Pediatric Primary Care Case Studies (76 page)

Epidemiology of Lead Poisoning

Plumbism has long been recognized as having significant impact on the well-being of children, but lead is inescapably present throughout the environment.
The results of the National Health and Nutrition Examination Survey (NHANES) in 1994 and again in 1999–2002 indicate the occurrence of lead toxicity in the United States is on the decline as a result of increased public awareness and legislation. Rates in non-Hispanic African American children remain higher than in non-Hispanic white or Mexican American children (CDC, 2005; Roberts & Riegart, 2002).

Despite this improvement, lead toxicity remains a major health concern. A high index of suspicion and careful monitoring of children from at-risk populations is vital in order to provide early detection and treatment. The risk factors are the same as for iron deficiency, which itself facilitates lead absorption in children. Both pica and lead poisoning have been found to be associated findings in the presence of iron deficiency anemia.

Pathophysiology of Lead Poisoning

As in the discussion of environmental toxins, children absorb more lead and are more sensitive to its effects than are adults (Cohen, 2007). Children’s bones store only 64% of the absorbed lead, whereas adults’ bones sequester approximately 95%. That leaves 36% of the lead burden in the child’s circulation and soft tissues where it results in acute toxic effects. Other deficiencies compound the rates at which iron is taken up into the body and the degree to which it is stored.

Lead competitively binds with many proteins: the sulfhydryl (SH) group of cysteine, the amino group of lysine, the carboxyl group of glutamic and aspartic acids, and the hydroxyl group of tyrosine (Piomelli, 2002). This widespread affinity for key proteins helps to explain the widespread effects within the body.

In blood, an elevated lead level interferes with heme synthesis by inhibiting essential mitochondrial membrane function and interfering with enzymatic functions. In lead toxicity, iron is blocked from being incorporated into protoporphyrin, despite the fact that it is available. However, in iron deficient states this lack of iron results in an accumulation of erythrocyte protoporphyrin in blood. Both situations result in elevated circulating levels of FEP (Piomelli, 2002). Therefore, an elevated FEP level with a microcytic RBC morphology could indicate either iron toxicity or iron deficiency.

The brain is very sensitive to exposure to heavy metals or other toxins, with children’s brains being even more susceptible. The effect of these toxins is primarily reflected in neurobehavioral and neurodevelopmental disorders such as cognitive deficits, developmental delays, inattention problems, and psychosocial disorders, and in central nervous system dysfunctions such as ataxia, seizures, paresthesias, paralysis, coma, or death. The extent of sequelae is influenced by the level of intoxication.

Which of Oswaldo’s physical findings would be suggestive of leukemia or another cancer?

The following findings could be suggestive of cancer:

•   Pallor

•   Fatigue

•   Purpura

•   Bleeding

Pathophysiology of Leukemia and Lymphoma

Although the specific cause of lymphoblastic leukemia is not known, in general cancers are known to stem from damage to DNA resulting in an uncontrolled overproduction of cells that overcrowd the bone marrow, crowding out normal cells. Because these abnormal cells are blood-borne, they can spread throughout the body and infiltrate organs and sites such as the liver, spleen, central nervous system, lymph nodes, and reproductive organs (Belson, Kingsley, & Holmes, 2007). These cells also develop abnormally long life spans. Leukemia may be the result of exposure to radiation or chemicals. Regarding chemical exposures, only benzene has been clearly demonstrated to cause cancer, but other agents, such as organophospates and other pesticides, have been noted as possible links (Belson et al., 2007).

Symptoms consistent with leukemias are typically present days to weeks before diagnosis. Disruption of hematopoiesis accounts for the most common presenting symptoms of anemia—infection, easy bruising, and bleeding. Other symptoms and signs of leukemia tend to be less specific (pallor, fatigue, fever, tachycardia, chest pain, malaise, and weight loss) and are attributable to anemia and a hypermetabolic state rather than to the direct effect of the cancer.

Multiple factors influence the outcomes for leukemia. Acute lymphoblastic leukemia (ALL) occurs most often in children and has a greater cure rate than acute myeloblastic leukemia (AML). Females tend to fare better than males. Whites tend to be diagnosed with ALL more often than African Americans, but Asian Americans and Hispanic Americans have survival rates higher than African Americans. Children between 1 and 10 years have greater survivability than older persons. Persons with Down syndrome have a greater likelihood of developing leukemia than do any other groups (Gamis et al., 2003; Robison et al., 1984). Overall survival rates drop off markedly if these cancerous cells are evident in the brain or central nervous system.

