THE PEDIATRICS CLERKSHIP - PART 7 potx

Heavy or prolonged menstruation Frequent or prolonged epistaxis Prolonged bleeding after injury, surgery circumcision, or invasive tal procedures PT INR Extrinsic system Elevated in DI

von Willebrand Disease

DEFINITIONMost common hereditary bleeding disorder

 Heavy or prolonged menstruation

 Frequent or prolonged epistaxis

 Prolonged bleeding after injury, surgery (circumcision), or invasive tal procedures

PT (INR) Extrinsic system Elevated in DIC, warfarin use, liver failure, myelofibrosis,

vita-min K deficiency, fat malabsorption, circulating anticoagulants, factor deficiencies

aPTT Intrinsic Elevated in factor deficiencies, circulating anticoagulants,

hep-arin use

If lengthened and platelet count is normal, consider qualitative platelet defect

Platelet count Related to bleeding time < 100,000/mm 3 —mild prolongation of bleeding time

D -dimer Intravascular fibrinolysis Present in most individuals, especially with cancer, trauma

Sensitive for active clotting, but not specific Assays for specific Quantitative Hemophilia A (VIII), hemophilia B (IX), von Willebrand factor

PT, prothrombin time; INR, international normalized ratio; aPTT, activated partial thromboplastin time.

vWF does not cross

placenta

A child presents with

epistaxis, prolonged

bleeding time, and a

normal platelet count

Think: von Willebrand’s

disease

Typical Scenario

 Increased aPTT and bleeding time

 Abnormal factor VIII clotting activity

 Quantitative assay for vWF antigen

 Reduced ristocetin co-factor activity

 Abnormal platelet aggregation tests

 Normal platelet count

TREATMENT

 Avoid unnecessary trauma

 Desmopressin

 Replacement therapy:

 Factor VIII concentrate

 Weight (kg) ×desired % replacement ×0.5

 Cryoprecipitate recommended only in life-threatening emergencies due

to the risk of human immunodeficiency virus (HIV) and hepatitis

 Inherited coagulation defects

 Hemophilia A: factor VIII deficiency

 Hemophilia B: factor IX deficiency

PATHOPHYSIOLOGY

Slowed rate of clot formation

SIGNS ANDSYMPTOMS

Patients with hemophiliamay lose large amounts ofblood into an iliopsoashematoma

Only 30% of male infantswith hemophilia bleed atcircumcision

 1 unit of VIII/kg—

increase 2%

 1 unit of IX/kg—

increase 1%

H Y P E R C O A G U L A B L E S TAT E S

DEFINITIONPredisposition to thrombosis

PATHOPHYSIOLOGYPrimary (inherited) or secondary (acquired) disturbances in the three areas ofVirchow’s triad:

 Endothelial damage (e.g., inflammation, trauma, burns, infection,surgery, central lines, artifical heart valves)

 Change in blood flow (e.g., immobilization, local pressure, congestiveheart failure [CHF], hypovolemia, hyperviscosity, pregnancy)

 Hypercoagulability (e.g., factor release secondary to surgery, trauma,malignancy); antiphospholipid antibodies, lupus, oral contraceptiveuse; genetic predispositions such as deficiencies of protein S, protein C,antithrombin III, or factor V Leiden; nephrotic syndrome, poly-cythemia vera, sickle cell anemia, homocystinemia, fibrinogenemiaSIGNS ANDSYMPTOMS

 Deep vein thrombosis (DVT)

 Pulmonary embolism (PE)

 Myocardial infarction (MI)

 StrokeDIAGNOSIS

ETIOLOGY

 Transmitted by female Anopheles mosquito

 Four species of Plasmodium:

SIGNS ANDSYMPTOMS

An 8-year-old American born

boy of Somali parents

presents with fever for 1

week after returning from

his vacation On examination

he has splenomegaly Think:

Malaria

Typical Scenario

 Traditional method: identification of organisms on thick and thin

pe-ripheral blood smears obtained when patient is acutely febrile

 Newer methods include polymerase chain reaction (PCR) and

im-munoassays

TREATMENT

 See CDC Web site for specific guidelines

 Chloroquine is used for P ovale, P vivax, P malariae, and

chloroquine-sensitive P falciparum.

