensitivity pneumonitis that can occur with exposure to cotton, linen, or hemp exposure. It is associated with histamine-related bronchospasm.
 
Ref: Carrier D.D., Newman L.S. (2003). Chapter 31. Pneumoconiosis. In M.E. Hanley, C.H. Welsh (Eds), CURRENT Diagnosis & Treatment in Pulmonary Medicine.

Q. 10

All of the following features are seen in asbestosis except-

 A

Diffuse pulmonary interstitial fibrosis

 B

Fibrous pleural thickening.

 C

Emphysema

 D

Calcific pleural plaques

Q. 10

All of the following features are seen in asbestosis except-

 A

Diffuse pulmonary interstitial fibrosis

 B

Fibrous pleural thickening.

 C

Emphysema

 D

Calcific pleural plaques

Ans. C

Explanation:

Ans is ‘c’ i.e., Emphysema

Asbestosis

  • There are two distinct geometric forms of asbestos –

(i)       Serpentine chrysolite

(ii)  Amphibole (crocidolite)

  • Serpentine chrysolite accounts for most of the asbestos used in industry.

o Both serpentine and amphibole can cause all asbestosis related disease except for mesothelioma, which is usually associated with amphibole (crocidolite).

Asbestos related diseases

  • Localized fibrous plaques which may be calcified.

o Diffuse pleural fibrosis

o Pleural effusion

o Parenchymal interstitial fibrosis (asbestosis).

o Lung carcinoma Most common neoplasm associated with asbestos exposure.

o Mesothelioma of pleura and peritoneum —) most specific neoplasm associated with asbestos exposure. o Laryngeal and colon carcinomas.

o Stomach carcinoma

Note: – Concomitant cigarette smoking greatly increase the risk of lung carcinoma but not that of mesotheloma.


Q. 11

Ferruginous bodies are seen in –

 A

Silicosis

 B

Bysinosis

 C

Asbestosis

 D

Baggassosis

Q. 11

Ferruginous bodies are seen in –

 A

Silicosis

 B

Bysinosis

 C

Asbestosis

 D

Baggassosis

Ans. C

Explanation:

Ans. is ‘c’ i.e., Asbestosis

“Ferruginous bodies are most commonly seen in asbestosis”.————————– Chandrasoma Taylor

o Ferruginous bodies represent foreign inorganic or organic fibers coated by complexes of iron and glycoproteins. o While ferruginous bodies are most commonly seen in asbestosis they are not diagnostic because it may be seen in other type of pneunoconiosis.

o When asbestos fiber is coated by iron and glycoprotein, this ferruginous body is called asbestos body-characteristic of asbestosis.

o Ferruginous bodies are best seen in section that have stained for iron with prussion blue.

o Microscopically ferruginous bodies give a Shikh Kebab appearance.


Q. 12

Asbestosis of the lung is associated with all of the following except-

 A

Mesothelioma

 B

Progression of lesion even after stopping exposure to asbestos

 C

Nodular lesions involving upper lobe

 D

Asbestos bodies in sputum

Q. 12

Asbestosis of the lung is associated with all of the following except-

 A

Mesothelioma

 B

Progression of lesion even after stopping exposure to asbestos

 C

Nodular lesions involving upper lobe

 D

Asbestos bodies in sputum

Ans. C

Explanation:

Ans. is ‘c’ i.e., Nodular lesions involving upper lobes

Pulmonary changes of asbestos exposure

o Pleural plaques are the most common manifestation of asbestos exposure. They are well-circumscribed plaques of dens collegen, often containing calcium. They develop most frequently on the anterior and posterolateral aspects of parietal pleura and over dome of diaphragm.

o There is diffuse interstitial fibrosis mainly involving lower lung fields. Involved part contains asteroid bodies —› golden brown, fusiform or beaded rods with a translucent center and consist of asbestos fibers coated with an iron-containing proteinaceous material.

o Other inorganic particulates may become coated with similar iron protein complexes and are called ferruginous bodies.

Option “B”

o Asbestosis is a pneumoconiosis caused by exposure to asbestos (a commercial name given to certain types of fibrous material).

o The disease occurs at least 5 to 10 yrs. after exposure.

o In many cases disease presents itself years after the exposure has ceased.


