The Urinary System Pathology. Dr. Methaq Mueen د.ميثاق معين

Transcription

1 The Urinary System Pathology Dr. Methaq Mueen د.ميثاق معين

2 objectives To Know normal anatomy physiology and histology of renal system To discuss Kidney pathology: congenital, cystic disease, Glmerular disease To know tubluointerstitial disease, UTI To discuss urinary bladder pathology

3 Structures of the Urinary System Kidneys Nephrons Renal Pelvis Ureters Urinary Bladder The Urethra

4 Functions of the Urinary System The urinary system performs many functions important to maintaining homeostasis Maintenance of water, salts, minerals and acids balance in the body Filters blood to remove urea and other waste products of metabolism from the bloodstream Urea the major waste product of protein metabolism Converts waste products and excess fluids into urine in the kidneys and excretes them from the body via the urinary bladder kidneys serve to convert more than 1700 L of blood per day into about 1 L of a highly concentrated fluid (urine). The kidney also serves as an endocrine organ, secreting such hormones as erythropoietin, renin, prostaglandins, and regulating vitamin D metabolism.

5 The Kidneys Filter blood constantly to remove waste products and excess water which are excreted as urine (95% water and 5% other wastes) 2 kidneys located retroperitoneally, one on each side of the vertebral column below the diaphragm consist of: Renal cortex The outer region of the kidney Contains over 1 million microscopic units called nephrons Medulla The inner region of the kidney Contains the urine collecting tubules

6 cotex cortex Medulla

7 Each human adult kidney weighs about 150 gm. Anatomically the ureter forms the pelvis (the dilated upper ureter) which is divided into 2 or 3 major calyces, each one giving 3 or 4 minor calyces. The kidney is divided into the cortex cm and medulla. The medulla consists of renal pyramids, the apices of which are called papillae, each related to a calyx.

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10 1. Renal Vein 2. Renal Artery 3. Renal Calyx 4. Medullary Pyramid 5. Renal Cortex 6. Segmental Artery 7. InterlobAR Artery 8. Arcuate Artery interlobular 9. Arcuate Vein 10. Interlobar Vein 11. Segmental Vein 12. Renal Column 13. Renal Papillae 14. Renal Pelvis 15. Ureter

11 Nephrons The functional units of the kidneys Form urine by the process of filtration, reabsorption, and secretion Reabsorption: is the return of substances that were removed from filtration back to the bloodstream Each nephron contains a glomerulus Cluster of capillaries surrounded by a cup-shaped membrane called the Bowman s capsule

12 S.E.M. T.E.M.

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14 How is Urine Made? Blood enters the kidneys through the renal artery and flows into the nephrons After being filtered by the capillaries of the glomerulus, the blood leaves the kidney through the renal vein Waste products that were filtered out of the blood remain behind in the kidney where they pass through urine-collecting tubules Urine is then transported to the renal pelvis and collected in preparation for entry into the ureters

15 The Renal Pelvis Funnel-shaped area in each kidney that is surrounded by the renal cortex and medulla Newly formed urine collects here before flowing to the ureters

16 The Ureters 2 narrow tubes (10-12 inches each) that transport urine from each kidney to the bladder Peristalsis moves urine down each ureter into the bladder

17 The Urinary Bladder Hollow muscular organ that is a reservoir or holding tank for urine before it is excreted from the body Located in the anterior portion of the pelvic cavity behind the pubic symphysis Lined with rugae that allow it to expand and contract Trigone smooth triangular area on the inner surface of the bladder located between the openings of the ureters and the urethra

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19 KIDNEY

20 Kidney PATHOLOGY CONGENITAL MALFORMATION CYSTS GLOMERULAR DISEASES TUBULAR/INTERSTITIAL BLOOD VESSELS OBSTRUCTION TUMORS

21 CONGENITAL AGENESIS HYPOPLASIA ECTOPIC HORSESHOE

22 Congenital anomalies Agenesis of the kidney(absence): Bilateral agenesis is incompatible with life, seen in stillborn. Unilateral type is uncommon. The opposite kidney is usually enlarged as a result of compensatory hypertrophy. Hypoplasia(small size kidney) : Is failure of the kidney to develop to a normal size. This anomaly may occur bilaterally, resulting in renal failure and early childhood death. Unilateral cases are more common. The opposite kidney is also enlarged due to compensatory hypertrophy.

