DR. ROOPAM JAIN, Professor & Head, Department of Pathology & Blood Bank

1. Dr. ROOPAM JAIN
PROFESSOR & HEAD
INFANCY &
CHILDHOOD
DISORDER

2. INFANCY & CHILDHOOD DISORDERS
 Congenital anomalies
 Prematurity and fetal growth restriction
 Perinatal infections
 Fetal hydrops
 Inborn errors of metabolism
 Sudden infant death syndrome
 Tumors

3. Dr. ROOPAM JAIN
Professor & Head

4. Definition
o SIDS is the sudden, unexplained death of an
infant younger than one year old.
o Some people call SIDS "crib death" because many
babies who die of SIDS are found in their cribs.

5. INCIDENCE OF
o SIDS is the leading cause of death in children
between one month and one year old.
o Most SIDS deaths occur when babies are between
2 months & 4 months old
o 6000-7000 babies die of SIDS every year in US
 male predominance
 the presence of intrathoracic petechiae
 linked the death to a sleep period (i.e., the time
when the majority of deaths occurred)

6. PATHOGENESIS
 A leading hypothesis - SIDS may reflect a delay or
abnormality in the development of nerve cells within
the brain that are critical to normal heart and lung
function.
 brainstems of infants who died with a diagnosis of
SIDS have revealed a developmental delay in the
formation and function of several serotonin-binding
nerve cell pathways within the brain.
 The most compelling hypothesis is that SIDS reflects
a delayed development of “arousal” and
cardiorespiratory control

7.  The serotonergic (5-HT) system of the
medulla is implicated in these “arousal”
responses, as well as regulation of other critical
homeostatic functions such as respiratory drive,
blood pressure & upper airway reflexes

8. Causes of SIDS ?!
A combination of physical and sleep environmental
factors can make an infant more vulnerable to SIDS.
These factors may vary from child to child.
o Brain abnormalities
o Low birth weight
o Respiratory infection

9. RISK FACTORS
 A “triple-risk” model of SIDS has been
proposed, which postulates the
intersection of three overlapping factors:
 (1) a vulnerable infant,
 (2) a critical developmental period(first 6 months
of life)
 (3) an exogenous stressor.

11. Risk Factors with Sudden Infant Death Syndrome

14. o Sleeping on a soft surface. Lying face down
on a fluffy comforter or a waterbed can block an
infant's airway. Draping a blanket over a baby's
head also is risky.

15. TUMORS
INFANCY & CHILDHOOD DISORDERS

16. BENIGN TUMORS
Hemangioma
Lymphatic Tumors
Fibrous Tumors
Teratomas
MALIGNANT TUMORS
Leukemia
Retinoblastoma
Neuroblastoma
Wilms Tumor
Hepatoblastoma
Hepatocellular Carcinoma
Soft Tissue Sarcoma
Others

17. Common paediatric benign tumours &
tumour-like lesions

18. Common paediatric malignant tumours

19.  In infants and children under 4 years of age:
MC malignant tumours are various types of
blastomas.
 Children between 5 to 9 years of age:
haematopoietic malignancies.
 In the age range of 10-14 years:
soft tissue & bony sarcomas.

20. Common paediatric benign tumours
& tumour-like lesions

21. Hemangioma
 Hemangioma. Hemangiomas are the most
common tumors of infancy
 In children, most are located in the skin, particularly
on the face and scalp, where they produce flat to
elevated, irregular, red-blue masses; some of the
flat, larger lesions are referred to as port-wine
stains
 Hemangiomas may enlarge along with the growth
of the child, but in many instances they
spontaneously regress

22. Lymphatic Tumors
 lymphatic origin
 lymphangiomas—are hamartomatous or
neoplastic, whereas others k/s lymphangiectasis.
 The lymphangiomas are usually characterized by
cystic and cavernous spaces.

