Renal Pathology part 5 Flashcards
Acute Pyelonephritis
-suppurative inflammation of the kidney caused by bacterial and sometimes viral (e.g., polyomavirus) infection, which can reach the kidney by hematogenous spread or, more commonly, through the ureters in association with vesicoureteral reflux
Acute Pyelonephritis hallmarks
- patchy interstitial suppurative inflammation, intratubular aggregates of neutrophils, neutrophilic tubulitis and tubular necrosis
- suppuration may occur as discrete focal abscesses or large wedge-like areas and can involve one or both kidneys
complications of acute pyelonephritis
- papillary necrosis is seen mainly in diabetes, sickle cell disease, and in those with urinary tract obstruction
- pylonephrosis is seen when there is total or almost complete obstruction, particularly when it is high in the urinary tract
- perinephric abscess is an extension of suppurative inflammation through the renal capsule into the perinephric tissue
After acute phase of pyelonephritis,
healing occurs
- neutrophilic infiltration is replaced by one that is predominantly composed of macrophages, plasma cells, and lymphocytes
- inflammatory foci are eventually replaced by irregular scars that can be seen on the cortical surface as fibrous depressions.
- such scars are characterized microscopically by tubular atrophy, interstitial fibrosis, and a lymphocytic infiltrate in a characteristic patchy, jigsaw pattern with intervening preserved parenchyma
Pyelonephritic scar is
almost always associated with inflammation, fibrosis, and deformation of the underlying calyx and pelvis, reflecting the role of ascending infection and vesicoureteral reflux in the pathogenesis of disease
Acute pyelonephritis can be associated with
- urinary tract obstruction
- instrumentation of the urinary tract
- vesicouteral reflux
- pregnancy
- gender and age
- preexisting renal lesions, causing intrarenal scarring and obstruction
- diabetes mellitus
- immunosuppression and immunodeficiency
Acute pyelonephritis usually presents with
- a sudden onset of pain at the costovertebral angle and systemic evidence of infection, such as fever and malaise
- there are often indications of bladder and urethral irritation, such as dysuria, frequency, and urgency
- urine contains many leukocytes (pyuria) derived from the inflammatory infiltrate, but pyuria does not differentiate upper from lower UTI
Indicates renal involvement in UTI
- the finding of leukocyte casts, typically rich in neutrophils (pus casts)
- casts are formed only in tubules
Diagnosis of UTI infection is established by
-quantitative urine culture
Uncomplicated acute pyelonephritis follows
a benign coures, and symptoms disappear within a few days after the institution of appropriate antibiotic therapy
-bacteria may persist in the urine though or there may be recurrence of infection with new serologic types of E. coli or other organisms.
In the presence of unrelieved urinary obstructor, diabetes, or immunodeficiency, acute pyelonephritis may
be more serious leading to repeated septicemic episodes
-superimposition of papillary necrosis may lead to acute renal failure
An emerging viral pathogen causing pyelonephritis in kidney allografts is
polymavirus
-latent infection with polyomavirus is widespread in general population, and immunosuppression of the allograft recipient can lead to reactivation of latent infection and the development of nephropathy resulting in allograft failure in up to 5% of kidney transplant recipients
Polyomavirus nephropahty
-characterized by infection of tubular epithelial cell nuclei, leading to nuclear enlargement and intranuclear inclusions visible by light microscopy (viral cytopathic effect)
Chronic pyelonephritis
- a disorder in which chronic tubulointerstitial inflammation and scarring involve the calyces and pelvis
- only chronic pyelonephritis and analgesic nephropathy affect the calyces
- important cause of kidney destruction in children with severe lower urinary tract abnormalities
- 2 forms: reflux nephropathy and chronic obstructive pyelonephritis
Reflux Nephropathy
- occurs early in childhood as a result of superimposition of a urinary infection on congenital vesicoureteral reflux and internal reflux
- may be unilateral or bilateral; thus, the continuous renal damage may cause scarring and atrophy of one kidney or involve both, leading to renal insufficiency
- vesicoureteral reflux occasionally cause renal damage in the absence of infection (sterile reflux), but only when obstruction is severe.