23 Renal (A) agenesis, and (B) hypoplasia. B

24 HYPOPLASIA

25 Congenital anomalies-cont Ectopic Kidneys: These kidneys lie within the pelvis. They are usually normal or slightly small in size. Because of their abnormal location can cause : kinking or tortuoisity of the ureters may cause some obstruction to urinary outflow. difficulty in labor in females. Misdiagnosis as pelvic tumors & abscesses. Have long renal artery that may have many complications like damage during surgery.

26 ECTOPIC (usually PELVIC)

27 Horseshoe kidneys: Fusion of lower poles of the kidneys that is continuous across the midline anterior to the great vessels. may cause many complications: 1. Partially obstructed the ureters, which result in hydronephrosis. 2. Recurrent UTI. 3. Stone formation.

28 HORSESHOE

29 Cystic Diseases Of The Kidney They are heterogeneous group comprising hereditary, developmental and acquired disorders. They are important for several reasons; 1. They are reasonably common and often represent diagnostic problems for clinicians, radiologists and pathologists. 2. Some forms are major causes of chronic renal failure. 3. They can occasionally be confused with malignant tumors.

30 Classification of CYSTIC DISEASES Polycystic kidney : Autosomal DOMINANT (AD-ULTS) Autosomal RECESSIVE (CHILDREN) ACQUIRED SIMPLE (dialysis-associated) cystic disease.. Parasitic cysts (e.g. hydatid cyst).

31 Autosomal Dominant Polycystic Kidney Disease Multiple expanding cysts of both kidneys that ultimately destroy the intervening parenchyma. It affects roughly 1 of every 400 to 1000 live births and accounting for about 5-10% 0f cases of chronic renal failure. It can be caused by inheritance of at least two Autosomal dominant genes of high penetrance: 1. PKD 1, present on chromosome 16, mutant in 90% of cases. 2. PKD 2, present on chromosome 4, mutant

32 Gross: Large kidney (4 kg) of each kidney, & present as abdominal mass. Mass of cysts of varying sizes up to 3 to 4 cm in diameter without intervening parenchyma. Mic: Cysts are filled with fluid (clear, hemorrhagic). Cysts arise from tubules or collecting ducts. Often have atrophic lining. Superimposed infection is common..

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34 Autosomal Dominant Polycystic Kidney Disease Clinical: Many of these patients remain asymptomatic until about the 4th or 5th decade of life when renal insufficiency occurs because the cysts initially involve only portions of the nephrones, so renal function is retained. Presentation (variable): flank pain, hypertension, hematuria, progressive renal failure Large lesions are palpable 40% have cystic disease of the liver (most common), spleen, pancreas, brain Berry aneurysms in circle of Willis and can cause death in about 4-10% of patients due to subarachnoid hemorrhage. Death due to uremia or hypertension 40% of patients die of coronary or hypertensive heart disease, 25% of infection, 15% of ruptured Berry aneurysm or hypertensive intracranial hemorrhage.

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38 Autosomal Recessive (Childhood) Polycystic Kidney Disease Is rare anomaly due to mutation of gene PKHD1 on chromosome 6 Perinatal, neonatal, infantile and juvenile types. The first 2 are the most common In all cases are associated with liver cysts (congenital liver cirrhosis). Mic: Gross: bilateral Small cysts in the cortex & medulla (sponge like appearance). Elongated channels at right angles to the cortical surface. Uniform lining of cuboidal cells (Originate from collecting ducts).

39 Morphology The kidneys are enlarged (bilateral) and have a smooth external surface. On cut section, numerous small cysts in the cortex and medulla give the kidney a sponge-like appearance. Smooth, Small, Sponge The cysts are dilated channels perpendicular to the corticomedullary junction. Cysts originate from collective tubules and are lined by uniform cuboidal cells In almost all cases, the liver has cysts with portal fibrosis as well as proliferation of portal bile ducts. Clinical Features; serious manifestations are usually present at birth, and the young infant might succumb rapidly to renal failure. Patients, who survive infancy, may develop congenital hepatic fibrosis. Liver: epithelium lined cysts and proliferation of bile ducts

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42 Acquired (Dialysis-Associated) Cystic Disease The kidneys of patients on chronic dialysis, sometimes exhibit numerous cortical and medullary cysts. The cysts measure 0.5-2cm, contain clear fluid, are lined by either hyperplastic or flattened tubular epithelium and often contain calcium oxalate crystals. Cause: They probably form as a result of tubular obstruction due to interstitial fibrosis or by oxalate crystals.

43 Acquired (Dialysis-Associated) Cystic Disease Most are asymptomatic, but sometimes the bleeding inside the cysts cause hematuria. The most important complication is the development of renal cell carcinoma in the walls of these cysts in about 7% of patients during 10 years period.