Q. 13

All of the following are seen in asbestosis except ‑

 A

Diffuse alveolar damage

 B

Calcify pleural plaques

 C

Diffuse pulmonary interstitial fibrosis

 D

Mesotheliomas

Q. 13

All of the following are seen in asbestosis except ‑

 A

Diffuse alveolar damage

 B

Calcify pleural plaques

 C

Diffuse pulmonary interstitial fibrosis

 D

Mesotheliomas

Ans. A

Explanation:

Ans. is ‘a’ i.e., Diffuse alveolar damage


Q. 14

Asbestosis is associated with –

 A

Ca Lung

 B

Ascites

 C

Adenocarcinoma

 D

a and b

Q. 14

Asbestosis is associated with –

 A

Ca Lung

 B

Ascites

 C

Adenocarcinoma

 D

a and b

Ans. D

Explanation:

Ans. is ‘a’ i.e., Ca Lung; ‘b’ i.e., Ascites


Q. 15

The following does not occur with asbestosis ‑

 A

Methaemoglobinemia

 B

Pneumoconiosis

 C

Pleural mesothelioma

 D

Pleural calcification

Q. 15

The following does not occur with asbestosis ‑

 A

Methaemoglobinemia

 B

Pneumoconiosis

 C

Pleural mesothelioma

 D

Pleural calcification

Ans. A

Explanation:

Ans is ‘a i.e., Methaemoglobinemia


Q. 16

The following does not occur with asbestosis –

 A

Methaemoglobinemia

 B

Pneumoconiosis

 C

Pleural mesothelioma

 D

Pleural calcification

Q. 16

The following does not occur with asbestosis –

 A

Methaemoglobinemia

 B

Pneumoconiosis

 C

Pleural mesothelioma

 D

Pleural calcification

Ans. A

Explanation:

Ans. is ‘a’ i.e., Methaemoglobinemia


Q. 17

Extensive pleural thickening and calcification especially involving the diaphragmatic pleura are classical features of:

 A

Coal worker’s pneumoconiosis

 B

Asbestosis

 C

Silicosis

 D

Siderosis

Q. 17

Extensive pleural thickening and calcification especially involving the diaphragmatic pleura are classical features of:

 A

Coal worker’s pneumoconiosis

 B

Asbestosis

 C

Silicosis

 D

Siderosis

Ans. B

Explanation:

B i.e. Asbestosis

  • Radiological features of Asbestosis:

–      Pleural thickening and calcification primarily localized along lateral chest wall and diaphragmQ.

–      Differentiated from postinflamatory and post-traumatic pleural thickening & calcification by it’s

Bilateral involvement and sharp costophrenic angles in asbestosisQ.

Pleural thickening & calcification may be seen following minor exposure whereas pulmonary fibrosis only follows significant exposure

  • Pulmonary fibrosis in asbestosis is bilateral and maximal at bases whereas in coal workers pneumoconiosis and Silicosis upper half of the lung is mainly involved.Q

Q. 18

A 48 years old man, resident of Baroda outskirts near a textile mill presents to his family physician with respiratory symptoms. Doctor advices X Ray chest which showed – fine reticular & nodular pattern in lower zone with loss of clarity of diaphragm & cardiac shadows. He also doubts about the presence of small pleural effusion.

The probable diagnosis is?

 A

Stannosis

 B

Asbestosis

 C

Silicosis

 D

Coal worker’s pneumoconiosis

Q. 18

A 48 years old man, resident of Baroda outskirts near a textile mill presents to his family physician with respiratory symptoms. Doctor advices X Ray chest which showed – fine reticular & nodular pattern in lower zone with loss of clarity of diaphragm & cardiac shadows. He also doubts about the presence of small pleural effusion.

The probable diagnosis is?

 A

Stannosis

 B

Asbestosis

 C

Silicosis

 D

Coal worker’s pneumoconiosis

Ans. B

Explanation:

B i.e. Asbestosis

–  Asbestos related lung disease presents with pleural effusion (small, blood stained, persistent, recurrent, bilateral), pleural plaques (bilateral, multifocal, exclusively involving parietal pleura along posterolateral & lateral chest wall b/w 6-10th ribs and sparing visceral pleura, apices & costophrenic angles), pleural calcification (bilateral diaphragmatic calcification with clear CP angles is pathognomic), diffuse pleural thickening (involves visceral pleura & 1/t impaired lung function), asbestosis, pseudotumor (round atlectasis) & malignancy.