23. Teratomas
 Teratomas may occur as benign, well-differentiated cystic
lesions (mature teratomas), immature teratomas, or as
malignant teratomas
 two peaks in incidence: the first at - 2 years of age & the
second in late adolescence or early adulthood
 Sacrococcygeal teratomas are the most common
teratomas of childhood (40%)
 Approximately 75% - mature teratomas
 about 12% - unequivocally malignant and lethal.
 The remainder is immature teratomas;

24. Sacrococcygeal teratoma

25. Common paediatric MALIGNENT
tumours

27. NEUROBLASTOMA
 Neuroblastic tumors include tumors of:
 Sympathetic ganglia
 Adrenal medulla
 These sites have cells derived from
primordial Neural Crest

28. NEUROBLASTOMA
 Among Neuroblastic tumors, Neuroblastoma is
the most common extracranial solid tumor of
childhood
 It is the most frequently diagnosed tumor of
infancy
 Median age of diagnosis is 18 months & 40% are
diagnosed during infancy

29. NEUROBLASTOMA
 Germline mutations in Anaplastic Lymphoma
Kinase (ALK) gene is the major cause of familial
predisposition to Neuroblastoma
 40% of cases arise in Adrenal medulla
 Other sites of involvement are:
 Paravertebral region of Abdomen (25%)
 Posterior Mediastinum (15%)
 Rest of the common sites are Pelvis, Neck & within
the Brain (Cerebral Neuroblastoma)

30. NEUROBLASTOMA
 Morphology (Grossly):
 Size ranges from small nodules (k/s in-situ lesions) to
large masses weighing more than 1 kg.
 In-situ lesions occur more frequently
 majority of which regress leaving only a focus of
fibrosis or calcification in the adult

31. NEUROBLASTOMA
 Morphology (Grossly):
 Some have fibrous pseudocapsules but others are
infiltrative invading surrounding structures
 On cut section:
 Soft
 Composed of Gray-tan tissue
 May show areas of Hemorrhage and Necrosis

33. NEUROBLASTOMA
 Morphology (Microscopically):
 Composed of:
 Sheets of small cells with dark nuclei
 Scanty cytoplasm
 Poorly defined cell borders
 Pleomorphism
 Mitotic activity
 Homer-Wright rosettes may be seen

35. NEUROBLASTOMA
 Clinical progress:
 In children under 2 years of age, Neuroblastoma
presents with large abdominal mass, fever and
weight loss
 In older children, they may not come into attention
until metastasis causing manifestations related to
affected organs such as:
 Bone Pain
 Respiratory Symptoms
 Gastrointestinal Symptoms

37. WILMS TUMOR
 Also known as Nephroblastoma
 In U.S.A., it is most common primary Renal tumor of
childhood
 Peak incidence is seen in the age group of 2-5 years
 95% cases occur before the age of 10 years
 5-10% cases involve both the kidneys
 Synchronous: If both kidneys affected at same time
 Metachronous: If affected one after another

38. WILMS TUMOR
 The exact cause of Wilms tumor is not clear but in rare cases,
heredity plays a role
 Risk factors:
 African-American race
 Family history of Wilms tumor
 Some cases can occur as a part of three syndromes:
 WAGR Syndrome
 Denys-Drash Syndrome
 Beckwith-Wiedemann Syndrome

39. WILMS TUMOR
 WAGR Syndrome:
 It includes Wilms tumor, Aniridia, Genitourinary system
abnormalities and Mental Retardation
 These cases carry germline deletion of chromosome 11p13
 This chromosome carry the first Wilms Tumor associated
gene WT1
 The lifetime chances of occurrence of Wilms tumor is 33%

40. WILMS TUMOR
 Denys-Drash Syndrome:
 It includes gonadal dysgenesis and early onset nephropathy
 These cases also carry germline abnormalities in WT1 which
affects DNA binding properties
 These cases have higher risk of Wilms tumor (~90%)

41. WILMS TUMOR
 Beckwith-Wiedemann Syndrome:
 This is clinically different from both WAGR & Denys-Drash
syndromes but this also has high risk of developing Wilms
Tumor
 This syndrome is characterized by enlargement of body
organs, macroglossia, ear abnormalities & abnormal large
cells in Adrenal Cortex
 The chromosome region implicated has been localized to
band 11p15.5 and termed as WT2

