Diseases of the kidney

Diseases of the kidney

1. DISEASES OF THE KIDNEY

2. Learning Objectives The normal functioning of the kidney. The Classification of Glomerular Diseases. The Glomerular Syndromes Pyelonephritis Diabetic Glomerulosclerosis Benign and Malignant Nephrosclerosis Hydronephrosis Tumors of the Kidney

3. The Kidneys A pair of bean-shaped organs located at the posterior wall of the abdomen Dimensions 11 cm long, 6 cm wide and 3 cm thick weighs about 160g

4. Kidney Functions Regulates extracellular fluid & osmolarity , electrolyte concentrations, & acid-base balance Excretes wastes Secretes renin Produces erythropoietin Converts vitamin D to active form

5. Clinicopathologic Classification of Glomerular Diseases . I. PRIMARY GLOMERULONEPHRITIS 1. Acute GN i ) Post-streptococcal ii) Non-streptococcal 2. Rapidly progressive GN 3. Minimal change disease 4. Membranous GN 5. Membrano -proliferative GN 6. Focal and diff use proliferative GN 7. Focal segmental glomerulosclerosis (FSGS) 8. IgA nephropathy 9. Chronic glomerulonephritis II. SECONDARY SYSTEMIC GLOMERULAR DISEASES 1. Lupus nephritis (SLE) 2. Diabetic nephropathy 3. Amyloidosis 4. Polyarteritis nodosa 5. Wegener’s granulomatosis 6. Goodpasture’s syndrome 7. Henoch-Schönlein purpura 8. Systemic infectious diseases ( bacterial e.g. bacterial endocarditis , syphilis, leprosy; viral e.g. HBV, HCV, HIV; parasitic e.g. falciparum malaria, fi lariasis ) 9. Idiopathic mixed cryoglobulinaemia III. HEREDITARY NEPHRITIS 1. Alport’s syndrome 2. Fabry’s disease 3. Nail-patella syndrome

6. CLINICAL MANIFESTATIONS

7. POSTSTREPTOCOCCAL GLOMERULONEPHRITIS 1 to 4 weeks after group A β -hemolytic streptococcal infection of pharynx or skin – types 12, 4 and 1 6 to 10 years Immune complexes produced against streptococcal antigen – endostreptosin and cationic antigen

8. POSTSTREPTOCOCCAL GLOMERULONEPHRITIS Microscopy Enlarged, hypercellular glomeruli , hypercellularity - due to infiltration of inflammatory cells, proliferation of endothelial cells and mesangial cells and in severe cases by crescent formation

9. POSTSTREPTOCOCCAL GLOMERULONEPHRITIS Immune fluorescence: granular deposits of IgG , IgM and C3 in the mesangium and along the basement membrane

10. POSTSTREPTOCOCCAL GLOMERULONEPHRITIS Clinical course Acute nephritic syndrome – 1 to 2 weeks after recovery from streptococcal infection Elevated ASO titers Decreased serum C3 95% recover; 1% progress to RPGN and others progress to CGN

11. RAPIDLY PROGRESSIVE GLOMERULONEPHRITIS Type 1 RPGN Goodpasture syndrome Idiopathic Type II RPGN (immune complex) Idiopathic Post infectious Systemic lupus erythematosus Henoch-schonlein purpura Others

12. RAPIDLY PROGRESSIVE GLOMERULONEPHRITIS Type III RPGN ( pauci -immune) ANCA associated Idiopathic Wegener granulomatosis Microscopic polyarteritis nodosa /microscopic polyangitis

13. RAPIDLY PROGRESSIVE GLOMERULONEPHRITIS Microscopy : proliferation of parietal cells and by migration of monocytes and macrophages into urinary space, neutrophils and lymphocytes may be present Obliterate bowman space and compress the glomerular tuft Fibrin strands between cellular layers Crescents

