Heavy Metals Poisoning (Iron) (Dar Al Uloom University) PDF

College of Medicine – ‫كلية الطب‬ Dr Asmaa F. Sharif Ph D., JMHPE, MSc., MBBCh – Course Name and ‫اﺳم ورﻗم اﻟﻣﻘرر‬ 9/23/2024 1...

College of Medicine – ‫كلية الطب‬ Dr Asmaa F. Sharif Ph D., JMHPE, MSc., MBBCh – Course Name and ‫اﺳم ورﻗم اﻟﻣﻘرر‬ 9/23/2024 1 No.  By the end of the lecture, the student should:  Circumstances & toxic dose of iron poisoning. a College of Medicine – ‫كلية الطب‬  Pathophysiology and mechanism toxicity of iron.  Clinical presentation of acute IRON toxicity.  Clinical presentation of chronic IRON toxicity.  Diagnosis & treatment of Iron Toxicity. – Course Name and ‫اﺳم ورﻗم اﻟﻣﻘرر‬ 9/23/2024 2 No.   Common & serious accidental poisoning in children under 6 years c (Many preparations & easily accessible) ocean College of Medicine – ‫كلية الطب‬  Attractive preparations  Frequently used during pregnancy & postpartum period.  suicidal attempts. L Serious iron ingestions in adults are usually associated with homicidulned – Course Name and ‫اﺳم ورﻗم اﻟﻣﻘرر‬ 9/23/2024 3 No.   Ingestions of less than 20 mg/kg of elemental iron usually cause no symptoms.  Ingestion of 20 to 60 mg/kg results in mild to moderate symptoms College of Medicine – ‫كلية الطب‬  Ingestion of more than 60 mg/kg may lead to severe morbidity. so tTaerat5098 ie Efftfentzp asiciiittir.is pplementsusedtotreatInefficiency 33 derivederomfumaricaaid.hasnisnerironcontentcomparedt.sn 12 tocauseGIside likely less usedin effect supplement Dietary 38 less likensto c auseconstipation – Course Name and ‫اﺳم ورﻗم اﻟﻣﻘرر‬ 9/23/2024 4 sateoptionfortons term No. 100 supplementation  Absorption:  Iron is absorbed in intestine. College of Medicine – ‫كلية الطب‬  Ferrous (Fe+2) form is more readily absorbed than ferric (Fe+3) iron. within cells. Distribution: a case  Iron is absorbed in ferrous form and is oxidized to ferric form  It is transported in blood bound to a protein called transferrin. of  The iron binding capacity (transferrin level) is usually 300-500 G ug/dl (TIBC) & normal serum iron level is 50-150 ug/dl. So, there is usually no free iron circulating in blood.  Citrate & ascorbate (in citrus fruits) can form complexes with too iron that ↑ absorption, while tannates in tea can ↓ absorption. 0 – Course Name and ‫اﺳم ورﻗم اﻟﻣﻘرر‬ 9/23/2024 5 No.  sm Two distinct toxic effects: mucosa (1) It causes direct caustic injury to theprimarytoheart.liver.org gastrointestinal College of Medicine – ‫كلية الطب‬ mucosa (2) It impairs cellular metabolism, primarily of the heart, liver, and central nervous system (CNS). or heart CNS liver  The caustic effects of iron on the gut cause the initial e symptoms of vomiting, diarrhea, and abdominal pain. Hemorrhagic necrosis of gastric or intestinal mucosa can lead to bleeding, perforation, and peritonitis. toxiceffett IEEE Zohair Al Aseri MD,FRCPC EM & CCM www.T FtEiIIation   Unbound (free) iron moves into cells and localizes near the mitochondrial cristae, resulting in uncoupling of co College of Medicine – ‫كلية الطب‬ oxidative phosphorylation and impairment of adenosine triphosphate synthesis. synthesis uncoupling oxidativePhosphorylation impaired ATPsynthesis  Cell membranes are injured by free radical-mediated lipid peroxidation. Zohair Al Aseri MD,FRCPC EM & CCM   Iron increases capillary permeability and induces both arteriolar and venodilation. e College of Medicine – ‫كلية الطب‬  Myocardial toxicity decreases cardiac output. bindto Ho 1reveH AidiI  Hypoperfusion and hydration of the iron molecule creates an excess of unbuffered protons, worsening metabolic acidosis.  