Organ Specific Anomalies
• Agenesis: complete absence of an organ
• Atresia: absence of an opening
• Hypoplasia: incomplete development or under-
development of an organ with decreased numbers of
cells
• Hyperplasia: overdevelopment of an organ
associated with increased numbers of cells
• Hypertrophy: increase in size with no change in
number of cells
• Dysplasia:) describes an abnormal organization of
cells
Embryonic Development
• Embryonic period
– weeks 1- 8 of pregnancy
– organogenesis occurs in this period
• Fetal period
– weeks 9 to 38
– marked by further growth and maturation
Perinatal Infection
• Transcervical (ascending)
– inhalation of infected amniotic fluid
• pneumonia, sepsis, meningitis
• commonly occurs with PROM—premature rupture
memb.
– passage through infected birth canal
• herpes virus– caesarian section for active herpes
• Transplacental (hematogenous)
– mostly viral and parasitic
• HIV—at delivery with maternal to fetal transfusion
– bacterial
• Listeria monocytogenes
Inborn Errors of Metabolism
(Genetic)
•PhenylKetonUria (PKU)
• Galactosemia
•Cystic Fibrosis (CF)
(Mucoviscidosis)
PHENYLKETONURIA (PKU)
• Ethnic distribution
– common in persons of Scandinavian descent
– uncommon in persons of African-American and Jewish
descent
• Autosomal recessive
• Phenylalanine hydroxylase deficiency leads to
hyperphenylalaninemia, brain damage, and mental
retardation
• Phenylalanine metabolites are excreted in the urine
• Treatment is phenylalanine restriction
• Variant forms exist
Cystic Fibrosis (Mucoviscidosis)
• Autosomal recessive
• Most common lethal genetic disease affecting
Caucasians
• 2-4% of population are carriers
– Uncommon in Asians and African-Americans
• Widespread disorder in (epithelial chloride transport)
affecting fluid secretion in exocrine glands
– epithelial lining of the respiratory, gastrointestinal,
and reproductive tracts
• Abnormally viscid mucus secretions
Etiology & pathogenesis:
• The primary defect is in the regulation of epithelial
chloride transport by a--- chloride channel protein--encoded by the cystic fibrosis gene.
• The impact of this defect in chloride transport differs in
various tissue example:
• In sweat gland ducts it leads to decreased reabsorption of
sodium chloride from the lumen, thus resulting in increase
concentrations of sweat chloride, the basis of clinical
diagnosis of CF.
Cellular Metabolism Of The Cystic Fibrosis
Transmembrane Regulator (CFTR)
Harrison’s Internal Med, 16th Ed
• In the airway epithelium: there is reduction of
chloride secretion into airways. Active sodium
absorption is also increase, both of these ions increase
water reabsorption from the lumen causing lowering
the water content of the mucus material leading to
viscid secretions
• The cystic fibrosis gene is located on chromosome 7
which encodes chloride channel protein.
• Pancreatic abnormalities are present in approximately 85 to
90% of patients.
• Thick viscid plugs of mucus may also be found in the small
intestine of infants. Sometimes these cause small bowel
obstruction, known as meconium ileus.
• The salivary glands are frequently involved, with histologic
changes include progressive dilation of ducts, squamous
metaplasia of the lining epithelium, and glandular atrophy
followed by fibrosis.
• In most cases, the diagnosis of cystic fibrosis is based on
persistently elevated sweat electrolyte concentrations (often
the mother makes the diagnosis because her infant tastes
salty) and characteristic clinical findings (gastrointestinal or
pulmonary) or a family history
• There are new reports suggesting an increased risk of
digestive tract cancer in patients with cystic fibrosis. These
cancers affect the entire gastrointestinal system, the biliary
tract, liver, and pancreas. The pathenogenesis of such
cancers is unclear.
• The pulmonary changes are seen in almost every case
and are the most serious complications of this disease.
These stem from the viscous mucus secretions of the
submucosal glands of the respiratory tree with
secondary obstruction and infection of the air
passages.
• obstruction of the epididymis and vas deferens, which
is responsible for azoospermia and infertility in 95%
of the males who survive to adulthood.