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45 ACQUIRED (DIALYSIS)

46 Simple Cysts Acquired, Incidental, very common These occur as single or multiple, usually cortical. The size range from 1-10 cm or more. They are translucent and filled with clear fluid. They are lined by a single layer of cuboidal or flattened epithelium. They are common postmortem findings. On occasion, hemorrhage into them may cause sudden pain, and calcification may be visible radiologically. The main importance of these cysts is in their differentiation from kidney tumors.

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49 Renal diseases can be divided according to the parts of kidneys into 1. Glomerular diseases 2. Tubular diseases. 3. Interstitium diseases. 4. Blood vessels diseases.

50 This division is useful because a. The early manifestations of each group of diseases tend to be distinctive. b. These groups differ in their pathogenesis, for e.g., glomerular diseases are often immunologically mediated, whereas tubular and interstitial disorders are more likely to be caused by toxic or infectious agents. However, it should be noted that: 1. The interdependence of renal components translated into that damage to one component is almost always affects secondarily the others. 2. All forms of chronic renal disease tend ultimately to damage all four components of the kidney thus, eventuates in chronic renal failure (end-stage kidney disease ESKD).

51 GLOMERULAR DISEASES

52 Glomerular Diseases: They constitute some of the major problems in nephrology; in fact they are the most common causes of chronic renal failure in humans. Clinical manifestations of renal disease; Acute Nephritic Syndrome: characterized by Gross hematuria (macroscopic). Mild to moderate proteinuria. Edema. Hypertension Typical example is Poststreptococcal glomerulonephritis. 2. Nephrotic Syndrome: Heavy Proteinuria (> 3.5 gram of protein / 24hours). Hypoalbuminemia. Severe edema. Hyperlipidemia & lipiduria. 3. Asymptomatic hematuria & / or Proteinuria: Mild Glomerular abnormality.

53 4. Rapidly Progressive Glomerulonephritis: Loss of renal functions in a few days or weeks. Manifested by active urine sediment (hematuria, Dysmorphic RBC S, RBC S Casts). 5. Acute Renal failure: Oliguria (< 500 cc) or Anuria (no urine flow). Recent onset of Azotemia.(in Latin: nitrogen = azot) 6. Chronic Renal failure: Prolonged symptoms & signs of Uremia. Can be the end result of all chronic renal diseases. 7. Urinary tract infection: Characterized by Bacteruria & Pyuria ( bacteria and leukocytes in the urine). 8. Nephrolithiasis: Characterized by Renal colic. Important notes: Azotemia: is a biochemical abnormality that means elevation of blood urea nitrogen (BUN) and creatinine levels, and is related largely to a decreased glomerular filtration rate (GFR). Could be Prerenal Azotemia (Hypoperfusion of kidneys), renal (due to kidney diseases), Postrenal Azotemia (obstruction below the kidney). Uremia: characterized by Clinical Signs, Symptoms & Biochemical abnormalities. Renal damage (impair excretory, endocrine, & metabolic functions of kidneys). Uremic patients frequently manifest secondary involvement of the gastrointestinal system (e.g., uremic gastroenteritis), peripheral nerves (e.g., peripheral neuropathy), and heart (e.g., uremic fibrinous pericarditis).

54 Principal Systemic Manifestations of Chronic Kidney Disease and Uremia Fluid and Electrolytes

55 Clinical Presentations of GN

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58 S.E.M. T.E.M.

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60 One of important function of Glomerular wall is Selective Permeability (high permeable to H2o & small solutes) while completely impermeable to molecules of size & molecular charge of Albumin. The podocyte is decisive to the glomerular barrier function by providing a distal resistance to the flow of water and a barrier to the filtration of proteins. It is also largely responsible for synthesis of GBM components

61 Histologic alterations There are 5 basic tissue reactions 1. Increased glomerular cellularity a. Proliferation of mesangial or endothelial cells. b. Leukocyte infiltration, including neutrophils, monocytes, and, in some diseases, lymphocytes. c. Formation of crescents(proliferation of parietal epithelial cells. 2. Basement membrane thickening, best seen in sections stained with (PAS). By EM, it can be resolved as one of 2 alteration;

62 a. Deposition of amorphous electron dense material, of immune complexes, on the endothelial or epithelial side of basement membrane, or within the GBM itself. b. Thickening of the BM proper, as occurs in diabetic glomerulosclerosis. 3. Hyalinization and sclerosis, made up of plasma proteins and collagen material deposited exracellularly. 4. Additional alterations include; accumulation of lipids, fibrin or other metabolic materials. 5. Intraglomerular vascular thrombosis The histologic changes can be further subdivided into; 1. Diffuse 2. Focal. 3. Global. 4. Segmental. 5. Mesangial

