Robbins Ch.

20 The Kidney
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1.

BRS Pathology - Table 17-1 Glomerular Diseases

(memorize this table)

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Tubular and interstitial disorders are frequently caused by what? Glomerular diseases are frequently caused by what? 1. What is azotemia? 2. What is it related to? Nephritic syndrome?

toxins or infectious agents

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immunologically mediated 1. elevated of BUN and creatinine 2. decreased glomerular filtration rate HEMATURIA, mild proteinuria, oliguria, azotemia, and hypertension - is due to glomerular disease and is dominated by the acute onset of usually grossly visible hematuria (red blood cells in urine), mild to moderate proteinuria, and hypertension; it is the classic presentation of acute poststreptococcal glomerulonephritis. *Hallmark = glomerular inflammation and bleeding -limited proteinuria <3.5g/day -oliguria and azotemia -salt retention with periorbital edema and HTN -RBC casts and dysmorphic RBCs in urine*** *Biopsy = hypercellular, inflamed glomeruli -immune-complex deposition activates complement -C5a attracts neutrophils, which mediate damage Examples = Post-strep GN, RPGN, IgA neph, Alport syndrome

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Nephrotic syndrome?

heavy PROTEINURIA, hypoalbuminemia, severe edema, hyperlipidemia, lipiduria - due to glomerular disease, is characterized by heavy proteinuria (more than 3.5 gm/day), hypoalbuminemia, severe edema, hyperlipidemia, and lipiduria (lipid in the urine). nephrotic syndrome is worse

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Which is worse, nephritic syndrome or nephrotic syndrome? 4 stages of renal failure:

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- diminished renal reserve - renal insufficiency - chronic renal failure - end-stage renal disease

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Basement membrane thickening in EM, how does the thickening happen?

immune complex deposition, synthesis of protein components Basement Membrane Thickening: - By light microscopy, this change appears as thickening of the capillary walls, best seen in sections stained with periodic acid-Schiff (PAS). - By electron microscopy such thickening takes one of two forms: 1) Deposition of amorphous electron-dense material, most often immune complexes, on the endothelial or epithelial side of the basement membrane or within the GBM itself. Fibrin, amyloid, cryoglobulins, and abnormal fibrillary proteins may also deposit in the GBM. 2) Thickening of the basement membrane due to increased synthesis of its protein components, as occurs in diabetic glomerulosclerosis. pink (eosinophilic) - Hyalinosis, as applied to the glomerulus, denotes the accumulation of material that is homogeneous and eosinophilic by light microscopy

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Hyalinosis, what do you seen microscopically?

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What is hyalinosis a common feature of? What is sclerosis characterized by? As kidney disease progresses, what are the 2 major histologic characteristics seen? What are the 3 types of Rapidly Progressive (Crescentic) Glomerulonephritis?

focal segmental glomerulosclerosis accumulations of extracellular collagenous matrix, either confined to mesangial areas as is often the case in diabetic glomerulosclerosis, or involving the capillary loops, or both. - focal segmental glomerulosclerosis - tubulointersitital fibrosis Type 1, 2, and 3: 1) Anti-GBM antibody 2) Immune complex 3) Pauci-immune - lack of immune anti-GBM or immune complexes by immunofluorescence and electron microscopy. - Most patients with this type of RPGN have circulating antineutrophil cytoplasmic antibodies (ANCAs) that produce cytoplasmic (c) or perinuclear (p) staining patterns, and play a role in some vasculitides. 1. nothing much 2. loss of foot processes (podocytes) - Electron microscopy discloses deposits in those cases due to immune complex deposition (type II). - Regardless of type, electron microscopy may show distinct ruptures in the GBM, the severe injury that allows leukocytes, proteins, and inflammatory mediators to reach the urinary space, where they trigger the crescent formation 3. nephrotic syndrome 1. effaced foot processes & sclerosis of focal segments (portions of structures are involved) 2. Nephrotic - alterations in glomerular basement membrane - proliferation of glomerular cells - leukocyte infiltration IgA Berger disease (IgA Nephropathy)

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1. What would you see via light microscopy (LM) for RPGN? 2. What would you see via electric microscopy (EM) for RPGN? 3. What would you see, nephritic or nephrotic syndrome? 1. What do you seen in focal segmental glomerulosclerosis? 2. Nephritic or nephrotic? Histologically what do you seen in membranoproliferative glomerulonephritis? In Berger disease, what kind of deposits would you see? What is the most common type of glomerulonephritis worldwide? In Alport syndrome, what type of abnormal collagen do you have?

