Materiały źródłowe

• #1 Lead Toxicity – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK541097/

  Lead poisoning Pathogenesis, mechanism […] Lead interacts with human physiology in two significant ways: it has a strong affinity for sulfhydryl groups and electron donor groups in general, such that lead ends up bound to and affecting a wide range of proteins. […] Because of its similarity to other divalent cations like calcium and zinc, it interferes with the vast array of cellular mechanisms that are regulated by and mediated by these cations. […] Because of the ubiquity of electron donor groups and divalent cations throughout the human body, the pathophysiology of lead toxicity is quite complex and involves virtually every organ system. […] From a neurologic perspective, lead is thought to undermine the normal synaptic pruning process in young brains, likely underlying the cognitive and behavioral changes seen in young children with excessive lead exposure. […] Peripheral neuropathy is a common manifestation of chronic lead toxicity in adults, but the mechanism underlying its development is poorly understood. […] The most severe neurologic manifestations of lead toxicity such as seizures and coma occur in acute lead encephalopathy, which is thought to be at least in part secondary to lead-induced cerebral microvascular changes leading to cerebral edema and resultant increased intracranial pressure.

• #2 Lead poisoning – Wikipedia

  https://en.wikipedia.org/wiki/Lead_poisoning

  The US Centers for Disease Control and Prevention and the World Health Organization state that a blood lead level of 10 g/dL or above is a cause for concern; however, lead may impair development and have harmful health effects even at lower levels, and there is no known safe exposure level. […] The primary cause of lead’s toxicity is its interference with a variety of enzymes because it binds to sulfhydryl groups found on many enzymes. Part of lead’s toxicity results from its ability to mimic other metals that take part in biological processes, which act as cofactors in many enzymatic reactions, displacing them at the enzymes on which they act. Lead is able to bind to and interact with many of the same enzymes as these metals but, due to its differing chemistry, does not properly function as a cofactor, thus interfering with the enzyme’s ability to catalyze its normal reaction or reactions.

• #3 Lead Toxicity | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/30343

  Broadly speaking, lead interacts with human physiology in two significant ways: it has a strong affinity for sulfhydryl groups and electron donor groups in general, such that lead ends up bound to and affecting a wide range of proteins. […] Because of its similarity to other divalent cations like calcium and zinc, it interferes with the vast array of cellular mechanisms that are regulated by and mediated by these cations. […] From a neurologic perspective, lead is thought to undermine the normal synaptic pruning process in young brains, likely underlying the cognitive and behavioral changes seen in young children with excessive lead exposure. […] Peripheral neuropathy is a common manifestation of chronic lead toxicity in adults, but the mechanism underlying its development is poorly understood.

• #4 Lead Toxicity: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/242605-overview

  The major mechanism of lead toxicity is due to increased generation of reactive oxygen species (ROS) and interference with generation of antioxidants. Lead causes the generation of ROS like hydroperoxide, hydrogen peroxide, and singlet oxygen. […] Lead inactivates glutathione by binding to GSHs sulfhydryl group, which causes GSH replenishment to become inefficient, thereby increasing oxidative stress. Lead also interferes with the activity of other antioxidant enzymes including superoxide dismutase and catalase. The increase in oxidative stress leads to cell membrane damage due to lipid peroxidation. […] The effects of lead poisoning on the brain are manifold and include delayed or reversed development, permanent learning disabilities, seizures, coma, and even death. The long-term effect of lead exposure is maximal during the first 2 or 3 years of life, when the developing brain is in a critical formative stage.

• #5 Lead Toxicity: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/242605-overview

  The major mechanism of lead toxicity is due to increased generation of reactive oxygen species (ROS) and interference with generation of antioxidants. Lead causes the generation of ROS like hydroperoxide, hydrogen peroxide, and singlet oxygen. […] Lead inactivates glutathione by binding to GSHs sulfhydryl group, which causes GSH replenishment to become inefficient, thereby increasing oxidative stress. Lead also interferes with the activity of other antioxidant enzymes including superoxide dismutase and catalase. The increase in oxidative stress leads to cell membrane damage due to lipid peroxidation. […] The effects of lead poisoning on the brain are manifold and include delayed or reversed development, permanent learning disabilities, seizures, coma, and even death. The long-term effect of lead exposure is maximal during the first 2 or 3 years of life, when the developing brain is in a critical formative stage.

• #6 Evaluation and management of lead exposure

  https://aoemj.org/journal/view.php?doi=10.1186/s40557-015-0085-9

  Lead causes health problems such as toxicity of the liver, kidneys, hematopoietic system, and nervous system. […] The mechanism of lead-induced oxidative stress has been described as the depletion of antioxidative reserves and the increased generation of reactive oxygen species (ROS), such as hydroperoxides. […] Lead inactivates GSH by binding to GSH’s sulfhydryl group, which causes GSH replenishment to become inefficient, thereby increasing oxidative stress. […] The main mechanism causing neurological abnormalities is the ionic mechanism that substitutes lead for calcium ions, allowing it to pass through the blood-brain barrier. […] By penetrating the blood-brain barrier, lead accumulates in astroglial cells, disrupting myelin sheath formation. […] Toxicity also arises from lead replacing divalent cations, which are necessary for cellular activity.

• #7 Lead Toxicity: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/242605-overview

  The major mechanism of lead toxicity is due to increased generation of reactive oxygen species (ROS) and interference with generation of antioxidants. Lead causes the generation of ROS like hydroperoxide, hydrogen peroxide, and singlet oxygen. […] Lead inactivates glutathione by binding to GSHs sulfhydryl group, which causes GSH replenishment to become inefficient, thereby increasing oxidative stress. Lead also interferes with the activity of other antioxidant enzymes including superoxide dismutase and catalase. The increase in oxidative stress leads to cell membrane damage due to lipid peroxidation. […] The effects of lead poisoning on the brain are manifold and include delayed or reversed development, permanent learning disabilities, seizures, coma, and even death. The long-term effect of lead exposure is maximal during the first 2 or 3 years of life, when the developing brain is in a critical formative stage.

• #8

  https://journals.lww.com/imsp/fulltext/2019/10020/sources_and_toxicological_effects_of_lead_on_human.3.aspx

  Lead acts by inducing oxidative stress due to inefficient replenishment of glutathione. […] Lead binds to GSH’s sulfhydryl group, inactivates GSH, and increases oxidative stress. Lead blocks the enzymes (-aminolevulinic acid dehydratase [ALAD], glutathione reductase, glutathione peroxidase, and glutathione-S-transferase) activity and further reduces GSH levels. Inducing lead in a human body at high level causes destabilization of cellular membrane through lipid peroxidation, which can cause hemolytic anemia. […] Neurological toxicity of lead is due to an ionic mechanism that permits calcium ions to pass through the blood-brain barrier (BBB). […] Lead toxicity increases oxidative stress, neurological abnormalities, affects the sodium ion concentration, other severe health complications, and even death.

• #9 Lead poisoning – Wikipedia

  https://en.wikipedia.org/wiki/Lead_poisoning

  The US Centers for Disease Control and Prevention and the World Health Organization state that a blood lead level of 10 g/dL or above is a cause for concern; however, lead may impair development and have harmful health effects even at lower levels, and there is no known safe exposure level. […] The primary cause of lead’s toxicity is its interference with a variety of enzymes because it binds to sulfhydryl groups found on many enzymes. Part of lead’s toxicity results from its ability to mimic other metals that take part in biological processes, which act as cofactors in many enzymatic reactions, displacing them at the enzymes on which they act. Lead is able to bind to and interact with many of the same enzymes as these metals but, due to its differing chemistry, does not properly function as a cofactor, thus interfering with the enzyme’s ability to catalyze its normal reaction or reactions.

