Pediatrics

2016
September

Paediatrics State Exam 2016/2017

Arman Motlagh and Arunthan Perinpasivam

Pavol Jozef Safarik University In Kosice

1a. Pneumonia in Newborns, Infants and Toddlers
Definition
Pneumonia is an infection of the lower respiratory tract that involves the
airways and parenchyma. According to morphology pneumonia can be classified
as:
• Bronchopneumonia – a patchy consolidation involving one or several

lobes
• Lobar pneumonia – classically involve the entire lung lobe relatively
homogenously.
• Interstitial pneumonia - inflammatory process predominantly involving
the interstitium, including the alveolar walls and the connective tissue
around the bronchoalveolar tree.
In infants the risk of hospital admission is most common and the risk of death is
greatest. Significant cause of morbidity and mortality in childhood.
Etiology
It is caused by a variety of viruses and bacteria, but in up to 50% of cases no
causative pathogen is identified. In general, viruses more common in younger,
while bacteria are more common in older children. Bacteria causes fewer cases
of pneumonia, but the morbidity and mortality is much higher than
viral. Transmission are often airborne droplets. Other causative agents could be
aspiration of food and gastric acid, congenital or foreign bodies.
Pathogens vary according to child’s age:

• Newborn (up to 28days): organisms from the mothers genital tract
o Group B Streptococcus
o E.coli
o Klebsiella
o Staph. Aureus
• Infants (up to 1year) and toddler (up to 3years)
o Respiratory viruses
§ RSV
§ Influenza
§ Adenovirus
o Bacterial agents
§ Strep. pneumonia
§ Chlamydia tracomatis
§ H. Influenza
§ Mycoplasma pneumonia

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Motlagh Paediatrics State Exam Perinpasivam
Clinical features
Viral Bacterial
General Fever, cough, tachypnea, High fever, chills, cough,
respiratory distress: nasal chest pain, tachypnea,
flaring, intercostal in restlessness, anxiety
drawings, grunting
Newborns Cyanosis, resp. fatigue Cough may not be present
Infant Poor/no feeding Poor/no feeding
Toddler Poor/no feeding Poor/no feeding

• Other symptoms include - cough, wheezing, stridor, tachypnea, lethargy,
fatigue, malaise and an “unwell” child.
• Localized chest, abdominal, or neck pain is a feature of pleural irritation
and suggests bacterial infection.
• Use of accessory muscles (SCM)
• Retraction of chest wall with inspiration (suprasternal, intercostal and
subcostal)
• In the afebrile baby always think of Chlamydia trachomatis and bordetella
pertussis (even if the characteristic “whooping cough” is not present)
Age Normal respiratory rate Tachypnea
Newborn 30-50 >60
Infant 20-40 >50
Child <5 20-30 >40

Diagnosis
• History (Hx): age, immunization, symptomology
• Physical examination: Signs of respiratory distress, tachypnea, SpO2,
cyanosis, tachycardia (10Bpm every 1°C of fever)
o Auscultation: decreased breath sounds, bronchial breathing,
crackles, wheezing and stridor
o Percussion: dull
• Laboratory:
o CBC, CRP, ESR↑ (Lymphocyte↑ - viral, neutrophils↑ - bacterial)
o Cultivation – sputum, pleural fluids, blood, throat swab
o ABG/SpO2

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• Chest x-ray (Cxr):
o May confirm the diagnosis but cannot differentiate between viral
and bacterial infection.
o Findings:
§ cavities containing fluid and air is characteristic of staph.
pneumonia
§ patchy, peripheral consolidation – viral pneumonia
§ lobar consolidation – bacterial infection
§ perihilar infiltrates – mycoplasma infection
§ pleural effusion, emphysema – reveals complications
o In case of serious disease, such as pleural abscess CT chest can be
utilized
Treatment
Most cases can be managed at home, but indications for admission include: SaO2
<93%, severe tachypnea and dyspnea, grunting, apnea, not feeding. Viral
infections can be prevented by vaccination.

• General: Fluid replacement – avoid over hydration, O2 for hypoxia ,
antipyretics, analgesics, expectorant, bronchodilators, zinc – accelerate
recovery from severe pneumonia
• Newborn:
o ampicillin or gentamycin
o macrolide (erythromycin, clarithromycin, azithromycin) –
c.trachomatis (atypical pneumonia)
• Infants:
o First line: Amoxicillin or amoxiclav (amoxicillin+clavulanate acid)
o Second line: cefotaxime
o macrolide (erythromycin, clarithromycin, azithromycin) –
mycoplasma pneumonia (atypical pneumonia)
• Toddler:
o Amoxicillin or macrolide

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1b. Nonconjugated Hyperbilirubinemia

Definition
Increased levels of bilirubin that causes yellow discoloration of the skin, sclera
and mucous membrane. It can be a result from increased production, impaired
conjugation or impaired hepatic uptake of bilirubin. It can also occur naturally in
newborns.
• Neonates: >5 mg/dL (>85µmL/L)
• Children: >2-3 mg/dL (40-50µmL/L)
Types of neonatal jaundice

Physiologic jaundice
All newborns have higher bilirubin levels (mainly unconjugated bilirubin) than
adults. Physiologic jaundice is a mild unconjugated hyperbilirubinemia that
affects nearly all newborns and resolves within the first several weeks after
birth. Bilirubin production in a newborn is 2-3 times higher than in adults. It is
caused by increased bilirubin production, decreased bilirubin clearance, and
increased enterohepatic circulation. Jaundice within 24h or longer than a few
weeks always pathological. The following factors contribute to the development
of physiologic jaundice:
• Inefficient hepatic excretion of unconjugated bilirubin
• Portal venous shunting through a patent ductus venosus
• Shortened red blood cell survival
• Immaturity of hepatic bilirubin clearance
• Hydrolysis of conjugated bilirubin - to the unconjugated form
• Low bacterial degradation of bilirubin - increased absorption of
unconjugated bilirubin
The peak total serum bilirubin level in physiologic jaundice typically is 5-6
mg/dL (86-103 µmol/L), occurs 48-120 hours after birth, and does not exceed
17-18 mg/dL (291-308 µmol/L). Higher levels of unconjugated
hyperbilirubinemia are pathologic and occur in various conditions.

Nonphysiologic jaundice
Breast milk (maternal milk) jaundice results from increased enterohepatic
circulation. Result from an unidentified component of human milk that enhances
intestinal absorption of bilirubin. Mechanism could be increased concentration
of beta-glucuronidase in breast milk. Beta-glucuronidase deconjugates intestinal
bilirubin, increasing its ability to be absorbed.

Maternal serum jaundice (Lucey-Driscoll syndrome) may result from the
presence of an unidentified inhibitor of UGT, which enters the fetus through
maternal serum. It is an autosomal recessive metabolic disorder affecting
enzymes involved in bilirubin metabolism
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ABO/Rh incompatibility
Neonatal jaundice can also result from an increased bilirubin load or from
ABO/Rh incompatibility. When infant is A, B or AB and anti-A or anti-B. The
mother will lack the A or B antigen. With regard to the latter, incompatibility can
have the following causes:
• Inherited red blood cell disorders - Sickle cell disease and hereditary
spherocytosis/ elliptocytosis
• Drug reactions
• Ineffective erythropoiesis - Thalassemia, vitamin B-12 deficiency, and
congenital dyserythropoietic anemia
Impaired conjugation of bilirubin

Deficiency of bilirubin-UGT leads to ineffective esterification of bilirubin, which
in turn results in an unconjugated hyperbilirubinemia. Reduced bilirubin
conjugation as a result of a decreased or absent UGT activity is found in several
acquired conditions and inherited diseases, such as Crigler-Najjar syndrome
(types I and II) and Gilbert syndrome. Bilirubin conjugating activity is also very
low in the neonatal liver.
Crigler-Najjar syndrome type 1 and 2

Crigler-Najjar syndrome is a congenital, familial, nonhemolytic jaundice
associated with high levels of unconjugated bilirubin. Crigler-Najjar syndrome is
a rare disorder caused by an impairment of bilirubin metabolism resulting in a
deficiency or complete absence of hepatic microsomal bilirubin-uridine
diphosphate glucuronosyltransferase (bilirubin-UGT) activity.
• Crigler-Najjar syndrome type 1 - Associated with neonatal unconjugated
hyperbilirubinemia (high levels) and kernicterus
• Crigler-Najjar syndrome type 2 (also called Arias syndrome) - Presents
with a lower serum bilirubin level; responds to phenobarbital treatment

Depending on the severity of a mutation’s effect on the enzymatic activity,
Crigler-Najjar syndrome type 1 (a complete absence of enzymatic activity) or
Crigler-Najjar syndrome type 2 (UGT level < 10% of normal) may result. The
differentiation between type 1 and 2 is not always easy, and both types are quite
possibly different expressions of a single disease.

Gilbert syndrome
Gilbert syndrome is a benign, familial disorder inherited in an autosomal
recessive pattern characterized by intermittent jaundice in the absence of
hemolysis or underlying liver disease. The condition is recognized to arise from a
mutation in the promoter region of the UGT1A1 gene, which results in reduced
UGT production.

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Etiology

Increased bilirubin Impaired hepatic Impaired bilirubin
production bilirubin uptake conjugation
Hemolysis Congestive heart failure Crigler-Najjar syndrome
types I and II
Dyserythropoiesis Portosystemic shunts Gilbert syndrome
Hematoma Drugs - Rifamycin, Neonatal physiologic
rifampin, probenecid jaundice
Breast milk jaundice
Liver diseases - Chronic
hepatitis, cirrhosis, and
Wilson disease

Clinical features
Ineffective erythropoiesis:
• Onset of asymptomatic jaundice
Crigler-Najjar (CN) syndrome type 1:
• Jaundice develops in the first few days of life and rapidly progresses by
the second week; patients may present with evidence of kernicterus,
manifestations as hypotonia, deafness, oculomotor palsy, lethargy and,
ultimately, death
Crigler-Najjar syndrome type 2:
• Usually, no clinical symptoms are reported with this disease entity
Gilbert syndrome :
• May manifest only as jaundice; at least 30% of patients are asymptomatic,
although nonspecific symptoms, such as abdominal cramps, fatigue, and
malaise, are common
Physiologic neonatal jaundice
• Clinically obvious in 50% of neonates during the first 5 days of life
Nonphysiologic neonatal jaundice
• Maternal serum jaundice (Lucey-Driscoll syndrome), it causes a transient
familial neonatal unconjugated hyperbilirubinemia, and jaundice occurs
during the first 4 days of life
Diagnosis
Crigler-Najjar syndrome type 1
• High serum unconjugated bilirubin levels, the results of liver tests is
normal.
• Conjugated bilirubin is absent from serum, and bilirubin is not present in
urine.
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• Bile from duodenum is light yellow because of small amounts of
unconjugated bilirubin. Bilirubin conjugates are nearly absent from the
bile.
• Lower bilirubin concentrations than does type I
• Higher bilirubin levels may be seen if coexisting hemolysis or intercurrent
illness is present.
• Distinguished from type 1 by chromatographic analysis of pigments
excreted in bile. bile contains significant amounts of conjugated bilirubin
Liver function testing
Liver enzyme levels are usually within the reference range. May be elevated, as a
result of intrahepatic cholestasis.

Percutaneous liver biopsy
Liver biopsy reveals normal histology. Bile is sometimes observed in the portal
triad, in dilated bile canaliculi, in hepatocytes, and in Kupffer cells.
Enzymatic assay of liver tissue reveals absent UGT activity in Crigler-Najjar
syndrome type 1 and diminished activity in Crigler-Najjar syndrome type 2.

Gilbert Syndrome
As a rule, Gilbert syndrome can be diagnosed by a thorough history and physical
examination and confirmed by standard blood tests.
• Hyperbilirubinemia is the only biochemical serum abnormality in Gilbert
syndrome.
• A polymerase chain reaction (PCR) - may be used as a screening test.
• A complete blood count (CBC), including a reticulocyte count and a blood
smear, is a useful screening test for excluding hemolysis.
• Increase in serum alkaline phosphatase (ALP)
Physiologic jaundice
In physiologic jaundice, the peak total serum bilirubin level is 5-6 mg/dL (86-
103 µmol/L), occurs at age 48-120 hours, and does not exceed 17-18 mg/dL
(291-308 µmol/L).

In breast milk jaundice, the bilirubin can increase to levels as high as 20 mg/dL,
necessitating the need for phototherapy and the discontinuation of
breastfeeding.

Increased production of bilirubin
Ineffective erythropoiesis (ELB production) is characterized by a marked
increase in fecal urobilinogen excretion and a normal or near-normal red blood
cell lifespan

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Treatment

• phenobarbital, ursodeoxycholic acid, calcium (infusions),
metalloporphyrins, cholestyramine, chlorpromazine, and alkalinization of
urine.
• Metalloporphyrins have been used as a synthetic analogue of heme to
inhibit the heme oxygenase enzyme, the rate-limiting step in heme
catabolism to bilirubin.
• Tin mesoporphyrin (SnMp) is the drug of choice (DOC) for clinical use
because of its increased potency, stability, and photophysical properties.

Gilbert syndrome, no medical therapy is needed.

Crigler-Najjar syndrome type 2,phenobarbital has been shown to decrease
bilirubin production.

Phototherapy and the discontinuation of breastfeeding.

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1c. Side effects of longterm treatment with
corticosteroids and preventions possibillities
Definition
The majority of side effects related to corticosteroid therapy, are a direct
consequence of the physiological effects of the drugs. The key to reducing side
effects is to use the lowest dose needed for the shortest possible duration.
Generally corticosteroid therapy can be indicated in:
o Allergy
o Asthma
o Post-transplantation
o Immune suppression
o Inflammation
o Familial hyperaldosteronism type 1
o Heart failure

Side Effects
• Immunodeficiency
o By suppression of the immune system

• Infection
o Opportunistic infections are more likely to develop in
immunocompromised patients. Therefore appropriate diagnostics,
antimicrobial treatment and supportive measures are keys to
successful management in patients receiving corticosteroid
therapy.

• Hyperglycemia
o Promoting breakdown of amino acids to glucose, while inhibiting
the action of insulin can lead to hyperglycemia, insulin resistance
and diabetes mellitus type 2.

• Osteoporosis
o Serious side effect due to increased risk of bone fractures followed
by decreased bone density.
o Corticosteroids will ↑osteoclast activity, ↓osteoblast activity
o If steroid therapy is given for more than 3 months, bone protective
therapy should be indicated.
§ Vitamin D
§ Calcium supplements
§ Bisphosphonates

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• Peptic Ulcer
o Increased risk of peptic ulcers can occur in response to therapy,
reacting with NSAID’s and increasing gastrointestinal side effects.
• Metabolic
o Corticosteroids cause movement of body fat to the face and torso,
resulting in moon face (secondary cushing’s syndrome).
o ↑Amino acid breakdown to glucose

• Hypertension and Peripheral edema
o Direct action on the kidneys
o ↑Sodium retention causing
§ Fluid retention
§ Hypertension
§ Peripheral edema

• Other side effects include
o Decreased growth in children
o Glaucoma
o Hirsutism (increased hair growth)
o Increased appetite
o Emotional disturbances – Euphoria/Depression
o Hypokalemia

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2a. Pneumonia in Older Children

Definition
Pneumonia is an infection of the lower respiratory tract that involves the
airways and parenchyma. According to morphology pneumonia can be classified
as:
• Bronchopneumonia – a patchy consolidation involving one or several

lobes
• Lobar pneumonia – classically involve the entire lung lobe relatively
homogenously.
• Interstitial pneumonia - inflammatory process predominantly involving
the interstitium, including the alveolar walls and the connective tissue
around the bronchoalveolar tree.
Etiology
It is caused by a variety of bacteria, but in up to 50% of cases no causative
pathogen is identified. In general, viruses more common in younger, while
bacteria are more common in older children. Transmissions are often airborne
droplets. Other causative agents could be aspiration of food and gastric acid,
congenital or foreign bodies.
• Older children >5years:

o Respiratory viruses
§ RSV
§ Influenza
§ Adenovirus
§ Parainfluenza
o Bacterial agents
§ Mycoplasma Pneumoniae
§ Strep. Pneumoniae
§ Chlamydia Pneumoniae
§ Mycobacterium Tuberculosis
§ Hemophilus Influenza
o Environmental factors:
§ Gender, (boys are more affected than girls)
§ Parental smoking (secondhand smoke)
§ Prematurity
§ Congenital abnormalities of heart and lungs

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Clinical features

Viral Bacterial
General Fever, chills, cough, High fever, chills, cough,
sputum, tachypnea, sputum, leukocytosis, chest
increased work of pain, tachypnea,
breathing restlessness, anxiety

• Cough is the prototype symptom in older children
• Localized chest, abdominal, or neck pain is a feature of pleural irritation
and suggests bacterial infection.
• Use of accessory muscles (SCM)
• In older children splinting on affected side with kneed drawn towards the
chest is typical.
Age Normal respiratory rate Tachypnea

Child <5 20-30 >40
Preschool age 3-6 22-34 >40
School age 6-12 18-30 >40
Adolescent 12-18 12-16 >20

Diagnosis
• History (Hx): age, immunization, symptomology
• Physical examination: Signs of respiratory distress, tachypnea, SpO2,
cyanosis, tachycardia (10Bpm every 1°C of fever)
o Auscultation: decreased breath sounds, crackles
o Percussion: dull
• Laboratory:
o CBC, CRP, ESR↑, lactate (Lymphocyte↑ - viral, neutrophils↑ -
bacterial)
o Cultivation – sputum, pleural fluids, blood, throat swab
o ABG/SpO2
o PCR (mostly for viral agents)
o Serology (mycoplasma IgM,IgG)

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• Chest x-ray (Cxr):
o May confirm the diagnosis but cannot differentiate between viral
and bacterial infection.
o Findings:
§ Typical lobar infiltrates, parapneumonic effusions
§ cavities containing fluid and air is characteristic of staph.
pneumonia
§ patchy, peripheral consolidation – viral pneumonia
§ lobar consolidation – bacterial infection
§ perihilar infiltrates – mycoplasma infection
§ pleural effusion, emphysema – reveals complications
o In case of serious disease, such as pleural abscess CT chest can be
utilized

Treatment
Most cases can be managed at home, but indications for admission include: SaO2
<93%, severe tachypnea and dyspnea, grunting, apnea, not feeding. Viral
infections can be prevented by vaccination.

• General: Fluid replacement – avoid over hydration, O2 (maintained
>92%), antipyretics, analgesics, expectorant, bronchodilators, zinc –
accelerate recovery from severe pneumonia
• Children >5years:
o Mycoplasma pneumonae is more common in this age group
§ First line treatment: Amoxicillin, consider macrolide
antibiotics if mycoplasma or chlamydia
§ Second line treatment: Staph. Aureus, consider using
macrolide or combination of flucloxacillin + amoxicillin
o Severe pneumonia
§ Co-amoxyclav, cefotaxime or cefuroxime IV

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2b. Conjugated Hyperbilirubinemia
Definition
Bilirubin is highly water-insoluble and therefor must be conjugated before
eliminated in urine and feces. High levels of bilirubin causes jaundice, yellow
discoloration of skin, sclera and mucous membranes.
Etiology

Common Uncommon
Hyperalimentation cholestasis Hepatic infarction
CMV infection Inborn errors of metabolism
(galactosemia, tyrosinemia)
Perinatal congenital infections Cystic fibrosis
(TORCH)
Inspissated bile from prolonged Biliary atresia
hemolysis
Neonatal hepatitis Choledochal cyst
Sepsis Neonatal iron storage disease

Classification
1. Hepatocellular jaundice
A condition, which is characterized by jaundice due to injury or damage to the
hepatocellular cells of the liver. Liver is not able to utilize bilirubin, resulting in it
accumulating in the blood.
• Infection: TORCH, Hep (A, B, C, E), Listeriosis, sepsis
• Drugs: paracetamol, valproic acid, isoniazide,rifampicin, halothane
• Metabolic disease: Galactosemia, glycogen storage disease, alpha-1
antitrypsin deficiency, neonatal hemosiderosis and wilsons disease.
2. Obstructive jaundice
Impaired excretion of bilirubin, leading to impaired bile flow to the intestine. It is
blocked and remains in the bloodstream. This might be due to blocked bile ducts
caused by gallstones, or tumors of the bile duct which can block the area where
the bile duct meets the duodenum. It could either be intrahepatic or
extrahepatic.
• Lab: ↑ALP, ↑GGT, ALT/AST normal
• CF: hyperlipidemia, pruritus, malabsorption of fat and vitamins.
• Stool: cholic
• Urine: contains bilirubin

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A. Intrahepatic cholestasis
Idiopathic neonatal hepatitis

Idiopathic neonatal cholestasis is a general term for inflammation of the liver. It
occurs shortly after birth in newborns (less than 3 months of age). But there is
an inflammation and dilation of intrahepatic bile ducts.
• Etiology: The specific cause of the problem cannot be identified.
• CF: jaundice, hepatosplenomegaly, dark urine, greyish stool from lack of
bile, other: poor growth, irritability and itching. Failure to thrive
• Dg: Blood test, CT, MR of liver and bile duct, liver biopsy – giant cell
transformation of hepatocyte
• Tx: No specific treatment, supportive, medication to stimulate bile flow,
vitamins A, D, E and K
• Prognosis: 80% recover, 20% develop liver cirrhosis and other liver
diseases.

Alagille syndrome
Alagille syndrome is a genetic disorder that can affect the liver, heart, skeleton
and kidneys. Liver damage is caused by abnormalities in the bile ducts,
narrowing, malformation, and reduced in number. As a result, bile builds up in
the liver and causes scarring that prevent the liver from eliminating wastes from
the bloodstream
• CF: Jaundice, pruritus, xanthomas, facial dysmorphy: triangular face, wide
forehead, pointed chin, abnormalities in blood vessels, cyst in kidney,
hepatomegaly, hypoplasia of small bile ducts.
• Dg: ↑↑ALP, liver biopsy
• Tx: Cholesyramine, phenobarbital

Byler disease
Progressive familial intrahepatic cholestasis (PFIC) is a class of chronic
cholestasis disorders that begin in infancy and usually progress to cirrhosis
within the first decade of life. The average age at onset is 3 months, although
some patients do not develop jaundice until later, even as late as adolescence
• CF: Failure to thrive, fat malabsorption, vitamin deficiency, rickets,
pruritus, jaundice, hepatomegaly, liver cirrhosis.
• Tx: With severe cirrhosis liver transplant is indicated.
B. Extrahepatic cholestasis
Cholestasis occurring outside the liver, caused by blockage of a bile duct or ducts.
It may be caused by a tumor or stricture, a gallstone , biliary atresia or other
damage in the duct, pancreatitis.

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3. Metabolic hyperbilirubinemia
A. Dubin-Johnson syndrome
Dubin-Johnson syndrome is an inherited, relapsing, benign disorder of bilirubin
metabolism. This rare autosomal recessive condition is characterized by
conjugated hyperbilirubinemia with normal liver transaminases, a unique
pattern of urinary excretion of heme metabolites (coproporphyrins), and the
deposition of a pigment that gives the liver a characteristic black color
• CF: Asymptomatic in most cases, but could have: nonpuritic jaundice,
nonspecific right upper quadrant pain, hepatosplenomegaly
• Dg: ↑ conjugated bilirubin, normal liver values, increase in the ratio of
urinary coproporphyrin I to coproporphyrin III, hepatobiliary
scintigraphy scans
• Tx: no specific treatment, generally good prognosis
B. Caroli disease
A rare congenital disorders of the intrahepatic bile ducts, characterized by
dilatation of the intrahepatic biliary tree. The term Caroli disease is applied if the
disease is limited to ectasia or segmental dilatation of the larger intrahepatic
ducts. This form is less common than Caroli syndrome, in which malformations
of small bile ducts and congenital hepatic fibrosis are also present
• CF: bilestasis, bilestone, cholangitis, portal hypertension, hematemesis or
melena due to bleeding varices, ascites due to portal hypertension.
• Most (64%) patients who have portal hypertension have autosomal
recessive polycystic kidney disease (ARPKD)
• Tx: ATB
Diagnosis
• Hx: Family, oversea travel, medication, blood transfusion, urine/stool
• Direct-reacting hyperbilirubinemia is predominantly conjugated
bilirubin, levels >2 mg/dL or >20% of the total bilirubin is considered
pathological.
• Evaluation of liver enzymes (aspartate aminotransferase, alkaline
phosphatase, alanine aminotransferase, and γ-glutamyl transpeptidase)
• Blood: CBC, CRP, ESR • Bacterial and viral cultures
• Serology, PCR • Hepatic ultrasound
• USG, MRCP • Liver biopsy
Treatment
• Treat underlying cause
• Correct abnormality – hypoglycemia, clotting abnormality, supplement of
vitamin ADEK
• Phototherapy for unconjugated bilirubinemia
• Treatment of anemia
• Treatment of liver failure

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2c. Defects in Metabolism of Carbohydrates
(Galaktosemia, Fructose Disorders, Glycogenoses

Definition
Carbohydrates account for a major portion of the human diet and are
metabolized into three groups of monosaccharaides:
• Galaktose
• Fructose
• Glucose
Failure to effectively use these molecules account for majority of inborn errors of
carbohydrate metabolism. Affected children are usually born with normal length
and weight, and without complications during pregnancy
Clinical findings
• Vomiting • Failure to thrive
• Lethargy • Cardiomyopathy
• Convulsions • Metabolic acidosis and
• Coma hypoglycemia
• Liver disease (hepatomegaly,
cholestasis with jaundice)

Inborn errors of metabolism should always be considered in every severely ill
neonate

1. Classical Galactosemia
• Deficiency of galactose-1-phoshphate uridyl transferase
• Autoimmune recessive inheritance
o ↑amount of lactose, leading to accumulation of galactose-1-
phosphate that is toxic to kidneys, liver and brain
Clinical features
Usually symptoms are progressive after start of dairy milk (day 3-4)
Acute Chronic
Vomiting Hepatic and renal failure
Diarrhea Increasing bilateral cataract
Jaundice Mental retardation (storage of galactose metabolites)
Impaired liver functions Ovarian dysfunction with abnormal pubertal development
Sepsis (often E-coli)

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Diagnosis Treatment
• Neonatal screening • Lactose free infant formula
• Reducing substances in urine • Restricted diet free from
• Enzyme studies in RBC’s lactose and galactose
• Hypoglycemia, albuminuria throughout lifespan
• Ketones in urine • Galactosemia is contra-
• Mutation analysis indication for breast feeding
2. Hereditary fructose intolerance

• Autoimmune recessive inheritance caused by mutation in ALDOb gene,
causing defect in enzyme Aldolase B
o Infants are healthy until they ingest fructose
Clinical features
• Vomiting
• Apathy
• Coma
• Progressive liver dysfunction with hepatosplenomegaly
• Hypoglycemia
• Renal tubular dysfunction (secondary Fanconi syndrome)
• Failure to thrive
Diagnosis Treatment
• Urine • Strict fructose restricted diet
o Positive reducing • Vitamin supplements
substances (screening)
o Renal tubular damage
• Hypoglycemia, liver
dysfunction
• Mutation analysis – 3 common
mutations

3. Glycogen storage disease

• Is a result of defects in the processing of glycogen synthesis or breakdown
within muscles, liver, and other cell types.
• Hereditary deficiency of one of the enzymes involved in
synthesis/degradation of glycogen
Etiology
• Genetic (inborn errors of metabolism)
• Acquired (intoxication with alkaloid castanospermine)

Classification
• Hepatic forms
• Myopathic forms
• Mixed myopathic and hepatic forms
A) Hepatic forms
• Type 1 (Von Gierke’s disease)
• Type 4 (Andersen disease)
• Type 6 (Her’s disease)
• Type 8 (Tarui’s disease)
• Deficiency of hepatic enzymes involved in glycogen
• Storage of glycogen in liver and ↓blood glucose
Clinical features Prognosis
Hepatomegaly Type 1 is poor, Death occur due to
hypoglycemia and lactic acidosis
Hypoglycemia
B) Myopathic forms
• Type 2 (Pompe’s Disease)
• Type 5 (McArdle)
• Results from deficiency of enzymes of the glycolytic pathway in muscles
• Increased glycogen in muscles
Muscle weakness Good prognosis
Cramps Bad prognosis for type 2 (Pompe)
Failure of lactate levels to rise after
exercise

C) Mixed myopathic and hepatic forms

• Type 3 (Cori’s disease)
• Has features of both 1 and 2

Hypoglycemia Good prognosis
Core muscle weakness
Hepatomegaly

Glycogen storage disease type 1 – Von Gierke’s Disease

• Most common type of glycogen storage disease
• Impairs liver to produce glucose from glycogen
• Causes severe hypoglycemia and increased glycogen levels in kidney and
liver
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Clinical features
• Hypoglycemia
• Hepatomegaly
• Lactic acidosis
• Hyperuricemia
• Enlargement of kidneys
• Impaired platelet aggregation
Diagnosis
• Monitored fasting
• Blood test (ABG, glycemia, fatty acids,
• Definite diagnosis by liver biopsy

Treatment
• Prevention of hypoglycemia
• Dietary compensation for inability of liver to produce glucose
• Diet 60-70% carbohydrates

Glycogen storage disease type 2 – Pompe’s Disease

• Autosomal recessive
• Damages muscle and nerve cell throughout the body
• Caused by accumulation of glycogen in lysosomal enzymes
Clinical features
• Cardiomegaly
• Hypotonia
• Cardiomyopathy
• Respiratory distress
• Muscle weakness
• Feeding difficulties
• Failure to thrive

Diagnosis
• Chest X-ray
• ECG, Echocardiography

Treatment
• Cardiac and respiratory complications are treated symptomatically
• If left untreated this disease is lethal

21

3a. Tuberculosis
Definition
Tuberculosis is a chronic necrotizing granulomatous disease caused by acid-fast
bacilli. The most common site of disease is the lung, and the most common extra-
pulmonary sites are the lymph nodes, pleura, bone and joints. TB is a major
cause of morbidity and mortality worldwide
Etiology and Transmission

Airborne infection, spread by respiratory droplets. Usually from adult to
children. Young children rarely spread infection because they rarely produce
sputum while coughing.

• Mycobacterium tuberculosis • Mycobacterium avium
• Mycobacterium bovis • Mycobacterium chelonei
Risk factors
• Children exposed to air droplets from adults with tuberculosis
• Harmless and malnourished children
• IV drug abusers
• HIV/AIDS
• Immunosuppression – transplantation, drugs, DM, CKD and malignancy
Pathogenesis
The causative organism is a slender, non-motile, non-spore- forming, non-toxin
producing bacillus. It is called “acid-fast” due to the waxy coat of organism.
Stained by specific Ziehl-Neelsen method.
• Bacilli enter the lung by air droplets, the bacilli become ingested by
alveolar macrophages in which they proliferate
• Macrophages present Ags to T-lymphocytes causing cellular immune
response. The interaction between the macrophage and the T-cells causes
granuloma formation in which the m.tuberculosis lays dormant.
• The initial lesion is called «Ghon complex» (primary complex). A small
pulmonary parenchymal lesion and a large hilar lymphadenitis.
• The parenchymal portion of the primary complex often heals completely
by fibrosis or calcification after undergoing caseous necrosis.
• The regional lymph nodes develop some caseous necrosis and fibrosis,
but heal less completely. Viable bacteria can persist in this focus for years
– latent tuberculosis.
• Following shortly after initial infection, infants and young children
usually develop tuberculosis
• The time between latent infection and disease is variable from several
weeks to years.
• Reactivation tuberculosis that occurs less than a years after primary
infection (due to reactivation of bacteria in foci) is rare in children but is
common in adolescents and young adults.
22

Clinical features
1. Primary pulmonary tuberculosis
• Asymptomatic in older infants and children
• Malaise, low-grade fewer, erythema nodosum (hypersensitivity 4)
• Failure to thrive, dyspnea, non-productive cough, wheezing (bronchial
obstruction by enlarged lymph nodes)
2. Progressive primary tuberculosis

• Rare complication in young children and HIV patients
• Progressive enlargement of primary focus and liquefaction occurs
• Evacuated into the adjacent bronchus – cavity formation
• High fever, sputum production, cough, weight loss
• ↓ breath sounds, rhales, hyper resonant percussion over cavitation
3. Reactivation tuberculosis
• Primary TB followed by a period of clinical latency
• Common in adolescents
• The pulmonary lesion is usually confined to the apical segments of upper
lobes – cavitation and endobrochial spread of bacilli
• Cough, hemoptysis, chest pain, pleural effusion (pleuritic pain), weight
loss, fever, night sweats
• Hyper resonant percussion above cavitation, wheezing, ↓ breath sounds
4. Extra pulmonary tuberculosis

• Lymph-node tuberculosis (mycobacterial lymphadenitis - scrofula)
• Includes cervical, supraclavicular and submandibular lymph-nodes.
• Lymph-nodes are non-tender and firm
• Usually unilateral
• Low-grade fever
5. Tuberculosis meningitis
• Serious complication of tuberculosis
• Brainstem often involved
• Common in children less than 5 years
• Meningeal irritation
6. Skeletal tuberculosis
• Tuberculosis of the spine (Potts disease), hip, fingers and toes
7. Miliary tuberculosis
• Common complication in infants and young children
• Hematogenous spread, dissemination of bacili to various organs (liver,
spleen, CNS and adrenals.
• Fever, malaise, weight loss, lymphadenopathy, hepatosplenomegaly

23

Diagnosis
• CXR features of TB:
o Primary TB: Small patchy opacities in the midlung fields (Ghon
complex) , often with large unilateral hilar lymphadenitis (Ranke
complex) minor pulmonary lesion, large cavitation
o Reactivation TB: Typically, lesions are found in the apical and
posterior segments of the upper lobes and the superior segments
of the lower lobe. This is a progression from patchy opacities and
consolidation to cavitation.

• Tuberculin skin test - TST (mantoux)
A tuberculin purified protein derivative (PDD) is used to elict delayed
hypersensitivity reaction. PPD is injected intradermaly and reaction is
assessed after 48-72 hours. Positive test indicate mycobacterial infection
or need for vaccination.
• 0-5mm à negative • False pos à prev BCG vac

• 6-14mm à positive • False neg à immune
• >15mm à strong positive suppressed

• Interferon gamma release assay (INF γ assay)
Alternative test with TST. It measures INF γ produced by T-cells in
response to M. Tuberculosis. High specificity not present in BCG and most
non-tuberculous mycobacteria.

• Culture of sputum/biopsy material
Acid-fast staining with Ziehl-Neelsen

• Miliary TB • Meningitis TB
o CT/ blood culture o CSF and MRI

24

Treatment

The cornerstone of TB treatment is multidrug therapy. This is necessary
because M. tuberculosis undergoes spontaneous mutation to drug resistance at a
frequency such that most patients with cavity lung disease, and therefore a high
burden of organism, are likely to harbor resistant mutants.

Isolation – isolate patients with possible TB infection in a private room with
negative pressure (so that the air is exhausted to the outside). Medical staff must
wear high-efficiency disposable masks sufficient to filter the tuberculous
bacillus. Continue isolation until sputum smears are negative for 3 consecutive
determinations (usually after 2-4 weeks of therapy).
Drug therapy:
• Initial therapy –4-drug regimen: isoniazid, rifampin, pyrazinamide, and
either ethambutol or streptomycin
• After 2 months – in fully susceptible isolate, pyrazinamide can be stopped.
Isoniazid and rifampin are continued as daily or intermittent therapy for 4
months. If isoniazid resistance is, discontinue isoniazid and continue
treatment with rifampin, pyrazinamide, and ethambutol for the entire 6
months.
• In patients with CNS, bones, joints and miliary TB – continue multidrug
treatment for up to 9-12 months.
• Prevention: BCG vaccination
Monitoring – patients diagnosed with TB should undergo sputum analysis for
Mycobacterium tuberculosis weekly until sputum conversion is documented.
Monitoring for toxicity includes liver enzymes, CBC and serum creatinine.
Adverse effect of drugs:
Pyrazinamide – toxic hepatitis, hyperuricemic gout
Rifampicin: toxic hepatitis, renal failure, pink secretions
Isoniazide: toxic neuritis, hepatitis
Ethambutol: optic neuritis with color blindness

25

3b. Nausea and Vomiting in Children
Definition
• Nausea is the sensation of unease and discomfort in the upper part of the
abdomen with the involuntary urge to vomit. Frequently accompanied by
autonomic changes such as tachycardia and ↑salivation.

• Vomiting (emesis) is forceful oral emptying of gastric contents. This is a
highly coordinated reflex process by the vomit center in medulla, that is
activated by afferent pathways from the following systems:
• Digestive system • Non-digestive systems
o Pharynx o Heat
o Stomach o Testis
o Small intestine o Sensitive CNS centers
o Vestibular system
Etiology
Many conditions may lead to nausea and vomiting, and most often it is a benign
result of feeding disorders, mild gastroesophageal reflux or gastroenteritis.
Causes of vomiting:

Infants Preschool Children School age/Adolescents
Gastroesophageal reflux (most Gastroenteritis (most common) Gastroenteritis (most

common) common)
Gastroenteritis Infections Infections
Infections Intestinal obstruction Peptic ulcer disease
Intestinal obstruction Inborn errors of metabolism Diabetic ketoacidosis
Inborn errors of metabolism Celiac disease Celiac disease
Feeding problems Appendicitis Appendicitis
Protein intolerance Increased intracranial pressure Alcohol/Drugs /Pregnancy
Torsion of testes Torsion of testes

Diagnosis
• History (Hx): Past symptoms, ingested food
• Physical examination: Inspection, dehydration, electrolyte disbalance,
abdominal distention
• Laboratory:
o CRP
o Electrolytes
o ABG/SpO2 /pH

26

Newborn/Infants:
• Viral gastroenteritis
o Associated with diarrhea and low grade fever
o Examination of stools (viral antigen - adeno/rota)

• Bacterial gastroenteritis
o Associated with dysentery
o Bloody diarrhea, pain, abdominal distention, high fever

• Gastroesophageal reflux disorder (GERD)
o Usually occurs during or after feeding
o Recurrent respiratory symptoms (cough, stridor, wheezing)
o Esophageal pH monitoring

• Congenital obstructive lesions
Pyloric stenosis Intestinal atresia Intussiception Hirshprung disease

Recurrent Bilious emesis Colic pain Aganglionic

projectle vomiting within 24-48h of Red currant jelly megacolon
after feeding life stool
Affects infants <4 Abdominal Lethargy Delayed passage og
months distention meconium within
24h
Diagnosis: Polyhydramnion Red currant jelly Abdominal
Ultrasound of during
stool distention
pylorus, jaundice pregnancy
Diagnosis: Bilious/feculent
Ultrasound, vomit
irrigography
with contrast
Diagnosis :
X-ray, contrast
enema, rectal
biopsy

• Food allergies
o Abdominal pain
o Diarrhea
o Diagnosis: IgE detection

27

• Inborn errors of metabolism
o Poor feeding
o Failure to thrive
o Lethargy
o Hepatosplenomegaly
o Jaundice
o Hypotonia
o Seizures
o Diagnosis: Electrolytes, glucose, newborn screening, genetic
analysis

• Systemic infection
o Associated with fever, lethargy, dysuria
o Diagnosis: CBC, ESR, CRP, blood culture, X-ray
Children/Adolescents:
• Viral/bacterial gastroenteritis
• Extra GI infections (otitis media, UTI, pneumonia)
• Appendicitis
• CNS diseases
• Meningitis
o Nuchal rigidity, photo/phonophobia, fever, CSF + PE
• Cyclic vomiting syndrome
o Three episodes of severe nausea with intermittent vomiting
interrupted by symptom free intervals
o Exclude metabolic, GIT or other CNS diseases

28

3c. Prematurity and Low Birth Weights complications
and consequences
Definition
Infants delivered before 37 weeks are termed premature. Low birth weight
(under 2500g) is due to prematurity or intrauterine growth restriction (IUGR).
Prematurity and IUGR are associated with increased neonatal morbidity and
mortality.

VLBW – very low birth weight (<1500gr) are predominantly premature, and is a
good predictor of infant mortality rate. VLBW accounts for over 50% of neonatal
deaths and 50% of handicapped infants.

Extreme preterm Very preterm Moderate to late preterm
< 28 weeks 28 up to 32 weeks 32 up to 37 weeks

Risk factors

Hypertension Smoking Placental abruption/
Diabetes mellitus Psychological stress preavia
Multiple gestation Low maternal BMI
Maternal infection Maternal celiac dx

Complications
1. Intraventricular hemorrhage
Characterized by bleeding from the immature capillary bed of the germinal
matrix lining the ventricles.

Classification
Grade 1 Grade 2 Grade 3 Grade 4
Hemorrhage Bleeding also Ventricles are Bleeding extends
confined to occurs inside the enlarged by the into the brain
germinal matrix ventricles, but accumulated tissue around the
they are not blood ventricle –
enlarged associated with
hydrocephalus

Risk factors Clinical findings Diagnosis Treatment
Birth <32w Bleeding occurs Cranial USG No specific
Weight <1500g within the first treatment
Asphyxia 48h after birth Grade 1 and 2
Hypoxia usually resorbs
Hypotension without problems
29

2. Periventrucular leukomalcia
Periventricular leukomalacia (PVL) is the most common ischemic brain injury in
premature infants. Premature infants with periventricular leukomalacia can
develop cerebral palsy (CP), intellectual impairment, or visual disturbances.
• Increased risk for preterm before 32w and birth weight under 1500g
• Ischemic necrosis of the white matter surrounding the lateral ventricles
could occurs due to immature, thin blood vessels and hypertension
• It´s diagnosed by cranial USG, usually 4-6th week of age.
3. Retinopathy of prematurity
Caused by the effects of 02 toxicity on the developing blood vessels of the
premature infants retina. It is the leading cause of blindness in infants <1500g
• CF:
o Persistent hypoxia à obliteration of retinal periphery, which can
cause bleeding
o Retinal detachment and cataract
o Photophobia
• Tx
o Laser treatment for hemorrhage or progressive vasoproliferation
o Surgery for retinal detachment
o Proper 02 administration can prevent retinopathy.

4. Neonatal respiratory distress syndrome (RDS)

Occurs after onset of breathing and is associated with insufficiency of pulmonary
surfactants. It is a hyaline membrane disease.
• Increased risk for infants born <32w
• Surfactant is normally produced by type 2 pneumocytes and prevents
atelectasis by reducing surface tension at low lung volumes.
• In hylaine membrane disease, patient have micro atelectasis à
hypoxemia and respiratory distress syndrome
• Cyanosis, flaring, tachypnea, chest wall retractions, grunting)
• Tx:
o Corticosteroids to mother to induce lung maturation
o Surfactants
5. Bronchopulmonary dysplasia (BDP)

Bronchopulmonary dysplasia is a form of chronic lung disease that develops in
preterm neonates treated with oxygen and positive-pressure ventilation
• Results from combination of lung immaturity
• 02 toxicity
• ventilator induced lung injury and inflammatory lung injury
• Tx: 02, bronchodilator, corticosteroids, pulmonary rehab.

30

6. Patent ductus arteriosus
Patent ductus arteriosus (PDA), in which there is a persistent communication
between the descending thoracic aorta and the pulmonary artery that results
from failure of normal physiologic closure of the fetal ductus, is one of the more
common congenital heart defects. It is common in premature infants with RDS.
• Creates a left – right shunt – acyanotic
• Continuous, machinery like murmurs (syst/dia)
• Tx.
o Indomethacin, ibuprofen – (PGE sensitive vessel)
o Surgical ligation
7. Hypoglycemia
Hypoglycemia is a common clinical problem in neonates, is less common in
infants and toddlers, and is rare in older children. It can be caused by various
conditions
• Result of decreased glycogen storage and increased glucose requirements
• Could cause seizures and neurologic damage
8. Unconjugated hyperbilirubinemia
Common due to immature liver enzymes and short life of RBC and increased RBC
mass.
• Tx.
o Phototherapy, exchange transfusion
• Increased risk for kernicterus due to decreased albumin/ immature blood
brain barrier
9. Necrotizing enterocolitis
Uncommon inflammatory process in the bowel wall that can lead to necrosis
o Primary seen in premature infants, but can also occur in infants with LBW
o May be caused by low BP, hypoxia and infection. It is associated with
formula feeding

Clinical finding Diagnisis Treatment
o Apnea X-ray o TPN

o Bradycardia o Pneumatosis o ATB
o Abdominal wall intestinalis o Surgery
distention o pneumoperitoneum

31

4a. Acute Bronchitis and Bronchiolitis
1. Acute Bronchitis
Definition
Clinical syndrome produced by inflammation of trachea, large bronchi (medium
and large sized airways) with/without obstruction with the predominant feature
of cough.
Etiology
Generally caused by viruses (>90%), and the rest are bacterial agents (primary
or secondary due to URTI)
• Viruses • Bacterial agents

o Adenovirus o Strep. pneumonia
o Influenza o Chlamydia pneumonia
o Parainfluenza o H. Influenza
o RSV o Mycoplasma
o Rhinovirus pneumonia
Risk factors
• Maternal smoking (during pregnancy)
• Preterm delivery with bronchipulmonary dysplasia
• Chronic cardiac or respiratory diseases (congenital heart disease)
• Allergies and immunodeficiency
Clinical features
• Sneezing
• Clear rhinorrhea
• Worsen over 2-3 days
o Fever
o Tachypnea
o Sharp, dry cough
o Expiratory wheezing
o Dyspnea ↑
o Poor feeding
Normal respiratory rate Tachypnea
Fever ↑breathing effort with costal muscles, nasal flaring
Tachypnea Hyperinflation of the chest
Sharp, dry cough Fine crackles
Expiratory wheezing Prolonged expiratory duration
Dyspnea Tachycardia
Poor feeding Cyanosis/pallor
Diagnosis
• Chest X-ray • ABG
• ELISA/PCR • Serology
32

Treatment
Supportive with
• O2
• Fluid IV
• Bronchodilators
• Ribavirin to patient with congenital defects or immunocompromised
patients

2. Acute Bronchiolitis
Definition
An Acute Inflammation of the bronchioles (small airways), which is usually
caused by viral infection.
Etiology
Usually secondary due to a viral URTI
• Viruses
o RSV (most common >50%)
o Adenovirus
o Influenza
o Rhinovirus
Clinical features
o Initial symptoms– nonspecific URTI symptoms
• After 3 days • Severe symptoms
o Dry cough o Poor feeding
with/without sputum o Lethargy
o Chest pain o Tachypnea
o Low-grade fever o Cyanosis
o Coarse, fine crackles
and wheezes
Diagnosis
• Chest X-ray, with exclusion of pneumonia

Treatment
Disease is self-limited
• Analgesics
• Antihistamines
• Cough suppressors


4b. Differential diagnosis of Hepatosplenomegaly
Hepatomegaly
Definition
Enlargement of the liver that indicate either primary liver disease or secondary
to a systemic disease. Confirmed by palpation, percussion and imaging methods.
Etiology
• Inflammation
• Excessive storage
• Infiltration
• Congestion
• Biliary obstruction
1. Inflammation
Hepatocyte enlargement Kupfer cell enlargement
Hepatitis • Sepsis • Sarcoidosis
• Autoimmune • Abscess • SLE
• Viral • Cholangitis
• Drug induced

2. Excessive storage
Fat Glycogen Other
Diabetes Glycogen storage disease ∝-antitrypsin deficiency
Obesity TPN Wilson’s disease
Metabolic liver disease Neonatal iron storage disease

3. Infiltration
Benign tumors Malignant tumors
Adenoma Hepatocellular carcinoma
Hamartoma Secondary tumor
Hemangioma
4. Congestive disease
• Congestive heart failure
• Cardiac tamponade
• Constrictive pericarditis
• Hepatic vein thrombosis
5. Biliary obstruction
• Congenital hepatic fibrosis
• Carroli’s disease
• Alargille syndrome
• Extrahepatic obstruction
34


Diagnosis
• History (Hx): Infection, Heart diseases, Drugs, IEM
• Physical examination: Palpation (liver edge), Percussion
• Other signs: jaundice, ascites, spider nevi
• Laboratory:
o Liver function test o Viral marker
o CBC o Coagulation factors
o Tumor marker o Copper level
• Stool/Urine:
o Bilirubin
• Imaging:
o Ultrasound
o CT/MRI
o Liver biopsy
Splenomegaly
Definition
Refers to enlarged size of the spleen and usually due to systemic conditions
rather than splenic disease. Diagnosis same as hepatomegaly.
Etiology
• Infection
o Viral (CMV, Hep A,B,C, EBV, HIV)
o Bacterial (Syphilis, TB, Staph. Aureus)
o Protozoa (Malaria)
• Hematological
• Hemolysis
• Chronic iron deficiency
• Extramedullary hematopoesis
o Polycythemia vera
o Myelofibrosis
• Malignancy
o Leukemia/lymphoma/metastatic tumor
• Inflammatory process
o SLE, Sjogrens syndrome, Amyloidosis, Sarcoidosis
• Portal hypertension
o Hepatitis A
o Inborn errors of metabolism
o Metabolic liver disease
• Storage disease
o Galactosemia, fructose intolerance, Gaucher lipodosis
35

Hepatosplenomegaly
Definition
Enlargement of both liver and spleen
Etiology
• Infection • Metabolic
o Acute liver hepatitis o Niemann-Pick disease
o Mononucleosis o Gaucher’s disease
o CMV o Hurler’s yndrome
o Rubella • Metabolic liver disease
o Malaria • Portal hypertension
o Typhoid fever • Amyloidosis/Sarcoidosis
• Hematological • Acromegaly
o Myeloproliferative • SLE
disease • Obesity
o Lymphoma
o Leukemia
o Pernicious anemia

o Sickle cell anemia
o Thalassemia

36

4c. Congenital viral and bacterial newborn’s infections
(TORCH, GBS, E-coli)
Definition
An infection acquired transplacentally during gestation , could cause intrauterine
infections or congenital infections.

