Acute Tubular Necrosis & SIADH By Dr. Imran Aslam AP North Surgical ward MHL.

Acute Tubular Necrosis

Background Definition: An abrupt or rapid decline in the renal function. A rise in serum BUN or creatinine concentration, with or without decrease in urine output, Transient and completely reversible. Normal Urine Out Put 70ml/kg /hr

The most common cause of ARF in the renal category. causes Prerenal Renal Postrenal The most common cause of ARF in the renal category. 2nd most common cause of ARF in hospitalized patients, after prerenal azotemia. Has well defined sequence of events

Pathophysiology Initiation phase characterized by acute decrease in GFR with a sudden increase in serum Cr and BUN concentrations. Maintenance phase sustained severe reduction in GFR and the BUN and Cr continue to rise. Recovery phase, tubular function is restored, an increase in urine volume (if oliguria was present) and gradual decrease in Cr and BUN

Ischemic ATN Continuum of prerenal azotemia. Initiation phase: Hypoperfusio n initiates cell injury that often leads to cell death. Maintenance phase Lasts 1-2 weeks. Tubulo-glomerular feedback also plays a role by causing constriction of afferent arterioles by the macula densa cells, which detect and increase salt load in the distal tubules. Recovery phase, regeneration of tubular epithelial cells

Nephrotoxic ATN Shared pathophysiological features Various mechanisms include direct toxicity, intrarenal vasoconstriction, and intratubular obstruction.

Ischemic ATN Subtle necrosis

Nephrotoxic ATN Necrosis limited to sensitive areas

History A good history is very important in diagnosis of ATN. Find out about: Recent hypotension Sepsis Muscle necrosis (e.g. h/o seizure, cocaine use) Exposure to contrast or nephrotoxic medications Hypovolumia Other risk factors for development of ATN like underlying renal disease from DM, HTN, etc.

sepsis

Muscle necrosis

Causes of Ischemic ATN Systemic vasodilation – sepsis, anaphylaxis DIC Renal vasoconstriction – cyclosporine, norepinephrine, epinephrine, amphotericin B, etc Hyperviscosity syndrome

Causes of Toxic ATN Exogenous Aminoglycosides Amphotericin B Radiocontrast media Endogenous Myoglobinuria Hemoglobinuria Crystals Multiple Myeloma

Endogenous toxins

Workup Lab studies Serum chemistries: BUN and serum Cr concentrations CBC Urinalysis Ultrasound CT Scan MRI Renal USG

Treatment General treatment Prevention Avoid nephrotoxic agents Dialysis

Prognosis Patients with oliguric ATN have a worse prognosis than patients with nonoliguric ATN. Rapid increase in serum creatinine (i.e. >3 mg/dL). Of the survivors of ATN, approximately 50% will undergo into chronic state.

Syndrome of Inappropriate antidiuretic Hormone (SIADH) Syndrome of Inappropriate antidiuretic Hormone

Characteristics SIADH is characterized by: fluid retention serum hypo-osmolarity dilutional hyponatraemia hypochloremia concentrated urine in the presence of normal or increased intravascular volume normal renal function

Pathophysiology Inappropriate ADH secretion occurs when there is disregulation of cells secreting vasopressin in posterior pituitary Ectopic source- ADH-secreting tum0rs

Causes: Increased hypothalamic production Infections Meningitis, encephalitis, abscess, HIV Vascular subarachnoid or subdural hemorrhage Neoplasm Drugs Chemotherapeutic agents Pulmonary diseases Pneumonia , Tuberculosis, Acute respiratory failure ,Positive pressure ventilation, Asthma & Atelectasis Idiopathic

Signs & Symptoms Decreased / Low urine output Symptoms of hyponatraemia Lethargy, apathy, disorientation, muscle cramps, anorexia, agitation Symptoms of water toxicity nausea, vomiting, personality changes, confusion If Na < 110 mEq/L seizures, bulbar palsies, hypothermia, stupor, coma

Lethargy vomiting

Seizures Coma

Investigation Serum Na < 135 Serum osmolality low Urine Na is inappropriately high, >20 mmol/L Urine osmolality is inappropriately high, CVP is high CXR CT-Scan

Management Demeclocycline & Lithium Treatment of underlying medical condition if exists Normalize serum sodium over 24 -48 hours Warning, if increase Na is too fast, there is a risk for pontine myelinolysis Normalize serum osmolality Correct excess extravascular fluid volume Restrict fluids 3% NaCl Loop diuretics Demeclocycline & Lithium

Management Demeclocycline & lithium Both drugs are nephrotoxic Demeclocycline can cause nausea, vomiting, and photosensitivity Lithium has a variety of neuropsychiatric side effects In severe cases, haemodialysis could be used