PEDIATRICS2 SE4 HIGH-YIELD REVIEWER: MODULE 4 (Neonatology, Nephrology, Genetics and Metabolic Diseases)

I. BIRTH INJURIES
SOFT TISSUE INJURIES
Injury Features Management
ERYTHEMA & ABRASIONS  Cause: labor dystocia Resolves spontaneously
PETECHIAE  Cause: sudden increase in intrathoracic and venous pressure Fades in 2-3 days
 Found only in NSD (breech deliveries)

ECCHYMOSES  Traumatic or breech deliveries Resolves spontaneously within 1 week

 Premature infants (thin skin)
 Complication: hyperbilirubinemia (extravascular accumulation of blood)
LACERATIONS  Cause: scalpel injury during caesarian section  Superficial wounds: adhesive strips
 Buttocks, scalp, thighs  Deeper wounds: sutures
SUBCUTANEOUS FAT NECROSIS  Well-circumscribed and indurated lesions Regress within several months
 Cause: ischemic injury to SQ fat
 Appear 6-10 days of age
 Skin red or purple WITHOUT local tenderness or warmth

HEAD INJURIES
Injury Features Management
CAPUT SUCCEDANEUM  Vaguely demarcated area of edema found in presenting part of the scalp Resolves early (48-72 hours)
 ASSOCIATED WITH: molding & overriding parietal bones
 EXTERNAL to periosteum
 CROSSES suture lines
CEPHAL HEMATOMA  Subperiosteal collection of blood Resolves late (2-8 weeks)
 ASSOCIATED WITH: rupture of capillaries Aspiration is CONTRAINDICATED
 NO EXTENSION across suture lines
 PARIETAL BONES usually involved
 Most common complication: Hyperbilirubinemia
SUBGALEAL HEMORRHAGE  LEAST COMMON BUT WORST  Volume replacement and blood products
 Collection of blood beneath the aponeurosis  Resolves over 2-3 weeks
 Firm, fluctuant mass increasing in size after birth
 Cause: rupture of emissary vein
 Severe anemia & hypovolemic shock
SKULL FRACTURES  Uncommon Linear fracture – NO TREATMENT
o Skull bones are less mineralized (compressible) Depressed fracture with neurologic signs –
o Bones separated by sutures (allows molding) SURGERY
 ASSOCIATED WITH: forceps delivery
 Most common: linear fractures
 Rare: depressed fractures
 Diagnosis: x-ray
FACIAL NERVE PALSY  Peripheral paralysis Resolves spontaneously
o Compression of peripheral part of the nerve
o Flaccid
o Entire ½ of face
o Ipsilateral side
 Central paralysis
o Contralateral CNS injury
o Spastic
o Lower ½ or 2/3 of face
o Contralateral
SUBCONJUNCTIVIAL HEMORRHAGE  VERY COMMON Reassure parents
 Bright red patches on bulbar conjunctiva Blood is absorbed within 1-2 weeks

INTRACRANIAL HEMORRHAGE
Features Diagnosis Complications
PERIVENTRICULAR-  MOST SERIOUS BRAIN LESION IN THE NEONATAL PERIOD Cranial ultrasound  Periventricular
INTERVENTRICULAR  Bleeding site: SUBEPENDYMAL GERMINAL MATRIX leukomalacia
HEMORRHAGE  Incidence increased with decrease in birthweight & AOG  Post-hemorrhagic
o Because germinal layer disappear during term hydrocephalus
 Predisposing factors: hypoxic-ischemic injury, pneumothorax,
hypovolemia, hypotension
 Manifestations: apnea, lethargy, poor muscle tone, convulsions, bulging
fontanel
SUBDURAL HEMORRHAGE  Very rare CT scan or MRI
 Seen in full term infants
 Cause: precipitous delivery (forceps)
 Associated with tears in the tentorium cerebella or falx cerebri
 COMPLICATIONS OF IVH
Complication Features Diagnosis Management
PERIVENTRICULAR  PRINCIPAL ISCHEMIC BRAIN LESION IN PREMATURE INFANTS  Ultrasound – cystic
LEUKOMALACIA  Necrosis of periventricular white matter changes
 Sequelae: cerebral palsy, visual and cognitive defects  MRI – more sensitive
POST-HEMORRHAGIC  MAJOR COMPLICATION Ultrasound – procedure of Shunt insertion
HYDROCEPHALUS  Progressive ventricular dilatation choice
 Manifestations: enlarging head circumference, apnea, lethargy, bulging fontanel, widely split sutures

NECK AND SHOULDER INJURIES

Injury Features Diagnosis Management
CLAVICLE FRACTURE  MOST FREQUENTLY FRACTURED X-ray (confirmatory)  Directed at minimizing pain
 Difficult delivery of the shoulders  Callus formation at 7-10 days
 Greenstick type – most common
 Asymptomatic
 Decreased movement of arm on the affected side
 Crepitus on palpation
 Irregularities along clavicle
BRACHIAL PALSY  Paralysis of muscles of the extremities For Erb-Duchenne: partial
 Mechanical trauma to the brachial plexus immobilization and proper positioning
 Cause: excessive traction on neck/shoulder, shoulder dystocia, after-coming head
in breech delivery
 2 main forms
o ERB-DUCHENNE (Upper Arm)
 MOST COMMON
 5th-6th cervical nerves
 ABSENT MORO on affected side
 Suspected when arms are extended
o KLUMPKE’S (Lower Arm)
 8th cervical to 1st thoracic
 Extremely rare
 Paralyzed hand
 NO GRASP REFLEX
 Horner’s syndrome
PHRENIC NERVE PALSY  Avulsion of 3rd, 4th, and 5th cervical roots X-ray: elevation of affected Spontaneous and complete recovery
 Apparent respiratory distress hemidiaphragm
 Affected side cannot contract Real-time UTZ

INTRAABDOMINAL ORGAN INJURIES

 Uncommon
 Suspect: pallor, irritability, abdominal distention WITHOUT evidence of external blood loss
 LIVER – most frequently injured
 Spleen rupture, adrenal hemorrhage, kidney injuries - rare

II. PERINATAL ASPHYXIA

 Hypoxia – partial or complete lack of oxygen in one or more tissues of the body
 Ischemia – reduction or cessation of blood flow to an organ
 Asphyxia – disruption of placental or pulmonary gas exchange
 CRITERIA FOR DIAGNOSIS – evidence of fetal distress plus ALL of the ff:
o Profound acidemia (pH < 7)
o Persistent APGAR scores of 0-3 for > 5 minutes
o Evidence of neurologic sequelae
o Multisystem organ failure
**if only 2 are present: BIRTH DEPRESSION
 FACTORS THAT INCREASE THE RISK
o Impairment of maternal oxygenation
o Dec. blood flow from mother to placenta
o Dec. blood flow from placenta to fetus
o Impaired gas exchange across the placenta
o Inc. fetal oxygen requirement
 HYPOXIC-ISCHEMIC ENCEPHALOPATHY
o Abnormal neurobehavioral state in which the predominant pathogenic mechanism is impaired cerebral blood flow
o 20-30% mortality; 30-50% of survivors develop permanent neurodevelopmental abnormalities

Multi-organ Systemic Effects of Asphyxia

System Effects
CNS  HIE
 Infarction
 Intracranial hemorrhage
 Seizures
 Cerebral edema
 Hypotonia/Hypertonia
CV  MI
 Poor contractility
 Cardiac stunning
  Tricuspid insufficiency
 Hypotension
 Cardiogenic shock
Pulmonary  Pulmonary HPN
 Pulmonary hemorrhage
 RDS
 Respiratory depression
 Persistent pulmonary HPN
Renal  Acute tubular or cortical necrosis
 Renal insufficiency or failure
Adrenal  Adrenal hemorrhage
GI  Perforation
 Ulceration w/ hemorrhage
 Necrosis
 GI hemorrhage
 NEC
 Liver failure
Metabolic  SIADH
 Hypo(Na, Ca)/Hyperkalemia
 Hypo/hyperglycemia
 Myoglobinuria
Integument  SQ fat necrosis
Hematologic  DIC
 Abnormal WBC count
 Thrombocytopenia
Sarnat’s Staging

Signs STAGE 1 STAGE 2 STAGE 3

LEVEL OF CONSCIOUSNESS Hyper-alert/Irritable Lethargic Stuporous/Comatose
MUSCLE TONE Normal Hypotonic Flaccid
DTRs Hyperactive Hyperactive Absent
POSTURE Normal Flexion Decerebrate
MYOCLONUS Present Present Absent
COMPLEX REFLEXES Normal Suppressed Absent
PUPILS Mydriasis Miosis Unequal
SEIZURES None Common Decerebrate
EEG Normal Low voltage Isoelectric/Burst suppression
DURATION < 24 hours 2-14 days Days to weeks
OUTCOME Good (100% normal) Variable (80% normal) Death in 50%; Severe neurologic sequelae

