Pathophysiology of Renal Failure

Pathophysiology of renal failure

Renal Failure:

Acute

Chronic

Acute renal failure

Occurs in 3 clinical patterns: 

(1) as an adaptive response to severe volume depletion and hypotension, with structurally intact nephrons; 

(2) in response to cytotoxic, ischemic, or inflammatory insults to the kidney, with structural and functional damage; and 

(3) with obstruction to the passage of urine.

Thus classified as prerenal, intrinsic, and postrenal  

Prerenal Failure

Problems lie in the inability of the circulatory system to deliver the proper perfusion to the kidney to produce a normal GFR (90 - 120 mL/min )

Causes:

a) hypovolemic states (haemorrage, dehydration)

b) impairment of renal autoregulation (seen with cyclooxygenase inhibitors like NSAIDs and aspirin, or angiotensin converting enzyme (ACE) inhibitors)

c) low effective plasma flow state (low cardiac output states –arrythmias, valvular disease, congestive heart failure, systemic vasodilation – sepsis, antihypertensives, congestion – cirrhosis with ascites -> hepatorenal syndrome)

Kidneys recover rapidly once underlying deficit is corrected

Intrinsic Renal Failure

Hallmark: structural injury (most common form – acute tubular injury (ATN), either ischemic or cytotoxic)

Initial phase of ischemic injury – loss of integrity of actin cytoskeleton leads to flattening of the epithelium, with loss of brush border, loss of focal cell contacts, and subsequent disengagement of the cell from the underlying substratum.

Inflammatory response is responsible for some features of ATN

Reduced GFR – caused by intrarenal vasoconstriction (mediators are unknown)

Urine backflow and intratubular obstruction (from sloughed cells and debris) are causes of reduced net ultrafiltration

hallmark of ATN is a failure to maximally dilute or concentrate urine (isosthenuria).

The injured kidney fails to generate and maintain a high medullary solute gradient because the accumulation of solute in the medulla depends on normal distal nephron function.

Glomerulonephritis can be a cause of AKI and usually falls into a class referred to as rapidly progressive glomerulonephritis (RPGN). The pathologic correlation of RPGN is the presence of glomerular crescents (glomerular injury) on biopsy; if more than 50% of glomeruli contain crescents, this usually results in a significant decline in renal function. Although comparatively rare, acute glomerulonephritides should be part of the diagnostic consideration in cases of AKI.

Postrenal Failure

Hallmark: severe urinary tract obstruction

Men: prostate enlargement from benign prostatic hyperplasia or prostate cancer

Women: cervical cancer

Other causes: 

obstruction by bladder, kidney stones (lodged in the urinary tract such that flow from both kidneys is obstructed), phimosis (non-retractable foreskin), neurogenic bladder

Chronic renal failure

Involves several stages 

Decreased renal reserve -> Renal insufficiency -> End-stage renal failure/uremia

Decreased renal reserve

Around 60% nephrons lost

Decrease in GFR

Serum creatinine levels consistently higher than average but within normal range (0.8 to 1.4 mg/dL )

Serum urea levels normal (blood urea nitrogen: 7 to 20 mg/dL) 

No apparent clinical signs

Renal insufficiency

Around 75% nephrons lost

Indicated by a change in blood chemistry and manifestation

GFR decreased to 20% normal

Significant retention of nitrogen wastes (urea and creatine) in the blood

Tubule function decreased

Results in failure to concentrate the urine and control the secretion and exchange of acids and electrolytes.

Osmotic diuresis occurs at the remaining functional nephrons filter an increased solute load

Marked by excretion of large volumes of dilute urine.

Erythropoiesis decreased, patient’s blood pressure elevated (why?)

End-stage renal failure/uremia

More than 90% nephrons lost

Occurs when GFR is negligible

Fluids, electrolytes, and wastes retained in body, all body systems affected

Marked oliguria (reduced urine output) or anuria (no urine output) develops