The following are common to many of the intrauterine infections: intrauterine
growth restriction, mactocephaly or hydrocephalus, intracranial calcifications,
chorioretinitis, cataracts, myocarditis, pneumonia, hepatosplenomegaly, direct
hyperbilirubinemia, anemia, thrombocytopenia
Etiology
T Toxoplasmosis
O Others: VZV, syphilis, parvovirus, HIV, neisseria, gonorrhea, chlamydia
R Rubella
C Cytomegalo virus
H Herpes simplex virus
Timing
• 1st trimester: congenital malformations, early spontaneous abortion
• 2nd trimester: active infant at time of delivery, manifestations may be
delayed
Clinical features
Intrauterine growth restriction (IUGR) Hepatosplenomegaly
Hydrops fetalis Congenital malformations
Anemia Premature / stillbirth
Thrombocytopenia Spontaneus abortion
Jaundice
Diseases
1. Toxoplasmosis
Transplacental transmission of Toxoplasma gondii after acute maternal
infection. Infection is most probably after exposure to cat feces or raw meat
• RF: 2nd trimester (10-24 week of gestation) has the highest risk for
adverse outcome
• CF: 90% are asymptomatic
o Hydrocephalus o Hepatosplenomegaly
o Chorioretinitis o Jaundice
o Diffuse cortical o Macrulopapular rash
calcification
• Dg:
o Serology o PCR for T. gondii
• Tx:
o Pyrimethamine and sufadiazine (up to 1 year)
37

2. Rubella
Rare in developed countries due to MMR vaccination. Presents in unimmunized
mother with fever and/or rash.
• RF: Risk of congenital defect is seen in 1st trimester
o 85% - 1st 8 weeks
o 50% - 9th – 12th week
o This could result in spontaneous or still birth
o Infection after 4 months of gestation doesn’t cause disease
• CF:
o Patent ductus arteriosus o Sen.neural hearing loss
o Cataract o Encephalitis
o Glaucoma o Retardation
• Dg:
o Serology
o Isolation of virus, trace blood, urine, CSF and PCR
• Tx: Maternal vaccination and prophylactic IVIG to mother after exposure
3. Cytomegalovirus
Most common congenital infection, it is considered number one cause of
sensorineural hearing loss, retardation, retinal disease and cerebral palsy.
• Transmission: Sexual, contact with young children
• CF: 90% asymptomatic
o Microcephaly o Periventricular
o Retardation complications
o Thrombocytopenia o Hepatosplenomegaly
o Anemia o Chorioretinitis
o Blueberry muffin rash o Hearing abnormalities
• Dg:
o Cultivation of saliva/urine
o PCR of urine – detect CMV DNA
• Tx: Ganciclovir
4. Herpes simplex virus

Infection by Herpex simplex 2 virus, acquired shortly before or during passage
through birth canal of infected mother.
• Classification
o Localised: skin, eyes, mouth, CNS
o Disseminated: multi organs, liver, lungs
• CF:
o Asymptomatic at birth
o Symptomatic 5-10 o Intrauterine infection
days after delivery § Microcephaly
§ Encephalitis § Choreoretinitis
§ Skin vesicles § Skin lesion
§ Conjunctivitis
• Tx: Acyclovir
38

5. Varicella zoster virus
Congenital malformation occur with maternal infection in 1st week of gestation
§ CF:
o Zigzag skin scaling o Rash Occur in children with
infected mothers 5
o Microcephaly o Pneumonia days before to 2 days
o Hydrocephalus o Hepatitis after delivery
o Cataract o Death
o Chorioretinitis
§ Dg:
o Virus isolation
o PCR, specific IgG
§ Tx:
o Varicella zoster Ig for prevention
o Acyclovir
6. Syphilis
Transplacental infection by Treponema pallidum, but also during delivery
(contact with syphilis chancre)
• CF:
Early Late
Hydrops fetalis Hutchindon triad
Stillbirth, prematurity Intestinal keratitis
Rhinitis, pneumonia, anemia Hutchinson incisor (N VIII – deafness)
Hepatosplenomegaly Saddle nose, swollen knee
Osteochondritis
• Dg:
o Serology
o PE, scraping
• Tx:
o PNC IV – if infection before 5 days prior to delivery (milder
disease)
o IgG Ab – if transplacental
7. GBS
8. E.coli

39

5a. Bronchial Asthma
Definition
Chronic inflammatory disorder of the airways resulting in episodes of reversible
bronchospasm causing airflow obstruction. It is one of the most common
pediatric pulmonary diseases. Associated with:
• Airflow limitation
• Airway hyper-responsiveness
• Inflammation of the bronchi
Etiology
• Genetic predisposition
• Sensitizers
o Allergens (pollen, dust)
o Cigarette smoke
• Triggers
o Infections
o Stress (exercise, dry/cold climate)
o Chemicals, drugs (aspirin)
o Food (shellfish, nuts)

Pathophysiology
• Eosinophilic inflammation
• Bronchial hyperreactivity/airway hyperresponsiveness
• Reversible airway obstruction
o Smooth muscle spasm in the small airways
o Mucosal edema
o Mucous hypersecretion

Clinical features
Worse at night, early morning

• Wheezing • Fatigue
• Dyspnea • Hyperinflation of chest
• Tachypnea • Tachycardia
o 2-5years >50b/min o 2-5years >130bpm
o >5years >30b/min o >5years >120bpm
• Cough • Prolonged expiratory phase
• Breathlessness • Expiratory stridor
• Cyanosis

40


Diagnosis
• History (Hx)
• Physical examination: Auscultation, skin pricle test
• Laboratory:
o ABG (SaO2)
o Eosinophils
o Specific IgE

• Imaging:
o X-ray (only to rule out other options)
o Spirometry

Treatment
Aim of treatment is to achieve and maintain clinical control
• Bronchodilator
o SABA – salbutamol
o LABA – salmeterol
o Ipratropium bromide
• Inhaled corticosteroids
o Buderonide (with salmeterol)
o Beclomethasone
• Leukotriene antagonist
o Montelukast
• 5-lipooxygenase inhibitor
o Zileuton
• Methylxanthines
o Theophylline
• Monoclonal antibody
o Anti IgE - omalizumab
• Antihistamine

41

5b. Differential diagnosis of Haematuria
Definition
Hematuria is defined as presence of blood in urine, it can further be divided into
macroscopic or microscopic hematuria, in macroscopic hematuria you will find
pink or red colored urin, while in microscopic hematuria there must be 5 or
more RBC in the visual field of the microscope.
Etiology
Glomerular Non-glomerular
Acute post strep. GN Renal tubules
IgA nephropathy Interstitial tissue
Henoch-Shonlein purpura Rest of urinary tract
Alport syndrome Exercise
Thin basement membrane nephropathy Drug
Rapid progressive GN Hematological disease
Lupus nephritis

Glomerular hematuria: erythrocytes pass through damaged filtration site of
glomeryli that deform the shape of the erythrocytes - acantocyte
Glomerular diseases
1. Acute post streptococcal glomerulonephritis
• Gen: Developes 2-3 weeks after sterptococcal infection (strep. throat)
• Eti: Deposition of Ag-Ab complex in the kidney
• CF: Nephritic syndrome, malaise, fatigue
• Dg: ASLO positive, decreased complement (C3)
2. Ig A nephropathy
• Gen: Common cause of hematuria in children
• Eti: Deposition of IgA in kidney, is associated with hyper cellularity
• CF: Hematuria in 1-2 days after inset of URTI
• Dg: Renal biopsy, normal C3
3. Henoch-Schonlein purpura
• Gen: Systemic vasculitis with IgA depositions
• Eti: Renal involvement in 50%, deposition of IgA
• CF: Triad of purpuric rash, arthritis and abdominal pain and hematuria,
proteinuria
4. Alport syndrome
• Gen: x-linked AR/AD inherited, mutation of collagen IV
• Eti: Defect in collagen biosynthesis, which is an important structural
component of the basement membrane in kidney, eyes and ears
• CF: Glomerulonephritis – End stage renal disease, hearing loss, ocular
manifestation, hematuria, proteinuria

42

5. Thin basement membrane nephropathy
• Gen: Common cause of hematuria, benign familial hematuria. AR/AD
inherited, associated with mutations of collagen IV
• CF: Microscopic hematuria, asymptomatic, no kidney involvement, no
systemic manifestation.
6. Rapid progressive glomerulonephritis

• Gen: Glomerulonephritis associated with rapid ↓kidney function
• Eti: Type 1 – Anti-GMB Ab – good pasture syndrome
o Type 2 – Immune complex – SLE, post infection
o Type 3 – ANCA – Wegeners granulomatosis
• CF: Rapid loss of renal funtion
o Oliguria, anuria
o Hematuria, proteinuria
o Hypertension, edema
7. Lupus nephritis
• Gen: Inflammation of kidney caused by SLE
• CF: Hematuria, proteinuria, hypertension, fever, edema
Non-glomerular diseases
1. Renal tumor/cyst
• Gen: Wilms tumor with flank pain, hematuria, abdominal mass
2. Urinary tract infection

• Gen: common cause of hematuria
• Pyelonephritis, urethritis, cystitis
• CF: dysuria, fever, flank pain, foul-smelling urin
3. Nephrolithiasis
• Gen: Struvute, phosphate, uric acid, calciumoxalate, cystine form stones.
• CF: colicky pain, nausea and vomiting
• Dg: X-ray, USG
4. Hypercalcuria
• Gen: increased Ca2+ in urine
• Eti: Hyperparathyroidism, immobilization, vit D intox, bone lesions
5. Drugs
• Gen: Anticoagulants, aspirin, chlorpromazine
Diagnosis
• Hx and PE, Urinalysis – dipstick, culture
• Lab: CBC, kidney function test
• Serology: Ab, complement, c3, c4, ANA, ANCA, ASLO, Ig
• Imaging: USG
• Renal biopsy
43

5c. Cutaneous infections in Children
Childhood Exanthems
Definition
A skin interruption occurring as a symptom of a general disease
Exanthem – Eruptive lesion on the mucous membrane
1. Measles/Rubeola
Etiology
• Inflammation caused by paramyxovirus
• Airborne transmission through cough/sneeze
• Incidence in preschool children without vaccination
Risk factors
• Immunosuppression
• Corticosteroid therapy
• Alkylating agents
• HIV
Clinical features
Prodrome Exanthematous Other
Fever (4day fever) Viremia 5-7days Anorexia
Cough Maculopapular rash Diarrhea
Coryza (head cold, fever, sneezing)
Conjuctivitis
Koplik spots
Complications
• Otitis media
• Pneumonia
• Sub acute sclerosing panencephalitis
• Myocarditis
Diagnosis
• Physical examination: Koplik spots
• Laboratory:
o ↓WBC and lymphocytes
o ↑AST/ALT
o Serology – IgM (viral)
o PCR
Treatment
Supportive treatment
• Vitamin A
• MMR Vaccine
44

2. Scarlet Fever
Etiology
• Inflammation caused by Group A strep
• Characterized by erythematous rash that may occur with streptococcal
pharyngitis
Clinical features
Fever (abrupt onset) Red tongue (strawberry tongue)
Headache Widespread rash
Vomiting Erythematous pharynx
Malaise Exudative tonsillitis
Sore throat Uvular edema
Diagnosis
• Throat swab: culture
o Anti Streptolysine O
Treatment
Complications
• Antibiotics:
• Otitis media
o Penicillin
• Abscess
o Erythromycin
• Sinusitis
• Rheumatic fever
• Acute glomerulonephritis

3. German Measles/Rubella
Etiology
• Disease that occur in childhood/adolescent during winter/spring
• Caused by rubella virus (togavirus)
• Congenital rubella syndrome caused by TORCH
Clinical features
Fever (low grade) Malaise Maculopapular rash in the face
Lymphadenopathy Sore throat
Diagnosis
o Clinical findings
o Serology

Complications Treatment
Arthritis/arthralgia Supportive treatment
Thrombocytopenia Prevention with MMR vaccine
Myocarditis
Encephalitis
45

4. Erythema Infectiosum
Etiology
• Inflammation caused by parvovirus B19
• Usually affects school age
Clinical features
Mild fever
Headache
Malaise
Sore throat
Bright red macules on face (slapped cheek appearance)
Diagnosis
• Clinical findings
• Serology

Arthritis/arthralgia Supportive treatment
Anemia
Thrombocytopenia

5. Impetigo Contagiosa
Etiology
• Superficial cutaneous infection caused by Strep. pyogenes or Staph.
Aureus
Clinical features
Honey colored crust covered lesions on hands and face
Often superimposed as atopic dermatitis/acne
Treatment
• Remove crust lesions
• Topical antibiotics
o Fucidin

46

6. Roseola Infantum
Etiology
• Inflammation caused by human herpes virus 6,7 (roseolovirus)
• Benign, self-limiting
• Usually affects children 6months-3years
Clinical features
High fever 3-4 days
Rash
Seizures (febrile)
Diarrhea
Diagnosis
• History
• Clinical findings

Aseptic meningitis Symptomatic treatment
Encephalitis Antipyretics
Hepatitis

7. Erysipelas & Cellulitis

Etiology
• Caused by Strep. pyogenes or Staph. Aureus
Clinical features
Cellulitis Erysipelas
• Raised, hot, tender • Superficial variant of cellulitis
erythematous area of skin • Bright red, edematous
• Fever, leukocytosis
Treatment
• Antibiotics: Penicillin

47

6a. Cystic Fibrosis
Definition
Cystic fibrosis (CF) is an autosomal recessive disorder than is most common life-
limiting genetic disorder among Caucasians (1:20 carriers). A gene located on
chromosome 7 codes for the protein cystic fibrosis transmembrane regulator
(CFTR), which is defective in CF.
Etiology
CFTR: cystic fibrosis transmembrane conductance
Progressive lung regulator.
Mutatuin of CFTR
damage • Expressed on the epithelial cells of airways,

• GIT, sweat gland and genitourinary system
Malabsorption • 1600-2000 mutations
• Delta F508 – deletion of phenylalanie at AA 508
Pancreatic • 5 classes:
insufsiciency o CL 1: lack of CFTR protein production
o CL 2: defect in protein transportation
Nasal polyposis o CL 3: defect in CFTR activation
o CL 4: ↓chloride transport though CFTR
o CL 5: ↓ production of CFTR
Hepatopathy

Pathogenesis
• Normally CFTR protein facilitates cAMP dep. Cl- conductance
• In epithelial cells (GIT, lung, GUT) there is movement of Cl- out of the cells
to the lumen
• In sweat glands, there is movement of Cl- from ductus into the cells
• In CF, epithelial cells secrete ↓Cl- and reabsorbs ↑Na+
• H2O moves inside cells together with Na+ which leads to ↓ luminal
hydration. This results in viscous mucous, biliary and pancreatic
secretions
• The CF cells in sweat gland ducts cannot reabsorb Na+ and Cl-
• Salt is found in ductus and transported to skin
Clinical features
1. Respiratory tract
• Recurrent respiratory tract infections
o S. aureus (MRSA) o P. Aeuruginosa
o H. Influenza o B. Cepacia complex
• Bronchitis, bronchiolitis, bronchiectasis, pneumonia
• Chronic sinusitis, nasal polyps
• Pneumothorax, cor pulmonale, respiratory failure
• Chronic productive cough, hemoptysis, digital dubbing, dyspnea,
wheezing, crackles, FTT, nasal obstruction, rhinolalia
48

2. Gastrointestinal tract
• Meconium ileus, meconium peritonitis, meconium plugs in neonates
• Distal intestinal obstruction syndrome in older children
• Pancreatitis, hepatic stenosis, billiary cirrhosis
• Volvulus, invagination, rectal prolapse
• Malabsorption, steatorrhea, diarrhea, vit ADEK deficiency
• Endocrine pancreatic insufficiency
3. Genitourinary tract
• Delayed puberty
• Male infertility – CBAVD
• Amenorrhea
• Cervicitis
4. Metabolic
• Hyperchloremic alkalosis – due to excessive Na+ loss
• Osteoporosis

Diagnosis

1. Newborn screening: measure immunoreactive trypsinogen (IRT)
2. Sweat test: chemical analysis of Cl- in sweat
• >60mmol/L – positive
• 40-60mmol/L – borderline
• <40mmol/L – negative
3. DNA testing – confirm CFTR mutation

Diagnostic criteria
Typical cystic fibrosis 2 elevated sweat test results on separate days
Family history of cystic fibrosis + Identification of 2 CF mutations
Positive newborn screening Abnormal nasal potential difference

49

Treatment
The main goal of treatment is to prevent progression of lung disease and to
maintain adequate nutrition and growth
1. Airway clearance
• Chest physio therapy
• Bronchodilators: albuterol, ipratropium bromide, inhalatory
corticosteroids
• Human recombinant dornase α: pulmozym
• Nebilized hypertonic saline inhalation
2. Antibiotics
• Ciprofloxacin (po. 28days)
• Tobramycin/kolistin (inhalation – 3months)
3. Nutrition
• Vit A,D,E,K supplement
• Pancreatic enzyme supplement: creon
• Diet: low fat, high calories, proteins
• Enteral nutrition (nasogastric tube, PEG)
4. Others
• Ursodecholic acid (UDCA): to prevent liver disease
• Insulin
• Salt supplement
• Surgery: meconium ileus, distal intestinal obstruction syndrome, nasal
polyps
5. Lung transplant
• End stage of CF
• Vienna/Prague
• No cure, help live longer

50

6b. Differential diagnosis of Proteinuria
Definition
Excessive protein in urine, defined as more than 150mg/24hours
Detection
• Easily done by urine dipstick test – Cheap, convenient, sensitive method
• Primarily detect albumin in the urine, less sensitive for other proteins.
Types of proteinuria

Glomerular Tubular Other
Selective Transient
Non-selective Orthostatic
Overflow
24 hour urinary protein excretion

Normal <30mg/24h
Microalbuminuria 30-300mg/24h
Proteinuria >300mg/24h
1.Tubular proteinuria
• Interstitial nephritis
• Analgesic nephropathy
• Chronic glomerulonephritis, associated with vesicourethral reflux
2. Glomerular proteinuria
• Proteinuria due to dysfunction of the glomerulus
Classification
Depending on the degree of damage of the glomeruli
• Selective
o Small molecular weight proteins – Albumin
• Non-selective
o Large molecular weight proteins – Immunoglobulins

Nephrotic syndrome
• Nephrotic proteinuria >50g/kg/day
• Hypoalbuminemia <25g/L

51

A) Selective proteinuria
Etiology

Congenital nephrotic Primary nephrotic syndrome Secondary nephrotic syndrome
syndrome
• Mutation of nephrin • IgA nephropathy • Diabetic neuropathy
• Minimal change disease • SLE
• Focal segmental • Henoch-Schonlein purpura
glomerulonephritis • Acute-poststreptococcal
• Membranous nephropathy glomerulonephritis
• Membranoproliferative
glomerulonephritis
B) Non-selective proteinuria
• Idiopathic nephrotic syndrome
• Chronic glomerulonephritis
• Alport syndrome (abnormal structure on glomerular basement
membrane)
3.Other
A) Transient
• Child present with proteinuria on dipstick
o Repeated rest – normal findings
Etiology Clinical Symptoms
Fever Proteinuria is mild
Exercise Glomerular in origin
Dehydration Resolve in few days
Cold exposure
Heart failure
Stress
B) Orthostatic
• Normal excretion
• In supine position, but significant proteinuria when upright
• Eti: associated with hemodynamic changes
C) Overflow
• Associated with increased productions of immunoglobulins lightchain
that are reabsorptive capacity of tubules
• Etiology
o Multiple myeloma
o Monoclonal gammapathy
52

6c. Primary and secondary immunodeficiencies (AIDS)
Definition
Reduced ability of the immune systems to fight infections. The immune system is
compromised or entirely absent

Immunodeficiency can be categorized as:
• Primary immunodeficiency: congenital
• Secondary immunodeficiency: acquired
Immune system:
• Ab mediated/B-cell immunity
• Cell mediated/T-cell immunity
• Phagocytosis
• Complement system
Suggestive of immunodeficiency
• Infections are chronic, severe or recurrent
• Infections resolve partially with ATB treatment and reoccur after ATB is
seponated
• Organism of infection is atypical or opportunistic
Classification
1. Phagocyte/neutrophil defect:
• Deep skin infection, abscess, osteomyelitis
• S.aureus, S.pyogenes
2. B cell defect/ Ab defect
• Infection with pyogenic bacteria
3. T-cell defect
• Infection with fungal, protozoa, intracellular microorganism (bac,vir)
4. Complement pathway:
• ↓ Nonspecific immunity, ↑ autoimmune disease (SLE, RA)
Types
B cell / Ab defect
1. X-linked agammaglobulinemia (Brutons disease)
• Gen: Defect in gene that encodes a cytoplasmic enzyme burton tyrosine
kinase. Absence of BTK cause failure of B-cells to mature and secrete Ig
• All five classes of Ig are affected, total Ig <2,5g/L
o Very low IgG and no IgM, IgA, IgD, IgE
o No Abs are formed after vaccination
o No B-cells (CD19) in peripheral blood
o Normal T cells

53

• CF:
o Recurrent pyogenic infection – begin 5-6 months of age
§ Otitis media, bronchitis, meningitis
§ Maternal IgG are catabolized
§ Recurrent episodes of diarrhea (salmonella, shigella)
• Tx:
o IVIG – 0,2g/kg once a month
o ATB for infection

2. Transient hypogammaglobinemia
• Gen: At birth an infants has serum IgG, this IgG is from the mother,
because maternal IgG is actively transported across the placenta to the
fetal circulation. Maximum transfer take place during the final 2 months.
• Between 3-6 months – physiological hypoglobulinemia, catabolism of
maternal IgG is only partly compensated by IgG synthesis by newborn
child.
• Only IgG can cross placenta, if IgM/IgA is found in cord blood, that is due
to premature Ab synthesis
• CF: RTI can occur
• Tx: Only symptomatic treatment and ATB, no IVIG

3. Selective IgA deficiency
• Gen: low levels of IgA (<0,05g/L) with normal levels of other Ig. It is a cell
mediated immunity (normal)
• CF: Increased association with:
o Allergies
o Recurrent URTI
o GIT disease
o Autoimmune disease
T cell deficiency
1. Di George syndrome
• Gen: It is a combined immunodeficiency, velocardio facial syndrome
• Eti: microdeletion at chromosome 22q11.2. Developmental defect
involving 3rd and 4th pharyngeal pouch.
o Congenital aplasia/hypoplasia of thymus and parathyroid gland
o Lymphopenia: decreased number of T-cells and decreased
function
• CF:
o Dysmorphic face, low-set ears, fish shaped mouth, micrognathia
o Hypoparathyroidism with hypocalcaemia within 24h of life –
tetany
o Congenital heart disease/ congestive HF
o Decreased cellular immunity, recurrent/chronic infections with
fungus, virus and protozoa
54

• Dg:
o Blood: ↓Ca2+, ↑P3+, absence of parathoromone
o Lateral x-ray: absent thymic shadow
o T-cells decreased in numbers
o ECHO, ECG
• Tx:
o Manage hypocalcemia
o Surgery for CHD
o Fetal thymus or bone marrow transplant
Phagocyte defect
1. Chronic granulomatous disease
• Gen: X-linked inheritance, inherited defect of NADPH oxidase enzyme
complex.
o Functional defect in the respiratory burst in PMNL and Mo
o Patients are unable to kill microorganism
• CF:
o Infection with opportunistic agents: s.epidermidis, serratia
within 1-2 year of life
o Active suppurative lymphadenitis (neck, axilla, groin), liver
abscess, osteomyelitis, skin sepsis.
o Fungal infection is difficult to treat, could lead to death
• Dg:
o Nitroblue tetrazolium test: measure ability of immune system to
convert the solution to blue color. In case of CGD the immune
system will not be able to convert the color, so it is colorless due to
lack of NADPH oxidase.
• Tx: prophylaxis
o ATB
o Antifungal
o INF gamma
o Bone marrow transplant
Secondary immuno deficiency

1. Immunosuppressive disease
2. AIDS/HIV
3. Acquired neutropenia: lymphomas, leukemia, hyper-splenism,
autoimmunity
HIV/AIDS
HIV: single stranded RNA virus of the retrovirus family, produce reverse
trancriptase that describes the viral RNA into DNA which can then be integrated
into the gost genome.
Types:
• HIV 1 – 99%
• HIV 2
55

• HIV infection is a progressive process with a variable period of latency
before the development of AIDS.
Transmission:
• Horizontal: blood, body fluids
• Vertical: from mother to infant
o Transplacentally
o During birth
o By breast feeding
Pathogenesis:
• HIV infects cells that express CD4 (especially T-helper cells) and cell of
the macrophage lineage (monocyte, dendritic cells).
• After the virus enter the cytoplasm, its RNA is reversely transcribed into
DNA which then becomes integrated into the host DNA.
• Virus is formed and leaved the cell to infect other cells
o Virus causes lutic infection of T-helper cells
o T-cytotoxic cells (CD8) are critical for controlling the disease (kill
infectious cells)
o As the disease progresses, the number of CD4 cells decreases,
activation of CD8 cells decreases and Ab production of B cells
decreases.
Clinical findings
• Adolescents: it results in the acute retroviral syndrome after 2-6 weeks of
incubation
o Fever, malaise, pharyngitis, LAD, maculopapular rash
• Infants: FFT, LAD, neuro developmental delay, hepatoplenomegaly,
diarrhea.
Classification
• Category N • Category B
• Category A • Category C
Category N - asymptomatic
• Children are asymptomatic or have one feature of category A
Category A – mildly symptomatic
• > of the following features:
o LAD o Dermatitis
o Hepatomegaly o Recurrent/persistent
o Splenomegaly URTI
o Parotitis

Category B – moderately symptomatic
• Recurrent/chronic diarrhea
• Fever lasting longer than 1 month
56

• Oropharyngeal candidasis longer than 2 months
• Bacterial meningitis
• Pneumonia
• Sepsis
• Anemia
• Neutropenia
• Thrombocytopenia
Category C – severely symptomatic
• Opportunistic infection:
o Pneumocystis pneumonia, LRT candidasis, cryptococcus, cerebral
toxoplasmos, disseminated bacterial/CMV infections
• Recurrent bacterial infections
o Sepsis, meningitis, pneumonia
• Encephalopathy
• Malignancy: Kaposi sarcoma, lymphoma
• Wasting syndrome
o Weight loss more than 10%
o Chronic diarrhea for more than a1 month
o Fever lasting more than 1 month
According to the levels of CD4 and total lymphocyte count
• Category 1 – no suppression
• Category 2 – moderate
• Category 3 – severe
Diagnosis
• HIV DNA PCR – 1 month of age
• HIV RNA PCR – 2-3 months
• Anti HIV IgA/IgM – after 18months
Treatment
• HAART
o Zidovudine – dual reverse transcriptase inhibitor
o Ritonavir – protease inhibitor
Indication
• All infants <12 months
• All children 1-5 years in categories C and some of B
• All children > 1-5 years with AIDS or clinical categories C and B, CD4
count < 200cells/mm3
Without treatment vertically infected children progress to AIDS within 5 months
Horizontally infected children progress to AIDS within 7-10 years
57

7a. Critical Heart diseases
Definition
Critical heart diseases are defined as congenital diseases or malformations of the
heart leading to life threatening symtoms
Diseases
Right to left shunt Left to right shunt
• Tetralogy of fallot • Aortic stenosis
• Transposition of great vessels • Pulmonary stenosis
• Tricuspid atresia • Coarctation of aorta
• Truncus arteriosus
• Total anomalous pulmonary venous return
A. Congenital heart diseases with Right to left shunt

1. Tetralogy of Fallot
Definition
• 10% of congenital heart diseases – most common cyanotic CHD.
Includes
• Ventricular septal defect
• Pulmonary stenosis
• Aorta overrides ventricular septal defect
• Right ventricular hypertrophy
Clinical findings Diagnosis Treatment

Pink tetralogy of fallot • ECG: Right • Complete surgical
• Mild pulmonary stenosis – Left to right shunt ventricular repair – ventricular
with or without cyanosis hypertrophy, right septal defect closure,
axis deviation pulmonary stenosis
Classic tetralogy of fallot
• Severe pulmonary stenosis – Right to left shunt • X-ray: Boot • Prophylaxis for
with cyanosis shaped heart, infective
translucency of endocarditis with
• Tachypnea/dyspnea
pulmonary vessels ATB’s until 6months
• Clubbing of fingers and toes
• Echo: Definitive after surgery
• Systolic murmur
diagnosis • Hypoxic spells – O2
• Tet spells
and propranolol
o Rapid drop in amount of oxygen in blood

o Cyanosis after crying, feeding or when
agitated
o Syncope, convulsions or death may
follow
58

2. Transposition of great vessels
Definition
• 5% of congenital heart diseases. There are separations of the systemic
and pulmonary circulation and death occurs quickly


• Central cyanosis • ECG: Right ventricular • Prostaglandin E to
• Tachypnea and tachycardia hypertrophy, right maintain ductal patency
• Signs of heart failure and axis deviation • Artificial dilation of
metabolic acidosis • X-ray: Pulmonary septal via surgery
vascularity • Correct MAC
• ECHO • Complete surgical repair

3. Tricuspid atresia
Definition
• 2% of Congenital heart defects. Absence of tricuspid valve leading to a
hypoplastic right ventricle
• A patent ductus arteriosus/ventricular septal defect and arterial septal defect
is necessary for survical
• Arterial septal defect moves blood back into systemic circulation while PDA
and VSD enable pulmonary circulation

• Severe cyanosis • ECG: Left ventricular • Prostaglandin E to
• Poor feeding hypertrophy, left axis maintain ductal patency
• Holocystolic murmur deviation • Subclavian artery to
• Tachypnea • X-ray: ↓Pulmonary pulmonary shunt
blood flow • Bidirectional
cavopulmonary shunt

59

4. Truncus arteriosus
Definition
• Developmental failure of separation of truncus arteriosus
• Single great artery arises from both ventricles and gives rise to systemic,
pulmonary and coronary circulation

Clinical findings Treatment

• Cyanosis • Surgical repair
• Heart failure
• Systolic ejection murmur
• Bounding arterial pulse
• VSD below the trunk mixes the
right and left blood
• Cardiomegaly
• Widened pulse pressure

B. Congenital heart diseases with Right to left shunt

1. Aortic stenosis
Definition
• 5% of congenital heart diseases
Types
• Valvular
• Subvalvular
• Supravalvular
• Asymptomatic • ECG: Left ventricular • Balloon valvuloplasty
• Fatigue hypertrophy • Replacement of valve
• Exertional dyspnea • X-ray: post stenotic
• Early systolic click murmur dilation of aorta
• Chest pain
• Syncope

60

2. Pulmonary stenosis
Types
Definition
• Valvular
• 10% of congenital heart
• Subvalvular
diseases
• Supravalvular

• Asymptomatic • ECG: Right ventricular • Balloon valvuloplasty
• Exertional dypnea and fatigue hypertrophy • Replacement of valve
• Systolic ejection murmur • ECHO
3. Coarctation of aorta
Definition
• 10% of congenital heart diseases, obstruction or narrowing of aorta
Types
• Preductal coarctation – infantile form
• Postductal coarctation – adult form
Preductal coartation
• Coarctation before patent ductus arteriosus
• Symptomatic early in life
o Cyanosis – localized to the lower half of the body due to delivery of
deoxygenated blood through patent ductus arteriosus
• Poor feeding • Surgery
• Shock • Prostaglandin E – to keep patent ductus
• Death if untreated arteriosus open
Postductal coartation
• Coarctation after closed patent ductus arteriosus
• Usually asymptomatic

• Leg claudication • Surgical repair
• Cold extremity
• Headache
• Epistaxis
• ↓Blood pressure in lower extremity
• Weak femoral pulse
• Pansystolic murmur – left interscapular area

61

7b. Differential diagnosis of lymphadenopathy
Definition
Defined as enlarged lymph nodes >1cm in diameter
Most common cause of enlarged lymphadenopathy is
o Infection
o Autoimmunity
o Malignancy
Generalized lymphadenopathy
• Enlargement of >2 noncontagious lymph node groups – due to systemic
disease
Localized lymphadenopathy
• Enlargement of 1 lymph node group – due to inflammation of an area
drained by these lymph nodes
Differential diagnosis of generalized lymphadenopathy

Infants Children Adolescents
• Syphilis • Viral infection • Viral infection
• Toxoplasmosis • EBV • EBV
• CMV • Toxoplasmosis • Toxoplasmosis
• CMV • CMV
• HIV • Syphilis
• HIV
Rare causes
• Congenital • Serum sickness • Serum sickness
chagas • SLE • SLE
• Congenital • Juvenile idiopathic • Juvenile idiopathic
leukemia arthritis arthritis
• Congenital TB • Leukemia, lymphoma • Leukemia, lymphoma
• Metabolic • TB • TB
storage disease • Measles • Measles
• Sarcoidosis • Sarcoidosis
• Chronic granulomatous • Chronic granulomatous
disease disease
62

Differential diagnosis of localized lymphadenopathy

Cervical Supraclavicular Ant/post Axillary Inguinal
auricular
• Oropharyngeal inf. • Mediastinal • Otitis media • Lymphoma • UTI
• TB malignancy • Viral inf. • Leukemia • STD
• EBV • Lymphoma • Brucellosis • Perineal
• CMV • TB infection
• Kawasaki disease • Metastatic
• Thyroid disease tumor
Diagnosis
• History (Hx): family history, weight loss, anemia, recurrent infection,
recent RTI, sexual behavior, travel history, social status (TB/HIV)
• Physical examination: Full body examination, local/generalized.
o Erythematous, tender, warm – acute bacterial inf.
o Nonerythematous, tender – systemic/viral inf.
o Firm, hard, nontender, immobile – lymphoma
o Matted lymph node - TB
• Laboratory:
o CBC – lymphocytes, PMNL, anemia, WBC
o Serology – EBV,CMV
• Imaging:
o CT chest – hilar lymphadenopathy
o X-ray
o Biopsy
§ Lymph node - Lymphoma
§ Bone marrow – leukemia, lymphoma
Treatment
Depends on the underlying cause of lymphadenopathy

63

7c. Vaccination – Principles, Schedule
Definition
A biological preparation that improves immunity to a particular disease. It
contains certain agents that resembles a disease causing microorganism and also
stimulates bodies immune system to recognize the foreign agents. It is one of the
most beneficial and cost effective disease prevention measures.

Immunization
• Active (vaccination)
o Administration of an Ag (a modified infectious agent or toxin)
results in active production of immunity
• Passive
o Transfer of the active product of the immune response (Ab,
effector T-cell) from an immune individual to an non immune
recipient.
Types
1. Whole organism – killed/attenuated
2. Purified macromolecules – toxoid, polysaccharide, surface antigen
3. Recombinant vaccine
Whole organism
• Killed/inactivated
o Vaccines that contain killed, but previously virulent
microorganisms that have been destroyed with chemicals, heat,
radioactivity or ATB
o Ex: HEP A, polio (salk), influenza, thyphoid, rabies, cholera,
pertussis
• Attenuated
o Live viruses that have been cultivated under conditions that
disable their virulent properties or which use closely related but
less dangerous organisms to produce a broad immune response
o Ex: Varichella zozter, measles, TB(BCG), mumps, rubella, yellow
fever.
Purified macromolecules
Inactivated toxoids
• Vaccines that consist of exotoxins that have been inactivated either by
heat or chemicals. These vaccines are intended to build immunity against
the toxins, but not necessarily the bacteria that produce the toxin
• Ex: Botulinum antitoxin, diphteria antitoxin

64

Capsular polysaccharide
• The virulence of some pathogenic bacteria depends primarily on the
antiphagocytic properties of their hydrophilic polysaccharide capsule
• Coating of the capsule with antibodies and or complement greatly
increase the ability of macrophages and neutrophils to phagocytose such
pathogens
• Ex: s.pneumoniae, n. Meningitis
Recombinant microbial antigens/ surface antigens

• The gene encoding any immunogenic protein can be cloned and
expressed in bacterial, yeas or mammalian cells using recombinant DNA
technology
• Ex: Hep B
Monoclonal antibody
• Against Respiratory syncytial virus (RSV)
Requirements of vaccine
• Complete protection from the disease caused by infection
• Lifelong protection
• Cause no adverse effect
• Can be given without other vaccines
• Administrated easily without discomfort
• Long storage life
Routs of administration:
• I.M – most inactivated vaccines
• S.C – most live attenuated
• P.O – rotavirus
Schedule
Birth HBV
2 months DTP, HiB, IPV, HBV, PCV
12 months MMR, HiB, MCC
18 months Varicella
4 years DTP, OPV, MMR
10 – 13 years Varicella, HBV – 1 month later, 6 months later
15 – 19 years DTP

Precaution, contraindications and adverse effect

• Anaphylaxis – use adrenaline
• Convulsions
• Local reactions – pain, swelling, redness
• General reactions . fever, head ace, malaise
• Use if improperly sterilized syringe, needle.
65

8a. Congenital Heart diseases with left to right shunt

Definition
• Structural dysfunction or deformity of heart present at birth. Clinically
range form asymptomatic to severe functional deficit and can be life
threatening
Etiology
• Idiopathic
• Multifactorial
o Genetic
§ Chromosomal abnormality (Trisomy 21,18,13, Turner
syndrome, Di George syndrome)
o Environmental
§ Infection during pregnancy – rubella
§ Drug abuse/alcohol
§ Maternal illness – DM/Phenylketonuria
§ Other – obesity or SLE in mother
Classification
Acyanotic Cyanotic
Left to right shunt Obstructive lesions • Right to left shunt
• Atrial septal defect • Coarctation of aorta
• Ventricular septal defect • Arterial stenosis
• Patent ductus arteriosus • Pulmonary stenosis

A) Left to right shunt
1. Atrial septal defects
Definition
• Accounts for 10% of all congenital heart diseases
• Communication of blood from left to right atrium due to atrial septal
opening
Types
• Secundum defect: 90% of cases, located near center of septum
• Primum defect: 5% og cases, located near AV valves
• Sinus venosus defect: 5% of cases, located near superior vena cava

66

• Usually asymptomatic • ECG: Right ventricular • Surgery for primum and
• Can be part of Holt-Oram hypertrophy, right sinus venosus defect
syndrome (Atrial septal defect, axis deviation • Catheter based closure
missing bone in arms) • X-ray: Cardiomegaly, for secundum defects
• Right heart failure – due to engorged pulmonary • ↑risk for paradoxical
volume overload in RV and artery emboli
pulmonary circulation • Echo: Definitive
• Exertional fatigue and dyspnea diagnosis
(recurrent RTI)
• Systolic ejection murmur - ↑flow
through pulmonary valve
• Pulmonary valve closes later
than aortic valve due to
prolonged ejection of blood

2. Ventricular septal defects

Definition
• Most common form of congenital heart disease – 20-25%. Commonly
associated with other congenital heart diseases – opening in ventricular
septum
Types
o Premembranosus ventricular septal defect – 70%
o Supracistal ventricular septal defect
o Muscular ventricular septal defect
• Asymptomatic at birth • ECG: Left ventricular • Small ventricular septal
• Heart failure – fatigue, hypertrophy, defect – usually close
diaphorersis with feeding and biventricular spontaneously within
poor growth hypertrophy 1year
• ↑RTI • X-ray: Cardiomegaly, • Moderate – large
• Murmur – the smaller the defect, engorged pulmonary ventricular septal defect
the louder the murmur artery – Surgical closure
o Pan systolic murmur at • Echo
lower left sternal border
o Palpated as thrill (↑flow
through defect)
o Large shunts – mid
diastolic murmur (↑flow
across mitral valve)
o Splitting of S2
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3. Patent ductus arteriosus
Definition
• Ductus arteriosus remains open after birth leading to blood flow from
aorta to pulmonary artery
• Small shunt – asymptomatic • ECG: Right ventricular • Prostaglandin E2–
• Larger shunt – Heart failure hypertrophy responsible for keep Patent
• Continuous machine like • X-ray: Engorged blood ductus arteriosus
murmur vessel • NSAID’s - ↑patent ductus
• Bounding pulse with widened arteriosus close
pulse pressure • Surgical close –
coiling/clipping

B) Obstructive lesions

1. Coarctation of aorta
Definition
• 10% of congenital heart diseases, obstruction or narrowing of aorta
Types
• Preductal coarctation – infantile form
• Postductal coarctation – adult form
Preductal coartation
• Coarctation before patent ductus arteriosus
• Symptomatic early in life
o Cyanosis – localized to the lower half of the body due to delivery of
deoxygenated blood through patent ductus arteriosus

• Poor feeding • Surgery
• Shock • Prostaglandin E – to keep patent ductus
• Death if untreated arteriosus open
Postductal coartation
• Coarctation after closed patent ductus arteriosus

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• Leg claudication • Surgical repair
• Cold extremity
• Headache
• Epistaxis
• ↓Blood pressure in lower extremity
• Weak femoral pulse
• Pansystolic murmur – left interscapular area
2. Pulmonary stenosis
Definition
Types
• Valvular
• Subvalvular
• Supravalvular

• Asymptomatic • ECG: Right ventricular • Balloon valvuloplasty
• Exertional sypnea and hypertrophy • Replacement of valve
fatigue • ECHO

3. Aortic stenosis
Definition
Types
• Valvular
• Subvalvular
• Supravalvular

• Asymptomatic • ECG: Left ventricular • Balloon valvuloplasty
• Fatigue hypertrophy • Replacement of valve
• Exertional dyspnea • X-ray: post stenotic
• Early systolic click murmur dilation of aorta
• Chect pain
• Syncope

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8b. Differential diagnosis of Unconsciousness
Definition
Consciousness- state of general wakefulness and responsive to environment. In
infants, crying when hungry or getting calmed by mothers voice suggest
consciousness.
Coma- state of deep, sustained, pathologic unconsciousness. The patient shows
no meaningful response to environmental stimuli.
Types
Somnolence Stupor Coma
• Patient is sleepy, • Patient is in deep • In light coma,
but can be state, but can be patient responds to
awakened by voice awakened by painful stimuli,
or touch painful stimuli with reflexes
• In deep coma,
patient no longer
responds to stimuli
Etiology
Structural/intrinsic causes:
Disrupts the brainstem reticular activity system and/or the cerebral
hemispheres
Structural/intrinsic causes
Head trauma Neoplasia CNS infection Vascular disease
• Contusion/concussion • Astrocytoma • Meningitis • Vasculitis
• Diffuse axonal injury • Glioma • Encephalitis • Cerebral
• Epidural hematoma • Abscess hemorrhage
• Empyema or infarction

Metabolic, toxic and other causes:
Disrupts the brainstem reticular activity system and/or the cerebral
hemispheres
Metabolic, toxic and other causes
Metabolic disease Exogenous Paroxysmal Systemic
toxins/drugs disease infection
• Hypoxia/ischemia • Opiates • Epilepsy • Sepsis
• Shock • Antidepressants • Migraine
• CO poisoning • Antiepileptics
• Hyper/hypoglycemia • Cyanide
• Unconjugated • Alcohol
hyperbilirubinemia • Heroine
• Diabetic ketoacidosis
• IEM
• Hepatic/uremic encephalopathy
• Fluid and electrolyte imbalance
70

Clinical approach
• Airway
• Breathing
• Circulation
Pediatric Glascow coma scale

Eye response/opening (1-4) Motor response (1-6) Verbal response (1-5)
• No opening to pain • No response • None
• To pain • Decerebrate • Moans to pain
• To speech extension • Cries to pain
• Spontaneous • Decorticate flexion • Irritable cry
• Withdraws to pain • Babbles
• Withdraws to touch
• Follows commands
• Lowest score 3
• Highest score 15
• Coma ≤ 8
General/neurological examination
Pupillary response Eye movements Respiratory pattern Motor responses
• Systematically small • Show brainstem • Cheyne-strauss • Spontaneous limb
pupils that react to integrity respiration (seen in movement
light are often due to • Occulocephalic reflex metabolic disease and • Appropriate
metabolic/toxic should be present in intoxication) o Withdrawal/grim
causes comatose patients • Central neurogenic acing after
• Symmetrically dilated (absence indicate hyperventilation painful stimuli
pupils that doesn’t brainstem lesion) (↑ICP, head trauma) • Inappropriate
react to light are o Decorticate
caused by (flexion of arms)
hypoxic/ischemic o Deceberate
causes (extension of
• Unilaterally enlarged arms/legs
pupils indicate brain posture)
herniation to one side
Diagnosis
• Physical examination
• Laboratory:
o CBC, CRP, ABG
o ESR
o Blood biochemistry (glucose, electrolytes, creatinine, lactate)
o Liver function (AST, ALT, GGT, albumin, bilirubin)
o Tox screen
Imaging
• CT (faster) • Lumbar puncture
• MRI (better) • EEG
71

8c. Sinusitis, Tonsillitis and Adenoids
1. Sinusitis
Definition
Inflammation of the sinuses
Etiology
o Usually self limited o Strep. pneumonia
o Rhinosinusitis o H. Influenza
§ RSV o M. Catarhalis
§ Rhinovirus o Staph. Aureus

Risk factors
• Viral URTI
• Allergic rhinitis
• Passive smoking
• Immunodeficiency
• Congenital factors
o Ciliary dysfunction
o Cleft palate
Clinical features
Nonspecific symptoms
Nasal congestion Hyposmia
Purulent nasal discharge Periorbital edema
Fever and cough Maxillary tooth discomfort
Halitosis Pain when bending forward
Diagnosis
• Physical examination: URTI
• Sinus aspirate culture
• Transillumination of sinus cavities – detection of fluid
• CT - opacification
Treatment
• Bacterial sinusitis
o ATB’s (7 days)
§ If intracranial complications – IV ceftriaxone
Complications
• Epidural abscess • Subdural empyema
• Meningitis • Brain abscess
• Sinus thrombosis

2. Tonsillitis
Definition
Inflammation of the tonsils – collection of lymphoid tissue
• Waldayer’s lymph ring
o Adenoid tonsil
o 2 tubal tonsils
o 2 palatine tonsils
o Lingual tonsil
Etiology
o Adenovirus o GAS (strep throat)
o Rhinovirus o Staph Aureus
o Influenza o S. pneumonia
o Coronavirus o M. pneumonia
o RSV o B. pertussis
o EBV o C. diphteria
o CMV/HIV o N. gonorrhea
o Treponema pallidum

Clinical features
Sore throat Fever
Red, swollen tonsils Cough
Dysphagia Headache
White pus on tonsils Malaise
Diagnosis
• Swab - culture
• PCR
• Lab: ESR, WBC, CRP
Treatment
• Viral tonsillitis resolve spontaneously (symptomatic treatment)
• Bacterial
o ATB’s: Penicillin, Erythromycin
• Tonsillectomy for chronic tonsillitis
Complications
• Post strep glomerulonephritis
• Acute respiratory failure
• Abscess


3. Adenoid
• Growth of adenoid tonsil in roof of nasopharynx
• Eti:
o EBV
o Allergy
o Environmental triggers
• Dg: Flexible endoscope
• Tx: Adenoidectomy
Nasal obstruction Chronic mouth breathing
Loud snoring Hyponasal speech
Choking Hyposmia
Restless sleep Apnea

74

9a. Congenital Heart diseases with Right to Left Shunt
Definition
• In right to left shunt some of the venous return passes from the right side
of the heart to the left and enters the systemic circulation with or without
going through the lungs
o Cyanosis
§ >50g/L of deoxyhemoglobin in blood
§ Polycythemic patients develop cyanosis faster
§ Anemic patients develop cyanosis later
Diseases
• Tetralogy of fallot
• Transposition of great vessels
• Tricuspid atresia
• Truncus arteriosus
• Total anomalous pulmonary venous return
• Hypoplastic left heart syndrome
• Pulmonary atresia

1. Tetralogy of Fallot
Definition
• 10% of congenital heart diseases – most common cyanotic CHD.
Includes
• Ventricular septal defect
• Pulmonary stenosis
• Aorta overrides ventricular septal defect
• Right ventricular hypertrophy
Pink tetralogy of fallot • ECG: Right • Complete surgical
• Mild pulmonary stenosis – Left to right shunt with ventricular repair – ventricular
or without cyanosis hypertrophy, right septal defect closure,
axis deviation pulmonary stenosis
Classic tetralogy of fallot
• X-ray: Boot shaped • Prophylaxis for
• Severe pulmonary stenosis – Right to left shunt with
heart, translucency infective endocarditis
cyanosis
of pulmonary with ATB’s until
• Tachypnea/dyspnea
vessels 6months after surgery
• Clubbing of fingers and toes
• Echo: Definitive • Hypoxic spells – O2 and
• Systolic murmur
diagnosis propranolol
• Tet spells

o Rapid drop in amount of oxygen in blood
o Cyanosis after crying, feeding or when
agitated
o Syncope, convulsions or death may follow
75

2. Transposition of great vessels
Definition
• 5% of congenital heart diseases. There are separations of the systemic
and pulmonary circulation and death occurs quickly

• Central cyanosis • ECG: Right ventricular • Prostaglandin E to
• Tachypnea and tachycardia hypertrophy, right maintain ductal patency
• Signs of heart failure and axis deviation • Artificial dilation of
metabolic acidosis • X-ray: Pulmonary septal via surgery
vascularity • Correct MAC
• ECHO • Complete surgical repair
3. Tricuspid atresia
Definition
• 2% of Congenital heart defects. Absence of tricuspid valve leading to a
hypoplastic right ventricle
• A patent ductus arteriosus/ventricular septal defect and arterial septal defect
is necessary for survival
• Arterial septal defect moves blood back into systemic circulation while PDA
and VSD enable pulmonary circulation

• Severe cyanosis • ECG: Left ventricular • Prostaglandin E to
• Poor feeding hypertrophy, left axis maintain ductal patency
• Holocystolic murmur deviation • Subclavian artery to
• Tachypnea • X-ray: ↓Pulmonary pulmonary shunt
blood flow • Bidirectional
cavopulmonary shunt

4. Truncus arteriosus
Definition
• Developmental failure of separation of truncus arteriosus
• Single great artery arises from both ventricles and gives rise to systemic,
pulmonary and coronary circulation
• Cyanosis • Surgical repair
• Heart failure
• Bounding arterial pulse
• VSD below the trunk mixes the right and left blood
• Cardiomegaly
76

5. Total anomalous pulmonary venous return
Definition
• Rare defect where child’s pulmonary veins don’t connect normally to the
left atrium. Redirected to the right atrium by an abnormal connection.
Condition leading to less O2 than the body needs.
• Atrial septal defect present to survive – allows mixed blood to get to the
left side of the heart and out to the rest of the body
Types (based on location of abnormal connection)

• Supracardiac
• Cardiac
• Infracardiac

• Cyanosis • USG - prenatally • Surgery
• Dyspnea • ECG
• Weak pulse • X-ray
• Poor feeding • ECHO
• Pounding heart

• Murmur

6. Hypoplastic left heart syndrome

Definition
• Group of anomalies that include underdevelopment of the left side of the
heart
• Neonate: Right ventricle maintains pulmonary circulation and systemic
circulation via patent ductus arteriosus
• Venous blood passes from left side through arterial septal defect to right
side
• Aorta is supplies via retrograde flow from patent ductus arteriosus

• Cyanosis • ECG: Right ventricular • Prostaglandin E to
hypertrophy maintain ductal patency
• X-ray: Cardiomegaly • Heart transplant
• ECHO • Surgery

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7. Pulmonary atresia
Definition
• Pulmonary valve leaflets are completely fused
• Blood entering the right ventricle regurgitates back into right atrium
o Reaches left heart through foramen ovale
§ Only source of pulmonary flow is patent ductus arteriosus

• Cyanosis • ECG: Left ventricular • Prostaglandin E to
• Respiratory distress hypertrophy maintain ductal patency
• Holocystic murmus • ECHO • Surgery depends on the
• Heart catheterization right ventricle size

78

9b. Differential diagnosis of Oedema
Definition
Abnormal increase of interstitial fluid within tissues. Fluid predominantly
transudate, but can also be exudate (with proteins and cells) if there is infection
or lymphatic obstruction.
Classification

Generalized Localized Anasarca
Severe, generalized edema with widespread
subcutaneous tissue swelling (liver, renal failure)
Classification

↑hydrostatic pressure Lymphatic obstruction
↓ plasma oncotic pressure Sodium retention dependent edema
↑ capillary permeability

Types
↑ Hydrostatic pressure
1. Heart failure
• Symmetrical, gravity dependent, painless, pitting edema
• CF: Infants – poor feeding, FTT, tachypnea
Right heart failure Left heart failure
Peripheral edema Orthopnea
Ascites Dyspnea
Hepatomegaly Lung crackles
Hepatojugular reflux Dull percussion
↑jugular venous pressure Gallop rhythm
• Dg: ECHO, ECG
2. Iatrogenic fluid overload

• Symmetric, painless pitting edema
• Suspected by history and medical reports
3. Constrictive pericarditis
• Same as heart failure, but x-ray reveals normal sized heart with
calcification
• Dg: CT, MRI
4. Deep venous thrombosis (DVT)

