Essential Revision Notes in Paediatrics for MRCPCH-Part 1

Prothrombintime (PT)

Prolongation of PT > 3 s above normal or INR 1 1.3 may indicate vitamin K deficiency

Failure of INR to normalize after a parenteral dose of vitamin K (1 mg/year of age up to a
maximum of 5 mg) suggests liver failure
Reflects the decreased synthesis of factor VII and IX which have short half-lives
Useful in monitoring progress of acute liver failure

Causes of hepatosplenomegaly

Cirrhosis (early) biliary atresia, sclerosing cholangitis, congenital hepatic fibrosis

Haematological thalassaemia, spherocytosis, sickle cell anaemia

Infection infectious mononucleosis, TORCH, malaria, septicaemia

Immune juvenile rheumatoid arthritis, systemic lupus erythematosus,

immunodeficiency states

Metabolic a1-antitrypsin deficiency, tyrosinaemia, cystic fibrosis

Proliferative leukaemia, lymphoma, Langerhans cell histiocytosis

Storage diseases Gaucher (long-term), Niemann- Pick, mucopolysaccharidoses

-Causesofhepatomegaiy SHIRT

patic biliary hypoplasia,

polycystic disease, congenital hepati

Storage/metabo&e

Defective lipid metabolism - Gaucher disease, Niemann-Pick disease,

hyperlipoproteinaemias, cholesteryl ester storage disease, camitinrdeficiency,

mucolipidoses

-Defective carbohydrate metabolism diabetes mellitus, glycosyltransferase

deficiency (types 1, 3, 4 and 6), hereditary fructose intolerance, galac

Cushing syndrome, mucopolysaccharidoses

-Defective amino acid/protein metabolism tyrosinaemia (type 1), urea cycle enzyme

disorders

-Defective mineral metabolism Wilson disease, juvenile haemochromatosis

-Defective electrolytetransport cystic fibrosis

-Defective nutrition protein calorie malnutrition, total parenteral nutrition

Deficiency of protease-a1-antitrypsin deficiency

-Defective bile flow progressive familial intrahepatic cholestasis syndrome

-H Haematological

Thalassaemia, sickle cell disease (chronic haemolysis and transfusion haemosiderosis),
acute lymphoblastic, acute myeloid and chronic myelocytic leukaemias.

Heart/vascular

Congestive cardiac failure, constrictive pericarditis, obstructed inferior vena cava,

Budd-Chiari syndrome

-I Infection

Viral infection - congenital rube1la, CMV infection, coxsackievirus, echovirus,

hepatitis A, B, C, D and E viruses, infectious mononucleosis

Bacterial infections - neonatal septicaemia, Escherichia coli urinary tract infection,

tuberculosis, syphilis

Parasitic infections - hydatid disease, malaria, schistosomiasis, toxoplasmosis,

visceral larva migrans

Fungal infection -coccidiomycosis

Inflammatory

Autoimmune liver disease

-l nflammatory bowel disease associated liver disease

R Reticuloendothelial

Non-Hodgkin lymphoma, Hodgkin disease, Langerhans cell histiocytosis

Rheumatological

Systemic juvenile chronic arthritis, systemic lupus erythematosus

-T Tumour/hamartoma

Primary hepatic neoplasms - hepatoblastomas, hepatocellular carcinoma (hepatoma)

Secondary deposits - neuroblastoma, Wilm's tumour, gonadal tumours
Vascular malformationhenign neoplasm - infantile haemangioendothelioma,

cavernous haemangioma

Trauma *

Hepatic haematoma

7. THE PANCREAS

7.1 Acute pancreatitis

Defined clinically as the sudden onset of abdominal pain associated with a rise in
amylase or lipase of at least three times the upper limit in the blood or urine
Rare in children
Involves premature activation of trypsinogen
Presents with epigastric or back pain. May have prominent nausea and vomiting. Less
commonly there may be fever, tachycardia, hypotension, jaundice, and abdominal signs
such as guarding, rebound tenderness and a decrease in bowel sounds

