Pathology Of Kidney

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Pathology of Kidney Disorders Dr. Venkatesh M. Shashidhar Associate Professor of Pathology Fiji School of Medicine

Components of Glomerulus: Capillary basement membrane Mesangium Bowman capsule Cells Endothelial Epithelial Mesangial

Anatomic Compartments Glomerulus Tubules Blood vessels Interstitium Collecting system (Callices & Pelvis)

Kidney Functions: Excretion metabolic waste/drugs. Water/fluid balance. Electrolyte balance. Acid-base balance. Blood pressure. Erythropoietin secretion.

Note the positions of Glomerulus Loop of Henley PCT, DCT, CT Cortex, Medulla, Pelvis. Anatomy of Kidney

JGA GFR  Renin  Angiotensin Blood Pressure

Kidney Diseases Developmental disorders Glomerular diseases Tubulo-interstitial diseases Urinary stones Obstructive uropathy Tumors

Congenital Anomalies: Agenesis – Potter syndrome Ectopia Fusion Dysplasia Simple cysts Polycystic kidney disease

Polycystic kidney disease Autosomal dominant (adult) (1:1,000) Autosomal recessive (infantile (1:30,000) Medullary cystic disease complex (1:10,000) Medullary sponge kidney Acquired cystic renal disease

Autosomal Dominant PKD Common kidney disease (1:1,000) 10% of all transplant/dialysis patients ADPKD-1 gene (polycystin) mutation 85% Bilaterally enlarged kidneys (>3,000g) Symptoms appear in adult life Renal failure 5-10 years thereafter

ADPKD Associated Conditions Liver cysts (30%) Splenic cysts (10%) Pancreatic cysts (5%) Cerebral aneurysms (20%) Diverticulosis coli

Kidney Disorders – clinical. A Asymptomatic hematuria/proteinuria N Nephrotic syndrome N Nephritic syndrome U Urolithiasis R Rapidly progressive glomerulonephritis I Interstitial and tubular diseases C Chronic renal disease

“ To be a great champion you must believe you are the best. If you’re not, pretend you are.” – Muhammad Ali

Nephritic Hematuria Proteinuria Hypoalbuminemia Oliguria (GFR  , Cr  , BUN  ) Edema (salt and water retention) Hypertension Nephrotic Proteinuria (“nephrotic range” >3.5g/24h) Hypoalbumimenia Edema Hyperlipidemia Lipiduria

Acute Post Strepto. GN: Synonyms : Incidence : Etiology : Clinical : Lab: Path: Clinical Course: Acute proliferative glomerulonephritis, acute post-infectious GN. Glomerular trapping of circulating anti-streptococcal immune complexes. Group A, B-hemolytic streptococci, type 12. Acute nephritic syndrome post-strept pharyngitis or pyoderma. Other infections. Nephritic urine with RBC casts. Evidence of streptococcal infection or serologic evidence of recent infection. Decreased serum complement. Children - Excellent prognosis. Adults - Worse prognosis, some develop progressive disease. Enlarged, hypercellular glomeruli with endothelial and mesangial cell proliferation. Acute inflammation. IgG and C3 in very coarsely granular pattern along GBMs. Discrete, subepithelial “hump-like” deposits. Peak incidence in children (3-14). Sporatic, mostly winter and spring.

Minimal Change GN: Synonyms : Incidence : Etiology : Clinical Features: Lab Features: Pathology : Clinical Course: Nil disease, lipoid nephrosis, foot process disease Idiopathic. Loss of net negative charge on capillary basement membrane. Nephrotic syndrome. History of recent URI in 30%. Association with Hodgkin’s lymphoma. Overlap with FSGS patients. Selective proteinuria. No specific laboratory findings. Spontaneous remission in 25-40%. Complete remission in 65-70% of patients. Steroid resistant patients may progress to FSGS. LM - Normal. IF - Negative. EM - Focal fusion/loss of foot processes. 80% of nephrotic syndrome in children (1-8 yrs.), mostly male. Adults in 2nd-3rd decade.

Membranous GN: Synonyms: Incidence : Etiology: Clinical: Lab: Path: Clinical Course: Epimembranous, extramembranous GN Immune complex disease. Idiopathic in most patients, associated with infections, drugs, carcinomas, and heavy metals. Nephrotic syndrome in 80%, asymptomatic proteinuria in 20%. Microscopic hematuria. Non-selective proteinuria ± hematuria. Excellent prognosis in children. Some adults develop ESRD. Exclusion of other diseases is required. Diffuse, uniform BM thickening with subepithelial projections (“spikes”). Diffuse, coarsely granular IgG and C3 deposits along basement membranes. Electron-dense subepithelial deposits. 40-60 Years, 50% of adult nephrotic syndrome.

