Peds path Flashcards Preview

Hydrocephalus 

Elevated unconjugated bilirubin during first week of life.

– Phase I – lasts 5 days in term infants and 7 days in preterm infants.

• Serum bilirubin level may reach 12-15 mg/dl

– Phase II – decline of serum bilirubin levels , lasts for 2 weeks.

– Clinical jaundice appearing in first 24 hours

– Total bilirubin > 15 mg/dl ( Hyperbilirubinemia)

– Conjugated bilirubin > 2 mg/dl

– Fetomaternal blood group incompatibility (Hemolytic Disease of the newborn)

– Crigler-Najjar syndrome type I & II

– Biliary atresia

– Neonatal hepatitis

• Erythroblastosis Fetalis

• Antibody induced hemolytic disease in the newborn that is caused by blood group incompatibility between mother and fetus.

• Most common antigens – Rh (D) and ABO blood group antigens

• Fetal RBCs reach maternal circulation in last trimester or during child birth

• Sensitization of mother to the foreign antigens – development of antibodies that can freely traverse the placenta to the fetus and cause hemolysis.

• Hemolysis leads to progressive anemia – intrauterine cardiac failure – Edema.

• Death in Utero – most extreme form of disease

• Hydrops Fetalis – most severe form in live born infants.

• Kernicturus – bilirubin encephalopathy

• Atautopsy– hepatosplenomegaly and bile stained organs

• Microscopically–

– Erythroblastic hyperplasia of the bone marrow

– Extramedullary hematopoiesis in the liver, spleen.

disorder of newborns in which very high levels of unconjugated bilirubin bind to, and injure the immature neurons of the CNS

• Characterized by bile staining of the brain, particularly of the basal ganglia and brain stem.

• Amniocentesis – high levels of bilirubin

• Human antiglobulin test (Coombs test) – Positive on fetal cord blood.

– Exchange transfusion – Phototherapy

Human anti D globulin within 72 hours of delivery

recessively inherited disease

• Characterized by complete absence of UDP-glucuronyltransferase activity.

• Unremitting unconjugated hyperbilirubinemia leading to bilirubin encephalopathy.

• Most patients die within first year of life

• Characterized by partial decrease in the activity of UDP-glucuronyltransferase activity.

• Hepatocytes have the capacity to synthesize this enzyme on treatment with Phenobarbital.

Biliary Atresia

• Complete obstruction of the lumen of the extrahepatic biliary tree within the first three months of life.

• 1:10,000 live births

aberrant intrauterine development of the extrahepatic biliary tree

– early onset neonatal cholestasis

– No jaundice free period after physiological jaundice

– Associated congenital anomalies (malrotation of abdominal viscera, congenital heart disease)

– Normally developed biliary tree is destroyed following birth (virus induced injury to biliary epithelium)

– Late onset neonatal cholestasis (4-8 weeks)

– Jaundice free interval

– No associated congenital anomalies

• Inflammation and fibrosing stricture of the hepatic and common bile ducts

• Periductal inflammation of intrahepatic bile ducts – progressive destruction of intrahepatic biliary tree

• Features of extrahepatic biliary obstruction – Marked bile ductular proliferation

– Portal tract edema and fibrosis

– Parenchymal cholestasis

• 75% survival if operated in first 60 days of life

• 20-30% survival if operated after 90 days of life

• 80% survival with transplantation.

• Giantcell transformation. (diffuse prominent)

• Ballooning

• Acidophilic degeneration

• cholestasis

75% of SIDS deaths have no associated risk factors.

Multifactorial

• 1. Vulnerable infant

• 2. Critical developmental period in

homeostatic control. (arousal and cardiorespiratory)

• 3. One or more exogenous stressors (hypercarbia/hypoxia/thermal stress)

• Multiple petechiae (80%) in Thymus,

visceral/parietal pleura and epicardium.

• Lungs: Congestion +/- pulmonary edema

• Hypoplasia of arcuate nucleus in the brain stem.

• Decrease in brain stem neuronal populations in some cases.

– Viral myocarditis

– Bronchopneumonia

– Congential aortic stenosis

– Anomalous origin of coronary artery from pulmonary artery

– Long QT syndrome (SCNSA + KCNQ1 mutations)(Sodium and potassium channel abnormalities.) 1%

– Fatty acid oxidation disorders (MCAD, LCHAD, SCHAD mutations) 5%

– Histiocytoid cardiomyopathy (MTCYβ mutations)

– Abnormal inflammatory responsiveness

(Partial deletion of C4a and C4b)

20 wks 

• Ascending from the vagina and cervix.

• Hematogenous dissemination from the placenta.

• Maternal to fetal transfusion at delivery(Hepatitis B and HIV)

• Direct contact at birth.

• From the environment post-partum.

• Accidental introduction at the time of

procedures - amniocentesis.

– Inhalation of infected amniotic fluid

– Passage through birth canal

– Chorioamnionitis

– Funisitis

– Pneumonia

– Sepsis

– Meningitis

• TORCHinfections.

• Congenital syphilis.

• Parvovirus B19.

• Human Immunodeficiency  Virus(HIV).