 Diagnostic procedures
o DIFFUSION-WEIGHTED MRI – preferred imaging modality in neonates & term infants
o ULTRASONOGRAPHY – preferred imaging modality in preterm infants
 Treatment
o THERAPEUTIC HYPOTHERMIA
 Start within first 6 hours after birth
 Core temperature down to 33-34OC
 Neuroprotective effects:
 Decreases rate of apoptosis
 Suppresses neurotoxic mediators
 Downregulates secondary mediators of injury
o SEIZURE CONTROL
 Phenobarbital – initial DOC
 Phenytoin – 2nd drug for refractory seizures
 Lorazepam
o SUPPORTIVE CARE
 Prevent hyperthermia
 Ventilation
 Hypercapnea – cerebral vasodilatation
 Hypocapnea – decreased CBF
 Oxygenation – hyperoxia may decrease CBF or exacerbate free radical damage
 Prevent hypoglycemia – may potentiate excitotoxic amino acids
 Prevent hypocalcemia – can compromise cardiac contractility
 Prevent SIADH
 Judicious fluid management – fluid restriction minimizes cerebral edema
o SPECIFIC MANAGEMENT
 Cardiac – dopamine
 Pulmonary – assisted ventilation
 Renal – furosemide
 Hematologic – fresh frozen plasma, cryoprecipitate
 Prognosis – dependent on
o Severity of encephalopathy
o Onset of seizures
o EEG pattern
** Poor prognosis associated with STAGE 3 (onset of seizures in first 12 hours, burst suppression EEG pattern)
o PREDICTORS OF DEATH OR SEVERE NEUROLOGIC DEFICITS
 Low APGAR score at 20 minutes
  Absence of spontaneous respirations at 20 minutes
 Persistence of abnormal neurologic signs at 2 weeks of age

III. CONGENITAL ANOMALIES

IV. RESPIRATORY DISTRESS IN THE NEWBORN

 FIVE COMMON SIGNS OF RESPIRATORY DISTRESS

o Retractions
o Tachypnea (> 60 breaths per minute)
o Nasal flaring
o Grunting – to increase functional residual capacity
o Cyanosis

Disease Features Diagnosis Management

HYALINE  Preterm infants Chest x-ray – CONFIRMATORY PREVENTIVE
MEMBRANE  Cause: primary absence or deficiency of pulmonary surfactant  Reticulogranular, ground-glass  Prevent prematurity
DISEASE o Phospholipids (80%) appearance  Betamethasone
o Neutral lipids (10%)  Air bronchogram o 48 hrs before delivery
o Surfactant specific proteins (10%)  “White out lungs” – in SEVERE RDS o 24-34 weeks AOG
 SP-A : for tubulin myelin formation SPECIFIC
 SP-B: lack/deficiency leads to loss of LAMELLAR BODIES (poor prognosis)  Exogenous surfactant
 Mature levels of surfactant present after 35 weeks o Prophylactic – given
 Signs & symptoms immediately after birth
o Difficulty initiating normal respiration o Rescue – given during the
o Expiratory grunting first 24 hours of life after
o Sternal & intercostal retractions diagnosis
o Nasal flaring, cyanosis, tachypnea
TRANSIENT  Due to delayed resorption of fetal lung fluid X-ray Resolves within 6-8 hrs; may last
TACHYPNEA  Seen in CS WITHOUT LABOR  Central perihilar streaking for 72 hours
OF THE o Vaginal route can squeeze out excess fluid  Hyperaeration
NEWBORN  Major presenting symptom: persistently high RR  Fluid in minor fissure
 Self-limited

NEONATAL  Route: ascending infection, aspiration during passage X-ray Penicillin/ampicillin and
PNEUMONIA  Predisposing factor: prolonged rupture of membranes (PROM)  Confluent opacified areas – usually basal aminoglycosides – DOC
 Pathogens: GROUP B STREP (major), E. COLI (most common), Listeria spp. o If upper airways – aspiration  Staphylococcus –
 Signs & symptoms pneumonia Oxacillin/Vancomycin
o Signs of respiratory distress  Diffusely granular appearance with air  Chlamydia – Erythromycin
o Non-specific signs bronchogram  Fungi – Amphotericin B
 Apneic spells Duration of tx:
 Thermal instability  10 days – culture negative
 Jaundice – early onset (due to E. coli)  14 days – culture positive
MECONIUM  Presence of meconium in the tracheobronchial airways Hx & PE Surfactant
ASPIRATION  Term or post-term infants  Risk factors Inhaled NO
SYNDROME  Cause: Acute or chronic hypoxia or vagal stimulation result in passage of  Meconium-stained amniotic fluid Extracorporeal membrane
meconium in utero  Signs of respiratory distress oxygenation
 Induces hypoxia via 3 pulmonary effects  Barrel-chest appearance
o Airway obstruction Chest x-ray
o Surfactant dysfunction  Coarse, irregular patchy infiltrates
o Chemical pneumonitis  Coarse streaking of both lung fields
 Many infants have persistent pulmonary HPN of the newborn  Increased AP diameter
 Prognosis  Flattening of diaphragm
o Mortality higher than non-stained infants  Pneumomediastnum or pneumothorax
o Depends on extent of CNS injury
PERSISTENT  Resulting from elevated pulmonary vascular resistance & altered pulmonary Hx Adequate resuscitation at birth
PULMONARY vasoreactivity Differential oxygenation Supportive management
HPN OF THE o R -> L extrapulmonary shunting of blood across foramen ovale & ductus  PaO2 in pre-ductal blood > post-ductal Mechanical ventilation
NEWBORN arteriosus blood Surfactant
 Cause: Hyperoxia-hyperventilation test Vasopressors
o At birth: decrease in PVR due to lung inflammation  MARKED IMPROVEMENT is noted PULMONARY VASODILATORS
o After 24 hrs: PAP has fallen to about 50% of systemic arterial pressure  Differentiates PPHN from cyanotic  Nitric oxide
o Normal: ductus arteriosus remains anatomically patent congenital heart disease  Inhaled prostacyclin
 Most common manifestation: LABILE HYPOXIA o NO IMPROVEMENT in CHD  Sildenafil
 Risk factors Chest x-ray  Mgso4
o Hypoxia  Clear lung fields Extracorporeal membrane
o Acidosis  Decreased vascular markings oxygenation
o Anemia/polycythemia  Heart size is normal or slightly enlarged
o Maternal diabetes 2D-Echo – GOLD STANDARD
EXTRAPULMONARY EXTRAVASATION OF AIR

Disease Features Diagnosis Management

PNEUMOTHORAX  Air from ruptured alveolus dissects up the (+) transillumination of chest – 100% O2/Nitrogen wash-out
vascular sheath into the mediastinum and into the bedside test technique
pleural space Chest x-ray – CONFIRMATORY Thoracentesis – 4th ICS AAL
 Manifestations: cyanosis, retractions, decreased  Hyperluscent area
IPSILATERAL breath sounds, cardiac impulse  Contralateral shift of mediastinal
shifted CONTRALATERALLY, pallor, distended structures
abdomen
PNEUMOMEDIASTINUM  Pathognomonic: SUBCUTANEOUS Chest x-ray Close observation
EMPHYSEMA  Air in the anterior mediastinum
(NO SHIFTING)
PULMONARY INTERSTITIAL  Rupture of air from alveoli or small airways into Chest x-ray
EMPHYSEMA the perivascular tissues of the lung  Bubbly appearance due to
 RADIOGRAPHIC DIAGNOSIS cystic lucencies
 Preterm babies who required prolonged assisted
ventilation with high pressures
 Signals BAROTRAUMAS

V. JAUNDICE, ANEMIA, BLEEDING

 Jaundice – yellowish discoloration of the skin, sclera, and other mucous membranes of the body
 Hyperbilirubinemia – total serum bilirubin level (TSB) exceeds more than 12 mg/dL
 Unconjugated Hyperbilirubinemia – elevation of the indirect-reacting or unconjugated bilirubin concentration of 2mg/dL (34 umol/L) or greater
 Conjugated Hyperbilirubinemia – elevation in the direct-reacting fraction of greater than 1.5mg/dL (26 umol/L) and more than 10%TSB
 Physiologic Mechanisms of Neonatal Jaundice:
o Increased bilirubin load on the liver cell
 Increased bilirubin production
 Increased RBC volume
 Decreased RBC volume
 Increased enterohepatic circulation of bilirubin
o Decreased clearance of bilirubin from plasma
 Decreased hepatic uptake
 Decreased ligandin
 Decreased bilirubin conjugation
 Decreased UDGPT activity
 Defective bilirubin excretion
 Bilirubin Metabolism:
o RBC – major source of bilirubin
o Conjugation – phase 2 metabolism; smooth endoplasmic reticulum of hepatocytes; adding glucoronic acid using glucoronyl transferase
 Clinical Manifestations:
o Jaundice follows a cephalocaudal progression
o Jaundice usually begins on the:
 Face – TSB 5mg/dL
 Mid-abdomen – TSB 15mg/dL
 Feet –TSB 20mg/dL
o Present few hours after birth or appear during the neonatal period
o Unconjugated Hyperbilirubinemia – bright yellow or orange
o Conjugated/ Direct Hyperbilirubinemia – greenish or muddy yellow

