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Congenital dis. Of kidney
Agenesis The absence of both kidneys is not compatible with life. Absence of one kidney, the other kidney undergoes compensatory hypertrophy to maintain normal renal function Hypoplasia failure of one kidney to reach adult size. , the other kidney undergoes compensatory hypertrophy
Persistant faetal lobulation Displacement or ectopic kidney Horse shoe Kd. The 2 Kds. are fused at one Pole Double ureter & pelvis Aberrant renal a. abn, site of renal art. Cong. Cysts of the kidney Solitary cyst. Or Multiple Cysts
(The horseshoe kidney is a form of ectopic kidney in which the poles of the two kidneys fuse in the pelvic cavity prior to ascending. This leads to a large U-shaped kidney which is unable to ascend to the level of L1 because it is blocked by the inferior mesenteric artery at the aorta. ) CYSTIC DISEASES OF THE KIDNEY ADULT POLYCYSTIC KIDNEY DISEASE AUTOSOMAL DOMINANT PKD (ADPKD) A very common form of PKD that does not manifest until mid-adulthood. Formation of very large, disparate cysts. Process can involve any part of the nephron. Renal failure occurs late-onset (adult) when it occurs, but it only occurs in about 50% of cases. The kidneys can withstand an incredible number of cysts before function is compromised. Etiology: Genetic, autosomal dominant A Genes located on the short arm of chromosome 16 (APKD1). Pathogenesis: • The basic pathologic process may be considered a proliferative /hyperplastic abnormality of the tubular epithelium. • In the early stages of cyst development, the cysts are connected to the tubules from which they arise and the fluid content is glomerular filtrate. • When the cyst diameter exceeds 2 mm, most detach from the patent tubule and the fluid content is derived from secretions of the actual lining epithelium. 1
• With time, the cysts enlarge and cause progressive damage to adjacent functioning nephrons. • Cysts develop along the entire length of the nephron Pathogenesis: • The basic pathologic process may be considered a proliferative /hyperplastic abnormality of the tubular epithelium. • In the early stages of cyst development, the cysts are connected to the tubules from which they arise and the fluid content is glomerular filtrate. • When the cyst diameter exceeds 2 mm, most detach from the patent tubule and the fluid content is derived from secretions of the actual lining epithelium. • With time, the cysts enlarge and cause progressive damage to adjacent functioning nephrons. • Cysts develop along the entire length of the nephron Epidemiology: • Relatively common, occurring in one in 500 to 1000 individuals. • Adult PKD is the third most common cause of end-stage renal disease. General Gross Description: • The disease is bilateral. • The kidneys are enlarged (can be massive, up to 4 kg each). • The kidneys overall remain reniform in shape but the parenchyma shows innumerable cysts of varying sizes from barely visible to 4 to 5 cm. • The fluid content may be clear to reddish brown. • Cysts found in both cortical and medullary regions. General Microscopic Description: • Most of the cysts are lined by non-descript, flattened to cuboidal epithelial cells. • Some cysts however show epithelia with features of proximal tubules, distal tubules and collecting ducts. • Tissues between the cysts may show unremarkable or atrophic nephron elements. Clinical Correlations: • usually present in the fourth to fifth decade of life with progressive renal insufficiency and bilaterally enlarged cystic kidneys. • Hypertension is a common complication
Extrarenal manifestations include: hepatic, pancreatic and splenic cysts; intracranial and aortic aneurysms; and cardiac valve abnormalities. INFANTILE AUTOSOMAL RECESSIVE PKD (ARPKD)
The cysts uniformly arise in the collecting ducts, rather than the whole nephron.
compared to ADPKD, the cysts are diffuse and evenly distributed.
Renal failure is virtually inevitable, usually occurring in childhood, but it can occur in
Associated with congenital Hepatic Fibrosis.
Etiology: Genetic, autosomal recessive. Pathogenesis: • The pelvis, calyces, papillae as well as the nephrons are believed to develop normally in the initial stages of renal genesis. • The cystic development of the collecting ducts are believed to occur subsequently by a hyperplastic process. Epidemiology: • Developmental disorder of the kidneys discovered in developing fetuses (by ultrasound) or in the newborn period (enlarged kidneys). General Gross Description: • The kidneys are bilateral and symmetrically enlarged but retain a reniform shape. • Cut surface of the kidneys shows elongate cylindrical spaces radially arranged from the medulla into the cortex. This feature blurs the normal distinct cortico-medullary junction. General Microscopic Description: • On microscopic examination, the cysts are elongate and cylindrical and radiate from the medulla to the cortex. • The cysts are lined by a single layer of cuboidal epithelium similar to that of the collecting ducts. Clinical Correlations • Cases are discovered antenatally if prenatal care includes utrasonographic studies. • Most cases that go to term die shortly after birth from respiratory difficulties due to the enlarged kidneys that have resulted in developmental pulmonary hypoplasia. • This disease is not invariably fatal. Those cases that survive infancy may subsequently develop hepatic portal fibrosis, portal hypertension and splenomegaly.