• Other infections(Listeria, parasitic  infections).

Syphilis

Listeria monocytogenes (late-onset sepsis)

Adenovirus (rare)

Varicella (rare)

Enterovirus

SLAVE

• Hematogenous through the placenta.

• Herpes simplex infection is an exception to this as most infections are due to:

– Direct contact at the time of delivery.

– Ascending infection.

 SGA infants.

 CNS changes:

 Hydrocephalus.

 Microcephaly.

 Periventricular calcification.

Pneumonitis

 Petechiae

Hepatomegaly with jaundice

 Splenomegaly

 Bony changes resembling osteomyelitis

 Chorioretinitis

• Ocular lesions:

– Cataracts.

– Corneal changes. 

– Microphthalmia.

• Cardiac lesions:

– Patent ductus arteriosus.

– Septal defects.

An autosomal recessive systemic disorder of exocrine glands characterized by

– Chronic pulmonary disease

– Deficient exocrine pancreatic function

– Other complications of inspissated mucus in a number of organs, including the small intestine, liver and the reproductive tract.

• Gene on chromosome 7 (7q31.2) encodes for a protein called the CF transmembrane conductance regulator (= CFTR).

• Phosphorylation of CFTR by protein kinase A using cAMP controls the chloride channel in the apical membranes of eccrine glands.

 In 70 % cases – 3 base pair deletion that results in loss of a phenylalanine residue at amino acid position 508(∆F508).

• The remaining patients exhibit multiple (more than 800) different mutations.

 Plugging of submucosal tracheobronchial mucous glands and ducts.

• Obstruction of bronchioles with mucus, associated with marked hyperplasia and hypertrophy of the mucus-secreting cells.

– Chronic bronchitis.

– Bronchiectasis.

– Lung abscesses.

• In this organ, there is the same mucous obstruction of ducts accompanied by:

– Secondary dilatation and cystic changes of the distal ducts and atrophy of secretory cells.

– Fibrosis.

– Destruction of parenchyma.

• These effects result in chronic pancreatitis in 85% of patients with CF.

• Discovered between age of 2-12 months.

• Child presents with symptoms of malabsorption secondary to pancreatic insufficiency:

– Foul-smelling steatorrhea.

– Malnutrition • Edema

• Hypoalbuminemia

– Failure to thrive.

– Nasal polyps

– Rectal prolapse

• Pilocarpine sweat test

– Normal sweat: chloride = 10 mEq/L.

– CF sweat, severe variant: chloride >60 mEq/L.

– CF sweat, mild variant: chloride = 40-60 mEq/L

• Genetic diagnosis

• Autosomal recessive disorder characterized by

– Progressive mental retardation caused by a deficiency of the hepatic enzyme phenylalanine hydroxylase.

• Point mutation in the PAH gene on 12q.

• Deficiency of Phenylalanine Hydroxylase (PAH) results in

– Hyperphenylalaninemia

– Formation of Phenylketones

• Hyperphenylalaninemia causes irreversible brain damage

– Complete interference with amino acid transport system in brain

– Inhibiting the synthesis of neurotransmitters

• Affected infant is normal at birth

• Mental retardation develops within few months

• Tend to have fair skin, blond hair and blue eyes.

• Mousy odour

An autosomal recessive deficiency of Galactose -1-phosphate uridyl transferase, the enzyme that catalyzes the conversion of galactose to glucose.

Infants fed milk rapidly develop hepatosplenomegaly, jaundice and hypoglycemia.

• Cataracts and Mental retardation.

extensive and uniform fat

accumulation in liver and marked bile ductal proliferation, cholestasis and fibrosis.

• Autosomal recessive disease characterized by chronic or intermittent jaundice and accompanied by a „black‟ liver.

• Defective transport of conjugated bilirubin from hepatocytes to canalicular lumen

• Associated defect in hepatic excretion of

coproporyphrins

accumulation of coarse, iron free, dark brown granules in hepatocytes and Kupffer cells.

pigment is located in lysosomes and it appears to be composed of polymers of epinephrine metabolites, not bilirubin pigment

• Familial conjugated Hyperbilirubinemia

defect in the excretion of conjugated bilirubin into the biliary canaliculi with the bilirubin being absorbed into the blood.

jaundice, attacks of intermittent epigastric discomfort and occasionally abdominal pain, and fever.

low-grade pigment deposition, dissociation of liver cells, occasional necrotic foci, and fibrin precipitation.

Chromosomal and genetic syndromes.

• Congenital immunodeficiency syndromes.

• >200 genetic syndromes are associated with an increased susceptibility to cancer.

– Down syndrome (Trisomy 21) - Acute leukemia.

– Deletion 13q - Retinoblastoma.

– Wiskott Aldrich syndrome - Lymphoma.

– Agammaglobulinemia - Acute lymphoblastic leukemia (= ALL).

• Lymphoma/Leukemia

• Medulloblastoma(CNSneoplasm)

• Neuroblastoma

• Rhabdomyosarcoma (Sarcoma) – Embryonal

– Alveolar

• Wilmstumor

• Bonetumors

– Ewing‟s sarcoma/PNET – Small cell osteosarcoma

poorly differentiated tumor arising from primitive neural crest cells

• normally give rise to the adrenal medulla and sympathetic ganglia.

