Poisoning with Metallic and Nonmetallic Irritants.pptx

This ppt briefly explains the clinical effects of Poisoning with Metallic and Nonmetallic Irritants.

1. Poisoning with Metallic & Non-Metallic Compounds NON-METALLIC Phosphorous METALLIC Iron Arsenic Mercury Lead Cadmium Presented by Dr. Pawan Shukla DM Toxicology Resident AIIMS Raipur 1

2. Phosphorous 2

3. Zinc & Aluminum phosphide Found in powder, paste or tablet form Low cost and highly toxic Aluminum phosphide is used as grain preservatives Anticoagulant based rodenticides causes bleeding/ Bruising MOA: Releases phosphine gas when exposed to moisture which is poisonous Upon ingestion, gastric acid convert phosphide to phosphine gas. This gas is absorbed from GIT into blood. Further causes inhibition of oxidative phosphorylation, free radical production with promotion of lipid peroxidation, and cholinesterase inhibition. Sudden death due to Cardiac arrhythmias or refractory shock and cardiac arrest 3

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5. CLINICAL FEATURES & DIAGNOSIS GI irritation: Nausea, Vomiting, hematemesis, abd pain. Shock with refractory hypotension caused by direct cardiac toxicity Cardiac arrhythmias, including bradycardia, supraventricular tachycardia, atrial fibrillation, atrial flutter, and ventricular arrhythmias Hemorrhagic pulmonary edema with tachypnea , cough, acute respiratory distress syndrome, and respiratory failure Less common features include hepatotoxicity, intravascular hemolysis with methemoglobinemia and/or kidney failure Diagnosis made by history and characteristic clinical signs. Exposed patients may also exhibit hypo or hyperkalemia and elevated lactate concentrations, although these findings are not diagnostic. 5

6. YELLOW PHOSPHOROUS Smoky stool syndrome: feces /vomitus glows in dark. ( mcq ) Phase-1: GI phase: Nausea, Vomiting, hematemesis, abd pain.Mortality is due to cardio-vascular collapse Phase-2: Symptoms seems to resolve. Lasts upto 1-2 weeks Phase-3: MODS involving mainly liver and brain encephalopathy 6

7. MANAGEMENT Gastric lavage ? Activated charcoal IV N-acetylcysteine: antioxidant Vitamin-C: antioxidant Fluid resuscitation for hypovolemic shock Treat electrolyte imbalance: hypoglycemia , hypokalemia , hypomagnesemia PLEX therapy for liver failure Vitamin-K for warfarin based rodenticide. 7

8. PLEX 8

9. 18/02 19/02 21/02 22/02 23/02 24/02 25/02 26/02 27/02 PLEX-1 PLEX-2 PLEX-3 PLEX-4 PLEX-4 TB 0.4 0.2 1.0 2.6 3.67 5.8 2.9 4.3 1.7 DB 0.1 0.2 0.3 1.45 2.14 3.3 1,45 2.6 0.88 AST 15 18 325 1299 230 199 89 187 103 ALT 17 9 86 349 97 90 52 93 62 UREA 10 14 28 19 18 10 11 6 7 CREAT 0.6 0.7 0.7 0,74 0.62 0.71 0.68 0.5 0.71 HB 12 10 9.8 10 9.5 7.6 9.0 TLC 4.4 3.5 4.9 6.2 12.3 6.9 11.5 PLT 249 133 95 77 77 60 112 PT 18.2 12.5 10.4 (11-13) INR 2.9 1.3 1.1 (0.8-1.1) APTT 31.6 66.4 19.6 (20-35) A 22 year old female patient ingested 1/4 th tube of RATOL paste on 18/02. Gastric lavage done within 2 hours. Malena developed after 4 days . Developed urine and blood infected during admission. Discharged on 03/03 after 14 days of admission. 9

10. IRON POISONING Accidental ingestion is common in children becoz of its attractive looks Intentional ingestion is common in adults mostly in females (~80%) IV iron overdose is rare and reflect dosing errors Oral iron preparations Ferrous gluconate (12 percent elemental iron) Ferrous sulfate (20 percent elemental iron) Ferrous fumarate (33 percent elemental iron) 10

11. Severe toxicity & death: Ingestion of >60mg/kg of elemental iron (suppose a female of 60kg ingested 40 tabs of Orofer-xt , means in total she has consumed 100x40tabs= 4000mg of elemental iron which is 66.6mg/kg hence fatal) Ingestion of 20-60mg/kg has low potential for Severe toxicity Clinical manifestations – The clinical features of acute iron poisoning after ingestion occur in five phases (often overlapping) I. Early gastrointestinal (GI) symptoms (persistent vomiting, hypovolemic shock, or altered mental status indicates moderate to severe poisoning) II. Latent (or relative stability) III. Shock and elevated anion gap metabolic acidosis IV. Delayed hepatotoxicity/hepatic necrosis V. Remote gastric outlet obstruction 11