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Type IV collagen

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Alport syndrome:

- thin basement membrane lesion - the most common cause of benign familial hematuria - is manifest by hematuria with progression to chronic renal failure, accompanied by nerve deafness and various eye disorders, including lens dislocation, posterior cataracts, and corneal dystrophy no, the disease can be suspected by LM, but the Dx is made only by immunocytochemical techniques

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Can you diagnosis Berger disease with light microscopy? Acute kidney injury or acute tubular necrosis is caused by what? Table 20-5 - pg 918 (highlighted)

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- ischemia - toxic injury - urinary obstruction - acute tubulointerstitial nephritis

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What is a neoplasm that can cause tubuleinterstitial nephritis? Most common cause of clinical pyelonephritis? 1) Vesicoureteral reflux: 2) What do you seen because of that?

multiple myeloma

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ascending infection

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1) urine goes back from bladder to ureters - Although obstruction is an important predisposing factor in ascending infection, it is incompetence of the vesicoureteral valve that allows bacteria to ascend the ureter into the renal pelvis. An incompetent vesicoureteral orifice allows the reflux of bladder urine into the ureters (vesicoureteral reflux) 2) increased infection - The effect of vesicoureteral reflux is similar to that of an obstruction in that there is residual urine in the urinary tract after voiding, which favors bacterial growth. acute suppurative inflammation of kidneys caused mostly by bacteria - Acute pyelonephritis is caused by bacterial infection and is the renal lesion associated with urinary tract infection. E. coli (O157:H7)

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What is acute pyelonephritis? Most common bacteria that causes pyelonephritis is what?

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Figure 20-32 "know what is going on there"

Typical coarse scars of chronic pyelonephritis associated with vesicoureteral reflux. The scars are usually polar and are associated with underlying blunted calyces. - Chronic pyelonephritis is a disorder in which chronic tubulointerstitial inflammation and renal scarring are associated with pathologic involvement of the calyces and pelvis
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Benign nephrosclerosis is a term used to describe what? Know what kind of a histologic picture you would see with benign nephrosclerosis / Figure 20-38 "know why that happens"

renal pathology associated with renal sclerosis of renal arterioles and small arteries

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Close-up of the gross appearance of the cortical surface in benign nephrosclerosis illustrating the fine, leathery granularity of the surface. - The kidneys are either normal or moderately reduced in size, with average weights between 110 and 130 gm. The cortical surfaces have a fine, even granularity that resembles grain leather (Fig. 20-38). The loss of mass is due mainly to cortical scarring and shrinking - On histologic examination there is narrowing of the lumens of arterioles and small arteries, caused by thickening and hyalinization of the walls (hyaline arteriolosclerosis) (Fig. 20-39). Corresponding to the fine surface granulations are microscopic subcapsular scars with sclerotic glomeruli and tubular dropout, alternating with better preserved parenchyma. In addition, the interlobular and arcuate arteries show a characteristic lesion that consists of medial hypertrophy, reduplication of the elastic lamina, and increased myofibroblastic tissue in the intima, which combine to narrow the lumen. This change, called fibroelastic hyperplasia, often accompanies hyaline arteriolosclerosis and increases in severity with age and in the presence of hypertension - Consequent to the vascular narrowing, there is patchy ischemic atrophy, which consists of (1) foci of tubular atrophy and interstitial fibrosis and (2) a variety of glomerular alterations. The latter include collapse of the GBM, deposition of collagen within the Bowman space, periglomerular fibrosis, and total sclerosis of glomeruli. When the ischemic changes are pronounced and affect large areas of parenchyma, they can produce regional scars and histologic alterations that may resemble those seen in renal ablation injury

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Malignant hypertension (+ gross morphology): Malignant Hypertension. What would you see histologically?

Malignant nephrosclerosis is the form of renal disease associated with the malignant or accelerated phase of hypertension; - Morphology. On gross inspection the kidney size depends 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- bitten" appearance.