ACQUIRED PKD PATHOGENESIS: Happens with renal failure patients on dialysis.
Cell Carcinoma is the most common complication..
SIMPLE RENAL CYSTS •That's just what they are.
II Glomerular Diseases
Glomerular Diseases • Glomerular diseases are one of the MC causes of CRF
• Primary glomerulopathies – glomeruli are injured &
the kidney is the only or predominant organ involved
• Secondary glomerulopathies – glomeruli are injured
during the course of a systemic disease
•They are bilateral and mostly immunologically mediated
•diffuse – all glomeruli are involved
• focal – only a certain proportion of the glomeruli are • global – entire glomerulus is involved • segmental – only a portion of the glomerulus is involved
Primary Glomerulopathies Acute diffuse proliferative glomerulonephritis Poststreptococcal Non-poststreptococcal Rapidly progressive (crescentic) glomerulonephritis Membranous glomerulopathy Minimal change disease Focal segmental glomerulosclerosis Membranoproliferative glomerulonephritis IgA nephropathy Chronic glomerulonephritis 4 involved
Systemic Diseases with Glomerular Involvement (Secondary) Systemic lupus erythematosus Diabetes mellitus Amyloidosis Microscopic polyarteritis/polyangiitis Wegener granulomatosis Henoch-Schönlein purpura Bacterial endocarditis Hereditary Disorders Alport syndrome Thin basement membrane disease Fabry disease Glomerular Diseases – Pathogenesis • immune mechanisms underlie most cases of 10 glomerulo-nephritis & many cases of 20 glomerulonephritis • glomerular deposits of Ig’s &/or complement components are found in > 70% of patient’s with glomerulonephritis
• • • • •
2 forms of antibody-associated injury have been established antibodies reacting in situ with Ag’s in the glomerulus insoluble fixed (intrinsic) glomerular Ag’s, or molecules planted within the glomerulus deposition of soluble circulating antigen-antibody complexes within the glomerulus
Immune Mechanisms of Glomerular Injury Antibody-Mediated Injury In Situ Immune Complex Deposition Fixed intrinsic tissue antigens NC1 domain of collagen type IV antigen (anti-GBM nephritis) Heymann antigen (membranous glomerulopathy) Mesangial antigens Others Planted antigens Exogenous (infectious agents, drugs) Endogenous (DNA, nuclear proteins, immunoglobulins, immune complexes, IgA Circulating Immune Complex Deposition Endogenous antigens (e.g., DNA, tumor antigens) Exogenous antigens (e.g., infectious products) Cytotoxic Antibodies
Immune Injury Activation of Alternative Complement Pathway
HISTOLOGIC ALTERATIONS Various types of glomerulonephritis are characterized by one or more of four basic tissue reactions.
Hypercellularity. Basement Membrane Thickening. Hyalinization and Sclerosis.
Some inflammatory diseases of the glomerulus are characterized by an increase in the number of cells in the glomerular tufts. This hypercellularity is characterized by one or more combinations of the following:
Cellular proliferation of mesangial or endothelial cells Leukocytic infiltration, consisting of neutrophils, monocytes ..
Formation of crescents. These are accumulations of cells composed of proliferating parietal epithelial cells and infiltrating leukocytes.
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 can be resolved as one of two alterations: 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; or thickening of the basement membrane proper, as occurs in diabetic glomerulosclerosis
and Sclerosis. By light microscopy ,the accumulation of homogeneous and eosinophilic material. By electron microscopy, the hyalin is extracellular and consists of amorphous substance, made up of plasma proteins that have exuded from circulating plasma into glomerular structures. Hyalinosis is usually a consequence of capillary wall injury and typically is the end result of various forms of glomerular damage. Additional alterations include intraglomerular thrombosis or accumulation of lipid or other metabolic materials.