 Non-Pathologic Unconjugated Hyperbilirubinemia

o Physiologic Jaundice
 Time of appearance: 2nd and 3rd day of life
 Pattern: peak between 2nd and 4th day of life at 5-6mg/dL
 Duration: disappears between 10 th and 14th day of life
 Bilirubin levels:
 Rise: <5mg/dL per 24 hours
 Maximum TB: <12mg/dL (Full-term); <15mg/dL (Pre-term)
 B2: <2mg/dL or 20% TB
o Jaundice Associated with Breastfeeding
 “Breastfeeding failure jaundice”
 Caloric deprivation or starvation
 Increased bilirubin during the first week of life
 Resolves with increased breastfeeding and amount of milk intake
 Associated with poor feeding practices and not in any change in milk composition
 Results in exaggerated enterohepatic circulation of bilirubin through starvation
o Breastmilk Jaundice
 Occurs after the first 3-5 days of life and may last into the 3rd week of life or beyond
 Pregnanediol – competitive inhibitor of UGT in vitro
 B-glucoronidase – enzyme that deconjugates bilirubin; enhances enterohepatic reabsorption of bilirubin which increases
hepatic bilirubin load
 Non-esterified fatty acids – inhibitors of hepatic UGT causing retention of unconjugated bilirubin
 Pathologic Jaundice
o Onset: within the 1st 24 hours of life
o TSB rises >5mg/dL/24 hours
o TSB > 12mg/dL (Full-term); 10-14mg/dL (Pre-term)
o Persistence of jaundice after the 2nd week of life
o Conjugated bilirubin greater than 20%
 Prolonged Indirect Hyperbilirubinemia: increased production of bilirubin or bilirubin load on the liver
o Hemolytic Disease of the Newborn: mostly IgG

RH Incompatibilty ABO Incompatibilty

 Mother: Rh (-)  Mother: blood type O
 Baby: Rh (+)  Baby: blood type A or B or AB
 Maternal production of antibodies after transplacental  Maternal transfer of blood group antibodies against
exposure to Rh (+) blood then transfer the antibodies fetal blood type resulting in hemolysis of fetal RBCs
into fetal circulation  Mother with blood type O has antibodies of mostly IgG
 Mother is Rh (-) and baby is Rh (+) class and reacts with A and B antigens
 Gilbert Syndrome – mild fluctuating unconjugated hyperbilirubinemia
 Crigler-Najjar Syndrome – familial jaundice

o Disorders of Enterohepatic Circulation

 Hirschprung’s Disease
 Meconium Ileus
 Prolonged NPO
 Sequelae of Unconjugated Hyperbilirubinemia
o Transient Encephalopathy
 CN8 injury
 Reversible
o Kernicterus
 Acute bilirubin encephalopathy
 Yellow staining of the brain, mostly the basal ganglia, CN nuclei and hippocampus
 1st phase: hypotonia, lethargy, poor feeding, poor suck
 2nd phase: hypertonia, opisthotonus, high-pitch cry, seizure
 3rd phase: hypotonia, long-term neurologic injury, extrapyramidal disturbance, deafness
 Management
o Phototherapy
 Indications: Pathologic jaundice
 Mechanisms: Photoisomerization and Structural Change
o Exchange Transfusion
o Pharmacotherapy
 Metalloporphyrins
 IV Immunoglobulin
 Phenobarbital: anti-convulsant
 Miscellaneous: frequent milk intake and oral administration of non-absorbable substances that bind bilirubin (activated charcoal,
agar)
 Hematologic Disorders in the Neonate
o Anemia: reduction in hemoglobin concentration, hematocrit or number of RBCs per cubic millimeter; lower limit of the normal range is 2 SD
below the mean for age and sex for the normal population
o Physiologic Anemia of Infancy
 Normal newborns have HIGHER hemoglobin and hematocrit levels and LARGER red blood cells
 Occurs during the first 6-8 weeks of life
 Hemoglobin drops to 9-11g/dL
 “Physiologic adaptation to extrauterine life”
 Requires no therapy
 Diet must have adequate folic acid and iron
o Anemia During the Neonatal Period
 Anemia of Prematurity
 Hemoglobin levels of 7g/dL at 4-8 weeks
 Reduced bone marrow erythropoietic activity
 Low EPO levels
 Hemorrhage
 Post-natal blood loss
 Intra-natal blood loss
 Pre-natal blood loss
 Feto-maternal blood loss
 Fetal-fetal
 Post-natal bleeding
 Failure of Red Cell Production
 Congenital
 Acquired: Viral diseases

 Acute Blood Loss

 Acute distress
 Low venous pressure
 Hemoglobin may be normal initially then drops quickly within 24 hours
 RBC: normochromic, macrocytic
 Normal serum iron
 Prompt treatment of anemia necessary to prevent death: NSS PRBC, iron
 Chronic Blood Loss
 Marked pallor disproportionate to the evidence of distress, CHF, hepatomegaly
 Normal or elevated venous pressure
 Low hemoglobin at birth
 RBC: hypochromic, microcytic, anisopoikilocytosis
 Low serum iron at birth
 Treatment: iron therapy
 Hemolysis
 Congenital Erythrocyte Defects
  Acquired Erythrocyte Defects
o Natural History of Hemolytic Disorders in the Newborn
 Half-life of IgG molecules: 28 days so hemolysis should resolve after the first 3 or 4 months
 Anemia can occur due to:
 Ongoing destruction of native cells by anti-blood group IgG
 Hypersplenism
 Replacement by transfused red cells
 Shortened RBCs
 Associated thrombocytopenia and bleeding may also complicate the hemolytic disease
o Laboratory Diagnosis
 CBC with platelet count
 Reticulocyte count
 RBC indices
 Peripheral blood smear
o Polycythemia of the Newborn: central hematocrit of 65% or higher
 Placental transfusion
 Placental insufficiency
 Endocrine and metabolic disorders
 Miscellaneous
 Clinical features: tachypnea and cyanosis, hypoglycemia, hypocalcemia, jitteriness, seizures, necrotizing enterocolitis
 Management: reduction of hematocrit by partial exchange transfusion
o Acquired Hemostatic Disorders
 Vitamin K Deficiency Bleeding (VKDB)
 Hemorrhagic disease of the newborn
 At birth, factors 2, 7, 9, 10 are physiologically LOW
 Lowest point is on day 3 of life
 Due to low body stores of vitamin K plus subsequent poor intake of vitamin K
 Minimum requirement: 25ug of vitamin K
 Conditions associated with deficiency of vitamin K dependent clotting factors: prematurity, diet, altered bacterial
colonization, hepatocellular disease, drugs
 Clinical manifestations: bleeding on days 2-4; sites of bleeding may be GIT, umbilicus, internal organs
 Laboratory findings:
RBC morphology Normal
aPTT Prolonged
PT Prolonged
Fibrin split products Normal
Platelets Normal
Clotting factors Decreased 2, 7, 9, 10
 Treatment: Vitamin K (prophylactic doses of 0.5-1mg vitamin K1 IM) and FFP transfusion

VI. HUMAN GENETICS AND METABOLISM

 Patterns of Inheritance
o Single Gene Disorders
 Mendelian
 Mitochondrial
o Multifactorial
o Other Atypical Patterns
 Autosomal Dominant
o Phenotype appears in every generation

o Any child of affected parents has 50% risk

o Male and female equally likely to transmit phenotype to children of either sex
o Examples: Neurofibromatosis and Achondroplasia
 Autosomal Recessive
o Majority of the cases
o Parents are carriers, phenotype typically seen only in siblings
o 1:4 (25% risk)
o Males and femailes are equally affected
o Examples: MSUD, PKU, Albinism, Mucopolysaccharidosis
 X-Linked Recessive
o Trait much higher in males
o An affected male transmit it to all his daughters
o Heterozygous females are usually unaffected but some may express the condition (abnormal X is activated)
o Examples: DMD, Hemophilia A, G6PD
 X-Linked Dominant
o Mom: affected (50% affected, 50% unaffected)
o Dad: affected (0% affected son, 100% affected daughter)
 Dysmorphology
o “Dys” – disordered, abnormal, painful
o “Morph” – shape or form
o Dysmorphic – children whose physical feautures, particularly facial, are not usually found in a child of the same age or ethnic background

o Clinical evaluation – History

 3 generations of pedigree
 Advanced maternal and paternal age
 History of abortion/ stillbirths
 Pregnancy history
 Neonatal history
 o Clinical evaluation – Examination
 Observation – Gestalt Diagnosis, variants of body structure, recognize major and minor malformations
 Malformation
 Morphological defect of an organ or a larger region of the body resulting from an intrinsically abnormal process
 Major – CHO, meningomyelocoele
 Minor – ear tags, epicanthal folds, simian crease
 Deformation
 Secondary defect caused by mechanical pressure or compression
 Presence of twins, uterine abnormalities, oligohydramnios, talipes equinovarus
 Disruption
 Morphological defects caused by an external factor which results to destruction of tissues
 Amniotic bands, viral infections, Rubella
 Amnion rupture sequence