42. WILMS TUMOR
 Morphology:
 Grossly:
 Tumor is large, solitary and well circumscribed
 10% cases are bilateral or multicentric
 On cut section,
• Soft
• Homogenous
• Tan to gray in color
• Occasionally foci of hemorrhage and necrosis
seen

43. Wilms tumor in the lower pole of the
kidney with the characteristic tan-to-gray
color & well-circumscribed margins

44. WILMS TUMOR
 Morphology:
 microscopically:
 Tumor is composed of sheets of small blue cells
 5% cases show features of anaplasia i.e. Presence of
cells with nuclei features:
• Large
• Hyperchromatic
• Pleomorphic
• With mitotic figures

45. Focal anaplasia was present in this Wilms tumor
in other areas, characterized by cells with
hyperchromatic, pleomorphic nuclei, and
abnormal mitoses.

46. WILMS TUMOR
 Clinical features:
 Large abdominal mass which may extend to pelvis
 Hematuria
 Abdominal pain
 Intestinal obstruction
 In some cases, pulmonary metastasis is present at
the time of primary diagnosis

47. Dr. ROOPAM JAIN
PROFESSOR & HEAD
Environmental &
Nutritional Diseases

48. Alarming environmental degradation
 1. Population explosion
 2. Urbanisation of rural & forest land to
accommodate the increasing numbers
 3. Accumulation of wastes
 4. Unsatisfactory disposal of radioactive and
electronic waste
 5. Industrial effluents and automobile exhausts

49. Environmental &
nutritional diseases
1. Environmental pollution:
 i. Air pollution
 ii. Environmental chemicals
 iii. Tobacco smoking
2. Chemical and drug injury:
 i. Therapeutic (iatrogenic) drug injury
 ii. Non-therapeutic toxic agents (e.g. alcohol, lead,
carbon monoxide, drug abuse)
 iii. Environmental chemicals

50. 3. Injury by physical agents:
 i. Thermal and electrical injury
 ii. Injury by ionising radiation
4. Nutritional diseases:
 i. Overnutrition (obesity)
 ii. Undernutrition (starvation, PEM, vitamin
deficiencies).

51. ENVIRONMENTAL POLLUTION
 Any agent— chemical, physical or microbial, that
alters the composition of environment is called
pollutant
 air pollution,
 environmental chemicals
 tobacco smoking.

52. AIR POLLUTION
 The adverse effects of air pollutants on lung depend
upon a few variables that include:
 i) longer duration of exposure;
 ii) total dose of exposure;
 iii) impaired ability of the host to clear inhaled particles;
 iv) particle size of 1-5 µm capable of getting impacted in
the distal airways to produce tissue injury.

53. ENVIRONMENTAL CHEMICALS
 1. Agriculture chemicals
 2. Volatile organic solvents
 3. Metals Pollution by occupational exposure to
toxic metals such as mercury, arsenic, cadmium,
iron, nickel & aluminium are important hazardous
environmental chemicals.
 4. Aromatic hydrocarbons - are contaminant in
several preservatives, herbicides and antibacterial
agents are a chronic health hazard.
 5. Cyanide- released by combustion of plastic, silk
 6. Environmental dusts

54. TOBACCO SMOKING
The relative risk of major diseases in tobacco
smokers compared from non-smokers
 i) Cancer of the lung: 12 to 23 times
 ii) COPD: 10-13 times
 iii) Cancers of upper aerodigestive tract (larynx,
pharynx, lip, oral cavity, oesophagus): 6 to 14 times
 iv) Aortic aneurysm: 6-7 times
 v) Other cancers by systemic effects (kidneys,
pancreas, urinary bladder, stomach, cervix): 2-3
times

55.  vi) Cerebrovascular accidents (CVA): 2-4 times
 vii) Coronary heart disease: 2 to 3 times relative risk
 viii) Sudden infant death syndrome: 2 times
 ix) Buerger’s disease (thromboangiitis obliterans)
 x) Peptic ulcer disease AC 70%higher risk in smokers.
 xi) Early menopause in smoker women.
 xii) In smoking pregnant women, higher risk of LBW
of foetus, higher perinatal mortality and intellectual
deterioration of newborn.

