Pathology Chapter 20 The Kidney [Pages 949-967]

renal pathology associated with sclerosis of renal arterioles and small arteries, resultant effect - focal ischemia of parenchyma supplied by vessels with thickened walls and consequent narrowed lumen what is the loss of mass from benign nephrosclerosis due to? What are some of the other changes? form of renal disease associated with malignant or accelerated phase of hypertension what do patients with malignant hypertension have? consequences of markedly elevated blood pressure on blood vessels throughout body what is the the morphology of malignant nephrosclerosis fibrionoid necrosis of arterioles gives what type of appearance in malignant nephrosclerosis? due to stimulation of renin secretion by cells of the juxtaglomerular apparatus, and subsequent production of the vasoconstrictor angiotensin II - large proportion of individuals with renovascular hypertension have elevated plasma or renal vein renin levels and almost all show a reduction of blood pressure when given drugs that block activity of angiotensin II most common cause of renal artery stenosis is, occurs frequently in men, 2nd type of lesion leading to stenosis is group of disorders is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and in many causes renal failure, and morphologically by thrombotic lesions in capillaries and arterioles in various tissue beds, including those of the kidney most frequently associated with consumption of food contaminated by bacteria producing Shiga-like toxins occurs following intestinal infection with strains of E.coli - sudden onset of bleeding manifestations, severe oliguria and hematuria, associated with microangiopathic hemolytic anemia 1. inherited mtuations of complement-regulatory proteins 2. diverse acquired causes of endothelial injury, including antiphospholipid antibodies, complications of pregnancy and oral contraceptives, vascular renal diseases, chemotherapeutic and immunosuppressive drugs, radiation - most commonly affects factor H, which normally breaks down alternative pathway C3 convertase and protects cells from damage by uncontrolled complement activation often associated with inherited or acquired deficiencies of ADAMTS13, a plasma metalloprotease that regulates function of von Willebrand factor (vWF) benign nephrosclerosis

cortical scarring and shrinking; patchy ischemic atrophy, consists of 1. foci of tubular atrophy and interstitial fibrosis 2. variety of glomerular alterations malignant hypertension and accelerated nephrosclerosis markedly elevated levels of plasma renin malignant arteriosclerosis small, pinpoint petechial hemorrhages may appear on the cortical surface from rupture of arterioles or glomerular capillaries, gives kidney 'flea-bitten' appearance onion-skinning because of its concentric appearance renal artery stenosis

occlusion by an atheromatous plaque at the origin of the renal artery; fibromuscular dysplasia thrombotic microangiopathies

typical hemolytic-uremic syndrome (HUS)

atypical hemolytic-uremic syndrome (HUS)

TTP

Pathology Chapter 20 The Kidney [Pages 949-967]

what are 2 pathogenic thrombotic microangiopathies that get triggered classically manifested by pentad of fever, neurologic symptoms microangiopathic hemolytic anemia, thrombocytopenia, and renal failure most common cause of deficient ADAMTS13 activity is in TTP what's the dominant feature? fairly common cause of chronic ischemia with renal insufficiency in older individuals, sometimes in absence of hypertension embolization of fragments of atheromatous plaques from the aorta or renal artery into intraparenchymal renal vessels occurs in elderly patients with severe atherosclerosis, especially after surgery on the abdominal aorta, aortagraphy, or intra-aortic cannulization sickle cell disease (homozygous) or trait (heterozygous) may lead to a variety of alterations in renal morphology and function, most common clinical and functional abnormalities are uncommon condition that occurs most frequently after an obstetric emergency, septic shock, or extensive surgery kidneys are favored site for ____ because of extensive blood flow and extremely limited collateral circulation from extrarenal sites clinical features of renal infarct Incompatible with life usually encountered in still born infants Failure of the kidney to develop to a normal size, more commonly unilateral, no scars, reduced number of renal lobes and pyramids Characterized histologically by the persistence in the kidney of abnormal structures- cartilage, undifferentiated mesenchyme, and immature collecting ducts- and by abnormal lobar organization Characteristic histologic feature is the presence of islands of undifferentiated mesenchyme, often with cartilage and immature collecting ducts Hereditary disorder characterized by multiple expanding cysts of both kidneys that ultimately destroy the renal parenchyme and cause renal failure Cysts involve only the ___ in ADPKD Most likely mutation causing ADPKD The consequent disruption of normal polycystin activity leads to changes in intracellular Ca2+ level, and given the second messenger effects of calcium, to 1. endothelial injury - in typical HUS causes Shigalike toxin to be released 2. platelet aggregation TTP is initiating event appears to be induced by very large multimers of vWF thrombotic thrombocytopenic purpura inhibitory autoantibodies and majority of those with such antibodies are women CNS involvement, renal involvement occurs in only about 50% of patients bilateral renal artery disease atheroembolic renal disease

sickle cell disease nephropathy; hematuria and diminished concentrating ability, patchy papillary necrosis, proteinuria common diffuse cortical necrosis - has features of ischemic necrosis renal infarcts clinically silent, but sometimes pain and tenderness localized to the costovertebral angle, associated with shower of red cells in urine Agenesis of the kidney Renal hypoplasia Multicystic renal dysplasia