 Dysplasia
 Abnormal organization of cells into the tissues and the morphologic results
 Varicosities, AV malformations, hemangioma, nevi, skeletal dysplasia
 Weber syndrome (macrodactyly)
o Patterns of Anomalies
 Syndrome
 Group of characteristic that occur together that are most commonly thought to be due to a single cause
 Chromosomal abnormalities
 Down Syndrome (Trisomy 21)
 Upslanted palpebral fissure, flat nasal bridge, low set ears, transverse simian crease
 Due to non-disjunction in meiosis I or II (abnormal separation of chromoses)
 Maternal age – risk factor
 Full trisomy – most common type
 Edward’s Syndrome (Trisomy 18)
 Triangular facies, cleft lip palate, rocker-bottom feet, overlapping of fingers
 Single Gene Disorder
 Crouton Syndrome (FGFR2)
 Premature craniosynostosis, abnormal head shape, U-shaped cleft palate, shallow
orbit, parrot-like
 Environmental Teratogens
 Fetal Alcohol Syndrome
 Small eye openings, smooth philtrum, thin upper lip
 Sequence
 Single problem in the morphogenesis that leads to a cascade of subsequent defects
 Initial insult
 Holoprosencephaly Sequence (Trisomy 13)
 3rd week of development
 Abnormal precordial mesoderm, hypotenism, cyclops, flat nasal bridge
 Pierre Robin Sequence
 9th-12th week of development
 Mandibular hypoplasia, tongue fused back, no fusion of palatal bones, microsognathia, U-shaped
cleft palate
 Oligohydramnios Sequence
 Renal agenesis 1st event
 Association
 Non-random occurrence in 2 or more individual of multiple anomalies not known to represent a syndrome or
sequence
 No gene abnormality found
 No cause or etiology
 VACTERL – Vertebral, Anal, Cardiac, Tracheoesophageal Fistula, Renal/ Radial, Limb
o Examination: Chromosomal analysis – 2 major dysmorphic features
 Anthropometry
 Body symmetry
 Examination checklist
 Psychomotor delay, speech delay, mental retardation
 Presence of hearing loss and abnormalities of the eye
 Diagnostic handles
 Apert Syndrome – Mitten hands
 Cornella de Lange Syndrome – Synophrys
 Turner/ Noonan Syndrome – Webbing of the neck
 Trisomy 13/18 – Holoprosencephaly
 Trisomy 13 – Cleft lip palate and omphalocoele
 X-ray – Osteogenesis imperfecta (multiple fractures, blue eyes)
 FISH – Prader Will Syndrome (obesity syndrome; deletion of SNRPN probe on chromosome 15)
 DNA analysis/ Mutation testing – Orofaciodigital Syndrome (tongue nodules, digital symmetry, brachydactyly)
 Photogramimetry
 MRI
 Metabolic testing
 Inborn Errors of Metabolism
o Disorders that arise from a block in the metabolic pathway, which can be due to either enzyme deficiency or abnormality of t ransport process
o Enzyme facilitates reaction
o Enzyme block
o Clinical clues: 5 most common presentations
 Acute Encephalopathy
 Due to small molecule disease
 Case: 3 day history of poor feeding and vomiting, increasing lethargy, seizures, comatose
  Maple Syrup Urine Disease (MSUD)
 MOST common IEM in the Philippines
 Deficiency in the activity of branched chain alpha keto acid dehydrogenase complex
 Results in accumulation of branched chain amino acids
 Normal-looking
 (++) ketones, low to normal glucose, (-) hyperammonemia

 Methylmalonic Aciduria (MMA)

 Rare
 Poor feeding, vomiting, lethargy, tachypnea, hypotonia, coma, MMA accumulation, normal-looking
 (+) ketones, normal range glucose, (+) hyperammonemia
 Urea Cycle Defects
 Urea is the major means of disposal of nitrogen waste
 Occurs in males, accumulation of ammonia: cerebral edema
 (++) hyperammonemia, normal ketones, normal glucose
 Chronic Encephalopathy
 Case: Intractable seizures and spasticity
 Phenylketonuria (PKU)
 Condition wherein the body cannot properly utilize phenylalanine because of deficiency in the
enzyme that metabolize this amino acid (phenylalanine hydroxylase)
 Tyrosine deficiency
 Mental retardation – most common clinical manifestation
 Spastic cerebral palsy, seizures, short but with normal weight, fair skin and light colored hair,
eczematoid rash, intractable itching, behavioral
 Diffuse Liver Disease
 Case: Refusal to feeding, vomiting, jaundice, lethargy, hepatomegaly, ascites, coagulopathy
 Galactosemia
 Deficiency of galactokinase, galactose 6-PO4 uridyl transferase or epimerase that will metabolize
galactose as source of energy
 Failure to thrive, hepatomegaly, prolonged neonatal jaundice, liver failure, cataract, sepsis, mental
retardation, reproductive problems
 Myopathy
 Renal Tubular or Glomerular Disease
o Laboratory clues
 ABG
 Glucose
 Ketones
 Ammonia
o Chronic Encephalopathy – organelle disease
 Lysosomal Storage Disorder
 Mental retardation, skeletal deformity, hepatosplenomegaly, coarse facial feature (due to deposition of GAGs),
cloudy cornea, cherry red spot
 Example: MPS II – Hunter Syndrome
 Mitochondrial Disorder
 Detoxification – excrete ammonia via urea cycle; metabolize some drugs
 Energy production from fat, sugar, ETC
 Peroxisomal Disorder
 School age
 B-oxidation
Zellweger, Rhizomelic CDP, XLALD
VII. CONGENITAL INFECTIONS
Disease Features Diagnosis Management
TOXOPLASMOSIS  CHORIORETINITIS – most frequent eye manifestation IgA antibody test Pyrimethamine
 OBSTRUCTIVE HYDROCEPHALUS ELISA Sulfadiazine
 DIFFUSE intracranial calcifications Leucovorin
 Cause: Toxoplasma gondii
SYPHILIS  Early s/sx MHA-TP, FTA - confirmatory Penicillin
o Osteochondritis
o Hemolytic anemia
o Hemorrhagic rhinitis
 Late s/sx
o Hutchinson’s teeth
o Healed retinitis
o 8th nerve deafness
o Saddle nose
o Saber shin
o Hydrocephalus
o Mental retardation
 Desquamation of palms and soles
RUBELLA  Sensorineural hearing loss Serology, specific IgM antigen Immunization is recommended
 Cataracts
 CHD – pulmonary artery stenosis or PDA
 BLUEBERRY SKIN PATCHES
 Microcephaly
 Jaundice
 Radioluscent bone disease
 IUGR
CYTOMEGALOVIRUS  MOST COMMON CONGENITAL INFECTION Gancyclovir
 Signs & symptoms
 o Jaundice with hepatosplenomegaly
o Thrombocytopenia
o Petechiae
o Severe CNS disease (microcephaly, SUBEPENDYMAL
PERIVENTRICULAR CALCIFICATIONS)
o Chorioretinitis
o Progressive sensorineural hearing loss
HERPES SIMPLEX  LOCALIZED Culture of blood and urine Acyclovir
o Discrete vesicles to large bullous lesions Serology NOT HELPFUL
o Keratoconjunctivitis
o Chorioretinitis
 DISSEMINATED
o Liver, adrenal, CNS

VARICELLA  Cicatricial skin lesions

 Dec. development of cells in the lower extremities
 ZIGZAG LESIONS in LE
 Constricting bands
 Features suggesting diagnosis of intrauterine infection
o Prematurity o ECTHYMA GANGRENOSUM –
o IUGR Pseudomonas spp.
o Hematologic manifestations o SALMON PINK PAPULES – Listeria
o Ocular manifestations monocytogenes
o CNS manifestations o VESICULAR RASH – Herpes virus
o Manifestations in other organ systems o BLUEBERRY MUFFIN RASH – Rubella,
o NON-IMMUNE HYDROPS – due to CMV, Parvovirus
Parvovirus B19  Other neonatal infections
 Cutaneous manifestations of organisms causing sepsis
Features Management
OMPHALITIS  Inadequate care of the cord
 S/sx: localized erythema of the cord
ORAL THRUSH  Due to Candida albicans
 Whitish patches on the side of the tongue, gingiva, or buccal
mucosa
NEONATAL TETANUS  Due to unclean delivery and unhygienic management of the
umbilical cord
 Occurs in mothers who have not received tetanus vaccination
 S/sx: inability to suck, spasms, stiffness, seizures
PNEUMONIA  Diffuse alveolar or interstitial disease, asymmetric, localized
 S/sx: poor feeding, lethargy, irritability, cyanosis, respiratory
distress

MENINGITIS  Common in late-onset sepsis

NECROTIZING ENTEROCOLITIS
 Risk factors (6 I’s) Antibiotics with ANAEROBIC COVERAGE
o Immaturity NPO
o Ischemia Parenteral feeding
o Infection Surgery (if with perforation)
o Intake
o Immunity
o Inflammatory mediators
 S/sx: abdominal distention, passage of blood-streaked stools,
PNEUMATOSIS INTESTINALIS
 Formula-fed infants
 Affects the small intestines

