CAUSES OF ACIDOSIS IN POISIONING and treatment-1.pptx

Causes of acidosis poisoning and treatment and it's complications

1. CAUSES OF ACIDOSIS IN POISIONING PUSHPA.T 152

2. ACIDOSIS It is a medical condition where there is an abnormal increase in the acidity of body fluids, particularly the blood. PH level falls below 7.35 It is due to excess production of acid or failing to remove the acid produced. Acidosis is often a sign of underlying health problem like kidney disease, diabetes or lung tissue and can become fatal if left untreated.

3. Types of acidosis: Metabolic acidosis: Characterized by low arterial pH, reduced plasma bicarbonate and compensatory hyperventilation. Occurs when an acid other than carbonic acid( due to co2 retention) accumulates in the body, resulting in fall in plasma bicarbonate. Causes: renal tubular acidosis, hypoaldosteronism, methanol, uremia, lactic acidosis, ethylene glycol, salicylates..

4. PATHOPHYSIOLOGY: Decrease in bicarbonate is the primary defect. This causes respiratory response resulting in stimulation of ventilation, this causes wash off co2 through lungs. Renal response : In metabolic acidosis, the plasma bicarbonate is low and therefore, the filtered load of bicarbonate will be reduced. The renal response is distal acidification system and increase in H+ excretion. Because the renal excretion of phosphate is essentially stable, this increased net acid excretion is largely in form of NH+.

5. ANION GAP: Calculated value used to help identify the cause of metabolic acidosis and other electrolyte disturbances It represents the differences between the measured cations and the measured anions in the blood stream. Formula : Anion gap: [Na]-([Cl]+ [HCO3-]) Normal serum anion gap = 8-12mEq/L ( when measured with K+ excluded) If potassium is included : AG: [Na + k] – [ Cl + HCO3] Normal: 12 – 16mEq/L

6. The gap is used to differentiate metabolic acidosis caused by loss of HCO3- ( normal gap) from acidosis caused by organic acids such as ketoacids, lactic acid, toxins like ethylene glycol, methanol etc Types of metabolic acidosis: High anion gap metabolic acidosis(HAGMA) Normal anion gap metabolic acidosis (NAGMA)

7. High Anion Gap Metabolic Acidosis: Acidosis with an increased anion gap is most commonly seen in ketoacidosis, renal failure, lactic acidosis, where there is endogenous production of anions distinct from Cl- , HCO3-. The toxins or disease introduces extra acid dissociates -> dissociates into H+ + anions These unmeasured anions replace HCO3- as buffer, so: HCO3- decreases ANION GAP increases

8. EXAMPLES: Methanol – Methanol when it reaches the liver Methanol  formaldehyde formic acid Methanol changes to formaldehyde by alcohol dehydrogenase, Formaldehyde changes to formic acid by aldehyde dehydrogenase. Formic acid accumulates and is the unmeasured anion leads to increased anion gap leading to metabolic acidosis and optic nerve toxicity leading to visual disturbances, blindness.

9. ETHYLENE GLYCOL: Found in : antifreeze, brake fluid, de icing agents. Sweet taste accidental ingestion in children or intentional poisoning. Ethylene glycol in the liver Ethylene glycol  glycaldehyde  glycolic acid oxalic acid Glycolic acid & oxalic acid accumulates and cause severe metabolic acidosis Oxalic acid binds to ca2+ and leads to calcium oxalate crystals causes hypocalcemia and cause kidney damage.

10. Salicylates : Ex: aspirin Salicylate poisoning directly stimulates the respiratory centre in the medulla leading to hyperventilation leading to respiratory alkalosis. Later the uncoupling oxidative phosphorylation in mitochondria  cells cannot use oxygen efficiently. So, there is shift to anaerobic metabolism lactic acid accumulation. Salicylic acid itself also contributes as an unmeasured anion  high anion gap metabolic acidosis.

11. Cyanide poisoning: Sources : Industrial exposure: metal polishing, electroplating, photographic solutions, plastics, rubber. Smoke inhalation, nitroprusside infusion.

12. Mechanism: Cyanide binds to cytochrome oxidase in the mitochondrial electron transport chain. This blocks oxidative phosphorylation  cells cannot use oxygen. Oxygen remains unused in blood histotoxic hypoxia. Therefore, Cells switch to anaerobic metabolism lactic acid accumulates high anion gap metabolic acidosis

13. Hydrogen sulphide : sources : Industrial exposure: petroleum refining, paper mills, sewers, natural gas. Just like cyanide poisoning, H2S binds to cytochrome oxidase in mitochondria blocks oxidative phosphorylation  cells switch to anaerobic metabolism  lactic acid accumulation. Lactic acid= unmeasured anion  high anion gap metabolic acidosis.

14. IRON TOXICITY: Sources : Accidental ingestion of iron containing supplements in children, intentional overdose ( suicidal). Mechanism : Excess iron  generates free radicals  oxidative stress cellular damage. Direct cytotoxic effect on mitochondria  impairs oxidative phosphorylation Cells switch to anaerobic metabolism  lactic acid accumulation Lactic acid= unmeasured anion  high anion gap metabolic acidosis Iron toxicity causes tissue hypoxia leading more lactic acidosis.

15. ISONIAZID POISONING: Mechanism : INH inhibits pyridoxine metabolism  decreased GABA synthesis CNS hyperexcitability  seizures Seizures and INH toxicity  increased anaerobic metabolism lactic acid accumulation. Lactic acid = unmeasured anion high anion gap metabolic acidosis Shock is seen in severe overdose  tissue hypoxia  more lactic acidosis.

16. Normal Anion Gap Metabolic Acidosis: It is metabolic acidosis with normal anion gap It is called hyperchloremic metabolic acidosis because Cl- rises to compensate HCO3- loss. Mechanism : Loss of bicarbonate : GI loss , renal loss( proximal RTA – type 2). Failure to excrete H+ : distal RTA (type1), hypoaldosteronism. Usually less severe than HAGMA. ABG: low HCO3-, mild decrease pH, normal anion gap

17. Carbonic anhydrase inhibitors: Drugs like Acetazolamide (most common) , topiramate, zonisamide. Mechanism: Carbonic anhydrase inhibition  blocks proximal tubular bicarbonate reabsorption  HCO3- stays in the tubular lumen  excreted in urine Leads to loss of plasma bicarbonate Then, Cl- rises to maintain electroneutrality so there is normal anion gap,,, mild metabolic acidosis develops.

18. Toluene poisoning: Sources: glue, paint, industrial solvents. Mechanism : Toluene is metabolized to hippuric acid in liver, Early on  hippuric acid accumulation  high anion gap metabolic acidosis. But with chronic/ repeated exposure, Hippurate is excreted with sodium & potassium loss of HCO3- and K+ in urine This leads to renal tubular acidosis, characterized by NAGMA and hypokalemia.

19. Ammonium chloride poisoning: NH4Cl  NH4+ + Cl- in the body NH4+is metabolized in the liver  converted to urea & H+ ions This generates a net acid load (H+) & increases Cl- concentration. Results in metabolic acidosis with normal anion gap ( hyperchloremic acidosis)

20. Respiratory Acidosis: Respiratory acidosis is characterized by reduced arterial blood pH, an elevated pCO2, and increase in plasma HCO3-. Pco2- is > 45 mm Hg due to hypoventilation/ impaired CO2 excretion leading to fall in blood pH Causes : Drugs like opioids, sedatives, anaesthetics COPD, asthma, severe pneumonia, ARDS

21. Opioids : like morphine , heroin, codeine, fentanyl act on opioid receptors in the medulla, This reduces the sensitivity of chemo receptors to CO2 and hypoxia. Causing decrease in respiratory rate and shallow breathing  hypoventilation with hypoventilation, alveolar ventilation falls causing hypercapnia. Elevated CO2 levels cause increase in H+  decrease in blood pH Patient presents with : CNS depression, pinpoint pupils, bradypnea/ apnea, CO2 narcosis.

22. Barbiturates: Barbiturates like phenobarbital ,thiopental are potent GABA – A agonists At toxic doses, they suppress the medullary respiratory centers in the brainstem. This leads to decrease in respiratory rate and tidal volume causing hypoventilation. Hypoventilation leads to decrease in alveolar ventilation  hypercapnia. Leading to increase in H+ levels causing decrease in pH( respiratory acidosis)

23. Benzodiazepines : Like lorazepam , diazepam, midazolam enhance the effect of GABA- A receptors, They usually cause sedation without major respiratory depression But in overdose or when combined with alcohol , opioids, barbiturates they can suppress medullary respiratory drive. This leads decrease in respiratory rate & shallow breathing  hypercapnia leading to respiratory acidosis.

24. Alcohol poisoning: Ethanol is CNS depressant, it enhances GABA-A activity and inhibits excitatory NMDA receptors. At high levels of alcohol in blood, it suppresses the medullary respiratory centers  decrease in respiratory rate, tidal volume. Hypoventilation  decreases alveolar ventilation CO2 retention Leading to hypercapnia & respiratory acidosis. Acute alcohol poisoning leads to mixed respiratory acidosis + metabolic acidosis.

25. Organophosphates : Organophosphates like parathion, malathion inhibit acetylcholinesterase leading to accumulation of acetylcholine at muscarinic, nicotinic & CNS receptors. This causes 3 pathways leading to respiratory failure  respiratory acidosis.

26. Central respiratory depression : Excess Ach stimulates muscarinic receptors in the brain initially leads to seizures, hyperactivity. Later, CNS fatigue & depression of medullary respiratory centers hypoventilation. Neuromuscular junction blockade: Excess Ach leads to persistent depolarization of skeletal muscles causing fasciculations, weakness paralysis of respiratory muscles.

27. Muscarinic effect: causes bronchospasm, bronchorrhea, laryngospasm  airway obstruction + poor gas exchange. All these cause hypoventilation, CO2 retention leading to respiratory acidosis.

28. Succinyl choline poisoning: Succinylcholine is a depolarizing neuromuscular blocker. It acts as an Ach agonist at the neuromuscular junction Phase 1 block: continuous stimulation of nicotinic receptors leads to persistent depolarization of motor end plate Muscle fasciculations  then paralysis. Phase 2 block: Receptor becomes desensitized  prolonged paralysis

29. Paralysis of respiratory muscles ( diaphragm, intercostals) leads to apnea+ hypoventilation Causing decreased alveolar ventilation  hypercapnia Hence respiratory acidosis.

30. Snake venom: Snake venom can cause respiratory acidosis mainly when the venom has neurotoxic or myotoxic effects that impair respiration Neurotoxic venoms: Ex: kraits, cobras, Elapidae family These venoms block neuro muscular transmission at neuromuscular junction Leads to paralysis of respiratory muscles Results in hypoventilation  CO2 retention respiratory acidosis.

31. Myotoxic venoms : Like sea snakes, viper bites Cause muscle necrosis, including respiratory muscles Leads to respiratory muscle weakness/ failure. Causing respiratory acidosis due to hypoventilation causing hypercapnia.