Membranoproliferative GN Etiology : Chronic immune complex GN. Associated with chronic infections, SLE, cancer, cirrhosis, heroin abuse, etc. Clinical : Nephrotic syndrome in 50%, acute nephritic syndrome in 20%. Recent history of URI in 50%. Hypertension and/or renal insufficiency. Lab : Hypocomplementemia of classic and alternate pathways. C3 nephritic factor (C3NEF). Circulating immune complexes. Clinical Course: Progressive deterioration of renal function ± short remissions. ESRD within 10 years in 50% of children and 80% of adults. Path: Diffuse proliferative GN with thickening of the glomerular capillary walls,, and GBM splitting (“tram-tracking”). Diffuse, coarsely granular C3 and IgG deposits along GBMs. Electron-dense subendothelial deposits. Incidence : Children and young adults (5-25 years).

Causes of nephrotic syndrome Disease Children (%) Adults (%) Minimal change GN 75 20 Membanous GN 5 40 MPGN I 5 5 Other GN 5 20

Chronic renal failure (uremia) General symptoms – weakness, fatigue Cardiovascular – hypertension, pericarditis G.I. – nausea, vomiting, diarrhea CNS – lethargy, confusion, coma Muscles – twitching, weakness Bones – osteodystrophy Metabolic – acidosis, P  K  , BUN  , Cr  . Endocrine - parathyroids 

Diabetic kidney diseases Glomerulosclerosis Arteriolosclerosis  Hypertension Pyelonephritis Papillary necrosis

Diabetic glomerulosclerosis Diabetes BM thickening Proteinuria  renal failure (leading cause of mortality in DM) nonenzymatic glycation (?), BM synthesis  , leaky. Pathology: Diffuse global thickening of BM Nodular sclerosis (K-W) Arteriolosclerosis Trapping of serum proteins Clin: Proteinuria (in 50% diabetics) ESKD (30%)

Diabetic Glomerulosclerosis Hyaline nodules

Diabetic Glomerulosclerosis KW lesion…

Benign Nephrosclerosis: Leathery Granularity due to minute scarring

Renal Artery stenosis - Atrophy Leathery Granularity Benign Nephrosclerosis

IgA Nephropathy (berger) Most common form of GN Young adults (15-30 years) IgA deposits in mesangium, varied severity Asymptomatic microscopic hematuria (40%) Bouts of macro hematuria (40%) Nephrotic syndrome (10%) Renal failure (10%)

Nephrosclerosis - Hypertension Benign sustained mild hypertension. hyaline arteriolosclerosis arterial fibrosis glomerular hyalinization, tubular atrophy Malignant BP>125 mm/Hg, retinal hemorrhage, papilledema, renal dysfunction fibrinoid necrosis of arterioles microthrombi

Thrombotic microangiopathy Morphologic finding in several diseases microangiopathic hemolytic anemia HUS, TTP, Malignant nephrosclerosis Systemic sclerosis

Renal infarcts Thromboemboli Mural thrombi (M.I., atrial fibrillation) Endocarditis Aortic thrombi (atherosclerosis) Cholesterol emboli

Acute Tubular Necrosis: Common cause of acute renal failure “ Dirty” brown casts in urine Oliguria  anuria  polyuria Azotemia Acidosis, K  Fluid retention Recovery 1-2 weeks

Acute Pyelonephritis Bacterial infection (E. coli 80%) Ascending / hematogenous Lower UTI precedes renal infection Fever, flank pain, neutrophilia Leukocyte casts in urine Healing - recurrence  chronic pyelonephritis

Acute Pyelonephritis with papillary necrosis (diabetes)

Pyelonephritis – Predisposing Cond. U Urolithiasis R Reflux (vesico-ureteric) I Infections of lower UT N Neoplasms (ureteric, vesical, prostatic) E External compression (e.g.) pregnancy retroperitoneal fibrosis

Chronic Pyelonephritis Pathology Destruction of renal tissue and fibrosis Cortical scars Loss of papillae Ectasia of calices Hydronephrosis Irregularly shrunken small kidney Chronic inflammatory infiltrates Tubular atrophy with casts (“thyroidization”)

Drug induced renal disorders: Acute tubular necrosis(toxic) Gentamycin, mercury, contrast agents. Acute tubulointerstitial nephritis (allergic) – methicillin, thiazides. Analgesic nepropathy (Phenacetin) chronic tubulointerstitial nephritis with papillary necrosis.

Urolithiasis: 1-5%, environment, males, pelvis Renal colic, dull ache in loins Urinary tract infection recurrent. Factors affecting: Urine pH, Infection, Metabolic, Pyrophosphates and citrate inhibit.