VIII. INFECTIONS IN NEONATES

 Neonatal Sepsis – clinical syndrome of bacteremia characterized by systemic signs and symptoms of infection in the first 4 weeks of life; more than 1 organ
system involved, especially respiratory if early onset
Classification of Neonatal Sepsis

Early Onset Late Onset Very Late Onset (Nosocomial)

Time of Onset Birth to 7 days, usually <72 hours 7 days to 30 days >30 days
Maternal Obstetric Complications Often present Usually absent Varies
Transmission/ Organism Source Vertical: Maternal genital tract Vertical or post-natal environment Environment/ community
Clinical Manifestation Fulminant course, multisystem Insidious, focal infection; meningitis Multisystem or focal
involvement; pneumonia is is common
common
Risk Factors for Sepsis

Early Onset Late Onset

o Prematurity o Prematurity
o Low birth weight o Prolonged hospitalization
o Premature/ PROM o Invasive procedures
o Maternal fever o Parenteral alimentation
o Chorioamnionitis o Prior use of antibiotics
o Maternal UTI o Medications
o Functional deficiencies of neonatal host defense mechanisms o Functional deficiencies of neonatal host defense mechanisms
 Prematurity
o Most important neonatal factor predisposing to infection
o Premature infants have a 3 to 10 fold higher incidence of infection than full-term infants
 Chorioamnionitis
o Elevated maternal temperature
o Uterine tenderness
o Maternal leukocytosis
o Fetal tachycardia
o Foul-smelling amniotic fluid
 Why are newborns prone to develop sepsis?
o Newborn specific immune mechanisms are anatomically competent yet antigenically inexperienced and functionally deficient
o Antibody responses to infection are poor
o Complement levels are low
o Decreased ability of the granulocytes and phagocytes to kill bacteria
o Deficient neutrophil chemotactic response
 Transmission of Infection
Transplacental Vertical Postnatal
o CMV and Rubella o Ascending route: following rupture o Direct contact with caregiver
o Listeria monocytogenes of membranes o Environmental/ contaminated
o Treponema pallidum o Passage through the birth canal equipment
by colonization
 Predominant Pathogens for Sepsis
Early Onset Late Onset
o E.coli o Coagulase negative staphylococcus epidermidis
 MOST common pathogen in the Philippines (nosocomial pathogen)
 Number 1 cause of early-onset sepsis o Staphylococcus aureus
 Also the common pathogen if infant is born at home o Gram-negative enteric bacilli
o Group B Streptococcus o Pseudomonas aeruginosa
 MOST common in developed countries o Enterococcus spp.
o Listeria monocytogenes o Fungal
o Haemophilus influenzae
o Enterobacter aeruginosa
o Klebsiella pneumoniae
o Staphylococcus aureus
 Clinical Signs of Sepsis
o Respiratory distress: tachypnea, retractions, grunting, nasal flaring, apnea
o Abnormal skin color perfusion: mottling, pale color, gray color, dealyed capillary refill time, jaundice
o Temperature instability: hypothermia, hyperthermia (rare)
o Feeding intolerance: vomiting, abdominal distension, poor feeding
o Abnormal HR and BP: tachycardia, bradycardia, hypotension
o Metabolic problems: hypoglycemia, hyperglycemia, metabolic acidosis
o Abnormal neurologic status: lethargy, hypotonia, seizures
 Evaluation of a Newborn for Sepsis
o History
 Maternal infection/ Chorioamnionitis
 Maternal colonization with GBS
 Gestational age/ Birthweight
 Duration of rupture of membranes
 Complicated delivery
 Medical intervention
o Laboratory Studies
 Evidence of infection
 Evidence of inflammation
 Evidence of multiorgan system disease
 Positive CBC screen
o Treatment of Sepsis
 Early onset
 Antimicrobial therapy with Ampicillin or Penicillin in combination with an Aminoglycoside (always with 2 drugs and
given IV)
 Late onset
 Best to initiate therapy with broad spectrum coverage that will be effective for most nosocomial pathogens
 Duration
 The duration of parenteral antibiotic therapy should be 10-14 days
 Gram (+): 10 days
 Gram (-): 14 days
 In the presence of meningitis, antibiotic treatment should be given for 14-21 days
 Gram (+): 14 days
 Gram (-): 21 days
 Adjunctive therapies
 IV IG
 Granulocyte transfusion
 Exchange transfusion
o Complications of Sepsis
 Bacterial meningitis
 DIC
 Septic shock
 Multiple organ failure
 IX. GLOMERULAR DISEASES
Hematuria:
 Presence of at least 5 RBC/hpf in the urine
 Upper urinary tract
o Originate within the nephron
o Tea-colored/ cola-colored urine
 Lower urinary tract
o Originate from the pyelocalyceal system, ureter, bladder or urethra
o Red/pink color
 Gold standard: examination of urine sediment
 Urine dipstick
o False (+): fever, exercise, alkaine pH >9, oxidizing agent (peroxide)
o False (-): ascorbic acid, formalin

Renal Diseases with Low C3

Acute Poststreptococcal Glomerulonephritis  Classic example of acute nephritic syndrome Treatment:
characterized by gross hematuria, edema,  Sodium and fluid resuscitation
hypertension and renal insufficiency  Diuretics
 Follows infection of throat or skin by  Calcium channel antagonists, vasodialtors,
nephritogenic strains of GAS ACE inhibitors –treat HPN
 Most common is ages 5-12 years old  Salt restriction
Clinical Diagnosis: **Antibiotics no role
 Acute nephritic syndrome
 Evidence of recent strep infection (ASO titer,
Anti-DNase B  most reliable if antecedent
to pyoderma, streptozyme test)
 Low C3 levels
Phases:
 Latent phase (longer latent period for skin
infection)
 Oliguric phase (hospitalize px) 
complications: renal failure, hypertensive
encephalopathy, CHF
 Diuretic phase (unrecognized hypovolemia)
 Early Convalesnce
Clinical Course:
 Low C3 up to 8 weeks
 Proteinuria up to 6 months
Membranoproliferative Glomerulonephritis  Most common cause of chronic
glomerulonephritis in older children and
younger adults
 Diagnosis made by renal biopsy
 Differenial to PSGN: C3 continues to be low
after 2 months
Renal Disease with Normal C3
IgA nephropathy  Most common chornic glomerular disease worldwide
 IgA deposits in mesangium of glomerulus
IgA nephropathy PSGN
Latency period Hematuria develops after 1-2 days 7-21 days between onset of a strep
after onset of URTI and resolves pharyngitis or impetigo skin infection
within 5 days and the development of AGN
C3 Normal Low initially then returns to normal in
8 weeks

Alport’s Syndrome  Hereditary nephritits (x-linked)

Thin Glomerular Basement Membrane Disease
Membranous Glomerulopathy
Rapidly prorgressive (Crescentic) Glomerulonephritis
SLE nephritis
Henoch-Schonlein Purpura Nephritis
Hemolytic Uremic Syndrome (HUS)
 Type IV collagen (major component of basement membranes)
 Associated with sensorineural hearing loss and ocular abnormalities (anterior lenticonus= pathognomonic)
Presence of persistent microscopic hematuria and isolated thinning of the GBM on EM
 Most common cause of nephrotic syndrome in adults
 Secondary form of membranous glomerulopathy is more common in children (SLE, syphilis, heap B and C)
 Develop acute renal failure associated with acute nephritic and/or nephrotic syndrome
 Pathognomonic: crescents
Multisystem Disease with Low C3
 Kidney disease is one of the most common
manifestations of SLE in childhood
 Class IV –diffuse proliferative (most common
and most severe form)
Multisystem Disease with Normal C3
 Anaphylactoid reaction
 Small vessel vasculitis (purpuric rash, arthritis, abdominal pain, glomerulonephritis)
 No thrombocytopenia
 Form eating inadequately cooked hamburgers
 Sudden onset of acute renal failure with preceding history of gastroenteritis
 Most common in children younger than 4 years old
 Characteristic triad: microangiopathic hemolytic anemia, thrombocytopenia, uremia
Proteinuria:
 Nephrotic range proteinuria: >2
 Transient proteinuria
o Usually does not exceed 2+ on dipstick
 Orthostatic proteinuria:
o Most common cause of persistent proteinuria in school-aged children and adolescents
o Mechanism: altered renal hemodynamics and partial renal vein obstruction in upright position
o No proteinuria in the morning, then becomes (+) throughout the day
 Fixed proteinuria:
Glomerular Proteinuria Tubular Proteinuria
Alterations of the size barrier and loss of anionic charges Injury to proximal tubular epithelium
Urine protein/creatinine ratio >1.0 Urine protein/creatinine ratio <1.0
With hypertension, hematuria or renal dysfunction May be a sign of a variety of renal disorders, involving tubulointerstitial compartment of
kidney