56. Major constituents of tobacco
smoke with adverse effects

57. Major adverse effects of tobacco smoking

58. Summary of the adverse effects of smoking

59. CHEMICAL AND DRUG INJURY
 1. Therapeutic (iatrogenic) agents e.g.
drugs, which when administered indiscriminately
are associated with adverse effects.
 2. Non-therapeutic agents e.g. alcohol, lead,
carbon monoxide, drug abuse.

60. CHEMICAL AND DRUG INJURY
THERAPEUTIC (IATROGENIC) DRUG INJURY
Adverse effects of drugs may appear due to:
 i) overdose;
 ii) genetic predisposition;
 iii) exaggerated pharmacologic response
 iv) interaction with other drugs
 v) unknown factors.

61. Iatrogenic drug injury

63. Iatrogenic drug injury

64. Iatrogenic drug injury

65. Iatrogenic drug injury

66. Adverse drug reaction.
Skin pigmentation caused by minocycline
(a long-acting tetracycline derivative)
Diffuse blue-gray pigmentation of the forearm

67. NON-THERAPEUTIC TOXIC AGENTS
1. ALCOHOLISM
 most of the alcohol-related injury to different
organs is due to toxic effects of alcohol and
accumulation of its main toxic metabolite,
acetaldehyde, in the blood.
 Other proposed mechanisms of tissue injury in
chronic alcoholism are free-radical mediated
injury and genetic susceptibility to alcohol-
dependence & tissue damage.

68. NON-THERAPEUTIC TOXIC AGENTS
1. ALCOHOLISM
Metabolism of ethanol in the liver

69. Complications of chronic alcoholism

70. NON-THERAPEUTIC TOXIC AGENTS
2. LEAD POISONING
 Lead poisoning may occur in children or adults
due to accidental or occupational ingestion.
 absorbed lead is distributed in two types of
tissues
 a) Bones, teeth, nails and hair b) Brain, liver,
kidneys and bone marrow

71. Complications of
lead poisoning

72. NON-THERAPEUTIC TOXIC AGENTS
3. CARBON MONOXIDE POISONING
 CO poisoning may present in 2 ways:
 Acute CO poisoning in which there is sudden
development of brain hypoxia characterised by
oedema and petechial haemorrhages.
 Chronic CO poisoning presents with nonspecific
changes of slowly developing hypoxia of the brain.

73. INJURY BY RADIATION
 most important form of radiation injury is ionising
radiation which has three types of effects on cells:
 i) Somatic effects which cause acute cell killing.
 ii) Genetic damage by mutations and therefore,
passes genetic defects in the next progeny of cells.
 iii) Malignant transformation of cells

74.  1. Skin: radiation dermatitis, cancer.
 2. Lungs: interstitial pulmonary fibrosis.
 3. Heart: myocardial fibrosis, constrictive pericarditis.
 4. Kidney: radiation nephritis.
 5. GI tract: strictures of small bowel and oesophagus.
 6 Gonads: testicular atrophy & destruction of ovaries.
 7. Haematopoietic tissue: pancytopenia due to bone
marrow depression.
 8. Eyes: cataract.

75. 4. DRUG ABUSE
 use of certain drugs for the purpose of ‘mood alteration’ or
‘euphoria’ or ‘kick’ but subsequently leading to habit-
forming, dependence & eventually addiction
 1. Marijuana or ‘pot’ is psychoactive substance – (leaves
of the plant Cannabis sativa) (contains
tetrahydrocannabinol ) (smoked or ingested.
 2. Derivatives of opium (heroin and morphine). Opioids
are derived from the poppy plant.
 3. CNS depressants - barbiturates, tranquilisers, alcohol.
 4. CNS stimulants e.g. cocaine and amphetamines.
 5. Psychedelic drugs e.g. LSD.
 6. lnhalants e.g. glue, paint thinner, nail polish remover,
aerosols, amyl nitrite.

76. Common Drugs of Abuse

77. Common Drugs of Abuse

78. The effect of cocaine on neurotransmission
The drug inhibits reuptake of the
neurotransmitters dopamine & norepinephrine
in the CNS & PNS