• Unilateral, painless edema on lower extremity, accompanied by redness,
tenderness and warmth
• RF: hypercoagulable state, immobilization, surgery, oral contraceptive
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↓Plasma oncotic pressure
• Occurs when albumin is not synthesized in adequate amount or lost from
circulation
1. Nephrotic syndrome
• Diffuse pitting edema, with ascites, periorbital edema, scrotal edema
• Dg: proteinuria >50mg/kg/day, hypoalbuminemia, hyperlipidemia,
edema
2. Protein losing enteropathy

• Associated with diarrhea (severe)
• Diffuse pitting, dependent, painless edema
• Celiac disease, chrons disease, short gut syndrome, giardiasis
3. ↓ albumin synthesis
• Can be due to chronic liver disease, associated with jaundice, ascites,
coagulopathy, encephalopathy
4. Malnutrition
• Kwashiorkor – protein malnutrition
• Marasmus - ↓ calorie intake with protein malnutrition
↑ Capillary permeability
1. Angioedema
• Allergic/anaphylactic
• Idiopathic
• Hereditary
• CF: sudden, focal asymmetric, non-dependent, erythematous
uncomfortable edema
2. Severe sepsis
• Painless, symmetrical edema
3. Soft tissue infection

• Cellulitis, painful, localized, erythematous edema with more demarcated
border than angioedema
Lymphatic obstruction
• Lymphedema, non-pitting
• Eti: Congenital,
o Lymphatic filariasis: ↑ fibrosis,
o Iatrogenic: after lymph node resection or radio therapy
Sodium retention dependent edema

• ↑ Salt intake with renal insufficiency
• ↑Tubular reabsorption of Na+
• ↑RAAS (AKI – renal hypo perfusion, Cushing’s disease)
80

9c. Neonatal screening, Birth trauma
Definition
Evaluation of the newborn baby is an important tool in pediatrics, and is
evaluation using APGAR score., a method that quickly assess the health of the
newborn child immediately after birth.
• The test is done on the baby 1 and 5 minutes after birth.
o 1 min test (how well was birth tolerated)
o 5 min test (how well is adaptation outside womb)
APGAR score
Score 0 Score 1 Score 2

Appearance (skin Generalized cyanosis Cyanotic No cyanosis
color) or paleness extremities
Pulse rate Absent <100 >100
Grimace (reflex No response Grimace when Cry and pull away
irritability) stimulated when stimulated
Activity (mucle None Some flexion Flexed arms and
tone) legs that resist to
extension
Respiration Absent Weak, irregular, Strong
gasping
Range:
• Excellent condition 7-10
• Moderate depressed 4-6
• Severely depressed 0-3
Physical examination
• Confirm fetal diagnosis
• Detect problems in fetal to neonatal transition
• Reveal congenital malformations
• Show effects of labor and delivery (trauma, asphyxia, drugs)
General observation
• SGA (small gestational age) – <2500g at term delivery
• AGA (normal gestational age) – 2500-4200g
• LGA (large gestational age) – >4200g or above 90th percentile
• Length – normal 45-55cm
• Head circumference – 34-35cm, micro/macrocephaly
Vital signs
• Heart rate – 100-160bpm
• Respiratory rate – 30-50b/min
• Temperature

81

Head
• Bulging fontanelle indicates hydrocephalus
o Trauma
o Shape
o Size
o Fontanelle
Face, eyes, mouth ears

• Face: Dysmorphic features (epithelial folds, cleft lip, flat nose)
• Eyes: Light reflex (abnormal red/white reflection of the eye - Leukocoria
• Mouth: Cleft palate, lip, micrognathia
• Ears: tympanic membrane (dull, gray, opaque)
Neck, chest
• Neck: mass, webbing
• Chest: chest wall deformity, breast engorgement, respiratory distress
Lungs
• Rate of breathing, breathing sounds, additional sounds
Heart
• Rate, rhythm, murmur
Abdomen
• Palpation of liver (masses, tenderness, distention, hernias)
o Always check the back
Genitalia
• Kidney, genitalia, anus should be checked for patency, position and anal
reflex
Extremity
• Legth/symmetry
• Polydactyli/Syndactyli
• Chronic hip dysplasia
Skin
• Color, hair, rash, nevi
Gestational age assessment

• Dubowitz/Ballard examination – physical and neuromuscular maturity
• Physical
o Skin textures
o Lanugo (Soft hairs on body, absent in premature)
o Plantar creases
o Breast
o Eyes and ears
o Genitals
82

• Neuromuscular
o Flexion of lef, hips and arms
o Muscle tone
o Laxity of joints
o Neonatal reflexes – grapping, sucking,stepping, babinski
Neonatal screening
Program designed to screen infants shortly after birth (2nd-5th day) for
conditions that are treatable, but not clinically evident during newborn period.
Not screening for these diseases could lead to irreversible states later in life
• Most screening tests measure metabolites/enzyme activity
Screened diseases
Amino acid metabolism disorders Biotinidase deficiency
Congenital adrenal hyperplasia Congenital hypothyroidism
Cystic fibrosis Fatty acid metabolism disorders
Galactosemia Glucose-6-phosphate dehydrogenase deficiency
Human immunodeficiency disease (HIV) Organic acid metabolism disorders
Phenylketonuria (PKU) Sickle cell disease and other hemoglobin dis.
Toxoplasmosis Maple syrup urine disease

Birth trauma
• Injury to fetus during birth process
• Caput succendancum
o Diffuse edematous dark swelling of scalp – across suture line
o Prolonged labor, preterm infants
o Caused by pressure of scalp against dilating cervix
• Cephalhematoma
o Subperiostal hemorrhage that does not cross the suture lines
§ Associated with skull fracture
o Caused by prolonged labor/instrumental vaginal delivery
• Spinal cord injuries
o In fetus with hyperextended “stargazing” posture or after
excessive rotational or longitudinal force is transmitted to neck
during breech
• Brachial plexus injury
o Flaccid arm, paralyzed hand
• Clavicular fracture
• Facial nerve injury
o Peripheral palsy of facial nerve

83

10a. Infective Endocarditis
Definition
Infection of cardiovascular structures including the heart valves, atrial and
ventricular endocardium, large intra-thoracic vessels and prosthetic vessels.
Types
• Acute or fulminant endocarditis: valvular destruction within <40 days
• Subacute endocarditis: rare in peadiatrics, valvular destruction >40 days
Etiology

Streptococcus Staphylococcus Enterococcus Pseudomonas
viridans aureus aeruginosa
HACEK Streptococcus Streptococcus Candida albicans
pyogenes pneumonia
Risk factors
• Coronary heart disease
o Ventral septal defect (VSD)
o Bicuspid aortic valve
o Aortic/pulmonary stenosis
• Atrial septal defect is not a risk factor à the pressure difference is small
• Fibromuscular dysplasia
• Immunocompromised patient
o Tumors o Artificial conduit
o Prematurity o Aggressive PICU tx
o Chronic steroid o Hospital environment:
treatment IV use, IV catheter
o Transplant/ dialysis o Male
o Pacemaker
Clinical features

Fever (high/low grade) Tachycardia Tachypnea
Pale, fatigue, malaise, Skin: Osler´s nodes, Hemorrhage in retina
weight loss splint hemorrhage in
nails
Brain abscess New heart murmurs Janeway lesions
84


Diagnosis
Dukes classification, the patient needs at least 2 major or 1 major + 3 minor or 5
minor criteria

Major criteria Minor criteria
Blood culture with specific MIO Fever > 38
ECHO – evidence of endocarditis Embolic pneumonia
New valvular regurgitation Immunologic phenomena
Blood culture (non specific MIO)
↑ESR, CRP, Leu, Crea, BUN, pro BNP

Pathogenesis
Endothelial injury leads to a sterile thrombus that becomes infected with
pathogen. This process leads to infective endocarditis and emboli
Complication
• Embolic phenomena (brain, kidney, spleen)
o Pulmonary infaction in right-sided heart failure
• Immunologic phenomena
o Immune complex deposition
o Arthritis, glomerulonephritis, vasculitis
• Direct injury to valves
o Stenosis/ insufficiency
• Myocardium injury
• Renal injury
• Splenomegaly: over 300g
Treatment
• ATB: 4-8 weeks IV (oxacillin and gentamycin)
• Surgery: remove thrombus
• NB: prophylatactic ATB in patients with ↑risk, good dental hygiene
Non infectious endocarditis

Non bacterial thrombotic endocarditis Libman-sacks endocarditis
Seen in malignancies which leads to a Seen in SLE
hypercoagable state
(leukemia, lymphoma)

85

10b. Hypoglycemia in Children
Definition
Hypoglycemia in infancy and childhood can result from a largy variety of
hormonal and metabolic defects. The term hypoglycemia is a medical emergency
due to glucose critical role for brain development and function.
Whipple triad
• Clinical symptoms of hypoglycemia
• Low blood glucose concentration
o Preterm neonate <1,1mmol/L
o Term neonate <1,7mmol/L
o Neonates >4days and older children <2,2mmol/L
Pathophysiology
Hypoglycemia is ↓insulin and ↑(GH, cortisol, glucagon, epinephrine)
• Lead to breakdown of proteins, lipolysis and hepatic glycogenolysis
• Defects in counter regulatory hormones, insufficient food intake and
defects of enzymes in gluconeogenesis/glycogenolysis can lead to
hypoglycemia
Etiology
• Transient neonatal hypoglycemia
• Inborn errors of metabolism
• Deficiency of counter regulatory hormones
• Overproduction of insulin
• Others:
o Idiopathic ketotic hypoglycemia
o Malnutrition
o Starvation
o Burns
o Excess alcohol
o Aspirin
1. Transient neonatal hypoglycemia

• First days of life are most dangerous for develoment of hypoglycemia
• Sufficient energy stores in te form of glycogen, adipose tissue and muscle
are required
• Risk factors:
o Premature infants
o Small for gestational age
o Infants of diabetic mother – hyperinsulinism
o Infants with birth asphyxia, respiratory illness, heart disease,
starvation – all have increased glucose use

86

2. Persistent hypoglycemia in childhood
• After 2nd-3rd day of life hypoglycemia is less common, but can occur due
to endocrine or metabolic disease
3. Inborn errors of metabolism

• Galactosemia
• Glycogen storage disease
• Hereditary fructose intolerance
• Fatty acid oxidation
• Maple syrup urine disease
4. Deficiency of counter regulatory hormones

• Panhypopituitarism
• Addison’s disease
• Isolated growth hormone deficiency
• Congenital adrenal hyperplasia
• Adrenocorticotropic hormone deficiency
5. Overproduction of insulin
• Beckwith-weidemann syndrome
o Clinical features:
§ Macroglossia / Macrosomia
§ Omphalocele
§ Ear lobe creases – gigantism
§ Organomegaly
• Insulinoma
• Insulin/sulfonylurea drug administration
• Iatrogenic or munchhausen syndrome by proxy
6. Idiopathic ketotic hypoglycemia

• Symptoms of hypoglycemia after prolonged period of fasting
o Clinical features:
Neonatal:
Irritability Lethargy
Poor feeding Breathing problems (grunting, tachypnea)
Hypothermia Tachycardia
Cyanosis Tremors
Decreased muscle tone Seizures

Children:
Due to ANS activation Due to neuroglycopenia
Irritability Weakness
Hunger Dizziness
Nausea Headache
Anxiety Blurred vision
Palpitations Seizures
87

• Diagnosis:
o Lab: Glucose, Free fatty acids, C-peptide, cortisol,
Adrenocorticotropic hormone, IGF-1, thyroxine, lactate, CBC,
electrolyte
o Urin stix
o ABG
o Tox screen

• Treatment:
o In case of emergency – 10% dextrose (8mg/kg/min) IV
o Treatment of underlying cause
o Hyperinsulinism – Diazoxide
o Adrenal insufficiency – Hydrocortisone
o Glucagon i.m. – Type 1 diabetics with severe hypoglycemia
(Glucagon resque)

• Prevention:
o Neonatal:
§ Early feeding after delivery
§ Mothers milk (colostrum)
o Childhood:
§ Treatment of underlying cause
§ Avoid starvation/fasting
• Complications:
o Developmental delay
o Heart failure
o Mental retardation
o Seizures
o Secondary epilepsy (often by congenital hyperinsulinism)

88

10c.Juvenile Idiopathic Arthritis
Definition
Most common rheumatic disease of childhood, it’s a autoimmune disease with 7
subclasses. Chronic arthritis lasting more than 6 weeks with an onset before 16
years.
Pathogenesis
Not fully understood, but two main components are subscribed
Immunologic susceptibility
• HLA gene polymorphism, alterations in gene coding for: TNFα, IL 1, IL 6
o External triggers: bacteria/viral infections: EBV, rubella, parovirus
• Activation of immune system: inflammation
Clinical features
Arthritis Non-specific feature
Swelling Moving stiffness
Pain Fatigue
↓ Motion Anorexia
↑ Heat Sleep disturbance
No erythema

Classification
Systemic Oligoarthritis
Polyarthritis – Rh - Polyarthritis – Rh +
Psoriatic arthritis Entheisis related arthritis
Undifferentiated arthritis

1. Systemic arthritis
• Fever of at least 2 weeks duration, daily for at least 3 days
• Arthritis in more than 1 joint lasting for less than 6 weeks
• Evanescent (non-fixed) rash which dissappears
o Trunk, arms, thigh
• Generalized lymphadenopathy
• Hepatomegaly/splenomegaly
• Serositis (pericaritis, peritonitis, pleuritis)
Lab Differential diagnosis

Microcytic anemia Infection: sepsis, osteomyelitis, bact. Endocarditis
↑WBC, platelets Malignancy: lymphoma, leukemia
↑CRP, ESR, ferritin Other autoimmune diseases: SLE, vasculitis,
reactive arthritis, rheumatic fever
Hypergammaglobulinemia
Hypoalbuminemia

89

2. Oligiarthritis
• Def: Arthritis affectiong 1-4 joints during the first 6 months of disease
o Persistent: not more than 4 joints during the course of disease
o Extended: more than 4 joints affected after first 6 months
• CF: asymptomatic involvement of knee, thigh, ankle
o Uveitis – 30%
o ANA + - 60%
3. Polyarthritis
RF - RF +
Symmetrical involvement of wrist, Rheumatic nodules
hand, knee and ankle
Morning stiffness
Deformity of joints
4. Psoriatic arthritis
• Arthritis and psoriasis, arthritis and dactylitis, nailpitting, oncholysis,
psoriasis in a 1st family.
• Psoriatic rash precedes arthritis.
5. Enthesis related arthritis

• Arthritis combined with enthesis: inflammation at the point of insertion
of tendon or ligament to bone
o Sacroiliac joint
o Achilles tendon
• CF: associated with uveitis, HLA B-27 Ag
6. Undifferentiated arthritis
• Arthritis that fulfills no criteria for the main categories or fits in more
than one category
• Dg: Diagnosis is done by exclusion
o Hx and PE
o Lab: CBC, diff. Blood count, CRP, ESR
o Synovial fluid analysis
o USG, X-ray, CT, MRI
Treatment

NSAID DMARDS Immunosuppressant Biological treatment
Ibuprofen MTX Azathioprine Etanercept
Naproxen Sulfasalazine Cyclosporine Adalimumab
Hydroxychloroquine cyclophosphamide Anakinra
• Steroids
• Physotherapy

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11a. Myocarditis and Pericarditis
Myocarditis
Definition
There is inflammation, necrosis and degeneration of the myocardium
Etiology

Infectious
Virus Bacteria Fungal Protezoal Parasitic
Coxackie Mycobacterium Aspergillus Trypanosoma Scistosoma
cruzi
Adenovirus Streptococcus Candida Larva
migrans
HCV,HIV,EBC M.pneumoniae Cryptococcus
HEP C, ECHO T.palldum

Immune mediated
Autoantigen Hypersensitivity
SLE, IBD, churg-strauss, sarcoidosis, Wegeners granulomatosis
giant cell myocarditis Drugs: sulfamide, TCA, cephalosporin

Toxic
Cocaine Ethanol Heavy metal Radiation

Pathophysiology
• Myocarditis is characterized by myocardial inflammation, injury or
necrosis, which eventually leads to fibrosis
• Cardiac enlargemen and disminished systolic function occur as a direct
result of myocardial damage.
• Typical signs of congestive heart failure occure: Shock, atrial/ventricular
arrythmias and sudden death
• Final result can be dilated cardiomyopathy
Clinical findings

Asymptomatic Fatigue, pale Tachycardia, ↓BP
Dyspnea, chest pain Fever, palpation Arrhythmia
Mimic acute cor. syn Gallop rhythm, murmur Hepatomegaly
Peripheral edema

91

Diagnosis
• ECG:
o sinus tachycardia o ST depression
o slow voltage o AV block III
o inverted T (borreliosis/coxsakie)
• X-ray:
o Cardiomegaly
o Pulmonary edema/effusion
• ECHO:
o ↓systolic function
o heart chamber enlargement
o second degree insufficiency
• Lab:
o CK, CK-MB, troponin, LDH, AST/ALT
• Biopsy:
o Only to differentiate between dialated cardiomyopathy or
myocarditis
Differential diagnosis
Hypoxia Hypoglycemia Metabolic diseases
Sepsis Anomalous left cor. art Aortic stenosis
Coarctation of aorta Fibroelastosis

Treatment
• Chronic heart failure: diuretics, ACE-inhibitors, ARB´s
• Dopamine, dobutamine
• Ig (IV), corticosteroids
• ATB if indicated
• Antiarrythmics
• Temporary pacemaker if AV-block
• Ventricular assist device (VAD), extra corporal membrane oxygenation
(ECMO)

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Pericarditis
Definition:
Pericardium is a double-layered sac, with a inner layer (visceral) and outer
(parietal). Pericardial sac contains 15-50ml of pericardial fluid and served to
lubricate the surface of the heart and prevents its deformation and dislocation.

Pericarditis is defined as inflammation of the pericardium

Etiology

Infective pericarditis
Viral Bacterial
Coxsakie B EBS Staphylococcus Streptococcus
ECHO RSV Meningococcus TB
HIV adenovirus H. influenza

Non-infective pericarditis
Systemic inflammation Metabolic
Rheumatic fever SLE Uremia (ESRD) Hypothyroidism
Systemic sclerosis Weg. Gran. Gaucher dx
Juv. idio.arth

• Malignant: lymphoma, leukemia: pericardial effusion
• Drug induced: procaonamide, hydralazine, izoniazid
• Post cardiotomy: 7-14 days after cardiac surgery
Clinical findings

Chest pain, fever Dyspnea Cough
Retrosternal pain Pericardial effusion Distant heart sounds
Muffled heart sound Tachycardia Jugular venous pressure
Pulsus pardoxus Cardiac tamponade

Diagnosis
• ECG:
o Low voltage o ST elevation
• X-ray: o Effusion
o Cardiomegaly • Lab:
o Pericardial effusion o CRP, Leu, antigents
• ECHO: • CT/MRI
Treatment
• Bedrest • ATB
• NSAID: ibuprofen • Treatment of RA (depress it
• Pericardial drainage
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11b. Seizures in Children
Definition
An episode of temporary dysfunctions of the brain caused by an abnormal,
uncontrolled electrical activity of the neurons
Categories
o Acute symptomatic seizures
Electrolyte imbalance Others
• Hypocalcemia • Hypoglycemia
• Hypomagnesemia • Meningitis
• Hypo/hypernatremia • Encephalitis
• Head trauma
• Tumor
• Brain abcess
• Acute stroke
• IEM

o Epilepsy and epileptic syndromes
§ Characterized by unprovoked seizures
o Febrile seizures
§ Seizures that occur in children 6months-5y with a
temperature ≥38C, that are not a result of CNS infection or
any metabolic imbalance
Epilepsy
Chronic neurological condition characterized by recurrent (≥2), unprovoked
seizures
Types
1. Partial seizures
• The electrical impulse arises from a localized area in one hemisphere of
the brain
• Simple partial seizure
o Conscioussness is not impaired
o Sensory (visual, auditory, somatosensory, olfactory)
o Motor (focal tonic/clonic) – most common
• Complex partial seizure
o Loss of conscioussness
o ↓Responsiveness, staring, looking around, hallucinations
• Secondary seizures
o Start as simple/complex partial seizure and spret to involve both
hemispheres - generalized tonic, clonic or tonic-clonic seizures

2. Generalized seizures
• Tonic-clonic seizures (grand mal)
o Dramatic, self-harming
o Strart with shouting-screaming, followed by loss of conscioussness
o Tonic phase
§ ↑muscle tone and rigidity followed by clonic phase
o Clonic phase
§ Urinary/fecal incontinence
§ Patients are amnestic of event
§ Postictal phase
• Nausea, vomiting, sleepiness, headache, semicoma
• Tonic
o Sudden loss of conscioussness and rigidity of entire body
o No jerks
• Clonic
o Repeated jerks
• Absence – (petit mal)
o Sudden behavioral arrest – staring, unresponsiveness
o Lasts for 10-20s
o Amnesia of seizure
o 5-8years of age - starts
• Myoclonic
o Shaking of entire body
o Sudden or brief
• Atonic seizures
o Loss of conscioussness
§ Falling down
o Loss of postural tone
3. Epileptic seizures
Disease that are identifible on the basis of: (typical age of onset, seizure type,
specific course of diase and EEG changes)
• Juvenile myoclonic epilepsy
• Benign rolandic epilepsy
• Infantile spasms
• Lennox-Graustat syndrome
• Mesiotemporal epilepsy
• Febrile convulsions

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Juvenile • Most common generalized epilepsy (13-18years)
myoclonic • CF: Myoclonic seizure including arm and shoulders,
epilepsy occuring in the morning
• Tonic-clonic, ansence seizure can also be seen
• Patient may spill of drop things
• Trigger: Alcohol, sleep deprivation, photic stimulation
Benign • Idiopathic focal epilepsy

rolandic • 3-13years
epilepsy • Nocturnal seizures – simple partial with/without sporadic
generalization
• Nearly all patients outgrow the disease
Infantile • Occur at 2-12months
spasms • CF: Sudden, brief axial seizures typically with tonic flexor
spasms of the waist, extremities and neck
• Part of West syndrome
• Eti: Tuberous sclerosis
• Tx:
o ACTH (Prednisone)
o Benzodiazepine (Valproate)
• Poor prognosis
Lennox-Gaustat • Devestating disease, present <5years
syndrome • CF: Mental retardation, slow wave activity on EEG, multiple
seizure types (tonic, atonic, myoclonic)
• Tx:
o Ketogenic diet
o Benzodiazepine (Valproate)
o Corpus callostomy
Poor prognosis
Mesiotemporal • Before puberty
epilepsy • Hippocampal sclerosis
• Temporal lobe epilepsy – seizures
o Complex partial seizure with prolonged impairment of
conscioussness
o Oroalimentary, gestural or reactive automatism
Febrile • Associated with fever in children between 3months-5years
convulsions • Types:
o Simple – last less than 15min (generalized tonic-clonic)
o Complex - >15min, occur repeatedly (one part of body)
• Outcome is benign – no damage to the brain
• Tx: Usually no treatment, but rectal diazepam can be used
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Status epilepticus
• Gen: Continous seizure activity or recurrent seizure activity with/without
regaining of conscioussness lasting >30mins
• Diagnosis:
o History
o Seizure description
o CBC, biochem:
§ Electrolyte
§ Glucose
§ BUN
§ Creatinin
§ NH3
o CSF analysis
o EEG
§ Spike/sharp waves (focal/generalized)
§ Genetic test: IEM
§ PET, CT, MRI
• Tx:
o Patial - (Carbamazepine, ianotrigin, gabapentine)
o Generalized – (Valproic acid, topiramate)
o Treat underlying cause
o Ketogenic diet

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11c.Bone Diseases (Osteomyelitis, Aseptic necrosis,
Osteoporosis)
Osteomyelitis
Definition
Infection and inflammation of the bone and the bone marrow
Classification
• Acute hematogenous osteomyelitis
o Spread from distant sites accompanied by bacteremia
• Subacute osteomyelitis
o Following inoculation by penetratin trauma, no systemic CF
• Chronic osteomyelitis
o Results from untreated or inadequately treated bone infection
Etiology
Neonates and children Older children
S. aureus s. aureus s.pyogenes
GBS s. pneumonia H. influenza
E.col p. aeuroginosa salmonella

Clinical features
• Generally the long bones are affected: femur, tibia, humerus, radius.
Usually only a single site of bone is involved.
• Infancy: infection occur in the metaphysis, FTT, irritability, drowsiness
• 1 year: infection can spread to the epiphysis (transphyseal vessels) and
cause puss to enter the joint spaceà suppurative arthritis
• Neonates: pseudosyst, pain with movement of affected limb, 2 or more
involved sites
• Older children: fever, pain, edema, erythema, warmth
Diagnosis
• CBC: ↑WBC, CRP, ESR
• Blood cultures
• X-ray:
o Exclude trauma
o Loss of periosteal flat line (early sign)
o Periosteal elevation and destruction (late signs)
• MRI, CT, bone scan
Treatment
• Pain relief, bed rest, splintage
• IV ATB à after culture
• Surgical drenage of subperiosteal abcess w/debriment of necrotic tissue
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Complications
• Disseminated systemic infection: septicemia, cerebral abcess
• Chronic osteomyelitis
• Septic arthritis
• Deformity due to epiphyseal invovement
Aseptic necrosis
Definition
Condition that occurs when bone tissue dies because of too little blood supply
Etiology
• Trauma: hip fractures, wrist, knee, shoulder
• Steroid use
• Alcohol
Clinical findings
• Pain at the affected site with weight bearsing
• Stiffness
Diagnosis
• Exclude infection, fracture and neoplasm
• X-ray
Treatment
• Reduce weight bearing
• Activity restricion
• Surgery:
o Core decompression o Bonegraft
o Osteotomy o Arthroplasty
Perthes disease
Definition
Idiopathic avascular necrosis (osteonecrosis) of the capital epiphysis of femoral
head. It´s caused by the interruption of blood supply to the growing capital
epiphysis of unknown etiology. It is common in children between 3-12 years
Clinical finding
• Atraumatic, painless limb wich leads to ↓internal rotation and abduction
Diagnosis
• X-ray, MRI
Treatment
• Usually selflimited, containment via cast or surgery
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Osteoporosis
Definition
Diminished bone density due to decreased bone volume, but normal
mineralization, together with osteopenia (↓ amount of bone tissue). Associated
eith pathologic fractures, it´s relatively uncommon in childhood.
Bone density < 2,0, below peak bone mass T score.

Events in childhood influence peak bone mass, adequate Ca2+ and vitamin D
intake weight bearing exercise to prevent late osteoporosis
Etiology

Primary Secondary
Osteogenesis imperfect Neuromuscular disease
Bruck syndrome Chronic illness
Marfan syndrome Endocrine disease
Ehlers-Danlos Drug induces
Idiopathic juvenile osteoporosis Inborn errors of metabolism

Clinical features
• Onset before puberty
• Long-bone and lower back pain
• Vertebral and metatarsal fracture
• Improvement after puberty
• Spinal deformities
Diagnosis
• Dual energy x-ray absorptiometry
• Lab: Ca2+, vit D, PTH, ALP
Treatment
• Treat underlying disease
• ↑Ca2+, vit D
• Bisphosponate
• Use lowest dose of corticosteroids

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12a. Dysrhythmias in Children
Definition
Dysrythmias/arrhythmia is the disturbance or loss or rhytm of the heartbeat.
They can lead to tachycardia, bradycardia or irregular beats (skip a beat/extra
beat)
Classification
• Atrial arrhytmias
o Sinus bradycardia (7)
o Premature atrial contractions (1)
o Supraventricular tachycardia (4)
• Junctional arrhytmias
o Premature junctional contraction (2)
• Ventricular arrhytmias
o Premature ventricular contraction (3)
o Ventricular tachycardia (6)
o Wolf-Parkinson-White syndrome (5)
• Heart blocks
o 1st degree AV block (8)
o 2nd degree AV block type 1 – Wenchebach/Morbitz I (9)
o 2nd degree AV block type 2 – Morbitz II (9)
o 3rd degree AV block (10)
Etiology
Drugs • Intoxication – cocaine, TCA
• Antiarrytmics (proarrhytmic, quinidine)
• Sympatomimetics (caffeine, theophyline, ephedrine)
• Digoxin
Infectious or post • Endocarditis, myocarditis

infectious • Lyme disease
• Diphteria
• Rheumatic fever
• Guillain-Barre syndrome
Merabolic/endocrine • Cardiomyopathy
• Electrolyte disbalance (especially K or Ca)
• Uremia
• Thyrotoxicosis
Structural lesion • Mitral valve prolapse
• Ventriculotomy
• Congenital heart defect
Other • Maternal SLE
• Idiopathic
101

Pathophysiology
Arrhytmia may be due to disorder of impulse generation (too fast/too slow),
disorders of impulse conduction (block/reentry) or combination of both
• Abnormal impulse formation (includes abnormal automaticity and
triggered activity)
o Abnormal automacity – (cells other than SA node starts firing
spontaneously, resulting in premature beats)
o Triggered activity –(cardiomyocytes contract twice, often caused
by electrical instability in myocardial cell membrane)
§ Hypokalemia, drugs, catecholamines
• Abnormal conduction (includes conduction delays re-entry and
accessory pathway)
o Conduction pathway – (can cause slow heart rate (AV block)
o Re-entry – (common cause of arrhytmia, occuring when
conduction path is partly slowed down)
o Accessory pathway – (accessory pathway, such as in Wolf-
Parkinson-White syndrome)
Treatment is required Treatment is not required

Supraventricular tachycardia Sinus arrhytmia
Ventricular tachycardia Wandering atrial pacemaker
3rd degree AV block with symptoms Isolated premature atrial contractions
First degree AV block

1. Atrial premature beats

• Gen: Common cardiac dysrhythmia characterized by premature
heartbeats originating in the atria
• CF: often completely asymptomatic, but can have skipped beat, or jolt in
the chest
• Dx: ECG, Holter monitor, cardiac event monitor
• Tx: Often benign and do not require treatment. In case of triggers of more
serious arrhytmias, beta-blockers can be used
• Diff Dx: Hyperthyroidism, structural heart dx, cardiomyopathy

2. Junctional premature beats

• Gen: Premature cardiac electrical impulses originating from the AC node
of the heart, or junction. Can be seen in healthy subjects, but more
commonly in some pathologic conditions
• Eti: Cardiac drug toxicity, electrolye imbalance, mitral valve surgery, cold
water immersion
• Dx: ECG, Holter monitor, Cardiac event monitor
• Tx: Often benign and do not require treatment.

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3. Ventricular premature beats
• Gen: Relatively common event where heartbeat is initiated by purkinje
fibers in ventricles rather than by SA node.
• Eti: Excess catecholamines, cardiomyopathy, drugs, hypoxia, MI, ischemia,
stress, thyroid problems
• CF: Abnormal ECG, dyspnea, arrhytmia, palpitations, dizziness
• Dx: ECG
• Tx: Isolated ventricular premature beats with benign characteristics
usually require no treatment. However medications include:
o Beta-blockers
o Calcium channel blockers
o Magnesium and potassium supplementation
• Diff Dx: If 3 or more premature beats occur in a row it may be called
ventricular tachycardia

4. Supraventricular tachycardia
• Gen: Abnormally fast heart rhythm arising from improper electrical
activity in the heart, such as from atrium, atrioventricular juntion or
accessory pathway
• Types: paroxysmal supraventricular tachycardia, atrial fibrillation, atrial
flutter and Wolf-Pakinson-White syndrome
• Eti: Re-entry or automacity
• CF: palpitations, shortness of breath, chest pain, rapid breathing, syncope
• Dx: ECG (may mimic VT, but important to distinguish for treatment)
• Tx: together with vagal maneuvers
o Adenosine
o Diltiazem, verapamil
o Amiodarone

5. Wolf-Parkinson-White syndrome
• Gen: Referred to pre-excitation syndrome. Caused by presence of
abnormal electrical conduction pathway between atria and ventricles.
The most common form of tachycardia
• CF: palpitations, shortness of breath, dizziness, syncope
• Dx: ECG (delta wave)
• Tx: Vagal maneuvers
o Cardioversion
o Verapamil
o Adenosine
o Esmolol
o Procainamide
o Digoxin
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6. Ventricular tachycardia
• Gen: Type of regular and fast heart rate that arises from improper
electrical activity in the ventricles of the heart. More serious prognosis
than SVT.
• Types of ventricular tachycardias:
o ventriucular tachycardia
o ventricular fibrillation
o torsades de pointes
• Eti: Typically re-entry mechanisms. Coronary heart disease, aortic
stenosis, cardiomyopathy, electrolyte disorders, MI
• CF: Weakness, palpitations, dizziness, shortness of breath, signs of
congestive heart failure, syncope, cardiac arrest
• Dx: ECG, (3 or more ventricular beats), Holter ECG, treadmill testing
• Tx:
o Defibrillation, cardioversion
o Procainamide
o Phynytoin
o Beta-blockers – (long term)
o Class III anti-arrhytmics (K- channel blockers) – (long term)
§ Amiodarone
§ Sotalol

7. Sinus bradycardia
• Gen: Slow heart rate
o Infants 0-3years: <100bpm
o 3-9 years: <60bpm
o 9-16years: <50bpm
• Eti: Cardiac hypothermia, hypothyroidism, metabolic acidosis, sepsis,
CNS injury, drug induced (digoxin, beta-blockers, amiodarone)
• Classification: disorders of SA node, disorders of AV node
• Dx: Palpation, ECG
• Tx:
o Atropine
o Isoprotenerol

8. 1st degree AV block

• Gen: In 1st degree AV block, the impulse conducting from atria to
ventricles through AV node is delayed and travels slower than normal
• Eti: Enhanced vagal tone, myocarditis, MI, electrolyte disbalance
• Dx: ECG
• Tx: Correction of electrolyte disbalance, treatment of underlying cause

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9. 2st degree AV block type 1 and 2 – Wenchebach/Morbitz I/II
• Gen: Disease of electrical conduction system between atria and ventricles.
Type 1 is considered more benign than type 2
• Eti:
o Type 1- Enhanced vagal tone, myocarditis, MI, electrolyte
disbalance
o Type 2 – Post inflammation, trauma of myocardium (rare in
children)
• CF: Dizziness, light headedness, syncope
• Dx: ECG
• Tx:
o Type I:
§ No therapy or theophyllin
§ Acute cases: atropine, isoproterenol
o Type II:
§ Pacemaker implantation

10. 3st degree AV block

• Gen: Also known as complete heart block, where impulse generated in SA
node does not reach the ventricles. Own rates of atria and ventricles
• Types:
o Congenital
o Acquired
• Eti:
o Congenital- Surgical heart disease, AV canal, maternal lupus
antibodies, muscular dystrophy, idiopathic
o Acquired – Surgical catheter, lyme dx, myopathy, diphteria,
endocarditis
• CF:
o Congenital- Asyptomatic in utero, can be hydrops or death of fetus
• Dx: ECG, (3 or more ventricular beats), Holter ECG, treadmill testing
• Tx:
o Congenital- Emergency pacemaker placement
o Acquired – Surgery (wait for recovery 6-10 days)
§ Without improvement – chronic pacemaker

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12b. Iron deficiency Anemias
Definition
Anemia due to not enough iron
Etiology
• Dietary deficiency • Blood loss
• Impaired absorption o Polymenorrhea
o Celiac disease o Parasitic infection
o Gastritis o Peptic ulcer
o Chronic inflammation o IBC
• Increased demand (growth)
Clinical features
• Gastrointestional • Cardiac
o Anorexia. Poor weight o ↑CO, cardiac
gain hypertrophy
o Atropic glossitis, pica • Skin
• CNS o Dry skin, thin hair,
o Fatigue, irritability pallor, nail ridges
Risk factor
• Children <5years • Adolescents
o Preterm/LBW o Hx of heavy menstrual
o Intro of cow´s milk blood loss
o Parasitic infections o ↓physical activity
o Poverty o Vegetarian diet
o Fat diet
o Malnutrition
Diagnosis
• Microcytic, hypochromic anemia
• ↓Hb, MCV, ferritin
• ↑TIBC (total iron binding capacity), transferin
• ↓serum iron
• BM aspiration
Treatment
• P.o iron supplement
• Diet: animal protein, green vegetables
• Folate, vit C
• I.V iron for those with
o Poor compliance
o Severe hemorrhage
o Acute diarrhea

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12c.Adrenal gland cortex diseases
Definition
Adrenal gland disorders (or diseases) are conditions that interfere with the
normal functioning of the adrenal glands. Adrenal disorders may cause
hyperfunction or hypofunction, and may be congenital or acquired.
Types
• Cushing´s syndrome
• Primary hyperaldosteronism
• Addison´s disease
• Adrenal crisis
Congenital adrenal hyperplasia

Definition
Belongs to the family of AR disease of cortisol biosynthesis. Cortisol deficiency ↑
the secretion of ACTH which in turn causes adrenocortical hyperplasia
Classification
Depending on the enzymatic step that is involved
• Mineralocorticoid deficiency or excess
• Incomplete virilization or premature puberty in males
• Virilization or sexual infertilism
Etiology
• 21 – hydroxylase deficiency
• 11B – hydroxylase deficiency
• 3B dehydrogenase deficiency
Histology
• Glomerulosa: mineralocorticoids
• Fasciculata: glucocorticoids
• Reticularis: sex hormones
• Medulla: catecholamine

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21 – hydroxylase deficiency
Accounts for 90% of congenital adrenal hyperplasia, mutation of CYP21 gene

Clinical finding
• General symptoms
o Dehydration o ↓BP
o Vomiting o ↓Glucose
o Diarrhea o Metabolic acidosis
o Poor feeding o Shock
o Arrythmia
• Glucocorticoid deficiency
• Mineralocorticoid deficiency
• Androgen excess
o Ambigous genitalia in female
o Postnatal visilization in both sexes
o Rapid growth and skelatal maturation
o Pubic, axillary hair appear, deep voice, acne
o Penis and clitoris enlargemant
Diagnosis
• ↓cortisol, ↑↑ACTH, ↑hydroxyprogesterone
• ↓aldesterone,↑renin, ↓Na+, ↑K+ (salt wasting crisis)
• ↑androgens
Treatment
• Hydrocortisone/flydrocortisone
• NaCl supplement
• Vaginoplasty and clitoral recession for females
11B - hydroxylase deficiency

Mutation of CYP 11B1

Clinical findings
• Mineralocorticoid excess: hypertention
• Androgen excess
Diagnosis
• ↓cortisol, renin, hypokalemia
• ↑ACTH, androgens, aldoseterone
• ↑deocycortisol
Treatment
• Glucocorticoid
• Vaginoplasty

108

3B – dehydrogenase deficiency

Clinical finding
• Mineralocorticoid deficiency
• ↑ Dehydroepiandrosteron (DHEA), but ↓ levels of testosterone and
estradiol.
o CHEA causes weak androgen
o Incomplete virilization in boys: bifid scrotum, cryptorchidism
o mild virilization in girls (mild ↑ of clitoris): precocious adrenarche
Diagnosis
• ↓cortisol, ↑ACTH,↑DHEA
• ↓aldosterone, ↑renin, ↓Na+, ↑K+
• ↓testosterone, estradiol
Treatment
• Hydrocortisone, NaCl, sex hormone replacement in puberty
Cushing’s syndrome
Definition
↑Plasma levels of glucocorticoids in other words hypercortisolism, which refers
to all causes of excess cortisol. In Cushing’s on the other hand the excess cortisol
is a result of an ACTH producing pituitary adenoma/tumor
Etiology
• ACTH dependent Cushings syndrome
o ↑ levels of ACTH with ↑ cortisol
o Pituitary tumor (adenoma, carcinoid) à Cushng´s in children >7yr
o Ectopic ACTH producing tumor: pancreatic, wilms, neuroblastoma
• Non ACTH dependent Cushings syndrome
o ↑ cortisol, ↓ ACTH
o Adrenal adenoma/carcinoma: symptoms due to ↑androgens,
estrogen, aldostreone
o Adrenal hyperplasia (McCune-Albright syndrome)
o Iatrogenic glucocorticoid administration (exogenous)

109

Clinical features
• Weight gain and central obesity, growth failure and short stature
• Skin changes: striae, thin skin
• Hyperpigmentation in ACTH dep C.S
• Older children – moon face, buffalo lump
• Hypertension, hyperglycemia, edema, hypokalemia
• Muscle wasting and osteoporosis leads to fractures
• ↓ Wound healing, ↑ infection
• Depression, psychosis, prim/seco amenorrhea, hirtuism, delayed puberty
Diagnosis
• Overweight dexametasone test
o Administer 1mg dexamethasone around midnight, measure at 09
in the morning.
o Cortisol levels > 100nmoi/l indicates CS
• 24h urinary free cortisol
o if >140nmol/l indicates CS
• Changed circardian rhythm
o ↑ at midnight, normal in the morning
• Dexamathasone supression test
o 2mg dexamethasone for 4 days, if ↓ more than 50% = CS
• ACTH levels
• Adrenal CT/MRI
• Pituitary MRI
• X-ray/CT: ectopic ACTH producing tumor
• K+ levels: suggest ectopic ACTH producing tumor
Treatment
• Supression of cortisol production (preoperatively):
o methyrapone, ketoconazole
• Surgery: resection of tumor
• Adjuvant radiotherapy
• Bilateral adrenalectomy
o Can cause Nelsons syndrome: hyperpigmentation due to ↑↑ ACTH

110

Primary hyperaldosteronism
Primary hyperaldosteronism is due to excess production of aldosterone by the
adrenal glands results in low renin levels. Secondary hyperaldosteronism is a
result from excessive renin stimulation of adrenal cortex.

Excess aldosterone production leads to Na+ and H2O retention, hypertension, ↑K+
excretion (hypokalemia)
Etiology
• Aldosterone producing adrenal adenoma (Conn syndrome)
o Unilateral, F>M
• Idiopathic hyperaldosteronism
o Bilateral adrenal cortical hyperplasia, M>F
Clinical findings
• Hypertension
• Na+ and H2O retention: renal, cardiac, retinal damage
• Hypokalemia: muscle weakness, fatigue, ECG changes (atr, ven ex sys)
• Hyperatremia: polyuria, polydipsia
• MAL due to K+/H+ exchange in cells
Diagnosis
• Plasma aldosterone-renin ration
o ↑A, ↓R = 1. HA
o ↑A, ↑R = 2. HA
• CT/MRI
• Urine: ↑K+, aldosterone
• Hypokalemia
Treatment
• Surgery: resection of adenoma
• Aldosterone antagonist
o Spironolactone: HT/hypokalemia
• Combiantion calcium channel blocker, diuretic, Na+ restriction
• Last: adrenalectomy

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Addison’s disease
Primary hypoadrenalism or Addison´s disease is the destruction if entire adrenal
cortex leading to deficiency of glucocorticoids, mineralocorticoid and sex
hormones. 90% of gland has to be involved before symptoms occur.
Pathogenesis
• ↓ levels of cortisol leads to feedback to ↑CRH and ACTH (H-P-A feedback)
• Addison´s disease differ from secondary hypoadrenalism (hypothalamic
pituitary disease. In which the minaralocorticoids and sex steroid
hormone production is intact, because of independent ACTH stimulation.
• It is a rare disease, which M>F, due to autoimmune background
Etiology
• Autoimmune adrenalitis
• TB: contries with high prevalence of HIV/AIDS
• Surgical removal of adrenal glands
• Hemorrhage or infarction
• Adrenal leukodystrophy (Schilder´s disease)
Clinical features

Weight loss Anorexia Nausea
Vomiting Weakness/syncope Confusion
Abdominal pain Diarrhea Cut/muc hyperpigment
Postural HT <110/70 ↓ glycemia, natremia ↑hyperkalemia
Ketosis

Diagnosis
• ACTH stimulation test: 60m after IV ACTH
o ↓cortisol,↑↑ACTH in primary, normal or ↓ in secondary
• Blood: electrolyte
• Adrenal Ab: Autoimmune adrenalitis
• ↑renin: due to ↓aldosterone
• X-ray: TB
Treatment
• IV hydrocortisone, 0,9% NaCl, dextrose
• Replacement therapy: All 3

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Adrenal crisis
A medical emergency, with extreme adrenal insufficiency due to ↓↓ cortisol
Etiology
• Addison´s disease
• Cushing syndrome: biosynthetic enzyme defect
• Pituitary disease
o Sheehan syndrome
o Pituitary adenoma
o Hypopituitarism
Clinical features
• Sudden pain in legs, lower back and abdomen
• Confusion, psychosis, slurred speech
• Severe lethargy
• Convulsion
• Fever
• ↑K+, Ca2+, ↓Na+, T4, glycemia
• Hypotension
• Syncope
• Vomiting, diarrhea due to dehydration
Diagnosis
• Lab: cortisol, glucose, electrolyte
• ACTH stimulation test
Treatment
• Hydrocortisone
• Fluid replacement

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13a. Heart failure and its treatment
Definition
• Heart failure occurs when the heart is unable to deliver adequate cardiac
output to meet the metabolic needs of the body
Factors affecting cardiac output

• Cardiac output = stroke volume x heart rate
• Preload
o Gen: End diastolic volume that stretches to right/left ventricle. It is
the initial stretching of the cardiomyocytes prior to contraction.
o Affected by venous pressure and rate of venous return (venous
tone and volume of circulating blood)
• Afterload
o Gen: Pressure of left ventricle during ejection
o Affected by pulmonary venous return, elasticity of vessels,
presence of outflow obstruction (aortic stenosis, coarctation aorta)
• Contractility
o Depends on sympathetic stimulation, catecholamines, anoxia,
hypoxia, acidosis, loss of myocardium (decreased)
Heart rate
• ANS stimulation – baroreceptor and chemoreceptor (hypoxia/anemia)
• Others – temperature, thyroid hormones, catecholamines
Pathogenesis
• When the heart fails, compensatory changes occur to maintain the cardiac
output and peripheral perfusion
• The include renin-angiotensin-aldosterone system (↑after and preload)
and the sympatoadrenal axis (↑HR, contractility, PVR)
• As heart failure progresses, these mechanisms become pathological as the
↑cardiac work (↑O2 demand) and (↓renal, hepatic and GIT perfusion)
Etiology
• Volume overload is the most common cause of heart failure leading to
congenital heart disease
Fetus Preterm neonate Infant/toddler

• Severe anemia • Fluid overload • Ventricular septal defect
(hemolysis, • Congenital heart • Cardiomyopathy
ISOimmunization) disease (patent ductus • Kawasaki disease
• Complete heart block arteriosus, ventricular • Supraventricular
(maternal SLE) septal defect) tachycardia
• Myocarditis • Cor pulmonale due to • Myocarditis
bronchopulmonary • Acute hypertension due
dysplasia to HUS
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Full term neonate Children and adolescents
• Congenital heart disease (coarctation • Rheumatic fever
of aorta, single ventricle, transposition • Acute hypertension
of great arteries, truncus arteriosus • Thyrotoxicosis
• Cardiomyopathies • Myocarditis
• Viral myocarditis • Endocarditis
• Anemia • Cor pulmonale
• Complete heart block
Clinical features
Fetus Older children (pulmonary/systemic congestion predominates)
• Poor feeding Pulmonary venous congestion Systemic venous congestion
• Poor weight gain • Dyspnea • Abdominal pain
• Fatigue • Tachypnea • Nausea
• Tachypnea • Orthopnea • Hepatomegaly
• Irritability • Fatigue/weakness • Edema and ascites
• Weak cry • Wheezing • ↑Jugular venous
• Pulmonary edema pressure
• Diaphoresis with
feeding • Gallop rhythm – • Hepatojugular reflex
3rd heart sound
• Wheezes
• Dyspnea (nasal
flare etc)
Diagnosis
• X-ray: Cardiomegaly, ↑pulmonary vascularity
• ECHO: show chamber size and congenital heart defect
o Assess ventricular function – fractional shortening (end diastolic –
end systolic diameter)
• BNP (B-type natriuretic peptide) – for cardiomyopathy/volume overload
Treatment
• General care Diuretics (first line treatment)
• Increased caloric diet for • Furosemide (loop diuretics)
infants • Spironolactone (potassium sparing)
• Older children: Salt • Chlorothiazide (together with furosemide)
restricted diet Inotropic agents
• Rest during day, sleeping in • Digoxin
upright position • Dopamine (used in ↓renal perfusion)
• Oxygen
ACE inhibitors, Angiotensin renin blockers
• Other:
β-blockers can be used
o Heart transplant Nitroprusside – vasodilation
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13b. Acute leukemias, Malign lymphomas
Leukemia
Definition
Malignant neoplasm of hematopoietic stem cells, characterized by diffuse
replacement of bone marrow by neoplastic cells. In most cases, cells spill over to
the blood, so large numbers can be detected in blood. Leukemia is considered as
the most common malignant neoplasm in childhood
Classification

Cell type Acute Chronic
Lymphocytic leukemia Acute lymphoblastic Chronic lymphoblastic
leukemia leukemia
Myelogenous leukemia Acute myelogenous Chronic myelogenous
leukemia leukemia

Etiology
• Mostly uncommon
• Genetic:
o Philadelphia chromosome 9 and 22
o Fanconi anemia
o Downs syndrome
• Environmental
o Radiation
o Chemical
o Drugs: alkylating agents
Acute leukemia
• Clonal proliferation of myeloid or lymphoid precursors with rapid
evolution of the disease
• Leukemic cells accumulate in the basement membrane, blood and other
sirrues (liver, spleen, lymphnodes) this leads to: ↓RBC, WBC, platelets
Acute lymphoblastic leukemia
• Peak age 2-3 years
• May present with significant bone marrow involvement or mediastinal
mass (lymphoblastic lymphoma) same rumor cells and same treatment
Acute myelogenous leukemia
• Seen in adolescents (15-19) and neonates

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Clinical features
• Basement membrane failure:
o Anemia: fatigue, pallor, tachycardia, dyspnea
o Neutropenia: ↑inflammation (fever, sepsis)
o Thrombocytopenia: ↑bleeding, bruising (petechia, ecchy mosis,
epistaxis)
• Increased WBC
o Leukostasis with dyspnea, headache, confusion, visual problems
o Hypoxia due to intravascular leukocyte aggregation and dumping
• Substance release
o Hyperuricemia: tumor lysis syndrome, acute gout, renal stone, AKI
o DIC: bleeding, bruising in acute myelogenous leukemia
• Tissue infiltration
o Bone pain
o Hepatosplenomegaly
o Lymphadenopathy
o Rarely CNS involvement (ALL)
o Testicular enlargement (ALL)
Diagnosis
• Peripheral blood film: leukemic blast cells
• BM aspirate: ↑ cellularity w/ >20% of blast cells, ↓erythropoesis
o AML-CD33, B cell ALL-CD10, T cell ALL-CD3
• CBC: ↓RBC, Hb, platelet, ↑WBC
• X-ray: mediastenal mass
• CSF analysis
• PTT, APTT, fibrinogen: to exclude DIC
Treatment
• AML
o IV chemo treatment: cytarabine, daunorubicine, etopiside
o Allogenic BM transplantation
o Prognosis: good for young patients, 75% complete remission
• ALL
o Combination chemotherapy: vincristine, dexamethasone,
asparaginase, daunorubicine
o Intrathecal cytarabine (↓ CNS involvement)
o Prognosis: excellent for children (70% complete remission) not so
good for adults

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Malignant lymphoma
Definition
Third most common cancer in children, it is a result of abnormal proliferation of
lymphoid tissue and occurs at any site where lymphoid tissue is found.
Lymphadenopathy at single or multiple sites, but extra nodal manifestations may
also occur (in non-Hodgkin’s lymphoma)
Classification
• Hodgkins lymphoma
o Localized to single lymph node, rarely extra nodal
• Non-hodgkins lymphoma
o Multiple lymph nodes, extra nodal
Hodgkin’s lymphoma
Rare disease affecting primarily lymph nodes.
• Males are more affected than women between 15-30 years
• It is associated with infectious mononucleosis
Pathology
Reed-Sternberg cells (binucleated cells)

