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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 fluidpneumonia, sepsis, meningitiscommonly occurs with PROM—premature rupture memb.passage through infected birth canalherpes virus– caesarian section for active herpesTransplacental (hematogenous)mostly viral and parasiticHIV—at delivery with maternal to fetal transfusion bacterialListeria 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 originadrenal gland – 40 %sympathetic ganglia – 60%In contrast to retinoblastoma, most are sporadic but familiar forms do occurMedian age at diagnosis is 22 months

Neuorblastoma Morphology

Small round blue cell tumorneuorpil formationrosette formationimmunochemistry – neuron specific enolaseEM – secretory granules (catecholamine)Usual features of anaplasiahigh mitotic rate is unfavorableevidence of Schwann cell or ganglion differentiation favorableOther prognostic predictors are used by pathologists and oncologists

Neuorblastoma

*Neuropil **Homer-Wright Rosettes
*
**

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





رفعت المحاضرة من قبل: ahmed Bashar
المشاهدات: لقد قام 7 أعضاء و 108 زائراً بقراءة هذه المحاضرة








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