12. I. Gastrointestinal ( 30 minutes to 6 hours ) Abdominal pain Vomiting (hematemesis) and diarrhea Melena Lethargy II. Latent (6 to 24 hours) Improvement in gastrointestinal symptoms III. Shock and metabolic acidosis ( 6 to 72 hours ) Hypovolemic, distributive, or cardiogenic shock with profound metabolic acidosis Respiratory failure Coagulopathy Acute kidney injury Central nervous system dysfunction IV. Hepatotoxicity (12 to 96 hours , severity is dose dependent) ■ Coagulopathy ■ Jaundice 12

13. V. Bowel obstruction (2 to 8 weeks , usually gastric outlet obstruction) Abdominal pain Vomiting Dehydration Diagnosis based upon a history of iron ingestion and clinical manifestations of poisoning. It is confirmed by the presence of visible iron pills on plain abdominal radiograph or an elevated peak serum iron level (≥500 mcg/dL [90 micromol /L]). In all Symptomatic patients Xray abdomen Plasma glucose, Serum electrolytes, RFT, LFT, CBC, Coagulation profile Peak serum iron level 4 to 6 hours after ingestion of regular iron 8 hours after ingestion of extended- release iron 3-year-old boy who ingested multiple iron tablets 13

14. Management Supportive care: Support airway, breathing, and circulation; treat hypovolemic shock with fluid boluses of normal saline (10 to 20 mL/kg) as needed Orogastric lavage - iron pills in the stomach seen in Xray Whole-bowel irrigation and Deferoxamine - iron pills visible on plain abdominal Xray and any one of the following: Symptoms of moderate to severe iron poisoning High anion gap metabolic acidosis Peak serum iron level ≥500 mcg/dL Asymptomatic or mildly symptomatic patients with >60 mg/kg elemental iron Deferoxamine: Chelating agent, IV, 15mg/kg/hour , for upto 24 hours 14

15. ARSENIC POISONING 15

16. How patients of arsenic presents A patient with rash or no signs or symptoms who has ongoing chronic arsenic exposure from drinking water, highly contaminated with arsenic A patient with non- specific symptoms ( eg , neurologic) and urine (or blood) tested for heavy metals and the total arsenic concentration is above the reference range A potential occupational exposure When using arsenic trioxide to treat a patient with promyelocytic leukemia A critically ill patient with acute inorganic arsenic or arsine gas poisoning ( very rare ) 16

17. Chemistry Arsenic is classified as a metalloid because it complexes with metals, but also reacts with other elements such as oxygen, hydrogen, chlorine, carbon, and sulfur. Arsenicals can be grouped according to their valence states: elemental (0), trivalent (+3), pentavalent (+5), and arsine gas (-3). They can further be grouped as inorganic and organic . In general, trivalent arsenicals are more toxic than pentavalent, and inorganic arsenicals are more toxic than organic. 17

18. Chemistry cntd … Elemental arsenic is rare; arsenic exists more commonly as organic or inorganic compounds. Inorganic arsenic exists in trivalent ( arsenite ; As³+) or pentavalent (arsenate; As5+) forms. Organic forms are methylated metabolites of inorganic forms. ( eg , monomethylarsonic acid, dimethylarsinic acid) 18

19. Absorption Arsenical compounds are well absorbed after ingestion or inhalation & skin The GI absorption of most water soluble trivalent and pentavalent arsenicals exceeds 90 percent Peak serum arsenic concentrations are reached approximately 30 to 60 minutes after a single oral dose. Low-level skin absorption from chronic application of arsenical products is possible, but absorption from single use is negligible. 19

20. Sources of exposure Drinking water : poisoning epidemic reported West Bengal, India, Bangladesh, USA, rural Australia Dietary ingestion: Apple & grape juice : arsenic containing pesticides Rice products : cereals, milk formulas, sweetners Chickens : to control intestinal parasites, arsenical compounds are used Ayurvedic, Homeopathic and Herbal preparations Alcohols : illicitly distilled alcohols Fish, Shellfish Occupational: Pesticide industry, Smelting & refining-dust inhalation Soil: occurs naturally, volcanic eruption 20