Classification
• Nodular sclerosing: (70%) – cervival and supraclavivular LN
• Lympocyte rish (5%) – often in peripheral LN
• Mixed cellularity (25%) – many different cells
• Lymphocyte depleted
Clinical findings
• Enlarged LN, usually cervical: painless, rubbery consistency
• Hepatisplenomegaly
• Systemic B-symptoms: fever, night sweats, weight loss
• Pruritus, fatigue, anorexia
• Symptoms due to no involvement of other organs (mediastenum – cough)
Diagnosis
• LN biopsy
• CBC: normal/ normocytic, normochromic anemia
• CXR: mediastenial mass
• ↑ESR: disease activity
• CT: method of choice for staging
• Serum LDH, if ↑ bad prognosis
• PET: used for staging, assesment of response and direction of treatment

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Ann Arbor staging classification
• Stage I: single LN, single extralymphatic organ
• Stage II: two or more LN regions on the same side of the diaphragm
• Stage III: involvement of LN regions or both sides of the diaphragm
• Stage IV: diffuse disseminated involvement
Treatment
• Early stage (I,II) no symptoms, brief chemotherapy with irradiation
• Advanced: cyclical combination of chemotherapy with irradiation
(40% - 5 year survival rate)
Non Hodgkin´s lymphomas

60% of all lymphoma

Etiology
• Sporadic
• Immunideficiency: HIV, severe combines immunodeficiency
• Geneticsyndrome: boom syndrome
• Pediatric NHL are diffuse, highly malignant and show little differentiation
Types
• Burkitt lymphoma
• Diffuse large B-cell lymphoma
• Lymphoblastic
• Anaplstic large cell lymphoma
Clinical finding
• Peripheral lymphadenopathy in multiople sites (painless and rubbery)
• Systemic B symptoms, tumor lysis syndrome
• According to involved sites
o Thoracic: cough, superior vena cava syndrome, dyspnea, pleural
effusion
o Abdomial: mass, intestinal obstruction, ascites
o Head and neck: nasal snuffiness, earache, hearing liss, tonsillar
enlargement
o Bone pain:
• Burkitt´s lymphoma: abd or head/neck disease, CNS and bone marrow
are often involved
• Lymphoblastic lymphoma: intrathoracic/mediastenal mass, CNS and BM
involvement
Diagnosis Treatment
• LN biopsy, • Systemic chemotherapy
immunophenotyping • Similar to ALL for T cell
• BM biopsy, CSF for lymphomas
infiltration • COAAD for B cell lymphoma
• CT and PET: for staging • Prognosis: is genarally goo
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13c.Primary monosymptomatic Nocturnal Enuresis
Definition
Involuntary urination while asleep after the age at which bladder control usually
occurs (18-24months). Diagnosis is not made before child reaches the age of 5
Types
• Primary nocturnal enuresis
o Bedwetting occuring after a child is old enough to stay dry, or
minimum nights per week with no long periods of dryness
• Secondary nocturnal enuresis
o After patient goes through a period of dryness (>6months)
Etiology
• Genetics
• Neurological developmental delay
• Stressful events
• UTI
• Small bladder
• Diabetes type 1
• Constipation (buildup of pressure on the bladder)
• Drug side effects
Mechanisms
• Lack of hormones: Arginine vasopressine reduces kidney’s urine output
production of urine at night.
o This cycle is not present at birth, and usually developed between
2-6years
• Ability to wake up when bladder is full
o Development of this sensory cycle begins in ages 1-3years
Diagnosis
• History: frequency of bedwetting, periods of dryness
• Screening for bladder abnormalities - Ultrasound
• Elimination of other pathological underlying causes
o Infection, diabetes, psychological stress (Encopresis)
Treatment
• Treatment of underlying cause
• Diabetes – insulin
• Infection – ATB’s
• Anatomical abnormalities – Surgery
• Psychological stress - therapy
• Motivational therapy


14a. Arterial Hypertension
Definition
Blood pressure above 95th percentile, measured 3 times indicates hypertension
• Pre hypertension – BP between 90th-95th percentile
• Normal – systolic and diastolic <90th percentile
Stages of hypertension
o Stage 1: >95th percentile, >99th percentile + 5mmHg
o Stage 2: >99th percentile + 5mmHg
o White coat hypertension (anxiety for doctor)
Etiology
• Primary hypertension
o Usually in obese adolescents – mildly ↑BP
o Etiology:
§ Obesity
§ Salt intake
§ Environmental stress
§ Lack of exercise
§ Genetic factor
§ Negative emotions
• Secondary hypertension
o Highly elevated BP – organ complications (common and early)
Etiology:
Renal hypertension (70%) Vascular hypertension (10%) Endocrine (10%)
Chronic renal parenchymal Umbilical arterial/venous Congenital adrenal
disease catheter hyperplasia
Polycystic kidney disease Renal artery thrombosis Hyperthyroidsm
Obstructive uropathy Renal vein thrombosis ↑Steroids
Acute nephritis Coarctation of aorta Pheochromocytoma
Chronic kidney disease Vasculitis Hyperaldosteronism
SLE Cushing syndrome
Neurological Tumors Medications Other
Secondary to pain Neuroblastoma Steroids Bronchopulmonary
dysplasia
↑Intracranial Wilms tumor Aminophylline, caffeine, Extracorporeal
pressure amphetamine, cocaine membrane oxygenation
Erythropoetin
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Clinical features
• Asymptomatic
• Headache
• Visual symptoms
• Epistaxis
• Altered conscioussness
Hypertensive crisis
• Acute and very high elevation of BP
o Urgent: no end-organ damage
o Emergent:
§ CNS: seiures, intracranial bleeding
§ Cardio: acute heart failure
§ Kidney: acute renal failure
§ Eyes: edema of optic nerve papilla
Diagnosis
o Confirm/exclude hypertension
o Evaluation of severity of hypertension (stage 1/2)
o History and physical examination
o Lab: Renal function, CBC, hormonal profile
o Urine: analysis
o Renal ultrasound, doppler, CT
o Find end-organ damage
o Heart: ECG, X-ray, ECHO
o Kidney: microalbumiuria
o Eyes: chronic changes on optic fundus
Treatment
Target BP:
Primary hypertension with/without end-organ damage <95th percentile
+ Diabetes (cardiovascular risk) <90th percentile
+ end-organ damage (LVH, retinopathy) <50th percentile
Chronic kidney disease <50th percentile
• Weight reduction
• Dietary approach to stop hypertension
• Salt restriction
o 4-8 years: 3,1g/day – Over 8 years: 3,8g/day
• Exercise - aeorobic
Indications for drug:
• Primary hypertensions lasts <6 months
• Secondary hypertension
• Symptomatic or 2nd stage
• End organ damage
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• ACE inhibitors
• Beta blockers
• Calcium channel blockers
• Diuretics
First choice Addition

Primary hypertension Thiazide Calcium channel blocker
Secondary hypertension Calcium channel blocker
Chronic kidney disease ACE inhitors Diuretics
Diabetes mellitus ACE inhibitors
It takes 3-4 weeks to stabilize blood pressure

Complications
• Left ventricle hypertrophy
• Arrhytmias
• Acute kidney injury
• Retinopathy

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14b. Congenital and acquired Coagulopathies
Hemostasis
Physiological balance of procoagulant and anticoagulant. Physiologic process in
which bleeding stops, or clot dissolves. (first step of wound healing)
1. Congenital (inherited) coagulation diseases

• Common and usually involve a deficiency of only one coagulation factor
A. Hemophilia A
• Def: Due to lack of factor VIII
• X-linked recessive disease
• Classification:
Mild Moderate Severe

• Bleeding after • Severe bleeding after • Spontaneous
trauma/surgery injury bleeding into muscle
• Plasma level of VIII • Bleeding spontaneously and joints
(>5 IU/dL) • Plasma level of VIII o Crippling
(1-5 IU/dL) arthropathy
• Plasma level og VIII
(<1 IU/dL)

Clinical features
Knees, ankles, elbows, hips, wrist Bleeding sites
Joint Painful, swollen, tender, warm, limitation of movement
Intracranial bleeds Extradural, subdural, intracerebral bleeding
Diagnosis
• ↑Activated thromboplastin time
• ↓Factor VIII
• Ultrasound, CT
Treatment
• IV infusion of factor VIII concentrate
o Complicatons: antibody against factor VIII, Infections
• Pressure dressing
• Rest
• Ice bag
• Physiotherapy
• Prophylaxis
• Compress
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B. Hemophilia B – Christmas disease
• Def: Caused by deficiency of factor IX
• X-linked recessive disease
• Identical clinical findings as Hemophilia A, but may be slower to bleed,
and 5 times more common
Treatment
• IV infusion of factor IX concentrate

C. Hemophilia C
• Def: Caused by deficiency of factor XI
• Autosomal recessive disease
• Clinical findings:
o No bleeding into joints
o Bruising
o Epistaxis
o Heavy menstrual bleeding
o Less severe than hemophilia A and B
Treatment
• IV infusion of factor XI concentrate

D. Von Willebrand disorder

Def: Inherited bleeding disease due to deficiency or abnormal function of von
Willebrand factor. Most common disease of coagulation. Factor VIII:C refers to
the pro-coagulant activity of factor VIII, measured by PT

Function:
• Facilitates platelet adhesion to the damaged endothelium
• Acts as the carrier protein for factor VIII:C, protecting it from breakdown
Types:
• Type 1 (Autosomal dominant, mild disease, most common)
• Type 2 (Autosomal dominant, mild-moderate, rare)
o Type 2b lead to thrombocytopenia
• Type 3 (Autosomal recessive, severe, rare)
Clinical findings
• Mucosal bleeding (nose and GIT)
• Excessive bruising
• Post traumatic bleeding
• Type III – looks like hemophilia A, but rarely have joint/ muscle bleeding

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Diagnosis
• ↑Activated thromboplastin time
• ↓Factor VIII:C
• Prolonged bleeding time
• Normal PT/INR
• ↓Von Willebrand factor
Treatment
Depends on the type and severity of disease
• Avoid NSAID’s, IM injections
• Local bleeding – pressure and tranexamic acid
• Desmopressin for type I and II
• IV factor Von Willebrand / factor VIII
2. Acquired coagulation disorder

Vitamin K deficiency
• Def: Vitamin K is necessary for formation of active factors II, VII, IX, X,
protein C and S
• Etiology:
o Malnutrition (decreased intake)
o Malabsorption
o Warfarin
• Clinical findings:
o Bruising o Birth defects in infants
o Petechiae o Cerebral/GIT
o Hematoma bleedings
• Diagnosis:
o ↑PT
o ↑Activated thromboplastin time
o ↑Prothrombin time , bleeding time, bleeding count – normal
• Treatment:
o Phytomenadion – vitamin K
o Treatment of underlying cause

3. Liver disease
• Def: Liver is the site of synthesis and clearance of most procoagulants and
anticoagulant proteins. Because all clotting factors (except VIII) are
produced in the liver, coagulation abnormalities are normal in patients
with liver disease
• Diagnosis: • Treatment:
o ↑Bleeding time o Fresh frozen plasma
o ↑PT, INR o Desmopressin
o ↑Activated o Vitamin K
thromboplastin time
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4. Disseminated intravascular coagulation (DIC)
• Def: It is the pathological activation of blood coagulation pathways that
occurs in response to variety of severe diseases
• Etiology:
Neonatal period Older children

• Severe asphyxia • Septicemia
• Sepsis • Trauma / burns
• Severe IUGR • Shock
• Respiratory distress syndrome • Hepatic failure
• Aspiration pneumonia • Anaphylaxis
• Necrotizing enterocolitis • Blood tranfusion reactions

Clinical features
Ischemic findings (earliest signs) Bleeding from mouth, nose, venepunture sites
Intracranial bleeding (cerebral dysfunction) Renal: oligura, hematuria, cortical necrosis
Myocardial dysfunction Skin necrosis/gangrene
Acute respiratory distress syndrome Microangiopathic hemolytic anemia
Diagnosis
• Lab:
o Platelet, fibrinogen ↓
o ↑Activated thromboplastin time
o ↑Prothrombin time, ↑Thrombin time
o ↑D-dimer,
o ↑Fibrin degradation product
o Thrombocytopenia <100,000 platelets and rapidly decreasing
Treatment
• Supportive therapy: Oxygen
• Platelet transfusion
• Fresh frozen plasma, cryoprecipitate


14c.Otitis Media, Masoiditis, Hearing screening
Otitis media
Definition
Otitis media is an inflammation or infection of the middle ear, tympanic
membrane, ossicles and Eustachian tube. It is the primary cause of hearing loss.
Types
1. Acute otitis media/ suppurative
2. Otitis media with effusions
3. Chronic suppurative otitis media
4. Adhesive ototis media
1. Acute suppurative otitis media

Usually follows an URTI, recurrent disease:
• episodes on 6 months or more four in 12 month
• more common in auntun and winter due to ↑ viral infection: obstruction
of ear, nose throat
Risk factor
Daycare Passive smoking Positive family history
No vaccination Male No breastfeeding
Left palate Cleft palate Short eustrachian tube
Immature immune sys Frequent URTI
Etiology
• S.pneumoniae • S.pyogenes
• H.influenza • S.aureus
• M.catarrhalis
Clinical features
• Otalgia: pulling on the ear/hair, lying down more
• Otorrhea: indicate perforation of eustrachian tube
• Head ace, irritability in young infant/ toddler
• Concurrent/ recurent URTI: cough, rhinorrhea
• Fever, lethargy
• GIT: anorexia, nausea, vomiting, diarrhea
Complications
• Otologic
o Hearing loss o Chronic suppurative
(conductibe and otitis media
sensorineural) o Cholestratoma
o Tymphanic membrane o N.VII palsy
perforation o Labyrinthitis
o Mastoiditis
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• Intracranial
o Meningitis
o Epidural ebcess
o Brain abcess
o Sigmoid sinus thrombosis
Diagnosis
• Otoscopy
• Tympanocenthesis: culture
• Tympanogram/metry
• Audimetry
Treatment
• 5 days of p.o amoxicillin/cefuroxime
2. Otitis media with effusion

Also called glue ear, characterized by persistent fluid (non-purulent) in the
middle ear that may be mucoid or serous. It often occurs after resolution of acute
otitis media. There is Eustachian tube dysfunction and negative middle ear
pressure that discharge a transudate from mucosa.
Clinical features
• Hearing loss or aural fullness
• No fever or otalgia
Diagnosis
• Pneumatic otoscopy
• Tymanometry
• Audiometry
Treatment
• Tympanostomy tube
• Hearing aid
3. Chronic suppurative otitis media

Perforated tympanic membrane, chronic inflammation of the middle ear that last
for more than 6 week

Clinical features
• Otorrhea: perforated TM
• Hearingloss
Treatment
• ATB drops: neomycin
• Aural toilet

4. Adhesive otitis media
Occurs when thin tympanic membrane becomes sucked into middle ear space
and get stuck.
Clinical finding
• Conductive hearing loss
• Chilesteatoma
Treatment
• ATB: amoxicillin
Hearing screening
Hearing impairment has major impact on a child´s development. Early
identification improves prognosis. If treated by 6 months most children develop
same level of language skill as peers.

• Universal screening
• High risk criteria
o Family history o ELBW <1500g
o In utero infection o Ototoxic medication
(TORCH) o Hyperbilirubinemia
o Cranifacial o Bacterial meningitis
abnormalities o Low APGAR score
Techniques
• Otoacustic emission testing (OAE)
o used successfully in most universal newborn screening programs,
are quick, easy to administer, and inexpensive, and they provide a
sensitive indication of the presence of hearing loss
o Results are relatively easy to interpret. OAE tests elicit no response
if hearing is worse than 30-40 dB
• Auditory brainstem evoked response (ABR)
o auditory evoked electrophysiologic response that correlates highly
with hearing, has been used successfully and cost-effectively to
screen newborns and to identify further the degree and type of
hearing loss.

Many children become hearing impaired after neonatal period and are not
identified by newborn screening

130

Mastoiditis
Mastoiditis is an inflammation of the mastoid air cells in the temporal
bone Technically; all cases of AOM are accompanied by mastoiditis by virtue of
the associated inflammation of the mastoid air cells. The etiology for mastoiditis
is the same as of OM, and it is generally a complication of OM. Blockage of the
antrum by inflamed mucosa entraps infection in the air cells by inhibiting
drainage and by precluding re-aeration from the middle-ear. Mastoiditis may be
arrested at any point.

Classification
It progresses in the following 5 stages:
• Stage 1 – Hyperemia of the mucosal lining of the mastoid air cells
• Stage 2 – Transudation and exudation of fluid and/or pus within the cells
• Stage 3 – Necrosis of bone caused by the loss of vascularity of the septa
• Stage 4 – Cell wall loss with coalescence into abscess cavities
• Stage 5 – Extension of the inflammatory process to contiguous areas
Clinical findings
• Otorrhea
• Fever, pain (behind the ear),
• hearing loss, poor-feeding, irritability
• Bulging of TM, auricle protrusion
• erythema, tenderness and edema over the mastoid area
Complications: facial nerve palsy, facial pain, subperiosteal abscess,
osteomyelitis, Bezold abscess (a deep abscess in the soft tissue of the neck)

Diagnosis
• CT and tympanocentesis
Treatment
• ATB: ceftriaxone, cefepine, ampicilin-sulbactam, vancomyzom
• Surgery: mastoidectomy

131

15a. Upper and lower Urinary tract infections
Classification
• Pyelonephritis – inflammation of renal parenchyme, calyx and renal
pelvis
• Cystitis – inflammation of bladder
• Urethritis – inflammation of ureter
Etiology
Usually from ascending infection – bacteria arise from the fecal flora, entering
the bladder via the ureter

Etiology
E-coli Proteus
Klebsiella Pseudomonas
Enterococcus S.saprophyticus
C.trachomatis

Risk factors
Females more than male Obstructive uropathy
Short urethra Urinary catheter
Uncircumsized male Bubble bath
Voiding dysfunction Megaureter
Vesicoureteral reflux Sexual activity

Pyelonephritis
Clinical findings
Neonate Infants >2 years
Jaundince Fever >48hours Urgency/ Frequency
Hypothermia/ Fever Diarrhea Dysuria, enuresis
Feeding problems Vomiting Abdominal pain
Vomiting Poor feeding Fever
Failure to thrive Hematuria Hematuria
Malodorous urine Malodorous urine

132

Cystitis
Clinical findings
Dysuria Urgency/frequency Suprapubic pain
Incontinence Malodorous urine Hematuria

Urethritis
Clinical findings
Dysuria Perineal discomfort Perineal erythema
Urethral discharge Itching Vaginal irritation

Diagnosis
UTI and pyelonephritis must be considered in young pediatric patients with
fever and/or nonspecific symptoms
• Urinanalysis: culture, nitrate, WBC, RBC
• Blood test: WBC, ESR, CRP
• Ultrasound: Dilatation of kidney parenchyme
• Urography
• Cystogram
Treatment
• Per oral/IV ATB’s
o Ampicillin and gentamycin – neonates
o Cephalosporin and gentamycin – infants /older children
o Vancomycin – toxic patients
• Anatomic abnormalities of the urinary tract
• Vesicoureteral reflux
• Ureteropelvic obstruction
• Fever of unknown origin
• Posterior urethral valves

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15b. Differential diagnosis of chronic cough
Definition
Cough is the most common syptom of respiratory disease
• Reflex response indicating irritation of nerve receptors (irritant/cough
receptors) located in the:
o Pharynx o Large bronchi
o Larynx o Stomach
o Trachea
• Stimuli
o Excessive secretions
o Aspirated foreign material
o Inhaled dust particles
o Noxious gases
o Infective agents/allergic process
• Chronic cough is cough lasting for more than 4 weeks
Atopic triad: asthma, allergic rhinitis, eczema
Condition Type of cough and clinical features Diagnosis
Asthma • Recurrent and seasonal • Spirometry (↓FEV1/FVC)
• Allergic stimuli • Eosinophilia
• Night/after exercise • Skin prick test
• Expiratory dyspnea, wheeze • Clinical airflow limitation
• Chest tightness, URTI • Trial of steroids
• Cold weather
• Atopic triad
Recurrent RTI • Recurrent with sputum • X-ray
(pneumonia/ production • Sputum analysis culture
bronchitis) • Moist cough • IgG
• Fever
Chronic sinusitis • Persistent • Sinus aspirate
• At night • Culture
• Post nasal drip • CT
• Nasal discharge

• Congestion
• Throat clearing
• Headache
Allergic rhinitis • Recurrent • Skin prick test
• Seasonal • Eosinophilia
• Rhinorrhea • IgE
• Atopic triad
• Triggered by allergic stimuli (dust,
pollen)
134

Condition Type of cough and clinical features Diagnosis
Pertussis • Persistent • Culture from
• Paroxysmal-insp. nasopharynx
• Whoop • Serology-IgM, IgG
• Vomit • Pertussis toxin
• Sputum
Foreign body • Abrupt onset of persistent cough • X-ray
aspiration • Staccato and paroxyysmal exp. • Bronchoscopy
• Wheezing
• Dyspnea
Cystic fibrosis • Persistent with sputum • Newborn screening
• Dyspnea • Sweat test >60mEq/L of Cl
• Wheezes • Genetic testing
• Digital clubbing
• Malnutrition

• FTT
• Steatorrhea with malabsorption
• Recurrent RTI
Aspiration • Persistent with eating/drinking • Clinical findings
(GERD) • Hoarseness of voice • Laryngoscopy
• Respiratory stridor • Serology
• PCR
Tuberculosis • Persistent • X-ray

• Appear when endobrachial tree is • Tuberculin test
affected • IFN gamma assay
• Moist cough with productive
hemoptysis

Habit cough • Psychogenic cough (persistent • Exclude other diseases
during day, but dissapears • Tests are normal
during night)
• Barky cough
• Refractory to treatment

135

15c. Numeric and structural anomalies of
autosomes and gonosomes
Definition
• Autosome – a chromosome that is not a sex chromosome
• Gonosome – a chromosome that is sex chromosome (X/Y)
Types
Autosomes Gonosomes
Down’s syndrome Turner syndrome

Patau syndrome Klinefelter syndrome
Edward syndrome Fragile X syndrome
Cri du chat syndrome Super female
Di George syndrome Super male
1. Autosomes
A) Down’s syndrome
Gen: Trisomy of 21 – most frequent liveborn chromosome abnormality
Increased risk with increased maternal age
Types
• Simple trisomy – 93%
• Mosaicism – 2%
• Translocation form – 3,5%
Clinical findings
• Mental retardation
• Dysmorphic facies
o Flattened nose o Shortened hands
o Slanted eyes o Single transverse
o Small ear, mouth palmar creas
o Flat head o Bent 5th finger
• Hypotonus
• Birth defects
o Heart– atrial/ventricular septal defect, patent ductus arteriosus
o GIT – duodenal atresia, celiac disease, Hirschprung disease, GERD
• Increased risk of infection and leukemia
Diagnosis
• Amniocentesis
• Karyotype analysis
• Chorionic villus sampling
Prognosis
• Live longer than ever before (40years)
136

B) Patau syndrome
Gen: Trisomy of 13 – 47XX / 47XY + 13
Clinical findings
Microcephaly Spina bifida
Short neck and cleft palata Polydactyli
Micropthalmia, eyes are close Heart defect- ventricular septal
Low set ears defect, patent ductus arteriosus
Intellectual disability

Diagnosis
• History Prognosis
• Physical examination • Short survival
• Fetal chromosome testing

C) Edward syndrome
Gen: Trisomy of 18 – 47XX / 47XY + 18
• Increased risk in female
Clinical findings
Intrauterine growth retardation Clenched hand with overlapping
Microcephali with occipital fingers
enlargement Club foot
Small mouth/jaw, cleft lip/palate, Heart–defect atrial/ventricular
short neck septal defect, patent ductus
Omphalocele, esophageal atresia arteriosus
Prognosis
Poor prognosis

D) Cri du chat syndrome

Gen: Deletion of short arm of chromosome 5
Clinical findings
Low birthweight Excessive drooling
Feeding problems Hypotonia
Small head and jaw Heart defect – atrial/ventriculo
Wide eyes with skin folds septal defect, patent ductus
Cat like cry arteriosus
Diagnosis
• History • Amniocentesis
• Physical examination • Chorionic villus sampling

137

E) Di George syndrome
Gen: Deletion of long arm on chromosome 22
Clinical findings
Thymic, parathyroid aplasia Palatal abnormality
Congenital heart disease Hypocalcemia
Microcephaly

2. Gonosomes
A) Turner syndrome
Gen: Monosomy of chromosome X – 45X
Most common sex chromosome abnormality in females
Types
• 45X – absence of whole chromosome
• 45X/46XX or 45X/46XY – mosaicism
• structural abnormalities of X/Y chromosomes
Clinical findings
Newborn Older children/adolescents
Webbing of neck Short stature
Protruding ears Dysmorphic phase – flattened nasal bridge,
epicanthal fold, shield chest
Lymphedema of hands and feet Visual impairments
Heart defect – bicuspid aortic valve, aortic stenosis, coarctation of aorta
Structural renal anomalies – horseshoe kidney – 60%
Hypothyroidism
Gonadal dysgenesis – estrogen deficiency (underdeveloped organ/infertility)
Normal intelligence, but learning difficulties – 70%

B) Klinefelter syndrome
Gen: Most common genetic cause of hypogonadism and infertility in men
• 47XXY karyotype – 70%
• Rarely diagnosed before puberty
Types
• 45X – absence of whole chromosome
• 45X/46XX or 45X/46XY – mosaicism
• structural abnormalities of X/Y chromosomes
Clinical findings
Decreased muscle mass and gynecomastia Small atrophic testes
Lack of development of secondary Small penis
characteristics (beard, pubic/axillary hair, Normal intelligence
pitched voice) Taller stature with long limbs
Decreased spermatogenesis and infertility
138

C) Fragile X syndrome
Gen: X-linked disease characterized with repeats of CGG triplet within the
mental retardation 1 gene
• Shows features not typical for x-linked disease
Clinical findings
Mental retardation (IQ-40) ADHD – 80%
Anxiety – 100%
Long face, large mandible, large elevated ears,
macroorchidism Seizures
Mitral valve prolapse Diabetes
Joint laxity, flat feet Strabismus
Autism – 30%

Diagnosis
• Karyotype analysis
• PCR
Treatment
• Valproate
• Ritalin
• SSRI

D) Super female
Gen: 47XXX
Clinical findings
• Often normal with normal fertility
• Some may present with slight mental retardation

E) Super male
Gen: 47XYY
Clinical findings
• Normal fertility
• High stricture, muscularity
• Behavior disease – aggressive, sexual deviations


16a. Vesicoureteral reflux and obstructive
uropathy, Undescended testis
1. Vesicoureteral reflux
Gen: Refers to the retrograde flow of urine from the bladder to the ureter and
kidney – usually congenital
Pathogenesis
Occurs when the submucosal tunnel of ureter between the mucose and detrusor
muscle is short or absent
• There is malfunctioning flap-valve mechanism
• Increased risk of infection – renal injury/scarring
Etiology
• Neurogenic bladder
• Ureteral dysfunction, ureterocele
• Bladder outlet obstruction

Grade
Grade 1 Reflux into distal ureter with/without dilation
Grade 2 Reflux into the pelvix calycec with/without dilation
Grade 3 Reflux into pelvis and cylyces with mild/moderate dilation
Grade 4 Reflux into grossly dilated uteter and pelvis
Grade 5 Massive reflux with significant rortousity and dilation of ureter and calyces

Clinical findings - Presents with features of UTI pyelonephritis
Neonate Infants Older children
Fever Fever Fever
Failure to thrive Failure to thrive Failure to thrive
Feeding problems Feeding problems Feeding problems
Diarrhea, vomiting

Diagnosis
• Voiding cystogram
• Ultrasound
• Renal scintigraphy

140

Treatment
• ATB prophylaxis
o Amoxicillin
o Co-trimoxazole
o Nitrofurantoin
• 1 year for grade 1,2
• 2 years for grade 3-5
• Target is gut flora, narrow spectrum is used to avoid resistence
• Surgery:
o Controversial
o Recommended for high grade reflux
o Ureteral re-implantation

2. Obstructive uropathy
Gen: Obstructive uropathy includes congenital and acquired lesions, which cause
obstruction to urinary system. They can lead to damage to renal parenchyme due
to back pressure or urinary tract infections
Pathogenesis
Occurs when the submucosal tunnel of ureter between the mucose and detrusor
muscle is short or absent
• There is malfunctioning flap-valve mechanism
• Increased risk of infection – renal injury/scarring
Etiology
• Congenital development defects of kidney and urinary tract
• Pelviureteral junction obstruction
• Vesico-ureteral obstruction, ureterocele, diverticuli of bladder
• Posterior urethral valves with subvesical obstruction
• Anterior urethral valves
• Urethral atresia, meatal stenosis
Clinical findings
• Signs of dehydration and intravascular volume depletion (partial
obstruction)
• Peripheral edema, hypertension (obstruction from renal failure)
• Palpable kidney or bladder
Diagnosis
• Lab: CBC, electrolytes, creatinine, BUN (eliminate renal failure)
• Urine: Microscopic hematuria, urine sodium decreased, elevated
osmolality
• Ultrasound, CT, X-ray, Pyelography
141

Treatment
• Transurethral catheter
• Analgesics
• Nephrostomy
• Ultrasound shockwave treatment (extracorporal lithotrypsi)

3. Cryptorchidism
Gen: Most common genital problem in pediatrics – undescended testis
• Absence of one/both testes in scrotum
If a testis is not functional in scrotum it may be
• In path to descent
• Inguinal canal
• Ectopically testes (outside inguinal canal, perineum, femoral canal)
• Underdeveoloped (hypoplastic)/severely abnormal (dysgenetic)
• Missing
Etiology
• Severe prematurity
• Positive family history
• Prenatal estrogen pressure
• ↓Intra abdominal pressure
Risk factors
• Prematurity, low birth weight
• Diabetes/obesity in mother
• Smoking, alcohol
Clinical features
• No palpable testes in scrotum
Diagnosis
• History
Treatment
• Watchful waiting
• 6-12 months – surgery (orchipexy)
• Hormonal treatment – hCG/gonadotropin releasing hormone

142

16b. Congenital and acquires Thrombocytopenias
and Trombocytopathies
Thrombocytopenia
Definition
Platelet count < 150 x 109/L
Clinical feature
• Petechial and mucosal bleeding, which is accompanied by epistaxis,
hematuria and positive fecal occult blood test
• Risk of serious and spontaneus bleeding occurs with
o platelet count <10 - 20 x 109/L
o major surgery or trauma
o concurrent coagulopathy
o anti coagulent therapy
Etiology
1. Increased platelet destruction/ consuption
2. Decreased platelet synthesis
3. Sequestration
4. Medication
1. Increased platelet destruction or consumption

Classification
A. Immunemediated
i. Immune throbocytopenia purpura
ii. Neonatal alloimmune thrombocytopenia purpura
iii. Maternal immune thrombocytopenia purpura
B. Non-immunemediated
i. Thrombotic thrombocytopenia purpura
§ Kasbach-Meritt syndrome
§ Upshaw-Schulman sydrome
A. Immune mediated
i. Immune thrombocytopenia purpura
Often follows a common viral infection (VZV, measles) in a otherwise healthy
child. Auto Ab are directed against the platelet surface. Predominantly in
children between 1-4 years. Chronic ITP if longer than 12 months

Clinical features
• Purpura
• Petechiae
• Mucosal bleeding
• Menorrhagia
143


Diagnosis
• Thrombocytopenia (<20x109/L)
• Platelet size: normal or big
• No anemia, normal WBC
• BM aspiration: ↑nr of megakaryocytes
Treatment
• Treat only if platelet count is very low
• Prednisone (1mg/kg/day), IV Ig
• Splenectomy and platelet infusion
ii. Neonatal alloimmune thrombocytopenia purpura

Occurs due to transplacental transfer of maternal Ab directed against fetal
platelets

Clinical features
• Neonate
o Generalized petechiae and purpura within the first days
o Increased risk of intracranial hemorrhage
Diagnosis
• Detection of maternal Ab
• Resolve within 2-4 months after delivery

Treatment
• IV Ig prenatally to the mother
iii. Maternal immune thrombocytopenia purpura

Occurs in children born to mothers with ITP or history if ITP. Passive transfer of
maternal antiplatelet Ab

Clinical feature
• Risk of hemorrhage, but less than in NATP
• Resolve within 2-4 months after delivery
Treatment
• Prenatal IV Ig
• Corticosteroids to mother

144

B. Non-immune mediated
i. Thrombotic thrombocytopenia purpura
Usually in adults and occasionally on adplescents

Etiology
• Idiopathic TTP, secondary TTP
• Congenital: familial TTP/HUS
• Acquired: infection, pregnancy, SLE, HIV, DIC, cancer
• Drug induced: valporic acid, carbamazepine, cotrimoxazole, vancomycin
• Deficiency of metalloproteinase ADAMTS -13
Pathogenesis
• Widespread adhesion and aggregation of platelets
o Microvascular thrombosis and thdombocytopenia
Clinical features
• Thrombocytopenia Thrombocytopenia
o ↓platelet, brusing, purpura

• M.a hemolytic anemia Fever
Microangiopathic
hemolytic anemia
o Anemia, jaundice
• Neurological symptoms
o Altered mental status
Neurological
o Stroke Renal failure symptoms
o Headache
• Renal failure
• Fever
Types
• Kasback-Meritt syndrome
o Giant hemangioma and intravascular coagulation:
thrombocytopenia
• Upshaw-Schulman syndome
o Hereditary form of TTP due to inherited deficiency of ADAMTS 13

Treatment
• Plasmapheresis
• Corticosteroids

145

2. Decreased platelet synthesis
Platelets are normal sized or small
A. Acquired disease of platelet synthesis

Occurs in BM failure or infiltration

Etiology
• Leukemia • Dehydration
• Lymphoma • Wiscitt-Aldrich syndrome
• Aplastic anemia • Thrombocytopenia absent
• Vit B12/folic acid deficiency radius (TAR) syndrome
• Viral infection

i. Wiscott-Aldrich syndrome
X-linked disease characterized by hypogammaglobulinemia, eczema and
thrombocytopenia (bloody diarrhea) due to a defect in cytoskeletal protein
found in lymphocytes and platelets

Diagnosis Treatment
• Tiny platelets are seen in • U.c blood/BM transplant
periphery • splenectomy
• Low Ig levels (IgM)

ii. TAR syndrome
Thrombocytopenia and bilateral radius anomaly, there is absence/hypoplasia of
megakaryocytes in marrow

Clinical findings
• Skelatal anomalies (ulna, lower extremity)
• Intolerance to cow milk formula
Treatment
• Often remits within first year of life
3. Sequestration
Thrombocytopenia develops in patients with massive splenomegaly and
hypersplenism. Spleen acts as a sponge for platelets

Clinical findings
• Mild anemia
• Leukopenia
Treatment
• Portal HT
• Hematological abnormalities
146

4. Disease of platelet function (thrombocytopathies)
Acquired disease of platelet function
Platelet dysfunction due to liver failure, kidney disease due to uremic toxins and
drugs (ASA, NSAIDs, valproic acid)
Congenital disease of platelet function

• Bernard-Soulier syndrome
o Gen: caused by absence or devere defect of VWF receptor on
platelet membranes
o CF: thrombocytopenia, giant platelets, ↑bleeding time (>20min)
• Glanzmann thromastenia
o Gen: caused by platelets fibrinogen receptor defect. Platelets are in
normal nr, morph, size in peripheral blood smear but bleeding
time is incresed.
o Tx: desmopressin (↑VWF and VIII levels, corrects bleeding time)
o Platelet transfusion
Thrombocytopenia develops in patients with massive splenomegaly and
hypersplenism. Spleen acts as a sponge for platelets

147

16c.The most frequent respiratory complications in
term Neonates (RDS, PPNH, Transitory Tachypnea of
newborn, MAS)
Definition
Respiratory diseases are the most frequent cause of admission to NICU for both
term and preterm infants
Clinical features
• Tachypnea >60 breaths/min
• Expiratory grunting – exhalation of gas through a partially closed glottis
• Intercostal retractions
• Nasal flaring
• Central cyanosis/pallor
Etiology
• Non respiratory cause of repiratory distress
o MAC
o Abdominal distention: bowel obstruction, necrotic enterocolitis,
congential diaphragmatic hernia
o Congenital heart disease: PDA, VSD, TGA
o Hemolytic anemia, polycythemia
• Respiratory causes
o Persistent pulmonary hypertension (PPNH)
o Meconium aspiration syndrome
o Pulmonary hypoplasia
o Respiratory distress syndrome – hyaline membrane disease
o Transitory tachypnea of newborns
Persistent pulmonary hypertension

Definition
Defined as the failure of the normal transition from fetal to neonatal circulation.
It is a syndrome characterized by marked pulmonary hypertension that causes
hypoxemia and right-to-left intracardiac shunting of blood. Due to perfusion!
Pathogenesis
• At birth, there is normally a dramatic cardiopulmonary transition and the
pulmonary arterial pressure decreases (<50% within 24h)
• In some newborns, this normal decrease of pulmonary vascular
resistance doesn’t occur and PPHN develops.
• Newborns have patent foramen ovale and PDA, the elevated pulmonary
vascular resistance leads to R-L shunting of blood and severe hypoxemia
with cyanosis occur.

148


Etiology

Meconium aspiration Birth depression
Infection Low body temperature
Idiopathic PPHN Congenital diaphragmatic hernia
Polycythemia Cyanotic heart disease
Pulmonary hypoplasia
Clinical features
• Signs of respiratory distress due to ↓CO could lead to shock
Asphyxia Tachypnea Tachycardia

Capillary refill time Respiratory distress Lactic acidosis
Hypotension Cyanosis Low APGAR
Murmurs
Diagnosis
• ECHO: ↑pulmonary artery pressure due to R-L shunting
• X-ray: underlying disease, rule out congenital heart disease
• ABG
• Blood: CBC, coagulation, electrolytes
• Congenital heart disease:
o Tetralogy og fallot
o Transposition of the great arteries
o Tricuspidal atresia, stenosis
o Total anomalous pulmonary venous return
• Primary lung disease
o Surfactant deficiency
o Aspiration
o Pulmonary hypoplasia
• Sepsis
Treatment
• Dopanime/dobutamine: improve myocardial function and ↑BP
• Assisted ventialation: most important
• NO (inhaled): effective pulmonary vasodilator
• ECMO: extracorporal membrane oxygenation
o System that bypasses the heart and lung
• Surfactans:
• Other
o Maintain body temperature
o Correct electrolyte disturbances, glucose, MAC
o Nutritional support
o Minimal stimularion/handeling of newborn.
149


Meconium aspiration syndrome

Definition
Meconium is the first substance discharged from the GIT in the perinatal period
and consists of a mixture of H2O, mucopolysaccharides, GI secretions, solids,
blood, minerals and lipids. Which makes the meconium very sticky. Aspiration of
the meconium through the trachea into the bronchial tree, sometimes down to
alveoli gives respiratory distress.
Pathogenesis
• Meconium develops in fetal intestine by 10th week of life, it is
approximately 200g at birth.
• Due to lack of strong peristalsis, good anal sphincter tone, low levels of
motilin and a cap of viscous meconium in the rectum, in utero passage is
uncommon till term.
• In utero hypoxia and acidosis induce a vagal response with increased
peristalsis and relaxed anal sphincter, which let meconium pass.
o This could be caused due to:
o Airway obstruction
o Interference with alveolar gas exchange
o Chemical pneumonitis
o Surfactant dysfunction
Clinical features

Hypoxemia Acidosis Hypercapnea
Pneumothorax Pneumomediastinum Respiratory distress
Atelectasis Pneumopericardium
Diagnosis
• X-ray: pneumonia, pneumothorax
• Physical exam: neonate covered with meconium and amniotic fluids
Treatment
• Airway clearing
• Ventilatory support (CPAP, mechanical ventilation)
• Surfactant
• Inhaled NO
• Steroid
• ECMO
• ATB if infection

150

Pulmonary hypoplasia
Incomplete development of lung tissue, characterized by reduction on the
number of lung cells , airways and alveoli that results in a lower organ size and
weight
Etiology

Congenital diaphragmatic hernia Fetal hydronephrosis
Cong. Cystic adenomatoid malformation Caudal regression syndrome
Mediastinal tumor Cervical teratoma
Fetal hydrops Ass. with oligohydramnion
Types
• Unilateral hypoplasia
o Any isolated developmental anomaly
o Often familial and asymptomatic
• Bilateral hypoplasia
o Secondary to oligohydramnion (potter syndrome, renal agenesis,
clubbed foot, facial dysmorphism)
o Chestwall deformity
o Diaphragmatic hernia
Clinical features
• Sevre repiratory distress, that could lead to respiratory failure
Diagnosis
• X-ray
• USG/MRI
Treatment
• ECMO
• Surfactant

151

Respiratory distress syndrome
Syndrome of premature infants caused by developmental insufficiency of
surfactant production and structural immaturity in the lungs. A disease of
ventilation
Etiology
• Surfactant: is produced by type 2 pneumocytes and prevents atelactasis
by reducing surface tension at low lung volumes.
• Patients have «microatelactasis» leading to hypoxemia and RDS
Clinical features
• Cyanosis
• Nasal flaring
• Tachypnea
• Chest wall retractions
• Grunting
Diagnosis
• X-ray: milky glass
• Silvermann retraction (criterias)
o Grade1 and 2
Treatment
• Corticosteroids to mother
• Surfactant: transbronchial
• 02 with CPAP (continious positive airway pressure)
• Intubation
• ECMO

152

Transient tachypnea of the newborn
Self-limited disease that occurs where this excessive lung fluid or clearance
mechanism are ineffective due to increased mucous secretion.
Etiology/risk factors
• Cesarian delivery
• Maternal astma/smoking
• Prematurity
• Premature rupture of membranes
• Low APGAR
Clinical features
• Repiratory distress signs
• Tachypnea
Diagnosis
• ABG
• Pulseoxymetry
• X-ray: prominent perihilar streaking
Treatment
• Supportive
o IV fluid, gavage feeding
o CPAP

153

17a. Acute kidney injury, Haemolytic-Uremic
syndrome
Acute kidney injury

Definition
Sudden decline in kidney function, with onset from days to weeks. Classical
symptoms would be ↑creatinin and urea, oliguria and edema

Defined according to RIFLE criteria, that is based on changes estimated
!!"#!!
creatinine clearance of urine output. Formula: eCCl = K x
!"#$

Criteria eCCl Urine output
Risk eCCl decrease by 25% <0,5ml/kg/h for 8 weeks
Injury eCCl decrease by 50% <0,5ml/kg/h for16 weeks
Failure eCCl decrease by 75% <0,5ml/kg/h for 24 weeks
Loss Persistent failure >4 weeks
ESKD Persistent failure > 3 months

Classification
• Pre-renal
• Renal (intrinsic)
• Post-renal
Pre-renal
Hypoperfusion of kidney with no parenchymal damage, if ischemia sustains it
could develop in to a renal problem (renal uremia)

Etiology
• Hypovolemia (↓true intravascular volume, hypoperfusion)
o Dehydration (80% of fluid is in ECF)
o GIT losses
o Salt-wasting renal or adrenal disease
o DI (central or nephrogenic)
o 3rd space losses (sepsis, trauma, nephrotic syndrome)
• Decreased effective intravascular volume (euvolemia, still hypoperfusion)
o Congestive heart failure
o Pericarditis and cardiac tamponade
o Hepatorenal syndrome
154

Renal
Acute tubular necrosis - ATN
• Ischemic/hypoxic
o Due to prolonged prerenal AKI or severe hypoxic insults (after
prolonged > 3 hrs surgery)
o Urinalysis: casts, PU, concentration ability
• Nephrotoxic
o Exogenous toxins (ATBs: aminoglycosides, amphotericin B,
iodinated contrast, NSAIDs, etc)
o Endogenous toxins (rhabdomyolysis, hemolysis)

Acute interstitial nephritis
• Idiopathic or hypersensitivity reaction to drugs or infectious agents (Abs
against tubular BM)
o Drugs: ATBs: penicillins, cephalosporins, anticonvulsants,
allopurinol, diuretics
o Infections: CMV, EBV, HBV, HIV
• Presents with rash, fever, arthralgia, uveitis, eosinophilia

Vascular disorders Glomerular disorders
• HUS • Acute glomerulonephritis
• TTP

• vasculitis

Postrenal
• Very rare
• Obstruction of UT anywhere from calyxes to external urethral orifice
• Congenital or acquired
• Both kidneys have to be affected
• Postrenal uremia is reversed when obstruction is relieved

Diagnosis
• History
• Volume status • Biochemical features
• USG o ↑K+, P3+,↑Screa,
• Urinalysis ↑Surea
o Normal: pre-renal AKI o ↓Na+, ↓Ca2+
o Abnormal: Renal AKI o MAC

Clinical features
• Oliguria
155

• Features of uremia
o nausea
o fatigue
o confusion
o coma
o pruritus
• Pulmonary edema- inappropriate volume replacement
Treatment
• Volume replacement
o Indicated for patients with prerenal AKI
o Avoid volume overload if renal AKI was developed, can cause
pulmonary edema
o 20ml/kg over 30 mins with isotonic saline
§ Glucose-containing solutions as maintenance fluid
• áRenal blood flow
o Dopamine and diuretics
• Stimulation of urine output
o Diuretics: mannitol, furosemide
o Only in patients with adequate blood volume
o Not used in anuric patients
• Hyperkalemia: > 6-7mmol/L
o Cardioprotective: Calcium gluconate
o Sodium bicarbonate
o Glucose and insulin
o Loop diuretics: ↑excretion
o β-mimetics: (salbutamol) shift K+ into cell
o K+ binding resoms: remove K+ from body

• MAC pH < 7.15, HCO3 < 8mmol/L
o IV NaHCO3 until pH 7.20, then oral NaHCO3
• Hypocalcemia:10% calcium gluconate
• Hyponatremia: hypertonic saline for <120mmol/L
• Nutrition: Na, K and P and protein restriction
• Renal replacement therapy: Dialysis – peritoneal dialysis is preferred for
small children
o For persistent hyperkalemia, volume overload,BUN, sever MAC

156

Hemolytic uremic syndrome
Definition
One of the most common AKI in children, more common on children than adults.
Similar to TTP (thrombocytic thrombocytopenia purpura) and often present
together.
Etiology
§ Diarrhea-associated HUS
o infection with E. coli (O157:H7) producing shiga-like toxin
§ Genetic form of HUS (VWF cleaving protease: ADAMTS 13, or complement
factor)
o Does not cause the disease, only predisposes
o Usually not diarrhea associated
o Indolent or relapsing
§ Can be superimposed on any disease associated with microvascular
injury (malignant HTN, SLEO, anitphosphlipid syndrome)
Pathogenesis
§ Microvascular injury: toxins cause endothelial damage
§ Capillary and arteriolar endothelial injury in kidney leads to localized
thrombosis, particularly in glomeruli, ↓GFR
§ Progressive platelet aggregationàconsumptive thrombocytopenia
§ Microangiopathic hemolytic anemia results from mechanical damage to
erythrocytes
Clinical features
§ 90% infants, toddlers
§ Hemorrhagic diarrhea
§ Sudden onset of pallor, irritability, weakness, lethargy
§ Oliguria, dehydration, volume overload depending on whether enteritis
or renal insufficiency predominates
§ CNS involvement: irritability, lethargy
Diagnosis
§ CBC and differential
o Rapidly progressive (microangiopathic hemolytic) anemia
o Thrombocytopenia
o Leukocytosis
§ BUN, crea: varies from mild elevations to ↑↑in anuric AKI
§ Urinalysis
o Microscopic hematuria, low grade PU
§ DD to inherited forms, exclude other causes of HUS

157

Treatment
§ Plasmapheresis (to remove Abs) and dialysis
§ Biological therapy: eculizumab
§ Supplementation of plasma
§ HUS not associated with diarrhea has poor prognosis

158

17b. Solid tumors in children (except Tumors of
central nervous system)
1. Neuroblastoma

Definition
A malignant embryonal tumor of peripheral sympathetic nervous system derived
from neural crest tissue. It is the most common extracranial solid tumor in
children
• Median age of presentation is 2 years
Etiology
• Unknown
• Familial
• Associated with other neural crest disorders:
o Neurofibromatosis 1, Hirschprung disease
• Around 50% arise in adrenal glands, the rest in paraspinal ganglia
• Metastasize to LN, long bones, skull, bone marrow, liver
Clinical findings
Neuroblastoma Paraneiplastic syndrome Metastasis
Asymptomatic Secretory diarrhea Fever
with/without abdominal
pain
Palpable mass in flank- Profuse sweating Failure to thrive
hard, smooth and non
tender
Neuroblastoma in the Hypertension – Bone pain
superior cervical catecholamine production
ganglion can result in
Horner syndrome
Horner syndrome Opsomyoclonus syndrome Peiorbital eccymosis
(ptosis, myosis, and
anhidrosis)

Diagnosis
• X-ray, CT, MRI
• Catecholamine metabolite in urin
• Bone scintigraphy for MTS
• Tumor biopsy
Treatment
• Surgical excision
• Neoadjuvant chemo/radiotherapy
o Vincristine, cyclophosphamide
159


2. Nephroblastoma

Definition
Also known as Wilms’ tumor, most common primary renal tumor of childhood
• Incidence: 2-5 years

Etiology
• Sporadic
• Familial – AD, FWT1/FTW2 gene
• Associated with certain syndromes such as WAGR syndrome
o Wilms’ tumor
o Aniridia (absence of iris)
o GUT malformation- cryptorchidism
o Fused kidney
o Mental retardation
Clinical findings
• Palpable abdominal mass with pain
• Painless hematuria
• Fever
• Hypertension
Diagnosis
• Ultrasound, CT, MRI
• 18F – PET scan
• Biopsy
Treatment
• Neoadjuvant chemotherapy (Vincristine)
• Nephrectomy – adjuvant chemo/radiotherapy
Prognosis
• Very good – 90% survival rate
• Bilateral Wilms’ tumors may lead to renal insufficiency or failure

160

3. Retinoblastoma

Definition
Most common retinal malignancy
o Incidence: 2years
o 2/3 have unilateral tumor, bilateral tumor common in <1year
Etiology
• Hereditary – associated with mutation and loss of function of RB1 gene
(tumor suppressor gene)
• Sporadic
Clinical findings
• Leukocoria – white pupillary reflex
• Strabismus
• Orbital inflammation (pain if secondary glaucoma develops)
Diagnosis
• Indirect ophtalmoscopy with slit lamp
• CT/MRI
Treatment
• Neoadjuvant chemotherapy
• Laser photocoagulation / cryotherapy
• Enucleation – remove eye
Prognosis
• Very good – 95% are cured

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4. Sarcomas

Definition
Can be divided into soft tissue sarcoma and bone cancer
• Soft tissue sarcoma – arise from muscle, fibrous and adipose tissue
• Bone cancer – Osteosarcoma, Ewing sarcoma
A) Rhabdomyosarcoma
• Incidence: 2-6 years and adolescence
• Associated with inactivation of p53 tumor suppressor gene/
neurofibromatosis type 1
o Occurs in head and neck, Gut, extremity and orbit
Clinical findings
• Depend on site of origin
• Present as mass taht may/may not be painful
• Symptoms due to compression of surrounding structures
o Periorbital edema
o Ptosis
o Paralysis of cranial nerve
o Hematuria
o Urinary retention
Diagnosis
• Tissue biopsy
• CT, MRI, bone scan
• Surgical excision
Prognosis
• Depends on metastasis

