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Greetings everyone. I am very busy with exams coming up in a few days, but I did want to share a recent slide - this one is related to lead poisoning.

Talk soon!
-Bob

Peripheral blood smear in a patient with lead poisoning

Organ Basis of ID

Blood. RBC’s.

Morphology

Red cell with basophilic stippling. (Indicates clustering of ribosomes).

Disease

Microcytic hypochromic anemia.

Etiology

Lead poisoning (aka Plumbism).

Pathogenic mechanism

Deficient HEME synthesis due to:

Inhibition of ALA dehydratase

Inhibition of Ferrochelase

Decreased incorporation of Iron into Heme.

Divalent lead “competition” with Calcium - systemically.

Other Structural changes seen

Possibly mild hemolytic anemia in CBC.

Other sites of involvement

Encephalopathy: Seizures, coma, violence. (PB, a divalent cation like Ca)

Kidneys: PCT Damage (Shows intra-nuclear inclusions (of Pb-Protein complexed.) Produces a FANCONI-Like syndrome as AA’s are lost in the urine – NO PCT re-absorption).

Gums: Show lines of hyperpigmentation that are blue/black.(lead sulfide deposition.)

Long Bones: Lead Lines, Pb deposited instead of Calcium.

Blood: Na/K ATPase Pump inhibited. Possible HEMOLYTIC anemia.

Other diseases w/ similar changes

Thalassemia.

Iron-deficiency.

Signs and Symptoms

Peripheral neuropathy in adults. (Wrist drop/ Foot drop).

Acute encephalopathy (CNS) in YOUNG children.

Older children show Behavior changes and developmental regression.

Constipation and colicky pain. (ANS involvement in GIT).

A chronic disease. Children present with a more abrupt onset of CNS problems. Adults present with headache, metallic taste, abdominal discomfort and personality changes.

Reversible disease in adults, not necessarily children.

Laboratory Investigations

Blood - for blood lead and erythrocyte protoporphyrin and Zn-protoporphyrin.

Urine – during chelation therapy for progress.

Screening questions and health department involvement.

Course of disease process

1.Lead ingestion via absorption, inhalation or consumption.

2.Pb’s high affinity for -SH (SULFHYDRYL GROUPS) inhibits Heme synthesis.

3.Iron won’t incorporate into Heme. - Protoporphyrin builds up. (Zn substitutes for Fe).

4.Ribsomes in RBC’s remain clustered – producing stippling.

5.Pb affects BBB permeability, complexes with proteins and incorporates where calcium normally acts.

6.Death is a possibility. The source must be removed.

Treat with EDTA/BAL chelation therapy combination.

3 important points

Protoporhpyrin accumulates – provides for testing

RBC’s become small with “little blue dots.”

Children at serious risk.

Clinical Vignette

A 19-month-old, previously healthy Hispanic child was found to have anemia during a routine screening examination; her hemoglobin level was 5.4 g per dL. The family lived in an older neighborhood and drank tap water from the city’s water supply which was recently chemically treated for contamination by Enteric bacteria.

The peripheral blood smear showed round, dark-blue granules within the red blood cells. During the workup, radiography of the child’s long bones was performed showing radiodensity in the epiphyses.

Which one of the following is the most likely diagnosis?

A. Beta-thalassemia

B. Carbon Monoxide Exposure

C. Lead toxicity

D. Sickle cell anemia

E. Gram-negative hemolysins.

This is what we are doing in Pathology. We present a slide or two everyday that we research in the midst of our work. Classes are sometimes 8 to 5 and then we have a day’s worth of studying leaving a hell of a lot of time for sleep, but it is better than working for the man.

Identify Organ Basis of ID

Small blood vessels with concentric rings of endothelium, connective tissue and/or epithelioid cells possibly.

Morphology

First of all, vessel appears thrombosed i.e.; the intravascualr coagulation of blood (noticed in the left side of the lumen in this photo). Note: endothelial loss by itself can lead to thrombosis. (See pg 94 Robbins). Secondly, possibly a vasculitis (inflammation of vessel walls, notice mild thickness, indicative of cellular infiltrate). Fibrinoid necrosis refers to the hyaline-like staining that occurs within the vasculature (not unlike how fibrin stains: clear, pink, glassy).

Disease

Rocky Mountain Spotted Fever (RMSF), caused by Rickettsia rickettsii, conveyed by the bite of a wood or dog tick. Obligate intracellular parasites.

Etiology

Intracellular infection of endothelial cells by rickettsia resulting in necrosis and rupture of small vessels.

Pathogenic mechanism

Kill by cytopathic effect- replicate in cytoplasm of endothelial cells the infected blood vessels cells lyse, causing internal hemorrhage, blockage of the blood vessels, and eventual death of the cells. Coagulation cascade activated.

Other Structural changes seen

CTL responses essential for removal of rickettsia, kill by NO. (Stimulated first by IFN-gamma and TNF from NK’s).

Other sites of involvement

GIT, muscles, CNS & heart potentially involved in advanced stages. Interstitial pneumonia possibly.

Other diseases w/ similar changes

Possibly other ricketsial diseases.

Signs and Symptoms

Abrupt onset high fever and severe headache, malaise followed by a rash that is initially macular but may become petechial or hemorrhagic. Rash (from extravasation of RBC’s) begins on extremities and spreads to entire body. 10% do NOT have a rash. May never present untl death. Disease is found in South-Central and Mid-Atlantic United States. 2/3 cases in children.

Laboratory Investigations

Clinical specimens from blood and reactions with Proteus antibodies (Weil-Felix reaction).

Course of disease process

Potentially lethal but curable. — Untreated cases may result in shock, myocardial or renal failure, DIC.

Highlight 3 important points

Endothelial cell damage launches clotting cascade which includes thrombosis AND bleeding. (Consumptive coagulopathy- clotting factors get used up). Should be treated with antibiotics. Abrupt fever with rash starting in extremities.

Clinical Vignette

A 35 year old dog handler from Tennessee developed a sudden fever and a strange rash of tiny red spots on his hands shortly after a turkey hunting weekend at his country house. An intracellullar organism was implicated. This disease was most likely caused by:

A. A lysogenic viral infection that has become lytic

B. Exotoxins involved in ADP-ribosylation

C. A type of necrosis that can be seen in the walls of small or medium-sized muscular blood vessels

D. A Primary infection that has progressed to a disseminated form

Extra note: Black measels - Howard T. Ricketts was the first to establish the identity of the infectious organism that causes this disease. He and others characterized the basic epidemiologic features of the disease, including the role of tick vectors. Their studies found that Rocky Mountain spotted fever is caused by the bacterium, Rickettsia rickettsii. This species is maintained in nature in a complex life cycle involving ticks and mammals; humans are considered to be accidental hosts and are not involved in the natural transmission cycle of this pathogen. Tragically, Dr. Ricketts died of typhus (another rickettsial disease) in Mexico in 1910, shortly after completing his remarkable studies on Rocky Mountain spotted fever.