• #10 Lead poisoning pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Lead_poisoning_pathophysiology

  Lead has no known physiologically relevant role in the body. […] The toxicity of lead comes from its ability to mimic other biologically important metals, most notably calcium, iron and zinc which act as cofactors in many enzymatic reactions. […] Following ingestion, lead is able to bind to and interact with many of the same enzymes as these are metals, but due to its differing chemistry, does not properly function as a co-factor, thus interfering with the enzyme’s ability to catalyze its normal reaction(s). […] Lead toxicity symptoms arise are thought to occur by interfering with an essential enzyme delta-AminoLevulinic Acid Dehydratase, or ALAD. ALAD is a zinc-binding protein which is important in the biosynthesis of heme, the co-factor found in hemoglobin. Lead poisoning also inhibits the enzyme ferrochelatase which catalyzes the joining of protoporphyrin IX and Fe2+ to form Heme. […] Delta -aminolevulinic acid dehydratase (ALAD) plays an important role in lead poisoning, and polymorphisms in the ALAD gene might affect the symptoms the individual patients experience.

• #11 Lead poisoning pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Lead_poisoning_pathophysiology

  Lead has no known physiologically relevant role in the body. […] The toxicity of lead comes from its ability to mimic other biologically important metals, most notably calcium, iron and zinc which act as cofactors in many enzymatic reactions. […] Following ingestion, lead is able to bind to and interact with many of the same enzymes as these are metals, but due to its differing chemistry, does not properly function as a co-factor, thus interfering with the enzyme’s ability to catalyze its normal reaction(s). […] Lead toxicity symptoms arise are thought to occur by interfering with an essential enzyme delta-AminoLevulinic Acid Dehydratase, or ALAD. ALAD is a zinc-binding protein which is important in the biosynthesis of heme, the co-factor found in hemoglobin. Lead poisoning also inhibits the enzyme ferrochelatase which catalyzes the joining of protoporphyrin IX and Fe2+ to form Heme. […] Delta -aminolevulinic acid dehydratase (ALAD) plays an important role in lead poisoning, and polymorphisms in the ALAD gene might affect the symptoms the individual patients experience.

• #12 PDB-101: Molecule of the Month: Lead Poisoning

  https://pdb101.rcsb.org/motm/196

  Lead ions poison proteins throughout the body, blocking their normal function. […] Unfortunately, when these lead ions get into our bodies, they can bind to proteins, displacing the proper metal ions and corrupting their function. The result can be deadly as proteins in the brain and other organs are poisoned. […] One of the proteins poisoned by lead is involved in the synthesis of heme: 5-aminolaevulinic acid dehydratase (ALAD), also known as porphobilinogen synthase. ALAD performs the first step in production of heme rings, using a zinc ion to help catalyze the reaction. As shown in PDB entry 1qnv, lead ions displace these zinc ions, making the enzyme inactive. This process blocks formation of new heme groups and leads to one of the common symptoms of lead poisoning: anemia. […] Lead poisoning has lasting effects because it slowly builds up in the body. It is cleared within a month or so from proteins in the blood, but it lasts for years in the brain and decades locked up in bones. Lead poisoning is particularly dangerous to growing children because proteins involved in development of the central nervous system are very sensitive to lead. […] Lead poisons these proteins by interacting with their calcium-binding sites and reducing their sensitivity to calcium levels. […] Enzymes use specific arrangements of amino acids to capture zinc and calcium ions. Lead is more agnostic than these two ions and can bind to both types of sites.

• #13 Lead poisoning pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Lead_poisoning_pathophysiology

  Lead has no known physiologically relevant role in the body. […] The toxicity of lead comes from its ability to mimic other biologically important metals, most notably calcium, iron and zinc which act as cofactors in many enzymatic reactions. […] Following ingestion, lead is able to bind to and interact with many of the same enzymes as these are metals, but due to its differing chemistry, does not properly function as a co-factor, thus interfering with the enzyme’s ability to catalyze its normal reaction(s). […] Lead toxicity symptoms arise are thought to occur by interfering with an essential enzyme delta-AminoLevulinic Acid Dehydratase, or ALAD. ALAD is a zinc-binding protein which is important in the biosynthesis of heme, the co-factor found in hemoglobin. Lead poisoning also inhibits the enzyme ferrochelatase which catalyzes the joining of protoporphyrin IX and Fe2+ to form Heme. […] Delta -aminolevulinic acid dehydratase (ALAD) plays an important role in lead poisoning, and polymorphisms in the ALAD gene might affect the symptoms the individual patients experience.

• #14 Pathways – Lead Poisoning

  https://sites.tufts.edu/leadpoisoning/pathways/

  Lead is particularly harmful to the body because it mimics metal ions, thus interfering with membrane proteins. […] When lead binds instead of calcium, the signaling pathway is interrupted. […] This affects the nervous system because synaptic transmission is often one of these interrupted pathways. […] When lead interrupts this pathway, signaling molecules called neurotransmitters cannot communicate with target cells across the synapse. […] Lead exposure interrupts this homeostasis and causes oxidative stress and eventually, cell death. […] Leads inhibition of -Aminolevulinic Acid Dehydratase (ALAD) causes the heme precursor, -aminolevulinic acid (ALA), to accumulate. […] This molecule can auto oxidize, causing more free radical species to be released. […] Oxidative stress associated with ALA can disrupt the activity of the neurotransmitter GABA.

• #15 Lead (Pb) Toxicity: What Are Possible Health Effects from Lead Exposure? | Environmental Medicine | ATSDR

  https://archive.cdc.gov/www_atsdr_cdc_gov/csem/leadtoxicity/physiological_effects.html

  Lead serves no useful purpose in the human body. Its presence in the body can lead to toxic effects, regardless of age, gender, or exposure pathway. […] The nervous system is the most sensitive organ system for lead exposure in children. […] On a molecular level, proposed mechanisms for toxicity involve fundamental biochemical processes. These include lead’s ability to inhibit or mimic the actions of calcium (which can affect calcium-dependent or related processes) and to interact with proteins (including those with sulfhydryl, amine, phosphate, and carboxyl groups). […] Lead’s high affinity for sulfhydryl groups makes it particularly toxic to multiple enzyme systems including heme biosynthesis. […] The National Toxicology Program and the American Academy of Pediatrics have concluded that there is sufficient evidence for adverse health effects in children and adults at blood lead levels (BLLs) 5 micrograms per deciliter (g/dL).

• #16 Lead Toxicity – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK541097/

  Lead poisoning Pathogenesis, mechanism […] Lead interacts with human physiology in two significant ways: it has a strong affinity for sulfhydryl groups and electron donor groups in general, such that lead ends up bound to and affecting a wide range of proteins. […] Because of its similarity to other divalent cations like calcium and zinc, it interferes with the vast array of cellular mechanisms that are regulated by and mediated by these cations. […] Because of the ubiquity of electron donor groups and divalent cations throughout the human body, the pathophysiology of lead toxicity is quite complex and involves virtually every organ system. […] From a neurologic perspective, lead is thought to undermine the normal synaptic pruning process in young brains, likely underlying the cognitive and behavioral changes seen in young children with excessive lead exposure. […] Peripheral neuropathy is a common manifestation of chronic lead toxicity in adults, but the mechanism underlying its development is poorly understood. […] The most severe neurologic manifestations of lead toxicity such as seizures and coma occur in acute lead encephalopathy, which is thought to be at least in part secondary to lead-induced cerebral microvascular changes leading to cerebral edema and resultant increased intracranial pressure.