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B) Osteosarcoma and Ewing sarcoma
• Osteosarcoma is associated with hereditary retinoblastoma
o Most common primary malignant bone tumor in children and
adolescents, followed by Ewing sarcoma
• Incidence: occur in 2nd decade of life
Location
• Osteosarcoma – epiphysis/metaphysis of long bone (femur, tibia,
humerus)
• Ewing sarcoma – femur and pelvis
Clinical features
• Long bone pain
• Tissue swelling
• Osteosarcoma – pathologic fractures
Diagnosis
• X-ray: sclerotic destruction, lytic lesion
• CT, MRI, bone scan
• Needle biopsy
Treatment
• Limb salvage surgery
• Amputation
Prognosis
• If metastasis – poor prognosis
o Bones / lungs

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17c.ALTE and sudden infant death syndrome
ALTE
Gen: Apparent life threatening event
• Episode that’s frightening and unexpected to the observer, characterized:
o Some form of apnea (central)
o Color change (cyanosis/pallor)
o Marked change in muscle tone (sudden limpness)
o Choking or gagging
• Peak incidence is 10-12 weeks of age
Etiology
• 50% of causes are identifiable
• GIT – 50%
o GERD
o Bowel disease – intussiception, volvolus
o Swallowing problems associated with vomiting, choking, gagging
• CNS – 30%
o Seizures (30%)
o Intracranial hemorrhage
o Brain malformations (Arnold-Chiar syndrome, hydrocephalus)
o Tumor/infection (meningitis, encephalitis)
• Respiratory – 20%
o Infections (RSV, pretussis, croup)
o Obstructive sleep apnea (macroglossia, microagnathia)
o Breath holding spells
o Laryngomalacia
• Cardiovascular – 5%
o Arrhytmia (long QT, WPW)
• Metabolic – 5%
o IEM
o Endocrine/electrolyte abnormalities
• Child abuse
Diagnosis
• History: Prematurity, prior apnea, level of consciousness at the time of
event, intercurrent illness
o Family history for SIDS, feeding history, social situation of family
• Physical examination: Focus on neurologic, respiratory, cardiac status
• Lab test: ABG, CBC, biochem (glucose, electrolytes, BUN, ammonia,
ketones)
o Chest x-ray – investigate pertussis + RSV
o Blood culture
o Barium study/pH – GERD
o CT, MRI, EEG, lumbar puncture – CNS
• Tx: Treament of underlying cause
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Sudden infant death syndrome
Gen: Sudden unexpected death of an apparently healthy infant (<1year), in
which the cause remains unexplained after thorough post-mortem examination
including autopsy, death scene investigation, review of medical records
• 8% of all infant deaths
Risk factors
• Maternal and antenatal factors
o Smoking
o Alcohol
o Drug abuse
o Low socioeconomic status
o Growth restriction
• Infant
o Age – 2-4 weeks
o Male (30-50%)
o Prone, side sleep position
o Positive family history of SIDS
o Prematurity
o No breastfeeding
o Previous ALTE
o Prolonged QT interval
• Fulminant (sepsis, pneumonia)
• Seizure
• Hypoglycemia
• GERD
• Dehydration
• Child abuse
• Accidental suffocation
Prevention
• Supine sleeping position
• Avoid soft bedding /bed sharing
• Smoking cessation both ante-post natal
• Avoid overheating and heavy clothing

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18a. Chronic kidney disease (CKD)
Definition
Final stage of numerous renal diseases resulting from progressive loss of
glomerular, tubular and endocrine function in both kidneys.
Etiology
Children <5 years Children >5 years
Congenital renal anomaly Focal segmental
§ Renal hypoplasia
§ Renal dysplasia
§ Obstructive uropathy
Congenital NS Chronic glomerulonephritis
§ Lupus nephritis
Polycystic kidney disease Inherited disorders
§ Alport syndrome
§ Juvenile nephronophtisis
HUS

Pathogenesis
Exact cause is unknown, but some hypethesis are:
§ Intact nephron hypothesis
o As nephrons are lost, the remaining nephrons undergo
hypertrophy with increased glomerular blood flow.
o Temporarily, preserves total renal function but causes progressive
damage to those glomeruli.
o With time, more nephrons are lost and the remaining are damaged
further.
§ Other factors contributing to progression of disease
o Proteinuria: has toxic effects in tubular cells
o Hyperphosphatemia: Ca2+ phosphate dep. in renal interstitium
and blood vessels
o Hyperlipidemia: oxidant-mediated injury to the glomeruli

Stages of CKD

Stage Description GFR /ml/min/1,73 m2
1 Normal or increased GFR >90
2 Mild decrease in GFR 60-89
3 Moderate decrease in GFR 30-59
4 Severe decrease in GFR 15-29
5 ESRD <15 or RRT

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According to albuminemia
A1 <30g/L Normal-mild ↑
A2 30-350g/L Moderate ↑
A3 >350g/L Severe ↑
Clinical features
§ Uremia:
o fatigue, malaise, nausea, vomiting,
o neurological features: polyneuropathu, mental slowing, confusion,
coma, puritus
§ Anemia: EPO defect
§ Renal osteodystrophy/ bone mineral disease
§ Growth failure
§ Cardiovascular disease: HT, hyperlipidemia, cardiac remodeling with
LVH, IHD, cardiomyopathies, type 4 cardiorenal syndrome
Clinical symptoms/ consequences

§ Lab: all electrolytes are ↑, Ca2+↓
§ ↓ vit D: Ca2+↓ leads to ↑PTH: bone wasting (renal bone dystrophy)
§ ↓ EPO: anemia
§ ↓ excretion of waste product: ↑urea: uremic syndrome
§ Fluid overload: ↑BP and CHF
§ ↑ atherosclerosis: ICD
§ ↑K+: arrhytmia
Diagnosis
§ Hx, PE
§ Lab
§ Urinalysis
§ Function test
§ Radiological
§ Biopsy
Treatment
§ Identify and treat reversible cause
§ Symptom control
o Anemia: Fe2+, folate, vit B12, EPO
o Edema: diuretics
§ Limit progression
o Control BP
o Control PTH/vit D
o CVS modification
o Diet: ↓proteins, ↓K+,↓P3+
§ Renal replacement treatment
o Dialysis: crea 600-700, urea 35mmol/L
§ Renal tramsplant: ↑ K+,acidosis
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18b. Principles and indications of formula feeding,
formula types
Definition
Indicated when breastfeeding is contraindicated or when mother’s milk is
unavailable, else breastfeeding is encouraged.
Contraindiactions
§ Maternal:
o Active TB, AIDS
o Malignancies: chemotherapy, radioactive drug
o Severe infections: HIV, HTLV, syphilis
o Postpartum psychosis
o Alcohol intake
§ Infant:
o Galactosemia
Requirements
§ 150-180 ml/kg/d
§ 1st 6 weeks, every 3h
§ As the child grows the number of feeds decreases and the colume of food
increses
Types of formula
§ Standard infant formulas usually cow’s milk based (fully adapted)
o Carbohydrates: Lacrose
o Adapted whey: caseine: 60:40
o Suitable as a sole source of nutrition for up to 12 months of age
o Do not contain Igs or other biologically active compunds
§ Special formulas
o Soy formula
§ Indicated for infants with severe lactose intolerance,
glactosemia or vegan parents, allergy to cow’s milk protein
§ The carbohydrate source is sucrose; protein source is soy
§ Supplemented with methionine, carnitin, taurine, Ca, Fe,
vitamins, trace elements
§ But contain ↑phytates and aluminium – inihibit absorption
of minerals
§ Many children with cow’s milk intolerance will also be
allergic to soy protein
o Hypoallergenic formulas
§ Proteins are partially or fully hydrolyzed into peptides and
free AAs
§ Indicated for infants with maldigestion of proteins or fat,
severe diarrhea or multiple food allergens (expensive)

168

o Low-lactose formulas
§ Carbohydrate source is glucose, galactose
§ Indicated for infants with lactose intolerance
o Preterm formulas
§ Either breast milk fortifiers or preterm formulas can be
used
§ Have high energy content and protein/energy ratio
compared to breast milk
§ Preterm formula has no Igs and biologically active
compounds (in contrast to fortified breast milk)
o Energy-dense formulas
§ 1kcal/ml: more than breast milk for children with failure to
thrive.
o Thickened formulas
§ For patients with GERD, contain starch
o Formulas for IEM
§ PKU, maple syrup urine disease
o Medium-chain triglyceride formulas
§ For patients with fat malabsorption (CF)
Preparation
§ Safe water (boiled)
§ Sterilized utensils (bottle, nipple)
§ Correct concentration of water ans formula
§ Always fresh prepared – never reheat!
Frequent change of formulas should be avoided
Special formulas should be used only when indicated
There are also follow-on formulas (cow’s milk or soy based)
§ Partially adapted
§ Introduced from 4-6 months
§ Not suitable as sole source of nutrition
Junior formulas: after 12 months
Complementary food should be introduced between 4-6 mo µτησ

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18c.Early and late onset of neonatal infections, Sepsis,
Prevention and treatment
Systemic and local infections are common in newborn period and may be
acquired in utero (transplacental/transcervical), during birth, or after birth
• Premature infants have increased risk due to their immature immune
system and prolonged periods of hospitalization (Premature <32weeks)
Neonatal sepsis
Divided into:
• Early onset sepsis
• Late onset sepsis

Neonatal sepsis – SIRS + documented infection
• SIRS Definition
o Body temperature >38C or <36C
o Tachycardia >2 SD above normal age
o Respiratory rate >2 SD above normal normal age/acute need for
mechanical ventilation
o WBC
§ Newborn – 10-25 x 109/L
§ 2months-6years – 6-17 x 109/L
§ >6years – 4.5-13 x 109/L
• Severe sepsis (sepsis + one of following)
o Cardiovascular dysfunction
§ Hypotension <5th percentile
§ MAC
§ Oliguria
§ Prolonged capillary refill time >5sec
§ ↑Lactate
1. Early onset sepsis

• Gen: Sepsis occurring within the 1st – 7th day after birth
• Eti: bacteria in mothers GUT (Infection begins in utero/intrapartum)
S. agalactiae E-coli
Listeria monocytogenes Klebsiella
H. influenza TORCH

• RF: Maternal amnionitis, preterm delivery
• CF: most infants have symptoms within 6hours after birth
Severe multiorgan system disease Respiratory failure
Shock Meningitis
DIC Peripheral gangrene

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2. Late onset sepsis
• Gen: Occurs later than 7days after birth. Seen in healthy full term infants
who acquire in infection from the environment
• Eti: more commonly associated with bacteremia and focal infection
o Meningitis, osteomyelitis, septic arthritis, pneumonia, UTI
S. aureus Strep
E-coli Klebsiella
P.aeuraginosa Candida
N. meningitis HSV
CMV Enterovirus

• CF: most infants have symptoms within 6hours after birth
Respiratory distress Temperature instability
Lethargy, poor feeding Hypotonia, apathy
Bulging fontanelle, seizure Jaundice, neutropenia, thrombocytop.
• Dx:
o Blood test: CBC (neutropenia, thrombocytopenia), ESR, CRP,
glucose, ABG (hypoxemia + MAC)
o Culture of blood, CSF, urine
o Lumbar pucture – CSF analysis
o X-ray
• Tx:
Early onset sepsis Late onset sepsis

ATB: ATB:
• Ampicillin + gentamycin • Ampicillin + gentamycin
• 2weeks – ampicillin + cefotaxime • 2weeks – ampicillin + cefotaxime
P.aeruginosa – piperacillin

Candida – Amphotericin B

Supportive care
Oxygen, ECMO
Fluid replacement
Inotropic drugs
Steroid – adrenal insufficiency
Correction of electrolytes
Treat underlying cause

Prevention
Maternal immunization (VZV,HBV,rubella)
Toxoplasmosis – appropriate diet, avoid cat feces
Treatment chorioamnionitis with ATB
Decr. Vertical transmission of GBS – intrapartum chemo prophylaxis
Treatment chlamydia
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Septic shock
• Gen: Severe sepsis + persistent hypoperfusion or hypotension despite
>40mL/kg of fluid replacement in 1 hour
o Requrement of vasopressors

Pathogenesis
o Overproduction of inflammatory cytokines (TNF-alpha, IL-1, IL-6)
that cause vasodilation and increased vascular permeability and
adherence of neutrophils to capillary walls
o Neu produce proteases + elastases that damage the vesel wall and
increase the capillary leak furthermore
o Causes hypotension and hypovolemia
o Arachidonic acid metabolites induce fever and tachypnea
o As SIRS progresses, there is activation of coagulation cascade with
DIC – bleeding of thrombotic events, ARDS, death

Clinical features
Initially Later
Temperature increased/decreased Hypovolemia
Tachycardia Increased capillary refill time
Tachypnea Cold extremities
Fatigue MAC
Chills Hypotension
Hyperventilation

Etiology
Bacteria Fungi Parasites Virus
E-coli Candida P-falciparum HSV
Klebsiella CMV
P. aeroginosa Enterovirus
N. meningitis
S. pneumonia
S. aureus
Salmonella

Risk factors
• Immunosuppression – corticosteroid use, AIDS, primary
immunodeficiency cyclophosphamide
• Surgerical procedure
• Invasive device – catheter, prothesis
• Hospitalization
• Splenic dysfunction
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Diagnosis
• Blood: CBC, biochem (CRP, ESR, lactate, procalcitonin, clotting factors,
electrolytes, IL-1,6,8, TNF-alpha, INR, crea, ALT, ALP, AST
• Urine culture/analysis
• Blood culture

Treatment
• IV fluid
• Vasopressor
• Empirical ATB
o Neonate – ampicillin + gentamycin, cefotaxime
o Older infant/children – Amoxicillin + clavulanate, cefotaxime
• Viral sepsis – acyclovir
• Nosocomial sepsis – tazobactam + piperacillin
• Hemodialysis if kidney fails

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19a. Acute poststreptococcal and Rapidly
progressive glomerulonephritis
Definition
General
Glomerulonephritis: conditions in which the glomerulus is damaged. It is one of
the main causes of end stage renal failure and there are two broad groups of
glomerulonephritis; primary and secondary.
• Primary glomerulonephritis is when the condition is limited to the

kidney whereas
• Secondary glomerulonephritis is when the glomerular disease is
secondary to systemic disease.
There are specific terms used to describe how much of each glomuerlus is
involved and also how many.
• Focal disease – only some of the glomeruli are damaged.

• Diffuse disease – all of the glomeruli are damaged
• Segmental disease- only part of the glomerulus itself is damaged.
• Global disease - the disease affects the entire glomerulus.
Nephritic syndrome: Is a set of symptoms that could often be seen in

glomerular diseases. The clinical picture is often:
Hypertention Haematuria
Proteinuria (mild to moderate) Edema
Salt and water retention in kidney Temporary oliguria and uremia
Azotemia: elevation of creatine and BUN (blood, urine and nitrogen)
Post-streptococcal glomerulonephritis (PSGN)

Usually in children, 1-3 weeks post strep. infection à sore throat, otitis media,
cellulitis
Etiology
• group A, β-hemolytic streptococcus (GAS) – strep. Pyogenes
Pathogenesis
• Ag/Ab immune complex formation.
• Ag/Ab complexes are deposited in the glomeruli causing inflammatory
reaction that damages the glomeruli
• There is a consumption of complement C3
Clinical features
• Execept the classic symptoms of acute nephritic syndrome there are also
systemic symptoms such as
• Malaise, fatigue, anorexia, headache and flank pain
174

Diagnosis
• Renal biopsy shows (usually not necessary):
• Hyper-cellularity of mesangial and endothelial cells
• Glomerular infiltrates of neutrophils
• Immune deposits of Ig and complement
• Kidneys are grossly enlarged

Treatment
• Supportive treatment with control of hypertension and edema
(antihypertensives, diuretics) and dialysis as needed.
• Corticosteroids can be administered if recovery is slow
• The prognosis is very good ; permanent renal failure is uncommon
Rapidly progressive glomerulonephritis (RPGN)

Definition:
It’s a syndrome with glomerular hematuria, rapidly developing acute renal
failure (one week to months) and focal glomerular necrosis and crescents in
glomeruli. Patient have acute nephritic and nephrotic syndrome.

Pathogenesis:
• Immune deposits in glomeruli:
o anti-GBM antibodies or immune complexes – SLE
• No immune deposits in glomeruli:
o ANCA-positive vasculitis (pauci – immune)
Types:
• Anti-GBM glomerulonephritis
• Immune complexes - SLE
• ANCA-positive vasculitis

Anti-GBM glomerulonephritis
Pathogenesis:
• Patients develop auto antibodies directed against glomerular basement
membrane Ags
• 2/3 of these patients have Goodpasture’s syndrome and present with
lung haemorrhage plus glomerulonephritis (pulmonary-renal syndrome)
• Target epitopes for the Abs are the k3 NC1 domain of collagen type 4 of
BM
• Goodpasture’s occur in young men (late 20’s) or men and women (60’s-
70’s)

175

Diagnosis: Urgent renal biopsy is important to confirm diagnosis
• There is local and segmental glomerular nephrosis and crescent
formation in Bowman’s space (macrophages and epithelial cell
aggregates)
• If biopsy shows IgG deposits and complement deposits on GBM

Symptoms: Presentation is usually explosive hemoptysis, fall of Hb, fever,
dyspnea, hematuria, proteinuria and hypertesion

Treatment:
o Plasmapheresis to remove circulating Abs
o Corticosteroids to suppress inflammation
o Cyclophosphamide to suppress further Ab synthesis
o The prognosis depends on percentage of crescents, serum
creatinine levels and the need for acute dialysis
ANCA-positive vasculitis
General:
• A group of patients with small vessel vasculitis and glomerulonephritis
have serum ANCA (anti-neutrophilic cytoplasmic antibodies) à can be
anti-proteinase 3 (PR3) or antimyeloperoxidase (MPO) positive.
• High mortality without treatment, patients require urgent intervention

Types:
• Wegener’s granulomatosis
• Microscopic polyangitis
• Churg-strauss syndrome

Pathogenesis:
• Pauci-immune GN with a few immune complexes in small vessels and
glomerular capillaries
Symptoms:
• Wegener’s granulomatosis: fever, rhinnorrhea , purulent , nasal ulcers ,
cough, hemoptysis , microscopic hematuria and proteinuria .
• Microscopic polyangitis: similar to wegener’s but with lung disease or
sinusitis (hemoptysis and hematuria )
• Churg strauss syndrome: triad of asthma, peripheral eosinophilia and
allergic rhinitis plus focal segmental necrotizing glomerulonephritis .
Treatment: combination of
• Plasmapheresis
• Methilprednisolone
• Cyclophosphamide
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19b. Breastfeeding, complementary feeding and
weaning
The best form of nutrition for growing infant compared to formula eating.
Breastfed infant grow faster.
• Duration- start within 30min, continous for 4-12months
• Frequency- 8-12 times/day (every 2-3 hours) for 10-15minutes
Composition
• Breastmilk is composed to meet nutritional requirements
• Colostrum (1st few hours)
o Think, creamy, white-yellow
o Immunologica boost, IgA + lymphocytes, protein, vitamines AEK,
zinc
• Mature breast milk
o Proteins – a-lactalbumin – 11-21g/L
o Whey: casein 80:20 (cow milk 20:80)
o 20% - amino acid + nucleotide
• Lipids
o 20-45g/L (50% of calories)
o Cholesterol- essential for CNS maturation
o (PUFA & LC PUFA (linoleic, arachidonic) – CNS, GIT maturation,
immunomodulation
• Carbohydrates
o 68 g/L
o Lactose- main source of galactose (important for CNS maturation)
• Biological active agents
o Immunologically active components: WBC, IgA, IgD, IgM, IgG
o Immunomodulating factors- lactoferrin, lysozyme, lactoperoxidase
o Hormone- TRH, T4, cortisol, IGF-1
o Vitamin
o Minerals- Na, K, Mg, Zinc, (with low renal solute load Fe)
Benefit
• Early:
o Optimal content, absorption of nutrients + bioactive substance
o Immune protection
o Convenience (sterile, low cost)
o Maternal-infant bonding
• Long term
o Decreased risk of infection-gastroenteritis, RTI, Otitis media
o Decreased risk of DM1, NEC, celiac dx, leukemia, lymphoma,
ovarian breast cancer (in mother)

177

Contraindications
• Maternal
o Active TB, AIDS
o Malignancies (chemotx, radioactive drug), HIV, HTLV, syphilis
o Postpartum psychosis
o Alcohol intake
• Infant
o Galactosemia
Common problems
Mother Infant
Sore nipple Inadequate milk intake lead to
dehydration
Mastitis Breast milk jaundice
Masalgia
Engorgement
Complementary food and weaning

• Transition from milk feeding to other
• Introduced after 17 weeks, but before 26weeks
• Need additional source of protein, iron and zinc
• Cereal with breast milk, formula + water (single grain – identity allergen)
• 1 single nutrient at a time, no new food for 5-7 days
• 2-3 servings of vegetables
• Cow milk after 1year
• Honey after 1 year – infant botulism
• Fruit juice 6 months

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19c.Acute infectious laryngitis, Acute epiglottitis
Acute laryngitis
Definition
Inflammation of larynx that has abrupt onset and lasts more than 3 weeks
Etiology
• Viruses (most common)
o RSV, influenza, parainfluenza, adenovirus, coxsackie
• Bacterial
o Corynebacterium diphtheria: pseudomembranes: grey-white
o Strep. Pyogenes/bordatella pertussis: whooping cough
Clinical features
• Disease is usually mild and self-limited
• URTI with flu-like symptoms: rhinorrhea, nasal congestion, sore throat,
hoarseness of voicea and dry, barky or brassy cough
• In severe cases there is aphonia, stridor and respiratory distress
o Nasal flaring, tachypnea, subcostal & intercostal retractions
Diagnosis
• Based on clinical features and laryngoscopy
• Laryngoscopy reveals inflammatory edema of vocal cords and subglottic
tissue
• Croup (larnygotracheobronchitis)
o Acute viral croup, spasmodic croup
• Acute epiglottitis
Treatment
• Usually self-limited
• Humidification of air
• Hydration
• Oral or i.m.: dexamethasone or racemic adrenaline

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Croup (Laryngotracheobronchitis)
Definition
Viral infection of the glottis and subglottic area
Etiology
• Parainfluenza viruses (75%)
• RSV
• Influenza A and B
• Adenovirus
• Measles
Epidemiology
• Typically a disease of toddlers, 2nd year of life
• Fall and winter
Clinical features
• URTI symptoms: rhinorrhea, cough, pharyngitis and low grade fever
which progresses into croup within 1-3 days
• Characteristic barky or brassy cough, hoarseness of voice & inspiratory
stridor which is worse at night
• With increased upper airway obstruction, there is respiratory distress
and complete obstruction which leads to hypoxia
• Wheezing is present if lower airways are involved
Diagnosis
• Clinical finding
• PCR of nasal secretion to detect virus
• Serology to detect viral Ags
• CXR usually not helpful (maybe steeple sign)
Treatment
• Humidification of air
• Oral or i.m. dexamethasone or inhaled budesonide or oral prednisolone
• Nebulized racemic adrenaline (↓subglottic edema by vasoconstriction)
• In severe cases intubation or tracheostomy

180

Epiglottitis
Definition
Medical emergency characterized by night fever, sore throat, dyspnea and
rapidly progressive respiratory obstruction
Etiology
• H. Influenza B (because of vaccination other agents prevailing
• S. Pyogenes
• S. Aureus
Epidemiology
• Children 2-4years, also seen in adults
Clinical features
• Sudden onset onset (2-6 hours) of fever, sore throat, hoarse voice and
inspiratory stridor
• Patient assumes characteristic tripod position: sitting upright, leaning
forward, open mouth – usually drooling
• In severe cases there is resp distress, cyanosis and coma
Diagnosis
• Laryngoscopy shows cherry red, swollen epiglottis, may provoke
laryngospasm
• Lateral x-ray – classic thumb sign (swollen epiglottis)
Treatment
• Requires endotracheal intubation or tracheostomy
• ATB therapy for 7-10 days: ceftriaxone, cefotaxime

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20a. Cystic diseases of the Kidney (Polycystic
kidney disease, Juvenile nephronophthisis)
Polycystic kidney disease (PKD)
General:
• Among the most common life – inherited diseases and a frequent cause of
kidney failure.
• Solitary or multiple renal cysts are common à50% of people >50yrs will
have a cysts
• Often asymptomatic, found incidentally on USG, may cause pain,
haematuria, bleeding into the cyst
• Malignant renal rumours arise more often in patients with cystic kidney
disease
• There are generally 2 types of PKD → the autosomal recessive type (seen
mainly in children) and the autosomal dominant type (seen mainly in
adults).
Signs and symptoms:
• The most common symptom in patients with polycystic kidney disease is
pain.
• The pain may be caused by enlargement of one or more cysts, bleeding,
which may be confined inside the cyst, or lead to gross hematuria with
passage of clots or a perinephric hematoma, urinary tract infection (e.g,
acute pyelonephritis, infected cysts, perinephric abscess, nephrolithiasis
and renal colic.
1. Autosomal recessive polycystic kidney disease:

• Very rare form with incidence of around 1:20,000 live births and often
leads to fetal or neonatal death.
• The kidneys are enlarged, with small cysts (< 5 mm) which are limited to
the collecting tubules. The etiology is a mutation in the PKHD-1 gene. The
diagnosis is often made in utero where on fetal USG we can
notice enlarged echogenic kidney with many small cysts (after 24th week
in severe cases or only after birth in less severe) and oligohydramnion.
• The patient's has a cystic kidney together with hepatic fibrosis
(an association was made between PKHD-1 gene alteration and Caroli's
disease → congenital hepatic fibrosis).
• Most of the babies die due to pulmonary hypoplasia → the result
of oligohydramnion from severe intrauterine kidney disease. The children
who do survive neonatal period will develop ESRD and will need kidney
transplantation or chronic dialysis.
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2. Autosomal dominant polycystic kidney disease (APKD):
• It is the most common hereditary disorder that leads to ESRD (10% of
all cases).
• Characterized by cyst formation in the ductal organs, especially in the
kidney and liver. Patients also have non-cystic, extrarenal manifestations
such as mitral valve prolapse, intracranial aneurysms, and hernias.
Etiology:
• A systemic disease resulting from mutation in the PKD-1 or PKD-2 gene
that encodes for transmembrane proteins called polycystin 1 or 2
respectively → play a role in calcium movement across the luminal
membrane.
Signs and symptoms:
• Bilateral multiple expanding cysts that become symptomatic usually in
the 3rd or 4th decade.
• Increase in size of the kidney with age
• Pain, hematuria, hypertension, renal insufficiency
• Abdominal discomfort and recurrent UTI's.
• Progressive decline in renal functions over a course of 20 years.
Diagnosis:
• From positive family history & screening.
• Imaging → USG, CT, MRI → showing multiple cysts and possibly liver cysts
as well.
• Evidence of renal dysfunction → proteinuria, elevated creatinine, urea
and BUN.
Treatment:
• No treatment was proven to stop or even slow cyst formation,
thus treatment is directed to preventing complications and preserving
renal functions.
• Blood pressure control (ACEI, ARB's) is needed to prevent end
organ dysfunction.
• Surgical decompression may be needed in some instances.
• In general the disease is fatal, but prognosis is improved these days due
to dialysis and renal transplantation possibilities.
183

Juvenile nephronophthisis
• General: Inherited cause of chronic tubulo-interstitial nephritis, leading
to multiple cysts of varying sizes at the corticomedullary junction and
medulla. It is autosomal recessive and patients develop end-stage renal
failure (ESRF) by adolescence. The protein products, named
nephrocystins, which become abnormal in this disorder, have primarily a
function in cilial structures.

Epidemiology
• 10-20% of end-stage renal failure (ESRF) in children.
• It occurs equally in males and females.
Etiology
• Mutations in 12 genes (called NPHP1-NPHP11 and NPHPL1)
• NPHP1 gene encodes the protein nephrocystin-1, mutated in one fifth of
all cases.
Types
• Infantile - median age of onset 1 year
• Juvenile - median age of onset 13 years
• Adolescent - median age of onset 19 years
Clinical features
• Polyuria
• Polydipsia
• Growth retardation
• Secondary enuresis
• Renal impairment.
• Renal failure with MAC, anaemia, renal osteodystrophy and end-stage
renal failure (ESRF).
• Once uraemia occurs - patients may have nausea, anorexia and
generalised lethargy.
Extrarenal manifestations
• Retinal degeneration (Senior-Loken syndrome)
• Retinitis pigmentosa
• Skeletal changes
• Cerebellar ataxia (Joubert's syndrome)
• Liver fibrosis

184

• Polycystic kidney disease
• Chronic pyelonephritis
• Urinary tract obstruction

Investigations
• Urinalysis - is usually normal; occasionally, few cells and casts.
• Ultrasound - multiple small medullary cysts (1 mm to 1 cm in size)
• Intravenous pyelogram - the kidneys are small, smooth with reduced
function. The nephrogram is prolonged and there are medullary striations
due to stasis within the tubules, producing the characteristic 'fan shape'.
• CT scan of urinary tract - kidneys are small, smooth, and contain
medullary cysts. This is more sensitive than ultrasound scanning.
• Renal biopsy can confirm the diagnosis.
• Genetic testing looking for homozygous deletions

Management
• Treat symptomatically, eg correct hypovolaemia.
• Treat associated renal failure - usually haemodialysis followed by renal
transplantation (the illness does not recur in the transplanted kidney).

Prognosis
• Most children will develop renal failure by mean age of 13 years.
• Renal transplantation in nephronophthisis are very encouraging and
suggest that these patients fare better than patients who receive renal
transplants for other conditions.

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20b. Tumors of the central nervous system
Anatomy
Brain
Cerebrum Cerebellum Brain stem Meninges
Occipital Frontal Parietal Temporal Coordination Heart beat Surround and
protect brain
Vision Reason Touch Memory Balance Breathing Dura mater
Emotions Pressure Hearing Arachnoid
Parts of Pain Pia mater
speech
Temp
CNS tumor
Begins when healthy cells in the brain change and grow uncontrollably forming
mass. Can be benign/malignant
• Types:
o Astrocytoma – 5-8years
o Brain stem glioma
o Ependymoma
o Germ cell tumor
o Medulloblastoma – common, <10years
1. Astrocytoma
Gen: begins when healthy astrocytes change and grow uncontrollably forming a
tumor. Locations:
• Cerebellum • Brain stem
• Cerebrum • Spinal cord
• Diencephalon
Classification grading:
• High grade – dont grow quickly
• Low grade – grow fast, spread further
Clinical findings
Headache Tiredness Seizures
Vision problems Impaired growth Fast growing head
Bulging ant. fontanelle
Diagnosis
• History and physical examination
• CT, MRI
• Biopsy
Treatment
• Surgery – depends on size, MTS
• Chemo/radiotherapy
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Risk factors
• Neurofibromatosis
• Li-Fraumeni syndrome
• Tuberous sclerosis
• Turcot syndrome

2. Brain stem glioma

Gen: Rare tumors that occur in children. Tumor that grow from glial cell –
aggressive and often diagnosed late (5-10years). Poor prognosis. Location:
• Pons
• Brain stem
• Diffuse – spreads freely, high grade tumor, aggressive, pons spread
• Focal – in 1 area (midbrain/medulla)
Clinical findings
Double vision Lack of facial control Headache
Seizures Weakness Balance problems
Difficulty chewing Difficulty swallowing
Diagnosis
• MRI
Treatment
• Not treatable with Surgery
• Steroids decrease edema

3. Ependymoma
Gen: Tumor that arises from ependymal (3rd most common). Location:
• 4th ventricle
• Rarely in pelvic cavity
• I- myxopapillary ependymoma
• II- subtype, variants of ependymoma
• III- anaplastic ependymoma
Clinical findings
Headache Visual loss (papilledema) V+N
Bilateral babinski sign Drowsiness Seizure
187

Diagnosis
• CT, MRI
Treatment
• Removal by Surgery
4. Germ cell tumor

Gen: Rare tumor that arise in germ cells (sperm & egg cells). Common in young
adolescents. Location:
• Testes
• Ovaries
• Abdomen
• Pelvis
• Brain (intracranial germ cell tumor)
• Pituitary/pineal gland
Clinical findings
Visual problems Hydrocephalus Hypothalamic/pituitary
dysfunction
Diagnosis
• CT, MRI
• Biopsy
Treatment
• Surgery
5. Medulloblastoma
Gen: Most common – arise from embryonal cells. High grade tumor. Locations:
• Cerebellum
• Spread through CSF to other surface of brain and spinal cord
Clinical findings
Behavioral change Headache N+V
Change in appetite Diplopia (papilledema) CN 6 Palsy
Increased ICP- drowsiness
Diagnosis
• MRI
Treatment
• Surgery
• Corticosteroids
188

20c.Obesity in childhood, Dyslipidemias, Importance of
prevention of atherosclerosis in Pediatric age group
Obesity in childhood
Definition
It is a state of excess adipose tissue mass, contributing to comorbidity. It is an
important pediatric health problem associated with complications in childhood
and morbidity and mortality in adulthood.

!"
Obesity can be defined with the help of BMI: ! ×703, it´s specific for age and
!
gender in children under 2 years
• Overweight: BMI 85th and 95th percentile
• Obesity: BMI >95th percentile
• Severe obesity: BMI >99th percentile

Waist-to-height ratio can also be used to assess the fat distribution
Waist/Height ˃0.5 has increased cardiovascular risk.

• Normal BMI : ˃5th percentile but <85th percentile.
Etiology
• Environmental factors: physical inactivity and sedentary behaviour, low
physical activity leads to excessive intake over requirements. Urban areas
provide little space for playing/ training Television and computers reduce
physical activity.
• Dietary intake and eating patterns: In western countries children eat
more than they need, foods are often energy-dense but nutrient-poor,
high intake of sugar and sweetened drinks.
• Socioeconomic conditions: poor children in developed countries and rich
children in developing world.
• Genetic factors: parental obesity is risk factor for obesity in the child
(80%). Obesity is a polygenic disease involving genes encoding proteins
that regulate metabolic rate, satiety, thermogenesis, etc.
• Syndromic forms of obesity: disorders that are caused by a single genetic
defect or by chromosomal abnormalities and have obesity as part of the
syndrome (e.g. Parder –Willi syndrome).
o In newborns symptoms include weak muscles, poor feeding, and
slow development.
o In childhood the person becomes constantly hungry which often
leads to obesity and type 2 diabetes.
o There is also typically mild to moderate intellectual impairment
and behavioral problems.
o Often the forehead is narrow, hands and feet small, height short,
skin light in color, and they are unable to have children.
189

• Medical conditions associated with obesity
o Endocrine disorders: hypothyroidism, hypercortisolism (Cushing’s
syndrome), GH deficiency,
o Hypothalamic-pituitary damage due to surgery, trauma or
irradiation,
o Side effects of drugs: Glucocorticoids, insulin, antiepileptics
(valproate), antipsychotics (risperidone).
Complications
• Psychological – social isolation and discrimination, decreased self-esteem
• Cardiovascular – hypertension, cardiac hypertrophy, IHD in adulthood
• Respiratory – obstructive sleep apnea, Pickwickian syndrome
• Hepatobiliary – NAFLD, gallstones
• Orthopedic – back pain, ankle sprains, and flat feet
• Metabolic – hyperlipidemia, insulin resistance/ T2 DM and metabolic
syndrome in adulthood
• Others – acanthosis nigricans, pseudotumor cerebri, PCOS
Diagnosis
• Dietary assessment
• Anthropometry – BMI, height, weight, waist/height
• Physical examination – BP, fat distribution, signs of complications
• Lab tests – glucose, lipids (total cholesterol, LDL, HDL, TGS), liver
enzymes (ALT, AST), hormone levels (T4, GH).
Treatment
• Dietary modification and physical activity - (water as beverage, no
coke/juice), ↓energy, fat, regular eating patterns, ↑ fruits/ vegetables,
↓portion size, ↑exercise
• Adolescents with severe obesity may receive drugs (Orlistat or Incretins)
or weight- reductive surgery.
190

Dyslipidemia
Because lipids are insoluble in water, they are transported in the plasma as
lipoproteins. Lipoproteins are macromolecular complexes of lipids and specific
proteins. Types of lipoproteins: Chylomicrons, VLDL, LDL and HDL.

Classification
• Hyperlipidemia
o Primary hyperlipidemia
o Secondary hyperlipidema
§ Disorders of VLDL and chylomicrons
§ Disorders of LDL
§ Combined hyperlipidemia
§ Disorders of HDL
§ Abetalipoproteinemia
Secondary hyperlipidemia
Usually present with elevated levels of TGs and cholesterol, low level of HDL.
Several underlying diseases could cause hyperlipidemia:
• Hypothyroidism • Hepatic dysfunction
• DM (poorly controlled) • Renal impairment
• Obesity • Drugs (OCP, corticosteroids,
• Nephrotic syndrome etc.)

Primary hyperlipidemia
a) Disorders of VLDL & chylomicrons
• Familial hypertriglyceridemia is an AD disorder
o Patients have a history of acute pancreatitis or retinal vein
thrombosis.
o ↑VLDL levels resulting in ↑ TG levels, serum cholesterol levels is
normal or slightly ↑.
• Familial hyperchylomicronemias are rare disorders
o May be due to lipoprotein lipase deficiency or apoproteins C-II
deficiency.
o Present in childhood with severe hypertriglyceridemia,
pancreatitis, retinal vein thrombosis and eruptive xanthomas,
hepatosplenomegaly.
o There is also fasting hyperchylomicronemia resulting in greatly
↑TG levels.
191

b) Disorders of LDL
• Familial hypercholesterolemias
o Result of ↓LDL receptors in the liver resulting in ↑concentrations of
LDL cholesterol
o LDL is not cleared by the liver.
• Heterozygous familial hypercholesterolemia
o May be asymptomatic or present with CAD in middle age (40s).
o Slightly ↑LDL, premature CVD, typical features are tendon
xanthomas and xanthelasmas.
• Homozygous familial hypercholesterolemia
o Characterised by total absence of LDL receptors and is very rare.
o Patients have greatly ↑cholesterol levels (˃16 mmol/L) and
typically die in adolescence from CAD (untreated).
o Atherosclerosis of coronary arteries, aorta, tendon xanthomas,
eruptive xanthelasma, the only cure is liver transplantation.
o Mutations in the apoproteins B-100 gene, is a single gene defect in
which LDLs cannot bind to their clearance receptor in the liver
(bind through apoproteins B-100).
o Clinical picture resembles heterozygous familial
hypercholesterolemia.
o Treatment is indicated in childhood → positive family history.
c) Combined hyperlipidemia
• Hypertriglyceridemia plus hypercholesterolemia.
• Patients have an ↑CV risk due to ↑LDL levels and HDL levels (due to
hypertriglyceridemia)
• AD familial combined hyperlipidemia is a relatively common disorder
characterised by ↑cholesterol & TG concentrations.
• Develops CHD in 60s and ↓ HDL, children present with metabolic
syndrome: hypertension, obesity, insulin resistance
d) Disorders of HDL
• Decreased levels of HDL and ↓ cholesterol.
• Tangier disease is an AR disorder where cholesterol accumulates in
reticuloendothelial tissues and arteries
o causing enlarged orange colored tonsils and hepatosplenomegaly,
CVD, polyneuropathy.
e) Abetalipoproteinemia
• Rare AR disorder, due to mutation on gene for TG transfer protein
o Resulting in ↓chylomicrons, TGs, VLDL, LDL and cholesterol,
malabsorption of fat, diarrhea and vit E deficiency
o loss of deep tendon reflexes, ataxia, HT.
192

Treatment of hyperlipidemias
• Lipid lowering diet:
o Chicken and poultry should be substituted for red meats, low-fat
cheeses.
o Polyunsaturated fats (vegetable oils) should be used instead of
saturated fats.
o Avoid excessive alcohol consumption and obesity.
• Lipid lowering drugs:
o HMG CoA reductase inhibitors (statins) such as simvastatin.
o Cholesterol absorption inhibitors (ezetimibe)
o Fibrates (e.g. fenofibrate) lower serum TG levels & LDL
o Bile acid sequestrants (resins), e.g. Cholestyramine, reduce LDL
cholesterol levels.
o Fish oils reduce plasma TG levels, Nicotinic acid ↓ total & LDL
cholesterol, but not commonly used due to side effects.
Prevention of atherosclerosis in pediatric age group

Atherosclerotic cardiovascular disease remains the leading cause of both death
and disability. Presence and extent of atherosclerotic lesions at autopsy after
unexpected death of children and young adults correlate positively and
significantly with established risk factors, namely low-density lipoprotein
cholesterol, triglycerides, systolic and diastolic blood pressure, body mass index,
and presence of cigarette smoking.
Health promotion
• Diet
o Healthy eating pattern
o Appropriate body weight
o Desirable lipid profile
o Desirable blood pressure
• Smoking
o No new initiation of smoking
o No exposure to enviromental tobacco smoke
o Complete cessation for those who smoke
• Physical activity
o Physical activity everyday
o Reduce sedentary time (TV, PC)
Identification of high risk patients for CVD

• Goals for pediatric care provider
o Good history of familial risk for CVS
o Measure BMI
o Blood pressure
o Diet and physical activity

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• Lipids and lipoprotein
o Cholesterol >170mg/dl
o LDL >110mg/dl
o TG >150mg/dl
o HDL<35mg/dl
• Blood pressure
o Systolic and diastolic pressure >90th percentile
• Body size
o BMI >85th percentile is risk of overweight

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21a. Sepsis in childhood
Definition
Sepsis is defined as SIRS plus a documented infection. SIRS is an exaggerated
inflammatory response that harms the body resulting from infectious or non-
infectious triggers (trauma, poisoning, bacteria, viruses, fungi, pancreatitis,
hypoglycaemia).
SIRS
The inflammatory cascade of SIRS involves:
• Overproduction of inflammatory cytokines (TNF-a, IL-1, IL-6) that cause
vasodilation and increased vascular permeability and adherence of Neu to
capillary walls.
• Neutrophils produce proteases and elastases that damage the vessel wall
and increase further the capillary leak.
• All that causes hypotension and hypovolemia.
• Arachidonic acid metabolites induce fever and tachypnea.
• As SIRS progresses, there is activation of coagulation cascade with DIC
causing bleeding of thrombotic events, ARDS and eventually MOF (liver,
kidneys, heart, bowels) and death.
SIRS criteria
o Body temperature >38C or <36C
o Tachycardia >2 SD above normal age (no stimuli such as drugs,
pain)
o Bradycardia <10th percentile for age for more than 30 minutes in
infants <1 year
o Respiratory rate >2 SD above normal normal age/acute need for
mechanical ventilation
o WBC
§ Newborn – 10-25 x 109/L
§ 2months-6years – 6-17 x 109/L
§ >6years – 4.5-13 x 109/L
Severe sepsis (sepsis + one of following)
o Cardiovascular dysfunction
§ Hypotension <5th percentile
§ MAC
§ Oliguria
§ Prolonged capillary refill time >5sec
§ ↑Lactate
o ARDS (bilateral infiltrates in CXR without left HF)
Septic shock is defined as severe sepsis plus persistent hypoperfusion or
hypotension despite >40ml/kg of fluid replacement in an hr – requirement for
vasopressors (noradrenaline, adrenaline, dopamine).

195

Clinical features
Initially Later
Temperature increased/decreased Hypovolemia
Tachycardia Increased capillary refill time
Tachypnea Cold extremities
Fatigue MAC
Chills Hypotension
Hyperventilation

Etiology
Bacteria Fungi Parasites Virus
E-coli Candida P-falciparum HSV
Klebsiella CMV
P. aeroginosa Enterovirus
N. meningitis
S. pneumonia
S. aureus
Salmonella

Risk factors
• Immunosuppression – corticosteroid use, AIDS, primary
immunodeficiency cyclophosphamide
• Surgerical procedure
• Invasive device – catheter, prothesis
• Hospitalization
• Splenic dysfunction
Diagnosis
• Blood: CBC, biochem (CRP, ESR, lactate, procalcitonin, clotting factors,
electrolytes, IL-1,6,8, TNF-alpha, INR, crea, ALT, ALP, AST
• Urine culture/analysis
• Blood culture

Treatment
• IV fluid
• Vasopressor
• Empirical ATB
o Neonate – ampicillin + gentamycin, cefotaxime
o Older infant/children – Amoxicillin + clavulanate, cefotaxime
• Viral sepsis – acyclovir
• Nosocomial sepsis – tazobactam + piperacillin
• Hemodialysis if kidney fails

196

21b. Disorders of thyroid gland
Thyroid gland consist of follicular cells and C-cells (parafollicular)
• Follicular cells
o Produce and excrete T3,T4
§ Increase bone marrow resorption, Calcium turnover
§ Increase response to catecholamine
§ Necessary for fetal growth and development
• C-cells
o Secrete calcitonin
§ Decrease calcium and P levels in blood
1. Hypothyriodism
Gen: There is an underactivity of the thyroid gland with decreased production of
T3 (thyroxine) and T4 (triodothyronin)

Classification
• Familial/sporadic
• Congenital – 2nd trimester
• Acquired – onset in childhood/adolescence
• Primary/secondary – hypothalamic-pituitary disease (reduced TSH drive)
Etiology
Congenital hypothyroidism
• Thyroid dysgenesis (aplasia, hypoplasia, ectopic thyroid gland)
• Dyshomonogenesis (inborn errors of thyroid hormone synthesis)
• Defects in thyroid hormone transport
• Iodine deficiency – endemic goiter, cretinism
• Maternal disease (thyrotropin-receptor blocking antibody)
• Maternal medications (amiodarone, radioiodine)
• Hypothalamic-pituitary disease, mutations, def of TSH, GH and prolactin
Juvenile/acquired hypothyroidism
• Chronic lymphocytic thyroiditis (Hashimoto thyroiditid with goiter)
• Iatrigenic (iodide-containing medications, expectorant, amiodarone,
lithium, metamizole, irradiation of thyroid, thyroidectomy)
• Iodine deficiency – endemic goiter
• Hypothalamix pituitary disease – cranial irradiation, trauma,
craniopharyngioma

Clinical features - neonates

Post mature Increased body weight Lethargy
Poor feeding Large fontanelle Often asymptomatic at birth
Increased bilirubin Prolonged jaundice Slow growth
Hypothermia Distended abdomen Skin molting
Bradycardia Respiratory distress Hoarse cry
197

Clinical features – children adolescents
Poor growth Developmental delay Delayed puberty
Dry and cold skin Pale, dry, thin hair Goiter
Galactorrhea Omyxedema Puffy face
Constipation Cold intolerance

Diagnosis
• Newborn screening for congenital hypothyroidsm
o ↑TSH, ↓T4, TBG, ↑TRB ab
• Lab:
o Primary hypothyroidism: ↓T4, ↑TSH
o Secondary hypothyroidism: ↓T4, ↓TSH
o Compensated euthyroid: Normal T4, , ↑TSH
o Hashimoto – anti-TPO, anti-TSHR, anti-thyroglobulin
• Ultrasound/scintigraphy
Treatment
• Oral T4
• Iodine replacement

2. Hyperthyriodism
Gen: overactivity of thyroid gland with increased production of T3, T4

Etiology
• Graves diasese – Autoimmune disease
• Toxic multinodular goiter
• Toxic solitary adenoma
• Excess ingestion of thyroid hormones
• Neonatal graves disease - transient congenital hyperthyroidism
• Secondary hyperthyroidism

Oprematurity Low birth weight Small gestational age
Poor weight gain Fever Flushing
Lid retraction Goiter Tachycardia
Diarrhea
Clinical features – children adolescents

Irritability Restlessness Warm and moist skin
Weight loss Palpitations Exophthalmos, goiter
Thyroid eye disease Tachycardia Tremor
Hyperkinesia Diarrhea Polyuria, polydipsia

198

Diagnosis
• Lab:
o ↑T3, T4
o ↓TSH, TSHR ab
o Anti TPO, anti thyroglobulin (positive in graves disease)
o Thyroid scintigraphy
Treatment
• Antithyroid drugs – methimazole
• Radioactive iodine
• Subtotal thyroidectomy

3. Thyroiditis
Gen: Inflammation of the thyroid gland
Classification
• Acute suppurative thyroiditis
• Subacute, non-suppurative thyroiditis
• Chronic lymphocytic thyroiditis (Hashimoto thyroiditis)
Etiology
• S. Viridans, S. Aureus, Pneumococcus
• De Quervain disease – mumps, adenovirus, coxsackie, EBV
• Hashimoto thyroiditis – Autoimmune dx, usually features of
hypothyroidism
o Lymphoid infiltration with atrophy and fibrosis
Clinical features
Fever Malaise Follows URTI
Pain/tenderness neck Pain radiation to ear, chest Unilateral/bilateral edema
Tracheal compression Dysphagia Hoarseness

Diagnosis
• FNA biopsy
• Lab:
o ↑TSH, ↓T4, anti TPO - chronic
o ↓TSH, ↑T3, T4 – subacute
o Euthyroid – acute suppurative
Treatment
• ATB
• Hormone replacement for Hashimoto disease

199

21c.Acute abdomen
Gen: As pathological abdominal condition characterized by sudden onset of
symptoms with quick progress and subsequent life-threatening consequences
• Acute abdominal pain is a frequent, non-specific symptom usually
associated with a self limited minor condition such as viral/bacterial
gastroenteritis, mesenteric lymphadenitis, constipation
• It is important to distinguish these patients with abdominal pain due to
serious life threat that requres surgery – appendicitis, bowel obstruction
o Children <2 years cannot describe/localize pain – crying and
drawing up legs
o Children >5 years can describe onset, duration and location of
symptoms
Associated with
N+V Fever Tenderness
Peritoneal irritation Diarrhea Constipation
Abdominal distention Guarding Palpable abdominal mass

Etiology
• Traumatic
• Non-Traumatic
o Inlammatory
o Obstructive
o Hemorrhagic

Intra abdominal Extra abdominal

Appendicitis UTI/pyelonephritis
Volvulus Tescticular torsion
Intussusception Inguinal hernia
Hirschprung disease Diabetic ketoacidosis
Meconium ileus Hemolytic uremic syndrome
Acute pancreatitis Henoch-Schonlein Purpura
1. Acute appendicitis
Gen: Common surgical emergency, rare <2 years, peak 5-30 years
• Inflammation of the veriform appendix
Pathogenesis
• Appendix can be obstructed by fecolith, bacteria gets trapped and cause
inflammation
• Increased intraluminal pressure cause obstruction of venous drainage
• Ischemia – Necrosis, gangrene – perforation

200

Clinical features
Infant/toddler Older children
Difficult to diagnose Diffuse periumbilical/epigastric pain
Drawing up legs, persistent legs V+N
Vomiting, diarrhea Low grade fever
Fever Constipation

Diagnosis
• Physical examination:
o Positice McBurney’s sign
o Rovsing sign – pain on right side, while palpation on left
o Blumberg sign – rebound
o Plenies sign – percussion tenderness
• Lab: CBC, ↑WBC, CRP, ESR
• Ultrasound
• CT when uncertain
Treatment
• Appendectomy

2. Intussusception
Gen: When the distal ileum or any segment of the colon invaginates into another.
Most commonly seen in infants 6months-2 years
• Intestinal infarction – perforation – peritonitis - Death
Clinical features
Spastic, colicky pain Flexed legs, loud cry
Vomiting, hematochezia Fever
Palpable mass

