IUHS Student-2-Student USMLE Step 1 Recall
Kidney
Diseases Affecting Tubules/Interstitium & Blood Vessels
Acute
Tubular Necrosis (ATN)
ATN is a clinicopathologic entity characterized morphologically by destruction of tubular epithelial cells and clinically by acute suppresssion of renal function...
it is the most common cause of acute renal failure, which signifies acute suppression of renal function and urine flow, falling within 24 hours to less than 400ml...
ATN accounts for 50% of cases in hospitalized patients...ATN is a reversible renal lesion that arises in a variety of clinical settings...most of these, ranging from severe trauma to acute pancreatitis, have in common a period of inadequate blood flow to the peripheral organs, usually accompanied by marked hypotension and shock...this pattern of ATN is called ischemic ATN...
mismatched blood transfusions and other hemolytic crises causing hemoglobinuria, and skeletal muscle injuries causing myoglobinuria, also produce a picture resembling ischemic ATN...
often associated with MIs...
in ATN, tubular damage prevents reabsorption of filtered sodium
kidney
is most sensitive to decreased blood flow, specifically the medulla of the
kidney, b/c of no colateral circulation...
ischemia is the major avenue for strutural and functional alterations in epithelial cells...
the structural changes include those of reversible injury, such as cellular swelling, loss of brush border, blebing, loss of polarity, and cell detachment, and those associated with lethal injury (necrosis and apoptosis)...
biochemically, there is depletion of adenosine triphosphate; accumulation of intracellular calcium, activation of proteases (calpain), which causes cytoskeletal rearrangement, and phospholipases, which damage membranes...
loss of cell polarity, increased sodium delivery to distal tubules, tubulo-glomerular feedback which incites vasoconstriction...luminal tubule obstruction...
hemodynamic alterations that cause reduced GFR...sublethal endothelial injury, leading to increased release of the endothelial vasoconstrictor endothelin and decreased production of the vasodilator nitric oxide and PGI2...
myoglobinuria with the rhabdomyolysis produces a toxic injury to the tubules...
ischemic ATN is characterized by focal tubular epithelial necrosis and apoptosis at multiple points along the nephron , with large skip areas in between, often accompanied by rupture of basement membranes and occlusion of tubular lumens by casts..."patchy tubular necrosis"...
proximal tubule and ascending limb are favorite targets of ischemia...
eosinophilic hyaline casts, as well as pigmented granular casts, are common, particularly in distal tubules and collecting ducts....these casts consist principally of Tamm-Horsfall protein (a specific urinary glycoprotein normally secreted by the cells of ascending thick limb and distal tubules) in conjunction with hemoglobin, myoglobin, and other plasma proteins...
urinalysis shows dirty brown granular casts and epithelial casts...
Acute Pyelonephritis
bacterial infection involving the renal pelvis, tubules, and interstitium...
ascending infection is the most common route...organisms involved include E. coli, proteus, klebsiella, and enterobacterium...
predisposing factors include urinary obstruction, vesicoureteral reflux, pregnancy, urethral instrumentation, diabetes mellitus, benign prostatic hypertrophy, and other renal pathology...
it may be difficult to distinguish cystitis from pyelonephritis...the presence of fever, costovertebral angel tenderness, and WBC casts in the urine are helpful clues to the diagnosis of pyelonephritis...
pathogenesis: bladder infection with reflux of urea into ureters...ascending infection...incompetent vesicoureteral junction...
Tubulointerstitial Nephritis
this group of renal diseases is charcterized by histologic and functional alterations that involve predominantly the tubules and interstitium...
tubulointerstitial nephritis can be acute or chronic...acute tubulointerstitial nephritis has an acute clinical onset and is characterized histologically by interstitial edema, often accompanied by leukocytic infiltration and focal tubular necrosis...
in chronic interstitial nephritis, there is infiltration with mononuclear cells, prominent interstitial fibrosis, and widespread tubular atrophy...
there is impaired ability to concentrate urine, evidenced clinically by polyuria or nocturia; salt wasting; diminished ability to excrete acids (metabolic acidosis); and isolated defects in tubular reabsorption or secretion...
sjogren's syndrome presents as a tubulointerstitial nephritis...