If suspicions of leukemia are strong, the initial evaluation would first include a complete blood count (CBC) and a peripheral blood smear (PBS). The red cell size may present as normocytic with decreased RBC production, and the MCV is occasionally increased. The presence of pancytopenia (thrombocytopenia/leucopenia/cytosis) and peripheral blasts suggest acute leukemia. The differential diagnosis of the finding of pancytopenia includes: aplastic anemia, viral infections such as infectious mononucleosis, and vitamin B
₁₂
and folate deficiency. The peripheral smear may also reveal tear-drop erythrocytes and leukocyte casts.
Blast cells in the blood smear may approach 90%, unless the WBC count is markedly decreased. Although the preliminary diagnosis can usually be made from the blood smear, bone marrow examination is the diagnostic gold standard. Blast cells in the bone marrow range between 30% and 95%. Immediate referral to a hematologist/oncologist is required.

A diagnosis of leukemia is unlikely in Oswaldo’s case; however, you will do initial basic blood testing (CBC) that will assure you that leukemia is not the cause of his symptoms.

What physical findings are suggestive of warfarin (rat poison) ingestion?

The following symptoms are suggestive of warfarin ingestion:

•   Nosebleeds

•   Bruising and purpura

•   Anemia secondary to acute blood loss

Pathophysiology of Warfarin Toxicity

The majority of accidental warfarin ingestions occur in children younger than 6 years of age and consist of ingestions of small amounts of warfarin. There are several long-acting coumarin derivatives, so-called Super warfarin anticoagulants (brodifacoum, diphenadione, chlorophacinone, bromodialone) commonly used as rodenticides. They produce profound effects and prolong anticoagulation. The mechanism of action of these common coumarin derivatives is to inhibit vitamin K1-2,3 epoxide reductase, preventing vitamin K from being reduced to its active form (Olson, Trickey, Miller, & Yungmann-Hile, 2008). The degree of this effect is based on dose and duration of exposure to warfarin. The oral bioavailability is excellent. Once in the system, it is bound to plasma protein (albumin) and distributed to the kidneys, lungs, and spleen. Anticoagulant effects typically occur 5–7 days after a single dose; however, the Super warfarin effects may persist for weeks to months.

Minor bleeding complications are usually noted from mucosal surfaces, but also increase the ease of bruising, nosebleeds, and hematuria. As the ingested amount of Super warfarin increases, major complications become evident. Major bleeding commonly includes hemorrhages from gastrointestinal, intracranial, and retroperitoneal sites, but could progress to massive bleeding from any organ system.

What characteristics from the history and physical relate to the possible diagnosis of hypothyroidism?

The following could suggest hypothyroidism:

•   Fatigue

•   Loss of developmental skills

•   Dullness

Pathophysiology of Hypothyroidism

Fatigue, constipation, poor feeding, delayed development, and the slow growth reported in Oswaldo’s case are consistent with a diagnosis of hypothyroidism. In infants with congenital hypothyroidism, symptoms become evident within weeks to months of birth. Among the presenting symptoms are prolonged jaundice, poor feeding, constipation, cool mottled skin, excessive sleepiness, decreased crying, umbilical hernia, and large fontanel and tongue (Avery, 1994). A decrease in growth velocity in the presence of anemia suggests the possibility of hypothyroidism. This anemia tends to be normo- or macrocytic anemia. This finding should not be confused with the megaloblastic anemia associated with folate or cobalamin deficiency. Anemia associated with hypothyroidism responds when the primary hormone deficiency is treated (Irwin & Kirchner, 2001).

Of those neonates diagnosed with hypothyroidism, 10% will develop normal thyroid levels within days to months of birth. For the other 90% of affected neonates, if their hypothyroidism is left untreated, severe developmental delay and mental retardation as well as growth delays result (Kliegman, Greenbaum, & Lye, 2004).

Acquired hypothyroidism has an insidious onset, with slowing of growth being the most common initial symptom. Linear growth is very dependent on the amount of circulating thyroid hormone; in the absence of this hormone, growth will cease completely until it is replaced. A goiter often appears early and can be noted on routine examination even before growth slowing occurs. Hypothyroidism also impacts energy level and may produce a dull expression in children. Other findings include pale, thick, cool skin; constipation; delayed deep tendon reflexes; slow pulse and lowered blood pressure; and dulling of the child’s cognitive ability, although these symptoms are reversible with hormone replacement therapy (Burchett, Hanna, & Steiner, 2009).

There are a few possible reasons for a young child to manifest signs and symptoms of hypothyroidism after the neonatal period. Delayed onset of congenital hypothyroidism occurs when the newborn has a vestigial or defective thyroid gland, which is incapable of meeting the demands of a growing child. Inhibition of thyroid hormone production within the gland itself is a more common explanation for the development of hypothyroidism. Inadequate dietary iodine is a cause that is common in less developed countries, but it is not a health concern in the United States (Kliegman et al., 2004). Some drugs may also block thyroid hormone production, and when prescribing lithium or iodine-containing drugs such as amiodarone, hormone level monitoring is essential (Taketomo, Hodding, & Kraus, 2008). Hypothyroidism from these causes can be reversed. Occasionally the body will have an autoimmune reaction to its own thyroid gland. In Hashmoto’s thyroiditis, the antibodies attack and destroy thyroid cells.