This multitude of effects, combined with severe gastrointestinal fluid losses, can lead to the development of shock, cardiovascular collapse, and death. hypoPerfusion Anaerobicrespiration LacticAcid hydration releasemoreH Acidosis fluidloss shock cardiovascular Tunbufferedprotons Hisbelt Acidosis Zohair Al Aseri MD,FRCPC EM & collapsedeath CCM  Systems affected: GIT: potent corrosive effect College of Medicine – ‫كلية الطب‬   Liver is target organ: portal vein transports iron to liver: ◦ Iron exits and comes into contact with hepatocytes  immediate damage of hepatocytes, periportal injury & necrosis  complete necrosis  hepatic failure. ◦ Lipid peroxidation & destruction of hepatic mitochondria.  Metabolic acidosis. bATP TBPH – Course Name and ‫اﺳم ورﻗم اﻟﻣﻘرر‬ 9/23/2024 9 No.  Cardiovascular System: Shock : Vasodilatation: Iron is potent VD so free circulating iron College of Medicine – ‫كلية الطب‬  damage of BV  release of histamine & serotonin  Peripheral vasodilatation  venous pooling. Coagulation defects caused by hepatic dysfunction a bleeding tendency & direct effects of iron on clotting factors (iron inhibits thrombin). Hemorrhagic gastroenteritis. Free iron cause direct damage to heart → ↓ myocardial contractility (negative inotropic effect on myocardium). – Course Name and ‫اﺳم ورﻗم اﻟﻣﻘرر‬ 9/23/2024 10 No.   First stage: within 6 hr: Mild & moderate toxicity: (GIT): College of Medicine – ‫كلية الطب‬  Hemorrhagic gastroenteritis. c  Absence of vomiting within the first 6 hr excludes serious toxicity Severe toxicity: (poor prognosis):  Shock + metabolic acidosis.  Second stage: 6-12 hr "honeymoon phase”:  Latent period of apparent improvement. movingt Ironto liverandspleen  Redistribution of free circulating iron from intravascular space into reticuloendothelial cells & intracellular compartment cellular toxicity. 9/23/2024 11 so – Course Name and ‫اﺳم ورﻗم اﻟﻣﻘرر‬ No.  Third stage: 12-24 hr (multisystem failure/ shock stage) College of Medicine – ‫كلية الطب‬ (poor tissue perfusion, metabolic acidosis, oxidative damage) ◦ Worsening of GI hemorrhage. ◦ Coma ◦ Renal insufficiency ◦ Liver insufficiency: jaundice, coagulation defects. ◦ Progressive pulmonary dysfunction ◦ Pancreatic & hepatic injury → hyperglycemia  Fourth stage weeks: (later sequlae): liver gastric scaring & pyloric stricture a – Course Name and ‫اﺳم ورﻗم اﻟﻣﻘرر‬ 0 9/23/2024 cirrhosis, 12 No.   History of exposure.  Clinical picture: ◦ Hemorrhagic gastroenteritis College of Medicine – ‫كلية الطب‬ ◦ Metabolic acidosis ◦ Shock  Investigations:  Laboratory findings:  Screening tests: Gastric fluid + H2O2 + deferoxamine → ferrioxamine (orange red color).  Serum iron level  Abdominal radiographs: Reveal tablets or diffuse densities – Course Name and ‫اﺳم ورﻗم اﻟﻣﻘرر‬ No. 9/23/2024 13 College of Medicine – ‫كلية الطب‬ – Course Name and ‫اﺳم ورﻗم اﻟﻣﻘرر‬ 9/23/2024 14 No.   The presence of gastrointestinal symptoms suggests a potentially serious ingestion, whereas their absence is College of Medicine – ‫كلية الطب‬ reassuring.  A serum iron level measured at its peak, 3 to 5 hours after ingestion, is the most useful laboratory test to evaluate the potential severity of an iron overdose.  Sustained-release or enteric-coated preparations may have erratic absorption, so a second level 6 to 8 hours after ingestion should also be checked.  However, Treat the patient, not the numbers. Zohair Al Aseri MD,FRCPC EM & CCM  ◦ Serum iron level: normal 1501 50  50-175 ug/dL , may reach 350 ug/dL normally. College of Medicine – ‫كلية الطب‬  350-500 ug/dL. Mild-to-moderate toxicity  >500 ug/dL (Hepatotoxicity).  500-1000 ug/dL Shock & systemic toxicity. o  > 1000 ug/dL (fatal). ◦ Liver function tests ◦ acid – base assessment. – Course Name and ‫اﺳم ورﻗم اﻟﻣﻘرر‬ 9/23/2024 16 No.   Prevent further exposure  Emergency & supportive treatment. College of Medicine – ‫كلية الطب‬  Decontamination:  Syrup of ipecac is not recommended because it aggravates GI volume losses & invalidates one of the most important symptomatic monitoring parameters (vomiting).  