Primary Glomerular Disease: Nephrotic Syndrome

 Idiopathic nephrotic syndrome –more common in males than females
o 90% idiopathic
 Present with mild edema, initially around eyes and in lower extremities
 Cardinal features:
o Heavy proteinuria
o Hypoalbuminemia
o Edema
o Hyperlipidemia

Minimal Change Disease  85%

 Most responsive to prednisone (>95%)
 T-cell dysfunction  loss in negativity of GBM
Mesangial proliferation  5% mesangial proliferation
Focal Segmental Glomerulosclerosis  10%
 Least responsive to prednisone (20%)

 Clinical Manifestations:
o Anorexia, irritability, abdominal pain and diarrhea
 Diagnosis:  Fluid resuscitation
o Urinalysis  IV administration of 25% human albumin
o Urinary protein excretion (>40 mg) o Adjunct therapy to reduce proteinuria in steroid-resistant
o Increased creatinine patients:
o High serum cholesterol and TAG levels  ACE inhibitors
o Normal C3 and C4  ARBs
 Treatment: o Calcium supplementation
o Prednisone  Immunization:
o Severe symptomatic edema: o Pneumococcal vaccine –given to child in remission and
 Low sodium diet off daily prednisone therapy
 Diuretics o Varicella vaccine

Secondary Nephrotic Syndrome:

 Age >8 y/o
 Hypertension, hematuria, renal dysfunction
 External symptomatology: rash, arthralgia or depressed serum complement levels
 Membranous nephropathy, membranoproliferative glomerulonephritis, postinfectious glomerulonephritis, lupus nephritis, HSP nephritis
Other causes: malaria, schistosomiasis, hepatitis B and C virus, Filaria, leprosy, HIV, malignancy

X. UTI, UROLITHIASIS
Acute Cystitis:
 Urinary bladder involvement
 More common in older children
 SSx:
o Dysuria
o Urgency and frequency
o Suprapubic pain
o Foul-smelling (malodorous) urine, cloudy urine
 2 types:
Acute Hemorrhagic Cystitis Eosinophilic Cystitis
 Caused by e.coli  Rare
 Attributed to adenovirus infections  SSx of cystitis and hematuria
 Blood will disappear in ~5 days  Treated with anti-histamines and NSAIDs
 Ultrasound: “tumoral growth” in the bladder with irregular bladder thickening
 Definitive Diagnosis: cystoscopy with biopsy
 Histology: bladder mucosal tissue with dense interstitial eosinophilic
infiltration
Acute Pyelonephritis:
 Involvement of upper urinary tract
 SSx:
o Fever
o Leukocytosis
o Abdominal flank/pain
o Vomiting and malaise
 In newborns and infants (<2 y/o), with nonspecific symptoms:
o Jaundice
o Poor feeding
o Irritability
o Weight loss

Asymptomatic Bacteriurua:
 (+) Urine culture without symptoms
 Exclusive in girls
 Do not treat!

UTI in Children:
 4th leading cause for admission or referral in pediatric nephrology
 Prevalence:
o 1st year of life: M>F
o >1 y/o: M<F
 Pyelonephritis is highest during 1st year of life
o Must be diagnosed at an early age because renal system is most vulnerable during this time
 In girls, there is increasing incidence of cystitis during the toilet training age (3-4 y/o)
o Attributed to voiding dysfunction wherein child is trying to retain urine to stay dry
 Risk factors:
o Female (shorter urethra)
o Uncircumcised male (flora in preputial sac)
o Vesicoureteral reflux (bacteria in ureter goes up to bladder then kidney)
o Toilet training (voiding dysfunction)
o Obstructive uropathy (stasis  bacterial overgrowth)
o Urethral instrumentation (introduces bacteria)
o Wiping from back to front
o Bubble bath (decreases surface tension in the urethra)
o Tight clothing (vulvar irritation)
o Pinworm infection (migrate to urethra)
o P fimbriated bacteria (adhere to wall of bacteria)
o Anatomic abnormality
o Urolithiasis (obstruction stasis)
o Neurogenic bladder (urinary incontinence)
o Sexual activity (Honeymoon cystitis d/t incomplete bladder emptying)
o Pregnancy (unable to empty bladder completely)
Specific Causes of UTI:
Vesicoureteral Reflux Retrograde flow of urine from bladder into ureter and renal pelvis may be due to:
 Anomaly of insertion of ureter into bladder  incompetent flap-valve mechanism
 Distal obstruction  increased intravesical pressure
Prevent recurrence
More kidneys exposed  higher chance of renal scaring  hypertension  renal insufficiency
Ureteropelvic junction obstruction Due to: congenital ultrasound, calculi, neoplasia, inflammation, postsurgical/trauma
Urinary stasis  pyelonephritis
Ultrasound: hydronephrosis
Posterior urethral valve Narrowing of prostatic urethra
Most common cause of severe obstructive uropathy in children
SSx:
 Small urinary stream caliber
Urge Syndrome (Vincent’s Curtsy) “Bladder sphincter dyssynergia”
Results in posturing maneuver:
 Curtsy dance and sitting on heels
 Compress urethra and prevent leakage of urine
 Results in uninhibited contraction of the bladder
VCUG: “spinning top deformity” –narrowing of urinary meatus and dilatation of proximal end
Lazy bladder Normal voiding frequency: 4-6x/day
Infrequent emptying of bladder  overflow incontinence
Meningomyelocoele, Spina Bifida occulta Neurogenic bladder
(occult dysgraphism) Characteristics:
 Sacral dimpling
 Absence of gluteal fold
 Weakness of lower extremities
 Arching of feet
Gait problems
P.fimbriated E.coli E.coli  most common cause of UTI
Pyelonephrogenic
K antigen Protects bacteria from phagocytosis
Accountable for virulence of bacteria
  Complications:
o Shock, septicemia especially in infants and renal parenchymal injury
o Permanent renal damage  occurs following pyelonephritis and more frequent in children who have multiple episodes
 Common etiologic agents:
o E.coli (most common)
o Klebsiella
o Proteus
 In 304 y/o  e.coli and proteus occur in equal amounts
o Staphylococcus saprophyticus
o Viral infections (adenovirus) –may cause hemorrhagic cystitis
 Diagnosis:
o History:
 OB history –oligohydramnios or hydronephrosis through fetal ultrasound
 Urinary bowel habits
 Previous episodes if UTI
 Siblings diagnosed to have VUR
o PE:
 Genital exam: phimosis and labial adhesions
o Urinalysis:
 Initial teset
 Pyuria: >5 WBC/hpf of freshly voided spun urine or >10 WBC/cumm on freshly voided unspun urine
 Symptomatic + Normal urinalysis = UTI likely
o Urine Culture and Sensitivity:
 Gold standard for diagnosis of UTI
 Methods of urine collection:
o Urine catheterization
o Suprapubic aspiration
 99% reliability
 High accuracy
o Midstream clean voided specimen
 After child has been toilet-trained
 Imaging Studies:
o Goal of imaging: identify anatomic abnormalities that predispose to infection
Ultrasound Hydronephrosis
Renal perinatal abscess
Enlarged kidneys
Pyonephrosis
Urinary bladder capacity
Postvoid residual
Wall thickness
DMSA renal scan Diagnostic test of choice for renal scars
Photopenia –area of inflammation or scarring
4-6 months after UTi = renal scars!
Voiding Cystourethrogram (VCUG) Indications:
 Any infant with febrile UTI
 Girls who had >2 UTIs in 6 months
 Bous >1 UTI in 6 months
 Any significant abnormality in renal sonogram
Purpose:
 Detect and grading of reflux
Diagnose:
 VUR  Only way to diagnose VUR
 “Spinning top deformity” in urge syndrome
 Posterior urethral valve

 Grading of VUR:
Low grade Grade I Nondilated ureter
Grade II Reflux into upper collecting system without dilatation
Moderate grade Grade III Reflux into dilated ureter and/or blunting of calyceal fornices
High grade Grade IV Reflux into grossly dilated ureter
(Unlikely to resolve) Grade V Massive reflux (tortuous with loss of papillary impressions)