• #17 Evaluation and management of lead exposure

  https://aoemj.org/journal/view.php?doi=10.1186/s40557-015-0085-9

  Lead causes health problems such as toxicity of the liver, kidneys, hematopoietic system, and nervous system. […] The mechanism of lead-induced oxidative stress has been described as the depletion of antioxidative reserves and the increased generation of reactive oxygen species (ROS), such as hydroperoxides. […] Lead inactivates GSH by binding to GSH’s sulfhydryl group, which causes GSH replenishment to become inefficient, thereby increasing oxidative stress. […] The main mechanism causing neurological abnormalities is the ionic mechanism that substitutes lead for calcium ions, allowing it to pass through the blood-brain barrier. […] By penetrating the blood-brain barrier, lead accumulates in astroglial cells, disrupting myelin sheath formation. […] Toxicity also arises from lead replacing divalent cations, which are necessary for cellular activity.

• #18 Lead Poisoning – BioPharma Notes

  https://biopharmanotes.com/lead-poisoning-symptoms-diagnosis-and-treatment/

  It is due to its ability to substitute other bivalent cations like Ca2+, Mg2+, Fe2+ and monovalent cations like Na+ which affect various fundamental biological processes of the body like intra and intercellular signaling, cell adhesion, protein folding and maturation, apoptosis, ionic transportation, enzyme regulation, release of neurotransmitters, etc. […] The lead replaces calcium ions and becomes competent to cross the blood-brain barrier (BBB). After crossing the BBB, lead accumulates in astroglial cells (containing lead binding proteins). Toxic effects of lead are more dangerous in the developing nervous system comprising immature astroglial cells that lack lead binding proteins. Lead easily damages the immature astroglial cells and obstructs the formation of myelin sheath, both factors involved in the development of BBB. […] Lead poisoning may produce progressive mental deterioration in children, followed by a steady loss of motor skills and speech. It may cause severe hyperkinetic and aggressive behavior disorders and a poorly controllable convulsive disorder.

• #19 Lead Toxicity | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/30343

  The most severe neurologic manifestations of lead toxicity such as seizures and coma occur in acute lead encephalopathy, which is thought to be at least in part secondary to lead-induced cerebral microvascular changes leading to cerebral edema and resultant increased intracranial pressure. […] From a hematologic perspective, lead causes anemia by interfering with the function of several enzymes involved in heme synthesis as well as enzymes involved in maintaining erythrocyte cell membrane integrity, which leads to decreased production and increased destruction of erythrocytes, respectively. […] From a renal perspective, lead can induce a global proximal tubule dysfunction leading to a Fanconi-like syndrome, and lead also competes with uric acid for excretion in the distal tubule, leading to higher blood concentrations of urate, which ultimately gets deposited as urate crystals in joints and is the mechanism underlying so-called saturnine gout.

• #20 A pharmacokinetic model of lead absorption and calcium competitive dynamics | Scientific Reports

  https://www.nature.com/articles/s41598-019-50654-7

  The distribution of lead in bone reflects these mechanisms; lead tends to be more highly concentrated at bone surfaces where growth and remodeling are most active, hence the bone lead distribution is age-dependent. […] The association of lead uptake and release from bone with the normal physiological processes of bone formation and resorption means that lead biokinetics is sensitive to these processes. […] Dysfunction of the blood brain barrier (BBB) is associated with neurological and neuropsychiatric symptoms. Lead can penetrate the blood brain barrier and affect key processes of neural development and function, such as cell migration and synapse formation, as well as function of glial cells. […] Lead affects virtually all neurotransmitter systems, but most mechanistic information is available on the glutamatergic, dopaminergic, and cholinergic systems.

• #21 Scientists Discover How Lead Changes the Brain to Impair Learning and Memory | Johns Hopkins | Bloomberg School of Public Health

  https://publichealth.jhu.edu/2000/lead-change

  Scientists at the Johns Hopkins School of Public Health have identified a molecular mechanism whereby lead poisoning cripples learning and memory. […] In this study we demonstrate that lead exposure decreased the amount of NMDA receptor gene and protein in a part of the brain called the hippocampus. This change is associated with impairments of nerve communication in the brain and of learning. […] This experiment showed that long-term exposure to lead in adult rats alters the expression of particular genes and proteins that make up the NMDA receptor. […] „We believe that lead, by decreasing these NMDA receptors, is interfering with calcium’s entry into the neuron,” says first author Michelle K. Nihei, PhD, research associate, Environmental Health Sciences, Johns Hopkins School of Public Health. „This is noteworthy since calcium is responsible for a huge cascade of cellular signals that ultimately propagate information and continue the nerve impulse on to the next synapse and neuron.” […] This was the first study to show not only that the NMDA receptor in animals was changed by lead, but also that the problems in learning and within the neuronal connections themselves were due to lead poisoning.

• #22 Lead Toxicity – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK541097/

  From a hematologic perspective, lead causes anemia by interfering with the function of several enzymes involved in heme synthesis as well as enzymes involved in maintaining erythrocyte cell membrane integrity, which leads to decreased production and increased destruction of erythrocytes, respectively. […] The classic appearance of basophilic stippling is thought to represent clumps of degraded RNA, which is normally cleared by an enzyme known as pyrimidine-5-nucleotidase that is inhibited by lead. […] From a renal perspective, lead can induce a global proximal tubule dysfunction leading to a Fanconi-like syndrome, and lead also competes with uric acid for excretion in the distal tubule, leading to higher blood concentrations of urate, which ultimately gets deposited as urate crystals in joints and is the mechanism underlying so-called saturnine gout. […] Lead is also known to be associated with the development of hypertension and subsequent cardiovascular disease; the mechanism is likely multifactorial and may involve increasing serum renin concentrations and activity as well as the development of neuropathy of the peripheral autonomic nervous system. […] Lead also has a multitude of effects on the endocrine system, including impairing thyroid function, growth and skeletal development, and reproduction. […] Finally, though the mechanism remains poorly understood, lead is very clearly associated with GI symptoms such as abdominal pain, constipation, and anorexia.

• #23 Lead Toxicity | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/30343

  The most severe neurologic manifestations of lead toxicity such as seizures and coma occur in acute lead encephalopathy, which is thought to be at least in part secondary to lead-induced cerebral microvascular changes leading to cerebral edema and resultant increased intracranial pressure. […] From a hematologic perspective, lead causes anemia by interfering with the function of several enzymes involved in heme synthesis as well as enzymes involved in maintaining erythrocyte cell membrane integrity, which leads to decreased production and increased destruction of erythrocytes, respectively. […] From a renal perspective, lead can induce a global proximal tubule dysfunction leading to a Fanconi-like syndrome, and lead also competes with uric acid for excretion in the distal tubule, leading to higher blood concentrations of urate, which ultimately gets deposited as urate crystals in joints and is the mechanism underlying so-called saturnine gout.