14. NEPHROTIC SYNDROME Massive proteinuria , with the daily loss of 3.5 gm per 24hours of urine or more of protein (less in children) Hypoalbuminemia , with plasma albumin levels less than 3 gm/dl Generalized oedema Hyperlipidemia Lipiduria

15. CAUSES OF NEPHROTIC SYNDROME

16. MINIMAL CHANGE DISEASE Common cause of nephrotic syndrome in children Peak age – 2 to 6years Selective proteinuria ( albuminuria ) Etiology No immune complexes Immune dysfunction resulting in visceral epithelial damage by cytokines In some cases, mutation in glomerular protein ( Nephrin )

17. MINIMAL CHANGE DISEASE Characterized by diffuse effacement of foot processes of epithelial cells in glomeruli that appear virtually normal by light microscopy Most characteristic feature is its usually dramatic response to corticosteroid therapy A , Ultrastructural characteristics of minimal change disease: effacement of foot processes ( double arrows ), absence of deposits, vacuoles (V), and microvilli in visceral epithelial cells ( single arrow ). B , Schematic representation of minimal change disease, showing diffuse effacement of foot processes.

18. CHRONIC GLOMERULONEPHRITIS Gross – symmetrical contracted kidneys having diffuse granular cortical surface Thinned out cortex and increase in peripelvic fat Micro – hyaline obliteration of glomeruli leads to eosinophilic acellular masses Hyaline arterial and arteriolar sclerosis and marked tubular atrophy Masson trichrome stain – complete replacement of all glomeruli by collagen (blue in color) Masson trichrome preparation shows complete replacement of virtually all glomeruli by blue-staining collagen

19. CHRONIC GLOMERULONEPHRITIS Slowly progress to CRF or death due to uremia Loss of appetite, anemia, vomiting or weakness Edema, proteinuria, hypertension or azotemia Treatment – dialysis or renal transplant

20. PYELONEPHRITIS Infection of renal pelvis, interstitium and tubules Acute – associated with bacterial UTI Chronic – bacterial infection and vesico ureteral reflux Gram –ve bacilli – E.coli, proteus and klebsiella Immunocompromised patients – polyoma virus and CMV

21. PYELONEPHRITIS Hematogenous – septicemia and infective endocarditis Ascending – most common Colonization of distal urethra and introitus Urethra to bladder during instrumentation, Multiplication in the bladder Vesicoureteral reflex Intrarenal reflex

22. ACUTE PYELONEPHRITIS Patchy interstitial suppurative inflammation, intra tubular aggregates of neutrophils and tubular necrosis Papillary necrosis – usually bilateral Pyonephrosis Perinephric abscess

23. ACUTE PYELONEPHRITIS Cortical surface exhibits grayish white areas of inflammation and abscess formation Acute pyelonephritis marked by an acute neutrophilic exudate within tubules and the renal substance.

24. CHRONIC PYELONEPHRITIS Gross – coarse, discrete corticomedullary deep V and Y shaped scar leading to asymmetrically contracted kidney Tubular atrophy in some areas and dilatation in some areas Dilated tubules with flattened epithelium filled with colloid casts ( thyroidization ) Varying degree of interstitial mononuclear inflammation and tubular atrophy Periglomerular fibrosis Obliterative intimal sclerosis of arterioles in scarred areas

25. CHRONIC PYELONEPHRITIS GROSS The kidneys are usually small and contracted, weighing less than 100 gm each, showing unequal reduction. The outer surface of the kidneys is irregularly scarred. These deep V and Y shaped scars are of variable size and show irregular depressions on the cortical surface. The pelvis of the kidney is dilated and calyces are blunted and may contain renal stone taking the shape of pelvicalyceal system called staghorn stone

26. CHRONIC PYELONEPHRITIS MICROSCOPY The interstitium shows chronic inflammatory infiltrate with pronounced interstitial fibrosis. Dilated atrophic tubules may contain colloid casts producing thyroidisation of tubules. The wall of dilated pelvicalyceal system shows marked chronic inflammation and scarring. Periglomerular fibrosis and hyalinisation of some glomeruli