Diagnosis
• History and Physical examination
• Ultrasound
• X-ray
• Gas/barium enema
Treatment
• Barium enema – disinvagination
• Surgery

201

3. Volvulus
Gen: Complete twisting of a loop of intestine around its mesentreric attachment
site, often associated with malrotation, which predisposes to volvulus
• Can occur at various sites of GIT, most common midgut volvulus – causes
blockage that may cut off blood flow
Clinical features
Distended abdomen Bile-stained vomiting
Bloody stool Constipation

Diagnosis
• Ultrasound, CT
• X-ray
• Barium enema
Treatment
• Coloscopy
• Surgery
4. Testicular torsion
Gen: Torsion of the spermatic cord structures and subsequent loss of blood
supply to the ipsilateral testicle
• Affects neonates and adolescents
• <6hours – 90-100% salvage rate
Pathogenesis
• In neonates – testicle hasnt descended into the scrotum where it becomes
attached within the tunica vaginalis, causes extravaginal testicular torsion
Clinical features
Pain Swelling
N + V Fever
Abdominal cremasteric reflex

Diagnosis
• History and Physical examination
• Ultrasound if neccessary
• Labs
Treatment
• Surgery – definitive treatment
• Manual detorsion

202

5. Hirschsprung disease
Gen: Constricted rectum and sigmoid colon due to lack of ganglionic nerve vells
and a dilated area above the constriction
Clinical features
No meconium passage within 48h Bile-stained/feculent vomiting due to obstruction
Distended abdomen Constipation turns to foul smelling diarrhea
Fever Megacolon may develop (↑risk of perforation,
peritonitis, enterocolitis)

Diagnosis
• Ultrasound
• Barium enema
• Anorectal monometry
• Biopsy – absence of ganglion cells
Treatment
• Surgery – endorectal pull through procedures

203

22a. Nephrotic syndrome
Definition
• Nephrotic syndrome is a syndrome characterized by: heavy proteinuria,
edema, hypoalbuminemia, and hyperlipideamia.
• It is a non-specific disorder which results from kidney damage. If left
untreated it may eventually lead to renal failure and decrease in GFR.
• It’s one of the glomerulopathies which are usually immunologically
mediated
• In nephrotic syndrome there’s a massively increased filtration of
macromolecules across the glomerular capillary wall. Due to
structural and functional abnormalities of the glomerular podocytes
Proteinuria (heavy) § >50mg/kg/day

Hypoalbuminemia § <25g/L
§ This is a result of the heavy proteinuria
Hyperlipidemia § Hypercholesterolemia
§ Hypertriaglyceridemia
Edema § Due to the hypoalbuminemia

Classification:
Congenital Primary Secondary

o Finnish typeà A mutation o Minimal Change Disease (MCD) o Metabolic
that affects the gene that o Focal Segmental • Diabetic nephropathy
encodes nephrin Glomerulosclerosis (FSGS) o Autoimmune
§ Nephrin is a o Membranous • Amyloidosis
transmembrane protein glomerulonephritis (MGN)
• Systemic Lupus

Erythematosus (SLE)

Pathophysiology of nephrotic syndrome
Proteinuria
• Podocytopathy
o There’s a decrease in the concentration of nephrin and podocine in
nephrotic syndrome
o There’s also a decrease in the number of podocytes
o The ‘slit membrane’ is lost
• Formation heteropores in the glomerular basement membrane
o These are 5-10µm in size
o They occur due to inflammatory cytokines and proteolytic
enzymes
o The result is a non-selective proteinuria
§ There’s passage of more, larger molecules through the
kidneys
204

• Loss of a negative charge on the Glomerular Basement Membrane
(GBM)
o This negative charge normally repels negatively charged proteins
o When this fails, so does the repulsion
Hypoalbuminemia
• Result of protein loss in the urine and stool
• Increased albumin catabolism à In the proximal tubules in nephrotic
syndrome
• Transfer of proteins to the extracellular fluid (ECF)
• In insufficient increase in protein synthesis à The hepatic albumin
synthesis increase isn’t enough to meet the loss
• Note: Proteinuria can’t solely result in hypoalbuminemia
o Daily protein intake of 70g and synthesis of 10-12g a day is enough
to compensate for the 3.5g a day loss in the urine
Edema
• There’s currently 2 theories as to why the edema occurs
• Underfilling theory
o Proteinuriaà hypoproteinemiaà decreased plasma oncotic
pressureà extravasion of fluidà decreased plasmatic volume
(hypovolemia)à stimulation of RAASà retention of Na+ and H2O
o This seems unlikely though as 2/3 of nephrotic syndrome patients
are normovolaemic of hypervolaemic
• Overflow theory
o This suggests there’s an increase in both Na+ and H20 retention in
the collecting ducts
o This is due to an overexpression of the Na+/K+-ATPase protein
o There’s also a decrease in Na+ and H20 excretion due to a
resistance of the kidneys to Anti Natriuretic Peptide (ANP)
Hyperlipidemia
• Increased synthesis of lipoproteins in hepatocytes as a compensatory
mechanism for hypoalbuminemia
o This increases LDL and VLDL without changing HDL
• There’s increased cholesterolemia
o There’s a negative correlation between cholesterol and albumin
• Decreased clearance of VLDL and chylomicrons as a direct response to
albuminuria

Clinical manifestations:
• Edema in various areas are the principal clinical findings of nephrotic
syndrome:
o Ankles
o Genitals
o Abdominal wall (ascites)
• Effusions in serous spaces: Pleural and pericardial effusions
• Hypertension
• Features of the underlying disorder in secondary nephrotic syndrome
205


Diagnosis:
Proteinuria > 50mg/kg/day
• Selective proteinuria • é permiability for small proteins as Albumin,
Transferin

• Selectivity index up to 0.1 and it has a good
• Non-selective proteinuria
prognosis

• é permeability for larger molecules
• Selective index of 0,3, which has a bad
prognosis
Hypoproteinemia <60g/L
Hypoalbuminemia <25g/L
Hyperlipidemia • Increased triglycerides
• Increased cholesterol
• Increased LDLs
• Increased VLDLs
Lipiduria
Increased urine osmolality
Cylinduria Hyaline casts
Microscopic hematuria

• A diagnosis is normally made using
o Clinical features
o Biochemical changes
o Proteinuria
• Renal biopsy
o The biopsy is done to evaluate
§ Grade of glomerular sclerosis
§ Extent of the damage to the kidneys
o They are contraindicated in patients with:
§ One kidney
§ Shrunken kidneys
§ Coagulopathies

Complications
• Edema
o Especially pulmonary edemas
• Protein malnutrition
o Loss of proteins
o Lack of vitamin D
• Cardiovascular events
o Increased lipids leads to atherosclerosis

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• Predisposition to infections
o Loss of IgG by urine in non-selective proteinuria causes alteration
of immunity
o Decreased IgG synthesis due to nephrotic syndrome
o Corticosteroid treatments can cause immunodeficiency
• Hypercoagulation
o Due to an increased synthesis of different blood factors due to
compensation of hypoalbuminemia in the liver
§ Factor V
§ Factor VIII
§ Von-Willebrand’s Factor
o Increased platelet aggregation
o Decreased antithrombin III activity
o Resistance to both protein C and protein S
o Increased risk of thrombosis and thromboembolic complications
§ Renal vein thrombosis
§ Pulmonary embolism
§ Cranial thrombosis
• Endocrine changes
o A loss of transport proteins for hormomones
o Decreased hormone production
o Most commonly there’s a decreased in
§ TSH
§ Sexual hormones
Treatment
• Diet: Achieve a normal protein intake of 0.8-1.0g/kg/da
• Diuretics: Loop diuretics like furosemide are given
• ACE inhibitors
o Decreased proteinuria to renal protective effect
o Antiproliferative effect
o Antifibrotic effect
• Sulodexide
o A glycosaminoglycan mixture that restores the glomerular
basement membrane electronegativity à It’s effect is questionable
though
• Steroids
o Decreased synthesis of inflammatory mediators and influences the
permeability of the Glomerular Basement Membrane
o Prednisone and prednisolone are given for approximately 7
months
o There’s a high incidence of side effects though

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• Cytostatic immunosuppressive agents
o Most commonly a combination of both cychlophosphamide and
prednisone
• This is the most effective but it has severe side effects including
§ Infertility
§ Myelotoxicity etc.
o Cyclosporine A and prednisone can be used
• Can cause nephrotoxicity though (which is counterintuitive but
last resort)
• Plasmapheresis

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22b. Fever and its treatment, Fever of unknown
origin (FUO)
Definition
Fever of unknown origin is defined as documented fever >38,3 C on several
occasions persisting for >2 weeks, with no clear diagnosis, despite thorough
investigations (1 week of hospitalization).
Normal temp 36,6 – 37,9

Subfebrile 37 - 38
Febrile 38 - 40
Hyperpyrexia 40-42
Hyperthermia >42
Pathogenesis
Body temperature is regulated by thermo sensitive neuron in anterior
hypothalamus. Fever should be considered a symptom of an underlying disease.
Three mechanisms can cause fever, pyrogenes, heat production exceeding loss,
defect heat loss.

Pyrogenes
• Endogenous pyrogens (IL-1, IL-6, TNF ALPHA, IFNs) are released into
circulation from inflammatory cells in response to exogenous pyrogens
(MIOs), inflammatory processes or malignancy.
• Cytokines reach the anterior hypothalamus causing production of PGE2
• PGE2 attaches to PG receptor in hypothalamus and raises hypothalamic
temperature set point
Heat production exceeding loss
• Examples include salicylate poisoning and malignant hyperthermia
Defective heat loss
• Examples include children with ectodermal dysplasia and victims of
severe heat exposure
Etiology
The causes can be organized into 4 main categories
• Infections
o Viral
o Bacteria
o Parasitic and fungal
• Inflammatory
• Neoplastic
• Miscellaneous

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Bacterial Parasitic and Inflammatory Neoplastic Miscellaneous
infections fungal infections
Otitis media, Parasites: Malaria, CT dx: KIA, SLE, Lymphomas, Drug induced
sinusitis, seishmaniasis, RA neuroblastoma, (ASA), heat
pharyngitis, sarcoma, stroke,
s.pneumonia, leukemia, thyrotoxicosis,
h.influenza, histocytosis, cyclic
m.catarhalis, ewing sarcoma neutropenia
s.pyogenes
Borelliosis, Fungi: Vasculitis: Ectoderma
brucellosis, histoplasmosis, Kawasaki, dysplasia,
thyphoid fever, coccidioidomycosis, wegeners vaccines,
syphilis, TB, blastomycosis diabetes
listeria insipidus
UTI, meningitis, IBD, juvenile
pneumonia, SLE, systemic
gastroenteritis JIA, hereditary
periodic fever
syndromes

Fever patterns
• Continuous fever
o Steady fever >38 (<1c fluctuation), seen in typhoid fever
• Remittent fever
o Within 24 hours fever fluctuates >2c but never returns to normal,
seen in infective endocarditis
• Intermittent fever
o High temperatures which (during the day) fall to normal or
subnormal levels
o With certain periodicity e.g. quotidian fever 24 hours periodicity
• Recurrent fever
o Periods of fever are interrupted by long afebrile periods, seen in
boreliosis
• Pel-Ebstein fever
o Temperature rise within few days and returns to normal, the cycle
repeats itself. Seen in Hodgkins lymphoma and brucelliosis
Clinical features
• Neonates: may not have fever but hypothermia despite an infection
• Children < 5 years: may have an exaggerated febrile response (>40c)
even with benign viral infections
• Older children and adolescents have temperature of >40c in severe
disorders only
Fatigue Irritability Feeling hot or cold

Shivering Facial flushing Tachycardia (↑1c–10bpm)
Bradycardia
210

Diagnosis
• History – Onset, after symptoms, travel, indications, systemic illnesses,
recurrent infections, etcetera.
• Physical examination – look for localizing symptoms (e.g. otalagia in
otitis media, lymphadenopathy and erythematous throat in pharyngitis)
• Lab: CBC, ESR, CRP, blood cultures, Ag testing
• Urinalysis
• CSF analysis: cell count, glu, pro, culture (exclude inf)
• CXR
• CT/MRI/USG
• BM/LN biopsy: leukemia, lymphoma
• Serology: ANCA, ANA, RF, virus, bacteria
Treatment
• Treatment of the underlying cause: ATBs, steroids, chemotherapy
• Hydration is the mainstay of therapy: 1c of fever increased basal fluid
requirements by 12%
• Antipyretics paracetamol and ibuprofen are indicated for temperatures
>39c or for children with chronic cardiopulmonary, metabolic or
neurologic disorders
• Children 6 months to 5 years are at increased risk for simple febrile
seizures
• Complications: dehydration, febrile sezures (iv diazepam)
37-38 Hydration, not overdressed

38-39 Antipyretic: paracet, ibux>6m, aspirin >12y
39-40 Tepid water bathings, sponging
>40 IV steroid, metamizol, refridgerated infusions

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22c.Disorders of calcium and phosphorus metabolism
General
Calcium and phosphorus are maily regulated by diet and hormones
PTH
• Parathyroid hormorne is secreted by parathyroid gland in response to
decreased calcium and/or increase phosphorus levels
• Increased calcium in serum by ↑bone resorption, ↑renal tubular
resorption of calcium and by activating (↑calicium resorption in Gut)
Vitamin D (calcitriol)
• Produced in skin after UV exposure and then activated in the kidneys and
ingested
• ↑both Calcium and PO4 by ↑absorption in gut, ↑renal tubular resorption
Calcitonin
• Secreted by C-cells of thyroid gland
• ↓Calcium and phosphorus by ↓bone resorption (↓Ca and PO4 release
from bone)
• ↑renal excretion of Ca and PO4
1. Hypocalcemia
Gen:
Neonate <1,8 mmol/L Infant/children (>1month) <2,1mmol/L
Etiology
• Hypoparathyroidism - ↓Ca, ↓Parathyroid hormone, ↑PO4
• Vitamin D deficiency – ↓Ca, ↓PO4, ↑Parathyroid hormone
• Hyperphosphatemia - ↓Ca, ↑PO4, ↑Parathyroid hormone
• Miscellaneous – acute pancreatitis, prematurity, IUGR, large blood
transfusion
Clinical findings – (neuromuscular excitability)

Infants Older children Complications
Apnea Tetany Intracerebral
calcifications
Laryngeal spasm Carpopedal spasm Cataract
Stridor, convulsions Clovstek sign, Trosseu sign Osteomalacia/rickets
Hyperreflexia
↑PTH lead to ↑Ca, but leads to calcificationof vessels, eyes, soft tissues, and bone
resorption
Diagnosis
• Blood: ↑Ca
• ECG: Long QT interval, predispose to torsades de pointes
Treatment
• Calcium supplementation, diet
• Calcitriol (vitamin D)
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2. Hypercalcemia
Gen:
Serum ca >2,7mmol/L
Etiology
• Vitamin D excess
• PTH excess
• Neonatal ↑calcemia – William syndrome
• Miscellanious – Bone trauma, bone malignancy, hypothyroidism
Clinical findings
N+V Polyuria/polydipsia Bradycardia
Arrhytmia Muscle weakness Hypotonia
Hyporeflexia Somnolence/coma Nephrolithiasis
Pancreatitis
Diagnosis
• Blood: ↑Ca
• ECG: Short QT interval, negative T wave in leads 2 and 3
Treatment
• Dietary calcium restriction
• Glucocorticoids - ↓intestinal absorption of Ca in vitamin D excess
• ↑diuresis with NaCl to excrete Ca
• ↑dietary phosphate to bind Ca
• Bosphosphonates - prevent Ca release from bones

3. Hypophosphatemia
Gen: Serum levels:
<1,4 mmol/L – Neonate <1,3 mmol/L – Infants <1,0 mmol/L – Children
Etiology
• Transcellular shift
o Glucose infusion, insulin
o Tumor growth
• ↓Intake .- uncommon
• Renal loss
o Hyperparathyroidism, rickets
o Diuretics - ↑PO4 excretion
o Autosomal dominant/autosomal recessive disease
o MAC – inhibits PO4 reabsorption
• Miscellaneous
o Vitamin D deficiency - ↓Ca, ↑PTH
o Hemodialysis
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Clinical findings
Proximal muscle weakness Atrophy Rickets
Rhabdomyolysis Cardiac dysfunction Tremor
Seizure Coma
Treatment
• Per Oral/IV PO4
4. Hyperphosphatemia
Gen: Serum levels:
>2,6mmol/L – Neonate >2,1mmol/L – Infants >1,8 mmol/L – Children
Etiology
• Transcellular shift
o Tumor lysis syndrome
o Hemolysis
• ↑Intake
o Enema/laxatives
o Cow milk
o Vitamin D excess
• ↓Excretion
o Renal failure
o ↓Parathyroidism
Clinical findings
Hypocalcemia sign Systemic calcification
Treatment
• Low PO4 diet
• CaCO3 – PO4 binder
• Dialysis if renal failure

5. Hyperparathyroidism
Gen: Overactivity of gland - ↑PTH >55pg/mL
Etiology
• Primary hyperparathyroidism
o Hyperfunction of the gland itself - ↑PTH
o Tumor: adenoma/carcinoma/hyperplasia
• Secondary parathyroidism
o ↑PTH secretion due to hypocalcemia – vitamin D deficiency,
chronic kidney disease
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Clinical findings
Weakness/fatigue Depression
Bone pain Myalgia
N+V Polyuria, polydipsia
Osteoporosis
Diagnosis
• Primary
o Serum PTH, ↑Ca
• Secondary
o Urine test
o DEXA scan
o Sestamib scintigraphy
o CT - malignancy
Treatment
• Treat underlying disease
• Surgery – remove tumor
• Calcimimetics
o Mimics Ca in blood
• Bisphoshphonate
6. Hypoparathyroidism
Gen: ↓level of PTH in serum - ↓Ca
Etiology
• Iatrogenic – during surgery accidentaly remove PT gland
• Congenital – Di George syndrome
• Autoimmune disease – autoimmune polyglandular syndrome
• Magnesium deficiency
• Pseudohypoparathyroidism - ↑Pth, but ↓Ca, ↑PO4 – receptor defect
Clinical findings
Muscle cramp Twitchin/paresthesia
Fatigue Brittle nails
Headache, depression Abdominal pain
Tetany
Diagnosis
• ↓PTH, ↓Ca, ↓PO4, ↓Mg
Treatment
• Ca supplement
• Vitamin D

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23a. Meningitis and encephalitis

Meningitis
Definition
Inflammation of the meninges, covering the brain
• Leptomeninges – involves inner layers (arachnoid + pia mater)
• Pachymeninges – involves outer layer (dura mater)
Etiology
Bacteria Viral
Neonates Infant/older children Aseptic meningitis
GBS S. pneumonia Enterococcus: echo/polio/coxsackie
E-coli N. meningitis Arbovirus: Wesy-Nile
L. Monocytogenes H. influenza Mumps: HSV, EBV, CMV, HIV
Klebsiella E-coli
Enterococcus Klebsiella Usually presents as
P. aeruginosa meningoencephalitis
Transmission
• Hematogenous spread – colonization of nasopharynx, bacteria enter CSF
• Inoculation via penetrating cranial trauma
• Invasion from nearby focus of infection (sinusitis, mastoiditis, OM)
Clinical findings
Neonates Children >3years
CNS signs: • Acute onset headache
Signs of neonatal sepsis • Nuchal rigidity
• Temperature instability • Fever
• Respiratory distress • Confusion
• Jaundice • Lethargy
• Apnea • Coma
Lethargy • N+V
Vomiting • Photophobia
Seizure • Seizures
• Poor feeding
• Bulging fontanelle
• Nuchal rigidity
Meningeal signs
• Babinski
• Kernig
• Laseque
• Nuchal rigidity
• Petechial skin rash – meningococcal meningitis
216

Diagnosis
• Lumbar puncture – CSF analysis
o Cloudy, purulent, ↑pressure, PMNL, ↑proteins, ↓glucose
• Lab: CBC, diff blood count
• CRP, procalcithonin, PCR
• Blood glucose, electrolytes
Treatment
• Empirical ATB’s
o For neonates – ampicillin + gentamycin/cefotaxime
o Infants/older children – Cefotaxime + vancomycin
• Mannitol – Prevent/decrease cerebral edema
• Dexamethasone
• Viral – supportive /symptomatic treatment, acyclovir for HSV
Encephalitis
Definition
• Inflammation of brain parenchyma – brain dysfunction associated with
meningitis
Etiology
Viral
Same as Aseptic meningitis
Enterococcus: echo/polio/coxsackie
Arbovirus: Wesy-Nile
Mumps: HSV, EBV, CMV, HIV
Usually presents as meningoencephalitis
Clinical findings
• Prodrome of non-specific features (cough, headache, sore throat,
abdominal pain, skin rash, fever)
• Progressive (lethargy, coma)
• Personality change, illusion/hallucinations
• Aphasia, ataxia, hemiparesis
• Seizures
Diagnosis
• CSF analysis
• EEG – slow wave activity/HSV - ↑wave in temporal region
• MRI
Treatment
• Supportive treatment
• Vaccine – Polio, MMR, TB
• Acyclovir – HSV, VZV
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23b. Acid-base disorders

General:
• The pH of blood is normally slightly alkaline 7.35-7.45
• A number of conditions cause changes of the pH
o pH >7.45 is alkalosis
o pH <7.35 is acidosis
• Acids are produced in large amounts by the body from:
o Metabolism of fats and carbohydrates (CO2 production)
o Diet
o Anaerobic glycolysis during exercise (lactic acidosis)
• Bases are formed from
Anionic aminoacids Consumption of organic anions
• Glutarate • Lactate
• Aspatate • Citrate

Mechanisms of Acid-Base Balance
• Buffer systems (1st line defence)
o Buffers are mixtures of weak acids and its conjugate base
o The bicarbonate buffer system (HCO3/CO2) is the most
important system
§ CO2 + H2O ⇌ H2CO3 ⇌ H+ +HCO3-
o Other buffers include:
§ Organic phosphate
§ Proteins
• Lungs (2 line of defence)
nd
o Works within minutes/hours

o CO2 produced by the bicarbonate buffer is excreted by the lungs
o The metabolism of O2 and glucose is also buffered with this
method
• Kidneys (3rd line)
o Works within hours/ days
o Controls the pH by reabsorption of HCO3- and excretion of H+

Changes:
• Acid base disorders result in changes of:
o Arterial pCO2 (32-45mmHg)
o Serum HCO3- (18-25mEq/L)
o Serum pH (7.35-7.45)

Classification:
• Metabolic Acidosis
• Metabolic alkalosis
• Respiratory acidosis
• Respiratory alkalosis

218

Metabolic Acidosis
General:
Methanol Uremia (CRF) Diabetic Propylene
ketoacidosis glycol
Infection, iron, IEM, Lactic acidosis Ethylen glycol Salicylates
isoniazid
• Characterized as:
o pH <7.35
o A primary reduction in HCO3
o Compensatory decrease in pCO2 à by hyperventilation
• Causes include:
o Increased acid formation: DKA, Lactic acidosis
o Increased acid ingestion: Diet, Ethylene glycol, Salicylates
o Decreased renal acid excretion: Renal tubular acidosis
o Increased loss of bicarbonate: Severe diarrhea

Classification
• High anion gap metabolic acidosis
o The anion gap is AG=Na+ - [Cl- + HCO3-]
o Causes include: MUDPILES

• Normal anion gap metabolic acidosis
o This is when the anion gap is 12±4
o Causes include:

Addison’s disease Bicarbonate loss Chloride ingestion
• GIT
• Renal tubular
acidosis
Drugs ABCD
• Acids

Clinical manifestations of metabolic acidosis
• CVS • Neurologic
o Decreased BP o Confusion
o Decreased cardiac output o Drowsiness
o Cardiac arrhythmias o Coma
o Pulmonary hypertension • GIT
• Metabolic o Nausea
o Hyperkalemia o Vomiting
o Insulin resistance • Respiratory
o Bone remineralisation o Hyprventilation (kussmall
§ Chronic academia breathing)
o Dyspnea

219

Treatment
• Treat the underlying cause
o Hemolysis? for acute kidney injury
o Toxins
• NaHCO3 in severe acidosis
o pH <7
• Rehydration

Metabolic alkalosis
General:
• Characterised as:
o pH of >7.45
o Primary increase of HCO3
o Compensatory increase in pCO2 à hypoventilation

Classification:
• Chloride – responsive
• Chloride-resistant
Causes include:
• Acid loss (vomiting)
• Alkali administration:
o Milk
o Bicarbonate
o Infusion
• Bicarbonate retention
o The most common causes of HCO3 retention are:
§ Decreased K+
§ Decreased plasma volume
§ Primary and secondary hyperaldosteronism
§ Hypokalemia
§ Gitelman syndrome
• Hypokalemic metabolic acidosis
• Hypocalciuria
• Hypomangnesaemia
§ Diuretics
§ Laxatives
a. Chloride - responsive (U-Cl < 15 mEq/L):

• Alkalosis is maintained by volume depletion (↓GFR & ↓ HCO3- excretion)
• Can be easily corrected by rehydration with NaCl

Etiology:
• Emesis & nasogastric suction
• Loop or thiazide diuretics
• CF
• Chloride-losing diarrhea
220

b. Chloride-resistant (U Cl >20mEq/L):
• ↑ BP: • Normal BP:
o Adrenal adenoma o Gitelman syndrome
o Adrenal hypoplasia o Bartter syndrome
o Cushing syndrome

o Renovascular disease

o Liddle syndrome

Both the disease are characterized by:
• Urinary loss of Na & Cl & water
• Loss of H+ and K+,
• Retention of Na+ &H2O
• Volume depletion & secondary hyperaldosteronism→ loss of H+ & K+.
CVS Metabolic Neurologic
• Decreased coronary • Anaerobic glycolysis • Tetany
blood flow (angina) o potassium • Seizures
• Arrhythmias (K+/H+ ATPase) • Lethargy
• Coma
• Tremor
GIT Respiratory
• Diarrhoea • Compensatory hypoventilation
o Also decreased pO2

Treatment
• Chlorine for Cl-sensitive metabolic alkalosis
o Give 0.9% saline
• Acetazolamide
o Increases HCO3 excretion
• Hydrochloric acid
o May cause sclerosis of peripheral veins
o Administered only by a central line
• Hemodialysis or hemofiltration à This is used for urgent correction of pH
Respiratory acidosis
• Characterized by pH < 7.35, primary ↑ pCO2 & compensatory ↑ in HCO3-
(HCO3- retention in kidneys)
Causes are states of hypoventilation (↓ minute ventilation)
• During anesthesia, drug overdose (opiates)
• Brain-stem damage due to trauma or tumors or encephalitis
• Lung disorders like asthma, pneumonia, atelectasis, bronchiolitis, CF,
COPD
• Neuromuscular disorders (guillian-barre, myasthenia gravis, polio,
botulism)

221

Clinical manifestations
• Features are similar to those of metabolic acidosis, but ventilation is
shallow and rapid (tachypnea) in patients with lung disorders → pO2 may
be low
• If respiratory acidosis develops rapidly (acute) it presents with
drowsiness, stupor & coma (CO2 narcosis), but if it is chronic (in COPD) it
is better tolerated & presents with sleep disturbances and memory loss
→it causes hyperkalemia & arrhythmias.
Treatment
• Treatment of underlying disorders
• Restoration of ventilation (intubation, mechanical ventilation)
• Bronchodilators (β2 agonists)
• Sodium bicarbonate is controindicated for chronic RAC
• O2 administration in patients with hypoxia. Caution in patients with
chronic RAC.
Respiratory alkalosis
• Characterized by pH > 7.45, primary ↓ pCO2 & compensatory ↓ HCO3- (
HCO3- excretion by kidney)
Etiology:
Causes are states by hyperventilation (↑ minute ventilation)
• Due to anxiety or pain, fever, sepsis, salycilates
• During mechanical ventilation
• As response to hypoxia (e.g. high altitude, anemia, asthma, aspiration
pneumonia)

• Acute RAL:
o Presents with confusion, paresthesia, cramps, loss of
consciousness (light headedness), hyperventilation
• Chronic RAL: is usually asymptomatic

Treatment
• ↑ inspired CO2 by rebreathing (paper bag) → only for anxiety
• Treatment of underlying disease

222

23c. Congenital abnormalities of digestive system
Gen/Function
• GIT – prominent part of immune system
• Absorption of nutrients from food, water, electrolytes
• Evacuate waste products
• Important to stimulate GIT by colostrum
o Encourage passing of baby’s first stool, clears excess bilirubin -
↓jaundice
• Stimulate immune system
Atresia Malpositions Other
Esophageal Gastroschisis Cleft lip/palate
Duodenal Omphalocele Meckels diverticulum
Intestinal Diaphragmatic hernia Meconium ileus
Ileocecal Volvulus Hirschprung disease
Rectal Malrotation
Anal
1. Cleft lip and palate

Gen: Facial and oral malformations that occur early in pregnancy
• They are due to failure of fusion of maxillary and pre-maxillary processes
• May be unilateral/bilateral
• Cleft lip
o Physical split/separation of two sides of upper lip and appears as a
narrow opening/gap in the skin of upper lip
• Cleft palate
o Split/opening in the roof of the mouth
o Involve the hard palate and soft palate
Etiology
• Genetics
o Van der Woude syndrome
o Perre Robin syndrome
o Patau syndrome – Trisomy 19
o Down syndrome – Trisomy 21
• Environmental factors – maternal folix acid deficiency, exposure to
alcohol, tobacco, steroid, anticonvulsive agents
Classification
• Incomplete soft palate cleft
• Complete soft palate cleft + hard palate cleft
• Complete soft palate with cleft lip
• Bilateral soft+hard palate cleft with cleft lip

223

Clinical findings
• Feeding problems – no negative pressure, no sucking
• Airway obstruction – tongue can prolapse into larynx with inspiration
• Otitis media, aspiration pneumonia, psychological problems
• Defects of teeth and alveolar ridge
Diagnosis
• Prenatal ultrasound
• Physical examination after birth
Treatment
• Surgical repair:
o Lips – 3 months
o Palate – 6-12 months
• Squeezable bottle + nipples
• Gastrostomy
• Palatial obdurator – prosthesis
AIM
• Separation of oral and nasal cavities
• Repositioning of the soft palate musculature to allow normal speech
production
• Prevent/minimize facial growth abnormalities
2. Esophageal atresia
Gen: Congenital condition that causes esophagus to end in blind-ended pouch
rather than connecting normally to stomach

Etiology
• 4th fetal week – when trachea and esophagus seperate
• Associated with polyhydramnion in 3rd trimester
Classification
1. Esophageal agenesis 2. Long gap, pure EA
3. EA with proximal tracheosophageal 4. EA with distal tracheoesophageal
fistula fistula (most common)
5. EA with proximal and distal TEF 6. TEF only
7. Congenital esophageal stenosis
Clinical findings
• Drooling
• Mucous and saliva bubbling from nose
• Choking, sneezing, coughing
• After swalling – cough, struggle – cyanotic (laryngospasm)
224

Diagnosis
• Nasogastric tube – no passage
• X-ray – tube coiled
• Barium
Treatment
• Surgical repair of atresia – end to end anastomosis + ligation of fistula
3. Pyloric stenosis
Gen: The pylorus muscle thickens and become abnormally large, blocking food
from reaching the small intestine
• Not present at birth, first symptoms present 1-4months (males 5:1)
Clinical findings
• Postprandial vomiting – projectile, non-bilious
• Persistent hunger
• Stomach contractions
• Dehydration – electrolyte imbalance
• Change in bowel movements
• Palpable hypertropic pylorus in RUQ, olive-shaped, firm, moveable mass
Diagnosis
• Blood test
• Ultrasound
• X-ray – barium string sign
Treatment
• Surgery – pyloromyotomy
• Correction of electrolyte imbalance
4. Pyloric atresia
Gen: Very rare condition
Eti: No known cause
Clinical findings
• Non-bilious projectile vomiting
• Feeding difficulty
• Abdominal distention
• Rupture of stomach occurs within 12 hours of life
Diagnosis Treatment
Ultrasound, distended abdomen Surgery
X-ray

225

5. Intestinal atresia
Gen: A malformation where there is narrowing or absence of a portion of the
intestine
Etiology
• Vascular accident in utero - ↓intestinal perfusion and ischemia
o Narrowing/complete obliteration of the intestinal lumen
• Superior mesenteric a/other major intesinal artery occlusion
• Associated with Down syndrome (duodenal atresia)
• Familian inherited – autosomal recessive disease
Types
• Duodenal • Ileocecal
• Jejunal • Rectal
• Ileal
Clinical findings
• Bilious emesis
• Abdominal distention
• No meconium passage
• Absent bowel sounds
• If bowel perforation – peritonitis and sepsis
Diagnosis
• X-ray – double bubble sign
• Polyhydramnion
Treatment
• Nasogastric tube – remove fluid
• IV fluid
• Surgery – duodenoduodenostomy
6. Gastroschisis
Gen: Defect in the anterior abdominal wall through which the abdominal content
freely protrude.
• There is no overlying sac
• Size of defect is usually <4cm
• Defect occur 5-8 weeks after conception
Etiology
• Blood supply distruption
• Genetics
• Aspirin
Diagnosis Treatment
Antenatal ultrasound Surgery
Maternal S-AFP
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7. Omphalocele
Gen: Abdominal wall defect that involves umbilical cord and the organs remain
enclosed in visceral peritoneum
• Protrudes in midline, throught umbilicus
Etiology
• Malrotation
• Edwards/Patau syndrome
Diagnosis Treatment
Amniocentesis Surgery
Maternal S-AFP

8. Midgut malrotation
Gen: During fetal life, the bowel rotates counterclockwise around the superior
mesenteric artery until the cecum arrives in the right lower quadrant and the
duodenum in the LUQ
• When rotation is incomplete/abnormal – malrotation is present resulting
in a narrow mesenteric root
o ↑risk of volvulus
Clinical findings
• Bilious emesis
• Volvulus – crampy abdominal pain, distention, bloody stool emesis
• Perforation – peritonitis and sepsis

Diagnosis Treatment
X-ray with barium Surgical repair
Ultrasound

9. Meckel’s diverticulum
Gen: Remnant of embryonic yolk sac (omphaloesenteric duct)
• It is an outpouch of distal ileum and often contains ectopic gastric tissue,
producing gastric acid
Clinical findings
• 90% asymptomatic
• Rectal bleeding
• Intestinal obstruction
• Volvulus
• Intussuception – perforation (peritonitis)
• Can mimic acute appendicitis
227

Diagnosis Treatment
Ultrasound Surgery – resection/excision
Barium enema
Scintigraphy with TC99 – meckel scan
Endoscopy

10. Hirschsprung disease

Gen: Constricted rectum and sigmoid colon due to lack of ganglionic nerve vells
and a dilated area above the constriction
Clinical features
No meconium passage within 48h Bile-stained/feculent vomiting due to obstruction
Distended abdomen Constipation turns to foul smelling diarrhea
Fever Megacolon may develop (↑risk of perforation,
peritonitis, enterocolitis)

Diagnosis
• Ultrasound
• Barium enema
• Anorectal monometry
• Biopsy – absence of ganglion cells
Treatment
• Surgery – endorectal pull through procedures

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24a. Oesophageal (GERD) and Stomach disorders
1. GERD
Gen: Most common esophageal disease in children
• Effortless retrograde movement of gastric content across the lower
esophageal sphincter (LES) into the esophagus

Physiologic GER (spitting up) is normal in infants <8-12months
• Factors contributing to GER: Liquid diet, horizontal position, large volume
of food, immature LES

Pathologic GER
• Diagnosed after 18months or if there is complications such as
o Oesophagitis
o Respiratory symptoms – cough, wheezing, pneumonia
o Failure to thrive
Etiology
Oesophagitis ↑Intra abdominal pressure
Cough, wheezing – asthma CF Hiatal hernia
Mechanism
• Intermittent LES relaxation whih occurs independently of swallowing
Clinical findings
Infantile reflux GER in older children
Postprandial regurgitation • Regurgitation, heartburn (retrosternal or epigastric
Signs of oesophagitis: burning sensation)
• Irritability • Abdominal pain, dysphagia
• Choking • Respiratory symptoms:
• Gagging o Wheezing, stridor, cough, aspiration
• Feeding aversion pneumonia
• Recurrent otitis media/sinusitis, hoarse voice
• Saudifer syndrome torticollitis
Diagnosis
• Upper GIT Endoscopy
• Barium swallow
• Laryngotracheobronchoscopy
• 24h Oesophageal monitoring

229

Treatment
• Conservative treatment
o Thickened feeds for infant
o Avoid tomato, drinks, chocolate
o Weight reduction?
• Pharmacotherapy – for pathologic GER
o Antacids – MgOH, AlOH3
o H2 receptor antagonist – Cimitidine
o PPI – Omeprazole
o Prokinetic agents – MCP, betanechol (↑LES pressure minimal
benefit)
• Surgery
o Fundoplication
Complications
• Barrets esopgagus
• Adenocarcinoma
2. Esophageal atresia
Gen: Congenital condition that causes esophagus to end in blind-ended pouch
rather than connecting normally to stomach

Etiology
• 4th fetal week – when trachea and esophagus seperate
• Associated with polyhydramnion in 3rd trimester
Classification
1. Esophageal agenesis 2. Long gap, pure EA
3. EA with proximal tracheosophageal 4. EA with distal tracheoesophageal
fistula fistula (most common)
5. EA with proximal and distal TEF 6. TEF only
7. Congenital esophageal stenosis
Clinical findings
• Drooling
• Mucous and saliva bubbling from nose
• Choking, sneezing, coughing
• After swalling – cough, struggle – cyanotic (laryngospasm)
Diagnosis
• Nasogastric tube – no passage
• X-ray – tube coiled
• Barium
Treatment
• Surgical repair of atresia – end to end anastomosis + ligation of fistula
230

3. Achalasia
Gen: Esophageal motor motility
• Disease of unknown etiology
• Characterized by failure of LES relaxation and oesophageal aperistalsis
• Associated with down syndrome, glucocorticoid insufficiency, Chagas
disease
Incidence
• Uncommon before school age, onset 9 years
Clinical findings – often misdiagnosed as GERD

• Progressive dysphagia
• Vomiting
• Weight loss
• Infant and younger children
o Recurrent pneumonia
o Nocternal cough
o Feeding difficulty
Diagnosis
• Barium swallow study
• Esopghageal monometry
• ↑LES pressure
• Upper GIT endoscopy – to rule out GERD
Treatment
• Surgery – myotomy
• Botox in LES
• Nifedipine
• Balloon dilation of LES
4. Hiatus hernia
Gen: A part of the stomach herniates through the esophageal hiatus of the
diaphragm
Types
• Sliding: 95%
o GE junction slides into thorax
o CF: Usually asymptomatic – sometimes GER
• Rolling: 5%
o Part of the stomach passes through the diaphragm and lies next to
esophagus
o CF: Fullness after eating, upper abdominal pain
Diagnosis Treatment
Physical examination Symptomatic treatment
X-ray, Barium swallow No direct treatment necessary
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24b. Disorders of puberty
Definition
Puberty is defines as a physiological phase lasting 2 to 5 years, during which the
genital organs mature.
Physiology
The onset of puberty is marked by:
• Pubarche (adrenal maturation) – appearance of pubic & axillary hair, oily
hair and skin, acne, body odor
• Gonadarche – there is ↑secretion of gonadal sex hormones as result of
hypothalamic-pituitary-gonadal axis maturation
o Males (testosterone) – facial, pubis, axillary hair, deep
voice,↑muscle mass,↑penile and testicular size
o Females (estradiol and progesterone) – breast development
(telarche), female body habitus,↑size of uterus, menarche
o Growth spurt of puberty
• The hypothalamic-pituitary-gonadal axis is active in the fetus and
newborn, but is suppressed in childhood until the onset of puberty.
• Adrenarche occurs several years earlier than gonadarche and it is
initiated by ↑production of adrenal androgen (DHEA)
• Factors affecting the initiation of puberty
o Height and weight (nutrition)
o Maturation of hypothalamus
o Onset of adrenal androgen activity
Types
• Delayed puberty
• Precocious puberty
Delayed puberty
Definition: No signs of pubertal development by age 13 in girls and 14 years in
boys.

Etiology:
• Constitutional delay in growth and puberty: ↓levels of GnrH, FSH,/LH and
sex hormones
o Patients have delayed onset of puberty and significant bone age
delay
o Spontaneous puberty usually begins when bone age reaches 11
years in girl and 12 years in boys
o Family history of delayed puberty (parent, sibling)
o No treatment required

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• Hypogonadotropic hypogonadism
o There is gonadal hormone insufficiency (delayed gonadarche) as a
result of hypothalamic or pituitary disorder
§ ↓GnRH /LH/FSH, ↓estrogen/progesterone or testosterone
o Causes
§ Isolated gonadotropic deficiency (GnRH)
• Kallmann sy
§ Abnormalities of CNS
• Pituitary adenoma, craniopharyngioma, gliomas,
germinomas
• Radiation, Infection
§ Anorexia nervosa (↓GnRH) & systemic illnesses (severe)
§ Hypothyroidism
• Hypergonadotropic hypogonadism
o There are elevated gonadotropin levels but low sex hormone levels
due to primary gonadal failure
§ ↑GnrH & FSH/LH,↓sex steroids
o Causes
§ Ovarian failure
• Ovarian dysgenesis (Turner sy)
• Premature ovarian failure (due to autoimmune
disorder, radiation, infection)
• Steroid biosynthetic defect (CAH)
§ Testicular failure
• Klinefelter sy
• Congenital gonadal disease (anorchia, cryptorchidism)
• Acquired gonadal disease (testicular torsion, orchitis,
radiation)
Treatment
§ Hormone replacement
o Females: initially ethanyl-estradiol until first menstruation occurs,
then estrogen-progesterone
o Males: testosterone
o Treat the underlying cause if possible
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Precocious puberty

Definition: Secondary sexual development before the age of 9 years in boys or 8
years in girls. For girls the normal developmental sequence Is thelarche,
pubarche and menarche (2-3 yrs later). For boys it is enlargement of testes
followed by appearance of pubic hair.

Etiology
• Central (true) precocious puberty
o Due to ↑production of hypothalamic/pituitary hormones:
o ↑GnRH, LH/FSH, sex hormones
o Causes include
§ CNS tumors (hamartoma, optic or hypothalamic glioma),
other CNS disorders (meningitis, radiation, encephalitis,
head trauma, epilepsy)
• Peripheral (false) precocious puberty
o GnRH independent: caused by oversecretion of sex steroid
o ↓GnRH,LH/FSH, sex hormones
• Causes include
o CAH
o McCune-Albright syndrome: characterized by precocious puberty,
cystic changes in bones, café-au-lait spots on skin
§ Puberty results from ovarian hyperfunction
o Adrenal adenomas and carcinomas
§ Carcinomas secrete DHEA, adenomas secret androgen or
estrogens
o Ovarian cysts in girls, ovarian tumors Leydig cell adenoma in
boys Idiopathic precocious puberty – if no cause is identified
Treatment
• To preserve height potential, psychological and social reasons
• Treat the underlying cause if possible: removal of hormone secreting
tumors
• Central precocious puberty can be treated by GnRH analogues (down-
regulate pituitary GnrH receptors and desensitization of pituitary)
• McCune-Albright syndrome – testolactone (oral tablets – inihibits
formation of estrogen from its precursors) or tamoxifen (antiestrogen)
Always assess
• Hormone levels (GnRH, LH/FSH, sex steroid hormones)
• USG of pelvis or abdomen (ovarian, adrenal tumor)
• Abd CT
• MRI (pituitary, hypothalamic and other CNS lesions)
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24c.Systemic lupus Erythematosus, Juvenile
Dermatomyositis and Scleroderma
Systemic lupus Erythematosus

General:
• SLE is an inflammatory multisystem disease characterized by the
presence of serum Ab against nuclear components (anti-nuclear Abs
ANAs)
• Arthralgia and rashes are the most common features (cerebral and renal
disease are the most serious complication)
• The F:M ratio is 9:1 and the peak age of onset ranges between 20:40
years.

Etiology
The cause is unknown and the disease is multifactorial with several predisposing
factors:
• Hereditary: Higher concordance in monozygotic than dizygotic twins
• Genetics: Genes linked to SLE development include HLA-B8; -DR3 and –
A1 and deficiency of complement genes C1q, C2 and C4
• Sex hormone status:
o Premenopausal women are mostly affected à estrogen hor. effect
o UV- light: can trigger
• Drugs: Imydazine, isomiazide or penicillamine can induce a mild lupus-
like syndrome
• Virus infections: such as EBV

Pathogenesis
• Cells die by apoptosis and their remnants (e.g. DNA and histones) appear
on their cell surface as self- Ags, normally these self-Ags are removed by
phagocytes but in SLE their removal is insufficient.
• These self-Ags are presented to T-cells which in they stimulate B-cells to
produce autoantibodies.
• The clinical manifestation of SLE are mediated by Ab formation and Ag-Ab
complex formation and deposition as well as complement activation,
influx of neutrophils and abnormal cytokine production (IL-10, INFa)
• SLE develops as a combination of availability of self-Ag and failure to
immune system to inactivate autoreactive B and T-cells

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General Joint and muscle Skin
• Fever (80%) • Arthritis with • Butterfly rash on face
• Malaise symmetrical small- • Vasculitis lesion on
• Tiredness joint arthralgia (90%), fingertips
• Depression joints are usually not • Round nails
• Weight loss swollen or deformed • Urticaria and purpura
• Myositis and myalgia • Photosensitivity
• Alopecia
• Raynaud’s
phenomenon
• Livedo reticularis
Hematology Kidney Lungs
• Anemia (of chronic • Lupus nephritis ( 30- • Pleural effusion,
disease) 50%) caused by pneumonitis and
• Hemolytic anemia immune system atelectasis
• Leukopenia/ complex deposition • Rarely pulmonary
lymphopenia on kidneys à can fibrosis
• Thrombocytopenia progress to nephrotic • Pulmonary
• Pancytopenia syndrome and renal hypertension
failure à may cause
death

Heart and CVS Nervous system GIT
• Pericarditis and • Epilepsy, cerebellar • Mouth ulcers
pericardial effusion, ataxia (mucocutaneous
myocarditis (causing • Peripheral ulceration)
arrhythmias) polyneuropathy • Mesenteric vasculitis
• Aortic valve lesion and • Migraine • Autoimmune hepatitis
cardiomyophathy • Aseptic meningitis • Pancreatitis
(rarely) • Stroke •
• Libman-sacs • Psychosis
endocarditis (aseptic) •
• Vasculitis
• Arterial and venous
thrombosis (increase
IHD and stroke)

Lupus nephritis
• Renal involvement is more prevalent in ped.onset SLE, when LN is
present in children is often more severe
o Persistent proteinuria greater than 0.5g/day/ or greater than 3+ if
quantitation not performed
o Cellular casts – may be red cell, hemoglobin,granular,tubular or
mixed
• Class IV which is diffuse, proliferative GN is tte most common and severe
• Renal biopsy to evaluate the extent of lupus involvement

Class I Minimal mesangial lupus nephritis
Class II Mesangial proliferative lupus nephritis
Class III Focal lupus nephritis
Class IV Diffuse lupus nephritis
Class V Membranous lupus nephritis
Class VI Advanced sclerosing lupus nephritis
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Diagnostic criteria (at least 4 of the following) DOPAMIN RASH
1) Facial skin erythema 2) Discoid erythema 3) Photosensitivity
4) Mouth ulcers 5) Arthritis 6) Serositis (pleuritis,
peritonitis, pericarditis)
7) Lupus nephritis 8) Hematologic 9) Neurologic
complications complications
10)Immunologic 11)ANAs
complications

Diagnosis
• Blood
o Anemia, leukopenia /lymphopenia, thrombocytopenia
o ↑ ESR, normal CPR
o ↑ urea and creatitine if renal involvement is present (late stage)
o ↓ albumin and increase urine protein / creatinine ratio in early
involvement ->proteinuria
o Autoantibodies (ANAs): anti-dsDNA, anti-Ro, anti-Sm and anti-La
o Hypocomplementemia, C3 and C4 levels are ↓, circulating immune
complexes
o IgG and IgM are high
• Histology
o Deposition of complement and IgG via IF in biopsies from kidney and
skin, immunoflorescence

Treatment
• Avoid sunlight and reduce CV risk factors
• Medication:
o NSAIDs for arthralgia in mild disease
o Topical corticosteroids and antimalarics (chloroquine and
hydroxychloroquine) for mild skin disease
o Systemic corticosteroids (prednisolone) for moderate to sever
disease
o Immunosuppressive drugs (azathioprine, cyclophosphamide,
cyclosporine A) are used in combination with oral corticosteroids
in patient with severe renal or cerebral involvement
o Biological therapy: belimumab – only biologic tx approved for SLE
• Plasmapheresis
• IVIG

Neonatal lupus syndrome

Gen: maternal SLE- Ab cross the placenta and affect the fetus.
CF: congenital 3rd degree AV-block with or without
• Endocardial fibroelastosis, structural anomalies of the heart,
• Erythema annulaee (around eyes),
• Hematocytopenia
237

Juvenile Dermatomyositis (JDM)
General: It is an inflammatory vasculopathy that affects primarily the skin and
skeletal muscle. It characterized by proximal muscle weakness and a
characteristic rash. It represents 20% of all inflammatory myositis and is the
most common inflammatory myopathy in children. The peak onset of JDM is
between 4-10 years
Pathogenesis
• There is activation of B and T –lymphocytes
o Causes vasculitis of small vessels of skeletal muscle
o There is immune complex deposition in blood vessels and muscles
o Etiology is unknown but JDM may follow infections, allergic
reactions or sun- exposure
o HLA polymorphism may also play a role (HLA-DR/DG)
Clinical features
• Slow progressive fashion with insidious onset of fatigue, malaise and
progressive muscle weakness, accompanied by low-grade fever and rash
• Muscle weakness
o Proximal muscles are usually affected such as hip and shoulder
girdles, neck muscles
o Patients have difficulty climbing stairs, getting out of chairs or off
the floor
o May have a positive Gower sign (use of hands on thighs to stand
from a sitting position)
o Muscles of upper airways pharynx and esophagus may be
involved causing dysphagia, dysphonia and GERD (esophageal
muscles)
• Rash/Skin Changes
o Classic JDM rash occurs on face, across cheeks but also on
shoulders and back (shawl sign)
o Heliotrope rash of eyelids (blue-violet discoloration of eyelids)
o Gottron papules (scaly red papules) are found over the
interphalangeal joints
o Dilated nail fold capillaries
o Lipodystrophy and calcinosis in longstanding or untreated cases
Diagnosis
• Diagnostic criteria
o Classic rash: heliotrope/Gottron papules
o Muscle weakness (proximal, symmetric)
o Increased muscle enzymes (CK, ALT,AST, LDH, Aldolase)
o EMS changes: myopathy, denervation
o Muscle biopsy: inflammation necrosis

238

Diagnosis (cont.)
• Normal CBC, ESR
• MRI (muscle inflammation)
• ANA+ in serum
Differential diagnosis of JDM
• Connective tissue diseases
o SLE, scleroderma, JIA, ANCA+ vasculitis
• Muscular dystrophy
o Duchenne, Becker
• Metabolic myopathies
o McArdle disease, Pompe disease
• Other disease
o Postinfectious myopathy, Myasthenia gravis, Inflammatory bowell
disease., Leukemia, Sarcoid myopathy
Treatment
• Methotrexate plus short-term use of systemic corticosteroids is the
mainstay therapy
• Hydroxychloroquine or dapsone can be used for skin manifestationsàno
effect on muscles
• In severe cases, cyclosporine or cyclophosphamide and IVIG can be uses
Juvenile scleroderma
Gen: Autoimmune disease that affects mainly skin: hard, tight in elastic skin and
subcutaneous skin. It is the most common type in pediatric or systemic sclerosis,
with organ involvement. The onset is typically before 16 years.