 Significant areas of chloroquine-resistant P falciparum exist In these

places, mefloquine or atovaquone–proguanil should be used

preparation for surgery

 FFP—treatment of bleeding from vitamin K deficiency, increased

inter-national normalized ratio (INR), liver disease, or during plasma

ex-change for TTP

 Cryoprecipitate—hypofibrinogenemia, hemophilia A, von Willebrand

factor deficiency, factor XIII deficiency

COMPLICATIONS

 Hemolytic, febrile, and allergic reactions

 Transfusion-related acute lung injury (TRALI)

 Disease transmission (e.g., HIV, hepatitis B virus [HBV], hepatitis C

virus [HCV], human T-lymphotropic virus [HTLV], cytomegalovirus

[CMV], parvovirus)

 Iron overload, electrolyte disturbances

 Fluid overload, hypothermia

M E T H E M O G L O B I N E M I A

ETIOLOGY

 Inherited:

 Deficiency of cytochrome b5 reductase

 Hgb M disease—inability to convert methemoglobin back to

hemo-globin

 Acquired—increased production of methemoglobin:

 Nitrites (contaminated water), xylocaine/benzocaine (teething gel),

sulfonamides, benzene, aniline dyes, potassium chlorate

PATHOPHYSIOLOGY

 Hgb iron in ferrous form

 Methemoglobin iron is in ferric form (<2%) and is unable to transport

One unit of whole blood is

450 mL and shouldincrease the hemoglobin by

1 g/dL and the hematocrit

by 3%

Life-threatening transfusionreactions are nearly alwaysdue to clerical errors(wrong ABO blood type)

SIGNS ANDSYMPTOMSDepends on the concentration:

TABLE 15-6 Transfusion reactions.

Acute hemolytic RBC incompatibility Fever, chills, nausea Stop transfusion Pretransfusion

36,000) (fatal 1 Hypotonic solution Hemoglobinuria, oliguria pressure and renal Accurate labeling,

Delayed Antibodies to minor 3–10 days post-transfusion Usually self-limited Chronically

hemolytic blood group antigens Falling hematocrit, fever, Supportive transfused patients

Allergic (1 in Antibodies to Hives, itching, local Antihistamines Pretransfusion

Washed cellular blood products

Anaphylactic Antibodies to IgA Cough, respiratory distress, Stop transfusion IgA-deficient

Shock, vascular instability, loss of consciousness

Febrile Antibodies to Fever, chills Stop transfusion Pretransfusion

nonhemolytic granulocytes Dyspnea, anxiety Demerol antipyretics

blood products

Transfusion- Antigranulocyte Bilateral pulmonary edema Supportive Do not use plasma

related acute antibodies in donor Cyanosis, hypoxemia products from

lung injury product Respiratory distress, cough implicated donor

ARDS-like picture Fever, chills

Circulation Hypervolemia Dyspnea, cyanosis, Diuretics Pretransfusion

overload Rapid infusion hypoxemia Oxygen diuretics

RBC, red blood cell; IgA, immunoglobulin A; CHF, congestive heart failure; DIC, disseminated intravascular coagulation; ARDS, adult respiratory distress syndrome.