Chronic obstructive pyelonephritis
- recurrent infections superimposed on diffuse or localized obstructive lesions lead to repeated bouts of renal inflammation and scarring, resulting in chronic pyelonephritis
- the effects of obstruction contribute to the parenchymal atrophy; indeed, it is sometimes difficult to differentiate the effects of bacterial infection from those of obstruction alone
- can be bilateral, as with posterior urethral valves, resulting in renal insufficiency unless the anomaly is corrected, or unilateral, as occurs with calculi and unilateral obstructive anomalies of the ureter
Chronic Pyelonephritis and Reflux Nephropathy Morphology
- kidneys usually irregularly scarred; if bilateral, the involvement is asymmetric
- coarse, discrete, corticomedullary scars overlying dilated, blunted, or deformed calyces, and flattening of the papillae
- dilated tubules with flattened epithelium may be filled with casts resembling thyroid colloid
- varying degrees of fibrosis
- Arcuate and interlobular vessels demonstrate obliterative intimal sclerosis in the scarred areas
Xanthogranulomatous pyelonephritis
-relatively rare form of chronic pyelonephritis characterized by accumulation of foamy macrophages intermingled with plasma cells, lymphocytes, polymorphonuclear leukocytes, and occasional giant cells
Chronic obstructive pyelonephritis may have
a silent onset or present with manifestations of acute recurrent pyelonephritis, such as back pain, fever, pyuria, and bacteria
-receive medical attention relatively late in their disease course because of the gradual onset of renal insufficiency and hypertension
Reflux nephropathy is often
discovered in children when the cause of hypertension is investigated
-radiographic studies show asymmetrically contracted kidneys with characteristic coarse scars and blunting and deformity of the calyces system
Loss of tubular function in reflux nephropathy gives rise to
polyuria and nocturia
Tubulointerstitial Nephritis Induced by drugs and toxins
-can trigger an immunology reaction, exemplified by the acute hypersensitivity nephritis induced by drugs such as methicillin; cause acute tubular injury; and cause subclinical but cumulative injury to tubules that takes years to result in chronic renal insufficiency
Acute Drug-Induced Interstitial Nephritis
-most frequently occurs with synthetic penicillins, other synthetic antibiotics, diuretics, NSAIDs, and miscellaneous drugs
Drug-induced acute interstitial nephritis begins
about 15 days after drug exposure and is characterized by fever, eosinophils, a rash in about 25% of patients, and renal abnormalities (hematuria, mild proteinuria, and leukocyturia)
-rising serum creatinine or acute kidney injury with oliguria develops in about 50% of cases, particularly in older patients
Acute Drug-Induced Interstitial Nephritis histologic exam
- interstitium shows variable but frequently pronounced edema and infiltration by mononuclear cells, principally lymphocytes and macrophages
- eosinophils and neutrophils may be present, often in clusters and large numbers, and smaller numbers of plasma cells and mast cells are sometimes also present
With methicillin and thiazides,
interstitial nonnecrotizing granulomas may be seen
Acute Drug-Induced Interstitial Nephritis Morphology
- Inflammation may be more prominent int he medulla her the inciting agent is often concentrated
- tubulitis is common
- variable degrees of tubular necrosis and regeneration are present
- glomeruli are normal except in some cases caused by NSAIDs, when minimal-change disease and the nephrotic syndrome develop concurrently
In analgesic nephropathy
-papillae can show various stages of necrosis, calcification, fragmentation, and sloughing
It is important to recognize drug-induced acute interstitial nephritis because
-withdrawal of the offending drug is followed by recovery, although it may take several months, and irreversible damage can occur
Acute Drug-Induced Interstitial Nephritis Clinical Features
-on occasion, necrotic papillae are excreted and may cause gross hematuria or renal colic due to ureteric obstruction
Papillary necrosis seen in
analgesic nephropathy diabetes mellitus urinary tract obstruction sickle cell disease focally in renal tuberculosis -caused by ischemia resulting from compression or obstruction of small blood vessels in the medulla