Types of glomerulonephritis The most common types with established pathological and clinical characteristics are: Acute diffuse post-streptococcal proliferative glomerulonephritis Rapidly progressive glomerulonephritis (crescentic glomerulonephritis). Membranous glomerulonephritis. Membranoproliferative glomerulonephritis Minimal change glomerulonephritis (lipoid nephrosis Focal glomerulosclerosis Focal glomerulonephritis. Chronic glomerulonephritis. Clinical Manifestations of Glomerular Disease asymptomatic proteinuria Nephrotic syndrome (proteinuria, hypoproteinemia, lyperlipidemia, edema) asymptomatic hematuria Glomerulonephritis (Nephritic Syndrome) (hematuria, proteinuria, hypertension, renal failure) acute glomerulonephritis (neprhitis with short term renal failure) crescentic glomerulonephritis (nephritis with rapidly progressive renal failure) chronic glomerulonephritis (chronic progression of renal failure) End Stage Renal Disease (irreversible renal failure) NEPHRITIC SYNDROME A group of renal diseases with the following common clinical features Hematuria Oliguria (GFR↓, Cr↑, BUN↑) Edema (salt and water retention) Hypertension Proteinuria Hypoalbuminemia NEPHROTIC SYNDROME A group of renal diseases with the following common clinical features Proteinuria (“nephrotic range” >3.5g/24h) Hypoalbumimenia Edema Hyperlipidemia Lipiduria
Acute Proliferative Glomerulonephritis characterized histologically by diffuse proliferation of glomerular cells with an influx of leukocytes Caused by deposition of immune complexes inciting Ag may be exogenous or endogenous Prototypical exogenous pattern is postinfectious glomerulo-nephritis Prototypical endogenous pattern is SLE Acute Post streptococcal Proliferative GN Aetiology Pathogenesis Naked Eye Develops 2 wks after upper resp.infection or skin infection by β hemolytic strept.group A Immune complex disease Both kidneys are slightly enlarged equal ,slightly pale With thin easily stripped capsule Smooth outer surface Cut section shows wide coreex &differentiated from medulla All glomeruli are enlarged hypercellular due to proliferation of endothelial and mesangeal cells Obliteration of capillary lumen and narrowing of Bowman 's space PNL & monocytes infiltration Red cell cast in distal tubules Interstitial oedema Discrete subepith. Deposits (humps)
Granular flourescence of glom. cap. wall & mesangium.for C & IgG
Clinical & lab. Finding
Fever , malaise Oedema of face Transient Mild hypertension ⇑Bl. Urea (mild) Oliguria Smoky urine(haematuria) Sp.gr. of urine high ⇑ESR , ⇑ Aso Low serum comp. • In children 95% recover • In adults 60% Complications • Acute R.F. • Rapidly prog. • Ch. G.N.
Rapidly Progressive (Crescentic) Glomerulonephritis (RPGN)
Deterioration of renal function over a period of days to weeks
Goodpasture Syndrome (Type I) Type II (With Immune Complexes) Type III (Without Immune Complexes)
RPGN is classified as follows Type I – Anti GBM disease/Goodpasture syndrome Type II – Immune complex mediated like MPGN, Lupus nephritis, Ig A nephropathy Type III – Pauci-immune ANCA associated Vasculitis like Wegner’s granulomatosis, Microscopic Polyangiitis Rapidly Progressive (Crescentic) Glomerulonephritis • Not a specific etiologic form of glomerulonephritis
•Characterized clinically by rapid & progressive loss of renal function with severe
• Death from renal failure within weeks to months if untreated
•divided into 3 groups based on immunologic findings Type I RPGN • anti-GBM disease with linear deposits of Ig’s & C3 • in some patients the anti-GBM Ab’s cross-react with pulmonary alveolar BM (Goodpasture syndrome) • exposure to viruses, solvents, various drugs & cancers have been implicated in triggering formation of the Ab’s Type II RPGN • immune complex-mediated disease • can be a complication of any of the immune complex nephritides • granular pattern of staining for Ig’s & C3 Type III RPGN • pauci-immune type • most of these patients have ANCA • some cases are associated with a systemic vasculitis Rapidly progressive glomerulonephritis Aetiology Pathogenesis IdiopathicMay follow acute Immune compex disease. orAntiglomerular b.m disease
As acute but the kidney is pale with petechaeal hemorrhage in cortex
Light microscopy •Glom.enlarged hypercellular with proliferation of endothelial,mesangial &capsular epithelium •More than 50% of glom.show crescent formation due to localized proliferation of capsular epith. there may be segmental necrosis with hemorrhage into Bowman's space. •Blood vessels may show malignant hypertension •Interst.oedema •Red cell casts& protein in tubules
Granular or linear flour. May be negative in pauci immune type Fibrin is seen in the crescents.
focal ruptures in the GBM
Clinical & lab. Finding
As acute but more sever
Fatal in weeks to 1 year.Due to : Acute R.F. Hypertension.
Goodpasture’s syndrome Definition: A form of rapidly progressive glomerulonephritis (Bilateral pulmonary hemorrhage +rapidly progressive GN) 11
Progressive decrease in kidney function, Accompanied by a cough with bloody sputum. More in children especially ♂
The disorder is characterized by deposits of antibodies in the basement membranes of both the kidney glomerulus and the lung alveoli, causing both glomerulonephritis and pulmonary (lung) bleeding. NEPHROTIC SYNDROME A group of renal diseases with the following common clinical features Proteinuria (“nephrotic range” >3.5g/24h) Hypoalbumimenia Edema Hyperlipidemia Lipiduria Important causes of N.S. : 1Glomerulonephritis esp. Membranous G.N. Membranoproliferative G.N Minimal lesion G.N. 234567SLE. Diabetic glomerulosclerosis Amyloidosis Infections as syphilis. malaria , viral hepatitis B Malignancy esp. lymphoma. Drugs as NSAI.