Causes of acutepancreatitis

Idiopathic
Pancreatitis associated with systemic illness
Trauma
Structural abnormalities of pancreas, pancreatic or common bile duct
Medications (valproate, L-asparaginase, prednisolone, azathioprine, 6-mercaptopurine,
frusemide, phenytoin)
Infections (mainly viral, e.g. mumps, enterovirus, Epstein-Barr virus, hepatitis A, CMV,
rubella, cosackievirus, rubeola, measles, influenza)
Gallstones
Familial (PRSSI, SPlNKI or CFTR mutation)
Post-endoscopic retrograde cholangiopancreatography
Metabolic

Diabetic ketoacidosis
Hypercalcaemia
Hypertriglyceridaemia
Cystic fibrosis

Recurrent acute pancreatitis is seen in 10% of children after a first episode of acute
pancreatitis and is commonly associated with structural abnormalities, idiopathic or
familial pancreatitis
Commonest cause of familial pancreatitis

Mutations in cationic trypsinogen gene (e.g. PRSSI) enhance trypsin activation
Mutations in the SPlNKl (serine protease inhibitor Kazal type 1.) gene result in an
abnormal pancreatic secretory trypsin inhibitor
Mutations of the CFTR (cystic fibrosis transmembrane conductance regulator) gene,
which reduces the pancreatic fluid secretion capacity,-increase the risk of keeping
activated trypsin in the pancreas for a longer period of time
The mainstay of current treatment is analgesia, intravenous fluids, pancreatic rest, and
monitoring for complications
Acute pancreatitis scoring system for children that predicts severity of disease and

mortality include the following parameters
Age (<7 years)
Weight (<23 kg)
Admission white blood cell count (>18.5 X 1og/litre)
Admission lactate dehydrogenase (>2000 lullitre)
48-hour fluid sequestration (>75 m/kg per 48 h)
48-hour rise in urea (>5 mgldl)
Each criterion is assigned a value of 1 point, cumulative score predicts the outcome
of patients

0 to 2 points - 8.6% severe, 1.4% death
2 to 4 points - 38.5% severe, 5.8% death

5 to 7 points - 80% severe, 10% death

Surgical management is limited to debridment of infected necrotic pancreas or

cholecystectomy or endoscopic sphincterotomy in the presence of gallstones

Essential' Revision Notes ill Paecji,~trbcs hl-the lLlfiC-/'(-/ i 211~E1dilion

Antibiotics are usually not necessary unless in severe pancreatic necrosis
Octreotide infusions may reduce pancreatic secretions in those with pancreatic fluid
sequestration

Complications of pancreatitis

Local Systemic -

Oedema Shock
Inflammation Pulmonary oedema
Fat necrosis Pleural effusions
Phlegmon Acute renal failure, coagulopathy
Pancreatic necrosis Haemoconcentration
Bacteraemia, sepsis
Sterile Distant fat necrosis
lnfected Vascular leak syndrome
Abscess Multiorgan system failure
Haemorrhage Hypermetabolic state
Fluid collections Hypocalcaemia
Pseudocysts Hyperglycaemia
Duct rupture and strictures
Extension to nearby organs

7.2 Chronic pancreatitis

Defined as a complex process beginning with acute pancreatitis and-progressingto end-
stage fibrosis as the result of recurrent and chronic inflammatory prmesses
It is the final common pathologic pathway of a variety of pancreatic disorders
Usually associated with genetic conditions like cystic fibrosis or hereditary pancreatitis

or is idiopathic
Cystic fibrosis is the most important cause of chronic pancreatitis in children. CFTR
mutation-associatedpancreatitis can be divided into four mechanistic subtypes, where
CFTK, is severe CFTR mutation phenotype and CFTb-, is mild or variable CFTR
mutation phenotype

Type 1 - CFT&ev/CFT&evgenotype
Type 2 - CFT&ev/CFT&-v genotype
Type 3 - CFTIz,, or CFT&-, plus a second pancreatitis modifier or susceptibility

gene (e.g. CFTR,,,/SPINKl)

Type 4 - CFT&,, or CFTG-, plus a strong environmental risk factor such as alcohol