• #24 Lead Toxicity – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK541097/

  From a hematologic perspective, lead causes anemia by interfering with the function of several enzymes involved in heme synthesis as well as enzymes involved in maintaining erythrocyte cell membrane integrity, which leads to decreased production and increased destruction of erythrocytes, respectively. […] The classic appearance of basophilic stippling is thought to represent clumps of degraded RNA, which is normally cleared by an enzyme known as pyrimidine-5-nucleotidase that is inhibited by lead. […] From a renal perspective, lead can induce a global proximal tubule dysfunction leading to a Fanconi-like syndrome, and lead also competes with uric acid for excretion in the distal tubule, leading to higher blood concentrations of urate, which ultimately gets deposited as urate crystals in joints and is the mechanism underlying so-called saturnine gout. […] Lead is also known to be associated with the development of hypertension and subsequent cardiovascular disease; the mechanism is likely multifactorial and may involve increasing serum renin concentrations and activity as well as the development of neuropathy of the peripheral autonomic nervous system. […] Lead also has a multitude of effects on the endocrine system, including impairing thyroid function, growth and skeletal development, and reproduction. […] Finally, though the mechanism remains poorly understood, lead is very clearly associated with GI symptoms such as abdominal pain, constipation, and anorexia.

• #25 Lead Toxicity – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK541097/

  From a hematologic perspective, lead causes anemia by interfering with the function of several enzymes involved in heme synthesis as well as enzymes involved in maintaining erythrocyte cell membrane integrity, which leads to decreased production and increased destruction of erythrocytes, respectively. […] The classic appearance of basophilic stippling is thought to represent clumps of degraded RNA, which is normally cleared by an enzyme known as pyrimidine-5-nucleotidase that is inhibited by lead. […] From a renal perspective, lead can induce a global proximal tubule dysfunction leading to a Fanconi-like syndrome, and lead also competes with uric acid for excretion in the distal tubule, leading to higher blood concentrations of urate, which ultimately gets deposited as urate crystals in joints and is the mechanism underlying so-called saturnine gout. […] Lead is also known to be associated with the development of hypertension and subsequent cardiovascular disease; the mechanism is likely multifactorial and may involve increasing serum renin concentrations and activity as well as the development of neuropathy of the peripheral autonomic nervous system. […] Lead also has a multitude of effects on the endocrine system, including impairing thyroid function, growth and skeletal development, and reproduction. […] Finally, though the mechanism remains poorly understood, lead is very clearly associated with GI symptoms such as abdominal pain, constipation, and anorexia.

• #26 Lead Toxicity | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/30343

  The most severe neurologic manifestations of lead toxicity such as seizures and coma occur in acute lead encephalopathy, which is thought to be at least in part secondary to lead-induced cerebral microvascular changes leading to cerebral edema and resultant increased intracranial pressure. […] From a hematologic perspective, lead causes anemia by interfering with the function of several enzymes involved in heme synthesis as well as enzymes involved in maintaining erythrocyte cell membrane integrity, which leads to decreased production and increased destruction of erythrocytes, respectively. […] From a renal perspective, lead can induce a global proximal tubule dysfunction leading to a Fanconi-like syndrome, and lead also competes with uric acid for excretion in the distal tubule, leading to higher blood concentrations of urate, which ultimately gets deposited as urate crystals in joints and is the mechanism underlying so-called saturnine gout.

• #27 Lead Toxicity – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK541097/

  From a hematologic perspective, lead causes anemia by interfering with the function of several enzymes involved in heme synthesis as well as enzymes involved in maintaining erythrocyte cell membrane integrity, which leads to decreased production and increased destruction of erythrocytes, respectively. […] The classic appearance of basophilic stippling is thought to represent clumps of degraded RNA, which is normally cleared by an enzyme known as pyrimidine-5-nucleotidase that is inhibited by lead. […] From a renal perspective, lead can induce a global proximal tubule dysfunction leading to a Fanconi-like syndrome, and lead also competes with uric acid for excretion in the distal tubule, leading to higher blood concentrations of urate, which ultimately gets deposited as urate crystals in joints and is the mechanism underlying so-called saturnine gout. […] Lead is also known to be associated with the development of hypertension and subsequent cardiovascular disease; the mechanism is likely multifactorial and may involve increasing serum renin concentrations and activity as well as the development of neuropathy of the peripheral autonomic nervous system. […] Lead also has a multitude of effects on the endocrine system, including impairing thyroid function, growth and skeletal development, and reproduction. […] Finally, though the mechanism remains poorly understood, lead is very clearly associated with GI symptoms such as abdominal pain, constipation, and anorexia.

• #28 Lead Toxicity | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/30343

  Lead is also known to be associated with the development of hypertension and subsequent cardiovascular disease; the mechanism is likely multifactorial and may involve increasing serum renin concentrations and activity as well as the development of neuropathy of the peripheral autonomic nervous system. […] Lead also has a multitude of effects on the endocrine system, including impairing thyroid function, growth and skeletal development, and reproduction. […] Finally, though the mechanism remains poorly understood, lead is very clearly associated with GI symptoms such as abdominal pain, constipation, and anorexia.

• #29 Environmental Medicine Matters » Mechanisms of lead-induced poisoning

  http://www.csn-deutschland.de/blog/en/mechanisms-of-lead-induced-poisoning/

  Population studies have demonstrated a link between lead exposure and subsequent development of hypertension and cardiovascular disease. The vascular endothelium is now regarded as the main target organ for the toxic effect of lead. Lead affects the vasoactive function of endothelium through the increased production of reactive oxygen species, inactivation of endogenous nitric oxide and downregulation of soluble guanylate cyclase by reactive oxygen species, leading to a limiting nitric oxide availability, impairing nitric oxide signaling. […] This review summarizes recent findings of the mechanism of the lead-induced toxicity and possibilities of its prevention.

• #30 Lead Toxicity – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK541097/

  From a hematologic perspective, lead causes anemia by interfering with the function of several enzymes involved in heme synthesis as well as enzymes involved in maintaining erythrocyte cell membrane integrity, which leads to decreased production and increased destruction of erythrocytes, respectively. […] The classic appearance of basophilic stippling is thought to represent clumps of degraded RNA, which is normally cleared by an enzyme known as pyrimidine-5-nucleotidase that is inhibited by lead. […] From a renal perspective, lead can induce a global proximal tubule dysfunction leading to a Fanconi-like syndrome, and lead also competes with uric acid for excretion in the distal tubule, leading to higher blood concentrations of urate, which ultimately gets deposited as urate crystals in joints and is the mechanism underlying so-called saturnine gout. […] Lead is also known to be associated with the development of hypertension and subsequent cardiovascular disease; the mechanism is likely multifactorial and may involve increasing serum renin concentrations and activity as well as the development of neuropathy of the peripheral autonomic nervous system. […] Lead also has a multitude of effects on the endocrine system, including impairing thyroid function, growth and skeletal development, and reproduction. […] Finally, though the mechanism remains poorly understood, lead is very clearly associated with GI symptoms such as abdominal pain, constipation, and anorexia.

• #31 Lead Toxicity | Treatment & Management | Point of Care

  https://www.statpearls.com/point-of-care/30343

  Lead is also known to be associated with the development of hypertension and subsequent cardiovascular disease; the mechanism is likely multifactorial and may involve increasing serum renin concentrations and activity as well as the development of neuropathy of the peripheral autonomic nervous system. […] Lead also has a multitude of effects on the endocrine system, including impairing thyroid function, growth and skeletal development, and reproduction. […] Finally, though the mechanism remains poorly understood, lead is very clearly associated with GI symptoms such as abdominal pain, constipation, and anorexia.