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Two histologic alterations characterize blood vessels in malignant hypertension (Fig. 20-40): - 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. This change represents an acute event; it may be accompanied by limited inflammatory infiltrate within the wall, but prominent inflammation is not seen. Sometimes the glomeruli become necrotic and infiltrated with neutrophils, and the glomerular capillaries may thrombose. - In the interlobular arteries and arterioles, there is intimal thickening caused by a proliferation of elongated, concentrically arranged smooth muscle cells, together with fine concentric layering of collagen and accumulation of pale-staining material that probably represents accumulations of proteoglycans and plasma proteins. This alteration has been referred to as onion-skinning because of its concentric appearance. The lesion, also called hyperplastic arteriolitis, correlates well with renal failure in malignant hypertension. There may be superimposed intraluminal thrombosis. The arteriolar and arterial lesions result in considerable narrowing of all vascular lumens, ischemic atrophy and, at times, infarction distal to the abnormal vessels.
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Shigga-like toxin E. coli strain? Hereditary disorder characterized by multiple expanding cysts of kidneys, destroys parenchyma, and caused renal failure? Be able to tell difference between childhood and adult polycystic kidney disease, grossly (Figure 20-47 AD)

O157:H7 polycystic kidney disease

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Figure 20-47: A and B) Autosomal-dominant adult polycystic kidney disease (ADPKD) viewed from the external surface and bisected. The kidney is markedly enlarged and contains numerous dilated cysts. D) Liver cysts in adult PKD

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Figure 20-47c: ARPKD

Fig. 20-47 C) Autosomal-recessive childhood PKD, showing smaller cysts and dilated channels at right angles to the cortical surface.
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Hydropnephrosis of the kidney what does it look like grossly? (Figure 20-50)

- Hydronephrosis of the kidney, with marked dilation of the pelvis and calyces and thinning of the renal parenchyma. - Hydronephrosis is the term used to describe dilation of the renal pelvis and calyces associated with progressive atrophy of the kidney due to obstruction to the outflow of urine. - The kidney may be slightly to massively enlarged, depending on the degree and the duration of the obstruction. The earlier features are those of simple dilation of the pelvis and calyces, but in addition there is often significant interstitial inflammation, even in the absence of infection. In chronic cases the picture is one of cortical tubular atrophy with marked diffuse interstitial fibrosis. Progressive blunting of the apices of the pyramids occurs, and these eventually become cupped. In far-advanced cases the kidney may become transformed into a thin-walled cystic structure having a diameter of up to 15 to 20 cm (Fig. 20-50) with striking parenchymal atrophy, total obliteration of the pyramids, and thinning of the cortex
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1. Benign tumor consisting of vessels, smooth muscle, and fat 2. What do you usually see it in? Kidney tumor "mahogany brown"

1. angiomyolipoma 2. tuberous sclerosis

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Oncocytoma - This is an epithelial tumor composed of large eosinophilic cells having small, round, benign-appearing nuclei that have large nucleoli. It is thought to arise from the intercalated cells of collecting ducts. - In gross appearance the tumors are tan or MAHOGANY BROWN, relatively homogeneous, and usually well encapsulated. However, they may achieve a large size (up to 12 cm in diameter). There are some familial cases in which these tumors are multicentric rather than solitary.

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Major types of renal cell carcinoma (adenocarcinoma of the kidney) Which type of renal cell carcinoma is associated with von Hippel Lindau syndrome? Morphology of Acute Pyelonephritis (pg 941 Blue box)

- clear cell carcinoma - papillary carcinoma - Chromophobe renal carcinoma - Collecting duct (Bellini duct) carcinoma clear cell carcinoma - current studies implicate the VHL gene in the development of both familial and sporadic clear cell tumors

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The hallmarks of acute pyelonephritis are patchy interstitial suppurative inflammation, intratubular aggregates of neutrophils, and tubular necrosis. The suppuration may occur as discrete focal abscesses involving one or both kidneys, which can extend to large wedge-shaped areas of suppuration (Fig. 20-28). The distribution of these lesions is unpredictable and haphazard, but in pyelonephritis associated with reflux, damage occurs most commonly in the lower and upper poles. - Figure 20-28 Acute pyelonephritis. Cortical surface shows grayish white areas of inflammation and abscess formation.
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Three complications of acute pyelonephritis are encountered in special circumstances.

- Papillary necrosis is seen mainly in diabetics and in those with urinary tract obstruction. Papillary necrosis is usually bilateral but may be unilateral. One or all of the pyramids of the affected kidney may be involved. On cut section, the tips or distal two thirds of the pyramids have areas of gray-white to yellow necrosis (Fig. 20-30). On microscopic examination the necrotic tissue shows characteristic coagulative necrosis, with preservation of outlines of tubules. The leukocytic response is limited to the junctions between preserved and destroyed tissue. - Pyonephrosis is seen when there is total or almost complete obstruction, particularly when it is high in the urinary tract. The suppurative exudate is unable to drain and thus fills the renal pelvis, calyces, and ureter with pus. - Perinephric abscess is an extension of suppurative inflammation through the renal capsule into the perinephric tissue