•in children: 95% of cases are due to primary glomerular diseases
• in adults: 60% of cases are due to primary glomerular diseases • MC 10 glomerular diseases causing nephrotic syndrome • minimal change disease (mostly children) • focal segmental glomerulosclerosis (all ages) • membranous glomerulopathy (mostly adults) • MC systemic diseases causing nephrotic syndrome • diabetes mellitus (mostly adults) • amyloidosis (mostly adults) • systemic lupus erythematosus (mostly adults) complications: apart from chronic renal failure •⇑ infections due to loss of Ig’s & complement •0 ⇑ thrombosis due to loss of anticoagulant factors 12
Membranous Glomerulopathy •MC cause of nephrotic syndrome in adults
• primary membranous GN (85% of cases) • secondary membranous GN • drugs (e.g., penicillamine, NSAIDs) • malignancies (esp. carcinoma of lung & colon, melanoma) • SLE • infections (e.g. hepatitis B & C, syphilis) • Hashimoto thyroiditis •secondary membranous GN is caused by deposition of immune complexes •primary membranous GN is caused by autoantibodies directed against an Ag on the
visceral epithelial cells •proteinuria is probably caused by C5b-C9 • damage to visceral epithelial cell membrane (10 MGN) • activation of epithelial & mesangial cells ⇒ release of proteases & oxidants ⇒ capillary wall damage morphology • diffuse thickening of glomerular capillary wall • EM reveals subepithelial deposits • spikes can be seen (silver stains ) • granular deposits of Ig’s & complement on IF • GBM becomes progressively thicker and compresses the capillary lumens Clinical Course • usually present with nephrotic syndrome
• important to rule out secondary causes • proteinuria is nonselective & does not usually respond well to corticosteroids • course is variable but generally indolent • only ~ 10% die or progress to CRF within 10
years Course & prognosis Remission & exacerbation then Ch. G.N.
Minimal Change Disease common in children Etiology: Idiopathic Drugs – NSAID Toxins – Mercury, Lead Infections – HIV, Mononucleosis Tumors – Hodgkin disease Patient usually normotensive, nephrotic sediment, normal renal function. (Lipoid Nephrosis) • peak incidence 2-6 years of age • MC cause of nephrotic syndrome in children • sometimes follows a respiratory infection or vaccination • ⇑ incidence in patients with Hodgkin disease • morphology • glomeruli are normal by light microscopy • epithelial cells exhibit diffuse loss of foot processes on EM • proximal tubular cells are often laden with lipid • no Ig or complement deposits detected by IF etiology & pathogenesis • evidence indicates an immune mechanism •immune dysfunction ⇒ circulating cytokine ⇒ injures visceral epithelial cells ⇒ proteinuria • some cases are caused by mutations in genes that encode slit diaphragm proteins clinical course • massive proteinuria, mostly albumin • renal function remains good, usually no ⇑ BP or hematuria • most children exhibit a dramatic response to cortico- steroid • long-term prognosis is excellent
Membranoproliferative Glomerulonephritis Membranoproliferative glomerulonephritis (MPGN) can present with the nephrotic syndrome, nephritic syndrome, or, most often, a mixture of the two. The two most common variants of MPGN are Type I MPGN (also called mesangiocapillary GN) Type II MPGN (also called dense deposit disease). Type I is much more common than type II, which is a rare Characterized by alterations in the GBM, proliferation of glomerular cells & leukocyte infiltration 14
MPGN accounts for 10-20% of cases of nephrotic syndrome in children & young adults
present with a combined nephritc/nephrotic picture
May be primary or secondary MPGN Primary MPGN is divided into types I & II
Pathogenesis type I MPGN • deposition of immune complexes with activation of both classical & alternative complement pathways • Ag’s involved in primary MPGN are unknown type II MPGN ⇓ serum C3, factor B & properidin, but normal serum C1 & C4 ⇒ activation of alternative complement pathway • > 70% of patients have C3 nephritic factor (C3NeF) •0 C3NeF stabilizes alternative pathway C3 convertase
Course : remissions & exacerbations finally end in chronic renal failure. Morphology glomeruli are enlarged, hypercellular & lobulated glomerular capillary wall has a “double contour” or “tram-track” appearance caused by duplication of the GBM with mesangial & monocyte interposition EM &IF Type I MPGN subendothelial electron-dense deposits granular deposits of C3 and often IgG, C1q & C4 Type II MPGN lamina densa is extremely electron-dense (dense-deposit disease) C3 is present in the GBM & mesangium (mesangial rings) IgG, C1q & C4 are usually absent Diseases of Urinary System 02
Diseases of the Tubules & Interstitium
• May occur secondary to : 1. glomerular disease 2. Vascular disease 3. Cystic disease 4. Metabolic :DM Primary interstitial Nephritis