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22. Distribution Arsenic readily enters RBC’s and then quickly distributes, initially to the liver, kidneys, muscle and skin, and ultimately to all tissues including the brain. Clearance from blood in three phases initially very rapid ( two to three hours ) in which more than 90 percent is cleared through redistribution and renal excretion, then gradually over three hours to seven days , followed by a slower clearance of ten days or more. The rapid clearance in the first two phases explains why blood testing is less reliable than urine testing for assessing chronic exposure ; blood testing can be helpful very early after exposure in cases of acute poisoning. Arsenic is handled similar to phosphate and incorporates into tissue in place of phosphate. Chronic ingestion of small amounts of inorganic arsenic results in the highest concentration in hair, nails, skin , and tissues rich in cysteine-containing proteins. Arsenic can also cross the placenta and accumulate in the fetus. 22

23. Metabolism The majority of trivalent arsenicals are metabolized via methylation , which decreases toxicity and increases elimination. Methylated forms are excreted in the urine. ( monomethylarsonic acid (MMA) followed by dimethylarsinic acid (DMA)) Pentavalent arsenicals and arsine gas are converted to trivalent arsenicals in vivo 23

24. Mechanism of toxicity Primary target organs for arsenic toxicity are the gastrointestinal tract, skin, bone marrow, heart, vasculature, kidneys, and peripheral nervous system. Trivalent arsenicals are considered the most toxic. It bind to sulfhydryl groups on proteins, glutathione, and cysteine and interfere with numerous enzyme systems, such as those involved in cellular respiration (inhibiting pyruvate dehydrogenase), gluconeogenesis and glucose uptake, and glutathione metabolism. Trivalent arsenic ( eg , arsenic trioxide) affects cardiac repolarization, prolonging the QT interval and increasing potential for ventricular dysrhythmias . Pentavalent arsenicals inhibit adenosine triphosphate production during both glycolysis and oxidative phosphorylation by substituting for phosphate with adenosine diphosphate. 24

25. CLINICAL FEATURES Develop over months to years Malignancies , Skin changes, Cardiac effects & Neurobehvioral changes Cancers: Inorganic arsenic exposures causes lung, bladder, skin, kidney, liver and prostate cancers Hyperpigmentation of skin: Raindrop pigmentation Arsenic keratosis : palm & soles, Blackfoot disease: peripheral vascular disease 25

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27. 27 Mees Lines

28. Neurologic Numbness & tingling: particularly in soles and later in hands Pain & weakness: Unable to walk due to intense burning pain in soles Intense pain even on light touch Stocking/glove distribution CVS Dysrhythmias Hypertension Coronary artery disease, Cerebrovascular d/s, PVD Liver : fibrosis, portal hypertension Diabetes : Positive association was found Bone marrow suppression causing pancytopenia 28

29. DIAGNOSIS History & examination: detailed history of exposure, occupation Biological sampling: Urine, Hair and fingernail. Drinking water sample If exposure is recent/ongoing: Urine sample is best, not blood (24hr sample >100mg) Chronic exposure: Hair- Pubic/axillary hair Nail- finger/toe nails Other tests: LFT, RFT, ECG and Urinalysis 29

30. MANAGEMENT Prevent ongoing exposure: Most important Identify the source of exposure and remove it Chelation therapy Chelation increases excretion (BAL) End point of therapy: urinary arsenic <50mcg/L Dimercaprol(BAL). Succimer (DMSA), Unithol (DMPS) More useful in acute toxicity Less useful in chronic poisoning Also used for other metals: zinc, copper Skin lesions: keratolytic agents- salicylic acid, retinoids, nicotinamide 30

31. MERCURY 31

32. Three toxic forms of Hg: elemental, inorganic, and organic . Elemental Hg : thermometers, barometers, BP machine etc. It volatilizes at room temperature and toxicity occurs due to inhalation and is extremely dangerous . Inorganic, and organic: undergoes environmental transformation, occurs as salts. 32

33. Elemental mercury toxicity Acute inhalation of elemental mercury vapor predominantly causes interstitial pneumonitis. Chronic exposure to vapors affects nervous system that may be severe and irreversible. Dhanbury tremors Hatters shake Concussio mercuralis The diagnosis of elemental mercury toxicity is confirmed by measuring Blood mercury- Acute exposure 24- hour urine mercury- chronic exposure 33

34. Inorganic mercury toxicity The acute ingestion of inorganic mercury salts cause severe abdominal pain accompanied by a hemorrhagic gastroenteritis and severe volume depletion within several hours of ingestion. Ultimately, death may occur from cardiovascular collapse and shock. Chronic exposure to inorganic mercury salts may cause neurologic symptoms and nephrotic syndrome. The diagnosis of elemental mercury toxicity is confirmed by measuring Blood mercury- Acute exposure 24- hour urine mercury- chronic exposure (MCQ’s- Acrodynia/ Pink disease/ Swift disease, Minamata disease) 34