Types: Juvenile systemic sclerosis, juvenile localized sclerosis - morphea

Pathogenesis
• It is an autoimmune disease of unknown etiology
• MPKs and other inflammatory cells migrate into affected tissues and
secrete cytokines
• Induce fibroblasts that promote fibrosis (collagen deposition
• Triggers include trauma, infection and possibly GVH reaction to
persistent maternal cells

• Juvenile systemic scleroderma
o Chronic, multisystem, connective tissue disorder
o There is induration and fibrosis of the skin with loss of subcutaneous
fat, sweat glands and hair follicles
§ Atrophic skin is shiny and waxy in appearance

239

o With progressive fibrosis of internal organs and muscle atrophy,
weakness occurs
§ Esophagus, GIT, heart, lungs, kidney
§ Affects knees, lips, elbows, mouth
o Raynaud’s phenomenon
o Pulmonary disease is the most common visceral manifestation à
pulmonary artery hypertension
o Other organs involved include GIT (dysphagia, gastroparesis) &
kidneys (renal artery disease)
• Localized scleroderma
o Onset is insidious
o Initially erythema around an area of waxy induration
§ Followed by indurated hypo/hyper-pigmented atrophic
lesions
o There are several subtypes
§ Plaque morphea – well defined circular areas of induration on
dermis
§ Linear (streaks) scleroderma- can be continued to extremities
of trunk or can involve face & scalp & extend into CNS (en
coup de sabre) resulting in seizure & headaches
Diagnosis
• Skin biopsy
• Elevated ESR, eosinophilia & increased Igs
• Anti-topoisomerase I (ANA) can be seen
o Especially in systemic scleroderma
• MRI can show CNS involvement in en coup de sabre

Treatment
• Localized scleroderma
o UV therapy for superficial lesions
o Methotrexate 15mg/m2 (1x weekly for 24 months p.o)
o Acidum folicum 2,5mg/weekly
o Prednison 1mg/kg/day (max 50mg/day) for 3 months
• Systemic scleroderma
o CCBs and sildenafil for Raynaud’s phenomenon
o Methotrexate and mycophenolate mofetil for skin disease
o Cyclophosphamide for lung involvement

240

25a. Growth disorders
Gen: Growth is regulated by genetic, hormonal, nutritional and environmental
factors (both pre and postnatally) that interact to culminate in a complex
process of constant replication of cells in all tissues
Human growth:
Characterized by several phenomena
• Dramatic fetal growth
• Deceleration of growth immediately after birth
• Prolonged growth during childhood
• Pubertal growth spurt
1. Short stature
Gen: Very frequent reason for referral to pediatric endocrinologist
• Normal height is determined according to age, sex, ethnic group and
family context
• We compare the projected adult height of a subject with their «target
height» or «genetic height»

𝐡𝐞𝐢𝐠𝐡𝐭 𝐦𝐨𝐭𝐡𝐞𝐫 ! 𝐡𝐞𝐢𝐠𝐡𝐭 𝐟𝐚𝐭𝐡𝐞𝐫 ! 𝟏𝟑
• Boys:
𝟐
𝐡𝐞𝐢𝐠𝐡𝐭 𝐦𝐨𝐭𝐡𝐞𝐫 ! 𝐡𝐞𝐢𝐠𝐡𝐭 𝐟𝐚𝐭𝐡𝐞𝐫 ! 𝟏𝟑
• Girls:
𝟐
Definition
• Height below -2 SDS (percentile 2,3) for age, sex and ethnical group
• Persistent low growth velocity (below -1 SDS/25 percentile)
Growth velocity
• Cm per year
o 12/2013 – 145
o 12/2014 – 152
o 152-145 =7cm/year
Growth measurement
• Newborn
o Length, weight, head circumference according to gestation age –
infantometer
• Children >2 years
o Height, weight, HC according to gender - stadiometer
Classification
• Proportionate
• Disproportionate
• Unknown origin
o Familial short stature
o Constitutional delay of growth and puberty
o Association of FSS and CDGP
241

Disproportionate short stature
• Achondroplasia – mutation of FGF3
• Hypochondroplasia
• Osteogenesis imperfecta – mutation of collagen gene
Proportionate short stature

Prenatal origin, fetal/placental/maternal
• Noonan syndrom
• Prader-Willis
• Turner syndrome
• Silver-Russel syndrome
2. Small gestational age

Gen: newborn is SGA when their birth weight and/or length are at least 2 SDS
below the mean for gestational age
• 80-90% of SGA children experience partial/complete catch up growth
during the first/second year of life – reaching normal height
• 10-20% remain short after 2 years of life
Postnatal origin
Endocrinopathies Organic pathology
Growth hormone deficiency Celiac disease
Hypothyroidism Inflammatory bowel disease
Chronic hypercortisolism Chronic renal failure
Long term exogenous administration Juvenile idiopathic arthritis
of glucocorticoids
Excess of sex steroid Heart disease
Pseudohypoparathyroidism DM I with bad compensation
Growth hormone deficiency

Congenital
Newborn Toddler/preschool age
After physiological delivery, normal Short stature – 2,5SD
height/length
In boys, micropenis Doll-like face
Lab: hypoglycemia Trunkal obesity
Brachydactyly
Etiology of acquired
• Craniotrauma
• Craniopharyngeoma
• Autoimmune hypophysitis
Diagnosis Treatment
History, family history, physical exam Treat underlying cause
X-ray – bone age Recombinant GH for: GH deficiency, Turner’s
Lab: CBC, ESR, biochem, hormone level syndrome, Chronic renal failure, SGA/IUGR,
MRI of pituitary gland SHOX gene deficiency
242

25b. Chronic glomerulonephritis (IgA
Nephropathy, Henoch-Schönlein Purpura), Alport
syndrome
IgA nephropathy

General: It is the most common form of glomerulonephritis worldwide.

Pathogenesis:
• It is an immune-complex mediated GN characterized by mesangial IgA
deposits and mesangial hyper-cellularity .
• The disease probably result from an exaggerated bone marrow and
tonsillar IgA immune response to viral or other Ags;
• it’s also associated with an abnormality in O-galactosylation of the hinge
region of IgA

Signs and symptoms: It usually occur in children or young males and either
present as
• Recurrent episodes of macroscopic hematuria during or following URT
infection or GIT infection (viral) or persistent asymptomatic microscopic
haematuria
• Nephrotic syndrome is uncommon (5%) and proteinuria may appear late
in the course of the disease
• Renal failure is seen in 25-30% of patients, especially in those with
proteinuria, hypertension or microscopic haematuria

Treatment:
• Corticosteroids (prednisone)
• Fish oil, tonsillectomy (in recurrent tonsillitis)
• ACE inhibitors for patients with proteinuria and hypertension
243

Henoch-Schönlein purpura
General:
• The commonest systemic vasculitis in children, good prognosis
• It is due to IgA immune complex deposition in small vessels à often after
URT infection
Clinical manifestations: à triad!
• Purpura: Non-blanching rash - typically on buttocks, lower limbs.
• Arthritis
• Abdominal pain à GI hemorrhage
• Kidney involvement : Hematuria, HT
Diagnosis:
• Based on clinical symptoms and confirmed by biopsy
• Blood test:
o ↑ creatinine, urea
o ↑ IgA level
o ↑ CRP, ESR
o ↓ platelet
Treatment:
• HSP is normally only requires symptomatic relief because it is self-
limiting - usually resolving within about 2 months.
• Immunosuppression when there is renal involvement or severe disease
o Corticosteroid and cyclophosphamide/ azathioprine
o IVIG
• Kidney involvement: Hemodialysis
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Alport syndrom
General:
• Inherited, heterogeneous disorders involving the basement membranes
of the kidney and frequently affecting the cochlea and eye as well
• Alport syndrome is caused by defects in the genes encoding alpha-3,
alpha-4, or alpha-5 chains of type IV collagen of the basement membranes
• Hematuria, hypertension, proteinuria
• Family history of Alport syndrome or renal failure
• Sensorineural deafness; Deafness in childhood
• Anterior lenticonus and perimacular flecks
• Lack of alpha-3,4,5 collagen IV chains in glomerular basement membrane
(GBM)
Diagnosis:
• Based on clinical symptoms and confirmed by biopsy
o Presence of splitting or lamellation of the GBM on electron
microscopy
o Genetic testing
o Audiometry
o Ophtalmic evaluation
o Renal USG
Treatment:
• No definite treatment
• ACE-inh, ARBs,
• Immunosuppression when there is renal involvement or severe disease
o Corticosteroid and cyclophosphamide/ azathioprine
o IVIG
• Kidney involvement: Hemodialysis

245

25c.Disorders of amino acid metabolism
(Phenylketonuria, disorders of ammonia detoxification)
1. Phenylketonuria
Gen: phenylalanine is an essential AA – normal levels in serum 60-120umol/L
• Deficiency of the enzyme phenylalanine hydroxylase (PAH) or it’s cofactor
tetrahydrobioprotein (BH4), leads to accumulation of phenylalanin in
body fluids and brain – hyperphenylalaninemia
• When plasma PHE is increased, they are metabolized to phenylketones
that are excreted in urine – phenylketonuria
• Severity of disease depends on the degree of enzyme deficiency
Types
• Classic PKU
• Malignant PKU
• Maternal PKU
A) Classic PKU
Gen: autosomal recessive - >400 mutation of PAH gene
• There is absolute enzyme deficiency (↓activity) leading to PHE levels
>1200umol/L
Clinical features
• Vomiting
• Excitability
• If untreated
o Light skin and hair (defective melanin synthesis)
o Eczema, hair loss, blue eyes, musty/mousy odor of urine
o Neurodeficit within the first year of life
o Psychomotor delay
o Mental retardation (IQ>50)
o Seizure and spasticityDiagnosis
Treatment
• Restriction of dietary PHE – no fish, meat, dairy products or eggs
• Breastfeeding is important
• Target plasma PHE level – 40-240umol/L for 1-10years, <1200umol//L
for >16years
• Saproprotein (KUVAN) – synthetic form of BH4
o New treatment - ↓PHE levels
B) Malignant PKU
Gen: is about 1-3% of patient with hyperphenylalaninemia
• There is a defect in production/recycling of BH4
• BH4 is necessary for metabolism of CNS neurotransmitters
• Infants develop a progressive and lethal CNS disease with choreic
movements
246

Diagnosis
• Neonatal screening (detection of ↑ in PHE)
• Plasma PHE concentration (↑PHE, ↓tyrosine)
• Genetic testing
Treatment
• Diet – low PHE
• Life long supplementation of neurotransmitter precursors (L-DOPA)
• Saproprotein
C) Maternal PKU
Gen: when pregnant women suffer from PKU
Clinical features – all in child

• Growth retardation
• Microcephaly
• Congenital heart disease
Treatment
• Strict dietary control
• Plasma PHE (<360umol/L)
2. Urea cycle defects

Gen: Genetic disease caused by mutation that results in a deficiency of 1/6
enzymes in the urea cycle
N-acetylglutamine synthase (NAGS)
Carbamylphosphate synthase (CPSI)
Ornithine transcarbamylase (OTC)
Argininosuccinate synthase (ASS)
Argininosuccinate ligase (ASL)
Arginase
These enzymes are responsible for removing ammonia from the blood stream
• Nitrogen accumulates in form of ammonia – hyperammonia
• Ammonia in CNS, cause irreversible brain damage, coma and death
Clinical features
Neonate Child
Irritability Failure to thrive
Poor feeding Crying
Vomiting Agitation
Seizures Refuse to eat
Lethargy Vomiting
Hypotonus Lethargy
Respiratory distress Coma

247

Diagnosis
• Neonatal screening – cannot detect all disease
• Hyperammonemia - >100umol/L in neonate
• Hyperammonemia - >35umol/L in children
• Plasma amino acid abnormal
Treatment
• Short term treatment
o >200umol/L
§ Stop protein intake
§ IV glucose
§ Remove NH3 (nabenzoate) replace Arginine
o >500umol/L
§ Dialysis, hemofiltration
• Long term treatment
o Limit protein intake
o Nabenzoate
o Replace essential AA Arginine
o NH3 target level <80umol/L

248

26a. Acute diarrhoea in children
Definition
Change in consistency of stools into liquid. ↑Stool volume (>10mL/kg/day), and
excessive frequency (>3 times/day)
• Causes excessive loss of fluid and electrolytes
• May be accompanied by fever and vomiting
• Classification according to etiology and pathogenesis
Pathogenesis
Secretory diarrhea
• Caused by enteric viruses, toxigenic E-coli (ETEC and EPEC), cholera,
cryptosporidium and giardia
• There is ↑intracellular cAMP of cGMP or Ca – active secretion of Cl and
H2O into the bowel lumen
• Profuse, watery, non-bloody diarrhea
Inflammatory diarrhea
• Caused by invasive pathogens such as EIEC, shigella, salmonella, yersinia,
campylobacter
• There is inflammation of bowel wall, leading to ↓reabsorption of fluid and
↑intestinal motility
• It is a dysenteric type of diarrhea (distal ileum and colon) causing bloody
diarrhea with abdominal pain and cramps
Etiology
• Infants
o Gastroenteritis (viral>bacteria)
o Food poisoning
o ATB
o Hyperthyroidism (rare)
• Bacteria (nausea, fever, dysenteric diarrhea (bloody and abd pain)
o Salmonella
o Shigella
o E-coli
o Yersinia
• Virus (nausea, vomiting, non-bloody, low grade fever)
o Rotavirus
o Norovirus
o Adenovirus
Transmission is fecal-oral route (hands, contaminated food)
249

Rotavirus
• Most common
• Antibodies are formed after infection – subsequent infection (mild and
asymptomatic)
• Severe diarrhea and vomiting – dehydration and fever
• Diagnosed by antigen in stool
• Prevention by proper hygiene and vaccination
Complications
• Dehydration and hypovolemia
• Risk factors
o Infants and toddlers due to ↑ECF/ICF, ↑body water content, ↑body
surface area
o Can lead to electrolyte disturbances, acid base balance disease
(MAC)
Assessment of dehydration
• Percent of weight loss (mild, moderate, severe)
• ↑capillary refill time (>22 is abnormal)
• Skin turgor (↓turgor) and ↑resp rate (MAC), BP, pulse
• General appearance
o Sunken fontanelle
o Dry mucous membrane
o Absent tears
o Sunken eyes
Diagnosis
• Lab: Na, K, Cl, CBC, BUN, Crea, CRP, procalcithonin
• ABG: HCO3, PaO2, PaCO2, pH
• Serum glucose
• Stool assay – fecal calprotectin, culture, antigen detection
Treatment
• Rehydration: oral rehydration solution/IV/nasogastric tube
Mild 30-50mL/kg Moderate 50-100mL/kg Severe 100-150mL/kg

100mL/kg/day for 1st 10kg
50mL/kg/day for 11-20kg
20mL/kg/day for >20kg
10mL/kg/watery stool
5mL/kg/vomiting
• Anti emetic
• Absorbents bind toxins
• Probiotics
• Zinc – (10mg <6months), (20mg older children)
• ATB -. Bacterial diarrhea
250

26b. Dysfunction of pituitary gland, Diabetes
insipidus
Definition
Endocrine organ that along with hypothalamus plays a critical role in regulation
of other endocrine organs. It is composed of two morphological and functional
distinct components.

Anterior lobe (adenohypophysis) Posterior lobe (neurohypophysis)
Growth hormone (GH) Oxytocin
Prolactin (PL) Antidiuretic hormone (ADH)
/vasopressin
Thyroid-stimulating hormone (TSH)
Follicle-stimulating hormone (FSH)
Luteinizing hormone (LH)
Adrenocorticotropic hormone (ACTH)

Diseases
• Hyperpituitarism (↑production)
o Ant. Pituitary adenoma
o Hyperplasia
o Malignancy
o Secretion by non-pituitary tumor
o Hypothalamic disease
• Hypopituitarism (↓production)
o Ischemia
o Surgery
o Radiation
o Inflammation
• Local mass effect (compression of optic nerve, ↑ICP)
• Posterior pituitary lesion (manifest via ↑/↓ of vasopressin)
Physiology
Prolactin Production of breast milk, inhibition of GnRh (gonadotropin relasing hormone)
GH Stimulates growth of bone and muscles
ACTH Stimulates synthesis and stimulation of adrenal cortical hormones
TSH Stimulates synthesis and secretion of T3 and T4
FSH Female: growth of ovarian follicle
Male: sperm production
LH Female: ovulation, estrogen and progesterone production
Male: testosterone production
ADH Water reabsorption in kidney
Oxytocin Contraction of pregnant uterus, secretion and excretion of milk

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Hyperpituitarism (HP)

General: Mostly rare in children

Etiopathogenesis:
• The products of anterior pituitary hormones exhibit feedback inhibition
on pituitary and hypothalamic pathway.
• Hyperpituitarism can be primary or secondary due to target hormone
deficiency, decreased feedback inhibition.

1. Pituitary tumor – adenoma
• ↑ hormone production
• Local effect of tumor – compression of optic chiasm, cranial nerves
(III,IV,VI), palsies – headache
• Inadequate production of the remaining hormones
Prolactinoma Hyperprolactinemia: galactorrhea, ↓gonadism

ACTHoma Cushings disease: ↑ACTH
GHoma Gigantism: ↑GH, IGF-1 (insulin-like growth factor 1)
Gonadotropin adenoma Never in childhood
TSHoma Hyperthyroidism
Pituitary carcinoma Rare, mostly funtional: secrete prolaction and ACTH

Diagnosis
• Lab: ↑hormonal levels (GH, ACTH)
• MRI of pituitary: can show any significant pituitary mass
• Visual field examination: perimetry, upper temporal quadrantopia and
bitemporal hemianopia

Treatment
• Remove tumor:
o Surgery: transsphenoidal excision
o Radiotherapy: when tumor is incompletel resected
o Medical therapy: shrink tumor by: somatostatin analogue and
dopamine agonsit
• Reduction of excessive hormone secretion
o Somatostatin analogues (for GHomas)
o Dopamine agonists (bromocriptine, for prolactinomas and
GHomas)
• Replacement of deficient hormones
o Hydrocortisone, levothyroxine, testosterone,
estrogen/progesterone, recombinant human GH
• Carcinomas may require chemotherapy

252

Hypopituitarism

General: Occur when 75% of parenchyma is lost. Can be selective/multiple
hormone deficiency. While selective deficiency could be caused by genetic or
congenital, multiple deficiencies is usually a result of tumor or destructive lesion
of pituitary. Panhypopituitarism: is when you have defect of all anterior pituitary
hormones, due to surgery, radiotherapy of pituitary gland.

Etiology

Congenital Neoplastic Vascular
Infection Traumatic Others

• Congenital genetic syndromes
o Kallmann’s syndrome – isolated gonadotropin deficiency (↓GnRH)
due to mutation in KAL1 gene ↓LH/FSH
o Septo-optic dysplasia – mutation in HESX 1 gene causes
forebrain abnormalities, optic nerve hypoplasia & hypopituitarism
(usually GH deficiency)
o POU1F1 – complete deficiency of GH and prolactin, variable TSH
deficiency (growth failure)
• Neoplastic
o Pituitary adenomas
o Cranyopharyngioma
o Meningiomas
o Gliomas
• Vascular (panhypopituitarism)
o Pituitary apoplexy –tumors enlarge rapidly, lead to hemorrhage or
infarction of the glandàsevere headache, double vision/loss of
vision, followed by life-threatening hypopituitarism
o Sheehan’s syndrome – there is pituitary infarction following
postpartum hemorrhage (low BP)
o Aneurysms
• Infective
o Basal meningitis (eg TB)
o Encephalitis, syphilis
• Traumatic
o Skull fracture
o Surgery
o Shaken baby syndrome
• Others
o Pituitary damage due to radiation, chemo, fibrosis
o Empty sella syndrome – no pituitary tissue apparent in sella
turcica in radiographic imaging: result of infarction or regression
of a pituitary tumor

253

Clinical features
• Compression: headache, visual disturbances, cranial nerve palsy
• ↓TSH – hypothyroidism (cold, dry skin, cold intolerance, mental slowness,
weight gain, constipation, reduced appetite)
• ↓ACTH – hypoadrenalism (hypotension, hyponatremia, stress intolerance
↓cortisol)
• ↓GH – growth failure in children, short stature
• ↓FSH/LH – hypogonadotropic hypogonadism (↓libido, loss of sexual hair,
delayed puberty, amenorrhea, erectile dysfunction)
• ↓Prolactin – hypoprolactineia (mammary atrophy,↓puerperal lactation)
• ↓ADH – diabetes insipidus (polyuria, polydipsia, dehydration)
Diagnosis
• MRI of pituitary nad hypothalamus
• Insulin tolerance test for ACTH and GH deficiency
o Insufficient levels of cortisol, GH after insulin administration
• Growth assessment
• Genetic analysis
• Blood: hormome levels
Treatment
• Hormone replacement therapy
o Hydrocortisone, Levothyroxine, Testosterone, estrogen,
progesterone
o Recombinant human GH, dopamine agonists (for prolactin
inhibition), desmopressin for ADH deficiency

Diabetes insipidus (DI)

General: Disease of body-water regulation. Thirst and H2O regulation are
controlled by ADH (synthesized in hypothalamus, neurohypophysis).

Physiology
• ↑plasma osmolality (>280mOsm/kg) sensed by osmoreceptors in the
anterior hypothalamus, stimulates the secretion of ADH. The secretion is
supressed with plasma osmolality <280mOsm/kg
• ADH act on V2reseptor in kidney, reabsorption of H2O and ↓diuresis. This
allows migration to collecting duct.
Definition: Characterized by the passage of large volumes of diluted urine.
Polyuria (>3L/day) and excessive thirst (polydipsia)

Types:
• Central (neurogenic) DI: ↓ secreation of ADH
• Nephrogenic DI: resistence/insensitivity of kidney to ADH action

254

Central (neurogenic) DI
Characterized by decreased secretion of ADH (ADH deficiency)
Etiology
• Hypothalamic-pituitary surgery
• Tumors: craniopharyngeoma, hypothalamic tumors
(glioma, meningioma), metastases
• Infections: TB, meningitis
• Hypophysistis
• Trauma or radiotherapy of head
• Familial: DIDMOAD
o AR disorder with DI
o Wolfram syndrome: optic atrophy, deafness
• Congenital- AD central DI; mutation in vasopressin gene
Nephrogenic DI
Characterized by resistance/insensitivity of the kidneys to ADH action

Etiology
• Familial form
o (ADH receptor gene defect
o (X-linked) or aquaporin-2 gene defect (AR)
• Renal disease (eg CKD, PCKD)
• Drugs (Lithium, rifampin, cisplatin)
• Hypokalemia, hypercalcemia
Clinical features
• Polyuria (>3L/day)
• Polidipsia
• Nocturia
• Primary and secondary enuresis
• Dehydration (due to polyuria 10-15L)
• Hypernatremia
• FTT, irritability, intermittent fever
Diagnosis
• ↑plasma osmolality (>300), ↓urine osmolality(<300)
• Electrolyte: Hypernatremia
• Fluid deprevation test
Treatment
• CDI: desmopressin (intranasal pray, p.o, i.m)
• NDI: correct underlying disease
o Thazide for polyuria: ↓plasma volume leads to H2O + Na+retention
in proximal convulted tubules
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Syndrome of inappropriate ADH secretion (SIADH) –
Schwarz-Barter Syndrome

General: Excessive ADH secretion, leading to water retention and hyponatremia
(euvolemic hyponatremia – Na+-dilution) this leads to ↓plasma osmolality but
↑urine osmolality

Etiology
• CNS (infection, trauma, hemorrhage, tumor, thrombosis)
• Lung disease (infection, asthma, positive pressure ventilation)
• Malignant tumors (producing ADH)
• Drug induced (opiates, antiepileptics, TCAs, SSRIs, chemotherapeutics)
Clinical features:
• Symptoms due to hyponatremia: confusion, nausea, coma
Criteria
• Hyponatremia <135mmol/l
• Hypotonic plasma (<270mOsm/kg)
• Excessive renal Na+ loss (>20mmol/l)
• No hypovolemia/fluid overload
• Normal renal, thyroid, adrenal function
• ↑ plasma ADH
Treatment
• Restriction of fluid (500-1000ml/day)
• Hypertonic saline
• Demeclocycline (inhibits action of ADH in kidneys)
• V2 receptor antagonists (vaptans)
256

26c.Non-infectious cutaneous disorders in children
(Atopic dermatitis, Urticaria, Seborrheic dermatitis,
Hemangiomas)
1. Atopic dermatitis
Gen: chronic pruritic cutaneous disorder with a strong genetic background
• Most cases present in period 3-6months
Etiology
• Positive family history and presence of atopic triad (dermatitis, asthma,
rhinitis)
Clinical features
Infant Toddler/older children
Itchy, scaly lesions Cracked, scales lesions
Lesions on face, trunk Lichenification on elbows, knee, retroauricular folds
Lesions are susceptible to superinfection (staph)
Diagnosis
• History and Physical exam
• Lab: ↑IgE, eosinophilia
Treatment
• Disease usually remits spontaneously between 2-5 years
• Antihistamines for itching
• Topical corticosteroids and tar
• Topical ATB’s for superinfection
2. Urticaria
Gen: skin rash with red, raised, itchy bumps
• Typically last a few days and do not leave long lasting skin changes
Etiology
• Environmental factors • Food
• Medications • Physical agents
Clinical features
Welts (raised areas surrounded by a red base)
Angioedema
Diagnosis
• Allergy testing
Treatment
• Antihistamines
• Corticosteroids
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3. Seborrheic dermatitis
Gen: dermatitis primarily affecting face, scalp and anterior chest
Etiology
• Idiopathic
• Immunosuppression
• Lack of nutrients (zinc)
Clinical features
Infant Adolescents
Cradle cap Cradle cap
Thick, waxy, yellow-white scales on scalp Thick, waxy, yellow-white scales on scalp
Dandruff (white, dry, scaling of scalp)
Diagnosis
Treatment
• Shampooing with zinc pyrithione
• Low dose topical ATB’s

4. Haemangiomas
Gen: benign vascular neoplasm thas has a characteristic clinical course
• Early proliferation followed by spontaneous involution
• Most common tumors of infancy
• Common cutaneoys sites:
o Head and neck 60%
o Trunk 25%
o Extremities 15%
Clinical features
Rapid growth from birth to 1month
Most growth from 4-6 months
Slows down and involutes usually by 7 years
Diagnosis
• Biopsy
Treatment
• Corticosteroids
• Surgery
o Excision
o Laser surgery


27a. Inflammatory bowel disease in children
Gen: Group of inflammatory conditions that are autoimmune and affect all or
part of digestive tract.
Common features:
• Produce inflammation of bowel
• Lack of proven causative agents
• Pattern of familial occurence
• Systemic manifestations
• Onset – pre-adolescence/young childhood
Classification
• Crohns disease
• Ulcerative colitis
• Unclassified ischemic bowel disease
Etiopathogenesis
• Genetic susceptibility
o Positive family history
o NOD2 gene mutation
o HLA gene polymorphism
• Environmental factors
o Good hygiene – development of IBD
o Breastfeeding – protection against IBD
o Smoking (+ulcerative collitis, -Crohns disease)
• Intestinal microflora
o Crohn disease - ↑anaerobic bacteria
o Ulcerative collitis – generally ↑bacteria
o IBD patients – have adherent and invasive bacteria in intestinal
wall (E-coli)
• Intestinal immune system
o Activation of Th-cells and Mpks, which secrete cytokines (TNF-α,
IL-1, IL-6), leading to WBC entering tissue and release chemokines
that damage the intestinal tissue
1. Crohn’s disease
Gen: May affect any part of GIT – terminal ileum + ascending colon
• One small area or multiple areas with normal bowel between
Pathology
• Cobblestone appearance of bowel
• Aphtous ulceration
• Inflammation – all layers of bowel (transmural) – deep ulcers and fissures
Clinical features – periodical symptoms

Diarrhea Right lower quadrant pain Malabsorption
Weight loss Steatorrhea Poor growth – delayed puberty
N+V, low grade fever Malaise, lethargy Hypoalbuminemia
259

Chronic disease:
• Bloody diarrhea
• Iron deficiency anemia
• Marasmus
• Urgency
Extraintestinal manifestations
Joints Migratory polyarthritis, sacroilitis
Eyes Conjunctivitis, uveitis, episcleritis
Skin Erythema nodosum, pyoderma gangrenosum
Liver/biliary tree Steatosis, cirrhosis, gallstones
Kidney Nephrolithiasis, hydronephrosis
Cardiac Pericarditis, cardiomyopathy
Malnutrition Malabsorption, intestinal loss
Hematologic Anema, venous thrombosis, vitamin B12 deficiency
Pancreatitis Secondary to medication (sulfasalazine, 6-
mercaptupurine, azathioprine)
Endocrine and Growth failure, thyroiditis, osteoporosis
metabolic
Neurologic Peripheral neuropathy, meningitis

Diagnosis
o Physical examination – mouth ulcer, anal fissure/abscess
• Lab:
o Anemia (iron deficiency anemia)
o ↑ESR, CRP
o ↓Albuminemia
o Calprotectin
o ASCA
o Colonoscopy and biopsy
o Contraindicated in acute phase
o CT with contrast
Treatment
• Diet – calories, vitamin and proteins
o Mild disease – ATB + aminosalicylate
o Moderate – corticosteroid + azathioprine + metothrexate
o Severe – anti TNF-α antibody (adalimumab, infliximab)
• Surgery
o Resection of damaged bowel
o Intestinal obstruction
260

2. Ulcerative colitis
Gen: Affects only
• Rectum – proctitis
• Descending and sigmoid colong – left side colitis
• Whole colon - pancolitis
Pathology
• Reddish, easily bleeding mucosa with ulcers and inflammatory
pseudopolyp
• Sudden transition between affected and unaffected parts
Clinical features
Bloody, mucous diarrhea Lower abdominal pain Similar to CD
Constipation in proctitis ↓albuminemia Toxic megacolon
Tenesmus Urgency Fever
Anemia Leukocytosis
Diagnosis
o Physical examination – rectal exam - blood
• Lab:
o Anemia (iron deficiency anemia)
o ↑ESR, CRP
o Calprotectin
o Positive ANCA
o Sigmoido, colonoscopy and biopsy
o X-ray – toxic megacolon
Treatment
• Diet – avoid spicy food, caffeine, lactose
o 5-aminosalicylate
o Corticosteroid, azathioprine
• Surgery
o Colectomy

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27b. Diabetes mellitus type 1
Gen: Disease of carbohydrate metabolism characterized by ↑level of glucose
due to inadequate secretion or utilization of insulin
Classification
• DM I – pancreas failure to produce insulin
• DM II – life style diabetes
• Gestational DM – woman with/without previousy diagnosed DM present
with ↑levels of glucose
Diabetes Mellitus type I

Gen: most common form in children and 2nd most common chronic disease of
childhood
• Autoimmune disease characterized by T-cell mediated destruction,
leading to loss of β-cells - ↓insulin production
Epidemiology
• Incidence of DM I is ↑ (nordic countries)
• Peak – 5-7 years, prepuberty, winter season
Etiology
• Genetic – HLA association, insulin gene, gene encoding for signal proteins
of T-cells (CTLA4, PTPN22)
• Environmental factors (triggers)
o Viral (coxackie, CMV, rubella, enterovirus)
o Chemicals (cytotoxic agents, alloxan
o Seasonal (autumn, winter)
o Dietary factors (cow milk, nitrates)
• Accelerators
o Stress, infection, cold weather, rapid growth

• ↓Risk of DM I
o Breast feeding
o Diet in the 1st year of life
o Adequate vitamin D intake

• Process occurs in genetically susceptible persons when triggered by
environment
• Autoimmune destruction of β-cells lead to ↓insulin production
• Autoantibodies that may play an important role in initiation of
autoimmune disease (insuling auto antibody)
• Glutamic acid – decarboxylase (GAD)
• Insulinoma associated protein 2 (IA-2)
• Autoantigen ZNT8 (zinc transporter 8 of islet of β-cells)
• Associations with other autoimmune dx (thyroid autoimmunity, celiac dx)

262

Clinical features – when >80% of β-cells are destroyed
Polyuria (osmotic diuresis) Polydipsia (due to urinary loss)
Weight loss Fatigue
Physical signs of dehydration Diabetic ketoacidosis
Kussmaul breathing
Diabetic ketoacidosis
Gen: leading cause of morbidity and mortality in children with DM I due to the
development of cerebral edema
• Hyperglycemia >11mmol/L
• Metabolic acidosis – venous pH <7,3
o Plasma bicarbonate <15mmol/L
Degree
• Mild – pH 7,2-7,3
• Moderate – pH 7,1-7,2
• Severe – pH <7,1
Management
• Proper and prompt due to risk of cerebral edema. Initial goals:
o Restore electrolyte and fluid balance
o Stabilize metabolic state with insulin
o Educate patients and parents about selfcare training
Diagnosis
• Blood glucose >11mmol/L
• Autoantibody positivity
• ↓insulin
• ↑Hba1c (long term glucose test)
• Screening for other autoimmune diseases
Treatment
• Goal:
o General well being
o Normal growth and development
o Normal puberty
o Prevetion of complications
• Insulin – Short acting/long acting – dose 1IU/kg/day – s.c injections
• Diet – meal planning, 60-70% of total/pump energy from carbohydrate
(starch)
• Exercise
Complications
• Acute – Diabetic ketoacidosis, hypoglycemia
• Chronic – retinopathy, neuropathy, nephropathy, cardiopathy

263

27c. Child abuse and neglect
Gen: Can include
• Physical abuse
• Sexual abuse
• Emotional/psychological abuse
• Neglect
1. Neglect
• Dirty children with poor hygiene and ↑infections, infants with poor
growth who gain weight in rapidly controlled environment (hospitals)
• Occurs when a childs basic needs for food, clothing, health, housing and
education are not met
2. Physical abuse
• Mothers – cause injury
• Fathers/stepfathers – serious head/abdominal injury
• Common injury
o Bruises – slap, marks, trunk, neck
o Fractures – ribs, scapula, vertebra – multiple, bone fracture
o Abdominal injury – infants and toddlers (liver, pancreas, spleen)
o Head trauma – shaking, blunt objects/trauma - leading cause of
death
o Abuse because of childs continous crying

3. Sexual abuse
Gen: Involvement of children in sexual activities that they cannot understand, for
which the are not developmentally prepared and cannot give consent
• Chronic event
• Abuser – male adult/adolescent, family member, teacher, neighbor
• Most sexual abuse – non-violent
• Precipitated by treats, bribery
• Approximately 80% of victims are girls
Sexual abuse come to attention when:

Child reports it – usually after repeated abuse
Child develops behavioral problems (aggressive, antisocial, sexualized)
The child has unexplained vaginal, penile, anal injury or STD
Diagnosis
• History from child
• Physical exam

264

4. Psychological abuse
Gen: Repeated pattern of caregivers behavior that makes the child believe they
are worthless, unloved, unwanted, endangered. Leads to:
• Behavioran and developmental problems in preschool children
• Learning problems in older children
• Criminal and antisocial behavior in adolescence
Risk factors for child abuse and neglect

Parental substance abuse
Maternal depression or mental illness
Domestic violence
Poor education and intellectual disability of parents
Poverty
Young parental age
Single parenthood
Parents were abused in childhood

Management
• Police/social service – investigation
• Munchhausen by proxy

265

28a. Malabsorption and Celiac disease
Definition
Malabsorption is characterized by defective absorption of fats, fat-water-soluble
vitamins, proteins, carbohydrates, electrolytes, minerals and water due to
diminished intestinal absorption of one or more dietary nutrients.
Clinical features
Chronic diarrhea Steathorrhea Weight loss
Anorexia Muscle wasting Growth failure
FTT Abdominal distention

Etiology
Celiac disease Short bowel syndrome
Whipple disease Congenital immunodeficiency
Chrons disease Tropical sprue
Cystic fibrosis Dermatitis herpetiformis
Bacterial overgrowth Abetalipoproteinemia
Celiac Disease (Celiac sprue)

General: It is a gluten-sensitive enteropathy. It is an immune-mediated disease
triggered by ingestion of gluten-containing foods (cereals, bread, etc.) Disease
improves when gluten is withdrawn.

Pathogenesis
• When gluten is broken down, it forms gliadin
• Gliadin interacts with gliadin-specific T-cells (Th cells and Tcytotoxic)
o T cells cause direct tissue injury or release cytokines (IFN-γ) which
also causes tissue inflammation & injury
• Furthermore, there are serum Abs (IgA antigliadin, IgA anti-endomysial
Abs, anti- transglutaminase Abs against tissue trans-glutaminase)
• There is also a genetic background with HLA-DQ2 allele found in almost
all patients
Clinical features
• Onset typically occurs in infants (intro of cereals) can occur at any age
• Generalized symptoms: FTT, chronic diarrhea, vomiting, abdominal
distension, anorexia and muscle wasting are present in most infants
• Hematologic: anemia due to iron malabsorption
• Skeletal: rickets, osteoporosis, enamel hypoplasia (Ca2+/Vit D
malabsorption)
• Neurologic: Peripheral neuropathy, epilepsy, tetany (thiamine; vit D, B12
and Ca2+ deficiency)
• Endocrinologic: Short stature, delayed puberty & secondary
hyperparathyroidism (malnutrition, Ca2+ Vit. D deficiency)
266

Diagnosis
• Endoscopy with small bowel biopsy - villous atrophy, crypt hyperplasia,
inflammation
• Serology: anti-EM, IgA antibodies, anti-TG2
• Genetic Tests: HLA-DQ2 is present in 95% of cases
• Blood tests: macrocytic anemia due to folate deficiency but also iron
deficiency anemia can be seen (microcytic)
• If IgA deficiency is present, IgG Abs to tissue endomysial and
transaminase should be checked
Treatment
• Gluten-free diet
• Mineral and vitamin replacement (Fe2+, Ca2+, folate, Vit. B12)
Short Bowel Syndrome

General: Malabsorption that follows massive intestinal resection (small
intestine) or congenital malformation of small intestines The severity of the
malabsorption and type of deficiencies depend on the segment and length of
small intestine removed

Etiology
Intestinal resection due to:
Crohn´s disease Volvolus +/- malrotation Necrotizong enterocolitis
Meconium ileus Trauma Hirschprung disease

Rescection of the jejunum is better tolerated than ilial resection. Ileum is the site
of absorption of bile salts and vit. B12

Clinical features
• Bile salt induced diarrhea: bile enters the colon & causes malabsorption
of water and electrolytes (Na2+)
• Steatorrhea and gallstone formation: due to bile salt loss
• Oxalate stones: bile salts in colon cause increased oxalate absorption with
oxaluria, oxalate stones
• B12 deficiency: Macrocytic anemia, glassitis, angular
stomatitis, neurological manifestations
• In jejunal resection the ileum compensates for loss of jejunal function
Treatment
• Oral rehydration solutions: to treat fluid and electrolyte disturbances
• Vit. B12 replacement
• Low fat diet to prevent steatorrhea
• Cholestyramine binds to bile salts and reduces their free concentration in
colour (decreased diarrhea)
• ATBs (metronidazole) to prevent / reduce bacterial overgrowth
• Anti-diarrheal drugs
267

Whipples disease
General: It is a rare infectious bacterial disease caused by Tropheryma Whpplei
(actinomycetes). Common in farmers, and those exposed to soil and animals.

Clinical features
Diarrhea Abdominal pain Weight loss
Arthritis and arthralgia Neurological problems Fever
Steatotthea Hyperpigmentation Uveitis

Diagnosis Treatment
• Physical examination • ATB
• Small intestine biopsy • Co-trimaxazole
• PCR (trimethaprime/sulfamethax
azole) for a year

Tropical sprue
General: Malabsorption disease commonly found in the tropical regions

Etiology: Unknown, might be infectious

Clinical features
Acute diarrhea Chronic diarrhea Indigestion
Fever Steatorrhea Cramps
Malaise Anorexia Weight loss

Complications
Vit A def Hyperkeratosis/skin scales
Vit B12/follate def Anemia
Vit D/Ca def
2+ Spasms, bone pain, numbness, tingelig sensation
Vit K def Bruises

Diagnosis
• Endocopy
• Vit deficiency
• Hx and PE
Treatment (3-5 months)
• Tetracycline
• Co-trimoxazole
• Vit supplement

268

Dermatitis Herpetiformis

General: Characterized by itchy, symmetrical eruption of vesicles with
deposition of IgA at demoepidermal junction. Associated with an asymptomatic
gluten-senesitve enteropathy

Clinical features:
• Rash at buttocks, back of neck, scalp, elbows, knee, back, groin of face
• The rashes are extremely itchy
Diagnosis
• Blood test: IgA Ab
• Skin biopsy
Treatment
• Dapsone
• Gluten-free diet
Bacterial overgrowth
General: Can result from conditions that after gastric pH or intestinal motility

Etiology:
• Partial bowel obstruction
• Diverticula
• Diabetes mellitus
• Scleroderma
Pathogenesis
• Bacterial growth leads to deconjugation of bile salts and consumption of
Vit. B12 which results in steatorrhea and vit. B12 deficiency
• Overproduction of lactate by bacteria can cause stupor and shock from
lactic acidosis
Diagnosis
• Cultivation of small bowel aspirate
• Lactulose hydrogen breath test – lactulose is digested by intestinal
bacteria and hydrogen is exhaled

Treatment
• Correction of underlying disease
• ATB: Metronidazole

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Congenital immunedeficieny
• Such as selective IgA deficiency, agammaglobulinemia, SCID, Wiskott-
Aldrich syndrome
• Due to chronic rotavirus infection, giardiasis and bacterial overgrowth
A beta lipoproteinemia
General: AR disorder, severe fat malabsorption from birth

Clinical features
• FTT, pale, foul-smelling stools, peripheral neuropathy (Vit. E def.)
Diagnosis
• Presence of acanthocytes in peripheral blood smear and extremely low
cholesterol
Treatment
• Fat soulable vitamine
• Linoleic acid
• Diet

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28b. Resuscitation of child, Hypovolemic and
anaphylactic shock
Definition
In children unconsciousness is uncommonly of cardiac origin but usually due to
airway obstruction.
Etiology
Neurological cause Meningitis Head injury
Encephalitis Seizures
Metabolic/ toxic causes Hypoglycemia Hyponatremia
Bacterial toxins Drugs
↓O2 supply to brain • Acute asphyxia – drowning
• Respiratory obstruction – foreign body,
asthma, epiglottitis, croup
• Hypovolemia – dehydration, hemorrhage
• Sepsis
• Anaphylaxis
Basic cardiac life support (BCLS)

Before the ABC approach, assess the level of consciousness of the child (do you
hear me?, are you ok?) And then shout for help

A-Airway
• Open the airways: head tilt and chin lift, if there are obvious foreign
bodies in the mouth, remove them with the finger
B-Breathing
• Look for chest movement, listen for breathing sounds and feel
for breathing with the cheek
• Give 5 rescue breaths; if there is still no response and no breathing start
CPR immediately (30:2), 2 professional rescuers 15:2
• If there is no response after 1 minute of CPR call an ambulance
C-Circulation
• Start CPR if there Is no breathing
• Assess the carotid, femoral or brachial pulse by palpation
• Check for any signs of circulation (movements, coughing, breathing)
• If there is no pulse or <60/min start chest compressions to create
artificial circulation

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CPR Procedure (30:2 or 2 professionals 15:2)
• Infants (upto 1year): Chest compressions 2 thumbs are used
• Children >1 year, one or 2 hands are used
• Location: lower part of the sternum 1 thumb over the xyphoid process
• Rate: 100/min
• Depth: 1/3 of the chest (about 4cm in infants and 5 cm in children) and
there should be appropriate chest decompression
• Rescue breaths: Place the mouth above the mouth and the nose of the
child, take a normal breath and exhale until chest rises, allow the chest to
fall and repeat.
• CPR should not be interrupted for more than 5-10 seconds for any reason
AED (automatic external defibrillator)
• For children > 8 years old an adult AED can be used
• For children 1-8 years old, use pediatric pads if available ; if not adult AED
is used
• For infants < 1 year, use AED only if instructions indicate that it is safe
Advanced cardiac lifesupport (ACLS)

Airway/Breathing
• Intubation (endotracheal or supraglottic tube) of the patient to establish
an airway; if it fails, use face mask
• Formula of endotracheal tube size (age in years)
o Length of tube (mm): age/2+12
o Internal diameter (mm): age/4+4
• Maintain ventilation via ambubag or mechanical ventilation
Circulation
• Establish IV access
o Most critically ill children are hypovolemic and require fluids
• Intraosseous route: if it’s not possible establish an IV access
o Distal/proximal tibia, anterior iliac crest
• Assess the rhythm via ECG via defibrillator
o Vfib/Vtach
o Asystole/PEA
Ventricular fibrillation and ventricular tachycardia
• The principal treatment is defibrillation: two paddles positioned on the
chest( one below the right clavicle and the other at apex of the heart – left
– mid – axillary line)
• 1. Shock with 2j/kgàCPR for 2 mins and the reevaluation
• 2. Shock with 4j/kg àCPR for 2 mins and reevaluation
• 3. Shock with 4j/kg (maximally 10j/kg)

• After 3rd shock administration of adrenalin 0.01mg/kg (max.1mg)
• Amiodarone 5mg/kg every 3-5 mins is the next recommended drug
Asystole/Pulseless electrical activity (PEA)
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• Non-shockable
• Asystole is characterized by an isoelectric ECG (ventricular fibrillation
should be excluded); In PEA are organized QRS complexes found on ECG
but no palpable pulses
• Adrenalin 0.01mg/kg every 3-5 mins is recommendedàCPR should
always be continued and the rhythm should be reevaluated every 2 mins
• Atropine 0.02 mg/kg is the next drug recommended In PEA, if the above
fails, but there is still P wave activity on ECG consider pacing the heart
(cardiostimulation with an external temporary pacemaker)
Always consider specific therapy for PEA depending on underlying cause
5H 5T
Hypovolemia Tension pneumothorax
Hypothermia Tamponade – cardiac
Hypoxia Toxins
Hypo/hyperkalemia Thrombosis pulmonary
H+ ions Thrombosis coronary
Shock
General: Acute circulatory failure characterized by inadequate perfusion of vital
organs and tissues. If it results in generalized cellular hypoxia with a shift of
normal aerobic cellular metabolism to less efficient anaerobic metabolism.

Types:
• Hypovolemic shock
• Cardiogenic shock
• Obstructive shock
• Distributive shock
1. Hypovolemic shock
General: The most common cause of shock in children. There is a decreased
circulatory volume due to excessive loss (external or internal) or inadequate
intake of fluid - ↓preload

Etiology:
• Bloodloss: external or internal hemorrhage
• Plasma loss: butns, hepatic failure, NS
• Water and electrolyte loss: diarrhea, vomiting, DI, DM

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Clinical features
• Initially: tachycardia, orthostatic hypotension and signs of dehydration
such a mucous membranes, decreased skin turgor, sunken eyes,
depressed fontanel (for water and electrolyte loss), prolonged capillary
refill time, decreased urinary output
• With time: cold, pale skin, sweating, MAC (due to anaerobic metabolism)
with hyperventilation, oliguria and anuria, weak peripheral pulses,
decreased BP, altered mental status (drowsiness, confusion, coma)
Diagnosis
• Hx and PE
• ABG
• Glucose, lactate
• Electrolytes
Treatment
• Volume replacement (increased preload & in that way CO)
o Fluid resuscitation – 20 ml/kg of 0.9% NaCl over 20 mins (can
be repeated 3-4 times, max. 60-80 m/kg in the first hour)
o Deficit replacement – 50% of calculated deficit over the first 4
hours; 50% over the next 4 hours (0,45% NaCl)
o Maintenance fluids - 0,45% NaCl or 5% glucose
o Replacement of ongoing losses
o Sometime colloids of blood components (RBCs, FFP) can be used
• Vasopressor agents
o Increase CO and BP
o Dopamine (3-15 ug/kg/min) alpha and beta agonist effect,
vasodilation, good perfusion of GIT and kidneys (prevents ATN)
o If it fails, adrenaline or noradrenaline are used
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2. Anaphylactic shock
General: It is the end result of a severe type I hypersensitivity reaction in
response to agents. It is accompanied by profund vasodilation and increased
capillary leak leading to decreased preload and impaired tissue perfusion.

