Aspirin Toxicity Management Essay

The basic unit of renal system is nephron. Each nephron contains a tuft of glomerular capillaries called the glomerulus, and a long tubule.  The glomerular vessels are tucked by epithelial cells, and the all together glomerulus is encapsulated in Bowman’s capsule. Glomerular filtrate from the capillaries, travel through Bowman’s capsule into the proximal tubule.  From the proximal tubule, the filtrate rush into the Loop of Henle. Each loop comprises of a thick ascending and thin ascending loop of Henle.  A short fragment is present at the end of thick ascending loop that contains specialised epithelial cells, known as the Macula Densa. Following Macula Densa, fluid enters the distal tubule, which is followed by cortical collecting tubule and eventually to cortical collecting duct(John E Hall, PhD – 2016)

The prime function of Macula Densa is to respond to any change in volume delivery to distal tube . Aspirin Toxicity Management Essay. Changes particularly in concentration of sodium chloride are the prime stimulator of Macula densa. As with decrease concentration of sodium and chloride, it brings two changes, firstly, It decreases resistance to blood flow in the afferent arterioles, which leads to increase glomerular hydrostatic pressure and helps return GFR towards optimum level. Secondly, it stimulate juxtaglomerular cells of the afferent and efferent arterioles, to release renin . Renin when released, functions as an enzyme to increase the formation of angiotensin I, which is converted to angiotensin II. Angiotensin II are the potent vasoconstrictor which constricts efferent arterioles .  One the other hand, increased formation of angiotensin II stimulates aldosterone secretion, which act on principal cells of renal tubule.The most important function of aldosterone is to increase sodium reabsorption(John E Hall, PhD – 2016).

Of the other hormones, Antidiuretic hormone carries much importance in regulating water balance. It is produced in response to change in volume status. The most important renal action of this hormone is to increase the water permeability of the distal tubule, collecting tubule, and collecting duct epithelia. When specific cells of the cardiac atria are stretched because of increased plasma volume  and increased atrial blood pressure, they secrete a peptide called atrial natriuretic peptide (ANP). Increased levels of this peptide, inhibit the reabsorption of sodium and water by the renal tubules, especially in the collecting ducts. This eventually leads to decrease sodium and water reabsorption followed by  increase in urinary excretion, which helps to return blood volume back toward normal(John E Hall, PhD – 2016). Aspirin Toxicity Management Essay.

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Major functions of kidneys include excretion of metabolic waste products and foreign chemicals, regulation of water and electrolyte balances, regulating the change in fluid osmolality and electrolyte concentrations. It also control arterial pressure, modulate acid-base balance, regulates erythrocyte production, secretion, metabolism of important vitamins, and excretion of hormones(John E Hall, PhD – 2016).

PATHOPHYSIOLOGY:

 Acute kidney injury  – Acute kidney injury is multifactorial.  The most important causes of acute kidney injury includes tubular necrosis, nephrotoxic drugs, nephritis and any disease leading to obstruction to outflow tract. Also toxic metabolites such as analgesics, if taken in lethal doses can cause acute renal shut down. Other toxins for renal system includes antibiotics but analgesic use such as Salicylic acid accounts for majority of cases leading to acute renal failure. Acute kidney injury can be classified as seen in the table below( N. Srisawat ,2010):

Chronic kidney injury:  Chronic kidney disease (CKD) is an irreversible deterioration in renal function. It usually develops over a period of years . Important causes of chronic kidney disease include Diabetes, hypertension, obesity and  autoimmune disorders. It begins with abnormality in biochemical markers but, excessive damage eventually leads to irreversible damage to renal parenchyma.Aspirin Toxicity Management Essay.  The important function lost in chronic kidney disease include loss of the excretory, metabolic and endocrine functions of the kidney leads to the clinical symptoms and signs of renal failure. The stages of chronic kidney disease are classified according to glomerular filtration rate. Stages of chronic kidney disease include (SR Vaidya – 2018)

Renal calculi: The aggregates of crystal which are composed of calcium and phosphate with some added proteins and glycoproteins, form renal stones which are termed as renal calculi. Renal stones vary greatly in size, from sand-like particles anywhere in the urinary tract to large round stones in the bladder. Various causes which include renal disease, poor dietary compliance can predispose to renal calculi.

DIABETIC NEPHROPATHY: The most important cause leading to chronic kidney disease is Diabetes, which progresses to Diabetic nephropathy. In patients with diabetes, there is a steady advance from moderately elevated albuminuria to dipstick-positive proteinuria, in association with evolving hypertensive and progressive renal failure(Z Cao -2011).

GLOMERULONEPHRITIS: Most types of glomerulonephritis are immunologically mediated and caused by deposition of antibody occurs in many types of glomerulonephritis and testing for circulating or glomerular deposition of antibodies may aid diagnosis. Glomerulonephritis is diagnosed according histopathological appearance.

ADULT POLYCYSTIC KIDNEY DISEASE: Adult polycystic kidney disease follows autosomal dominant trait pattern. Small cysts  develop from infancy or childhood and enlarge slowly and irregularly. The surrounding normal kidney tissue is compressed and progressively damaged.

Traumatic injury (rhabdomylosis).  The common pathway for injury increase accumulation of  intracellular free ionized cytoplasmic and mitochondrial calcium. This abnormal accumulation of intracellular calcium leads to  mitochondrial dysfunction, resulting in skeletal muscle cell death. ATP depletion due to mitochondrial dysfunction causes dysfunction of the pumps and the release of intracellular muscle constituents, includinng creatine kinase  and other muscle enzymes, myoglobin, and various electrolytes(PA Torres – 2015). Aspirin Toxicity Management Essay.

BIOCHEMICAL STUDIES:

Biochemical studies related to aspirin toxicity includes Arterial blood gasses, electrolytes, urinalysis, lactate and salicylate levels. Also creatinine clearance is important to monitor renal functions.

ABG status The initial effect of salicylate is stimulation of the depth of respiration due to increased

production of carbon dioxide and greater use of oxygen. As salicylate penetrates into the central nervous system it stimulates the respiratory centre to give further increased depth and also rate of respiration. This causes the blood level of carbon dioxide to fall causing blood pH to rise and this results in respiratory alkalosis.

In response, kidneys are stimulated to excrete large amounts of bicarbonate so the blood pH falls. With subsequent increase in acidosis,  blood pH can drop too far in children or more severely-poisoned adults resulting in metabolic acidosis(AR Temple -1978)

As in this patient the ABGs shows metabolic acidosis without compensation. As the PH is acidic with decrease bicarbonate and carbon dioxide level. Also with decrease sodium suggestive of dehydration. The clinical data suggest increase lactate which is relevant with salicylate poisoning. Aspirin Toxicity Management Essay.

Serum Electrolytes: Increased excretion of bicarbonate, Na+ and K+ excretion are also increased.As the solute concentration increase which cause increase water excretion. This results in hypokalaemia and dehydration(P Gaudreault – 1982)

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Urinalyses: Test for Proteinuria to detect High levels of protein due to kidney damage..

Creatine and Blood Urea Nitrogen:   Aspirin is eliminated almost exclusively via the kidneys, so the serum creatinine concentration for any indication of renal failure and hence dialysis.As with progressive renal damage, there is increase creatinine indicating progressive renal damage.  Creatinine clearance in beneficial to monitor glomerular filtration rate. The two most widely used equations include :

GFR = urinary [S] x urine volume

plasma [S] x unit time

Lactate: Salicylates uncouple oxidative phosphorylation which results in anaerobic metabolism, resulting in accumulation of lactate.

Salicylate levels:Therapeutic serum salicylate concentrations fall between 10 to 30 mg/dL values above 40 mg/dL  are associated with toxicity.  Severe clinical detoriation with aspirin intoxication can occur after the ingestion of 10 to 30 g by adults and as little as 3 g by children.

Anion Gap: The anion gap is generally elevated in the setting of salicylate toxicity

Treatment:

Treatment priorities are (1) immediate resuscitation with stabilization of airway, breathing, and circulation; (2) correction of volume depletion and metabolic derangements; (3) GI decontamination; and (4) reduction in body salicylate burden. (GF O’Malley -‎2007) Aspirin Toxicity Management Essay.

Circulation:  Aspirin-poisoned patients may be hypotensive and aggressive volume resuscitation is warranted in such patients.

Decontamination:  Activated charcoal (AC) effectively absorbs aspirin, and at least one initial dose should be given to all alert and cooperative patients and all intubated patients via orogastric tube who present within two hours of ingestion.( PA Chyka – 2005)

Alkalinization of serum and urine: Adults with salicylate poisoning and clinical signs of toxicity be treated with alkalinization of the serum and urine(AT Proudfoot – 2004). Alkalinization or serum and urine with sodium bicarbonate is the mainstay and  is an essential component of management of the aspirin-poisoned patient . The usual initial dose of sodium bicarbonate is  given as an intravenous bolus. This is followed by a sodium bicarbonate infusion. Hypokalemia must be corrected or prevented for alkalinization to be effective.

Monitoring:  A salicylate concentration and blood gas should be drawn every one to two hours until both the serum salicylate concentration is falling and the acid-base status is stable or improving for two consecutive measurements. Urine pH and serum potassium should be checked hourly. ( PI Dargan – 2002)

Hemodialysis — The efficiency of salicylate removal can be enhanced by hemodialysis . Indications for hemodialysis include clinical deterioration or failure of improvement despite intensive supportive care, lack of success in alkalinizing serum and urine, renal insufficiency or failure, severe acid-base disturbance, altered mental status, and acute lung injury(DN Jurlink – 2015). Aspirin Toxicity Management Essay.