Urolithiasis – stones: Infection 6% Other 1% Cystine 6% Uric acid 12% Magnesium ammonium phosphate (struvite, or "triple phosphate") 75% Calcium oxalate (or phosphate)

Hypercalcemia / Hypercalciuria Primary (increased intestinal absorption of Ca) Idiopathic (most common) Milk-alkali syndrome Vitamin D excess Sarcoidosis Secondary (release of Ca from bones) Renal osteodystrophy Hyperparathyroidism Osteolytic metastases (e.g. breast cancer) Paraneoplastic syndromes (PTrP)

Urolithiasis with hydronephrosis:

Urolithiasis – sites of impaction

Causes of Obstructive Uropathy

Urolithiasis: Incidence : Etiology : Clinical Features : Lab : Path : Clinical Course : Environmental, metabolic, infectious. Develop silently until episode of renal colic. Cause obstruction, pain, infection, hydronephrosis, and hydroureter. Gross or mcroscopic hematuria. Chemical analysis to identify type of stone. Characteristic radiographic findings. May recur. Complications are the problem. Calcium phosphate or oxalate - Hard, sharp. Uric acid - Smooth. Staghorn - Cast of calyceal system. Common, male predominance. Treatment : Surgery, lithotomy, or ultrasonic lithotripsy to remove stone. Treatment of metabolic process, if indicated. Adequate hydration.

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Renal tumors Benign Adenoma, oncocytoma, angiomyolipoma, fibroma (rare!) Malignant: Renal cell carcinoma (common – adults) Wilms tumor (childhood) Transitional cell carcinoma of renal pelvis

Renal Papillary Adenoma Papillary Common Histopathology similar to renal Cell Carcinoma. < 3cm – benign > 3cm - malignant All tumors considered malignant until proved otherwise.

Oncocytoma (DCT epithelia, benign)

Wilm’s Tumor Incidence : Etiology : Clinical Features: Lab : Path: Clinical Course: Embryonic renal tissue (metanephric blastema). Genetic abnormalities. Palpable abdominal mass. Abdominal pain, fever, anorexia, nausea/vomiting. Hematuria. No specific clinical laboratory findings. Diagnosis by radiographic techniques. 5-yr. Survival 80%. Metastases to lung, liver, bone, brain. Gross: Solitary/multiple cystic mass, sharply delineated. Soft, bulging, gray-white with focal hemorrhage and necrosis. Micro: Triphasic mesenchymal stroma, tubules, and solid areas (blastema). Primitive glomeruli, skeletal muscle, cartilage, bone, etc. (embryonic tissues) Most common renal tumor of childhood. Peak age - 2.5 - 3.5 years. Treatment: Prompt resection with chemotherapy ± radiotherapy. Synonyms : Nephroblastoma.

Renal Cell Carcinoma Most common renal tumor Peak age – 60y M:F = 3:1 Incidence increasing world wide Tobacco; Obesity, genetics (VHLgene, familial cases) Von Hippel-Lindau syndrome Hemangioblastoma cerebellum retina Bilateral renal cysts, Clear cell type RCC – common.

RCC - Pathology Yellow orange tumor –Hypernephroma. Partially encapsulated Extends into renal vein tubular clear cell (77%) papillary (15%) granular, chromophobe, sarcomatoid (5%)

RCC – Clinical Features: Classical triad (hematuria, flank pain, mass) (<10%) Hematuria (50%) most common symptom Metastases-hematogenous and local abdominal Paraneoplastic syndromes (PTH, Epo, amyloid) 5 year survival = 40%

Renal Cell Carcinoma: Incidence : Etiology : Clinical Features : Lab : Path : Clinical Course: Cells of proximal convoluted tubule. Risk factors are smoking, obesity, analgesic abuse, APCKD. Hematuria*, flank pain, palpable mass. Frequently metastasize (lungs, bone, skin, liver, brain). Gross or microscopic hematuria. Specific Dx by radiographic techniques. 5-yr. survival 40%. Poor prognosis with metastases. Gross: Large yellow mass with hemorrhage and necrosis. Invade renal vein. Micro: Usually clear or granular cells with little anaplasia. Other histologic variants (“great mimicker”). 5 th and 6 th decades, most common primary renal malignancy. Treatment : Chemotherapy, surgery, immunotherapy. Synonyms : Hypernephroma, clear cell carcinoma.

Wilms tumor Childhood tumor (2-5y) 98%< 10 years Most common tumor in childhood Sporadic, unilateral (90%) Bilateral more common in familial cases (20%) Familial syndromic (5%), nonsyndromic (5%) WAGR sy – Aniridia, genital abn, Mental Ret. WT1 Beckwith Wiedemann sy - Hemihypertrophy – WT2

Transitional Cell Carcinoma: 5-10% of adult renal ca. Etiology: Analgesic abuse, dye, rubber etc.. Multiple common. Malignant cells in urine Desquamated tissue may cause obstruction. Hematuria & pain.

Wilms Tumor Features: Lobulated tumors mass –encapsulated Histology: mixture of immature cells metanephric, stromal, tubular Chemotherapy + surgery = 5 years = 90% Children < 2 years better prognosis

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Pathology Of Kidney

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