–  Asbetosis may present with fine to coarse reticulonodular pattern causing loss of clarity of diaphragm & cardiac shadow (Shaggy heart) on x ray. HRCT (investigation of choice) shows subpleural pulmonary arcade, pleural based nodular irragularities, parenchymal bands & septal lines

Round atelectasis occurs mostly in peripheral, lower, dorsal (posterior) lobes adjacent to visceral pleuraQ and presents with Comet taiVVaccum cleaner/ Crow’s feet sign and Swiss cheese air bronchogramQ

Predilection for Lower ZoneQ
(Whole lung may be involved with predominant lower zone involvement)

Asbestosis Related Lung Disease:

Asbestos is the generic term used for heat resistant fibrous silicates. They are classified into 2 groups. 1) Straight, rigid, needle like Amphiboles (eg commercial crocidolite = blue/black asbestos & amosite = brown asbestos; and non- commercial contaminating amphiboles such as actinolite, tremolite & anthophyllite); 2) Serpentines (nonamphiboles) such as commercial chrysolite = white asbestos.

– Aspect (length-to-diameter) ratio decides carcinogenicity. Amosite & crocidolite are relatively malignant, whereas anthophyllite, chrysotile and tremolite are benign. – Apart from pleural effusion, which may be present as early as 5 years post exposure, the typical abnormalities do not appear until 20 years or more after initial exposure.

– D/t asbestos, exposure may occur in asbestos industry, ship building & textile 


Q. 19

Mesothelioma is caused by – 

 A

Asbestosis

 B

Silicosis

 C

Baggasois

 D

Anthracosis

Q. 19

Mesothelioma is caused by – 

 A

Asbestosis

 B

Silicosis

 C

Baggasois

 D

Anthracosis

Ans. A

Explanation:

Ans. is ‘a’ i.e., Asbestosis 

Asbestosis

o There are two distinct geometric forms of asbestos –

i)    Serpentine chrysolite

ii)   Amphibole (crocidolite)

o Serpentine chrysolite accounts for most of the asbestos used in industry.

o Both serpentine and amphibole can cause all asbestosis related disease except for mesotheloma, which is usually associated with amphibole (crocidolite).

Asbestos related diseases

o Localized fibrous plaques which may be calcified.

o Diffuse pleural fibrosis

o Pleural effusion

o Parenchymal interstitial fibrosis (asbestosis).

a Lung carcinoma –> Most common neoplasm associated with asbestos exposure.

o Mesothelioma of pleura and peritoneum -4 most specific neoplasm associated with asbestos exposure. o Laryngeal and colon carcinomas.

o Stomach carcinoma

Note – Concomitant cigarette smoking greatly increase the risk of lung carcinoma but not that of mesotheloma.


Q. 20

All of the following features are suggestive of asbestosis except –

 A

Occurs within five years of exposure

 B

The disease progresses even after removal of contact

 C

Can lead to pleural mesothelioma.

 D

Sputum contains asbestos bodies

Q. 20

All of the following features are suggestive of asbestosis except –

 A

Occurs within five years of exposure

 B

The disease progresses even after removal of contact

 C

Can lead to pleural mesothelioma.

 D

Sputum contains asbestos bodies

Ans. A

Explanation:

Ans. is ‘a’ i.e., Occurs within five years of exposure 

Characteristics of asbestosis

i)         The disease does not usually appear until 5-10 years of exposure.

ii)       Once established, the disease is progressive even after removal of the worker from contact. Option c has been explained (see previous explanation) about option

o When asbestos fiber is coated by iron and glycoprotein. it is called asbestos body. o Asbestos body is characteristic of asbestosis and may be seen in sputum.



