The kidneys perform several important functions including removing waste, regulating electrolytes and blood pressure, activating vitamin D, and stimulating red blood cell production. Acute renal failure refers to a sudden, usually reversible loss of kidney function over days or weeks and is commonly caused by decreased blood flow to the kidneys (pre-renal) or direct kidney damage (intrinsic). Pre-renal acute renal failure, which accounts for 60-70% of cases, is often due to low blood volume from causes like bleeding, burns, or diarrhea. It can typically be reversed by restoring blood volume and pressure through fluid resuscitation.

1. Renal failure

2. Function of the kidneys The kidneys are responsible for: 1- removing wastes from the body. 2-regulating electrolyte balance and blood pressure. 3- converting Vit D into its active form. 4-stimulating RBC production by synthesizing erythropoietin.

3. Renal failure Failure of the excretory function of the kidneys,leading to retention of nitrogenous waste products of metabolism. Failure of the regulation of fluid & electrolytes status . Failure of the endocrine function of the kidney.

4. Acute renal failure : Refers to a sudden and usually reversible loss of renal function, which develops over a period of days or weeks. Chronic renal failure : Refers to an irreversible deterioration in renal function which classically develops over a period of years

5. ACUTE RENAL FAILURE

6. ACUTE RENAL FAILURE Acute renal failure (ARF) refers to a sudden and usually reversible loss of renal function ( rapid decline in glomerular filtration rate), which develops over a period of days or weeks and is usually accompanied by a reduction in urine volume. (>50%) decrease in glomerular filtration rate (GFR) over a period of hours to days, with an accompanying accumulation of nitrogenous wastes in the body. There are many possible causes and it is frequently multifactorial. The clinical picture is often dominated by the underlying condition (e.g. septic shock, trauma).

7. ARF complicates approximately 5% of hospital admissions and up to 30% of admissions to intensive care units. Oliguria (urine output 400 mL/d) is a frequent but not invariable clinical feature (50%). ARF is usually asymptomatic and diagnosed when biochemical monitoring of hospitalized patients reveals a recent increase in blood urea and creatinine concentrations.

9. Intrinsic renal cause.

10. Post-renal cause.

11. Systemic diseases acting via one or more of these 3 categories.

12. Causes of ARF Acute Renal Failure Pre-renal Intrinsic renal Post-renal Tubular Interstitial Vascular Glomerular

14. has two major components:glomerulus tubule: proximal loop of Henle distal collecting

15. Causes of ARFPre-renal ARF Accounts for 60-70% of cases of ARF Represents physiologic response to mild-moderate renal hypoperfusion Renal parenchymal tissue is not damaged therefore rapidly reversible upon restoration of RBF and glomerular filtration pressure Elderly and those with pre-existing renal disease at increased risk

16. Causes of ARFPre-renal ARF I. Absolute decrease in effective blood volume( Hypovolemia): A. Hemorrhage, burns, dehydration B. GI fluid loss: vomiting, surgical drainage, diarrhea C. Renal fluid loss: diuretics, osmotic diuresis (e.g., diabetes mellitus), hypoadrenalism D. Sequestration in extravascular space: pancreatitis, peritonitis, trauma, burns, severe hypoalbuminemia II.Relative decrease in blood volume ( ineffective arterial volume ) Hypotention. A.Congestive heart failure B. Systemic vasodilatation: sepsis, antihypertensives, , anaphylaxis . C.Liver failure. E. massive pulmonary embolus.

17. Causes of ARF Pre-renal ARF III.Arterial occlusion (Renal artery occlusionstenosis): Bilateral thromboembolism. Thromboembolism of a solitary kidney.

18. Causes of ARF Intrinsic Renal Causes Accounts for 25-40% of cases of ARF Types: ATN ( Acute Tubular Necrosis ) 85% Interstitial nephritis 10% Acute glomerulonephritis <5% Intrarenal vascular disease <5%

19. Causes of ARFIntrinsic Renal Causes I-. Acute tubular necrosis A. Ischemia B. NephrotoxinsC.Sepsis syndrome A. Ischemia As for severeprerenal ARF (hypovolemia, low cardiac output, renal vasoconstriction, systemic vasodilatation), obstetric complications (abruptioplacentae, postpartum hemorrhage)

20. B. Nephrotoxins 1. Exogenous: Antibiotics (aminoglycosides, cephalosporin , amphotericin B ) Iodinated contrast agents. Chemotherapy (e.g., cisplatin ) Organic solvents (e.g., ethylene glycol) 2. Endogenous: Intratubular pigments ( hemoglobinuria as in hemolysis, myoglobinuria as in rhabdomyolysis). Intratubular proteins (myeloma) . Intratubular crystals( uric acid, oxalate) ( tumor lysis syndrome ).