 Again, depends on concentration

 <30%: treatment not needed

 30–70%: IV methylene blue

 If no response: hyperbaric O2

 Oral ascorbic acid (200–500 mg)

P O R P H Y R I A

DEFINITION ANDETIOLOGY

Protoporphyrin is essential molecule of heme proteins Porphyria refers to a

group of disorders characterized by an inherited deficiency of the heme

biosynthetic pathway

SIGNS ANDSYMPTOMS

 Photosensitivity (with edema and blister formation)

 Neurologic (myalgias, numbness, tingling, back and extremity pain, loss

of deep tendon reflexes)

 Absolute/primary (defect of hematopoietic stem cell):

 Polycythemia vera (increase in all cell lines)—mean age 60 years

 Elevated erythropoeitin level (hypoxia, e.g., cyanotic congestive

heart disease, renal tumors)

 Relative/secondary (e.g., dehydration, burns)

EPIDEMIOLOGY

Very rare in children

SIGNS ANDSYMPTOMS

 Headache, weakness, dizziness

 Splenomegaly or two of the following:

D I S O R D E R S O F W H I T E B L O O D C E L L S Neutropenia

DEFINITIONAbsolute neutrophil count (ANC) <1,500/mm3:

 Mild 1,000–1,500

 Moderate 500–1,000

 Severe <500ETIOLOGY

 Increased susceptibility for infection

 Stomatitis, gingivitis, recurrent otitis media, cellulitis, pneumonia, andsepticemia

A 3-year-old girl has had

fever, anorexia, and

fatigue for the past month

She has lost 5 kg She has

pallor, cervical adenopathy,

splenomegaly, skin

ecchymoses, and petechiae

Think: Acute leukemia.

Typical Scenario

ANC =Total WBC ×(Segs

+Bands)

SIGNS ANDSYMPTOMS

SIGNS ANDSYMPTOMS

 Fatigue, anorexia, lethargy, pallor

 CBC: anemia, abnormal white count, low platelet count

 Electrolytes, calcium, phosphorus, uric acid, lactic dehydrogenase

(LDH)

 Chest x-ray (mediastinal mass)

 Bone marrow—hypercellular, increased lymphoblasts

 Cerebrospinal fluid (CSF)—blasts

TREATMENT

 Four phases:

 Remission induction: cytoxan, vincristine, prednisone, L

-asparagi-nase, and/or doxorubicin

 Consolidation: may add 6MP, 6TG, or cytosine arabinoside

 Maintenance therapy: 2 years—methotrexate and 6MP, may add

vin-cristine and prednisone

 CNS prophylaxis: Methotrexate to CSF, may have radiation to the

head

 Infection prevention—antibiotics, isolation if necessary

Acute Myelogenous Leukemia (AML)

Marrow exam is essential

to confirm the diagnosis ofALL

ETIOLOGYPredisposing factors

SIGNS ANDSYMPTOMS

 Manifestations of anemia, thrombocytopenia or neutropenia, includingfatigue, bleeding, and infection

 Chloroma—localized mass of leukemic cells

 Bone/joint pain

 Hepatosplenomegaly

 Lymphadenopathy

DIAGNOSIS

 >25% myeloblasts in the bone marrow, hypercellular

 Abnormal white count, platelet count, and anemia

 Bone destruction and periosteal elevation on x-ray

 Infection prevention—isolation, antibiotics

 RBC transfusions for anemia

 Platelet transfusions for bleeding

 Complete remission in 70–80%

Chronic Myelogenous Leukemia (CML)

DEFINITIONClonal disorder of the hematopoietic stem cell with specific translocation

ETIOLOGYPhiladelphia chromosome t(9;22)(q34;q11)

EPIDEMIOLOGYTends to occur in middle-aged people

SIGNS ANDSYMPTOMS

CML often gets diagnosed

when CBC is performed for

other reasons

Juvenile Chronic Myelogenous Leukemia (JCML)

DEFINITION

 Clonal condition involving pluripotent stem cell

 <2 years

EPIDEMIOLOGY

Ninety-five percent diagnosed before age 4

SIGNS ANDSYMPTOMS

 Skin lesions (eczema, xanthoma, café au lait spots)

 Lymphadenopathy

 Hepatosplenomegaly

DIAGNOSIS

 Monocytosis

 Increased marrow monocyte precursors

 Philadelphia chromosome absent

 Blast count

 <5% (peripheral blood)

