Forensic Medicine and Clinical Toxicology Department Metabolic Acidosis

Forensic Medicine and Clinical Toxicology Department Metabolic Acidosis And Acid Base Balance

Acid-Base Balance n Acid-Base balance is: n the regulation of HYDROGEN ions.

Acid Base Balance n The body produces acids daily n n • • n 15, 000 mmol CO 2 50 -100 m. Eq Nonvolatile acids Cellular metabolism produce CO 2 which combines with water to form carbonic acid(H 2 CO 3)which can dissociate into H+ and HCO 3 Acidemia is state of elevated H+ concentration measured in units of ph cells have narrow p. H range within which they function optimally The lungs and kidneys attempt to maintain balance

Hydrogen ions n The more Hydrogen ions, the more acidic the solution and the LOWER the p. H n The lower Hydrogen concentration, the more alkaline the solution and the HIGHER the p. H

p. H The acidity or alkalinity of a solution is measured as p. H. n The more acidic a solution, the lower the p. H. n The more alkaline a solution , the higher the p. H. n Water has a p. H of 7 and is neutral. n The p. H of arterial blood is normally between 7. 35 and 7. 45 n

Buffer Systems n Regulate p. H by binding or releasing Hydrogen n Most important buffer system: n n Bicarbonate-Carbonic Acid Buffer System CO 2 + H 2 O <--> H 2 CO 3 <--> HCO 3 - + H+ (Blood Buffer systems act instantaneously and thus constitute the body’s first line of defense against acid-base imbalance)

Respiratory Regulation n Lungs n help regulated acid-base balance by eliminating or retaining carbon dioxide n p. H may be regulated by altering the rate and depth of respirations n changes in p. H are rapid, n occurring within minutes n normal CO 2 level n 35 to 45 mm Hg

Renal Regulation n Kidneys n the long-term regulator of acid-base balance n slower to respond may take hours or days to correct p. H § kidneys maintain balance by excreting or conserving bicarbonate and hydrogen ions n normal bicarbonate level n 22 to 26 m. Eq/L.

Factors Affecting Balance n Age n especially n Gender infants and the elderly and Body Size n amount of fat n Environmental n Lifestyle n stress Temperature

Acid Base Balance n Assessment of status via bicarbonatecarbon dioxide buffer system n CO 2 + H 2 O <--> H 2 CO 3 <--> HCO 3 - + H+ n ph = 6. 10 + log ([HCO 3] / [0. 03 x PCO 2])

Normal values of Arterial Blood Gases (ABG) n The Components n n p. H / Pa. CO 2 / Pa. O 2 / HCO 3 / O 2 sat / BE Desired Ranges n n n p. H - 7. 35 - 7. 45 Pa. CO 2 - 35 -45 mm. Hg Pa. O 2 - 80 -100 mm. Hg HCO 3 - 21 -27 O 2 sat - 95 -100% Base Excess - +/-2 m. Eq/L

Respiratory Acidosis n Mechanism n n Hypoventilation or Excess CO 2 Production Etiology COPD n Neuromuscular Disease n Respiratory Center Depression n Late ARDS n Inadequate mechanical ventilation n Sepsis or Burns n Excess carbohydrate intake n

Respiratory Alkalosis n p. H, CO 2, Ventilation n CO 2 → HCO 3 ( Cl to balance charges � hyperchloremia) n Causes n Intracerebral hemorrhage n Salicylate and Progesterone drug usage n Cirrhosis of the liver n Sepsis

Metabolic Alkalosis n n n p. H, HCO 3 PCO 2 by 0. 7 for every 1 m. Eq/L in HCO 3 Causes n Vomiting n Diuretics n Chronic diarrhea n Hypokalemia n Renal Failure

Metabolic acidosis n Metabolic acidosis is a clinical disturbance characterized by an increase in plasma acidity. blood p. H is low (less than 7. 35) due to increased production of H+ by the body or the inability of the body to form bicarbonate (HCO 3) in the kidney. Metabolic acidosis should be considered a sign of an underlying disease process. Identification of this underlying condition is essential to initiate appropriate therapy.

Metabolic acidosis n is a process that, if unchecked, leads to acedemia Its causes are diverse, and its consequences can be serious, including coma and death. Together with respiratory acidosis, it is one of the two general causes of acedemia. metabolic acidosis

Causes n n Inability to excrete the dietary H+ load n Renal failure n Hypoaldosteronism - Type 4 RTA n Diminished H+ secretion - Type 1 (distal) RTA Increased H+ load n Lactic acidosis : n n circulatory failure, drugs and toxins, and hereditary causes Ketoacidosis : n Diabetes, alcoholism, and starvation

causes n Ingestions : n Salicylates, methanol, ethylene glycol, isoniazid, iron, sulfur, toluene, ammoniumchloride, phenformin/metformin n GIT HCO 3 loss : n Diarrhea n Pancreatic, biliary, or intestinal fistulas n Ureterosigmoidostomy n Cholestyramine n Renal HCO 3 loss : n n Type 2 (proximal) RTA Acetazolamide

diagnosis n History n Metabolic acidosis can result in a variety of nonspecific changes in several organ systems, including, but not limited to, neurologic, cardiovascular, pulmonary, gastrointestinal, and musculoskeletal dysfunction. Symptoms are often specific to and a result of the underlying etiology of the metabolic acidosis.

Head, eyes, ears, nose, throat (HEENT) n Tinnitus, blurred vision, and vertigo can occur with salicylate poisoning. n Visual disturbances, dimming, photophobia, scotomata, and frank blindness can be seen in methanol intoxication. n Cardiovascular n Palpitations n Chest pain n Neurologic n Headache n Visual changes

n Pulmonary : n Subjective dyspnea from the patient's observation of hyperventilation n Gastrointestinal n Nausea and vomiting n Abdominal pain n Diarrhea n Polyphagia n Musculoskeletal n Generalized n Bone pain muscle weakness

Physical Neurologic n Cranial nerve palsies may occur with ethylene glycol intoxication. n Retinal edema may be seen in methanol ingestions. n Lethargy, stupor, and coma may occur in severe metabolic acidosis, particularly when it is associated with a toxic ingestion. n Cardiovascular: n Severe acidemia (ie, p. H <7. 10) can predispose a patient to potentially fatal ventricular arrhythmias, and it can reduce cardiac contractility and the inotropic response to catecholamines, resulting in hypotension and congestive heart failure.

n Pulmonary: n Patients with acute metabolic acidosis demonstrate tachypnea and hyperpnea as prominent physical signs. n Hyperventilation, in the absence of obvious lung disease, should alert the clinician to the possibility of an underlying metabolic acidosis. n Musculoskeletal: n Chronic metabolic acidosis (eg, uremia, renal tubular acidosis [RTA]) is associated with substantial bone disease from bone buffering of calcium carbonate. n n Long bone malformations in pediatric patients (eg, vitamin D resistant, rickets) Fractures in adult patients

Laboratory Diagnosis Arterial blood gas (ABG) 1. Look at the p. H n is the primary problem acidosis (low) or alkalosis (high) 2. Check the CO 2 (respiratory indicator) n is it less than 35 (alkalosis) or more than 45 (acidosis ) 3. Check the HCO 3 (metabolic indicator) n is it less than 22 (acidosis) or more than 26 (alkalosis)

n Serum chemistry n Sodium, potassium, chloride, and bicarbonate levels are used in the calculation of serum anion gap (SIG). Phosphate, magnesium, as well as serum albumin levels are used to calculate the SIG. n Hyperkalemia often complicates metabolic acidosis. n Glucose level is commonly elevated in DKA, and it may be low, normal, or mildly elevated in alcoholic ketoacidosis. n The BUN and creatinine levels are elevated in uremic acidosis.

n Complete blood cell count: n An elevation of the WBC count is a nonspecific finding, but it should prompt consideration of septicemia, which causes lactic acidosis. n Urinalysis: n A urine p. H is normally acidic at <5. 0. In acidemia, the urine normally becomes more acidic. If the urine p. H is above 5. 5 in the face of acidemia, this finding is consistent with a type I RTA. n Ethylene glycol toxicity may present with calcium oxalate crystals, which appear needle shaped, in the urine

n Imaging Studies n n If iron ingestion is suspected, perform imaging studies on the abdominal area, including the kidneys, ureters, and bladder. Other Tests n Anion gap (AG): Calculation of the AG is often helpful in the differential diagnosis of metabolic acidosis. The AG is equal to the difference between the plasma concentrations of the measured plasma cation (ie, Na+) and the measured anions (ie, chloride [Cl-], HCO 3 -). n AG calculation = (Na+) - ([Cl-] + [HCO 3 -])

A normal AG is traditionally listed as 8 -16 m. Eq/L, with an average value of 12. n The anion gap allows for the differentiation of 2 groups of metabolic acidosis: n Metabolic acidosis with a high AG is associated with the addition of endogenously or exogenously generated acids. n Metabolic acidosis with a normal AG is associated with the loss of HCO 3 or the failure to excrete H+ from the body. n

n High AG n Lactic acidosis - Lactate, D-lactate n Ketoacidosis - Beta-hydroxybutyrate, acetoacetate n Ingestions - Salicylate, methanol or formaldehyde (formate), ethylene glycol (glycolate, oxalate), paraldehyde (organic anions), sulfur (SO 4 -), phenformin/metformin n Pyroglutamic acidemia (5 -oxoprolinemia) n Massive rhabdomyolysis (release of H+ and organic anions from damaged muscle) n DR. MAPLES: D-DKA; R-renal; M-methanol; A-alcoholic ketoacidosis; P-paraldehyde, phenformin; L-lactic (ie, CO, HCN); E-

n Normal AG (ie, hyperchloremic acidosis) : n GI loss of HCO 3 -, diarrhea n Pancreatic fistula n Renal HCO 3 - loss - Type 2 (proximal) RTA n Renal dysfunction n Some cases of renal failure n Hypoaldosteronism (i. e. type 4 RTA) n Hyperventilation n Ingestions : n Ammonium chloride, acetazolamide, hyperalimentation fluids, some cases of ketoacidosis, particularly during treatment with fluid and insulin

n The osmolal gap is the measured plasma osmolality minus calculated osmolality. The serum osmolality is composed of all osmotically active substances including ionic and nonionic substances such as serum ions, glucose, and BUN. Other substances such as alcohols, excess serum lipids and proteins, and delivered substances such as mannitol all contribute to the serum osmolality.

n n n The calculated osmolality is : 2 X plasma [Na+] + [glucose]/18 + BUN/2. 8. Normal osmolal gap is 10 -15. Metabolic acidosis with elevated osmolal gap indicates methanol and ethylene glycol ingestions.

n Ketone level: n Elevations of ketones indicate diabetic, alcoholic, and starvation ketoacidosis. . n Serum lactate level: n Lactic acidosis is considered present if the plasma lactate level exceeds 4 -5 m. Eq/L in an acidemic patient. Salicylate levels n Therapeutic salicylate levels range up to 20 -35 mg/d. L. n Plasma levels exceeding 40 -50 mg/d. L are in the toxic range. n Plasma levels provide some information as to the severity of intoxication: 40 -60 mg/d. L is considered mild; 60 -100 mg/d. L is moderate; and greater than 100 mg/d. L is considered severe. n n The normal plasma lactate concentration is 0. 5 -1. 5 m. Eq/L.

n n Iron levels n Iron toxicity is associated with lactic acidosis. n Iron levels greater than 300 mg/d. L are considered toxic. Electrocardiography: n An ECG may be used to detect abnormalities result from the effects of electrolyte imbalances (hyperkalemia).

Treatment Emergency Department Care: n n The initial therapeutic goal for patients with severe acidemia is to raise the systemic p. H above 7. 1 -7. 2, a level at which dysrhythmias become less likely and cardiac contractility and responsiveness to catecholamines will be restored. Metabolic acidosis can be reversed by treating the underlying condition or by replacing the bicarbonate. The decision to give bicarbonate should be based upon the pathophysiology of the specific acidosis, the clinical state of the patient, and the degree of acidosis.

n Treating the underlying conditions in high AG states usually is sufficient in reversing the acidosis. n Treatment with bicarbonate is unnecessary, except in extreme cases of acidosis when the p. H is less than 7. 17. 2. n Given as slow IV infusion to lessen the effect of CO 2 generation during buffering. The goal is to restore p. H to approximately 7. 2

n Caution with bicarbonate therapy is indicated because of its potential complications, including the following: n Volume overload n Hypokalemia n CNS acidosis n Hypercapnia n Tissue hypoxia via leftward shift of hemoglobin-oxygen dissociation curve n Alkali stimulation of organic acidosis (lactate) n Overshoot alkalosis

n Consultations: Metabolic acidosis secondary to ingestions (eg, salicylate, methanol, ethylene glycol) often requires dialysis therapy, and a nephrologist should be consulted early in the case management. Toxicological consultation should also be considered in such cases. Dialysis is the preferred treatment for patients with significant metabolic acidosis in the setting of renal failure.

n Medication Many drugs may be used in the management of a patient with metabolic acidosis. They range from antibiotics for septic shock to toxin antidotes. Bicarbonate is an agent that is considered across the numerous differentials of metabolic acidosis. Its use generally is limited to severe cases of acidosis (p. H <7. 1 -7. 2). n Alkalinizing agent n This agent is used in the treatment of metabolic acidosis. n Sodium bicarbonate (Neut) n Bicarbonate ion is produced when it dissociates and neutralizes the hydrogen ions and raises urinary and blood p. H.

n Adult n n Total bicarbonate deficit = Base deficit X bicarbonate (0. 50. 8) X body weight (kg) Pediatric n The following formula may be used to estimate dose to be administered in children: HCO 3 - (m. Eq) = 0. 5 X weight (kg) X [24 - serum HCO 3 - (m. Eq/L)] Formula has many limitations, but practitioner can roughly determine amount of bicarbonate required and subsequently titrate against p. H and anion gap

Thank you