Acute Kidney Injury - Rapid decline in renal filtration function

Acute Kidney Injury Pre Renal Adaptive response to severe volume depletion and hypotension Structurally intact nephrons Intrinsic Response to cytotoxic, ischemic, or inflammatory insults to the kidney Structural and functional damage Post Renal Obstruction to the passage of urine

Prerenal AKI Most common form of AKI 2 major causes: – Hypovolemia Renal fluid loss Decreased intake of fluids – Altered renal hemodynamics resulting in hypoperfusion Low cardiac output state due to pulmonary hpn leading to left heart failure Systemic vasodilation due to antihypertensives

Acute Kidney Injury Pre Renal Adaptive response to severe volume depletion and hypotension Structurally intact nephrons Intrinsic Response to cytotoxic, ischemic, or inflammatory insults to the kidney Structural and functional damage Post Renal Obstruction to the passage of urine

Intrinsic AKI Major causes: – Renovasculat Obstruction – Diseases of the Glomeruli or vasculature – Acute Tubular necrosis Ischemia Infection, with or without sepsis Toxins: exogenous, endogenous – Interstitial Nephritis Allergic Infection Inflammatory, nonvascular – Intratubular obstruction

ACUTE KIDNEY INJURY Tubulointerstitial disease - acute interstitial nephritis – Due to baterial, viral and other miscellaneous infection Streptococcus, staphylococcus, legionella, salmonella, Brucella, yersinia – Interstitial edema with cortical and medullary infiltration by mononuclear cells and polymorphonuclear leukocytes and patchy areas of tubule cell necrosis

– Chronic form: fibrosis, predominance of mononuclear, widespread atrophy, luminal dilatation and thickening of the tubule basement membranes – Defects in renal function Proximal tubule dysfunction – Selective reabsorptive defects – hypokalemia, – Aminoaciduria – Glycoasuria – Phosphaturia – Uricosuria – Bicarbonaturia

– Defects in urinary acidification and concentrating ability Hyperchloremic metabolic acidosis – Maximal Urine pH <5.3 – Caused by reduced capacity to generate and excrete ammonia due to reduction in renal mass

Functional consequences of tubulointerstitial disease FUNCTIONAL CONSEQUENCES OF TUBULOINTERSTITIAL DISEASE DEFECTCAUSE(S) Reduced glomerular filtration rateObliteration of microvasculature and obstruction of tubules Fanconi SyndromeDamage to proximal tubular reabsorption of glucose, amino acids, phosphate, and bicarbonate Hyperchloremic acidosis1.Reduced ammonia production 2.Inability to acidify the collecting duct fluid (distal renal tubular acidosis) 3.Proximal bicarbonate wasting Tubular or small-molecular-weight proteinuria Failure of proximal tubule protein reabsorption Polyuria, isosthenuriaDamage to medullary tubules and vasculature HyperkalemiaPotassium secretory defects including aldosterone resistance Salt wastingDistal tubular damage with impaired sodium reabsorption

Modifiers influencing the progression of renal diseases Risk factors for progressive loss of renal function – Systemic HPN – Diabetes – Activation of RAAS system

Poor cho control will aggrevate renal progression in both diabetic and non diabetics Angiotensin II produces intraglomerular HPN and stimulate fibrogenesis Aldosterone Serves as an indeoendent fibrogenic mediator of progression loss apart from its role in modulating Na and K homeostasis