Q. 21

Pleural mesothelioma is associated with

 A

Asbestosis

 B

Berylliosis

 C

Silicosis

 D

Baggosis

Q. 21

Pleural mesothelioma is associated with

 A

Asbestosis

 B

Berylliosis

 C

Silicosis

 D

Baggosis

Ans. A

Explanation:

Ans. is ‘a’ i.e. Asbestosis 

  • Both pleural and peritoneal mesotheliomas are associated with asbestos exposure.
  • Although mesothelioma is the cancer most strongly related to asbestos exposure, the most common cancer associated with asbestos exposure is lung cancer (both squamous cell and adenocarcinoma)

Q. 22

All of the following features are seen in asbestosis except-

 A

Diffuse pulmonary interstitial fibrosis

 B

Fibrous pleural thickening

 C

Emphysema

 D

Calcific pleural plaques

Q. 22

All of the following features are seen in asbestosis except-

 A

Diffuse pulmonary interstitial fibrosis

 B

Fibrous pleural thickening

 C

Emphysema

 D

Calcific pleural plaques

Ans. C

Explanation:

Answer is C (Emphysema):

Emphysema has not been mentioned as a .feature of .4sbestos related lung disease.


Q. 23

True statements about asbestosis

 A

Causes Lung Ca

 B

Pleural mesothelioma

 C

Peritoneal mesothelioma

 D

All of the above

Q. 23

True statements about asbestosis

 A

Causes Lung Ca

 B

Pleural mesothelioma

 C

Peritoneal mesothelioma

 D

All of the above

Ans. D

Explanation:

Answer is D (All of the above) :

Asbestosis may be associated with Bronchogenic carcinoma, Mesotheliomas (pleural and peritoneal) and Pulmonary fibrosis.


Q. 24

Which of the following is true about pneumoconiosis?

 A

Pleural plaques of asbestosis is always symptomatic

 B

Silicosis is not associated with increased risk of Tuberculosis

 C

Asbestosis and smoking act synergistically to cause lung cancer

 D

Coal Workers Pneumoconiosis is associated with Lung cancer

Q. 24

Which of the following is true about pneumoconiosis?

 A

Pleural plaques of asbestosis is always symptomatic

 B

Silicosis is not associated with increased risk of Tuberculosis

 C

Asbestosis and smoking act synergistically to cause lung cancer

 D

Coal Workers Pneumoconiosis is associated with Lung cancer

Ans. C

Explanation:

Answer is C (Asbestosis and smoking act synergistically to cause lung cancer):

Asbestosis and smoking act synergistically to cause lung cancer.

‘There is significant interactive effect of smoking and asbestos exposure that results in greater risk of Lung Cancer than what would be expected from the additive effect of each factor’ – Harrison

Asbestosis and smoking act synergistically to cause lung cancer

  • Lung cancer is the most common cancer associated with asbestos exposure.
  • Persons with more exposure are at greater risk of disease
  • There is significant interactive effect of smoking and asbestos exposure that results in greater risk than what would be expected from the additive effect of each factor

Pleural Plaques in Asbestosis may be asymptomatic and imply onlprior exposure to Asbestos

  • Pleural Plaques are believed to be the most common manifestations suggesting Asbestos exposure
  • They are characterized by thickening or calcification along the parietal pleura particularly along the lower lung fields, the diaphragm and the cardiac border.
  • Without additional manifestations pleural plaques imply only exposure, not pulmonary impairment
  • These are usually asymptomatic although if extensive, they may be associated with breathlessness

Coal Workers Pneumoconiosis is not associated with Increased Risk of Lung Cancer

  • CWP is not associated with an increased risk of Tuberculosis or Primary Lung cancer 

Silicosis is associated with an increased risk of Tuberculosis

  • Silicosis is associated with an increased risk of Tuberculosis and Primary Lung Cancer

Q. 25

Lower lobe fibrosis is seen in :

 A

Silicosis

 B

Sarcoidosis

 C

Cystic Fibrosis

 D

Asbestosis

Q. 25

Lower lobe fibrosis is seen in :

 A

Silicosis

 B

Sarcoidosis

 C

Cystic Fibrosis

 D

Asbestosis

Ans. D

Explanation:

Answer is D (Asbestosis):

Lower lobe fibrosis is seen in Asbestosis.