WBC casts in urine...
methicillin, penicillins, rash and oliguria...indinavir...
Benign Nephrosclerosis
benign
nephrosclerosis is the term used for the kidney
associated with sclerosis of renal arterioles and small arteries...
the resultant effect is focal ischemia of parenchyma supplied by the thickened narrowed vessels...some degree of nephrosclerosis is present at autopsy with increasing age, more in blacks than whites. preceding or in the absence of hypertension...
hypertension and diabetes mellitus, however, increase the incidence and severity of the lesions...
medial and intimal thickening, as a response to hemodynamic changes, genetic defects, or both...
hyaline deposition in arterioles, caused partly by extravasation of plasma proteins through injured endothelium and partly by increased deposition of basement membrane matrix...
in gross appearance, the kidneys are either normal in size or moderatly reduced to average weights between 110 and 130 gm...
the cortical surfaces have a fine, even granularity that resembles grain leather...
on histologic examination, there is narrowing of the lumens of arterioles and small arteries, caused by thickening and hyalinization of the walls (hyaline arteriolosclerosis)...
in addition to arteriolar hyalinization, the interlobular and arcuate arteries exhibit a characteristic lesion that consists of medial hypertrophy, reduplication of the elastic lamina, and increased myofibroblastic tissue in the intima, with consequent narrowing of the lumen...this change, called fibroelastic hyperplasia, often accompanies hyaline arteriolosclerosis and increases in severity with age and in the presence of hypertension...
unusually causes renal insufficiency or uremia...
Malignant Nephrosclerosis
malignant nephrosclerosis is the form of renal disease associated with the malignant or accelerate phase of hypertension...
this dramatic pattern of hypertension may occasionally develop in previously normotensive individuals but often is superimposed on preesixting essential benign hypertension, or secondary forms of hypertension, or an underlying chronic renal disease, particularly glomerulonephritis or reflux nephropathy...
it is also a frequent cause of death from uremia in patients with scleroderma...
malignant hypertension is relatively uncommon, occurring in 1-5% of all patients with elevated blood pressure...
in its pure form, it usually affects younger individuals, with a high preponderance in men and in blacks...
the initial event appears to be some form of vascular damage to the kidneys...
this most commonly results from long-standing benign hypertension, with eventual injury to the arteriolar walls, or it may spring from arteritis or a coagulopathy...
in either case the result is increased permeability of small vessels to fibrinogen and other plasma proteins, endothelial injury, and platelet deposition...
this leads to the appearance of fibrinoid necrosis of arterioles and small arteries and intravascular thrombosis...
mitogenic
factors from platelets (platelet derived growth factor), plasma and other cells
cause intimal smooth hyperplasia of vessels,
resulting in the
hyperplastic arteriosclerosis
typical of malignant
hypertension and further narrowing of the lumens...
the kidney size is dependent on the duration and severity of the hypertensive disease...small, pinpoint petechial hemorrhages may appear on the cortical surface from rupture of arterioles or glomerular capillaries, giving the kidney a peculiar "flea-bit-ten" appearance...
fibrinoid necrosis of arterioles...this appears as an eosinophilic granular change in the blood vessel wall, which stains positively for fibrin by histochemical or immunofluorescence techniques...in addition, there is often an inflammatory infiltrate within the wall, giving rise to the term necrotizing arteriolitis...
in the interlobular arteries and arterioles...there is intimal thickening caused by a proliferation of elongated, concentrically arranged cells, smooth muscle cells, together with fine concentric layering of collagen....
characterized by diastolic pressures greater than 130mmHg...papilledema retinopathy, encephalopathy, cardiovascular abnormalities, and renal failure...