27. DIABETIC GOMERULOSCLEROSIS MICROSCOPIC FEATURES Diffuse involvement of the glomeruli showing thickening of the glomerular basement membrane. Diffuse increase in the mesangial matrix with mild proliferation of mesangial cells and exudative lesions (fibrin caps and capsular drops) Diffuse glomerulosclerosis

28. DIABETIC GOMERULOSCLEROSIS MICROSCOPIC FEATURES There are one or more hyaline nodules within the lobules of glomeruli , surrounded peripherally by glomerular capillaries with thickened walls. These nodular lesions of diabetic glomerulosclerosis are also called as Kimmelstiel -Wilson (KW) lesions or intercapillary glomerulosclerosis . Th e nodules are PAS-positive and contain lipid and fibrin. Nodular glomerulosclerosis

29. HYPERTENSIVE CHANGES BENIGN NEPHROSCLEROSIS GROSS FEATURES Both the kidneys are affected equally and are reduced in size and weight, often weighing about 100 gm or less. The capsule is often adherent to the cortical surface. The external surface of the kidney is finely granular and shows V-shaped areas of scarring. The cut surface shows firm kidney and narrowed cortex.

30. HYPERTENSIVE CHANGES BENIGN NEPHROSCLEROSIS Microscopy : a) Hyaline arteriolosclerosis that results in homogeneous and eosinophilic thickening of the wall of small blood vessels. b) Intimal thickening due to proliferation of smooth muscle cells in the intima . c) variable degree of atrophy of parenchyma

31. Causes of ‘small contracted kidney’ Chronic GN (granular appearance) Chronic pyelonephritis (U-shaped scars) Benign nephrosclerosis (V-shaped scars). Amyloidosis of the kidney,

32. HYPERTENSIVE CHANGES MALIGNANT NEPHROSCLEROSIS The kidneys are variable in size - small in size, shrunken reduced in weight and have finely granular surface. enlarged, oedematous and have petechial haemorrhages on the surface producing so called ‘flea-bitten kidney’.* Cut surface shows red and yellow mottled appearance

33. HYPERTENSIVE CHANGES MALIGNANT NEPHROSCLEROSIS MICROSCOPY Necrotising arteriolitis develops on hyaline arteriolosclerosis. The vessel wall shows fibrinoid necrosis, a few acute inflammatory cells and small haemorrhages . Ischaemic changes include tubular loss, fine interstitial fibrosis and foci of infarction necrosis.

34. Causes of flea-bitten kidney Malignant nephrosclerosis , Acute post-streptococcal GN, Rapidly progressive GN, Haemolytic-Uraemic Syndrome Thrombotic thrombocytopenic purpura Henoch-Schonlein purpura .

35. HYDRONEPHROSIS Aseptic dilatation of the renal pelvis or calyces . May be associated with obstruction but may be present in the absence of obstruction. Accompanied destruction of kidney parenchyma.

36. Etiology Can be Unilateral or bilateral. Unilateral maybe extramural, intramural or intraluminal Bilateral causes are either congenital or acquired

37. Causes of Unilateral hydronephrosis Extramural Compression by growth ( CA cervix, carcinoma rectum) Retroperitoneal fibrosis

38. B. Intramural Congenital PUJ obstruction Ureterocele Neoplasm of ureter Narrow ureteric orifice Stricture ureter following removal of stone, pelvic surgeries or tuberculosis of ureter.