Silicosis, Sarcoidosis and Cystic Fibrosis are all associated with Upper Lobe Fibrosis

Upper Lobe Fibrosis

Fibrotic Disease

  • Old Granulomatous Infection  (Tuberculosis; Histoplasmosis; Coccidioidomycosis)
  • Sarcoidosis
  • Silicosis, Berylliosis
  • Coal Worker’s Pneumoconiosis
  • Ankylosing Spondylitis
  • Radiation Pneumonitis
  • Chronic Hypersensitivity Pneumonitis

Airway Disease

  • Cystic Fibrosis
  • Allergic Bronchopulmonary Aspergillosis (ABPA)

 Fibrotic Disease

  • Idiopathic Pulmonary Fibrosis
  • Asbestosis
  • Collagen Vascular Disease
  • (SLE; Systemic Sclerosis; RA)
  • Drugs
  • (Busulphan; Bleomycin; Methotrexate etc.)

Airway Disease

  • Chronic Aspiration
  • Basal Bronchiectasis

Q. 26

Which of these pneumoconiosis is not a notifiable disease under Factory’s act 1948 in India:

March 2011

 A

Byssinosis

 B

Bagassosis

 C

Silicosis

 D

Asbestosis

Q. 26

Which of these pneumoconiosis is not a notifiable disease under Factory’s act 1948 in India:

March 2011

 A

Byssinosis

 B

Bagassosis

 C

Silicosis

 D

Asbestosis

Ans. B

Explanation:

Ans. B: Bagassosis

Notifiable disease under Factory’s act 1948 and Indian Mines act 1952 in India is silicosis, asbestosis, byssinosis etc. The Factories Act, 1948(Amended On 1987)

  • The Factories Act is the principal legislation, which governs the health, safety, and welfare of workers in factories.
  • The Act extends to the whole of India.
  • Mines and Railways workers are not included as they are covered by separate Acts.
  • The new Act addressed the issues of safety, health, and welfare.
  • Many amendments were aimed to keep the Act in tune with the developments in the field of health and safety.
  • However, it was not until 1987 that the elements of occupational health and safety, and prevention and protection of workers employed in hazardous process, got truly incorporated in the Act.
  • A factory under the Act is defined as a place using power, employs 10 or more workers, or 20 or more workers without power or were working any day of the preceding 12 months.
  • However, under section 85, the state governments are empowered to extend the provisions of the Act to factories employing fewer workers also.
  • This section has been used to extend the coverage of the Act to workplaces like power looms, rice mills, flour mills, oil mills, saw mills, pesticide formulating units and other chemical units where hazards to health are considered to put workers at risk.
  • The Act does not permit the employment of women and young in a dangerous process or operation.
  • Children are defined, “who have not attained an age of 15 years”, are not permitted to be hired (Sec. 2, 67) and need to have medical fitness certificates if he/she is has to work and age is not confirmed (Sec 69).
  • Section 11 to 20 deal with provision of environmental sanitation that protect the worker from hazardous environment.
  • Cleanliness of the working place, privy, benches, stairs, wall etc. are explained (Sec. 11).
  • Disposal of wastes and effluents should be without any risk (sec. 12).
  • Ventilation, temperature inside factory, dust and fumes emission, lighting, artificial humidification, overcrowding (minimum of 50 cubic meters per person) are specified (Secs. 13-17).
  • There should be a provision for same and cool drinking water and provision of water in the latrine and urinal.
  • One latrine for 25 female workers but one for 25 male workers up to 100 and one for 50 thereafter.
  • One urinal for 50 person up to 500 men and after that one for every 100 more
  • Safety measures like fencing of machines, protection of eyes by use of goggles, precautions against fire, dangerous fumes, etc. are defined (Secs 21-40).
  • Facilities for washing, and sitting, canteens, creche (one for more than 30 women) and first aid appliances are provided (Secs. 42-48).
  • One Welfare Officer for 500 or more workers is suggested (Sec. 49).
  • There is provision for one weekly holiday, and not more than 48 hours in a week an adult worker should work.
  • There is at least half an hour rest after a stretch of 5 hours of continuous work.
  • No women should be employed between 7 p.m. and 6 a.m. (Secs. 51-66).
  • No person less than 14 years of age should work in the factory.
  • No child should work more than 4 hours a day and should not work in the night between 10 p.m. to 6 a.m.
  • One full wage leave should be given to an adult worker for every 20 days of work and one for every 15 days to the child worker. 12 weeks of maternity leave should be given to a woman.
  • If an accident occurs in any factory causing death or bodily injury or prevents a worker from working for more than 48 hours, the manager must immediately send notice to the prescribed authority (i.e. Labour commissioner).
  • Following are the Notifiable Diseases:

– Lead poisoning or its sequelae

– Lead tetra-ethyl poisoning or its sequelae

– Phosphorus poisoning or its sequelae

Mercury poisoning or its sequelae

– Manganese poisoning or its sequelae

– Arsenic poisoning or its sequelae

–  Poisoning by nitrous fumes

Carbon bisulphite poisoning

– Benzene and its derivatives poisoning or its sequelae

– Chrome ulceration or its sequelae

– Anthax

– Silicosis

– Poisoning by halogens or its derivatives of hydrocarbons

– Pathological manifestation due to radium, radioactive substances, or X-rays

Primary epitheliomatous cancer of the skin

– Toxic anemia

– Toxic jaundice due to poisonous substances

– Oil acne or dermatitis due to mineral oil or its derivatives in any form

– Byssinosis

– Asbestosis

– Occupational or contact dermatitis caused by direct contact with chemical or paints. It could be primary irritants or allergic sensitisers.

– Noise induced hearing loss

– Beryllium poisoning

– Carbon monoxide

Coal miner’s pneumoconiosis

–  Phasgene poisoning

Occupational cancers

– Isocyanates poisoning

– Toxic nephiritis

These diseases were inserted by act 20 of 1987.


Q. 27

Mesothelioma is closely associated with which of the following:      

September 2011, March 2013 (f, h)

 A

Silicosis

 B

Anthracosis

 C

Byssinosis

 D

Asbestosis

Q. 27

Mesothelioma is closely associated with which of the following:      

September 2011, March 2013 (f, h)

 A

Silicosis

 B

Anthracosis

 C

Byssinosis

 D

Asbestosis

Ans. D

Explanation:

Ans. D: Asbestosis

Mesothelioma, a rare form of cancer of the pleura and peritoneum, has been shown to have a strong association with the crocidolite variety of asbestos

Mesothelioma/Malignant mesothelioma

  • It is a rare form of cancer that develops from the mesothelium.
  • It is usually caused by exposure to asbestos.
  • Its most common site is the pleura, but it may also occur in the peritoneum, the pericardium, or the tunica vaginalis.
  • Most people who develop mesothelioma have worked on jobs where they inhaled asbestos, or they have been exposed to asbestos dust and fiber in other ways.
  • It has also been suggested that washing the clothes of a family member who worked with asbestos can put a person at risk for developing mesothelioma.
  • Unlike lung cancer, there is no association between mesothelioma and smoking, but smoking greatly increases the risk of other asbestos-induced cancers.
  • The symptoms of mesothelioma include shortness of breath due to pleural effusion or chest wall pain, and general symptoms such as weight loss.
  • The diagnosis may be suspected with chest X-ray and CT scan, and is confirmed with a biopsy and microscopic examination.
  • A thoracoscopy can be used to take biopsies.
  • It allows the introduction of substances such as talc to obliterate the pleural space (pleurodesis), which prevents more fluid from accumulating and pressing on the lung.
  • Despite treatment with chemotherapy, radiation therapy or sometimes surgery, the disease carries a poor prognosis.
  • Indeed, the relationship between asbestos and mesothelioma is so strong that many consider mesothelioma a “signal” or “sentinel” tumor.
  • In rare cases, mesothelioma has also been associated with irradiation, intrapleural thorium dioxide (Thorotrast), and inhalation of other fibrous silicates, such as erionite.
  • Screening tests might diagnose mesothelioma earlier than conventional methods thus improving the survival prospects for patients.The serum osteopontin level might be useful in screening asbestos-exposed people for mesothelioma.
  • The level of soluble mesothelin-related protein is elevated in the serum of about 75% of patients at diagnosis and it has been suggested that it may be useful for screening.