Renal
Artery Stenosis
unilateral renal artery stenosis is a relatively uncommon cause of hypertension, responsible for 2-5% of cases, but it is of importance b/c it is potentially curable form of hypertension, surgical treatment being successful in 70-80% of carefully selected cases...
furthermore, much early knowledge of renal mechanisms in hypertension has come from studies of experimental and human renal artery stenosis...
constriction in one renal artery results in hypertension and that the magnitude of the effect is roughly proportional to the amount of constriction...
hypertensive effect is due to stimulation of renin secretion by cells of the juxtaglomerular apparatus and the subsequent production of the vasoconstrictor angiotensin II...
a large proportion of patients with renovascular hypertension have elevated plasma or renal vein renin levels, and almost all show a reduction of blood pressure when given competitive antagonists of angiotensin II...
further,
unilateral renal renin hypersecretion can be normalized after renal
revascularization, in association with a decrease in blood presssure...
sodium retention also contributes to hypertensive state...endothelin and loss of NO, also...
most common cause or renal artery stenosis (70% of cases) is occlusion by an atheromatous plaque at the origin of the renal artery...
this lesion occurs more frequently in men, the incidence increasing with advancing age and diabetes mellitus...the plaque is usually concentrically placed, and superimposed thrombus often occurs...
the second type of lesion leading to stenosis is so-called fibromuscular dysplaia of the renal artery...this is a heterogeneous group of lesions characterized by fibrous or fibromuscular thickening and may involve the intima, the media, other adventitia of the artery...medial type is the most common...
a ischemic kidney develops and is reduced in size and shows signs of diffuse ischemic atrophy, with crowded glomeruli, atrophic tubules, interstitial fibrosis, and focal inflammatory infiltrate...
This is one of the surgically correctible causes for hypertension. The thickened and tortuous renal arteries can be replaced with grafts...
patients resemble those presenting with essential hypertension...
on occasion, a bruit can be heard on auscultation of the kidneys...elevated plasma or renal vein renin, response to angiotensin-converting enzyme inhibitor, renal scans, and intravenous pyelography may aid in diagnosis, but arteriography is required to localize the stenotic lesion...
as noted, the cure rate after surger is 70-80% in well selected cases...
Thrombotic Microangiopathies
represent a group of disorders with overlapping clinical manifestations that are characterized morphologically by thrombosis in capillaries and arterioles througout the body and clinically by microangiopathic hemolytic anemia, thrombocytopenia, and, in certain conditions, renal failure...
the renal failure is associated with platelet or platelet-fibrin thrombi in the interlobular renal arteries and glomeruli, together with necrosis and thickening of the vessel walls..
the morphologic changes may be similar to those seen in malignant hypertension; but in these conditions, they may preceed development of hypertension or may be seen in its absence...
Classic (Childhood) Hemolytic-Uremic Syndrome
most cases (75%) occur in children after intestinal infection with verocytotoxin-producing E. coli...
the disease is one of the main causes of acute renal failure in children...it is characterized by the sudden onset, usually after a GI or influenza-like prodromal episode, of bleeding manifestations (especially hematemesis and melena), severe oliguria, hematuria, a microangiopathic hemolytic anemia, and prominent neurologic changes...
hypertension is present in about half the patients...
thrombotic microangiopathy, which reflects predominantly endothelial injury in the small renal arterioles, is the hallmark of a group of diseases that includes hemolytic uremic syndrome...
Hemolytic-Uremic Syndrome
clearly
related to the shiga-like toxin...the
toxin has a variety of effects on endothelium, causing increased adhesion of
leukocytes; increased endothelin production and loss of endothelial nitric oxide
(both favoring vasoconstriction); and in the presence of cytokines, such as TNF,
endothelial lysis...
the resultant endothelial effects enhance both thrombosis and vasoconstriciton, resulting in the characteristic microangiopathy...
verocytotoxin also binds to erythrocytes, activates monocytes, and affects platelet funciton...
thrombotic microangiopathy, which reflects predominantly endothelial injury in the small renal arterioles, is the hallmark of a group of diseases that includes hemolytic uremic syndrome...
in gross appearance, the kidneys may show patchy or widespread renal cortical necrosis...
on microscopic examination, the glomeruli show thickening of capillary walls, due largely to endothelial and subendothelial swelling, and deposits of fibrin related materials in the capillary lumens, subendothelially, and in the mesangium...
interlobular and afferent arterioles show fibrinoid necrosis and intimal hyperplasia and are often occluded by thrombi...