A small percentage of patients with analgesic nephropathy develop
urothelial carcinoma of the renal pelvis
Nephropathy associate with NSIADs
- acute kidney injury
- acute hypersensitivity interstitial nephritis
- acute interstitial nephritis and minimal-change disease
- membranous nephropathy with nephrotic syndrome
3 types of nephropathy can occur in persons with hyperuricemic disorders
- acute uric acid nephropathy
- chronic urate nepropathy
- nephrolithiasis
Acute uric acid nephropathy
- caused by precipitation of uric acid crystals in the renal tubules, principally in collecting ducts, leading to obstruction of nephrons and the development of acute renal failure
- particularly likely to occur in individuals with leukemias or lymphomas who are undergoing chemotherapy (tumor lysis syndrome); the drugs kill tumor cells, and uric acid is produced as released nucleic acids are broken down
- precipitation of uric acid is favored by the acidic pH in collecting tubules
Chronic urate nephropathy (gouty nephropathy)
- occurs in a subset of patients with protracted forms of hyperuricemia
- the monosodium rate crystals deposit int he acidic milieu of the distal tubules and CDs as well as in the interstitium, and form distinct birefringent needle-like crystals either in the tubular lumens or in the interstitium
- urate deposits evoke a mononuclear response that contains foreign-body giant cells (typhus)
- tubular obstruction by the urate causes cortical atrophy and scarring
Nephrolithiasis
-uric acid stones are present in 22% of individuals with gout and 42% of those with secondary hyperuricemia
Disorders associated with hypercalcemia
- such as hyperparathyroidism, multiple myeloma, vitamin D intoxication, metastatic cancer, or excess calcium intake (milk-alkali syndrome)
- May induce the formation of calcium stones and deposition of calcium in the kidney (nephrocalcinosis)
extensive degrees of calcinosis under certain conditions may lead to
chronic tubulointerstitial disease and renal insufficiency
- earliest function defect is inability to concentrate urine
- other tubular defects may also occur
- slowly progressive renal insufficiency may develop
Acute Phosphate Nephropathy
- extensive accumulations of calcium phosphate crystals in tubules can occur in patients consuming high doses of select oral phosphate solutions in preparation for colonoscopy
- not hypercalcemic, but excess phosphate load causes marked precipitation of calcium phosphate, typically presenting as renal insufficiency several weeks after exposure
- patients with acute and reversible injury typically recover partial renal function
Light-Chain Cast Nephropathy (Myeloma Kidney)
- caused by non renal malignant tumors
- tubulointerstitial involvement caused by complications of tumor or therapy
- overt renal insufficiency occurs in half of those with multiple myeloma and related lymphoplasmacytic disorders
Factors that contribute to renal damage in Light-Chain Cast Nephropathy
- Bence-Jones proteinuria and cast nephropathy
- Amyloidosis of AL type
- Light chain deposition disease
- Hypercalcemia and hyperuricemia
Bence-Joines porteinuria and cast nephropathy
- main cause of renal dysfunction is related to Bence-Jones (light-chain) proteinuria, and correlates with the degree of proteinuria
- some Ig light chains are directly toxic to epithelial cells, apparently because of their intrinsic physiochemical properties
- Bence-Jones proteins combine with the urinary glycoprotein under acidic conditions to form large, histologically distinct tubular casts that obstruct the tubular lumens and induce a characteristic inflammatory reaction
Light-chain deposition disease
-in some patients, light chains (usually kappa) deposit in GBMs and mesangium in non fibrillar forms, causing a glomerulopathy, and in tubular basement membranes, which may cause tubulointerstitial nephritis
Light-Chain Nephropathy Morphology
- tubulointerstitial changes
- Bence-Jones tubular casts appear pink to blue amorphous masses, concentrically laminated and often fractured, which fill and distend the tubular lumen
- some casts are surrounded by multinucleate giant cells that are derived from activated macrophages
- adjacent interstitial tissue usually shows an inflammatory response and fibrosis