This means suppurative inflammation of the pelvicalyceal ayatem and the renal parenchyma; it is usually bilateral. affects the women more than men. Most commonly, it occurs as a result of urinary tract infection. Incidence About 3 to 7 out of 10,000 people. Predisposing factors • Obstruction of the urinary tract with stasis of urine • vesicoureteric reflux: )Normally, the urine does not ascend along the ureters during micturition due to the oblique course of the intravesical portion of the ureter, which provide a sphincter-like effect during contraction of the bladder.) If this effect is disturbed due to congenital or acquired reasons, the urine will ascend along the ureter and may even reach the kidneys during bladder emptying. • Bilharsisis. • Instrumentation of the urinary tract. • Diabetes mellitus due to ??? • Female more due to short urethra. • Pregnancy due to hormonal relaxation of smooth muscle and pressure of the gravid uterus. Causative organism : any pyogenic bacteria as E.coli, B. proteus, B pyocyaneus, Klebsiella and Strop . foecalia. Routes of infection: 1. Ascending infection from the lower urinary tract. 2. Lymphatic spread from the intestinal tracL 3. Blood borne infection complicating boils or carbuncles. Pathology: Acute pyelonephritis Chronic pyelonephritis
Acute pyelonephritis Grossly: The plevicalyceal system is acutely inflamed, the renal parenchyma shows multiple foci of suppuration which appear as yellow streaks radiating from the renal papillae, to expand into "abscesses" in the cortex. Microscopically: The pelvicalyceal system is acutely inflamed. The renal parenchyma is congested and infiltrated by neutrophils which collect in the interstitial tissue or within the tubular lumena to form abscesses. Fate : It may resolve, kill by acute renal failure or progress to chronic pyelonephritis Chronic pyelonephritis Chronic pyelonephritis results when the kidneys become increasingly damaged due to repeated urinary infections. Or unresolved acute attack Incidence 1 in 4 of the people who are diagnosed as having chronic kidney failure have chronic pyelonephritis. Grossly : The kidneys are unequally shrunken with multiple irregular depressed scars On cut section, these scars extend from deformed calyces towards the surface . Thickened,opaque pelvicalyceal mucosa Microscopically: Periglomerular fibrosis. Tubular atrophy . In foci tubules are dilated and filled with hyaline casts giving an appearance reseinbling thyroid follicles ( thyroidization). Infiltration of interstitial tissue by chronic inflmmatory cells and neutrophils. Tubulointerstitial nephritis caused by drugs Drugs may produce renal injury by three mechanisms: 1. An immunologic (allergic, hypersensitivity) reaction leading to an acute interstitial nephritis. 2. Direct nephrotoxicity leading to acute tubular necrosis. 3. Slowly progressive damage to the tubules leading to a
chronic tubulointerstitial nephritis. Acute drug induced tubulointerstitial nephritis may be induced by synthetic penicillins (methicillin, ampicillin), sulfonamides, rifampin, diuretics (thiazides) and non steroidal antin-flammatory drugs (phenyl butazone). It is characterized clinically by acute renal insufficiency that typically starts two weeks after the beginning of drug administration. Acute tubular necrosis, due to direct nephrotoxicity may be induced by antibiotics (gentamicin) and antifungal agents (amphotericin B). It leads to acute renal failure. Chronic tubulointerstitial nephritis may be induced by heavy usage of analgesic , mainly those containing phenacetin (analgesic nephropathy). It may end in chronic renal failure. Acute tubular necrosis ATN Ichemia and exposure to nephrotoxins that poison the kidney are the two main causative agents of acute tubular necrosis Two types 1. anoxic tubular necrosis (lower nephron nephrosis) 2. toxic tubular necrosis Anoxic tubular necrosis may be caused by: 1. Mismatched blood transfusion. 2. Crush injuries. 3. Burns. 4. Shock. Toxic tubular necrosis may be caused by: 1. Poisons eg mercuric chloride, phosphorous, carbon tetrachloride, insecticides. 2. Some drugs eg. gentamicin, amphotericin B. VASCULAR DISEASES OF THE KIDNEY Renal Artery Stenosis Unilateral renal artery stenosis accounts for 2% to 5% of renal hypertension, resulting from excessive renin secretion by the involved kidney.
70% of stenoses are caused by obstructive atheromatous plaques at the origin of the renal artery The remainder by fibromuscular dysplasia. Fibro or fibromuscular thickening of intema,media or adventia (3 types:intimal,medial or advential) Ischaemic kidney Small size due to ischemic atrophy Arteries in ischemic kidney are protected from high pressure Contra lateral non ischemic kidney Arteries will show hyaline arteriolosclerosis Bilateral cortical necrosis very rare . ischaemic in origin, it appears probable that vascular spasm followed by thrombosis. Causes: 1. Toxaemia of pregnancy. 2. Severe infections: Such as pneumonia, diphtheria and scarlet fever. Grossly: cortex of both kidneys, with the exception of a very thin surface layer (supplied by the capsular arteries), is bright yellow outlined with red. Microscopically: coagulative necrosis of the cortex of both kidneys. Clinically: There is oliguria or anuria with the development of acute renal failure. Necrosis of the renal papillae Papillary necrosis It is a rare condition there is necrosis of the papillae of both kidneys. Sometimes it is accompanied by necrosis of the medulla and in this case, the disease is called renal medullary necrosis. It is an ischaemic necrosis may be due to an accompanying pyelonephritis due to some predisposing factors such as 1. diabetes mellitus, 2. excess intake of phenacetine or 3. chronic alcoholism. HYDRONEPHROSIS It is the dilatation of the pelvis and calyces of the kidney leading to pressure atrophy of the kidney tissue.