• Second most common solid malignant tumor in children.

• Before age of 5

• Germline mutation in ALK gene – familial predisposition to neuroblastoma.

• < 2 years - Mass in abdomen, mediastinum, or other sites, fever, weight loss

• Older children – Signs of metastatic disease – bone pain, respiratory or gastrointestinal symptoms.

• Blueberry muffin baby – disseminated neuroblastoma – multiple cutaneous metastasis with deep blue discoloration of the skin

• 40 % arise in adrenal medulla.

• Remainder arise anywhere along the sympathetic chain

– paravertebral region of the

abdomen (25%)

– posterior mediastinum (15%). .

• Size varies from minute nodules to tumors weighing >1 kg in weight

• With increasing size, areas of: – Necrosis.

– Hemorrhage.

– Cyst formation.

• Gross calcification in 40-50%.

the tumor cells are concentrically arranged about a central space filled with neuropil. No lumen.

Found in neuroblastomas

Small, round, blue cell tumor with sheets of small, primitive-appearing cells with dark nuclei, scant cytoplasm, and poorly defined cell borders

a faintly eosinophilic fibrillary material that corresponds to neuritic processes of the primitive neuroblasts.

• Bone.

• Lymph nodes.

• Liver.

• Bone marrow.

• Subcutaneous tissue.

• Elevated blood levels of catecholamines

• Elevated urine levels of catecholamine metabolites

– Vanillylmandelic acid (VMA)

– Homovanillic acid (HVA)

• X –ray abdomen – calcification in tumor can be picked up

• Age of the patient

– < 1 year excellent prognosis – 1-5 years – intermediate

– > 5 years – poor prognosis

• Deletion distal 1p and gain of distal 17q - poor prognosis

• N-myc amplification – extrachromosomal double minute chromatin bodies or homogenously staining regions (HSR) on other chromosomes – poor prognosis

• Telomerase overexpression - poor prognosis

• Tyrosine kinase receptor A (Trk-A) – increased expression indicates good prognosis

malignant embryonal neoplasm derived from nephrogenic blastemal cells

• Most common primary renal tumor of childhood

• Peak incidence – 2-5 years of age

• 10% cases associated with

– WAGR syndrome – deletion of WT1 gene

– Denys-Drash syndrome –dominant, negative inactivating mutation of WT1 gene

– Beckwith-Wiedemann syndrome – mutation of putative WT2 gene – overexpression of IGF2 protein

– Mutations of β-catenin gene (10% of sporadic

WT)

• Macroglossia

• Omphalocele

• Gigantism

• Adrenal cortical cytomegaly

• Visceromegaly

• Islet cell hypertrophy

• Renal medullary dysplasia

• Gonadal dysgenesis

• Renal abnormalities

• WT-1 gene mutation

• 90% chance of Wilms‟ tumor

• Aniridia

• Genitalabnormalities • Mentalretardation

• WT-1(11p13)

• 33%ChanceofWilms

Seenintherenal parenchyma adjacent to approximately 40% of unilateral tumors and nearly 100% of bilateral tumors

Triphasic pattern: Embryonal tumor – recapitulates the normal development of the kidney.

• Blastema – sheets of small round blue cells

• Stroma – fibrocytic or myxoid in nature. May have striated muscle.

• Epithelium - abortive tubules and glomeruli

• Cells with hyperchromatic nuclei, >3 times larger than those in adjacent cells of similar type.

• Enlarged, bizarre, multipolar mitoses.

Correlates with acquired TP53 mutations

• Usually comes to clinical attention due to the detection of an abdominal mass by a parent when bathing or clothing a child.

• Other common presentations:

– Abdominal pain.

– Hematuria.

– Hypertension.

– Acute abdominal crisis secondary to traumatic rupture.

• “3L‟s”:

– Regional lymph nodes.

– Lungs.

– Liver.

• Metastatic sites other than these three sites are unusual and should suggest other diagnoses

Retinoblastoma 

• 40% congenital - RB1 gene - multiple tumors – bilateral

• 60% sporadic-unifocal, unilateral.

Within first 2 years 

– White pupil (= leukocoria).

– Squint (= strabismus).

– Poor vision.

– Spontaneous hyphema (= hemorrhage into the anterior portion of the eye).

– Red, painful eye.

Microscopy 

REtinoblastoma 

• Extension into optic nerve and/or subarachnoid space (CSF) with intracranial spread.

• Invasion of blood vessels, especially in the highly vascular choroid, with subsequent hematogeneous metastases.

• Frequent complication is secondary glaucoma

• Always fatal if untreated.

• 90% survival with early diagnosis and modern therapy.

– Osteogenic sarcoma.

– Ewing sarcoma/PNET.

– Pinealoblastoma.

sacrococcygeal region

 75%-composedof histologically mature tissue elements

• 12%malignant

• 13%immature

– Proportion of immature elements important.

≤ 4 months - benign

At 1year 50% malignant

At 5years 100% malignant