Q. 28

Lung Carcinoma is most commonly associated with:

March 2005

 A

Silicosis

 B

Asbestosis

 C

Coal dust

 D

Beryllium

Q. 28

Lung Carcinoma is most commonly associated with:

March 2005

 A

Silicosis

 B

Asbestosis

 C

Coal dust

 D

Beryllium

Ans. B

Explanation:

Ans. B: Asbestosis

Cigarette smoking is the most important cause of lung cancer. About 90% of lung cancers arise due to tobacco use. Other causes of lung cancer include the following: Passive smoking, or secondhand smoke, presents another risk for lung cancer. Air pollution from motor vehicles, factories, and other sources probably increase the risk for lung cancer. Asbestos exposure increases the risk of lung cancer nine times. A combination of asbestos exposure and cigarette smoking raises the risk to as much as 50 times. Another cancer known as mesothelioma (a type of cancer of the lining of the chest cavity called the pleura or of the lining of the abdominal cavity called the peritoneum) is also strongly associated with exposure to asbestos.

Lung diseases, such as chronic obstructive pulmonary disease (COPD), also create a risk for lung cancer. A person with COPD has a four to six times greater risk of lung cancer even when the effect of cigarette smoking is excluded. Radon exposure poses another risk. Radon is a by-product of naturally occurring radium, which is a product of uranium. Silicosis is associated with pulmonary fibrosis. X-ray of chest shows rounded opacities in the upper lobes after 15-20 years (simple silicosis). Calcification of hilar nodes may produce ‘eggshell’ pattern.

Beryllium may produce acute pneumonitis, but it is more commonly associated with a chronic granulomatous disease similar to sarcoidosis.


Q. 29

Pleural calcification is seen in:

 A

Asbestosis

 B

Mesothelioma

 C

Pulmonary infarction

 D

Anthracosis

Q. 29

Pleural calcification is seen in:

 A

Asbestosis

 B

Mesothelioma

 C

Pulmonary infarction

 D

Anthracosis

Ans. A

Explanation:

Ans. Asbestosis


Q. 30

Asbestosis all are features except

 A

Pleural cancer

 B

Lung carcinoma

 C

Pleural effusion

 D

Atelectasis

Q. 30

Asbestosis all are features except

 A

Pleural cancer

 B

Lung carcinoma

 C

Pleural effusion

 D

Atelectasis

Ans. D

Explanation:

Ans. is ‘d’ i.e., Atelectasis

Asbestos-Related Diseases :‑

  • Asbestos is a family of proinflammatory crystalline hydrated silicates that are associated with pulmonary fibrosis, carcinoma, mesothelioma, and other cancers.
  • There are two distinct geometric forms of asbestos:
  1. Serpentine chrysolite – most of the asbestos used in industry
  2. Amphibole (crocidolite)
  • Both serpentine and amphibole can cause all asbestos related diseases except for mesothelioma, which is usually associated with amphibole (crocidolite).

Asbestos related diseases consist of :‑

  • Localized fibrous plaques which may be calcified.
  • Diffuse pleural fibrosis.
  • Pleural effusion.
  • Parenchymal interstitial fibrosis (asbestosis).
  • Lung carcinoma —> Most common neoplasm associated with asbestos exposure.
  • Mesothelioma of pleura and peritoneum —> most specific neoplasm associated with asbestos exposure. o Laryngeal and colon carcinomas.
  • Stomach carcinoma.

Q. 31

Asbestosis causes all except

 A

Shaggy heart borders

 B

Honeycombing

 C

Hilar lymphadenopathy

 D

Basal peribronchial fibrosis

Q. 31

Asbestosis causes all except

 A

Shaggy heart borders

 B

Honeycombing

 C

Hilar lymphadenopathy

 D

Basal peribronchial fibrosis

Ans. C

Explanation:

Ans. is ‘c’ i.e., Hilar lymphadenopathy

  • Asbestosis causes fibrosis in the lower lobes of the lung.
  • Pleural plaque formed by asbestosis most commonly affects anterolateral and posterolateral aspects of parietal pleura and over the dome of diaphragm


Transforming growth factor Beta

Transforming growth factor Beta

Q. 1

During angiogenesis recruitment of pericytes and periendothelial cells is due to ‑

 A

VEGF & PDGF

 B

Angiopoietins, TGF & PDGF

 C

TGF, VEFG & PDGF

 D

VEGF, IL-2, IL-6

Q. 1

During angiogenesis recruitment of pericytes and periendothelial cells is due to ‑