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65 Pathogenesis Although little is known about etiologic agents and triggering events, it is clear that immune mechanisms underlie most forms of primary glomerulopathies, and many of the secondary forms. Immune-mediated mechanisms; 1. Ab-mediated, a. Insitu immune complex deposition, In this form of injury, immune complexes are formed locally by antibodies that react with intrinsic tissue antigen or with extrinsic antigens "planted" in the glomerulus from the circulation. Fixed intrinsic antigens for e.g. (BM)like Goodpasterur syndrome (Ab against glomerular and pulmonary BM) The pattern of immune deposition by immunofluorescence microscopy is linear. Planted antigens (exogenous as infectious agent or drug and endogenous as DNA, immunoglobulins) The pattern of immune deposition by immunofluorescence microscopy is granular b. Circulating immune complex deposition Endogenous Ag (DNA, tumor) Exogenous Ag (infectious products)

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67 Pathogenesis-cont 2. Cell-mediated. T cell-mediated injury may account for some cases of glomerulonephritis (GN) 3. Activation of alternative complement pathway.

68 Localization of immune complexes in the Glomerulus 1. Subepithelial humps, 2. Epimembranous deposits, 3. Subendothelial deposits, 4. Mesangial deposits, 5. Basement membrane. EN, endothelium; EP, epithelium; LD, lamina densa; LRE, lamina rara externa; LRI, lamina rara interna; MC, mesangial cell; MM, mesangial matrix.

69 GLOMERULAR DISEASES Primary Glomerulonephritis Acute diffuse proliferative GN Rapidly progressive GN Membranous GN Lipoid nephrosis (minimal change disease) Focal segmental glomerulosclerosis Membranoproliferative GN IgA Nephropathy Chronic GN Secondary (Systemic) Diseases Systemic lupus erythematosus Diabetes mellitus Amyloidosis Goodpasture s syndrome Polyarteritis nodosa Wagener s granulomatosis Henoch-Scholein purpura Bacterial endocarditis. Hereditary Disorders Alport s syndrome Fabry s disease

70 Nephritic Syndrome Injury.proliferation of the cells within the glomeruli(endothelium and mesangial cells), accompanied by leukocytic infiltrate. This inflammatory reaction injures the capillary walls(formation of holes in the basement membrane),. permitting escape of red cells into the urine, and induces hemodynamic changes that lead to a.reduction in the GFR. The reduced GFR is manifested clinically by oliguria, fluid retention, and azotemia. Hypertension is the result of both the fluid retention and excessive renin release Clinical Symptoms: Oliguria(due to decreased GFR) Azotemia (elevated creatnine and BUN) Hypertension (due to retention of salt and excessive renin secretion) mild-moderate Protinuria >150mg but <3.5g BUN/Creatinine level of >15 Hematuria best defined as red cell casts and RBC with dysmorphic membranes Commonly defined as smoky brown urine

71 ACUTE GLOMERULONEPHRITIS Nephritic Holes in the membrane Hematuria, Hypertension, Hardly any urin(oliguria), Azotemia in children following a strep infection POSTSTREPTOCOCCAL (old term) HYPERCELLULAR GLOMERULI INCREASED ENDOTHELIUM AND MESANGIUM IgG, IgM, C3 along GMB FOCALLY(Hump) 95% full recovery

72 RAPIDLY PROGRESSIVE GLOMERULONEPHRITIS Clinical definition, NOT a specific pathologic one CRESCENTIC Anti-GBM Ab IMMUN COMPLX Anti-Neut. Ab

73 Crescentic glomerulonephritis (PAS stain)

74 NEPHROTIC SYNDROME Syndrome of Glomerular dysfunction that is characterized by increased loss of proteins in the urine due to increased basement membrane permeability CLINICAL MANIFESTATIONS Massive proteinuria without hematuria [>3.5g/ day] Hypoalbuminemia [<3g/dl] Periorbital edema then Generalized edema Due to d plasma oncotic pressure Hyperlipiduria and Oval Fat Bodies Hyperlidemia and Hypercholesterolemia due to loss of lipoproteins and alterations in liver production of lipoproteins Increase in Infections due to loss of low weight globulins and complement Loss of anticoagulants hypercoagulable state

75 NEPHROTIC SYNDROME Only MASSIVE PROTEINURIA HYPOALBUMINEMIA EDEMA LIPIDEMIA/LIPIDURIA NUMEROUS CAUSES:

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