- on occasion, casts rupture tubules, evoking granulomatous inflammatory reaction
- amyloidosis, light-chain deposition disease, neprocalcinosis, and infection may also be present
Light-Chain Cast Nephropathy Clinical Features
Light-Chain Cast Nephropathy Clinical Features -most common, chronic kidney disease develops insidiously and progresses slowly during a period of several months to years
- another form occurs suddenly and is manifested by acute kidney injury with oliguria
- precipitating factors include dehydration, hypercalcemia, acute infection, and treatment with nephrotoxic antibiotics
- Bence-Jones proteinuria occur in 70% of individuals with multiple myeloma; the presence of significant non-light-chain proteinuria (e.g., albuminuria) suggests AL amyloidosis or light-chain deposition disease
Bile Cast Nephropathy
- hepatorenal syndrome refers to impairment of renal function in patients with acute or chronic liver disease with advanced liver failure.
- serum bilirubin levels can be markedly elevated, particularly in jaundiced patients, with bile cast formation (choleric nephrosis) in distal nephron segments
- casts can extend to proximal tubules, resulting in both direct toxic effects on tubular epithelial cells and obstruction of the involved nephron
- analogous to that with myeloma protein and myoglobin casts
- tubular bile casts can range from yellowish-green to pink and contain variable degrees of sloughed cells or cellular debris
- reversibility of renal injury depends on the severity and duration of liver dysfunction
Nephrosclerosis
- the term used for the renal pathology associated with sclerosis of renal arterioles and small arteries and is strongly associated with hypertension, which can e both a cause and a consequence of nephrosclerosis
- affected vessels have thickened walls and consequently narrowed lumens, changes that result in focal parenchymal ischemia
- ischemia leads to glomerulosclerosis and chronic tubulointerstitial injury, and produces a reduction in functional renal mass
Nephrosclerosis at autopsy is associated with
advanced age, is more frequent in blacks than whites, and may be seen in the absence of hypertension
-hypertension and diabetes mellitus, however, increase the incidence and severity of the lesions
Two processes participate in arterial lesions in association with nephrosclerosis
- medial and intimal thickening, as a response to hemodynamic changes, ranging, genetic defects, or some combination of these
- hyalinization of arteriolar walls, caused by extravasation of plasma proteins through injured endothelium and by increased deposition of basement membrane matrix
Nephrosclerosis Morphology
- kidneys are either normal or moderately reduced in size
- cortical surfaces have a fine, even granularity that resembles grain leather
- loss of mass is due mainly to cortical scarring and shrinking
Nephrosclerosis histologic exam
- narrowing of the lumens of arterioles and small arteries, caused by thickening and hyalinization of the walls (hyaline arteriolosclerosis)
- microscopic subcapsular scars with sclerotic glomeruli and tubular dropout, alternating with better preserved parenchyma
- interlobular and arcuate arteries show medial hypertrophy, replication of the internal elastic lamina, and increased myofibroblastic tissue in the intimate, all of which narrow in the lumen (fibroelastic hyperplasia)
- patchy ischemic atrophy, which consists of foci of tubular atrophy and interstitial fibrosis and a variety of glomerular alterations
- collapse of GBM, deposition of collagen within Bowman space, periglomerular fibrosis and total sclerosis of glomeruli
3 groups of hypertensive patients with nephrosclerosis are at increased risk of developing renal failure
- people of African descent, people with severe blood pressure elevations, and persons with a second underlying disease, especially diabetes
- renal insufficiency may supervene after prolonged hypertension, but rapid renal failure results from the development of the malignant or accelerated phase of hypertension
Malignant nephrosclerosis
- renal vascular disorder associated with malignant or accelerated hypertension