• #32 Lead poisoning; a neglected potential diagnosis in abdominal pain | BMC Gastroenterology | Full Text

  https://bmcgastroenterol.biomedcentral.com/articles/10.1186/s12876-020-01284-1

  Lead can cause abdominal pain through several mechanisms. Lead will negatively affect the motility of intestines. […] A significant correlation between constipation and lead poisoning was revealed in this study. […] There was also an association between platelet (PLT) count and BLL. […] A significant correlation between lead poisoning and lab tests. […] Lead interferes with the production of heme. […] Presence of paresthesia is due to the neuropathic effects of lead. […] Lead also disrupts the fluid normal hemostasis in neurons which results in high cellular pressure and consequent segmental demyelination in neurons. […] Lead poisoning should be considered as a potential diagnosis in patients with positive history of opium or ayurvedic medicine intake; however, differential diagnosis of lead poisoning in abdominal pain should be correlated with local epidemiologic data on lead poisoning.

• #33 Immunological effects of occupational exposure to lead (Review)

  https://www.spandidos-publications.com/10.3892/mmr.2017.6381

  It is well-known that occupational and environmental exposure to several factors, including benzene, heavy metals, chemicals and mineral fibers, is associated with the risk of developing a great number of diseases. […] However, little is known about the influence of heavy metals, such as lead, on the immune system in human populations. Lead is a heavy metal still used in many industrial activities. Human exposure to lead can induce various biological effects depending upon the level and duration of exposure, such as toxic effects on haematological, cardiovascular, nervous and reproductive systems. Several studies demonstrated that exposure to lead is associated to toxic effects also on the immune system, thus increasing the incidence of allergy, infectious disease, autoimmunity or cancer.

• #34 Immunological effects of occupational exposure to lead (Review)

  https://www.spandidos-publications.com/10.3892/mmr.2017.6381

  CD4+ Th cell function is mostly sensitive to the immunotoxic effects of lead. Several studies have demonstrated that lead is able to improve Th2 cell development and affect Th1 cell proliferation. […] However, the exact mechanisms of lead interactions with the immune system in humans still remain unclear. […] It is well-established that exposure to lead can promote the development of several diseases and disorders through different mechanisms of toxicity. The hypothesis that the immune system represents a critical target for lead-induced toxicity has been suggested by recent epidemiological and experimental studies. In particular, lead can affect both cellular and humoral immune response by altering Th cell function and increasing susceptibility to the development of autoimmunity and hypersensitivity.

• #35 Lead Toxicity: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/242605-overview

  The major mechanism of lead toxicity is due to increased generation of reactive oxygen species (ROS) and interference with generation of antioxidants. Lead causes the generation of ROS like hydroperoxide, hydrogen peroxide, and singlet oxygen. […] Lead inactivates glutathione by binding to GSHs sulfhydryl group, which causes GSH replenishment to become inefficient, thereby increasing oxidative stress. Lead also interferes with the activity of other antioxidant enzymes including superoxide dismutase and catalase. The increase in oxidative stress leads to cell membrane damage due to lipid peroxidation. […] The effects of lead poisoning on the brain are manifold and include delayed or reversed development, permanent learning disabilities, seizures, coma, and even death. The long-term effect of lead exposure is maximal during the first 2 or 3 years of life, when the developing brain is in a critical formative stage.

• #36 Lead (Pb) Toxicity: What Are Possible Health Effects from Lead Exposure? | Environmental Medicine | ATSDR

  https://archive.cdc.gov/www_atsdr_cdc_gov/csem/leadtoxicity/physiological_effects.html

  There is no identified threshold or safe level of lead in blood. […] In children, there is no identified threshold or safe blood lead level below which no risk of poor developmental or intellectual function is expected. […] Lead inhibits the bodies of growing children from absorbing iron, zinc and calcium, minerals essential to proper brain and nerve development. […] Acute exposure to very high levels of lead may produce encephalopathy in children. […] Adverse health effects occur in children at BLLs 5 g/dL. […] The neurological effects in an adult exposed to lead as an adult can be neuropathy, and may be different from those of an adult exposed to lead as a child when the brain was developing. […] Lead inhibits the body’s ability to make hemoglobin by interfering with several enzymatic steps in the heme synthesis pathway.

• #37 Lead poisoning could reduce gene expression in humans | ScienceDaily

  https://www.sciencedaily.com/releases/2020/08/200807102334.htm

  Scientists have unveiled a correlation between high blood lead levels in children and methylation of genes involved in haem synthesis and carcinogenesis, indicating a previously unknown mechanism for lead poisoning. […] Lead poisoning causes symptoms such as abdominal pain, kidney failure and infertility, among others, but the most damaging effects are seen in children, where it causes neurological and developmental deterioration; however, a number of mechanisms behind it have been elusive. […] Increased blood lead levels correlated positively with aberrant, increased methylation of DNA responsible for the expression of genes. The genes affected were ALAD, which synthesizes a key compound in the development of red blood cells; and p16, a tumour suppressor gene, which is frequently inactivated in different types of cancer. […] This study has established the correlation between blood lead levels and aberrant methylation of DNA.

• #38 Azthena logo with the word Azthena

  https://www.news-medical.net/health/Lead-Poisoning-Pathophysiology.aspx

  Lead circulates in the body bound to red blood cells. O nly a small fraction is present in the plasma. However, if the level of lead in the blood exceeds 2.9 mol/L, red cell binding becomes saturated, meaning the fraction of lead in plasma begins to increase. Lead in the plasma gradually gets distributed to various organs and tissues. B ecause the process is slow, it usually takes long-term exposure over months or years before clinical toxicity occurs. […] The clinical toxicity eventually observed as a result of lead poisoning occurs due to lead distribution to target tissues, especially the nervous system, bone marrow and kidneys. Lead poisoning results in various different health problems including hypertension, coronary artery disease, peripheral artery disease and stroke, although the underlying mechanisms involved are not fully understood.

• #39

  https://www.who.int/news-room/fact-sheets/detail/lead-poisoning-and-health

  Lead is distributed to the brain, liver, kidney and bones. It is stored in the teeth and bones, where it can accumulate over time. […] Once lead enters the body, it is distributed to organs including the brain, kidneys, liver and bones. Lead is stored in the teeth and bones, where it accumulates over time. Lead stored in bone may be released into the blood during pregnancy and expose the fetus. […] Lead exposure can have serious consequences for the health of children. Exposure to very high levels of lead can severely damage the brain and central nervous system causing coma, convulsions and even death. Children who survive severe lead poisoning may be left with permanent intellectual disability and behavioural disorders. […] There is no known safe blood lead concentration; even blood lead concentrations as low as 3.5 g/dL may be associated with decreased intelligence in children, behavioural difficulties and learning problems.

• #40 Azthena logo with the word Azthena

  https://www.news-medical.net/health/Lead-Poisoning-Pathophysiology.aspx

  Lead circulates in the body bound to red blood cells. O nly a small fraction is present in the plasma. However, if the level of lead in the blood exceeds 2.9 mol/L, red cell binding becomes saturated, meaning the fraction of lead in plasma begins to increase. Lead in the plasma gradually gets distributed to various organs and tissues. B ecause the process is slow, it usually takes long-term exposure over months or years before clinical toxicity occurs. […] The clinical toxicity eventually observed as a result of lead poisoning occurs due to lead distribution to target tissues, especially the nervous system, bone marrow and kidneys. Lead poisoning results in various different health problems including hypertension, coronary artery disease, peripheral artery disease and stroke, although the underlying mechanisms involved are not fully understood.

