Lead Flashcards
What is the pathway of lead toxicity?
lead, Pb, interacts with essential metals, proteins, and nucleic acids –> leads to disruption of metabolic processes –> can disrupt ultrastructures, eg organs –> leads to organ and organ system dysfunction –> clinical manifestations
what is the normal level of lead in the blood, and when do you see clinical manifestations?
lead normal levels : 0.1 ppm, lead toxic levels: 0.35 ppm
lead has an affinity for sulfhydryl groups–> disrupts CAC, mito chondria, etc
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what are the major systems affected by lead poisoning?
lead affects: 1. hematopoietic
lead affects: 2. nervous
lead affects: 3. renal
what are the minor systems affected by lead poisoning?
lead minorly affects: 4. lungs
lead minorly affects: 5. GI
lead minorly affects: 6. liver
subcellular effects of lead?
subcellular affects of lead: 1. enzymes–changes the enzyme configuration; e.g. will bind to active site and distort it–>disrupts activity
subcellular affects of lead: 2. disrupts protein synth, Hb being the main one
subcellular affects of lead: 3. heavily interacts with mitochondria–> lots of sulfhydryl groups there; leads to reduced ATP synth and lead-SH enzyme interaction
subcellular affects of lead: 4. RBC effects–disrupts heme synth, increases RBC fragility, reduced iron uptake, and reduced Na?K dep ATPase
–all RBC effects lead to anemia (and death of red cells)
What are the organs lead affects, and the clinical manifestations?
organs lead affects: 1. Kidney; acute– tubular necrosis in the mito; Fanconi’s syndrome; chronic– nephropathy and fibrosis
organs lead affects: 2. Brain– encephalopathy–lead in blood causes capillary damage–>leads to fluid leaking and edema in the brain–>brain swelling–>anoxia–>malacia; lead alters neurochemistry and herefore behaviour; also alters nerve conduction (limp wrists)
organs lead affects: 3. repro system–chromosome breakage, gametotoxic (sperm v sensitive), embryotoxic, and teratogenic
how is lead a carcinogen?
lead, Pb, is immunosuppresive–macrophages have lots of SH groups, and Abs have lots of SH groups–>leads to cancer
how does lead affect heme biosynth?
Pb inhibits ALAD in mito
hemotological effects of lead
hemotological effects of Pb: 1. anemia; RBCs are hypochromic and microcytic;
hemotological effects of Pb: 2. basophilic stippling–dots on RBCs
hemotological effects of Pb: 3. increased osmotic fragility, due to increased lipid peroxidation
hemotological effects of Pb: 4. stimulates erythropoeisis– increased activity in attempt to replace RBCs, but ineffective
hemotological effects of Pb: 5. Inhibits heme synthesis–ALA dehydratase and ferrochetelase are inihib’d, ALA synthetase and coprogenase are stim’d (trying to bring up RBC count); ALAd and ferrochet have many SH groups
treatment for lead
treatment for lead: chelation therapy; can use Ca-EDTA which binds lead and is excreted in urine;
treatment for lead: penicillin–>chelates a bit of lead, then give Ca-EDTA
treatment for lead: BAL–british anti-lewocytes–>contain SH groups; lipid sol, gets it out of your brain
how does lead affect the endocrine system?
lead affects the endocrine system by impairing thyroid and adrenocorticoid thyroid hormone function
how does lead affect hte CV system?
lead affects the CV system by causing hypertension and ECG changes (action potential effects)
who are the populations at risk for lead poisonings?
Populations at risk for Pb poisonings:
- children
- pregnant women–>fetus can’t excrete or metabolie lead (crosses placenta)
- other–those with thalessemia or sickle cell anemia
- genetic susceptibilities– mutations in ALAD; vit D receptor gene; hemochromatosis (iron storage disease); – HFE protein, associated with Pb and Fe absorption; ApoE genotype–associated with CNS trauma or injury