 Classification og VUR:
Type Cause
Primary Congenital incompetence of valvular mechanism of vesicouretral junction
Primary associated with other malformations of the ureterovesical Ureteral duplication
junction Ureterocoele with duplication
Ureteral ectopia (ureter does not enter the bladder)
Paraureteral diverticula
Secondary to increased intravesical pressure “Himman Syndrome” (nonneuropathic baldder)
Neuropathic bladder
Secondary to inflammatory process Severe bacterial cystitis
Foreign bodies
Vesical calculi
Secondary to surgical procedures involving the uereterovesical Surgery
junction
  Management:
o Indications for hospital admission:
 Neonates (fail to compartmentalize infection so UTI can easily lead to sepsis)
 Urosepsis
 Dehydration
 Inability to tolerate oral medications
o Treatment for pyelonephritis:
 10-14 day couse of antibiotics (IV then shift to oral when afebrile)
 Drugs:
 Ampicillin + gentamycin
 Cefriaxone (milder)
 Cefixime
 Ciprofloxacin (patients >17 y/o)
o Do not use in patients <17 y/o due to potential joint and cartilage damage
o Treatment for acute cystitis:
 3-5 day course
 Drugs:
 Trimethoprim-sulfamethoxazole (cotrimoxazole) –if C/S results not yet available
 Amoxicillin
 Nitrofurantoin
o Not used in febrile UTI
 1st generation cephalosporins (cefixime and cephalexin)
o Prophylaxis for UTI:
 Indications:
 Neurogenic bladder
 Obstructive uropathy
 VUR
 Calculi
 Important:
 Given only 30-35% of original dose
 Older children  given at night
 Infants  any time
 Drugs:
 Cephaliexin
 Cotrimoxazole
 Nitrofurantoin
 Nalidixic acid
UROLITHIASIS:
 Urolithiasis –stone in the urinary tract
 Nephrolithiasis –stone within renal pelvis
 Nephrocalcinosis –calcium deposits within renal parenchyma
 Types of stones
o Calcium oxalate –most common
o Struvite –if concomitant with UTI
 Staghorn calculus –struvite stone
 Pathogenesis:
o Stone formation due to increase in concentration of crystals (supersaturation)
o Decreased concentration of inhibitors (citrate, diphosphonate, magnesium)
 Clinical Manifestations:
o Gross or microhematuria
o Urinary frequency
o Dysuria
o Bladder spasm
o Incontinence
o Pyuria
o Abdominal pain/ flank pain
o Recurrent UTI
 Complications:
o UTI –most common in childhood
o Obstruction
 Diagnosis:
o Family history: family history of nephrolithiasis, arthritis, gout or renal disease
o Dietary history
 Imaging studies:
o Plain abdominal film
 Struvite and cysteine stone less radiopaque
o Noncontrast helical CT scan of abdomen and pelvis
o Renal ultrasound
 Shadowing
 Hypercalciuria
o Urinary calcium excretion more than 4 mg/kg/day
o Urine Ca/Cr >0.2
o Causes: idiopathic, distal RTA, loop diuretics, steroids
 Treatment:
o Increased fluid intake (1st line therapy)
 Maintain specific gravity at <1.010
o Limit salt
o Prompt treatment infection
 o Hypercalciuria:
 Thiazides (increase Ca reabsorption in DCT)
 Potassium citrate (inhibit stone formation)
o Uric acid stones
 Allopurinol (xanthine oxidase inhibitor)
 Urinary alkalinization (prevent supersaturation)
o Stones <5 mm in diameter less likely to pass
o Surgical management, percutaneous lithotripsy, extracorporeal shock waves lithotripsy (destruction of stones with shock waves)

XI. HPN
Definition of Hypertension (2001 National High Blood Pressure Education Program Working Group (NHBPEP):
 Normal BP –both systolic and diastolic BP <90 th percentile
 Prehypertensive –systolic and/or diastolic BP ≥90 th percentile but <95 th percentile or if BP exceeds 120/80 mmHg especially in adolescents (even if 90 th percentile for age,
gender and height)
 White-coat hypertension –BP levels that are above 95 th percentile when measured in a physician’s office or clinic and who is normotensive outside clinical setting
o Seen in 25-30% of cases
o Diagnosing this condition normally requires ambulatory BP monitoring (ABPM)
 Blood Pressure Measurement
o Children > 3 years of age –BP should be measured at least once during health care visit
o Children < 3 years of age –in special circumstances
o Revised BP tables now include 50 th, 90th, 95th and 99th percentile by sex, age and height
o Systolic and diastolic BP are of equal importance; if there is disparity between the two, the higher value determines the BP category
 Definition of Hypertension:
o Hypertension
 Either systolic and/or diastolic BP ≥95 th percentile measurement upon 3 or more separate occasions
 In infants < 1 year old: SBP is used to define hypertension
o Stage I Hypertension
 SBP and/or DBP between the 95 th percentile and 5 mmHg above the 99 th percentile
o Stage II Hypertension
 SBP and/or DBP ≥99th percentile and 5 mmHg above
 Etiology:
o Secondary Hypertension in children is most commonly due to:
 Renal abnormalities
 Cardiovascular disease
 Endocrinopathies
 CNS causes

o Causes of Hypertension per age group:

Newborn Infancy to 6 years old 6 to 10 years old Adolescence
Renal artery thrombosis or embolus (UA Renal parenchymal disease Renal parenchymal disease Essential hypertension
catheter) Renal artery stenosis Renal artery stenosis White-coat hypertension
Renal vein thrombosis Coarctation of aorta Essential hypertension Renal parenchymal disease
Congenital renal malformation Medications (corticosteroids, etc.) Endocrine causes Subastance abuse (cocaine,
Coarctation of aorta Endocrine causes amphetamine and caffeine)
Renal artery stenosis Endocrine causes
Bronchopulmonary dysplasia
 Clinical Manifestations:
o Children and adolescents with primary hypertension are usually asymptomatic
o With substantial hypertension, headache, dizziness, epistaxis, anorexia, visual changes and seizure may occur
o Cardiac failure, pulmonary edema and renal dysfunction may occur
 Screening Evaluation of Hypertension –History
History Possible Cause of Hypertension
Neonatal History: use of umbilical artery catheter Reno-vascular hypertension; renal artery thrombosis/ emboli
CNS, head trauma, headache, visual disturbance, lethargy, seizures, tremors, morning Elevated ICP
vomiting
Hearing: Hearing loss Renal disease (ex. Alport syndrome)
Lead poisoning
CVS: palpitations, irregular pulses Catecholamine excess (pheochromocytoma)
Renal: edema, history of UTI or unexplained fever, abnormal urine color, flank pain, Reflux nephropathy
dysuria, tea-colored urine Glomerulonephritis; CKD
Skin: rash, sweating, pallor Catecholamine excess
Thyroid dysfunction
Renal casculitis
Respiratory: epistaxis, difficulty breathing
Recent medical history: recent pharyngitis or impetigo, exposure to sources of e.coli Post-infectious glomerulonephritis
Hemolytic uremic syndrome
Medications –sympathomimetics, oral contraceptives, corticosteroids Side effect of medication
Substance abuse: cocaine, amphetamine, anabolic steroids, etc. Drug-mediated effects
Family History: Hypertension, early MI, diabetes, stroke Essential hypertension
Sexual history: post-menarchal female actively engaged in sexual intercourse Preeclampsia
Growth history: excessive weight gain or loss, change n growth percentiles Obesity, thyroid dysfunction
Dietary history: types and amount of food ingested; salt crabbing Obesity, essential hypertension
Sexual History: Stress factors at home and school Stress

PE finding Possible etiology

General:
Obesity Essential hypertension
Truncal obesity Consider Cushing’s syndrome, steroid Hx
Growth retardation Consider chronic renal disease
Vital signs:
Tachycardia Catecholamine excess or hyperthyroidism
BP difference in extremities If upper extremity BP > lower extremity BO, consider coarctation of aorta
Head and Neck:
Elfin facies Williams syndrome
Moon facies Cushing syndrome, corticosteroid therapy
Thyroid enlargement Hyperthyroidism
Webbed neck Turner syndrome
Tonsilar hypertrophy Sleep- disordered breathing, sleep apnea
Eyes:
Retinal changes Suggest severe HTN and secondary etiology
Papilledema Intracrainial HTN
Skin:
Acne, hirsutism, striae Cushing syndrome, steroid therapy
Café-au-lait spots and/or neurfibromas Neurofibromatosis
Ash leaf spots and/or adenoma sebaceum Tuberous sclerosis
Rash Secondary renal disease; lupus; HSP
Acanthosis nigricans T2DM
Neurologic:
Neurologic deficits Chronic or acute severe hypertension with stroke
Chest:
Murmur Coarctation of the aorta
Apical heave Left ventricular hypertrophy
Abdomen:
Abdominal bruit Reno-vascular disease
Mass Hydronephrosis, PKD, renal tumors, neuroblastoma

 Evaluation for Identifiable Causes:  Evaluation for co-morbidity:

o History including sleep history o Fasting lipid panel
o Family history o Fasting glucose
o Risk factors o Drug screen
o Diet  Evaluation for Target-Organ Damage:
o Smoking and drinking habits o Echocardiogram –LVH
o PE o Retinal exam
o BUN/ creatinine  Additional Evaluation as Indicated:
o Electrolytes o ABPM
o Urinalysis and urine culture o Plasma renin determination
o CBC o Renovascular imaging
o Renal ultrasound o Arteriography
o Plasma and urine steroid levels
o Plasma and urine catecholamines