As Iron tablets clump together as their outer coatings dissolve: Gastric lavage will be of no value & AC does not bind iron well, but it can be used if there is a co-ingestion. – Course Name and ‫اﺳم ورﻗم اﻟﻣﻘرر‬ 9/23/2024 17 No.  Gastrotomy has been performed to remove iron from the College of Medicine – ‫كلية الطب‬  stomach, Clump when coat dissolved  but the success of whole-bowel irrigation generally obviates the need to consider surgery for the sole purpose of decontamination. Zohair Al Aseri MD,FRCPC EM & CCM   For significant ingestions, whole-bowel irrigationI with a polyethylene glycol electrolyte lavage solution (PEG- ELS) is routinely recommended. College of Medicine – ‫كلية الطب‬  The solution is either taken orally or administered through a nasogastric tube. The usual rate of administration of See PEG-ELS is 20 to 40 mL/kg/hr in young children and 1.5 to 2 L/hr for teenagers or adults, continued until the rectal effluent is clear and there is no radiographic evidence of pill fragments.  Whole-bowel irrigation is contraindicated in the presence of bowel obstruction, perforation, or ileus. 000 Zohair Al Aseri MD,FRCPC EM & CCM   Enhanced elimination:  Hemodialysis and hemoperfusion are not effective in College of Medicine – ‫كلية الطب‬ removing iron due to its large volume of distribution.  Exchange transfusions 3 have been recommended for severely symptomatic patients with serum iron levels exceeding 1000 ug/dL. – Course Name and ‫اﺳم ورﻗم اﻟﻣﻘرر‬ 9/23/2024 20 No.  Specific antidote: Deferoxamine mesylate (desferal): Indications: 0 ◦ repetitive vomiting ◦ metabolic acidosis College of Medicine – ‫كلية الطب‬ ◦ mental status changes ◦ shock 0 ◦ serum iron level > 500 ug/dL hepatotoxicity Dose: Serious toxicity / serum level: >500 ug/dL: (10-15 mg/kg/hr/ 4- 12hrs IV infusion) up to 1 g/day. Mild symptoms: (90mg/kg IM) Continue treatment until clinical resolution, no urine color change or serum iron < 100 ug/dL.  Ttt for more than 24 hrs. is not routinely recommended (pulmonary. 9/23/2024 21 Ocular, auditory toxicity)  Mechanism of action: College of Medicine – ‫كلية الطب‬  Deferoxamine has very high and selective affinity for iron.  Each molecule binds tightly to one atom of non-transferrin bound iron.  + it can pass through cell walls detoxify both extracellular and intracellular labile iron pools.  The presence of ferrioxamine turns the urine a “vin rose” color, which reflects the excretion of chelated iron.  Deferoxamine is not affecting iron in hemoglobin, hemosiderin, ferritin. c – Course Name and ‫اﺳم ورﻗم اﻟﻣﻘرر‬ 9/23/2024 22 No.  Mechanism: 00  Ferritin is iron storage proteins. College of Medicine – ‫كلية الطب‬  When excess dietary iron is absorbed, body produces more ferritin.  Ferritin is greatly abundant in heart & liver, spleen, bone 0_ marrow, there is a large amount in these organs however, so excess iron causes tissue destruction.  Iron Overload is characterized by increased levels of ferritin, haemosiderin (another storage protein that mainly the result of cell damage and is often found engulfed by macrophages that are scavenging regions of damage). – Course Name and ‫اﺳم ورﻗم اﻟﻣﻘرر‬ 9/23/2024 23 No.  excessive f Accumulation Causes: of Iron  Repeated blood transfusion as in thalassemia major or sickle cell College of Medicine – ‫كلية الطب‬ disease  Rarely due to defect in (iron storage protein) causing excessive iron absorption. Effect:  Iron deposition in parenchymal tissues  fibrotic changes & functional impairment. – Course Name and ‫اﺳم ورﻗم اﻟﻣﻘرر‬ 9/23/2024 24 No. College of Medicine – ‫كلية الطب‬ – Course Name and ‫اﺳم ورﻗم اﻟﻣﻘرر‬ 9/23/2024 25 No.