35. CHELATION THERAPY Preferred DMSA ( Dimercaptosuccinic acid) Dose- 10mg/kg, PO, TDS x 5days f/b BD x 14 days If patient is unable to take orally BAL (Dimercaprol or British anti-lewisite) Dose- 5mg/kg/dose, IM, every 4 hours for 48 hours Then 2.5mg/kg/dose, IM, every 6 hours for 48 hours f/b 2.5mg/kg/dose, IM, every 12 hours for 7 days MANAGEMENT OF ORGANIC MERCURY TOXICITY No effective treatment No chelators (As it increases the mobilization of mercury to the brain) 35

36. LEAD 36 Lead tetroxide, Pb 3 O 4 Lip liner- Lead sulphide

37. Can cause acute and chronic poisoning Blood lead level (BLL) is used for assessing the exposure level but symptoms vary among individuals. Among adults, major source of lead exposure is OCCUPATIONAL 37

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39. Toxicokinetic and Toxicodynamic Distributed extensively throughout tissues: bone, teeth, liver, lung, kidney, brain, and spleen Excretion: kidney. Unabsorbed lead is excreted in urine. Lead is carried bound to the RBC hence decreases the heme biosynthesis causing anemia. In bone, Pb alters circulating levels of vitamin D, affecting Ca homeostasis and osteocyte function- lead lines seen in xrays Pb substitutes for Ca as a secondary messenger in neurons, blocking voltage-gated Ca channels, inhibiting influx of Ca and subsequent release of neurotransmitter and decreases nerve conduction. Chronic poisoning- lead palsy: wrist/foot drop Lead crosses the BBB and concentrates in the gray matter cause lead encephalopathy Lead crosses the placenta 39

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41. Acute toxicity Abdominal pain- LEAD COLIC Joint/muscle aches, fatigue Decreased libido Headaches Difficulty concentrating, short-term memory deficits, and Irritability. ( These symptoms may also occur with long- term exposure of over one year) Chronic toxicity - long- term exposure may produce Anemia Decline in neurocognitive function- LEAD ENCAPHALOPATHY Tremor-  LEAD PALSY Hypertension & kidney failure- LEAD NEPHROPATHY 41

42. MANAGEMENT OF PATIENTS WITH ELEVATED BLL In patients with BLL >5 mcg/dL and ongoing exposure, regardless of symptoms, Interventions are indicated to minimize short- and long- term adverse effects. All patients with elevated BLL or exposure to lead should undergo education and exposure reduction . Chelation therapy for adult patients with a BLL >80 mcg/dL and also for patients with BLL >50 mcg/dL & significant symptoms or signs of lead toxicity In some circumstances, chelation therapy may also be appropriate for patients with  BLL >50 mcg/dl with mild symptoms 42

43. CADMIUM 43

44. Cadmium (Cd) can cause severe acute or chronic toxicity. Most cases are due to chronic exposure . Occurrence : coal burning, waste incineration, and the use of phosphate fertilizers. cigarette smoke, food consumption, drinking water, and incidental ingestion of soil Uses: pigmenting agents, resistant coating on metal, photography, nickel-Cd batteries, rubber. Smoking 20 cig/day absorbs 1mcg of cadmium via lungs Tobacco smoke (a one pack a day smoker absorbs same amount from the average daily diet) 44

45. Mechanism of Toxicity Chronic, low-level cadmium exposure can affect a variety of organs, with the kidneys and bones being the principal targets. Renal Effects May cause tubular and glomerular damage with resultant proteinuria Latency period of ~10 yrs Nephropathy is progressive & irreversible Skeletal Effects Bone lesions occur late in severe chronic poisoning Pseudo fractures Mixed pattern of Osteomalacia and osteoporosis (Itai-Itai “Ouch-Ouch” disease) Cadmium replaces calcium and phosphorus in bones 45

46. Most patients with chronic cadmium toxicity are asymptomatic for kidney disease, although they may have symptoms of osteoporosis. Patients with cadmium-associated kidney disease may have mild laboratory abnormalities that are detected as part of evaluation of unrelated presentation. Diagnosis 24 hour urine cadmium – reflects exposure over time an total body Cadmium in hair – not reliable The increased excretion of at least one tubular protein should be demonstrated to confirm the diagnosis of cadmium nephrotoxicity ( ß 2 -macroglobulin, metallothionein RBP) 46

47. Treatment No specific therapy for Cd induced CKD Cd induced osteomalacia - large doses of Vit-D In experimental studies chelators can reduce mortality, but chelation generally results in significant adverse effects 47

48. Thank You 48