- occasionally develops suddenly in previously normotensive individuals but more often is superimposed on preexisting essential hypertension, secondary forms of hypertension, or an underlying chronic renal disease, particularly glomerulonephritis or reflux nephropathy
- also a frequent cause of renal failure in individuals with systemic sclerosis
Fundamental lesion in malignant nephrosclerosis
vascular injury
- initial insult seems to be some form of vascular damage to the kidneys that might result from a variety of disorders, including longstanding hypertension, arteritis, or a coagulopathy, alone or in combination
- initiating event injures endothelium and results in increased permeability of the small vessels to fibrinogen and the plasma proteins, focal death of cells of the vascular wall, and platelets deposition
- can lead to fibrinoid necrosis of arterioles and small arteries, which activation of platelets and coagulation factors causing intravascular thrombosis
Malignant Nephrosclerosis Morphology
- kidney size varies depending on duration and severity of 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-bitten appearance
Fibrinoid necrosis of arterioles
- in this form of necrosis, cytologic details is lost and the vessel wall takes on a smudgy eosinophilic appearance due to fibrin deposition
- inflammation is usually not seen or is minimal
- sometimes the glomeruli become necrotic and infiltrated with neutrophils, and the glomerular capillaries may thrombose
Malignant Nephrosclerosis Interlobular arteries and arterioles
- intimal thickening caused by proliferation of elongated, concentrically arranged smooth muscle cells, together with fine concentric layering of collagen and accumulation of pale-staining material that probably represents deposition of proteoglycan and plasma proteins
- onion-skinning
- hyperplastic arteriolitis
- may be superimposed intraluminal thrombosis
Malignant Nephrosclerosis Clinical Features-
systolic pressures greater than 200 mmHg and diastolic pressure greater than 120 mmHG, papilledema, retinal hemorrhages, encephalopathy, cardiovascular abnormalities, and renal failure
- most often,e early symptoms related to increased intracranial pressure and include headaches, nausea, vomiting, and visual impairments, particularly scooters or spots before the eyes
- hypertensive crises are sometimes encountered, characterized by loss of consciousness so even convulsions
- at onset, may only be marked proteinuria and microscopic or macroscopic hematuria, but renal failure soon ensues
- medical emergency
Renal Artery Stenosis
- unilateral renal artery stenosis is responsible for 2-5% of hypertensive cases, and is important to recognize because it is potentially curable by surgery
- hypertension secondary to renal artery stenosis is caused by increased production of renin from the ischemic kidney
- elevation in bp is due to stimulation of renin secretion by the juxtaglomerular apparatus and the subsequent production of vasoconstrictor angiotensin II
Most common cause of renal artery stenosis is
narrowing at the origin of the renal artery by an atheromatous plaque
-occurs more frequently in men, and the incident increase with advancing age and diabetes mellitus
Renal artery stenosis plaque
- usually concentrically placed, and superimposed thrombosis often occurs
- second most frequent cause of stenosis is fibromuscular dysplasia of renal artery–fibrosis or fibromuscular thickening that may involve the intimal, the media, or the adventitia of the after
Renal artery stenosis are more common in
women and tend to occur in younger age groups (i.e, third and fourth decades)
Ischemic kidney in renal artery stenosis
- is reduced in size and shows signs of diffuse ischemic atrophy, with crowded glomeruli, atrophic tubules, interstitial fibrosis, and focal inflammatory infiltrates
- arterioles usually protected from the effects of high pressure, thus showing only mild arteriolosclerosis
- contralateral nonischemic kidney may show more severe arteriolosclerosis, depending on severity of the hypertension
Renal Artery stenosis clinical course
- resemble patients with essential hypertension
- on occasion, a bruit can be heard on auscultation of affected kidney
- elevated plasma or renal vein renin, response to ACE inhibitor, renal scans, and IV pyelography may aid with diagnosis, but arteriography is required to localize stenotic lesion