• #41 Lead poisoning | PPT

  https://www.slideshare.net/SajadAlramahy/lead-poisoning-7794639

  Lead poisoning is a medical condition caused by increased levels of the heavy metal lead in the body, and this can interfere with a variety of body processes and causes toxicity to many organs and tissues. […] Lead may be taken in through direct contact with mouth, nose, and eyes, and through breaks in the skin. Organic lead can be absorbed through the skin to a limit extend while The main sources of absorption of inorganic lead are from ingestion and inhalation. The main body compartments that store lead are the blood, soft tissues, and bone; the half-life of lead in these tissues is measured in weeks for blood, months for soft tissues, and years for bone. […] In adults, 94% of absorbed lead is deposited in the bones and teeth, but children only store 70% in this manner, a fact which may partially account for the more serious health effects on children.

• #42 Lead poisoning | PPT

  https://www.slideshare.net/SajadAlramahy/lead-poisoning-7794639

  Lead poisoning is a medical condition caused by increased levels of the heavy metal lead in the body, and this can interfere with a variety of body processes and causes toxicity to many organs and tissues. […] Lead may be taken in through direct contact with mouth, nose, and eyes, and through breaks in the skin. Organic lead can be absorbed through the skin to a limit extend while The main sources of absorption of inorganic lead are from ingestion and inhalation. The main body compartments that store lead are the blood, soft tissues, and bone; the half-life of lead in these tissues is measured in weeks for blood, months for soft tissues, and years for bone. […] In adults, 94% of absorbed lead is deposited in the bones and teeth, but children only store 70% in this manner, a fact which may partially account for the more serious health effects on children.

• #43 Lead Poisoning: A Persistent health Hazard-General and oral aspects – Biomedical and Pharmacology Journal

  https://biomedpharmajournal.org/vol10no1/lead-poisoning-a-persistent-health-hazard-general-and-oral-aspects/

  After absorption, a major proportion of lead gets bound to various body tissues, like hard tissues (dense bone, hair, teeth, etc.), soft tissue (brain, kidney, bone marrow, etc.). […] Bones are the primary reservoir of lead content (95%) where half life of lead is decades long. Release of lead from the bones also serves as a persistent source of toxicity even after the cessation of any external source of lead toxicity. […] Effects of lead have the maximum predilection for the nervous system which happens to be the most sensitive target for lead induced toxicity. Involvement of the central nervous system as well as the peripheral nervous system is quite common in lead exposure. […] There are several mechanisms by which lead exposure damages the human nervous systems. Direct effects on the nervous system are divided into morphological and pharmacological.

• #44 Azthena logo with the word Azthena

  https://www.news-medical.net/health/Lead-Poisoning-Pathophysiology.aspx

  The exact pathophysiologic mechanism of lead poisoning is not yet clear, but it is known that lead competes with other minerals in cellular systems, especially calcium and zinc. It therefore disrupts several cellular processes that depend on these minerals. Examples include: […] Lead poisoning has more damaging effects on children than it does on adults because children absorb five times more lead when exposed than adults do. The lead can also cause serious neurodevelopmental problems in children due its damaging effects on growing nerve cells and the developing brain. In children exposed to lead from birth onward, the level of lead in the blood peaks at around 18 to 24 months, which is a key period in terms of neurological development, when children are rapidly acquiring various different skills. Synapse formation between nerve cells (synaptogenesis) is also rapid during this period and some studies have indicated that inhibition of this process is one of the main pathological mechanisms that leads to nervous system injury in children.

• #45 Azthena logo with the word Azthena

  https://www.news-medical.net/health/Lead-Poisoning-Pathophysiology.aspx

  The exact pathophysiologic mechanism of lead poisoning is not yet clear, but it is known that lead competes with other minerals in cellular systems, especially calcium and zinc. It therefore disrupts several cellular processes that depend on these minerals. Examples include: […] Lead poisoning has more damaging effects on children than it does on adults because children absorb five times more lead when exposed than adults do. The lead can also cause serious neurodevelopmental problems in children due its damaging effects on growing nerve cells and the developing brain. In children exposed to lead from birth onward, the level of lead in the blood peaks at around 18 to 24 months, which is a key period in terms of neurological development, when children are rapidly acquiring various different skills. Synapse formation between nerve cells (synaptogenesis) is also rapid during this period and some studies have indicated that inhibition of this process is one of the main pathological mechanisms that leads to nervous system injury in children.

• #46 A pharmacokinetic model of lead absorption and calcium competitive dynamics | Scientific Reports

  https://www.nature.com/articles/s41598-019-50654-7

  Lead affects long term potentiation (the neurophysiological substrate for learning and storing information) in three-fold way: by increasing its threshold, by reducing its magnitude and by shortening its duration. […] The BBB normally excludes plasma proteins and many organic molecules, and limits the passage of ions. With disruption of this barrier, molecules, ions and water enter the brain more freely and, given the slow lymphatic drainage, lead to edema and increased intracranial pressure. […] The particular vulnerability of the fetus and infant to the neurotoxicity of lead may be due in part to immaturity of the blood-brain barrier and to the lack of the high-affinity lead-binding protein in astroglia, which sequester lead.

• #47 Evaluation of Blood Lead Levels and Their Effects on Hematological Parameters and Renal Function in Iranian Lead Mine Workers

  https://brieflands.com/articles/healthscope-95917

  Lead toxicity has become a growing health concern in countries such as Iran. However, little information is available on the assessment and evaluation of the health effects of lead exposure in mine workers. […] The present study assessed the occupational exposure to lead and examine the association of blood lead (PbB) levels with hematological and kidney function parameters in mine workers. […] The results showed a linear and significant relationship between the PbB level and B-ZPP, U-ALA, U-coproporphyrin, and U-creatinine levels in states of PbB levels 20 g/dL in a time and dose-dependent manner. A significant relationship was observed between the PbB level and the years of occupational exposure to lead and the B-urea level (P-value 0.03). […] Chronic occupational exposure to lead decreased hematocrit, RDW-CV, MCV, MCH, and HGB values but did not significantly change RBC counts. Therefore, a regular assessment of routine blood parameters (such as CBC and ZPP) and renal function indices can be effectively used to monitor the toxic effects of lead exposure.

• #48 Evaluation of Blood Lead Levels and Their Effects on Hematological Parameters and Renal Function in Iranian Lead Mine Workers

  https://brieflands.com/articles/healthscope-95917

  The critical effects of lead in the body are mainly attributed to its interference with numerous enzymes involved in heme synthesis, such as the inhibition of -aminolevulinic acid dehydratase (ALAD), and changes in some metabolite concentrations (e.g., delta-aminolevulinic acid in the urine (ALA-U), coproporphyrin in urine (CP), and zinc protoporphyrin (ZPP) in the blood). […] It has been reported that acute exposure to a high concentration of lead can cause proximal tubular damage, glycosuria, and aminoaciduria. Moreover, chronic occupational exposure to lead is associated with a high incidence of renal dysfunction, which is characterized by glomerular and tubulointerstitial changes (changes in blood and urinary creatinine and blood urea levels), resulting in chronic renal failure, hypertension, hyperuricemia, and gout. […] The results indicated a significant correlation between the PbB level and B-creatinine level and urinary creatinine. […] Therefore, in addition to PbB levels, the years of exposure to lead should be considered an important parameter in evaluating lead-induced renal disorders.