It is due to gradual, incomplete or intermittent obstruction to the flow of urine. Grossly: The kidney is enlarged in size, the outer surface May be lobulated. The pelvis and calyces are dilated with, atrophy and fibrosis of the renal tissue. Microscopically: There is atrophy of the tubules and the glomeruli with fibrosis. Causes of hydronephrosis: In the urethra: leading to bilateral hydroureter and hydronephrosis. 1.Nodular hyperplasia of the prostate and cancer prostate. 2.Stricture of the urethra wether congenital, traumatic or due to gonorrhea. In the urinary bladder: If the cause is in the bladder neck it will cause bilateral hydronephrosis, but elsewhere it will cause unilateral hydronephrosis. 1.Bilharzial stricture: Either in the ureteric orifice or causing bladder neck obstruction. 2.A large stone in the urinary bladder. 3.Tumours: As carcinoma or papilloma of the urinary bladder. In the ureter: Leading to unilateral hydroureter and hydronephrosis: 1.Congenital causes as congenital stricture or aberrant renal artery pressing the ureter. 2.Stone in the ureter, 3.Bilharzial stricture. 4.Tuberculosis of the ureter. . 5.Endometriosis with pelvic lesions, followed by scarring. 6.Cancer cervix in females infiltrating the ureter. 7.Ectopic kidney leading to kinking of the ureter. 8. Retroperitoneal fibrosis: It is an idiopthic disease leading to the formation of dense fibrous tissue extending from the lower part of the vertebral column and extends laterally to involve the ureter. Renal Stones UROLITHIASIS Renal calculi Risk Factors – Increased conc. of solutes – change in urinary Ph – decreased urinary volume – infection Types 1.Calcium oxalate(phosphate)stones 75% )hypercalcinuria, hypercalcemia, excess) 2.Magnesium Ammonium phosphate stones10-15% )alkaline urine due to infection(
3.Uric acid stones 6% ) gout, leukemias, acidic urine) 4.Cystine stones 1-2% Pathogenesis : For calcium stones ↑ urine conc. of the stone constituent (supersaturation) Hypercalcemia with hypercalcuria hyperparathyroidism, bone metastases, ↑ Ca++ absorption ↓ renal reabsorption Hypercalcuria without hypercalcemia For Magnesium Ammonium phosphate stones Infection with urea splitting organism →alkaline urine →ppt.Mg Amm Phosphate For uric acid stones Gout & leukemia,lymphomas 50% form without hyperuricuria unexplained tendency to excrete a persistantly acid urine pH 5.5 favouring stone formation For cystine stones genetically determined defect in renal transport of amino acids Effects &complications of renal stones Renal colic Hematuria Obstruction Infection Stricture Squamous metaplasia TUMOURS OF THE KIDNEY TUMOURS OF THE KIDNEY Tumours of the kidney tissue & Tumours of the renal pelvis Tumours of the kidney tissue: Benign tumours adenoma, fibroma, lipoma, angiomyolipoma and oncocytoma. Malignant tumours: i) Primary - Renal cell carcinoma (Hypernephroma). - Embryoma (Wilms tumour or Nephroblastoma) ii) Secondaries from:
- Carcinomas of the lung, breast and prostate. - Sarcomas, like osteosarcoma. - Malignant melanoma and choriocarcinoma.