 Management:
o Management is directed to underlying disease, exacerbating factors, comorbidities and magnitude of BP elevations
o Non-pharmacologic measures:
 Dietary changes (DASH –Dietary Approaches to Stop Hypertension: increased intake of fruits and vegetables, low-fat dairy and whole grains
and reduced consumption of foods high n saturated fat and refined sugar)
 Reduced sodium intake
 Increased physical activity
 Decreased sedentary activities
 Weight loss
 Family-based, school-based, community-based
o Pharmacologic Treatment:
 Stage II Hypertension
 Symptomatic hypertension
 Hypertensive target organ damage
 DM
 Persistent hypertension despite non-pharmacological management
Hypertensive Urgency Hypertensive Emergency
Elevations in SBP and DBP associated with: Elevations in SBP and DBP associated with end organ injury of the brain, heart and or
 Severe headache kidneys
 Vomiting Clinical manifestations:
 Shortness of breath  Hypertensive encephalopathy
 Nosebleeds  CHF
 Severe anxiety  Pulmonary edema
May progress to a hypertensive emergency requiring decrease in BP within 12-24 hours  ARF
 Stroke
 Head trauma
 MI
 Adrenergic crisis
 Dissecting aorta
 Aneurysm
 eclampsia
 Goal of Therapy:
o Slow reduction because of the need to preserve cerebral autoregulation
o Eventual goal is BP <90 th percentile for height, age and sex
 o Route of administration: preferred method of treatment is infusion of parenteral medication with close hemodynamic monitory in an intensive care unit
o Greatest risk for severe hypertensive treatment is too rapid reduction in BP
o Risk is higher with administration of bolus injections than IV infusions
 Outpatient Management of Hypertension:
o ACE inhibitors
 Check serum K and creatinine
 Cough and angioedema with captopril less with enalapril
o ARBs
 Check serum K and creatinine
o Calcium channel blockers
 May cause tachycardia
o Diuretics
o Most useful for hypertensive emergencies:
 Nicardipine
 May cause reflex tachycardia
 Hydralazine
 Should be given q4h when IV bolus
 Labetalol
 Asthma and overt heart failure relative contraindications

XII. RENAL FAILURE

 Oliguria –passage of insufficient volume to maintain homeostasis
 Anuria –complete cessation of urine
 Polyuria –excessive urine output >2 ml/kg/hr
Acute Renal Failure (ARF):
 Sudden loss of renal function due to inadequate renal perfusion
 Cardinal feature: reduction of GFR
 pRIFLE criteria:
Risk Incresed creatinine x 1.5 or UO <0.5 ml/kg/hr x 8 hrs
GFR decreased by 25%
Injury Increased creatinine x2 or UO <0.5 ml/kg/hr x 16 hrs
GFR decreased by 50%
Failure Increased creatinine x 3 or UO <0.3 ml/kg/hr x 24 hrs or
GFR decreased by 75% or anuria x 12 hrs

Creatinine >4 mg/dl or

eCCl <35 ml/min/1.73m2
Loss Persistent AKI
Complete loss of renal function > 4 weeks
End-stage End-stage Kidney Disease

 Classification of ARF:
Prerenal ARF (55-60% of ARF)
 “prerenal azotemia”
 Transient diminished effective circulating
arterial volume  inadequate renal
perfusion  decrease in delivery of oxygen
and energy sources  decreased GFR
 Complete recovery of renal function
expected upon return of renal perfusion
 Cause: decreased effective intravascular
volume
 Constriction due to RAAS activation
Renal ARF (35-40% ARF)
 Renal parenchymal damage, sustained
hypoperfusion/ischemia
 Glomerular (glomerulonephritis)
 Vascular (HUS, malignant hypertension,
renal artery/vein thrombosis)
 Interstitial damage (acute interstitial
nephritis)
 Tubular disease (acute tubular necrosis,
intratubular obstruction)
Postrenal ARF (5% of ARF)
 Obstruction of the urinary tract distal to the
kidney
 Posterior urethral valves, ureteropelvic
junction obstruction, ureterovesical junction
obstruction, ureterocoele, tumor,
urolithiasis, hemorrhagic cystitis, neurogenic
bladder

 Clinical Manifestations:
o Oliguria, edema, hypertension, dyspnea, pallor, vomiting, lethargy, anorexia
 Laboratories:
o CBC
 Anemia  dilutional or hemolytic
 Thrombocytopenia  SLE, HUS
 Leukopenia  SLE, sepsis
 High eosinophil count (acute interstitial nephritis)
o Urinaysis
o Electrolyte and Acid-Base balance
 Hyponateremia
 Dilutional, more commonly due to overload
 Hypocalcemia
 Due to inadequate vitamin D production by kidney
 Hyperkalemia
 Decreased GFR decrease in excretion
 Common cause of death in ARF
 Metabolic acidosis
 Decrease GFR  decrease excretion

 GFR
o Used clinically to follow course of renal disease
o Formula: k x L/ PCr
o Proportionality constant:
  1st year of life: 0.45
 Children and adolescent girls: 0.55
 Adolescent boys: 0.7
 Urinary sediment and Indices
o Most important factor in determining cause of ARF
o Urinary sediments:
 Granular cast  ARF
 Hyaline cast (Broad cast)  CRF
 RBC cast  glomerulonephritis
o Urinary Indices
Pre-renal Intrinsic Renal
Urinary specific gravity >1.020 <1.020
Urine Na (mEq/L) <20 >40
FeNa (%) <1% >2%
Urine osmolality >500 <350
BUN/ creatinine ratio >20 <20

 Treatment:
o Hyponatremia:
 Na >120 mEq/L  fluid restriction
 Na <120mEq/L  more aggressive tx since child is at higher risk for seizures
 Correct to 125 mEq/L with hypertonic saline followed by fluid restriction
 No need to bring up to 140 mEq/L
o Hyperkalemia
 Indicated in cardiac conduction abnormalities
 Antagonism:
 10% calcium gluconate
 Redistribution:
 Glucose (insulin 25%), albuterol, NaCHO 3
 Removal
 Furosemide, Sodium polysterne sulfonate resin
o Hyperphosphatemia
 Calcium containing phosphate binders to prevent GI absorption
 Avoid reaching Ca x Phosphorus product of 55 in serum
o Hypocalcemia
 Oral calcium carbonate or other calcium salts
 Severe or symptomatic hypocalcemia: 10% calcium gluconate
o Metabolic acidosis
 Oral or parenteral sodium bicarbonate or oral sodium citrate solutions
 Hypocalcemia can also occur if acidosis is corrected with Ca gluconate and if Ca is not yet corrected
 Ensure serum Ca is at safe level
o Dopamine
o Diuretic therapy:
 IV furosemide
 IV mannitol
o Anti-hypertensive therapy:
 IV sodium nitroprusside
 Nicardipine
 Labetalol
 Diazoxide
 Hydralazine
 Enalapril
o Seizure control:
 Diazepam
 Renal Replacement Therapy:
o Indications for Dialysis:
 Severe metabolic acidosis unresponsive to medical management
 Persistent hyperkalemia (peak T waves of ECG)
 Calcium/ phosphorus imbalance with hypocalcemic tetany
 Neurologic symptoms
 Volume overload with evidence of hypertension and/or pulmonary edema
 BU >100-150 mg/dl
o Types of dialysis:
 Intermittent hemodialysis (stable hemodynamic status)
 Peritoneal dialysis (most commonly employed in neonates and infants)
 Continuous renal replacement therapy (unstable hemodynamic status)

Chronic Kidney Disease:

 Renal injury (proteinuria) and/or GFR <60 ml/min/1.73m 2 for 3 months
 May be congenital, acquired, inherited or metabolic renal disease
 Causes:
<5 years old >5 years old
Congenital abnormalities (dysplasia, obstructive uropathy, renal hypoplasia) Acquired diseases (glomerulonephritis)
Inherited disorders (familial juvenile nephronophthisis, alport syndrome)
  Stages of CKD:
Stage Description GFR
Stage 1 Kidney damage with normal GFR >90
Stage 2 Kidney damage with mild decrease in GFR 60-89
Stage 3 Moderate decrease in GFR 30-59
Stage 4 Severe decrease GFR 15-29
Stage 5 Kidney failure <15 or on dialysis

 Pathogenesis:
o Hyperfiltration injury –final common pathway for glomerular destruction
 Damage to surviving glomeruli
 Presence of few glomeruli increases filtration by each glomerulus  glomerular injury
 Clinical Manifestations:
o Pallor (anemia)
 Epo deficiency
 Iron or folate deficiency
o Short stature/ growth failure
o Renal osteodystrophy
 High bone turnover disease
 Most common
 Secondary hyperparathyroidism
 Osteitis fibrosa cystica
 Low bone turnover disease
 Due to oversuppression of PTH
 Osteomalacia
 Adynamic bone disease
o Sallow
o Edema, hypertension, volume overload (GN/NS)
o Failure to thrive, dehydration, UTI
 Treatment:
o Nutrition:
 Restriction of dietary phosphorus, potassium, sodium
 Recommended dietary allowance
 2.5 g/kg/day of high biologic value protein (animal)
 Water-soluble vitamin supplementation (vit. B and C)
o Renal Osteodystrophy
 Vitamin D administration and calcium
o Growth:
 Recombinant human growth hormone
o Anemia
 Recombinant human Epo
 Darbopoietin
o Hypertension
 Furosemide, ACE inhibitors, ARBs, CCBs, Beta-blockers
o Renal replacement therapy:
 Peritoneal dialysis, hemodialysis, renal transplantation