 <30% (marrow)

TREATMENT

 Complete remissions have occurred with stem cell transplant

 Majority relapse, with overall survival of 25%

 Lymphoid malignancy arising in a single lymph node or lymphoid

re-gion (liver, spleen, bone marrow)

 Large cell or histiocytic

SIGNS ANDSYMPTOMS

 Fever, night sweats

 Weight loss, loss of appetite

 Cough, dysphagia, dyspnea

 Lymphadenopathy—lower cervical, supraclavicular

Reed–Sternberg cells arecharacteristic of Hodgkin’slymphoma

Suspicious lymph nodesare:

 Painless, firm, andrubbery

 In the posterior triangle

DIAGNOSISDiagnosis and staging

 CBC, erythrocyte sedimentation rate (ESR)

 Serum electrolytes, uric acid, LDH

 Chest x-ray

 Computed tomography (CT) of chest, abdomen, and pelvis

 Lymph node or bone marrow biopsy

STAGING

 Stage I—One lymph node involved

 Stage II—Two lymph nodes on same side of diaphragm

 Stage III—lymph node involvement on both sides of diaphragm

 Stage IV—bone marrow or liver involvement

TREATMENT

 Radiation for stage I or II disease

 Chemotherapy for stage III or IV

D I A B E T E S

See Table 16-1

DEFINITION

Syndrome characterized by disturbance of metabolism of carbohydrate,

pro-tein, and fat, resulting from deficiency in insulin secretion or its action

EPIDEMIOLOGY

Diabetes is the most common endocrine disorder of the pediatric age group

PATHOPHYSIOLOGY

 Decreased glucose utilization

 Increased glucose production

SIGNS ANDSYMPTOMS

 Triad of polyuria, polydipsia, and polyphagia

 Weight loss and enuresis are common symptoms

 Vomiting, dehydration, abdominal pain

H I G H - Y I E L D F A C T S I N

Endocrine Disease

TABLE 16-1 Diabetes

Severe insulin deficiency Insulin increased, normal, or

decreased Insulin resistance

Increased risk with obesity

Hyperosmolar coma HLA-DR3 and -DR4 (chromosome 6)

Glucosuria, ketonuria, random glucose Fasting glucose > 140 mg/dL

HLA, human leukocyte antigen.

Think of testing urineglucose with the onset ofenuresis in a previouslytoilet-trained child

 Fasting blood glucose >126 mg/dL

 Random blood glucose >200 mg/dL

 Relative or absolute insulin deficiency

 Precipitating factors—stress, infection, traumaSIGNS ANDSYMPTOMS

Polyuria, polydipsia, fatigue, headache, nausea, vomiting, tachycardia, airhunger

LABORATORY FINDINGS

 Increased hemoglobin (Hgb) and hematocrit (Hct) tion)

(hemoconcentra- Increased white blood cell (WBC) count

 Decreased serum sodium (Na) (pseudohyponatremia)

 Normal or increased potassium (K)

 Decreased HCO3TREATMENT

 Slow fluid and electrolyte replacement

 Insulin regular (0.1 U/kg/hr)

 Glucose (add glucose when blood glucose is 250–300 mg/dL)COMPLICATIONS

Transient Hyperinsulinemia

ETIOLOGY

 Excessive insulin secretion in infants

 Small-for-gestational-age (SGA) or premature infants

A 10-year-old girl has a

2-hour postprandial blood

glucose of 300 mg/dL and

a large amount of glucose

and trace ketones in her

urine She has lost 1 kg of

weight Think: Type I

diabetes, and start

treatment with insulin

Typical Scenario

Insulin-dependent diabetes

mellitus in children is

associated with blood

islet–cell antibodies and

 Fetal hypoxia

 Born to mother with poorly controlled diabetes

 Surreptitious insulin administration

 Can be caused by genetic mutations

 Also may be caused by a β-cell dysregulation, such as due to an isolated

islet cell adenoma

 Increased serum ferritin

 Increased transferrin saturation

is >90th percentile andhead circumference is at

the 50th percentile Think:

Hyperinsulinism

Typical Scenario

A 14-year-old boy with an8-year history of diabetesmellitus has had frequentadmissions for DKA in thepast 18 months His schoolperformance has beendeteriorating Recently, hehas had frequent episodes

of hypoglycemia He isTanner stage 2 in pubertaldevelopment, is growing at

a normal rate, and has

mild hepatomegaly Think:

of 16/min, blood pressure40/20 mm Hg, rectaltemperature of 36.2, and

an unusual odor on hisbreath He has ageneralized tonic–clonic

seizure Think: DKA, and

check a serum glucose

Typical Scenario

Juvenile Graves’ Disease

 Thyroid-stimulating hormone (TSH) receptor antibody

SIGNS ANDSYMPTOMS

 Gradual onset (6–12 months)

 Severe tachycardia leading to cardiogenic shock

 Central nervous system (CNS) manifestations

are rare in the early

neonatal period due to

placental transfer of

maternal thyroid hormone

Look for hypothyroidism in

Down’s syndrome, Turner’s

syndrome, and Klinefelter’s

syndrome

 Slowed development, late teeth, late milestones, small size.

 Eventual mental retardation if left untreated

The risk of malignancy ishigher in solitary thyroidnodules

Rapid and painlessenlargement of a thyroidgrowth may suggestneoplasia

SIGNS ANDSYMPTOMS

 Clinical manifestation of hypercalcemia

 Muscle weakness, anorexia, nausea, vomiting, constipation, polydipsia,polyuria, loss of weight, fever

 Furosemide (increased Na and Ca excretion)

 Prednisone (decreased intestinal absorption of Ca)

H Y P O PA R AT H Y R O I D I S M

DEFINITIONDecreased PTH

DIAGNOSIS

 Decreased serum Ca

 Increased serum P

 Markedly decreased PTHDIFFERENTIALDIAGNOSIS

Pseudohypoparathyroidism (markedly increased PTH—PTH ness)

A 10-year-old girl has

severe abdominal pain and

gross hematuria She

passes a calculus in her

urine She had received no

medication and has no

family history of renal

stones Think: Primary

Pay attention to heart rate

with treatment for

hypoparathyroidism:

Bradycardia is an indication

to stop calcium infusion

A newborn with ambiguous

genitalia is a medical and

social emergency

 21-hydroxylase deficiency (90%)

 11 β-hydroxylase deficiency

 3 β-hydroxysteroid dehydrogenase

SIGNS ANDSYMPTOMS

 Ambiguous genitalia in female

 Normal genitalia at birth in males, develop premature isosexual

devel-opment

 Salt wasting (two thirds of cases)

 Vomiting, dehydration, and shock at 2 to 4 weeks of age

DIAGNOSIS

 Normal karyotype

 Hyponatremia, hypochloremia, hyperkalemia, hypoglycemia

 Markedly increased 17-hydroxyprogesterone

TREATMENT

 Fluid and electrolyte replacement

 Normal saline (NS) 20 mL/kg bolus, then maintenance plus ongoing

Characteristic pattern of obesity with hypertension (HTN) due to abnormally

high level of cortisol

ETIOLOGY

 Bilateral adrenal hyperplasia (Cushing’s disease)—pituitary tumor

 Adrenal tumors (adenoma, carcinoma)

SIGNS ANDSYMPTOMS

 Truncal obesity, rounded moon facies, buffalo hump, purple striae, acne

 HTN, muscle weakness

DIAGNOSIS

 Elevated serum cortisol

 Elevated 24-hour urine test for free cortisol

 Dexamethasone suppression test

 Normal if a single dose of 0.3 mg/m2at 11 P.M results in plasma

corti-sol of <5 g/dL at 8 A.M the next morning

 Polycythemia, lymphopenia, and eosinopenia

 Abdominal computed tomography (CT) (adrenal tumors)