Renal Cell Carcinoma
6th to 7th decade Male predominance 3:1 Yellow round mass, 3 -15 cm Often invade renal vein and extend into the inferior vena cava Chromosome 13 General features A tumour which arises from the epithelial cells of the renal tubules Renal cell carcinoma is generally tumor of adults >55 to 60 y The male to female ratio is about 2:1 One of the many peculiarities of renal cell carcinoma is its occasional regression in the absence of all treatment, a phenomenon found also with gestational choriocarcinoma, malignant melanoma, neuroblastoma, Renal cell carcinoma is the most common "recipient" of the curious phenomenon of metastasis of a cancer into another cancer. Lung carcinoma is the most common "donor," the resulting microscopic appearance leading to interesting problems of interpretation Conditions that may be complicated by renal cellcarcinoma are the following: Von HippelLindau (VHL) disease. Renal cell carcinoma occurs in about 40% to 50% of individuals with this syndrome. Acquired cystic disease. Half of the patients on long term dialysis develop an acquired form of polycystic renal disease, which in a few cases has been complicated by the appearance of renal cell adenomas and carcinomas. Adult form of polycystic kidney disease Von Hippel-Lindau (VHL) syndrome VHL Hemangioblastomas of the cerebellum and retina. Renal cysts. Renal cell carcinomas (nearly all, if they live long enough) bilateral, often multiple. Clinical features Renal carcinoma usually presents with Hematuria (59%)
Flank pain (41%), or Abdominal mass (45%). Weight loss (28%), Anemia (21%), Fever (7%), and Symptoms caused by a metastatic deposit (10%). Grossly most renal cell carcinomas are well delineated and centered on the cortex In about 5% of the cases, multiple tumor nodules are seen scattered throughout the organ In a typical case, the cut surface shows a solid golden yellow tumor sharply separated from the surrounding tissues by a fibrous pseudocapsule Hemorrhage, necrosis, calcification, and cystic change Microscopically, the tumor cells may be large with clear cytoplasm, resulting from the accumulation of glycogen (clear cell type) or may be smaller in size with granula cytoplasm (granular cell type), or most often there is a mixture of clear and granular cells (mixed cell type). The stroma of the tumour is scanty, very vascular with areas of haemorrhage and necrosis. Tubular, papillary, and cystic formations may be present. Spread: Locally to adjacent renal tissue more to pelvis and late to capsule Hematogenous spread to-------- . – Invasion of left testicular vein in males will cause left side varicocele Lymphatic Paraneoplastic syndrome: RCC is known for its hormonal & hormone like effect e.g. it can produce parathyroid like hormone hypercalcemia
Wilm ’s tumor
Also known as nephroblastoma (currently the preferred term), embryoma, carcinosarcoma, adenosarcoma, and adenomyosarcoma. Childhood tumor .Primarily in infants, 50% before the age of 3 years and 90% before the age of 6 years Only exceptionally seen as a congenital neoplasm No appreciable sex predilection. There are 2 specific genetic loci predisposing to Wilms' tumor. 23
Chromosome 1 -loss of cancer suppression gene WT -1 Clinical features The classic clinical presentation of Wilms' an abdominal mass felt by the mother Hypertension Proteinuria Hematuria and pain are rare. Grossly solitary, well circumscribed, rounded, soft. variable size rapidly growing, destroying the kidney infiltrating the renal capsule. Infiltration of renal pelvis & ureter is rare & late The cut section is solid and pale gray or tan cystic change, necrosis, and hemorrhage Microscopically Most Wilms' tumors show a representation of three major components: Undifferentiated blastema, The blastematous areas are extremely cellular and composed of small round-to-oval primitive cells; Mesenchymal (stromal) tissue The mesenchymal elements usually have a spindle-cell fibroblast-like configuration smooth muscle and skeletal muscle. Epithelial tissue. formation of embryonic tubular (and sometimes glomerular) structures that closely recapitulate the appearance of normal developing metanephric tubules (and glomeruli) but the proportions vary widely. Some tumors are biphasic, and still others are monophasic (monomorphous). Spread and metastases In advanced cases, local spread occurs in the perirenal soft tissues. From here, the tumor may involve the adrenal glands, bowel, liver, vertebrae, and paraspinal region; Invasion of the renal vein is common, but extension into the renal pelvis or ureter is a rare and late event. Metastases in regional lymph nodes are found in 15% of the cases.
The most common sites of distant metastases are lungs, liver, and peritoneum. bone metastases in only 1% of the cases Tumours of the renal pelvis: Benign such as villous papilloma, haemangioma and fibroma. (2) Malignant i) Primary carcinoma such as transitional cell carcinoma, squamous cell carcinoma sacroma (rare). ii) Secondary (rare). DISEASES OF THE URINARY BLADDER Congenital anomalies 1. Ectopia vesica (exostrophy: The anterior bladder wall and the overlying part of the anterior abdominal wall are defective, It may be complicated by urinary tract infection, squamous or glandular metaplasia of the urothelium and carcinomas. 2. Epispadius: The urethra opens on the dorsum of the penis. 3. Hypospadius: The urethra opens on the ventral surface of the penis. 4. Patent urachus: A fistulous tract between bladder & umbilicus, discharging urine 5. Valves (mucosal folds) in the posterior urethra: Which may lead to obstruction. CYSTITIS Clinical Manifestations: frequency, pain, dysuria Causes: 1Infections: E. coli, Proteus, et al; TB, Candida, Chlamydia, Schistosomiasis, Adenovirus 2 Radiation & chemotherapy 3 Prolonged catheterization. Morphologic Types: Acute: nonspecific, hemorrhagic, suppurative, or ulcerative Chronic: nonspecific, cystitis follicularis & eosinophilic cystitis
Special Forms of Cystitis: Interstitial Cystitis (Hunner’s ulcer) painful chronic cystitis MC seen in women Predisposing factors: 1. Bilharziasis 2. Stasis of urine: due to obstruction nodular hyperplasia of prostate, stricture of the urethra and tumours of the urinary bladder. 3. Inflammation of nearby organs, such as kidneys, ureters, prostate, vulva, vagina, cervix and urethra. 4. Trauma to the urinary bladder by stones or catheter. 5. General diseases, such as diabetes. 6. Females are more commonly affected due to short wide urethra Grossly : wall is thickened , oedematous, red and congested and may be areas of haemorrhage,ulceration and necrosis. Chronic non specific cystitis: may follow acute or may start as such Grossly : The wall is thickened, congested with increased fibrosis granularity of the mucosa reduction of the lumen of the urinary bladder. In chronic cystitis one of the following lesions may be added t Leukoplakia: whitish patches due to squamous metaplasia with keratinisation. occurs usually due to irritation stones, or bilharzial ova. Follicular cystitis: In which the mucosa of the trigone shows minute greyish nodules due to the presence of lymphoid follicles even with germ centers, in the sub-epithelial tissues. Calcareous (encrusted) cystitis: The trigone and surrounding parts show multiple, whitish, hard, granular elevated patches due to precipitation of Ca salts in the mucosa. It is usually accompanied with alkaline urine. Emphysematous cystitis: caused by gas-forming bacteria associated with gas filled vesicles in the bladder wall. About 50% of the patients are diabetic. Malakoplakia: rare condition associated with immune deficiency states. The mucosa of trigone shows multiple nodular yellow soft thickenings 1-4 cm Microscopically, chronic inflammatory cells foreign body giant cells containing calcified material known as Michaelis - Gutmann bodies ( an end result of bacterial degradation.)