Organ Pathology
• Plugging of ducts with viscous mucus and loss of ciliary
function of respiratory mucosa
• Pancreas
– atrophy of exocrine pancreas with fibrosis
– islets are not affected
• Liver
– plugging of bile canaliculi with portal inflamation
– biliary cirrhosis may develop
• Genitalia
– Absence of vas deferens and azoospermia
• Sweat glands
– normal histology
Neonatal Respiratory Distress Syndrome
(RDS)
•
Incidence is inversely proportional to
gestational age
• The cause is lung immaturity with decreased
alveolar surfactant
– surfactant decreases surface tension
– first breath is the hardest since lungs must be
expanded
– without surfactant, lungs collapse with each breath
RDS Risk Factors
• 1) Prematurity
– by far the greatest risk factor
– affected infants are nearly always premature
• 2) Maternal diabetes mellitus
– insulin suppresses surfactant secretion
• 3) Cesarean delivery
– normal delivery process stimulates surfactant
secretion
RDS Pathology
• Gross
– solid and airless (no crepitance)
– sink in water
– appearance is similar to liver tissue*
• Microscopic
– atelectasis and dilation of alveoli
– hyaline membranes composed of fibrin and cell
debris line alveoli .
– minimal inflammation
Necrotizing Enterocolitis
• Incidence is inversely proportional to
gestational age
– approaches 10% with severe prematurity
• Pathogenesis
– not fully understood
– intestinal ischemia
– inflammatory mediators
– breakdown of mucosal barrier
Necrotizing Enterocolitis
Sudden Infant Death Syndrome
Definition
– sudden death of an infant under 1 year of age
which remains unexplained after a thorough case
investigation, including performance of a complete
autopsy, examination of the death scene, and
review of the clinical history
Also called crib death
TUMORS
Benign •
Malignant •
BENIGN
•
•
•
•
Hemangiomas
Lymphatic Tumors
Fibrous Tumors
Teratomas (also can be malignant)
Congenital Capillary Hemangioma
At birth
At 2 years
After spontaneous regression
Teratomas
• Composed of cells derived from more than
one germ layer, usually all three
• Sacrococcygeal teratomas
– most common childhood teratoma
– frequency 1:20,000 to 1:40,000 live births
– 4 times more common in boys than girls
• Approximately 12% are malignant
– often composed of immature tissue
– occur in older children
Sacrococcygeal Teratoma
Malignant Tumors
• Cancers of infancy and childhood differ biologically and
histologically from their counterparts occurring later in life.
• The main differences are:
– Incidence and type of tumor
– Prevalence of underlying familial or genetic aberrations
– Tendency of fetal and neonatal malignancies to regress
spontaneously or cytodifferentiate
– Improved survival or cure of many childhood tumors,
INCIDENCE AND TYPES
• The most frequent childhood cancers arise in the
hematopoietic system (leukemia & lymphoma), nervous
tissue (including the central and sympathetic nervous
system, adrenal medulla, and retina), soft tissues, bone,
and kidney.
• Histologically, many of the malignant pediatric
neoplasms are unique. In general, they tend to have a
more primitive (embryonal)
• These tumors are frequently designated by the suffix blastoma, for example, nephroblastoma (Wilms' tumor),
hepatoblastoma, and neuroblastoma.
Neuroblastomas
• Second most common malignancy of
childhood
• Neural crest origin
– adrenal gland – 40 %
– sympathetic ganglia – 60%
• In contrast to retinoblastoma, most are
sporadic but familiar forms do occur
• Median age at diagnosis is 22 months
Neuorblastoma Morphology
• Small round blue cell tumor
– neuorpil formation
– rosette formation
– immunochemistry – neuron specific enolase
– EM – secretory granules (catecholamine)
• Usual features of anaplasia
– high mitotic rate is unfavorable
– evidence of Schwann cell or ganglion
differentiation favorable
• Other prognostic predictors are used by
pathologists and oncologists
Neuorblastoma
**
*
**Homer-Wright Rosettes
*N
Clinical Course and Prognosis
• Hematogenous and lymphatic metastases to liver, lungs
and bone
• 90% produce catecholamines, but hypertension is
uncommon
• Age and stage are most important prognostically
– < 1 year age: good prognosis regardless of stage
• Amplification of N-myc oncogene
– present in 25-30% of cases and is unfavorable
– up to 300 copies on N-myc has been observed
• Risk Stratification
– low risk: 90% cure rate
– high risk 20% cure rate