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Figure 20-38

Figure 20-38 Close-up of the gross appearance of the cortical surface in benign nephrosclerosis illustrating the fine, leathery granularity of the surface.
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Autosomaldominant (adult) polycystic kidney disease (ADPKD) ADPKD Morphology.

is a hereditary disorder characterized by multiple expanding cysts of both kidneys that ultimately destroy the renal parenchyma and cause renal failure

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- In gross appearance, the kidneys are usually bilaterally enlarged and may achieve enormous sizes; weights as high as 4 kg for each kidney have been reported. The external surface appears to be composed solely of a mass of cysts, up to 3 to 4 cm in diameter, with no intervening parenchyma (Fig. 20-47A and B). - However, microscopic examination reveals functioning nephrons dispersed between the cysts. - The cysts may be filled with a clear, serous fluid or, more usually, with turbid, red to brown, sometimes hemorrhagic fluid. As these cysts enlarge, they may encroach on the calyces and pelvis to produce pressure defects. The cysts arise from the tubules throughout the nephron and therefore have variable lining epithelia. On occasion, papillary epithelial formations and polyps project into the lumen. Bowman capsules are occasionally involved in cyst formation, and glomerular tufts may be seen within the cystic space - About 40% have one to several cysts in the liver (polycystic liver disease) that are usually asymptomatic. is genetically distinct from adult polycystic kidney disease. Perinatal, neonatal, infantile, and juvenile subcategories have been defined, depending on the time of presentation and presence of associated hepatic lesions. The first two are the most common; serious manifestations are usually present at birth, and the young infant might succumb rapidly to renal failure

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Autosomalrecessive (childhood) polycystic kidney disease (ARPKD)

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ARPKD Morphology.

- The kidneys are enlarged and have a smooth external appearance. On cut section, numerous small cysts in the cortex and medulla give the kidney a spongelike appearance. Dilated elongated channels are present at right angles to the cortical surface, completely replacing the medulla and cortex (Fig. 20-47C). - On microscopic examination, there is cylindrical or, less commonly, saccular dilation of all collecting tubules. The cysts have a uniform lining of cuboidal cells, reflecting their origin from the collecting ducts. - In almost all cases the liver has cysts associated with portal fibrosis (Fig. 20-47D) and proliferation of portal bile ducts.
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Typical Hemolytic Uremic Syndrome: Atypical Hemolytic Uremic Syndrome:

- This is the best-characterized form of HUS. Most cases occur following intestinal infection with strains of E. coli (the most common being O157:H7) that produce Shiga-like toxins - Atypical HUS occurs mainly in adults in a number of different settings. More than half of those affected have an inherited deficiency of complement-regulatory proteins, most commonly factor H, which normally breaks down the alternative pathway C3 convertase and protects cells from damage by uncontrolled complement activation. 1. The antiphospholipid syndrome, either primary or secondary to SLE (lupus anticoagulant). In this setting the microangiopathy tends to follow a chronic course. 2. Complications of pregnancy or the postpartum period. So-called postpartum renal failure is a form of HUS that usually occurs after an uneventful pregnancy, 1 day to several months after delivery. The condition has a grave prognosis, although recovery can occur in milder cases. 3. Vascular diseases affecting the kidney, such as systemic sclerosis and malignant hypertension. 4. Chemotherapeutic and immunosuppressive drugs, such as mitomycin, cyclosporine, cisplatin, and gemcitabine. 5. Irradiation of the kidney. - TTP is classically manifested by the pentad of fever, neurologic symptoms, microangiopathic hemolytic anemia, thrombocytopenia, and renal failure. it is usually caused by antibodies (either autoimmune or drug-induced) or genetic defects that lead to functional deficits in ADAMTS13. - The most common cause of deficient ADAMTS13 activity is inhibitory autoantibodies, and the majority of those with such antibodies are women. central nervous system involvement is the dominant feature, whereas renal involvement occurs in only about 50% of patients.

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A variety of miscellaneous conditions or exposures are occasionally associated with atypical forms of HUS. These include:

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Thrombotic thrombocytopenic purpura (TTP) - pg 952-953

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Nephrolithiasis: (figure 20-51)

Nephrolithiasis (renal stones) is manifested by severe spasms of pain (renal colic) and hematuria, often with recurrent stone formation.
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Table 20-12: Types of Kidney Stones

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Table 20-3: The Glomerular Syndromes

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Table 20-7: Causes of Nephrotic Syndrome

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Table 20-11: Summary of Renal Cystic Diseases