21. Causes of ARFIntrinsic Renal Causes II. Interstitial nephritis A. Allergic: antibiotics (e.g., -lactams, sulfonamides, trimethoprim, rifampicin), nonsteroidal anti-inflammatory agents, diuretics, captopril B. Infection: bacterial (e.g., acute pyelonephritis, leptospirosis), viral (e.g., cytomegalovirus), fungal (e.g., candidiasis) C. Infiltration: lymphoma, leukemia, sarcoidosis D. Idiopathic

22. Causes of ARF Intrinsic Renal Causes III. Disease of glomeruli ( Acute Glomerulonephritis) PostinfectiousGlomerulonephritis. Anti-basement membrane antibody disease

23. IV. Vascular : Vasculitis. Malignant hypertension. Microscopic polyarteritis. Causes of ARF Intrinsic Renal Causes

24. Causes of ARF Post-renal Causes of ARF Account for 5% of cases of ARF ARF occurs when both urinary outflow tracts are obstructed or when one tract is obstructed in a patient with a single functional kidney. -Bladder outlet obstruction -Bilateral ureteral obstruction ( unusual ). Ureteral obstruction in a solitarey kidney. ( obstruction by : Calculi, blood clot, sloughed papillae, cancer, external compression e.g., retroperitoneal fibrosis) -Urethra stricture .

26. Types of Acute Renal Failure REVERSIBLE PRE-RENAL ACUTE RENAL FAILURE When haemodynamic disturbances produce acute renal dysfunction that has the potential to be rapidly reversed ( reversable ),by early recognition and treatment . ESTABLISHED ACUTE RENAL FAILURE (ATN ) May develop following severe or prolonged under-perfusion of the kidney (pre-renal ARF). In such cases, the histological pattern of acute tubular necrosis is usually seen.

27. REVERSIBLE PRE-RENAL ACUTE RENAL FAILURE When haemodynamic disturbances produce acute renal dysfunction that has the potential to be rapidly reversed ( reversable ),by early recognition and treatment .

28. REVERSIBLE PRE-RENAL ACUTE RENAL FAILURE Pathogenesis The kidney can regulate its own blood flow and GFR over a wide range of perfusion pressures. When the perfusion pressure falls-as in hypovolaemia, shock, heart failure or narrowing of the renal arteries-the resistance vessels in the kidney dilate to facilitate flow. Vasodilator prostaglandins are important. ( this mechanism is markedly impaired by NSAIDs ). If autoregulation of blood flow fails, the GFR can still be maintained by selective constriction of the post-glomerular (efferent) arteriole. This is mediated through the release of renin and generation of angiotensin II, which preferentially constricts this vessel. (ACE inhibitors interfere with this response) . More severe or prolonged under-perfusion of the kidneys may lead to failure of these compensatory mechanisms and hence an acute decline in GFR..

29. The renal tubules are intact and become hyperfunctional; that is, tubular reabsorption of sodium and water is increased, partly through physical factors associated with changes in blood and urine flow and partly through the influence of angiotensins, aldosterone and vasopressin. This leads to the formation of a low volume of urine which is concentrated (osmolality > 600 mOsm/kg) but low in sodium (< 20 mmol/l). These urinary changes may be absent in patients with impaired tubular function, e.g. pre-existing renal impairment, or those who have received loop diuretics

30. Clinical assessment Features of the underlying cause There may be marked hypotension and signs of poor peripheral perfusion, such as delayed capillary return. Pre-renal ARF may occur without systemic hypotension, particularly in patients taking NSAIDs or ACE inhibitors . Postural hypotension(a fall in blood pressure > 20/10 mmHg from lying to standing) is a valuable sign of early hypovolaemia. The cause of the reduced renal perfusion may be obvious, but concealed blood loss can occur into the gastrointestinal tract, following trauma (particularly where there are fractures of the pelvis or femur) and into the pregnant uterus. Large volumes of intravascular fluid are lost into tissues after crush injuries or burns, or in severe inflammatory skin diseases or sepsis. Metabolic acidosis and hyperkalaemiaare often present.

32. The clinical findings.( hypotention , decrease urine output , metabolic acidosis …)

34. MANAGEMENT OF PRE-RENAL ACUTE RENAL FAILURE: Establish and correct the underlying cause of the ARF. If hypovolaemia is present, restore blood volume as rapidly as possible (with blood, plasma or isotonic saline (0.9%), depending on what has been lost). Monitoring of the central venous pressure or pulmonary wedge pressure as an adjunct to clinical examination may aid in determining the rate of administration of fluid. Critically ill patients may require invasive haemodynamic monitoring to assess cardiac output and systemic vascular resistance, and the use of inotropic drugs to restore an effective blood pressure . Correct metabolic acidosis. Restoration of blood volume will correct acidosis by restoring kidney function. Isotonic sodium bicarbonate (e.g. 500 ml of 1.26%) may be used.

35. PROGNOSIS OF PRE-RENAL ACUTE RENAL FAILURE If treatment is given sufficiently early, renal function will usually improve rapidly; in such circumstances residual renal impairment is unlikely. In some cases, however, treatment is ineffective and renal failure becomes established