39. C. Intraluminal Stone in the renal pelvis Sloughed papilla in papillary necrosis

40. Bilateral Hydronephrosis Result of urethral obstruction ; but may also be caused by one of the lesions described above occurring on both sides

41. Causes of Bilateral hydronephrosis Congenital Congenital stricture of external urethral meatus, pin-hole meatus. Congenital posterior urethral valve. Acquired BPH Carcinoma prostate Postoperative bladder neck scarring Inflammatory / traumatic urethral stricture Phimosis Carcinoma cervix Bladder carcinoma

42. GROSS Kidney may have slight to massive enlargement Earlier features are those of simple dilation of the pelvis and calyces In far-advanced cases, kidney may become transformed into a thin-walled cystic structure having a diameter of up to 15 to 20 cm with striking parenchymal atrophy, total obliteration of the pyramids, and thinning of the cortex. Hydronephrosis of kidney, with marked dilation of the pelvis and calyces and thinning of the renal parenchyma

43. MICROSCOPY The wall of hydronephrotic sac is thickened due to fi brous scarring and chronic inflammatory cell infiltrate. Progressive atrophy of tubules and glomeruli along with interstitial fi brosis . Stasis of urine in hydronephrosis causes infection ( pyelitis ) resulting in filling of the sac with pus, a condition called pyonephrosis

44. TUMORS OF THE KIDNEY Benign - rare Renal papillary adenoma-from tubular epithelium Renal fibroma Angiomyolipoma - associated with tuberous sclerosis Oncocytoma - from intercalated cells of collecting duct Malignant Renal cell carcinoma Clear cell carcinoma Papillary carcinoma Chromophobe carcinoma Collecting Duct carcinoma Urothelial carcinoma of renal pelvis

45. RENAL CELL CARCINOMA 6 th -7 th decade Risk Factors: Cigarette smoking Obesity Hypertension Family history of the disease Patients with inherited diseases like von Hippel Lindau disease Hysterectomy is associated with doubled risk Dialysis patients with acquired cystic disease of kidney show greater risk

46. EPIDEMIOLOGY The incidence of renal cell carcinoma is rising steadily. More common in men than women, male to female ratio is 1.6:1. Blacks at an higher risk than whites.

47. CLASSIFICATION OF RCC Clear cell carcinoma - 70% to 80% 95% sporadic,5% familial associated with VHL disease 98% of clear cell carcinoma have (3p-) which harbor VHL gene Papillary carcinoma - 10% to 15% Trisomy 7 in familial, trisomy 7, 16 and 17 and loss of y in male in sporadic In familial form - MET proto oncogene Chromophobe carcinoma - 5% Arises from intercalated cells of collecting dusts and have excellent prognosis Collecting duct (Bellini duct) carcinoma - 1%

48. RENAL CELL CARCINOMA Gross- usually arise from upper pole spherical bright yellow masses with hemorrhage and necrosis Typical cross-section of yellowish, spherical neoplasm in one pole of the kidney.

49. CLEAR CELL CARCINOMA Growth pattern varies from solid to trabecular or tubular. The tumour cells have rounded or polygonal shape and abundant clear or granular cytoplasm . The tumours have delicate vasculature.

50. MORPHOLOGY Papillary carcinoma – cuboidal or low columnar cells arranged in papillary fronds Interstitial foam cells are present in papillary core Psammoma bodies may be present Chromophobe carcinoma- pale eosinophilic cells with perinuclear halo in solid pattern Collecting duct carcinoma- irregular channels lined by atypical epithelium within a prominent fibrotic stroma

51. SIGNS AND SYMPTOMS Classic triad of: Hematuria Flank pain Abdominal mass Signs: Malaise, weight loss and anorexia Anemia Varicocele. enlargement of testicle on left side Pallor Constipation Hypertension Hypocalcaemia Leg and ankle swelling

52. DIAGNOSIS Physical examination: Fever High blood pressure Lab tests:   Complete blood count Urine analysis Serum calcium Imaging tests: Ultrasound abdomen  Abdominal CT scan MRI scan PET scan Renal angiography Intravenous pyelogram Chest x ray Bone scan Biopsy Fine needle aspiration Core needle biopsy