 Pituitary magnetic resonance imaging (MRI) (pituitary adenoma)

DIFFERENTIALDIAGNOSIS

 Exogenous obesity

 Normal growth rate

 Urinary corticosteroids suppressed by dexamethasone

Combination ofhyperkalemia andhyponatremia clue todiagnosis of congenitaladrenal hyperplasia

In congenital adrenalhyperplasia, blood should

be drawn for steroid profilebefore the administration

of hydrocortisone

Cushing’s disease is a state

of hypercortisolismsecondary toadrenocorticotropichormone (ACTH)-producingpituitary adenoma

Growth retardation may bethe early manifestation ofCushing’s syndrome

Virilization may indicateadrenal carcinoma

Most urgent tests forcongenital adrenalhyperplasia:

1 Serum glucose

2 Serum electrolytes

Other tests: cortisol,testosterone, 17-OHprogesterone

 Pediatric endocrine, surgical, and neurosurgical consultation

 Adrenalectomy and radiotherapy (adrenal tumors)

 Transsphenoidal resection of pituitary adenoma

 Primary adrenal insufficiency

 Destruction of adrenal cortex

 Autoimmune

 TuberculosisETIOLOGY

 Weakness, nausea, vomiting, weight loss, salt craving

 Hyponatremia, hyperkalemia, hypoglycemia

 Chest x-ray (small heart)

 Decreased cortisol level (<5 g/dL) that fails to rise after ACTH istration

In Cushing’s syndrome, free

cortisol in urine is always

not exclude the diagnosis

Glucocorticoid therapy for

acute adrenal insufficiency

should be continued for 48

hours Dosage must be

increased during periods of

stress

 May occur in isolation

 Also seen in the MEN II (bilateral), von Hippel–Lindau,

neurofibro-matosis type I, and familial carotid body tumor syndromes

SIGNS ANDSYMPTOMS

 Nonspecific symptoms

 Headache, palpitations, increased sweating

 Tremor, fatigue, chest or abdominal pain, and flushing

 Vanillylmandelic acid (VMA)

 Abdominal ultrasound (US)

 Abdominal CT and MRI

Primary (Pituitary Adenoma)

 Growth hormone (GH)-secreting adenoma

Siblings of a patient with apheochromocytoma should

be periodically evaluatedbecause of increasedfamilial incidence

The most useful screeningtest for pheochromocytoma

is blood pressure

Hypertensive paroxysmsare an important diagnosticclue

After successful surgery of

a pheochromocytoma,catecholamine excretionreturns to normal in about

Increased urinarynorepinephrine indicates anextra-adrenal site of apheochromocytoma,whereas increasedepinephrine indicates anadrenal lesion

H Y P O P I T U I TA R I S M

DEFINITIONDeficiency of more than one pituitary hormone

 Midline anomalies (septo-optic dysplasia, cleft palate)

 Craniopharyngioma

 Head trauma

 CNS surgery

 CNS irradiationSIGNS ANDSYMPTOMS

 Depends on missing hormone

 GH deficiency (poor linear growth, hypoglycemia)

 In neonates (hypoglycemia and micropenis)

 LH and FSH (pubertal delay)TREATMENT

Replacement directed toward the hormonal deficiency

P I T U I TA RY T U M O R

MOSTCOMMONProlactinoma

SIGNS ANDSYMPTOMS

 Headache

 Amenorrhea

 GalactorrheaDIAGNOSIS

Increased prolactin (up to 1,000 ng/mL)

TREATMENTSurgical resection except if isolated prolactinoma, then try medical treatmentfirst

S H O RT S TAT U R E

DEFINITIONHeight below the 5th percentile (2 standard deviations below the mean).NORMAL

 Chronological age (CA) =Bone age (BA) =Height age (HA)

 Normal growth 5 cm/year

An infant has hypoglycemia

and a micropenis Think: