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Acute Tubular Necrosis

Acute Tubular Necrosis: Pathogenesis & clinical findings Severe systemic volume depletion (e.g., vomiting, diarrhea) Septic shock** Cardiogenic shock** Cholesterol embolization syndrome (rare) Severe hypotension ↓ Mean arterial pressure reduces renal perfusion pressure which ↓ renal blood flow Renal vascular autoregulation fails to maintain renal perfusion Tubular cell hypoxia & depletion of adenosine triphosphate (ATP) (primary energy carrier in cells) Cell ion pump failure, cell swelling, & cell membrane disruption Ischemic tubular necrosis (renal tubular cell injury secondary to ↓ blood flow) Myoglobinuria Hemoglobinuria Aminoglycosides Ethylene glycol Amphotericin Cisplatin ↓ Efficiency of kidney reabsorption & excretion Kidney removes ↓ potassium (K+) from the blood volume Hyperkalemia** (high K+ concentration in the blood) ↑ Serum K+ levels induce abnormal cardiac electrical conduction patterns & excessive cardiac excitability Fatal cardiac dysrhythmia (irregular heartbeat pattern) Kidney removes ↓ urea from the blood volume Kidney removes ↓ creatinine from the blood volume Azotemia (↑ serum urea & creatinine) Uremic toxins systemically impair neutrophil function Uremic toxins (indoxyl sulfate or paracresyl sulfate) induce oxidative stress in the brain through accumulation of reactive oxygen species (ROS) ↑ Risk of infection ROS damage neuronal membranes & ion channels & induce dysfunctional mitochondria in the brain Authors: Adam Bubelenyi Reviewers: Britney Wong Luiza Radu Jessica Revington Veronica Hammer* Braden Manns* * MD at time of publication **See corresponding Calgary Guide slide Dysfunctional brain mitochondria cannot properly metabolize purines & urea Brain cannot use any metabolic or cellular pathways requiring ATP ↓ Cerebral neuronal signaling Legend: Pathophysiology Mechanism Sign/Symptom/Lab Finding Intravenous (IV) administration of iodinated contrast medium Tumor lysis syndrome Cancer cell apoptosis (cell death) releases ↑ uric acid & phosphate Heme-containing pigments Medications Uric acid & calcium phosphate crystals precipitate in renal tubules Nephrotoxic substances damage renal tubular cells through unique mechanisms Lipid peroxidation (oxidative degradation) of lipid bilayer weakens renal tubular cell membranes Damage to mitochondria in tubular cells causes depletion of ATP Formation of oxygen free radicals in renal tubular cells Impairment of ATP- dependent processes Activation of pro-inflammatory cytokines & enzymes in the kidney ↑ Renal tubular cell permeability Disruption of protein synthesis & enzyme function in renal tubular cells Degradation of tubular cell membrane lipids & proteins Free radicals oxidize tubular cell proteins & impair structure & function Toxic tubular necrosis (renal tubular injury due to nephrotoxic substances) Acute Tubular Necrosis Acute kidney injury via renal tubular cell damage & cell death Denudation (removal of surface tissue layers) & erosion of the tubular basement membrane Kidney removes ↓ sodium (Na+) & water from the blood volume ↓ Bicarbonate reabsorption from the proximal tubule of the kidney Necrotic tubular cells fall into tubular lumen Ongoing tubule damage ↓ ability to concentrate urine solutes ↓ Bicarbonate neutralization of acids in the blood Necrotic tubular cells release intracellular contents Obstruction of tubular lumen impedes glomerular filtration ↓ Urine osmolality (low urine solute concentration) ↑ Water in blood volume dilutes Na+ serum concentration Metabolic acidosis (blood pH <7.35) Muddy brown granular casts ↓ Glomerular filtration rate (GFR) Hyponatremia** (low Na+ concentration in the blood) ↑ Na+ retention in the circulatory blood volume & ↓ Na+ excretion in the urine ↓ Urine output Accumulation of ROS activates microglia & releases pro-inflammatory cytokines ↑ Fluid retention in the circulatory system Aggressive IV fluid rehydration in septic shock or cardiogenic shock patients Cerebral inflammation ↑ oxidative damage to neurons & glial cells Fluid overload Uremic encephalopathy Pulmonary edema (excess fluid accumulation in lung alveoli & interstitium) Published November 15, 2025 on www.thecalgaryguide.com Complications Disruption of DNA & RNA synthesis within renal tubular cells Tubular epithelial cells in urine Epithelial cell casts in urine (cast composed of epithelial cells embedded in a matrix) ↓ Ability to clear bacteria in urine ↑ Risk of urinary tract infection