 A

VEGF & PDGF

 B

Angiopoietins, TGF & PDGF

 C

TGF, VEFG & PDGF

 D

VEGF, IL-2, IL-6

Ans. B

Explanation:

Ans. is ‘b’ i.e., Angiopoietins, TGF & PDGF

Angiogenesis

o Blood vessels formation in adults is known as angiogenesis or neovascularization. It can occur by two ways:‑

1) Angiogenesis from pre-existing blood vessels

             The major steps in this process are :-

i)           Vasodilatation by NO, and VEGF-induced increased permeability of the pre-existing vessel.

ii)          Preoteolytic degradation of basement membrane by metalloproteinases (MMPs) and disruption of cell­to-cell contact between endothelial cells by plasminogen activator.

iii)        Migration of endothelial cells towards angiogenic stimulus.

iv)        Proliferation of endothelial cells, just behind the leading front of migrating cells.

v)         Maturation of endothelial cells.

vi)        Recruitment of periendothelial cells (pericytes and vascular smooth muscle cells) to form the mature cells.

2) Angiogenesis from endothelial precursor cells (EPCs)

             EPCs can be recruited from the bone marrow into tissues to initiate angiogenesis.

Growth factors involved in the process of angiogenesis

o VEGF is the most important growth factor in adult tissues undergoing angiogenesis.

o The most important receptor for VEGF is VEGFR-2, a tyrosine kinase receptor.

o VEGF induces the migration of EPCs in the bone marrow, and enhances the proliferation and differentiation of these cells at sites of angiogenesis.

o FGF 2 can also stimulate endothelial cell proliferation, differentiation and migration.

o Newly formed vessels are fragile and need to become stabilized, which requires the recruitment of pericytes and smooth muscle cells (periendothelial cells). Angiopoietin I and 2 (Ang 1 & 2), PDGF and TGF-0 participate in stabilization process.

Remember

  • VEGF transcription is regulated by the transcription factor HIF, which is induced by hypoxia.

Q. 2

Fibrosis is due to

 A

TGF- r3

 B

TNF

 C

IL – 7

 D

IL- 10

Q. 2

Fibrosis is due to

 A

TGF- r3

 B

TNF

 C

IL – 7

 D

IL- 10

Ans. A

Explanation:

Ans. is ‘a’ i.e., TGF-


Q. 3

Which is not the action of TGF –

 A

Anti-inflammatory

 B

Proliferation of fibrous tissue

 C

Inhibition of metalloproteinases

 D

Anaphylaxis

Q. 3

Which is not the action of TGF –

 A

Anti-inflammatory

 B

Proliferation of fibrous tissue

 C

Inhibition of metalloproteinases

 D

Anaphylaxis

Ans. D

Explanation:

Ans. is ‘d’ i.e., Anaphylaxis

Transforming Growth factor beta:

Transforming growth factor β (TGF- β) is the most important cytokine for the synthesis and deposition of connective tissue proteins.

It is produced by most of the cells in granulation tissue, including alternatively activated macrophages.

The levels of TGF-β in tissues are primarily regulated not by the transcription of the gene but by the posttranscriptional activation of latent TGF-β, the rate of secretion of the active molecule, and factors in the ECM, notably integrins, that enhance or diminish TGF-β activity.

TGF-β stimulates fibroblast migration and proliferation, increased synthesis of collagen and fibronectin, and decreased degradation of ECM due to inhibition of metalloproteinases.

TGF-β is involved not only in scar formation after injury but also in the development of fibrosis in lung, liver, and kidneys that follows chronic inflammation.

TGF-β is also an antiinflammatory cytokine that serves to limit and terminate inflammatory responses. It does this by inhibiting lymphocyte proliferation and the activity of other leukocytes.


Q. 4

Fibrosis is due to ‑

 A

TGF beta

 B

TNF alpha

 C

IL 7

 D

IL l0

Q. 4

Fibrosis is due to ‑

 A

TGF beta

 B

TNF alpha

 C

IL 7

 D

IL l0

Ans. A

Explanation:

Ans. is ‘a’ i.e., TGF beta



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