• #49 Lead Toxicity – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK541097/

  Lead poisoning Pathogenesis, mechanism […] Lead interacts with human physiology in two significant ways: it has a strong affinity for sulfhydryl groups and electron donor groups in general, such that lead ends up bound to and affecting a wide range of proteins. […] Because of its similarity to other divalent cations like calcium and zinc, it interferes with the vast array of cellular mechanisms that are regulated by and mediated by these cations. […] Because of the ubiquity of electron donor groups and divalent cations throughout the human body, the pathophysiology of lead toxicity is quite complex and involves virtually every organ system. […] From a neurologic perspective, lead is thought to undermine the normal synaptic pruning process in young brains, likely underlying the cognitive and behavioral changes seen in young children with excessive lead exposure. […] Peripheral neuropathy is a common manifestation of chronic lead toxicity in adults, but the mechanism underlying its development is poorly understood. […] The most severe neurologic manifestations of lead toxicity such as seizures and coma occur in acute lead encephalopathy, which is thought to be at least in part secondary to lead-induced cerebral microvascular changes leading to cerebral edema and resultant increased intracranial pressure.

• #50 Lead Toxicity: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/242605-overview

  The major mechanism of lead toxicity is due to increased generation of reactive oxygen species (ROS) and interference with generation of antioxidants. Lead causes the generation of ROS like hydroperoxide, hydrogen peroxide, and singlet oxygen. […] Lead inactivates glutathione by binding to GSHs sulfhydryl group, which causes GSH replenishment to become inefficient, thereby increasing oxidative stress. Lead also interferes with the activity of other antioxidant enzymes including superoxide dismutase and catalase. The increase in oxidative stress leads to cell membrane damage due to lipid peroxidation. […] The effects of lead poisoning on the brain are manifold and include delayed or reversed development, permanent learning disabilities, seizures, coma, and even death. The long-term effect of lead exposure is maximal during the first 2 or 3 years of life, when the developing brain is in a critical formative stage.

• #51 Mechanisms of lead-induced poisoning – PubMed

  https://pubmed.ncbi.nlm.nih.gov/19644200/

  Lead is a ubiquitous environmental toxin that is capable of causing numerous acute and chronic circulatory, neurological, hematological, gastrointestinal, reproductive and immunological pathologies. The mechanism of lead induced toxicity is not fully understood. The prime targets to lead toxicity are the heme synthesis enzymes, thiol-containing antioxidants and enzymes (superoxide dismutase, catalase, glutathione peroxidase, glucose 6-phosphate dehydrogenase and antioxidant molecules like GSH). The low blood lead levels are sufficient to inhibit the activity of these enzymes and induce generation of reactive oxygen species and intensification oxidative stress. Oxidative stress plays important role in pathogenesis of lead-induced toxicity and pathogenesis of coupled disease. The primary target of lead toxicity is the central nervous system. There are different cellular, intracellular and molecular mechanisms of lead neurotoxicity: such as induction of oxidative stress, intensification of apoptosis of neurocites, interfering with Ca(2+) dependent enzyme like nitric oxide synthase.

• #52 Lead Toxicity – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK541097/

  Lead poisoning Pathogenesis, mechanism […] Lead interacts with human physiology in two significant ways: it has a strong affinity for sulfhydryl groups and electron donor groups in general, such that lead ends up bound to and affecting a wide range of proteins. […] Because of its similarity to other divalent cations like calcium and zinc, it interferes with the vast array of cellular mechanisms that are regulated by and mediated by these cations. […] Because of the ubiquity of electron donor groups and divalent cations throughout the human body, the pathophysiology of lead toxicity is quite complex and involves virtually every organ system. […] From a neurologic perspective, lead is thought to undermine the normal synaptic pruning process in young brains, likely underlying the cognitive and behavioral changes seen in young children with excessive lead exposure. […] Peripheral neuropathy is a common manifestation of chronic lead toxicity in adults, but the mechanism underlying its development is poorly understood. […] The most severe neurologic manifestations of lead toxicity such as seizures and coma occur in acute lead encephalopathy, which is thought to be at least in part secondary to lead-induced cerebral microvascular changes leading to cerebral edema and resultant increased intracranial pressure.

• #53 Lead poisoning – Wikipedia

  https://en.wikipedia.org/wiki/Lead_poisoning

  The US Centers for Disease Control and Prevention and the World Health Organization state that a blood lead level of 10 g/dL or above is a cause for concern; however, lead may impair development and have harmful health effects even at lower levels, and there is no known safe exposure level. […] The primary cause of lead’s toxicity is its interference with a variety of enzymes because it binds to sulfhydryl groups found on many enzymes. Part of lead’s toxicity results from its ability to mimic other metals that take part in biological processes, which act as cofactors in many enzymatic reactions, displacing them at the enzymes on which they act. Lead is able to bind to and interact with many of the same enzymes as these metals but, due to its differing chemistry, does not properly function as a cofactor, thus interfering with the enzyme’s ability to catalyze its normal reaction or reactions.

• #54 Lead Toxicity – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK541097/

  From a hematologic perspective, lead causes anemia by interfering with the function of several enzymes involved in heme synthesis as well as enzymes involved in maintaining erythrocyte cell membrane integrity, which leads to decreased production and increased destruction of erythrocytes, respectively. […] The classic appearance of basophilic stippling is thought to represent clumps of degraded RNA, which is normally cleared by an enzyme known as pyrimidine-5-nucleotidase that is inhibited by lead. […] From a renal perspective, lead can induce a global proximal tubule dysfunction leading to a Fanconi-like syndrome, and lead also competes with uric acid for excretion in the distal tubule, leading to higher blood concentrations of urate, which ultimately gets deposited as urate crystals in joints and is the mechanism underlying so-called saturnine gout. […] Lead is also known to be associated with the development of hypertension and subsequent cardiovascular disease; the mechanism is likely multifactorial and may involve increasing serum renin concentrations and activity as well as the development of neuropathy of the peripheral autonomic nervous system. […] Lead also has a multitude of effects on the endocrine system, including impairing thyroid function, growth and skeletal development, and reproduction. […] Finally, though the mechanism remains poorly understood, lead is very clearly associated with GI symptoms such as abdominal pain, constipation, and anorexia.

• #55 Lead poisoning pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Lead_poisoning_pathophysiology

  Lead has no known physiologically relevant role in the body. […] The toxicity of lead comes from its ability to mimic other biologically important metals, most notably calcium, iron and zinc which act as cofactors in many enzymatic reactions. […] Following ingestion, lead is able to bind to and interact with many of the same enzymes as these are metals, but due to its differing chemistry, does not properly function as a co-factor, thus interfering with the enzyme’s ability to catalyze its normal reaction(s). […] Lead toxicity symptoms arise are thought to occur by interfering with an essential enzyme delta-AminoLevulinic Acid Dehydratase, or ALAD. ALAD is a zinc-binding protein which is important in the biosynthesis of heme, the co-factor found in hemoglobin. Lead poisoning also inhibits the enzyme ferrochelatase which catalyzes the joining of protoporphyrin IX and Fe2+ to form Heme. […] Delta -aminolevulinic acid dehydratase (ALAD) plays an important role in lead poisoning, and polymorphisms in the ALAD gene might affect the symptoms the individual patients experience.