Multicystic renal dysplasia ADPKD Nephrons, so renal function is retained until the 4 th or 5th decade PKD1 Cellular proliferation, basal levels of apoptosis, interactions with the ECM, and secretory function of the epithelia

Pathology Chapter 20 The Kidney [Pages 949-967]

changes in Morphology of ADPKD Clinical features of ADPKD Bilaterally enlarged, cysts usually filled with turbid, red-brown sometimes hemorrhagic Accelerated progression in blacks, males, and in the presence of HTN, some have extrarenal congenital abnormalities including liver cysts; mitral valve prolapse Mutations of the PKHD1 on 6p21-p23, kidneys are enlarged with a smooth external appearance, small cysts in cortex and medulla Hepatic involvement Medullary sponge kidney Nephronophthisis and adult onset medullary cystic disease Nephronophthisis Acquired (dialysis-aquired) cystic disease 1. 2. 3. 4. 5. 6. 7. 8. 9. Congenital anomalies Urinary calculi Benign prostatic hypertrophy Tumors Inflammation Sloughed papillae or blood clots Pregnancy Uterine prolapse or cytocele Functional disorders Hydronephrosis

Morphology of autosomal-recessive (childhood) polycystic kidney disease Patients who survive infancy and juvenile usually have Lesions consisting of multiple cystic dilations of the collecting ducts in the medulla, adults, Presence of a variable number of cysts in the medulla, usually concentrated at the corticomedullary junction; cortical tubulointerstitial damage is the cause of eventual renal insufficiency Affected children present first with polyuria and polydipsia, sodium wasting and tubular acidosis also prominent Cysts contain clear fluid, lined by either hyperplastic or flattened tubular epithelium, can develop into renal cell carcinoma Causes of urinary tract obstruction

Describes dilation of the renal pelvis and calyces associated with progressive atrophy of the kidney due to obstruction to the outflow of urine Morphology of UTO

Earliest manifestation is inability to concentrate the urine reflected by polyuria and nocturia, distal tubular acidosis, renal salt wasting, secondary renal calculi, and chronic tubulointerstitial nephritis with scarring and atrophy of the papilla and medulla Results in oliguria or anuria Four main types of calculi

When obstruction is sudden and complete, GFR is reduced, there is dilation of the pelvis and calyces, and often significant interstitial inflammation Bilateral partial obstruction

Type of stone formed largely after bacterial infections Type of stone common in individuals with hyperuricemia and diseases involving high cell turnover

Complete bilateral obstruction 1. Calcium stones- composed of calcium oxalate 2. Triple stones/struvite stones- composed of magnesium ammonium phosphate 3. Uric acid stones 4. Cysteine stones Magnesium ammonium phosphate Uric acid stone

Pathology Chapter 20 The Kidney [Pages 949-967]

Type of stones from genetic defects in the renal reabsorption of AA Morphology of renal stones Clinical features renal stones Present invariably within the cortex and appear grossly as pale yellow-grey well circumscribed nodules, 3cm size separates those which metastasize from those which do not Benign tumor consisting of vessels, smooth muscle, and fat, present in up to of patients with tuberous sclerosis, susceptible to spontaneous hemorrhage Tumor composed of large eosinophilic cels having small, round, benign appearing nuclei that have large nucleoli, eosinophilic cells have numerous mitochondria, tumors are tan-mahogany brown Tumors most often in older individuals, males, gross yellow color, tumors arise from tubular epithelium, tobacco is the most significant risk factor Causes of autosomal dominant renal familial cancers Most common type of renal cancer, most cases are sporadic, loss of sequence on short arm of chrom 3 Papillary growth pattern, both familial and sporadic, MET protoncogene for hepatocyte growth factor, DCT, hemorrhagic and cystic, most common type in patients who develop dialysis-associated cystic disease, composed of cuboidal or low columnar cells arranges in papillary formations Cells with prominent cell membranes and pale eosinophillic cytoplasm, usually with a halo around the nucleus Nests of malignant cells enmeshed within a prominent fibrotic stroma, rare variant showing irregular channels lined by highly atypical epithelium with a hobnail pattern 3 classic diagnostic features of renal cell carcinoma Cysteine stones Mostly unilateral, favored sites for formation are within the renal calyces and pelves and in the bladder Smaller stones are more hazardous, producing colic and uretal obstruction, larger stones manifest with hematuria Renal papillary adenoma

Angiomyolipoma Oncocytoma

Renal cell carcinoma Von hippel-lindau syndrome, hereditary clear cell carcinoma, hereditary papillary carcinoma Clear cell carcinoma Papillary carcinoma

Chromophobe renal carcinoma Collecting duct carcinoma

Renal cell carcinomas also produce a number of One of the most common characteristics of RCC Most common locations of metastases for RCC Produce noticeable hematuria, may block urinary outflow and lead to palpable hydronephrosis and flank pain. Prognosis for this tumor is not good

CV pain, palpable mass, and hematuria (also associated with generalized constitutional symptoms such as fever, malaise, weakness and weight loss) Paraneoplastic syndromes Tendancy to give rise to metastases before giving rise to local signs or symptoms Lungs and bones Urothelial carcinomas of the renal pelvis