Etiology
• Foods (shellfish, strawberries, egg, nuts)
• Insect bites or stings (bees)
• Drugs (penicillin, NSAIDs, procaine, cephalesporins)
• Vaccines
Clinical features
• Generalized: profound vasodilation such as warm extremities,
hypotension, tachycardia, hypovolemia (capillary leak)
• Skin: erythema, hives/urticaria
• Respiratory tract: Rhinorrhea, bronchospasm (dyspnea, wheezes, stridor)
• GIT: Vomiting, diarrhea, abdominal cramps
• CNS: altered mental status (drowsiness), confusion, coma

Diagnosis
• Hx and PE
• Alergen detection with skin prick test later
Treatment
• ABC approach (establish airway)
• Fluid resuscitation
• Adrenaline (0,05 – 3 g/kg/min IM) treatment of choice
• Antihistamines and steroids (dexamethasone)

275

28c.Antibiotic therapy in children
Gen: antibiotics are natural or synthetic chemical substances that suppress the
growth/destroy bacteria, fungi or parasites. They can be classified according to:
• Narrow spectrum • Bacteriostatic/bactericidal
• Extended spectrum • Mechanism of action
• Broad spectrum
According to mechanism of action ATB’s can be:
• Cell wall synthesis • Folate metabolism
inhibitors inhibitors
• Protein synthesis inhibitors • RNA synthesis inhibitors
• DNA synthesis inhibitors
1. Cell wall synthesis inhibitors

Beta lactams
Gen: May include penicillins, cephalosporins, carbapenems
• All have a beta-lactam ring
• Mechanism of action:
o Block bacterial cell wall synthesis by binding to and inactivating
penicillin-binding protein (bacterial enzymes)
A) Penicillins
1st • Normally facilitates the cross-linkage between peptidoglycan
Generation chains
• Include penicillin V, penicillin G
• Tx: streptococcus, meningococcus, lyme dx, syphilis, scarlet fever,
endocarditis
2nd • Anti-staphylococcal
Generation • Include flucloxacillin, nafcillin
• Tx: staphylococcus, erysipelas, impetigo, sepsis, osteomyelitis,
septic arthritis
3rd • Extended spectrum
Generation • Include amoxicillin, ampicillin (often combined with clavulanic
acid)
• Tx: 1st gen, gram- (E-coli, H. Influenza, salmonella, shigella, UTI,
sepsis, pneumonia, otitis media, sinusitis, meningitis)
4th • Anti-pseudomonal
Generation • Include piperacillin (often combined with clavulanic acid,
tazobactam)
• Tx: gram+, gram-, MIO’s, pseudomonas aeruoginosa
Side effects– hypersensitivity with urticaria, fever, rash, anaphylaxis, diarrhea,

hemolytic anemia

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B) Cephalosporins
1st • Cephalexin
Generation
2nd • Cefuroxime
Generation • Tx: RTI’s, UTI’s (cystitis)
3rd • Broad spectrum
Generation • Cefotaxime
• Tx: serious infections (septicemia, pneumonia, meningitis,
peritonitis, epiglottitis)
Side effects- similar to effects of penicillin
C) Carbapenems
• Broadest spectrum ATB’s
• Meropenem
• Tx: Serious nosocomial infections (multi-resistant, mixed
aerobe/anaerobe infections) - meningitis
D) Others
• Vancomycin, daptomycin
• Inhibits cell wall synthesis, directly binds to D-Ala (making a cap)
• Tx: Meningitis (MRSA), enterococcus, sepsis, infections from
medical devices, osteomyelitis, septic arthritis
Side effects- Phebitis at infusion site, fever, chills, shock due to histamine release
in rapid infusion

2. Protein synthesis inhibitors
Gen: May include macrolides, aminoglycosides, tetracyclines, lincosamines,
linezolid, chloramphenicol
• Block protein synthesis by binding to specific subunit on bacterial
ribosome
A) Macrolides
• Erythromycin, clarithromycin, azithromycin
• Inhibit protein chain elongation
• Used in patients with allergy to penicillins
• Tx: RTI, whooping cough, chlamydia
Side effects: Epigastric distress, transient deafness, cholestatic jaundice

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B) Aminoglycosides
• Gentamycin, streptomycin, tobramycin
• Block translation of mRNA
• Active against gram-, and some gram+ (not anaerobes)
• Tx: pneumonia, UTI, S.aureus, group B strep, Strep viridans,
pseudomonas, enterococcus
Side effects: ototoxicity, vestibular and auditory/cochlear dysfunction, renal

toxicity, nerumuscular blockage (paralysis)

C) Tetracyclines
• Tetracycline, doxycycline
• Block tRNA binding to ribosome
• Broad spectrum ATB’s, but limited use due to spread resistance
• Tx: gram+, gram-, vibrio cholera, chlamydia, mycoplasma
Side effects: photo-toxicity, nausea, vomiting, neutrophilia, thrombocytopenia

3. DNA synthesis inhibitors
Gen: DNA synthesis inhibitors used only for adolescents. Usage is limited.
Quinolones
• Ciprofloxacin
• Inhibit topoisomerase required for cell division
• Broad spectrum ATB’s
• Tx: Gram septicemia, RTI, UTI, gonorrhea, urethritis, chlamydia
trachomatis, STD
Side effects: usually well tolerated, joint/cartilage toxicity, nausea, vomiting,

phototoxicity

4. Folate metabolism inhibitors

Gen: Decrease folate metabolism.
Sulphonamide, trimethoprim
• Sulfamethaxazole, trimoxazole
• Block synthesis of DNA and RNA bases
• Used in combination
• Tx: Pneumocystis jiroveci, pneumonia, UTI, RTI
Side effects: Steven-Johnson syndrome (epidermal necrolysis), folate deficiency,

megaloblastic anemia, kernicterus
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4. RNA synthesis inhibitors
Gen: Block transcription of bacterial DNA (RNA)
Rifampin
• Rifampin, rifabutin
• Tx: M. Tuberculosis, gram+, gram-, leprosy
Side effects: toxic hepatitis, renal failure, pink body secretions (sweat, urine,
tears)

279

29a. Viral hepatitis and Chronic hepatitis
Definition
Inflammation of the liver caused by different viruses. In most pediatric patients
the acute phase is asymptomatic or presents as mild clinical disease. Morbidity is
related to the rare causes of fulminant liver failure and to the chronic disease
caused by hepatitis viruses B, C, D
Etiology
• Hepatitis A, B, C, D, E
• HSV, CMV, EBV
• VZV, HIV
Characteristics of viral hepatitis

Features HAV HBV HCV HDV HEV
Viral RNA DNA RNA RNA RNA
Transmission Feco-oral Parenteral. Parenteral. Parenteral. Feco-oral
Sexual, Sexual, rarely Sexual,
perinatal perinatal perinatal
Incubation ~ 1 mnt 2-6 mnt 1-2 mnt Causes 1-2 mnt
period disease only
in people with
acute HBV, co-
infection or
superinfection
Fulminant Rare Yes Rare Yes Yes
hepatic Co-infection
failure
Chronic No Yes Yea Yes No
disease superinfection
Increased No Yes Yes No No
risk for HCC
Types
Acute Infection
• Often asymptomatic or mild nonspecific illness without icterus
o HAV, HBV and HCV, especially in young children
• Symptomatic acute hepatitis can be seen with
o HAV, HEV and HBV +/- HDV
• Preicteric (prodromal)phase lasts approx. 1 week and is characterised by
anorexia, malaise, abdominal discomfort, nausea and vomiting
• Infants with perinatal HBV may have immune complexes causing
urticarial and arthritis
• Icteric phase is characterised by jaundice and tender hepatosplenomegaly
• Resolution of hyperbilirubinemia and normalization of transaminases
may take 6-8 weeks

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• Fulminant hepatitis/hepatic failure
o Seen with HBV +/- HDV & HEV
o Jaundice, fever, anorexia, vomiting, abdominal pain, fetal
hepaticus, hepatic encephalopathy and coagulopathy
Chronic Infection
• Most commonly asymptomatic (70%) until complications develop
o liver cirrhosis, HCC, ascites, hepatosplenomegaly, portal
hypertension, coagulopathy, caput medusa
• In the remaining cases it can present as
o chronic symptomatic fever and abdominal discomfort
• It is commonly seen with HBV +/- and HCV
Diagnosis

HAV Anti – HAV IgM and PCR positive for acute infection
Anti – HAV IgG for past infection
HBV Anti – HBc IgM , HBsAG and HBV – DNA for acute infection
Anti – HBc IgG and anti – HBs for past infection/immunity
Anti – HBc IgG, HBsAG for chronic infection
HCV Anti – HCV and HCV RNA for acute and chronic
HDV Anti – HDV IgM and HDV RNA plus HBsAG for acute infection
Anti – HDV IgG and HBsAG for chronic infection
HEV Anti – HEV IgM and HEV RNA for acute infection
Anti – HEV IgG for past infection

• Liver biochemistry: ↑ ALT/AST, ALP, GGT, bilirubin, INR and albumin,
ammonia, cholestterol, electrolytes, copper, ceruloplasmin
• Blood: CBC, platelet count, WBC’s – anemia, leukopenia,
thrombocytopenia
• ANA, anti – LKM Ab, ANCA, ↑ IgG for autoimmune hepatitis
• Imaging ( liver biopsy for definitive diagnosis)
o USG of liver biliary tree and pancreas
o ERCP or MRCP
Clinical features
The clinical features are the consequence of
• Portal hypertension(impaired hepatic blood flow) – ascites, varices &
variceal bleeding, caput medusa, splenomegaly with pooling of WBC’s and
platelets( increased risk for infections and bleeding )
• Impaired hepatocellular function – coagulopathy, decreased albumin
(peripheral edema), elevated ammonia ( hepatic encephalopathy),
malaise, palmar erythema and gynecomastia
• Chronic cholestasis: pruritus and further jaundice, malabsorption of fat
soluble vitamins

281

Treatment
• Ascites: Na+ and water restriction, furosemide
• Variceal bleeding: endoscopic ligation and infection (adrenaline)
• Malnutrition: vitamins A, D, E, K
• Encephalopathy: lactulose, ATB’s, liver dialysis
• Coagulopathy: Vit K, FFP
HAV HBV HCV HDV HEV
Supportive i.v Supportive in INF-alpha and Controlling HBV Supportive
fluids antipuretic acute infection ribavirin infection
agents INF-alpha,
prevention by Iamivudine,
vaccine adefovir for
chronic infection
prevention by
vaccine
Chronic hepatitis
General: It is characterised by the development of cirrhosis and its
complications and by progressive hepatic failure

Etiology
• Congenital disorders
o Biliary atresia
o Tyrosinemia
o Galactosemia ( untreated )
o Alpha 1 antitrypsin deficiency
• Older children
o Chronic hepatitis B and C
o Autoimmune hepatitis
o Wilson’s disease
o Primary sclerosing cholangitis
o CF
o Biliary obstruction
o NAFLD
o Anti-Epileptics

282

29b. Metabolic disorders of water, sodium and
potassium
Metabolic disorders of water

Total body water content (TBWC), at 24 weeks of gestation TBWC is 80% of total
body weight. Where 45% is extracellular and 35% is intracellular. While in a 1
year old the TBWC is 60%
Dehydration
General: It is a common reason for hospitalization, It is the main cause of
morbidity and mortality among children.

Risk factors
• Increased metabolic rate
• Increased Body surface area
• Increased body water contents
o 75% for newborns,
o 60% for infants and toddlers)
• Increased ECF/ICF ratio
Etiology
• Infectious
o Gastroenteritis: diarrhea and vomiting
• Non-infectious:
o GIT losses:
o Vomiting due to pyloric stenosis, IEM, food intolerance, metabolic
acidosis
o Diarrhea due to food intolerance
• Renal losses
o DKA, diuretics, DI, AKI (with polyuria)
• Increased insensible water loss
o Increased sweating, fever
• Inadequate fluid intake
Assessment level of dehydration
• Mild - < 5% weight loss
o Patient is alert and thirsty
o Initial signs (HR, RR, BP), Skin turgor are normal
o CRT <2 secs
o Mucous membranes are moist
o Acral parts of the body are warm, urine output is normal
283

• Moderate – 5-10% weight loss
o Patient is lethargic or imitable
o There is tachycardia or normal or increased RR
o Skin turgor is slightly decreased and fontanels are depressed
o CRT <2secs
o Mucous membranes are dry
o Acral parts are warm, there is oliguria
o Eyes are sunken
o BP is normal
• Severe - >10% weight loss
o Patient is drowsy or comatose
o There is tachycardia, hypotension and tachypnea
o There is reduced skin turgor (Markedly) and fontanels are sunken
o CRT >3secs
o Mucous membranes are very dry and the tongue is coated
o Acral part are cold, there is anuria
o Eyes are sunken and tearing is absent
Fluid replacement therapy
• Oral rehydration - For mild and moderate dehydration
o Replacement of deficit
§ Over 3-4 hours – small amounts (5-10 ml or ORS every 5-10
mins)
§ For mild dehydration, 50ml per kg.
§ For moderate dehydration 100ml per kg
o Maintenance fluids
§ 100ml/kg/day for 1st 10 kg of body weight
§ 50ml/kg/day for next 10kg (up to 20 kg)
§ 20ml/kg/day for every other kg (20kg)
o Replacement of ongoing losses
§ 10ml/kg for every watery stool
§ 5mll/kg for every vomiting episode
• IV rehydration – for severe dehydration/shock
o Fluid resuscitation
§ 20ml/kg of 0.9% NaCl –up to 3 times (within 1 hour)
o Replacement of deficit – 150ml/kg
§ 50% within 4 hours – 50% within next 4 hours (0.9% NaCl)
o Maintenance fluids and ongoing losses

284

Sodium and potassium

Classification
Disorders of Sodium (Na) Disorders of potassium (K)

• Hyponatremia • Hypokalemia
o With hypovolemia • Hyperkalemia
o With euvolemia
o With hypervolemia
• Hypernatremia
A. Disorders of Sodium
1. Hyponatremia
Definition:
• Na <135 mmol/l
a) Hyponatremia with hypovolemia

• Occurs due to salt loss in excess of water loss
Etiology:

Vomiting, diarrhea Hemorrhage Burns
Pancreatitis Osmotic diuretics Diuretics
Adenocortical insufficiency Renal diease

Pathogenesis
• With fluid loss, the patient becomes hypovolemic and volume receptors are stimulated
(overriding the osmoreceptors) leading to both thirst and non-osmotic release of ADH
• The body defends circulating volume in expense of osmolarity
• Clinical features are rarely related to hyponatremia, but are usually the result of
hypovolemia and extracellular volume depletion
Clinical manifestation

Thirst Muscle cramps Nausea and vomiting
Postural hypotension Loss of skin elasticity Tachycardia
Neurological signs Confusion and coma

Treatment:
• Treatment of the underlying disease
• ↑ salt intake (60-80 mmol/day oral of iv)
• Oral rehydration solution
• In severe case isotonic saline
285

b) Hyponatremia with euvolemia
General:
• It results from intake of water in excess of the kidney's ability to excrete it
• There is dilutional hyponatremia and hypoosmolarity (there is no change of overall
body Na)
Etiology:
• Syndrome of inappropriate ADH secretion (SIADH) which is due to tumors, pulmonary
lesions (TB), CNS disturbances (eg. cerebral hemorrhage, meningitis), drugs
(carbamazepine) and metabolic causes (drug withdrawal)
• Psychiatric illnesses (psychogenic polydypsia)
• Hypothyroidism
• Secondary adrenal insufficiency due to pituitary disease
• Iatrogenic water overload (infusion of 5% glucose)
• Are usually seen if hyponatremia develops rapidly and occur at serum Na concentration
<110mmol/L
• Hyponatremic encephalopathy due to movement of water into brain cells (cerebral
edema) in response to ↓ extracellular osmolarity (effort to equalize ICF and ECF
osmolality)
• Headache
• Confusion
• Restlessness with myoclonic jerks
• Generalized convolutions and coma
Diagnosis
• ↓ Na +
• ↓ serum osmolality
• ↑ urine osmolality
Treatment:
• Fluid restriction (max 800ml/day)
• Hypertonic saline (3% na) plus furosemide ( only in patients with severe neurologic
signs)
• Vaptans (eg. tolvaptan) à ADH receptor antagonists
• OBS: Rapid correction of hyponatremia with hypertonic solution can cause central
pontine myelinolysis
c) Hyponatremia with hypervolemia

General:
• Occurs due to water gain in excess of salt gain
• There is ↑ in body Na content but there is proportionally greater ↑ in body water content
• It is seen in edema forming disorders such as CHF, liver cirrhosis, and nephrotic
syndrome where ↓ circulatory volume (hypovolemia) cause ↑ stimulation of SNS, RAAS
and ADH à This leads to excessive water retention and slight Na retention
• Edemas due to volume overload
• Neurological signs

Diagnosis:
• ↓ Na +
• ECV excess
Treatment:
• Treatment of underlying disease
• Fluid and Na restriction
• Loop diuretics (furosemide)
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2. Hypernatremia
General:
• Serum Na >145 mmol/L
• It is not common and almost always indicates a water deficit
Etiology
• Diabetes insipidus - central or nephrogenic
• Deficient water intake in elderly, infants or coma patients à exaggerated by ↑ GIT losses
(vomiting, diarrhea)
• Osmotic diuresis (hyperglycemia, mannitol)
• Iatrogenic (administration of hypertonic saline)
• Drugs with high Na content (tetracyclines, lithium)
• Primary hyperaldosteronism (Conn's disease)

v Hypernatremia ↑ plasma osmolality and cause thirst (unless there is no thirst sensation
or access to water, hypernatremia will not occur e.g. DI patients)
• Non specific: Nausea, vomiting, fever and confusion
• Polydypsia, polyuria and thirst due to DI, drug history
Diagnosis
• ↑ serum Na and ↑ serum osmolality
• ↓ urine osmolality in DI
Treatment:
• Treat the underlying disease (desmopressin for central DI, withdrawal of drugs)
• Water replacement either p.o or i.v (in severe cases >170 mmol/l give 0.9% Na; in less
severe cases >150 mmol/l give 0.45% Na
• Avoid rapid correction of serum Na because it can lead to brain edema
B. Disorders of potassium
General:
• K concentration is regulated by 3 mechanisms:
K uptake into the cell Renal excretion of K Extrarenal losses

• ↑ by insulin, b- adrenergic • ↑ by aldosterone • Via GIT
stimulation, theophyline
• $ by a-adrenergic stimulation,
acidosis, cell death/damage
1. Hypokalemia
Definition:
• Serum K <3.5 mmol/L
Etiology:
• Loop diuretics (furosemide), thiazide diuretics!
• Hyperaldosteronism, Cushing's syndrome
• Starvation
• Inadequate K+ intake
• Redistribution of K into cells (B-agonists à bronchodilators, insulin or alkalosis)
• ↑ GIT losses (vomiting, diarrhea)
• Renal diseases (renal tubular damage, Bartter's syndrome, Liddle syndrome)

287

• Severe hypokalemia (<2.5 mmol/L)
o Muscle weakness
o Cardiac arrhythmias
o ↑ the risk of digoxin toxicity
• Can cause symptomatic hyponatremia
• ECG: inverted T-waves, prominent U wave, ST depression, prolonged PR interval

Treatment
• Treat the underlying disease
• K supplementation (usually p.o),
• IV in severe cases (20mmol/h, never as bolus)
2. Hyperkalemia
Definition
• Normal level – 3,3-5,0 mmol/l
• Serum K levels >5.0 mmol/L
• Severe hyperkalemia is defined as > 6 mmol/l. à defined as a medical emergency
• Pseudohyperkalemia à venepuncture, hemolysis, thrombocytosis, and erythrocytosis.
Etiology
• ↓ renal elimination of K
o Acute renal failure
o Drugs (k sparing diuretics, heparin, ace inhibitors)
o Addison's disease (hypoaldosteronism)
§ Aldosterone: water and sodium absorption and potassium excretion.
o Rhabdomyolysis
• Redistribution of K out of the cells (to ECF)
o Diabetic ketoacidosis
o Metabolic acidosis
o Tissue necrosis (severe burns, rhabdomyolysis)
o Vigorous exercise
• Excessive rapid intake of K (iv or po)
o Potassium chloride, transfusion of stored blood, salt substitutes
• Occur if K >7.0 mmol/L
• Cardiac arrhytmias à sinus bradycardia, sinus arrest, VT, Vfib, asystole
• Include ECG changes (peaked T waves, ↓P wave size and wide QRS complex)
• Sudden death
• Muscle weakness
• Kussmaul breathing if associated with metabolic acidosis
Diagnosis
• Serum k+
• ECG
Treatment:
• Calcium gluconate protects myocardium from K+à does not alter K concentration
• Diuretics
• Glucose + insulin infusion à redistribution of k+ into cells
• Na bicarbonate to correct acidosis ( if acidosis is present)à NaHCO3
• Ion exchange resins à bind potassium
• Hemodialysis

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29c.Cardiomyopathies
Gen: The heart muscle is abnormal, and it’s harder for the heart to pump and
deliver blood to the rest of the body. Types:
• Dilated cardiomyopathy
• Hypertrophic cardiomyopathy
• Restrictive cardiomyopathy
Etiology
• Unknown • Pregnancy complications
• Genetics • Alcohol/drug abuse
• Metabolic disease
1. Dilated cardiomyopathy
Gen: Most common. Pumping ability of the heart becomes less forceful – left
ventricle becomes enlarged/dilated and cant effectively pump blood out of the
heart
Etiology
Result of:
• Coronary heart disease
• Viral infection
• Chemotherapy
• Drug/alcohol use
Clinical features – similar to heart failure

Cough Poor feeding Irritability
Dyspnea Pallor Sweating
Poor weight gain Wheezing Palpitation
Orthopnea Syncope Neurodeficit
Edema
Diagnosis
• ECHO
• Doppler Ultrasound
• Chest x-ray – cardiomegaly, pulmonary edema
• Cardiac catheterization
• Biopsy in case of heart transplant
Treatment
• Diuretics – furosemide
• ACE inhibitors
• β-blockers
• Devide implantation
o Implantable cardioverter defibrillator
o LVAD
o Biventricular pacemaker
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2. Hypertrophic cardiomyopathy
Gen: ↑in left ventricle wall thickness – hard to pump blood
Etiology
• Idiopathic
• Genetic disease (AD)– mutation in heart sarcomere protein genes
Clinical features
Sudden cardiac death Dyspnea Syncope
Angina Split 2nd heart sound Jugular venous pulse
Holosystic murmur Palpitations Orthopnea
Congestive heart failure Dizziness S3 gallop sound
Systolic ejection crescendo-
decresendo murmur
Diagnosis
• ECHO
o Left ventricular hypertrophy
o Left atrium enlargement
o MP/MR
• Heart catheterization
• X-ray
• Cardiac MRI
• ECG – Left ventricle hypertrophy, axis deviation BBB
Treatment
• β-blocker
• Avoid: Digoxin, diuretics, inotropics, nitrates
• Surgery
o Left ventricular myomectomy
o Mitral valve replacement
o Pacemaker
o Heart transplant
3. Restrictive cardiomyopathy
Gen: <5% of cardiomyopathies. Heart muscle becomes rigid and less elastic, and
cant expand properly
Etiology
• Idiopathic • Storage disease
Clinical features
Diastolic heart failure Edema Hepatosplenomegaly
Ascites Arrhytmias Cough
Dyspnea Pulmonary edema Chest pain, syncope
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Diagnosis
• ECG
o Nonspecific ST and T changes, prominent P wave
o Right ventricular hypertrophy
• ECHO
Treatment
• Anticoagulation
• Antiarrhytmics
• Heart transplant
• 2 year survival rate – 50%

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30a. Malnutrition and failure to thrive
Malnutrition
Definition
Leading cause of childhood morbidity and mortality worldwide (<5 years of age).
Malnutrition is characterized by protein or energy malnutrition and is often
associated with vitamin, other nutrient deficiencies, micronutrient deficiencies
Protein-energy mutation
• Maramus: inadequate energy intake in all forms
• Emaciation: extreme weight loss, loss of subcutaneous fat with a weight-
for-height < 70%, depleted body fat stores, muscle mass
• Kwashiorkor: protein deficiency with adequate energy intake
o Hypoalbuminemic, edematous malnutrition with relative
preservation of subcutaneous fat but marked muscle atrophy
o Weight loss is 60-80% for ageàweight for height may be accurate
due to edema

Failure to thrive
Malnutrition in infants and toddlers may cause FTT. Child fails to meet the
expected standards of growth. FFT is diagnosed when weight falls or remains
below the 3rd percentile for age or when weights is <80% of the height/length
Etiology
Insufficient intake of macro/micronutrients – primary
• Inadequate diet: poverty, insufficient breast milk, alternative
diet, anorexia nervosa, CAN, Munchhausen by proxy
• Inability to feed: poor feeding technique, impaired suckingl, swallowing
(cleft palate, cerebral palsy), heart failure and CHDs
• Impaired food retention: vomiting (IEM,áICP, GIT obstruction, bulimia)
and GERD
Pathological losses of nutrients/impaired absorption - secondary
• Malabsorption or maldigestion: celiac disease, CF, short bowel sy, cow’s
milk intolerance, persistent diarrhea, IEM, IBD
Increased nutritional requirements – secondary
• Infections, eg HIV, TB, hepatitis, UTIs, parasitic infections of GIT
• Malignancies, eg leukemia, lymphomas
• Endocrine abnormalities, eg hyperthyroidism
• Acidosis, eg CKD, renal tubular acidosis

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Clinical features of malnutrition
• Depend on the severity and duration of malnutrition
• ↓subcutaneous fat, initially of belly, extremities, buttocks
• Atrophy of muscles and skin
• Atrophy of orbital fat – ghost-like facies
• Bone deformities (rachitic rosary, craniotabes due to Vit D deficiency)
• Hypothermia, bradycardia, hypoglycemia, anemia
• Distended abdomen
• Sometimes dehydration
Vitamine deficiency
Vit A def blindness, xerophtalmia, acne
Vit B12 def macrocytic anemia, glossitis, paresthesias and dementia
Vit B3 def. pellagra (4D: Diarrhea, Dermatitis, Dementia, Death)
Vit C def. scurvy

Kwashiorkor
• Generalized edema
• Hepatosplenomegaly
• Sparse and depigmented hair
• Skin lesions
Failure to thrive

Weight < 3rd percentile for age or weight-for length < 80%
• Wasting
o Acute malnutrition
o Normal height for age but low weight for height
• Stunting – chronic malnutrition
o Low height for age but normal weight for height
o Growth failure/short stature
Diagnosis
• Dietary assessment – number, volume and composition of food
• Anthropometry – weight, height (>2yrs) / length (<2yrs), head
circumference (<3 yrs), skin fold thickness, mid-arm circumference, BMI
• Bone age – x-ray of left hand and distal forearm
• Puberty staging – Tanner
• Bone density – DEXA
• Laboratory :
o CBC, differential – anemia, immunodeficiencies
o Serum creatinine and electrolytes – CKD, RTA
o Liver function tests – liver disease, IEM
o ESR ,CRP, ferritin – inflammation, infection
o ↓Serum albumin
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• Stool microscopy and culture – infections, parasites
• Urinalysis and dipstick – UTI, renal disease
• Serum concentrate of micronutrients
Complications
• ↑Susceptibility to infection: atrophy of lymph nodes, thymus,
↓complement
• Hypoglycemia: ↓gluconeogenesis,↓glycogenolysis
• Hypothermia
• Bradycardia with HF
• Growth stunting /delayed psychomotor dev. in chronic malnutrition
• Delayed Puberty
Treatment
• Nutritional rehabilitation
o Start with 20% more than recent intake or 50%-75% of the
normal energy requirements to avoid refeeding syndrome
o Caloric intake can be ↑10-20% per day
o ↑protein (anabolism), vitamins & electrolytes (Ca2+, Mg2+, K+, PO4)
o Enteral nutrition, if contraindicated parenteral nutrition

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30b. Congenital malformations of central nervous
system
Neuronal tube defect (NTD)
General: In the normal human embryo, the neuronal plate arises approximetly
18 days after fertilization. The neural tube is what develops to become the brain
and spinal cord. The neural crest cells form PND, meninges and adrenal medulla.
During the 4th week of development, the neuronal plate invaginates alon the
embryonic midline to forn the neural groove. The neural tube is forme as closure
of the neural groove proceeds from the middle of the groove and progresses
toward the ends in both directions with completion between day 24 for the
cranial end and day 26 for caudal enda. Disruption of the normal closure process
leds to neuronal tube defect.

Classification
• Anterior NTD
o Anencephaly
o Encephalocele
• Posterior NTD
o Spina bifida
Precioitating factors for CNS malformations
• Chromosomal, genetic and metabolic abnormalities
• Congenital infections (TORCH)
• Exposure to irradiation, drugs and maternal illness during pregnancy
(obesity, diabetes, fever)
Anencephaly
General: Severe CNS malformation where the fetus is born without a brain. It
occurs when the head end of NT fails to close

Clinical features
• Blind
• Deaf
• Unable to feel pain
• Unawareness of surroundings
Diagnosis
• USG
• AFP screening
Prognosis
• Death (No brain, you dead bro!)

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Encephalocele
General: NTD characterized by sac-like protrusions of the brain and the
membranes that cover it through openings in the skull. Encephalocele: groove
down the middle of the skull, or between the forhead and nose, or the back side
of the skull.

Clinical features
Craniofacial abnormalities Developmental delay
Neurological deficit Ataxia
Hydrocephalus Vision problems
Quadripregia Growth retardation
Microcephaly Seizures

Diagnosis
• Hx and PE
Prevention
• Follic acid: 400µg/day
Treatment
• Reperative surgery
• Shunts
Spina bifida
General: Birth defect where there is incomplete closing of the backbone and
membranes around the spinal cord.

Types: Etiology
• Spina bifida occulta • Genetics
• Meningocele • Enviromental factors
• Meningomyelocele • Folic acid deficiency
• DM/obesity/drugs

1. Spina bifida occulta
General: the mildest form, outer part of some of the vertebra is not completely
closed. The splits in the vertebra are so small that the spinal cord doesn’t
protrude

Clinical feature Diagnosis
• Mostly asymptomatic • X-ray
• Hair growing on the site • USG
• Dimple in the skin • AFT screening
• Birth mark

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2. Meningocele
General: Least common form: vertebra develop normally, but the meninges are
forced into the gaps between the vertebrae

Etiology
• Teratoma
• Tumors of sacrococcyx and presacral space
• Currarino syndrome
Clinical feature
• Asymptomatic • Paralysis
• Hydrocephalus • Pain
• Bowel/bladder dysfunction

3. Meningomyelocele
General: Infused portion of spinal colums allows the spinal cord to protrude
through an opening. The meningeal membranes that cover the spinal cord also
protrude through the opening forming a sac enclosing the spinal elements.

Clinical feature
Paralysis Loss of sensation Deformity of hip, knee, foot
Loss of muscle tone Learning disability Pressure sore
Latex allergy Arnold-Chiari II malf. Hydrocephalus

Diagnosis
• Fetal USG
• MSAFP - amniocentesis
Treatment
• Surgery
• Symptomatic- shunts
Microcephaly
General: Neurodevelopmental disease, head circumference <3rd percentile. No
treatment, only symptomatic treatment

Etiology
• Congenital
• Chronic disease (trisomy 21,18,13)
• Congenital infection . TORCH
• Acquired: Stroke, Zika virus
Clinical feature
• Seizures, spastic quadriplegia
• Impaired intellectuality, ↓head size

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30c.Metabolic disorders of liver, Liver insufficiency
Definition
The liver has a major role in synthesis, degradation and regulation of pathways
involving carbohydrates, proteins, lipids, trace elements and vitamin
metabolism. Many metabolic abnormalities or specific enzyme deficiencies
(involving these pathways) can affect the liver.

Metabolic disease
General: Metabolic disease mimic infections, intoxications and hematologic and
immunologic diseases and may present with:
• Recurrent vomiting, failure to thrive, short statue, edema / anasarca
• Jaundice, hepatomegaly (+ splenomegaly), FHF
• Hypoglycemia, hyperammonemia, bleeding (coagulopathy)
• Developmental delay, hypotonia, seizures, unusual odors
Etiology
• Disorders of carbohydrate metabolism
o Galactosemia (classic)
o Hereditary fructose intolerance (aldolase deficiency)
o Glycogen storage diseases (types I, III, IV, VI, VIII)
• Urea cycle defects
• Disorders of metal metabolism
o Wilsons disease
o Neonatal hemochromatosis
o Indian childhood cirrhosis
• Disorders of bilirubin metabolism
o Crigler-Najjar (type I/II) – Unconjugated hyperbilirubinemia
o Gilbert disease – Unconjugated hyperbilirubinemia
o Dubin-Johnson syndrome – Conjugated hyperbilirubinemia
• Miscellaneous
o α1 – antitrypsin deficiency
o Cystic fibrosis
o Polycystic kidney disease (AR/AD)
• Disorder of aminoacid metabolism
o Tyrosinemia
o Organic acidemia
• Disorder of lipid metabolism
o Gaucher disease
o Tay-sachs disease
o Niemann-pick disease
o Wolman disaese

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Diagnosis
• Hypoglycemia
• Hyperammonemia
• ↑ transamiases
• Acidosis
• Hypoprothrombinemia
Wilson´s disease
General: It is an AR inherited disease of copper metabolism in which copper
accumulates in brain, liver and cornea. There are mutations of ATP7B gene
which codes for exertion and copper incorporation into ceruloplasmin. Results in
accumulation of copper in liver (hepatocytes) initially and with time in brain,
kidneys and eyes

Clinical features:
• Hepatosplenomegaly
• Chronic hepatitis
• Acute hepatic failure ( hemolytic anemia)
• Cirrhosis with portal hypertension, varices and coagulopathy
• Ascites
• Neurologic: intentional tremor, choreiform movements, parkinsonism,
lack of motor coordination (ataxia
• Kayser-Fleischer ring is also seen in cornea
• Psychiatric features include depression, personality changes, anxiety
Diagnosis
• ↓ serum ceruloplasmin levels (<20 mg/dL)
• ↑urinary copper excretion (>100g/day)
• Kayser-Fleischer rings
• Liver biopsy: ↑hepatic copper content (>250 mg/g )
• Coombs negative hemolytic anemia
Treatment
• Dietary restriction of copper (liver, shellfish, chocolate)
• Copper-dietary agents (D-penicillamine)
• Zinc salts – inhibit GIT absorption of copper

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Neonatal hemochromatosis
General: Rare form of FHF that manifests in the first few days of life. It’s a
gestational alloimmune disease. Develops when pregnant mother is exposed to
fetal hepatocyte cell surface Ag. Maternal IgGs cross the placenta and induce
hepatic injury (congenital alloimmune hepatitis)

Clinical featues
• Prematurity, IUGR, and renal dysgenesis
• Hepatomegaly, hypoglycemia, hypoalbuminemia, hyperferritinemia
and hyperbilirubinemia
• Coagulopathy, refractory to Vit. K
Diagnosis
• Sever liver injury and extra hepatic siderosis (buccal mucosa)
• MRI can detect iron storage in other organs, e.g pancreas
Treatment
• Iron-chelating agents (deferoxamine)
• Plasma exchange
• IVIGs
Prognosis
• Poor a rapidly fatal progressive illness
α 1 – antitrypsin deficiency
General: α1 – antitrypsin (100-200mg/dl) is a serine protease inhibitor
synthesized by the liver and it protects the alveoli from destruction by
neutrophil enzymes (elastases, proteases). A small percentage (20%) of infants
homozygous for α1- antitrypsin deficiency present with neonatal cholestasis.
30% of them with progress to chronic liver disease resulting on cirrhosis and
liver failure.
Pathogenesis
• Not fully understood, but accumulation of abnormally folded antitrypsin
seems to cause liver damage
Clinical features:
• Neonates: jaundice, acidic stools and hepatomegaly
• Older children: hepatosplenomegaly, symptoms of chronic liver disease
or cirrhosis
• Adults: COPD, emphysema – dyspnea, wheezing, rales
Diagnosis
• Genetic testing
Treatment: α1-antitrypsin inf, liver transplant, symptomatic tx

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31a. Childs growth and development, Puberty
Growth
• Assessment of growth includes measurement of length/height, weight,
head circumference at every visit – plotted on growth chart
o BMI measurement
o Compared with statistical norms
• Special measurements more useful than single measurements to detect
deviations
• Normal growth patterns have spurts and plateus
• Many biophysiologic and psychosocial problems can affect growth
o Large shifts – attention!
o Large discrepancies in height, weight and head circumference
o Inadequate caloric intake – usually weight falls first, then head
circumference
Rules of thump for growth

A) Weight
• Weight loss in first few days: 5-10% of birth weight
• Return to birth weight: 7-10 days
• Double birth weight: 4-5months
• Triple birth weight: 1 year
• Daily weight gain:
o 20-30g for the first 3-4 months
o 15-20g for the rest of the 1st year
B) Height
• Average length: 20in at birth, 30in at 1year
• At age 4 years, the average child is double birth length or 40in
C) Head circumference
• Average HC: 35cm at birth
• HC↑: 1cm/month for the 1st year (2cm/month for first 3 months, then slower)
Development
• Determined by genetic factors (determines potential) and environment
(influences extent)
• Environmental influence can be grouped into:
o Prenatal (metabolic infections)
o Perinatal (hypoxia, asphyxia, prematurity
o Postnatal (hyperbilirubinemia, infection)
o Psychosocial factors

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4 areas of development
• Gross motor function
• Fine motor function, vision
• Speech, language, hearing
• Social, emotional, behavioral
o Psychomotor development progresses in 2 patterns:
§ Craniocaudal § Proximodistal
Assessment of developmental progress
• Median ages for skill achievement tells us about when half of a standard
population achieve that level – wide timescale within normal range
o Normal development – within range
o Progress, but at normal rate
o Plateu: no progress in development
o Regress: a previously learned skill is lost
Limit ages: <2SD – the time by which a particular developmental milestone
should have been reached
• Preterm infants are calculated from expected date of delivery, up to 2
years
Developmental milestones in the 1st 2 years of life

• Gross motor – starting from 2months
• Fine motor – starting from 3,5months
• Communication and language – starting from 1,5months
• Cognititve – starting from 2months
Puberty
Gen: well defined sequence of changes in the development from child to adult
• Between early childhood and approximately 8-9years of age, the H-P-
gonadal axis is dormant
o Undetectable serum concentrations of LH and sex hormones
• 1-3years before clinical onset: ↓serum levels of LH (during sleep) –
pulsatile fashion caused by discharge of hypothalamic GnRH
• LH causes enlargement and maturation of gonads and excretions of sex
hormones – seconary sex characteristics
• In girls, ovulation occur – LH surge
Clinically evident puberty

Both: development of acne, axillary hair, body odor, mood changes
Female Male
Thelarche – breast development 8- Testicular enlargement – to >4mL
12years volume
Pubarche – pubic hair development 8- Pubic hair – growth between 10-14days
12years
Menarche – first menses – after 2,5 of Height spurt – when testicular volume is
onset of puberty 12-15mL, after a delay of 18months
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31b. Anemias (except for Iron deficiency anemias)
Definition
Hemoglobin below reference range for age
Normal values:
2weeks 13-20g/dL
6months-6years 10,5-14g/dL
7years-12years 11-16g/dL
Female 12-16g/dL
Male 14-18g/dL
• Impaired red cell formation
o Deficiency, BM failure, dyshematopoetic anemia
• Blood loss
• Hemolytic anemia – corpuscular/extracorpuscular
Etiology
• Decreased erythropoesis
o Decrease of structural elements
o Bone marrow insufficiency
• ↑Blood loss
o Bleeding (extravascular loss)
o Destruction of erythrocytes (intravascular loss)
• Combines reasons
• Hemolysis
• Infection, inflammation, chronic disease
Clinical features
Fatigue Irritability
Pallor (skin, nail bed) Poor feeding, anorexia
Orthostatic hypotension Poor growth
Dyspnea on excertion Tachycardia
Hemolysis – jaundice Headache
Diagnosis
• History: Diet, family history, environmental exposure
• Lab: RBC, Hb, HCT, MCV, MCH, ROW, reticulocyte
Hypochromic/microcytic Macrocytic Normocytic

IDA Normal newborn Acute blood loss
Thalassemia ↑Erythropoesis Infection
Chronic inflammation Post splenectomy Renal failure
Severe malnutrition Liver disease CT disease
Sideroblastic anema Megaloblastic/aplastic Malignancy
anemia
Obstructive jaundice Bone marrow infiltration
Down’s syndrome Hemolysis
Early iron deficiency
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1. Megaloblastic anemias
Gen: anemia of macrocytic classification that results from inhibition of DNA
synthesis during red blood cell production
• Presence of megaloblasts in the bone marrow + macrocytes in the blood
Etiology
Vitamin B-12 deficiency Folic acid deficiency
Inadequate dietary intake Inadequate intake
Defective vit B12 absorption Defective absorption
Defective vit B12 transport ↑Requirements
Disease of vitamin B12 metabolism ↑Excretion, disease of folic acid metabolism

Clinical features
Pallor Vitamin B12 deficiency
Lethargy Apathy
Fatigue Weakness
Anorexia Hypotonia
Sore, red tongue Peripheral neuropathy
Glossitis Spastic paresis
Diarrhea
Diagnosis
• Red cell changes - ↓Hb, ↑MCV
• Blood smear – macrocytes, macroovalocytes, anisocytosis, poililocytosis,
Cabot-rings, Howell-Jolly bodies
• WBC – Neutrophils ↓ - hypersegmentation, thrombocytopenia
• Vitamin B12↓
• Schilling urinary excretion test
Treatment
• Vitamin B12 supplement (i.m/p.o)
• Folic acid supplement (i.m/p.o)
• Diet: Green vegetables, liver, spinach, avocado, aspargus
2. Congenital pure red cell aplasia – Diamond Blackfan anemia

Gen: congenital erythroid aplasia that causes lowe red blood cell counts without
affecting other blood components
Clinical features
Normocytic/macrocytic anemia with ↓erythroid progenitors in BM
Craniofacial malformations (cleft palate)
Thumb/upper limb abnormalities
Heart defects
Urogenital malformations
Growth delay, ↓birth weight
Malignant potential (ALL, AML, HCC)
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Diagnosis
• Anemia
• Reticulocytopenia
• BM biopsy
Treatment
• Prednisone
• Packed red cell transfusion
• Bone marrow transplant

3. Congenital aplastic anemia – Fanconi anemia

Gen: Rare, inherited disease, autosomal recessive
Clinical features
Congenital anomalies Hyperreflexia
Patchy brown pigmentation of skin (café au lait) Hypogenitalism
Short stature Microcephaly
Skeletal abnormalities Microphtalmia
Strabismus Deafness
Renal and heart abnormalities ↑risk of malignancy
Petechie/bruises Fatigue
Pallor
Diagnosis
• Macrocytosis – anemia
• Neutropenia
• Pancytopenia
• BM aspiration
• Chromosome studies of lymphocytes
Treatment
• Supportive:
o Packed red blood cell and platelets
o Androgen treatment
o Chelaton treatment in iron overload
• Active:
o Bone marrow transplant

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4. Acquired aplastic anemia
Gen: BM failure that is caused by secondary etiology or idiopathic
Etiology
• Primary (idiopathic)
• Secondary
Drugs Toxins Infections
Cytostatics Benzene Viral (Hep ABC)
ATB (sulfonamide, chloramphenicol) Carbon tetrachloride HIV, EBV, CMV
Anticonvulsant Glue Irradiation
Antirheumatic Tluene Malnutrition
Antidiabetics Immunologic dx Chemicals
Antimalarial Graft vs host dx Insecticides
Clinical features

Anemia Leukopenia
• Pallor, fatigue, loss of appetite • ↑risk of infections, oral ulcers
Thrombocytopenia Hyperplastic gingivitis

• Petechie, easy bruising, epistaxis
Diagnosis
• Anemia – normocytic, normochromic
• Leukopenia: granulocytopenia
• Bone marrow:
o ↓ or absent hematopoetic cells, replacement by fatty acids
• Normal chromosomal analysis
Treatment
• Allogenic bone marrow transplantation
• Immunosuppresice treatment with antithymocyte globulins
• Cyclosporine, methylprednisone

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5. Hemolytic anemia
Gen: anemia due to hemolysis – abnormal breakdown of RBC
Etiology
Corpuscular defects/intrinsic cause
• Membrane defects – hereditary spherocytosis/elliptocytosis, stomatocytosis,
acantocytosis
• Enzymal defects – G6PD deficiency, pyruvate kinase deficiency
• Hb defects – Thalassemia, sickle-cell anemia
• Congenital dyserythropoetic anemia
Extracorpuscular defects/extrinsic cause

• Immune
• Non immune
Clinical features
Signs of anemia Failure to thrive
Hemolysis - ↑excretion into biliary tract Pulmonary HT – syncope, chest pain,
(gallstones) dyspnea – RVHF, peripheral edema, ascites
A) Hereditary spherocytosis
Gen: AD abnormality of erythrocytes caused by mutation in genes relating to
membrane proteins that allow the erythrocytes to change shape
Pathogenesis
• Membrane instability – dysfunction/deficiency of red cell skeletal protein
ankyrin/spectrin
• Sequestration of red cells in spleen due to erythrocyte deformity
• Premature red cell destruction
Clinical features
Anemia Jaundice – kernicterus in newborns
Splenomegaly Hypoxia
Diagnosis
• Anemia, ↑bilirubin • Microspherocytes
• ↓MCV, ↑MCHC • Hyperdense cells
• Reticulocytosis • Bone marrow
• ↓Red blood cell survival • Normoblastic, hyperplasia
• Blood smear
Treatment
• Folic acid supplement
• Leukocyte-depleted red cell transfusion
• Splenectomy
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B) Hereditary elliptocytosis
Gen: is due to various defects in the skeletal proteins, resuts ↑membrane rigidity
and ↓cellular deformability. AD inheritance
Clinical features
Anemia Jaundice – kernicterus in newborns
Splenomegaly Hypoxia
Treatment
• Transfusion
• Prophylactic folic acid
• Splenectomy

C) Hereditary stomarocytosis
Gen: the cells contain ↑Na and ↓K
Treatment
• No specific treatment – transfusion and folic acid

D) Pyruvate kinase deficiency

Gen: AR inherited metabolic disease which affects the survival of RBC
Clinical features
Anemia Gallstones
Jaundice Leg ulcers
Splenomegaly
Diagnosis
• CBC
• Liver test
Treatment
• Transfusion
• Splenectomy
E) Glucose 6 phosphate dehydrogenase deficiency

Gen: X-linked recessive genetic disease that predispose to hemolysis
Etiology
• Drugs: antimalaric, sulfonamide, aspirin, hemna
• Fava beans
• Infections
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Clinical features
Neonatal jaundice (kernicterus) DKA
Chronic anemia (non spherocytic) AKI
Diagnosis
• CBC, reticulocytes, LDH
• Liver test
• G6PD - ↓
Treatment
• Avoid food/drugs
• Splenectomy

6. Sickle cell disease

Gen: hereditary blood disease caused by an abnormality in Hb found in RBC –
form sickle cell shaped cells. AD inheritance
Genetics
• Transmitted as an incompete AD-trait
• Homozygotes(2abnormal genes) dont synthesize HbA
o 90-100% of red cells are HbS
• Heteozygotes (1 abnormal gene) have red cell containing HbS (20-40%)
Pathophysiology
• Valine substituted with glutamic acid
• Sickle cells destroyed – hemolytic anemia
• ↑blood viscosity and impaired blood flow - thrombi
Clinical features
Vaso-occlusive crisis (hand foot syndrome) Bone crisis – osteonectrosis, dactylitis
CNS crisis- thrombosis/bleeding/seizures Pulmonary crisis – dyspnea, hypoxemia,
acute chest syndrome
Priapism Splenic sequestration crisis
Liver, biliary sytem, kidney – Cardio – cardiomegaly, myocardial
hepatomeagaly, gallstones, ↑renal flow, dysfunction
proteinuria, nephrotic syndrome
Eyes/ears – retinopathy, sensorneuronal Erythroblastopenic
hearing loss
Diagnosis
• Anemia • Blood smear: sickle cells
• Reticulocytosis • ↓ESR
• Neutrophilia • PCR
• ↑platelet • Electrophoresis
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Treatment
• Prevention
• Vaccine – pneumococcus, H.influenza
• Transfusion
• Hydroxycarbamide (hydroxyura
• BM transplantation

7. Thalassemias
Gen: Inherited AR blood disease characterized by abnormal formation of Hb
Etiology
• α-thalassemia – deletion of 1/more α-genes
• β-thalassemia – point mutations in 1/more both genes
Clinical features
Failure to thrive Anemia
Jaundice, gall stones Hepatosplenomegaly
Abnormal faces (malar eminence, frontal Osteoprosis
bossing, depression of bridge of nose)
Fractures Leg ulcers
Growth retardation Primary menorrhea/delayed puberty in
male
Complications
• Develop as a result of
o Chronic anemia
o Chronic transfusion
o Poor compliace with chelation treatment
• Endocrine disturbances
• Liver failure, cirrhosis
• Heart failure
• Bony deformitites
Cause of death
• Congestive heart failure • Sepsis
• Arrhytmia • MOF due to hemochromatosis
Treatment
• Transfusion (Hb<7g/dL)
• Chelation treatment
• Splenectomy
• BM transplant
• Folic acid, Hep B vaccine

8. Autoimmune hemolytic anemia
Gen: Altered immune response resulting in production of antibody against the
patients own red cells causing hemolysis
Types
• Warm
o Eti: idiopathic or secondary to other disease
o Common form
o Reacts at body temp 37C
o Occur at any age (↑over 40years)
• Cold
o Eti: idiopathic or secondary to pneumonia, inf. mononucleosis
o Optimal thermal activitiy below 30C
o Usually not severe
o IgM attaches to erythrocyte in the cold – after warmin complement
remains and lyss of cell occurs
9. Drug induced hemolytic anemia

Gen: Patient produces antibody against a drug, its metabolites or the RBC coated
with the drug
Drugs
• Methyldopa
• Procainamide
• Penicillin
• Cephalosporin
10. Alloimmune hemolytic anemia

Gen: A foreign antigen stimulates the hosts immune system to produce a
corresponding antibody called alloantibody
Types
• Hemolytic transfusion reaction
o Acute-wrong ABO blood is transfused
o Delayed
11. Erythroblastosis fetalis

Gen: Rh- mother, Rh+ infant
Clinical features
o Severe anemia
o Compensatory spleein and liver enlargement
Treatment
• Prevent sensitiazation, -Rh Ig
• Intrauterine transfusion of affected fetus

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31c.Foreign body aspiration
Gen: as a child explore and interact with the world they will find objects and
have a tendency to put it into the mouth, that could lead to airway obstruction
• Ingestiion – esophagus
• Aspiration - airways
Most objects lodge in right main bronchus, 10% in trachea/larynx
Etiology
• Variety of foods
• Toy parts
Clinical features
Violent paroxysm of cough/choking/gagging – airway obstruction
Asymptomatic: lodging of foreign body
Complications:
• Obstruction • Pneumonia
• Erosion • Fever
• Infection • Hemophtysis
• Persistent cough • Atelectasis
Diagnosis
• Caregiver witness aspiration
• Positive symptomatology
• Child reports it
• X-ray: PA + lateral
• Bronchoscopy
Treatment
• Endoscopic removal
Laryngeal forign body

Gen: Lodge in supra/subglottis area
• Complete obstruction – asphyxia
• CF: Sudden respiratory distress/inability to speak/cough
• Tx: Heimlich maneuvre, endoscopic removal
Tracheal forign body

Gen: Choking/aspiration 90%
• Stridor/wheeze – 50-60%
Bronchial forign body

Gen: Persistent cough with sputum production
• Persistent wheezing
• Persistent/recurrent pneumonia - atelectasis
312


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2016

Paediatrics State Exam 2016/2017

Pavol Jozef Safarik University In Kosice

• Bronchopneumonia – a patchy consolidation involving one or several

Pathogens vary according to child’s age:

1b. Nonconjugated Hyperbilirubinemia

Types of neonatal jaundice

Impaired conjugation of bilirubin

Crigler-Najjar syndrome type 1 and 2

• Bronchopneumonia – a patchy consolidation involving one or several

• Older children >5years:

Age Normal respiratory rate Tachypnea

Idiopathic neonatal hepatitis

2. Hereditary fructose intolerance

3. Glycogen storage disease

Motlagh Paediatrics State Exam Perinpasivam

C) Mixed myopathic and hepatic forms

Clinical features Prognosis

Glycogen storage disease type 1 – Von Gierke’s Disease

Glycogen storage disease type 2 – Pompe’s Disease

Etiology and Transmission

2. Progressive primary tuberculosis

4. Extra pulmonary tuberculosis

• 0-5mm à negative • False pos à prev BCG vac

Gastroesophageal reflux (most Gastroenteritis (most common) Gastroenteritis (most

Pyloric stenosis Intestinal atresia Intussiception Hirshprung disease

Recurrent Bilious emesis Colic pain Aganglionic

4. Neonatal respiratory distress syndrome (RDS)

5. Bronchopulmonary dysplasia (BDP)

o Apnea X-ray o TPN

• Viruses • Bacterial agents

Motlagh Paediatrics State Exam Perinpasivam

4. Herpes simplex virus

6. Rapid progressive glomerulonephritis

2. Urinary tract infection

7. Erysipelas & Cellulitis

damage • Expressed on the epithelial cells of airways,

24 hour urinary protein excretion

Secondary immuno deficiency

A. Congenital heart diseases with Right to left shunt

Clinical findings Diagnosis Treatment

Clinical findings Diagnosis Treatment

Clinical findings Treatment

Differential diagnosis of generalized lymphadenopathy

Recombinant microbial antigens/ surface antigens

Precaution, contraindications and adverse effect

2. Ventricular septal defects

Clinical findings Treatment

Clinical findings Diagnosis Treatment

Clinical findings Diagnosis Treatment

Pediatric Glascow coma scale

Motlagh Paediatrics State Exam Perinpasivam

Motlagh Paediatrics State Exam Perinpasivam

Clinical findings Diagnosis Treatment

Clinical findings Diagnosis Treatment

Types (based on location of abnormal connection)

Clinical findings Diagnosis Treatment

6. Hypoplastic left heart syndrome

Clinical findings Diagnosis Treatment

Clinical findings Diagnosis Treatment

2. Iatrogenic fluid overload

4. Deep venous thrombosis (DVT)

2. Protein losing enteropathy