Pancreatic insufficiency is a sign of chronic pancreatitis but is not diagnostic. The
pancreas has marked functional reserve and has to be severely damaged before
functional loss can be clinically recognized

Faecal elastase < 150 pg/g i s quite specific for exocrine pancreas insufficiency

lnvasive pancreatic stimulation tests are the standard for assessment of pancreatic

insufficiency but are not usually indicated

Chronic pancreatitis with calcifications can be identified on abdominal radiography or
by transabdominal ultrasonography. When present, the diagnosis of chronic pancreatitis
can be made with 90°h confidence
Other abdominal imaging methods used include computed tomography, endoscopic
retrograde cholangiopancreatogram, endoscopic ultrasonography, and magnetic
resonance imaging or MRCP (magnetic resonance cholangio pancreatography)
Genetic testing for PRSSI, SPINKI, CFTR and other mutations can be performed if there
is history of recurrent acute pancreatitis, unexplained chronic pancreatitis or presence of
a positive family history of hereditary pancreatitis

8. FURTHER READING

American Academy of Pediatrics. 2004. Management of hyperbilirubinemia in the newborn
infant 35 or more weeks of gestation. American Academy of Pediatrics clinical practice
guidelines. Pediatrics; 114:1, 297-31 6.

Decker BC. 2004. Pediatric Gastrointestinal Disease, 4th edn. Ontario, Canada: BC Decker
Inc.
Dhawan A, Cheeseman P, Mieli-Vergani G. 2004. Approaches to acute liver failure in
children. Pediatric Transplantation 8, 584-588.

Kelly, D (Ed). 2004. Diseases of the Liver and Biliary System in Children, 2nd edition.

Oxford: Blackwell Publishing.
North American Society for Pediatric Gastroenterology, Hepatology and Nutrition 2004.
Guideline for the evaluation of cholestatic jaundice in infants: recommendations of the
North American Society for Pediatric Gastroenterology, Hepatology and Nutrition. Journal

of Paediatric Gastroenterologyand Nutrition 39, 115-128. .

Chapter 13

Jmmunology

Waseern Qasirn and Bobby Gaspar

CONTENTS 471
477
1. Introduction

2. The immune system

2.1 Haematopoietic stem cells
2.2 T- and B-cell development
2.3 Antibody structure
2.4 Complement
2.5 Recognition of antigens
2.6 Cytokines

3. Investigation of a child with primary immunodeficiency

3.1 History
3.2 Examination
3.3 Investigations

4. Immunoglobulins and B-cell deficiencies

4.1 X-linked agammaglobulinaemia
4.2 Autosomal recessive congenital agammaglobulinaemia
4.3 IgA deficiency
4.4 Common variable immunodeficiency (CVID)

5. Combined immunodeficiencies

5.1 Severe combined immunodeficiency (SCID)
5.2 Combined immunodeficiency

6. Miscellaneous immunodeficiency syndromes

6.1 Wiskott-Aldrich syndrome
6.2 Di George syndrome
6.3 CD40 ligand deficiency (X-linked hyper-lgM syndrome)
6.4 X-linked lymphoproliferative syndrome (Duncan syndrome)
6.5 Purine nucleoside phosphorylase (PNP) deficiency
6.6 Ataxia telangiectasia
6.7 Chronic mucocutaneous candidiasis

Essenti,~1 Rcvisiol?Notes in R~edi,itric..stijr the I\.1 KCP(:H 2nd Edition

7. Defects of neutrophils
7.1 Congenital neutropenia
7.2 Schwachman-Diamond syndrome
7.3 Cyclical neutropenia
7.4 Leukocyte-adhesion deficiency
7.5 Chronic granulomatous disease
7.6 ChGdiak-Higashi syndrome
7.7 Rac deficiency

8. Defects of the interferon-ylinterleukin-12axis 490

9. Bone marrow/haernatopoietic stem-cell transplantation (BMT/HSCT) 492

10. Routine vaccination in the immunosuppressed 493

11. Complement deficiency states 493

12. Hypersensitivity reactions 494

13. Immunosuppressants and immune-modulating agents 494

14. Further reading 495