Tumours of the urinary bladder Benign tumours • Transitional cell papilloma: commonly near the ureteric orifices and bladder neck. It usually recurs after removal considered potentially malignant. It is considered by some authors as grade I carcinoma Grossly: multiple delicate finger-like processes. Microscopically: multiple delicate vascular connective tissue stroma, covered by layers of transitional epithelial , regularly arranged , no criteria of malignancy. • Inverted papilloma a benign epithelial tumor, more in adult and elderly males, mostly located in the trigone, bladder neck, or prostatic urethra. It is usually solitary presents with haematuria and obstruction. • Others: o Fibroma, o Leiomyoma, o Rhabdomyoma, o Neurofibroma, o Angioma and o Myxoma
Malignant Tumors Are common occurring more in males above the age of 40 years Precancerous lesions: a) Urinary bladder bilharziasis: It may be due to : Mechanical irritation of the ova Tryptophan metabolites as a carcinogenic agents which are usually present in high concentration in the urine. Metaplastic changes including cystic glandularis squamous metaplasia. b) Transitional cell papilloma. c) Aniline dyes used by dye workers. d) Cigarette smoking. e) Chronic irritation by stones, chronic cystitis. f) Leucoplakia. g) Congenital anomalies (ectopia vesica).
Site: The region of the trigone, as a consequence, partial or complete blockage of one or both ureters is frequent. Types : Transitional cell carcinoma Squamous cell carcinoma Adenocarcinoma TRANSITIONAL CELL TUMORS of the URINARY BLADDER comprise ~ 90% of all bladder tumors ~ 80% of patients with TCC are between 50 - 80 years old Gross Morphology: The better differentiated urothelial neoplasms commonly project into the lumen and have a delicate papillary appearance. In contrast poorly differentiated neoplasms are solid ulcerative lesions that frequently show evidence of infiltration of the bladder wall. Microscopic appearance: Over 90% are transitional cell carcinoma. Squamous or glandular differentiation commonly occur in transitional cell carcinoma (especially in invasive types). Grading : The International World Health Organisation histologic grading system for urothelial neoplasms recognize 4 histologic grades: Grade I transitional cell carcinoma shows • well formed papillary structures • lined by epithelium that is cytologically normal but thicker than 7 layers. • Invasion is uncommon. Grade II transitional cell carcinoma shows • well formed papillary and solid areas. • mild to moderate cytologic atypia • a greater degree of pleomorphism. • Invasion may occur. Grade III transitional cell carcinoma • predominantly solid invasive growth pattern • with or without a papillary structure • shows cytologic anaplasia • high mitotic rate. Grade IV transitional cell carcinoma: 28
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Most of these lesions are sessile, cauliflower-like, necrotic and ulcerated. Microscopically papillary areas are absent, cellular atypia and pleomorphism are so marked that the transitional cell nature may be obscured. Mitotic figures are frequent.
Prognosis: depends on histologic grade & stage papillomas & grade I tumors – 98% 10 yr. survival rate grade III tumors – 40% 10 yr. survival rate
Squamous Cell Carcinoma of the URINARY BLADDER It is common where bilharziasis is common (squamous metaplasia). Well differentiated keratinizing squamous cell carcinoma tends to form large bulky mass. Since foci of squamous cell differentiation are common in high grade transitional carcinoma, the term squamous cell carcinoma should be reserved for those tumours that are squamous throughout. Adenocarcinoma: May arise from: a) urachal remanents in the dome of the bladder. 2) areas of cystitis glandularis. (after metaplasia by bilharziasis). Non epithelial neonlasms: a) Paraganglioma (pheochromocytoma). b) Mesenchymal neoplasms: i) Leiomyoma and leiomyosarcoma. ii) Embryonal rhabdomyosarcoma (sarcoma botroides) in young children.
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