• #56 Lead Toxicity – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK541097/

  Lead poisoning Pathogenesis, mechanism […] Lead interacts with human physiology in two significant ways: it has a strong affinity for sulfhydryl groups and electron donor groups in general, such that lead ends up bound to and affecting a wide range of proteins. […] Because of its similarity to other divalent cations like calcium and zinc, it interferes with the vast array of cellular mechanisms that are regulated by and mediated by these cations. […] Because of the ubiquity of electron donor groups and divalent cations throughout the human body, the pathophysiology of lead toxicity is quite complex and involves virtually every organ system. […] From a neurologic perspective, lead is thought to undermine the normal synaptic pruning process in young brains, likely underlying the cognitive and behavioral changes seen in young children with excessive lead exposure. […] Peripheral neuropathy is a common manifestation of chronic lead toxicity in adults, but the mechanism underlying its development is poorly understood. […] The most severe neurologic manifestations of lead toxicity such as seizures and coma occur in acute lead encephalopathy, which is thought to be at least in part secondary to lead-induced cerebral microvascular changes leading to cerebral edema and resultant increased intracranial pressure.

• #57 Lead Toxicity – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK541097/

  From a hematologic perspective, lead causes anemia by interfering with the function of several enzymes involved in heme synthesis as well as enzymes involved in maintaining erythrocyte cell membrane integrity, which leads to decreased production and increased destruction of erythrocytes, respectively. […] The classic appearance of basophilic stippling is thought to represent clumps of degraded RNA, which is normally cleared by an enzyme known as pyrimidine-5-nucleotidase that is inhibited by lead. […] From a renal perspective, lead can induce a global proximal tubule dysfunction leading to a Fanconi-like syndrome, and lead also competes with uric acid for excretion in the distal tubule, leading to higher blood concentrations of urate, which ultimately gets deposited as urate crystals in joints and is the mechanism underlying so-called saturnine gout. […] Lead is also known to be associated with the development of hypertension and subsequent cardiovascular disease; the mechanism is likely multifactorial and may involve increasing serum renin concentrations and activity as well as the development of neuropathy of the peripheral autonomic nervous system. […] Lead also has a multitude of effects on the endocrine system, including impairing thyroid function, growth and skeletal development, and reproduction. […] Finally, though the mechanism remains poorly understood, lead is very clearly associated with GI symptoms such as abdominal pain, constipation, and anorexia.

• #58 Mechanisms of lead-induced poisoning – PubMed

  https://pubmed.ncbi.nlm.nih.gov/19644200/

  Population studies have demonstrated a link between lead exposure and subsequent development of hypertension and cardiovascular disease. The vascular endothelium is now regarded as the main target organ for the toxic effect of lead. Lead affects the vasoactive function of endothelium through the increased production of reactive oxygen species, inactivation of endogenous nitric oxide and downregulation of soluble guanylate cyclase by reactive oxygen species, leading to a limiting nitric oxide availability, impairing nitric oxide signaling. This review summarizes recent findings of the mechanism of the lead-induced toxicity and possibilities of its prevention.

• #59 Lead poisoning could reduce gene expression in humans | ScienceDaily

  https://www.sciencedaily.com/releases/2020/08/200807102334.htm

  Scientists have unveiled a correlation between high blood lead levels in children and methylation of genes involved in haem synthesis and carcinogenesis, indicating a previously unknown mechanism for lead poisoning. […] Lead poisoning causes symptoms such as abdominal pain, kidney failure and infertility, among others, but the most damaging effects are seen in children, where it causes neurological and developmental deterioration; however, a number of mechanisms behind it have been elusive. […] Increased blood lead levels correlated positively with aberrant, increased methylation of DNA responsible for the expression of genes. The genes affected were ALAD, which synthesizes a key compound in the development of red blood cells; and p16, a tumour suppressor gene, which is frequently inactivated in different types of cancer. […] This study has established the correlation between blood lead levels and aberrant methylation of DNA.

• #60 Immunological effects of occupational exposure to lead (Review)

  https://www.spandidos-publications.com/10.3892/mmr.2017.6381

  CD4+ Th cell function is mostly sensitive to the immunotoxic effects of lead. Several studies have demonstrated that lead is able to improve Th2 cell development and affect Th1 cell proliferation. […] However, the exact mechanisms of lead interactions with the immune system in humans still remain unclear. […] It is well-established that exposure to lead can promote the development of several diseases and disorders through different mechanisms of toxicity. The hypothesis that the immune system represents a critical target for lead-induced toxicity has been suggested by recent epidemiological and experimental studies. In particular, lead can affect both cellular and humoral immune response by altering Th cell function and increasing susceptibility to the development of autoimmunity and hypersensitivity.

• #61

  https://www.who.int/news-room/fact-sheets/detail/lead-poisoning-and-health

  Lead is distributed to the brain, liver, kidney and bones. It is stored in the teeth and bones, where it can accumulate over time. […] Once lead enters the body, it is distributed to organs including the brain, kidneys, liver and bones. Lead is stored in the teeth and bones, where it accumulates over time. Lead stored in bone may be released into the blood during pregnancy and expose the fetus. […] Lead exposure can have serious consequences for the health of children. Exposure to very high levels of lead can severely damage the brain and central nervous system causing coma, convulsions and even death. Children who survive severe lead poisoning may be left with permanent intellectual disability and behavioural disorders. […] There is no known safe blood lead concentration; even blood lead concentrations as low as 3.5 g/dL may be associated with decreased intelligence in children, behavioural difficulties and learning problems.

• #62 Lead poisoning – Wikipedia

  https://en.wikipedia.org/wiki/Lead_poisoning

  The US Centers for Disease Control and Prevention and the World Health Organization state that a blood lead level of 10 g/dL or above is a cause for concern; however, lead may impair development and have harmful health effects even at lower levels, and there is no known safe exposure level. […] The primary cause of lead’s toxicity is its interference with a variety of enzymes because it binds to sulfhydryl groups found on many enzymes. Part of lead’s toxicity results from its ability to mimic other metals that take part in biological processes, which act as cofactors in many enzymatic reactions, displacing them at the enzymes on which they act. Lead is able to bind to and interact with many of the same enzymes as these metals but, due to its differing chemistry, does not properly function as a cofactor, thus interfering with the enzyme’s ability to catalyze its normal reaction or reactions.

• #63 Lead exposure, toxicity, and poisoning in adults: Clinical manifestations and diagnosis – UpToDate

  https://www.uptodate.com/contents/lead-exposure-toxicity-and-poisoning-in-adults-clinical-manifestations-and-diagnosis

  Acute lead poisoning can present with severe symptoms of toxicity or with nonspecific signs and symptoms, depending in part on how much lead has been absorbed. […] In addition, chronic exposure to high, modest, or even low concentrations of lead may produce no symptoms but increase the risks for long-term development of adverse health outcomes. […] The consequences of lead exposure may be reduced by taking an occupational and environmental health history to identify the exposures, recognizing the early signs and symptoms of elevated blood lead levels (BLLs) and lead poisoning, having a low threshold for suspecting asymptomatic lead exposure based on an occupational and environmental history or medical findings, and checking BLL in such cases to verify the diagnosis and provide appropriate advice and treatment. […] This topic will focus on identification of sources of lead exposure and the clinical manifestation and diagnosis of short-term and long-term lead toxicity in nonpregnant adults.

Zobacz więcej